Sleep Apnea Occurring During REM Sleep is Significantly Associated with Type 2 Diabetes

June 15, 2009

June 15, 2009 (EurekAlert) - A multi-ethnic study in the June 15 issue of the Journal of Clinical Sleep Medicine reports that there is a statistically significant relationship between obstructive sleep apnea (OSA) episodes occurring during rapid eye movement (REM) sleep and type 2 diabetes.

Results indicate that the adjusted odds ratio for type 2 diabetes was 2.0 times higher in patients with REM-related OSA, defined as havng an REM apnea-hypopnea index (AHI) of 10 or more breathing pauses per hour of REM sleep. The prevalence of type 2 diabetes was 30.1 percent in participants with OSA and 18.6 percent in those without OSA; however, the overall association between OSA and diabetes became non-significant after controlling for covariates such as body mass index (BMI), age, race and gender. Middle-aged participants with OSA had an adjusted odds ratio for type 2 diabetes that was 2.8 times higher than younger or middle-aged people without OSA. Hispanics and older patients referred for OSA evaluation had a higher prevalence of type 2 diabetes; this relationship was not affected by OSA.

According to principle investigator Kamran Mahmood, MD, MPH, of the University of Illinois at Chicago, the researchers were surprised by the significant association of REM-related OSA with type 2 diabetes.

"We believe that REM-related OSA is a marker of early OSA, especially in women and patients younger than 55 years," said Mahmood. "Generally, OSA is worse in REM sleep compared to non-REM sleep because of neurologically mediated impairment of skeletal muscles of upper airway and ventilation. This may be the reason for closer association of REM-related OSA and type 2 diabetes."

The study gathered data from 1,008 consecutive patients who were evaluated for OSA by comprehensive polysomnography at the University of Illinois at Chicago; 66.9 percent were African American, 16.9 percent were Caucasian, 14.9 percent were Hispanic and 1.3 percent were Asian. OSA was defined as an AHI of five or more breathing pauses per hour of sleep and was diagnosed in 745 individuals (74 percent); the 263 adults (26 percent) who did not have OSA served as the control. Men comprised 52.8 percent of the OSA group but only 28.5 percent of the control group.

According to the authors, the findings are consistent with several studies on the association of OSA with glucose tolerance, insulin resistance and type 2 diabetes. REM-related OSA is more common in mild-to-moderate cases of OSA, especially in women and in patients younger than 55 years of age. Sleep fragmentation caused by OSA may reduce REM sleep time, which could explain a high REM AHI.

Mahmood said that the results highlight the need to educate minority groups about OSA and its complications. The authors encourage awareness campaigns and making OSA screening part of all obesity management programs.

According to the American Academy of Sleep Medicine, OSA is a sleep-related breathing disorder that involves a decrease or complete halt in airflow despite an ongoing effort to breathe. It occurs when the muscles relax during sleep, causing soft tissue in the back of the throat to collapse and block the upper airway. This leads to partial reductions (hypopneas) and complete pauses (apneas) in breathing that can produce abrupt reductions in blood oxygen saturation. Brief arousals from sleep restore normal breathing but can cause a fragmented quality of sleep. Most people with OSA snore loudly and frequently, and they often experience excessive daytime sleepiness.

Posted by dlife at 12:14 PM | Comments (0)

What is the Relationship Between Hepatocellular Carcinoma and Type 2 Diabetes Mellitus?

June 11, 2009

June 11, 2009 (EurekAlert) - Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third leading cause of cancer-related deaths. Type 2 diabetes mellitus has been associated with HCC. However, the relationship between type 2 diabetes mellitus and the underlying liver cirrhosis, and the effects of antidiabetic therapy on HCC risk have not yet been fully evaluated.

A research team led by Dr. Valter Donadon from Pordenone Hospital addressed this question. Their study will be published on May 28, 2009 in the World Journal of Gastroenterology.

Four hundred and sixty five HCC patients, 618 cirrhosis patients and 490 control subjects were enrolled in this study. They evaluated the odds ratio (OR) for HCC by univariate and multivariate analysis. Moreover, OR for HCC in diabetic subjects treated with insulin or sulphanylureas and with metformin were calculated.

The prevalence of diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control group. By univariate and multivariate analysis, the OR for HCC in diabetic patients were respectively 3.12 (95%CI: 2.2-4.4, P < 0.001) and 2.2 (95%CI: 1.2-4.4, P = 0.01). In 84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC. Moreover, we report an OR for HCC of 2.99 (95%CI: 1.34-6.65, P = 0.007) in diabetic patients treated with insulin or sulphanylureas, and an OR of 0.33 (CI 0.1-0.7, P = 0.006) in diabetic patients treated with metformin.

This study demonstrates that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients. In male HCC, patients with type 2 diabetes mellitus, their data shows a direct association of HCC risk with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.

Posted by dlife at 02:17 PM | Comments (0)

Death Rates Same for Diabetes and Heart Disease Patients Receiving Drug Therapy or Surgery

June 07, 2009

June 7, 2009 (EurekAlert) - There is no difference in mortality among patients with type 2 diabetes and stable heart disease who received prompt bypass surgery or angioplasty compared to drug therapy alone, according to a landmark study focused exclusively on patients with both conditions. The study, which was led by investigators at the University of Pittsburgh Graduate School of Public Health, published in the June 11 issue of the New England Journal of Medicine and presented at the American Diabetes Association 69th Scientific Sessions, also found that while prompt bypass in patients with more severe heart disease did not lower mortality, it lowered their risk of subsequent major cardiac events.

"More than 20 million Americans suffer from type 2 diabetes and many of these people also have heart disease," said Sheryl F. Kelsey, Ph.D., principal investigator of the study and professor of epidemiology, University of Pittsburgh Graduate School of Public Health. "We began this study because we don't know how best to treat this deadly duo that is affecting more and more people at increasingly younger ages. Our results provide needed guidance about which approaches can best help these patients."

The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) study began recruiting patients in 2001. The results are based on 2,368 patients with both type 2 diabetes and stable heart disease who were under a physician's care to control their cholesterol and blood pressure. Patients were randomized to receive drug therapy plus undergo prompt revascularization to restore blood flow—either angioplasty to open blocked arteries or bypass surgery―or to receive drug therapy alone. The investigators also looked at which of two diabetes drug treatment strategies resulted in better outcomes – insulin-providing (increasing the amount of insulin) or insulin-sensitizing (lowering the body's resistance to its own insulin, such as metformin or rosiglitazone). The study was not a comparison between angioplasty and bypass surgery, but rather a comparison between a prompt procedure and medical therapy alone.

The results show that five-year survival rates did not differ significantly between the revascularization group (88.3 percent) and the drug therapy group (87.8 percent). In addition, there was no significant difference in survival between those who received insulin-providing drugs (87.9 percent) and those who received insulin-sensitizing drugs (88.2 percent). However, in the group that received bypass surgery, the rate of all major cardiovascular events (heart attacks, strokes and death) was significantly lower (22.4 percent) compared to those who received drug therapy alone (30.5 percent). This benefit appeared to be greatest in those who underwent bypass and received insulin-sensitizing drugs.

"We observed that patients with more severe heart disease did better over time when they received bypass early compared to those who received drug therapy alone," said Robert L. Frye, M.D., professor of cardiovascular medicine, Mayo Clinic College of Medicine, and BARI 2D study chairman. "Those who underwent bypass surgery seemed to do particularly well on insulin-sensitizing drugs. Although this result is preliminary because we did not set out to answer this question with our study design."

"Overall, the BARI 2D results reassure us that our current major drug treatments for diabetes are equally appropriate," said Saul Genuth, M.D., director of the diabetes management center of BARI 2D and professor of medicine, Case Western Reserve University. "They also indicate that when a patient with type 2 diabetes has more severe heart disease it may be better to do bypass surgery early than to wait and simply treat with medication. For patients with milder disease who are candidates for angioplasty, it is appropriate to treat with drug therapy first."

Posted by dlife at 09:41 AM | Comments (0)

Regulating the Sugar Factory in Diabetes

May 21, 2009

May 21, 2009 (EurekAlert) - Scientists in Sydney and Boston believe they may have identified a gene that controls abnormal production of sugar in the liver, a very troublesome problem for people with diabetes.

The liver is the sugar factory for the body - when blood sugar (glucose) levels fall, the liver makes and releases more. In people with diabetes, especially Type 2 diabetes, the liver doesn't stop making sugar when it should, so blood sugar levels can rise overnight while they sleep even though they haven't eaten.

Dr Jenny Gunton, diabetes specialist and endocrinologist from Sydney's Garvan Institute of Medical Research, in collaboration with Dr Xiao Hui Wang and Professor Ronald Kahn from Harvard Medical School and Joslin Diabetes Centre in Boston, have published their findings in the journal Cell Metabolism, now online.

"A lot of my patients will complain that they go to bed with a blood sugar of 5 and wake up with a blood sugar of 12," said Dr Gunton.

"It upsets people when their blood sugar behaves as if they're getting up in the night and having a really big snack. I have to tell them it's just one of those unfair things about having diabetes."

People with Type 2 diabetes do not produce enough insulin in the pancreas after a meal. At the same time, they are less able to use that insulin to move glucose into fat and muscle cells, a condition known as 'insulin resistance'.

With her colleagues in Boston, Gunton has been studying a transcription factor, or kind of 'master regulator', called ARNT, which controls expression of other genes involved in processes like glucose breakdown and insulin production. In an earlier study, the group showed that there is 90% less ARNT in insulin-producing cells of people with Type 2 diabetes.

The current study looks at how ARNT might be affecting the liver, and its results confirmed Dr Gunton's suspicions. "We've shown that there's likely to be decreased ARNT in the liver of people with Type 2 diabetes compared to people without Type 2 diabetes," she said.

"Working with mice, we found that glucose levels were elevated and there was glucose production from a 'precursor', a source not normally metabolised."

Other results in the study show that to some extent ARNT is regulated by insulin, so that insulin resistance in itself will contribute to a decrease in ARNT. If liver cells are treated with insulin, there will be a small increase in ARNT protein. The insulin will also help move the ARNT into the nucleus of the cell, where it does its job as a master regulator.

The paper concludes that a decline in ARNT isn't limited to the beta cells of people with Type 2 diabetes. ARNT is also reduced in other important diabetes-related tissues like the liver.

Dr Gunton believes that if a new drug could be developed to increase ARNT activity in the liver, then it may be possible to shut down abnormal sugar production and improve blood sugar control in people with diabetes.

Posted by dlifenews at 12:17 PM | Comments (0)

More Than a Bad Night's Sleep

May 21, 2009 (EurekAlert) - Sleep apnea has long been known to be associated with obesity. But a new study published in the June issue of Diabetes Care finds that the disorder is widely undiagnosed among obese individuals with type 2 diabetes – nearly 87 percent of participants reported symptoms, but were never diagnosed.

For those with untreated sleep apnea, it doesn't just mean their sleep is disrupted; existing research shows that it can also mean an increased risk of heart disease and stroke.

"The high prevalence of undiagnosed, and therefore, untreated sleep apnea among obese patients with diabetes constitutes a serious public health problem," said Gary Foster, PhD, lead author and director of the Center for Obesity Research and Education at Temple University.

The new study, called Sleep AHEAD, looked at 306 obese patients with type 2 diabetes already enrolled in the Look AHEAD trial, a 16-site study investigating the long-term health impact of an intensive lifestyle intervention in 5, 145 overweight or obese adults with type 2 diabetes.

Each participant had a sleep study (polysomnogram) that measures various breathing and brain activity during sleep. Participants also filled out a series of questions about symptoms related to sleep (snoring, sleepiness during the day), and had their weight, height, waist and neck circumferences measured.

Researchers found that 86.6 percent of participants had sleep apnea, yet reported never being diagnosed. More than 30 percent of these had between 16 and 20 episodes per hour where they would stop breathing, and 22 percent had more than 30 episodes per hour, considered severe sleep apnea. Most of these also had a larger waist circumference, which researchers found, along with higher BMI, to be significantly associated with sleep apnea.

Obesity has long been known to be associated with sleep apnea, but researchers say that these findings are alarming.

"Doctors who have obese patients with type 2 diabetes need to be aware of the possibility of sleep apnea, even if no symptoms are present, especially in cases where the patient has a high BMI or waist circumference," said Foster.

Currently, more than half of obese or overweight individuals have diabetes, the seventh leading cause of death in the United States.

Posted by dlifenews at 11:03 AM | Comments (0)

Obstructive Sleep Apnea, Retinopathy Linked in Diabetes

May 19, 2009

May 19, 2009 (EurekAlert) - The eyes may be the window into the soul, but they may also contain important medical information. According to new research to be presented at the American Thoracic Society's 105th International Conference in San Diego on May 19, patients with diabetes who have retinopathy should also be screened for obstructive sleep apnea (OSA).

"We know from our earlier research that 23 percent of men with type 2 diabetes have OSA and this is under-recognized and under-treated," said Sophie D. West, M.D., of the Oxford Centre for Respiratory Medicine in the United Kingdom, who led the research. "This study suggests that OSA is linked to retinopathy in type 2 diabetes."

The researchers analyzed data from 118 men who had participated in the earlier study on the prevalence of OSA in type 2 diabetes in Oxford, England, and who also had retinal images to review. (All patients with type 2 diabetes in the U.K. are offered annual retinal screening to look for signs of retinopathy.) The images were studied by ophthalmology graders for evidence of retinopathy and the sleep study data was reviewed to determine the presence or absence of OSA.

The researchers found that retinopathy was present in more than half—54 percent—of those who had OSA, compared to fewer than a third—31 percent—of those without OSA, independent of the effects of glucose control, age, body mass index, high blood pressure and the duration of the diabetes. This was statistically significant.

"These results suggest an association between OSA and retinopathy that should be further investigated," said Dr. West. "While the study only analyzed data from men, there is no reason to believe that gender would play a role in the results."

There has been very little work previously regarding the relationship between OSA and retinopathy. Previous studies have found strong links between poor glucose control and high blood pressure with retinopathy and these have been the main areas upon which treatment has been targeted in diabetes in order to prevent retinopathy from developing and to delay its progression. However, in this study, OSA had a far stronger relationship with retinopathy than did glucose control or high blood pressure.

"While there is clearly more research to be done, there is an immediate implication to consider," said Dr. West. "Our message would be for doctors and nurses who see patients with type 2 diabetes to consider whether they could have OSA and whether they should therefore be referred for a sleep study."

Symptoms of possible OSA include snoring, apneas (stopping breathing) and daytime sleepiness. "Future research will try to determine whether the treatment for OSA, that is continuous positive airway pressure (CPAP), can delay the development or progression of retinopathy, associated with diabetes."

Posted by dlifenews at 09:49 AM | Comments (1)

Type 2 Diabetes: An Epidemic Among America's Youth

May 18, 2009

May 18, 2009 (PR Newswire) - With the number of children suffering from type 2 diabetes growing at an alarming rate, physicians gathered Saturday to discuss strategies for prevention and treatment of the disease among children and adolescents at the American Association of Clinical Endocrinologists (AACE) 18th Annual Meeting & Clinical Congress.

"Type 2 diabetes is extremely complex," said A. Jay Cohen, MD, FACE, session moderator and pediatric endocrinologist. "The rapid rise in obesity, physical inactivity and the consumption of excessive calories seems to have led to the epidemic of children with type 2 diabetes."

The National Institutes of Health (NIH) is conducting two clinical trials in order to identify the children at risk for type 2 diabetes and to demonstrate the effectiveness of lifestyle intervention among youth. The first trial, HEALTHY, is following a group of about 6,400 children through middle school, from sixth to eighth grade, to determine if modifications in exercise programs and nutrition in the school environment can reduce the risk of children having the disease. Researchers are tracking the youth's body mass indices (BMIs), fasting glucose levels and fasting insulin levels to show the health benefits of lifestyle adjustments. TODAY, the second trial, is exploring the best treatment options for children with type 2 diabetes.

"It is imperative to expose the social, behavioral and environmental factors which have led to this epidemic," said Francine R. Kaufman, MD, pediatric endocrinologist and Study Chair of both trials.

Children with type 2 diabetes may be afflicted with other conditions associated with type 2 diabetes, including obesity, hypertension, hyperlipidemia (elevated cholesterol), and potential risks of infertility such as Polycystic Ovarian Syndrome. These youth also have an increased risk of developing long-term complications, including heart disease, stroke, kidney disease, and nerve damage.

With results from the HEALTHY trial anticipated to be released this fall, Dr. Kaufman remains optimistic: "The research from these trials will allow us to identify and implement the necessary lifestyle changes that will ultimately foster the health and well-being of not only those at risk but generations of children to come."

Posted by dlifenews at 10:16 AM | Comments (0)

Type 2 Diabetes Rears Its Ugly Head Long Before Diagnosis

May 13, 2009

May 13, 2009 (Newswise) - Signs and symptoms of type 2 diabetes can present themselves as long as 10 years before diagnosis and most people have no idea before the damage is done.

Type 2 is a condition where the body does not produce enough insulin and the cells ignore the insulin it does have. Insulin is essential for the body to be able to use glucose for energy. After eating, the body breaks down all of the sugars and starches into glucose, which is the fuel for the cells in the body. When glucose builds up in the blood instead of going into the cells, over time, damage to the heart, kidneys, nerves and eyes is likely. Type 2 is the most common and fast-growing form of diabetes. The risk factors include:
• Blood pressure higher than 130 over 80.
• Waist line bigger than 35 inches in women, and 40 inches in men.
• HDL or “good” cholesterol less than 40 in men, and 50 in women.
• Triglyceride levels over 200.
• Fasting glucose over 100.

Some experts believe replacing sugar with high fructose corn syrup in processed foods in the United States and Canada in the 1990s has played a role in the rise of type 2 diabetes cases. High fructose corn syrup is made by changing the sugar in corn starch to fructose, another form of sugar. It has become popular because it extends the shelf life of processed foods and is cheaper than sugar. It has also become a popular ingredient in many sodas and fruit-flavored drinks.

“The problem with high fructose corn syrup is that it promotes central obesity or a big stomach, one of the major factors in type 2 diabetes,” Hamilton said. “Another problem with it is that it fools your body into thinking you are hungry. I don’t think you need to eliminate it from your diet, you just need to be aware of how much of it you are consuming on a daily basis because too much can lead to serious weight gain.”

There are some ways to rid your body of type 2 diabetes:
• Exercise at least 30 minutes at a time, five days a week.
• Lose weight.
• Talk to your doctor about medication to lower your triglycerides and LDL cholesterol.

Most patients with diabetes die from heart and blood vessel related problems, in particular heart attacks and strokes. The underlying causes of diabetes are often under treated because there is little or no pain involved.

“Having three or more of the risk factors associated with type 2 diabetes over an extended period of time is the equivalent of already having a heart attack,” Hamilton said. “These risk factors need to be treated aggressively in order to curb the problem and give you a better chance at a longer, healthier life.”

Posted by dlifenews at 10:10 AM | Comments (0)

Connections Between Diabetes and Alzheimer's Disease Explored

May 11, 2009

May 11, 2009 (EurekAlert) - Amsterdam, The Netherlands, May 11, 2009 – Modern societies face the increasing burden of age-related diseases, in particular Alzheimer's disease (AD) and type 2 diabetes (T2D). There is some evidence that the causes underlying both diseases are linked. Do AD and T2D represent the endpoint of aged, exhausted, and dysfunctional cells having reached their maximal life expectancy or are AD and T2D the consequences of living in superabundance including excessive food supply, work demands, psychosocial stress, and an excessive sedentary life style? In a special issue of the Journal of Alzheimer's Disease (April 2009), nineteen contributions examine the possible connections between AD and T2D.

Numerous epidemiological studies have described the incidence of both AD and T2D in the Western world and extensively defined common environmental risk factors. Guest Editors Angelika Bierhaus and Peter P. Nawroth, both of the University of Heidelberg, have assembled a group of prominent investigators to explore the connections between AD and T2D pathologies using literature reviews of current human studies, overviews of animal models, reviews of basic pathophysiology findings, and biochemical analyses.

In the introduction Bierhaus and Nawroth note that several pathological features have been identified as common denominators of AD and T2D including impaired glucose/energy metabolism, altered insulin-signaling pathways, mitochondrial dysfunction, oxidative stress, and inflammation.

Daniel Kopf and Lutz Frölich report a systematic review of fourteen studies that examined the risk of incident Alzheimer's disease in diabetic patients. All studies reported risk ratios greater than one with four studies showing statistically significant excess risk.

Pablo Toro, Peter Schönknecht, and Johannes Schröder follow with the results of a study of almost 200 subjects born between 1930 and 1932. For those with either mild cognitive impairment (MCI) or with AD, there was an increased tendency for T2D.

José A. Luchsinger and Deborah R. Gustafson present a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and T2D with AD. The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosylation, cerebrovascular disease, and products of adipose tissue metabolism. The implication of these associations is that a large proportion of the world population may be at increased risk of AD given the trends for increasing prevalence of overweight, obesity, hyperinsulinemia, and T2D. However these associations may also present a unique opportunity for prevention and treatment of AD.

Ceramides are a type of lipid molecule that are both neurotoxic and causes insulin resistance. Ming Tong and Suzanne M. de la Monte report on their investigation of the role of ceramides as mediators of neurodegeneration using an in vitro culture model. Exposure to two different ceramides impaired energy metabolism, viability, and insulin and insulin-like growth factor signaling mechanisms, and resulted in increased levels of AβPP-Aβ and pTau, while an inactive ceramide analogue had no significant effect on these parameters.

Following this line of investigation, Lascelles E. Lyn-Cook, Jr., Margot Lawton, Ming Tong, Elizabeth Silbermann, Lisa Longato, Ping Jiao, Princess Mark, Jack R. Wands, Haiyan Xu and Suzanne M. de la Monte used pairs of mice fed a high-fat diet (HFD) or a normal diet and found that mild neurodegeneration and brain insulin resistance resulted from the high-fat diet. They found that ceramide production increased in the HFD mice and that obesity, T2D and nonalcoholic steatohepatitis (NASH) might all be mediated by the excess ceramides.

In the area of possible therapies for AD, Nikolaos Tezapsidis, Jane M. Johnston, Mark A. Smith, J. Wesson Ashford, Gemma Casadesus, Nikolaos K. Robakis, Benjamin Wolozin, George Perry, Xiongwei Zhu, Steven J. Greco, and Sraboni Sarkar write about a possible use of leptin to reduce the affects of AD. They speculate that a deficiency in leptin levels or function may contribute to systemic and central nervous system abnormalities leading to AD.

Three articles focus on the role of oxidative stresses and the development of AD. Paula I. Moreira, Ana I. Duarte, Maria S. Santos, A. Cristina Rego, and Catarina R. Oliveira write about the processes underlying the pathogenesis of Alzheimer's disease, including impaired glucose/energy metabolism, mitochondrial dysfunction, oxidative stress and altered insulin-signaling pathways. V. Prakash Reddy, Xiongwei Zhu, George Perry, and Mark A. Smith discuss how oxidative stress plays a major role in diabetes as well as in Alzheimer's disease and other related neurological diseases. The advanced glycation end products and lipid peroxidation products are ubiquitous to diabetes and Alzheimer's disease and serve as markers of disease progression in both disorders. Sajjad Muhammad, Angelika Bierhaus, and Markus Schwaninger review some recent findings on the role of reactive oxygen species in diabetes-induced vascular dysfunction and the consequent cerebral ischemia and compare them with key findings in AD.

Allan Jones, Philipp Kulozik, Anke Ostertag, and Stephan Herzig review common metabolic and inflammatory processes implicated in the pathogenesis of both T2D and AD. In particular, they emphasize the role of critical transcriptional checkpoints in the control of cellular metabolism, insulin sensitivity, and inflammation. These transcriptional regulators might hold great promise as new therapeutic targets in the potentially combined treatment of type 2 diabetes and Alzheimer's disease. Other inflammatory processes might be involved in both AD and T2D. Ivica Granic, Amalia M. Dolga, Ingrid M. Nijholt, Gertjan van Dijk, and Ulrich L. M. Eisel investigate how both inflammation and the inducible nuclear factor NF-κB might be involved in both diabetes mellitus and Alzheimer's disease. Clement T. Loy and Stephen M. Twigg discuss how advanced glycation end products (AGEs) and growth factor dysregulation may link diabetes and AD.

Receptor for Advanced Glycation Endproducts (RAGE) is a superfamily of cell molecules which serves as a receptor for amyloid-β peptide (Aβ). Increased expression of RAGE is observed in regions of the brain affected by Alzheimer's disease (AD), and Aβ-RAGE interaction in vitro leads to cell stress with the generation of reactive oxygen species and activation of downstream signaling. Shi Du Yan, Angelika Bierhaus, Peter P. Nawroth, and David M. Stern suggest that RAGE may be a therapeutic target for AD.

Masayoshi Takeuchi and Sho-ichi Yamagishi contribute a study of Toxic Advanced Glycation End-products (TAGE). These AGEs can cause oxidative stress in numerous types of cells, which could contribute to the pathological changes of diabetic vascular complications and AD. Akihiko Taguchi discusses how RAGE-mediated chronic inflammation can initiate a degenerative positive feedback loop between endothelium and neuronal cells. Elzbieta Kojro and Rolf Postina explore how RAGE and Amyloid-beta protein precursor (AβPP) proteolysis can be affected by insulin and how proteolysis of RAGE may prevent transport of Aβ across the blood-brain barrier.

A contributing factor to oxidative stress can be excess free iron. Sandro Altamura and Martina U. Muckenthaler review experimental evidences for an involvement of iron in Alzheimer's disease and Parkinson's disease. They also propose a role for iron in atherosclerosis, another frequent disorder of aging.

Michael Morcos and Harald Hutter report that the classical model organism in aging research, the nematode Caenorhabditis elegans (C. elegans), shares many similarities at the molecular level to pathological processes found in humans. C. elegans has an accessible and well characterized nervous system and features several genes homologous to human genes implicated in AD like amyloid-β protein precursor, presenilins and tau.

Posted by dlifenews at 10:19 AM | Comments (0)

Too Much or Too Little Sleep Increases Risk of Diabetes

April 21, 2009

April 21, 2009 (EurekAlert) - Researchers at Université Laval's Faculty of Medicine have found that people who sleep too much or not enough are at greater risk of developing type 2 diabetes or impaired glucose tolerance. The risk is 2½ times higher for people who sleep less than 7 hours or more than 8 hours a night. The findings were published recently on the website of the journal Sleep Medicine.

The researchers arrived at this conclusion after analyzing the life habits of 276 subjects over a 6-year period. They determined that over this timespan, approximately 20% of those with long and short sleep duration developed type 2 diabetes or impaired glucose tolerance versus only 7% among subjects who were average duration sleepers. Even after taking into account the effect attributable to differences in body mass among the subjects, the risk of diabetes and insulin resistance was still twice as high among those with longer and shorter sleep duration than average sleepers.

The researchers also point out that diabetes is not the only risk associated with sleep duration. A growing number of studies have shed light on a similar relationship between sleep and obesity, cardiovascular disease, and overall mortality. The authors observe that among adults, between 7 and 8 hours of nighttime sleep appears to be the optimum duration to protect against common diseases and premature death.

However, it seems that fewer and fewer people sleep the optimum number of hours. A survey conducted in 1960 showed that American adults slept an average of 8 to 8.9 hours a night. By 1995, that average had dropped to 7 hours. A study conducted in 2004 by the National Center for Health Statistics found that one-third of adults aged 30 to 64 slept less than 6 hours a night.

Posted by dlifenews at 10:29 AM | Comments (0)

Mount Sinai Researchers Discover Novel Mechanisms That Might Causally Link Type 2 Diabetes to Alzheimer's Disease

April 10, 2009

April 10, 2009 (EurekAlert) - A recent study by Mount Sinai faculty suggests that a gene associated with onset of type-2 diabetes also decreases in Alzheimer's disease dementia cases. The research, led by Dr. Giulio Maria Pasinetti, MD, Ph.D., The Aidekman Family Professor in Neurology, and Professor of Psychiatry and Geriatrics and Adult Development at Mount Sinai School of Medicine, was published this week in the scientific journal, Archives of Neurology.

"This new evidence is of extreme interest," Dr. Pasinetti tells us, "especially because of the evidence that approximately 60% of Alzheimer's disease dementia cases have at least one serious medical condition primarily associated with type-2 diabetes, a chronic condition which includes high blood glucose content (hyperglycemia) and reduced sensitivity to insulin, among other conditions."

"The relationship between type-2 diabetes and Alzheimer's disease is elusive," says Dr. Pasinetti. Not all subjects with type-2 diabetes are affected by Alzheimer's disease, and similarly, not all Alzheimer's disease cases are diabetic. However, in the last few years, epidemiological evidence indicates that, relative to healthy elderly subjects, people of the same age affected by type-2 diabetes are twice as likely to develop Alzheimer's disease dementia. The reason is not known. The new study from Dr. Pasinetti, reported in this week's issue of Archives of Neurology, provides insight into a potential mechanism that might explain the relationship between type-2 diabetes and Alzheimer's disease onset and progression.

Dr. Pasinetti and colleagues found that a gene known as proliferator-activated receptor coactivator 1 - (PGC-1 ), a key regulator of glucose content currently investigated as a potential therapeutic target for type-2 diabetes, is also decreased in Alzheimer' disease dementia cases. Most importantly, Dr. Pasinetti reports that PGC-1 decreased in Alzheimer' disease dementia cases with progression of the clinical disease and positively correlates with brain accumulation of β-amyloid, an abnormal protein highly linked to Alzheimer' disease dementia and brain degeneration. This evidence is of high interest to the field and suggests, for the first time, a strong relationship between decreased content of a gene responsible for type-2 diabetes in Alzheimer's disease dementia cases, says Dr. Pasinetti.

"Of considerable interest," continues Dr. Pasinetti, "is the evidence found in further mechanistic studies in our laboratory, indicating that promoting PGC-1 content in brain cells, using a transgenic mouse model of Alzheimer's disease, attenuates hyperglycemic-mediated production of β-amyloid, highly linked to Alzheimer' disease dementia. These findings are very exciting, and for the first time tentatively link type-2 diabetic metabolic defects to increasing dementia mediated by β-amyloid production."

The discovery in Dr. Pasinetti's laboratory has staggering societal implications: there are currently more than 5 million Americans affected by Alzheimer's disease dementia, and the disease incidence is expected to skyrocket in the three decades as the population ages. The question now is how we can translate this evidence into the development of novel approaches for disease prevention and treatment.

Dr. Pasinetti and his colleagues are optimistic that if they find that PGC-1α can be manipulated pharmacologically, these studies will provide important insights to be used in the formulation of novel treatments and possible preventative strategies in Alzheimer's disease.

Posted by dlifenews at 09:17 AM | Comments (0)

Reducing Sugar and Increasing Fiber Intake May Improve Diabetes Risk Factors in Latino Teens

April 06, 2009

April 6, 2009 (EurekAlert) - Reducing sugar intake by the equivalent of one can of soda per day and increasing fiber intake by the amount equivalent to one half cup of beans per day appears to improve risk factors associated with type 2 diabetes in Latino adolescents, according to a report in the April issue of Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

Almost 40 percent of Mexican American adolescents age 12 to 19 were overweight or at risk for overweight from 2003 to 2006, according to background information in the article. "Latino children are more insulin resistant and thus more likely to develop obesity-related chronic diseases than their white counterparts," the authors write. "To date, only a few studies have examined the effects of a high-fiber, low-sugar diet on metabolic health in overweight youth, and to our knowledge, none have tested the effects of this type of intervention in a mixed-sex group of Latino youth."

Emily Ventura, M.P.H., of Keck School of Medicine, University of Southern California, Los Angeles and colleagues conducted a 16-week study to examine if reductions in added sugar intake or increases in fiber intake would affect risk factors for developing type 2 diabetes in 54 overweight Latino adolescents (average age 15.5). Participants were split into three groups: control, nutrition (receiving one nutrition class per week) or nutrition plus strength training (receiving one nutrition class per week along with strength training twice a week).

Fifty-five percent of participants decreased their sugar intake by an average of 47 grams per day (equal to the sugar in one can of soda) and 59 percent increased their fiber intake by an average of 5 grams per day (equal to the fiber in a half cup of beans) across all intervention groups, including controls. Participants who decreased their sugar intake had an average 33 percent decrease in insulin secretion and those who increased their fiber intake had an average 10 percent reduction in visceral adipose tissue volume. "A reduction in visceral fat indicates a reduction in risk for type 2 diabetes, considering that to a greater degree than total body fat, visceral fat [fat surrounding the internal organs] has been shown to be negatively associated with insulin sensitivity," the authors note.

"Those who increased fiber intake had a significant reduction in body mass index (-2 percent vs. 2 percent) and visceral adipose tissue (-10 percent vs. no change) compared with those who decreased fiber intake," the authors write.

"Our results suggest that intensive interventions may not be necessary to achieve modifications in sugar and fiber intake. Accordingly, nutritional guidance given in the primary care or community setting may be sufficient to promote the suggested dietary changes in some individuals," the authors conclude. "In addition, policies that promote reduced intake of added sugar and increased intake of fiber could be effective public health strategies for the prevention of type 2 diabetes in this high-risk population."

Posted by dlifenews at 09:54 AM | Comments (0)

Glitazones Have Not Yet Been Sufficiently Investigated

April 01, 2009

April 1, 2009 (EurekAlert) - There is so far a lack of scientific evidence that glitazones are better than alternative therapies at reducing mortality or complications caused by blood vessel damage in people with type 2 diabetes. As long-term studies are lacking, reliable conclusions on the long-term benefit or harm of these oral antidiabetics are presently possible only to a limited extent. Available studies provide indications that patients could benefit from one of the two currently approved active substances (pioglitazone); however, these studies also provide indications of potential disadvantages, including an increased risk of heart failure. This is the conclusion of a report by the German Institute for Quality and Efficiency in Health Care (IQWiG), Cologne, which was published in January 2009 and for which an English-language summary is now available.

No antidiabetic of first choice

Glitazones improve insulin sensitivity in the adipose tissue, skeletal muscle, and liver. As a result, glucose uptake by the adipose tissue and muscle tissue increases, while the release of glucose from the liver is inhibited. However, glitazones, which are available as tablets, are not regarded as an antidiabetic of first choice and therefore have only limited approval in Europe. They are only allowed to be used as monotherapy if patients do not tolerate metformin or if other contraindications for the use of this drug exist.

In combination therapy, glitazones should only be prescribed if blood-glucose levels are insufficiently controlled by metformin or a sulfonylurea alone. A 3-drug therapy in combination with sulfonylurea and metformin is also possible: however, glitazones are only approved in this therapy regimen if a previous combination of sulfonylurea and metformin failed to achieve the desired success. Pioglitazone can also be used in combination with insulin.

Long-term use has not been sufficiently tested

The aim of the report, which was commissioned by the German Federal Joint Committee, was to assess the benefit of the long-term treatment of pioglitazone and rosiglitazone versus placebo, or versus other blood-glucose lowering drug or non-drug interventions, or versus each other.

A total of 7 eligible studies on pioglitazone and 16 eligible studies on rosiglitazone were identified and included in the evaluation. However, in IQWiG's opinion, the long-term benefit and harm of glitazones have still not been sufficiently investigated.

Results from studies on rosiglitazone are only available for a treatment period of up to 12 months; however, oral antidiabetics are used for several years, if not decades. A 4-year study on rosiglitazone (ADOPT study) does not correspond to the current approval status in Europe and therefore could not be evaluated.

Only one large long-term study on pioglitazone available

The current evidence is slightly better for pioglitazone. Although only a small number of clinical comparisons have been conducted, these include a long-term study lasting 34.5 months that recruited about 5000 patients (PROactive study). The PROactive study was a comparison of a therapy optimization regimen with and without pioglitazone (including the potential use of other blood-glucose lowering drugs such as metformin or a sulfonylurea). However, according to IQWiG, the results of this study also need to be verified and confirmed in further clinical comparisons.

Both manufacturers of glitazones, GlaxoSmithKline (rosiglitazone) and Takeda Pharma (pioglitazone), supported IQWiG's benefit assessment by providing comprehensive, previously unpublished data.

No proof of an additional benefit with regard to mortality and late vascular complications

IQWiG found no proof in the available study data of an additional benefit of glitazones with regard to late micro- and macrovascular complications of type 2 diabetes (e.g., cardiac disease, stroke, eye or kidney damage) or mortality.

However, the findings provide indications of an advantage of pioglitazone for a composite outcome of all-cause mortality, non-fatal myocardial infarction (excluding silent myocardial infarction), and stroke. In addition, patients who had previously suffered a stroke seemed to benefit from pioglitazone, as strokes recurred less frequently in patients using this treatment. These indications were inferred from secondary outcomes of the PROactive study; no superiority of pioglitazone was shown for the primary outcome.

Advantage of glitazones with regard to hypoglycaemia

IQWiG sees proof of an additional benefit of glitazones with regard to the outcome "hypoglycaemia" both for pioglitazone and rosiglitazone. According to the findings, patients with type 2 diabetes experience hypoglycaemic events less frequently if they use metformin and a glitazone than if they use a combination of metformin and a sulfonylurea (with comparable lowering of blood-glucose levels).

Potential disadvantages: heart failure, oedema, and bone fractures

However, this potential additional benefit is counteracted by indications of higher risks: in the PROactive study, more cases of heart failure were diagnosed in the treatment arm receiving therapy optimization with pioglitazone, in part including cases of serious heart failure leading to hospitalization. In addition, oedema occurred, which is why more participants discontinued the study. Moreover, women more often experienced fractures.

In addition, for the combination of pioglitazone and metformin, the findings provide indications of more serious adverse events compared with metformin and vildagliptin, another new antidiabetic. Moreover, other heart diseases (e.g., heart attacks and angina pectoris) seem to be more common than in the combination of metformin and a sulfonylurea.

Weighing benefits and harms

In the opinion of the Institute and the external experts involved in the report, the potential benefits and harms of glitazones must be carefully weighed against each other. In order to make reliable statements on their advantages and disadvantages, good quality studies lasting several years are definitely needed. The risk potential of glitazones has been discussed in an increasingly controversial manner over the past 2 years, in particular concerning the possibly higher rate of heart attacks in patients treated with rosiglitazone, though at present there is still a lack of large studies of good methodological quality to make reliable conclusions about these risks. However, in the next few years several such clinical comparisons will be completed.

Procedure of report production

The preliminary results (preliminary report) were published by IQWiG in mid-June 2008 and interested parties were invited to submit comments. After the end of the commenting procedure, the preliminary report was revised and the final report sent to the contracting agency, the Federal Joint Committee, at the end of November 2008. The documentation of the written comments will be published in a separate document simultaneously with the final report.

Posted by dlifenews at 09:46 AM | Comments (0)

Plain-Language Guides Compare Insulin Treatments for Type 2 Diabetes

March 27, 2009

March 27, 2009 (NewsWise) - The Agency for Healthcare Research and Quality (AHRQ) released a pair of plain-language guides for consumers and clinicians comparing the efficacy, effectiveness, and side effects of newer premixed insulin analogues to conventional insulin (human insulin) and other preparations used to control Type 2 diabetes.

The consumer guide – Premixed Insulin for Type 2 Diabetes: A Guide for Adults – is a primer on diabetes, diabetes testing, and treatments. The guide distinguishes the differences among insulin analogues that last all through the day, insulin used at meal time, and the newer premixed insulin analogues that are both effective all through the day and after meals, a time when blood sugar levels can suddenly rise. Finally, the guide offers a cost comparison chart for different types of treatments under generic and brand names.

The clinician guide - Premixed Insulin Analogues: A Comparison with Other Treatments for Type 2 Diabetes - covers the same information as the consumer guide, but also includes a level of confidence scale for the information included in the guide, based on the systematic review of literature and assists clinicians choose the appropriate type of insulin based on patients’ physiologic need.

The new guides on treatments for type 2 diabetes show that:

* When newer premixed insulin analogues were compared to long-acting insulin analogues (insulin lasting all through the day), the premixed insulin analogues were better at lowering A1c and at lowering blood sugar after meals. The long-acting insulin analogues were found to be better at lowering fasting blood sugar levels, and showed fewer incidents of hypoglycemia and less weight gain.

* When conventional insulin (premixed human insulin) was compared with newer premixed insulin analogues, the latter was better at lowering blood sugar after meals, but both kinds of insulin were equally as effective at lowering A1c and lowering fasting blood sugar levels. They showed similar incidents of hypoglycemia and weight gain.

Premixed Insulin for Type 2 Diabetes: A Guide for Adults and Premixed Insulin Analogues: A Comparison with Other Treatments for Type 2 Diabetes are the newest in a series of comparative effectiveness guides from AHRQ’s Effective Health Care program. Other AHRQ guides compare treatments for prostate cancer, osteoarthritis, pills for hypertension, pills for type 2 diabetes, depression and other conditions.

More information about AHRQ’s guides and the Effective Health Care program can be found at www.effectivehealthcare.ahrq.gov.

Posted by dlifenews at 10:34 AM | Comments (0)

Less of a Stink in Diabetes Patients?

March 16, 2009

March 16, 2009 (EurekAlert) - Hydrogen sulfide (H2S) is commonly associated with smell of rotten eggs, stink bombs and blocked drains but lower blood levels of the gas are possibly linked to cardiovascular complications in some male patients with type II diabetes, according to research recently presented by researchers at the Peninsula Medical School in the South West of England at the Annual Diabetes UK Professional Conference in Glasgow this week and published in Diabetic Medicine.

H2S is produced naturally within our bodies, along with other chemical compounds such as nitric oxide, where it is believed to help regulate blood pressure. Research shows that a balance between these compounds relates to good health, whereas an imbalance could indicate disease. In the case of diabetes, common complications of the disease are high blood pressure and microvascular dysfunction, which leads to damage of the tiny blood vessels (microvessels) that deliver blood, oxygen and nutrients to the eyes, skin, nerves and kidney.

Dr. Matt Whiteman of the Peninsula Medical School and colleagues from the Peninsula National Institute for Health Research (NIHR) Clinical Research Facility have compared the levels of H2S in blood samples taken from healthy people and male patients with type II diabetes and found markedly decreased levels of H2S in the diabetes patients. Lower H2S levels were associated with clinical markers of impaired microvessel function suggesting that a loss of this blood pressure lowering gas could be a contributing factor in the development of vascular complications in patients with diabetes.

Previous work on H2S has almost exclusively been carried out on animals in the laboratory however work carried out at PMS in the recently opened Peninsula NIHR Clinical Research Facility has been the first to investigate the role of H2S in any disease in humans. Dr. Whiteman commented: "Our previous work in the test tube has shown the potential for H2S to mediate blood pressure regulation. However, this is the first study examining H2S levels in a human disease with relevant clinical indices of vascular health."

He added: "It would appear that in this study, male patients with diabetes have lower levels of H2S in their blood compared to otherwise healthy males of the same age. Lower levels of H2S could effect how blood vessels dilate. Although these are early days in a new field of research, manipulation of H2S levels by novel or existing pharmacological or even dietary means in the future could help treat or prevent cardiovascular complications caused by diabetes and other related conditions."

Posted by dlifenews at 09:37 AM | Comments (0)

Muscling In On Type 2 Diabetes

February 26, 2009

February 26, 2009 (EurekAlert) - Research by kinesiology investigator Dustin Hittel, PhD, has proven that muscle in extremely obese individuals produces large amounts of a protein called myostatin, which normally inhibits muscle growth—suggesting that for Type 2 diabetics, and the very obese, the task of getting healthy may be more difficult than initially thought.

It has been known for some years that naturally occurring mutations in the gene which controls myostatin results in double—muscling in cattle, dogs and even humans. Many in the body building community believe that blocking myostatin is a shortcut to the Arnold Schwarzenegger body.

The flipside is that producing too much myostatin has been linked with muscle wasting conditions such as HIV-AIDS, starvation and now, Type 2 diabetes.

Hittel believes this may be due to a pre-diabetic condition known as insulin resistance that "tricks" the muscles into thinking the body is starving despite the fact that blood sugar levels are skyrocketing.

"When that happens, the body reverses muscle production using myostatin," says Hittel. "This is particularly worrisome because losing muscle mass further erodes your ability to control your blood sugar with exercise."

One of the tell-tale signs of the transition between insulin resistance and full-blown Type 2 diabetes is a loss of muscle mass.

"Losing muscle mass makes sense from an evolutionary perspective since having large muscles during famine puts you at a serious risk for starvation," explains Hittel. "Unfortunately, this survival mechanism has left us ill-equipped to deal with a Western lifestyle—lots of calories, little exercise—and it has laid the groundwork for the current epidemic of Type 2 diabetes."

"The goal of my research is to understand how obesity, diet and exercise influence our metabolism and interact with our genome. This research sheds some light on an important part of the puzzle."

Posted by dlifenews at 09:40 AM | Comments (1)

It’s Risky Business To Ignore Diabetes

February 17, 2009

February 17, 2009 (Newswise) - American Diabetes Association urges the nearly 60 million Americans who are at risk for developing type 2 diabetes to take the Diabetes Risk Test.

WHAT: On Tuesday, March 24th, 2009, the Association will observe the 21st Annual American Diabetes Alert Day – a one-day call to action encouraging all Americans to take the Diabetes Risk Test and find out if they are in danger of developing type 2 diabetes.

WHO: The American Diabetes Association is leading the fight against the deadly consequences of diabetes and fighting for those affected by the disease. The Association funds research to prevent, cure and manage diabetes; delivers services to hundreds of communities; provides objective and credible information; and gives voice to those denied their rights because of diabetes. Founded in 1940, our mission is to prevent and cure diabetes and to improve the lives of all people affected by diabetes.

WHEN: Tuesday, March 24, 2009

WHY: Diabetes is a silent killer that slowly takes away people’s health, their money, their time, and their dreams. It’s a silent killer because people can have diabetes for years and not even know it. Diabetes affects so many of your readers – nearly 24 million children and adults in the United States have diabetes, and another 57 million Americans have pre-diabetes, where blood glucose levels are higher than normal but not yet high enough to warrant an official diagnosis.

One in five Americans is at risk for developing type 2 diabetes or may have the disease and not even know it. If left untreated, it can lead to deadly complications including heart disease, kidney failure, blindness, stroke and amputation, which is why it’s so important to make them aware of their own risk.

HOW: To let your readers know about The Diabetes Risk Test and American Diabetes Alert Day. Interviews with an American Diabetes Association spokesperson are available upon request.

The Diabetes Risk Test is free and is available in English and Spanish by calling the Association at 1-800-DIABETES (1-800-342-2383) or online at www.diabetes.org/alert.

Posted by dlifenews at 04:12 PM | Comments (0)

Physicians Agree Moderate Weight Loss Will Help Patients Manage Their Type 2 Diabetes

January 21, 2009

January 21, 2009 (Newswise) - Physicians say they are counseling their overweight type 2 diabetes patients to lose weight, but patients say that the message is not getting through, according to a new survey announced today by the Behavioral Diabetes Institute.

Eight in 10 physicians surveyed said that they discuss weight issues with their patients every/almost every visit, yet half as many patients – only four in 10 – report having these discussions with such frequency. In particular, roughly half of overweight patients and a third of obese patients say their physician seldom or never discusses their weight with them.

Almost all of surveyed physicians (85 percent) acknowledge that losing even a little weight can help manage type 2 diabetes. When discussing weight issues with their patients, 90 percent of physicians surveyed report that they tell their overweight patients to lose weight. However, when the surveyed patients were asked whether or not their doctor ever suggested that they lose weight, only 66 percent of them said yes.

“Type 2 diabetes is often associated with obesity. Losing weight can help to improve blood glucose, blood pressure, cholesterol and so much more. But it is notoriously difficult to lose weight and to keep it off and this can be even more difficult for someone with diabetes,” said Founder and Chief Executive Officer of the Behavioral Diabetes Institute William Polonsky, PhD, CDE. “Genetics and our immediate, food-rich environment play large roles in making weight loss tough, but disconnects between physicians and patients can make weight loss efforts even more difficult and frustrating.”

The phone survey conducted by Yankelovich, part of The Futures Company, assessed the behaviors, opinions and attitudes of 703 people with type 2 diabetes and 200 physicians that treat patients with type 2 diabetes. The survey was conducted in the fall of 2008 on the heels of the release of the American Diabetes Association and the European Association for the Study of Diabetes consensus statement placing increased focus on weight management as a treatment consideration in type 2 diabetes care.

According to the U.S. Centers for Disease Control and Prevention (CDC), 23.6 million people in the United States have diabetes, an increase of more than 3 million in two years. This means that 7.6 percent of the U.S. population has diabetes, mostly type 2 diabetes, which is linked with obesity, improper diet and a lack of exercise. Estimates show that another 57 million people have pre-diabetes, a condition that puts people at increased risk for diabetes. In addition, about two-thirds of U.S. adults—133.6 million—are overweight. Of these, 63.3 million are obese.

The survey also found that when physicians and their type 2 diabetes patients are talking about weight loss, it is not always in specifics. While more than half of patients do report having been referred to a dietitian or diabetes educator, told to eliminate certain foods from their diet and receiving literature about weight loss, only 27 percent of patients say their physician prescribed specific recommendations for exercise and less than 20 percent say their physician suggested a commercial diet plan such as Weight Watchers. And, even though more than half of the physicians said their patients understand that diabetes medications can cause weight gain, only 34 percent of surveyed patients report being warned by their physician that this could occur.

In addition to the communication gap, the survey found a number of other barriers impacting physicians’ and patients’ abilities to properly manage weight as part of diabetes treatments.

• Physicians see patients’ reluctance to change lifestyle as the biggest barrier to achieving the level of care they would like for their patients.

• While some physicians say that their patients don’t try hard enough to lose weight, they also recognize that willpower alone is not enough. However, nearly half of surveyed patients (46 percent) believe that losing weight is mostly a matter of willpower and if they try hard enough, they can lose weight.

• Physicians see the lack of support for education services and prevention by the healthcare system as another major barrier to successful treatment of type 2 diabetes.

“There are effective strategies for overcoming the weight management obstacles patients with type 2 diabetes face. Physicians and patients can start by talking together about the best ways to manage weight by developing a comprehensive plan of action that includes diet, exercise and the right medications,” Dr. Polonsky said.

For more information about behavioral strategies for successful weight loss and diabetes management, visit the Behavioral Diabetes Institute (www.behavioraldiabetes.org).

Easy Tips for Patients with Type 2 Diabetes to Successfully Manage Their Weight:

• Ask your doctor about diabetes therapies that help control blood glucose and weight

• Work with a diabetes-knowledgeable dietitian or diabetes educator to develop a realistic weight loss plan and set specific goals for action

• Educate your loved ones about diabetes and your needs; ask for their support

• Adjust your immediate home environment so that it supports, rather than sabotages, your weight loss efforts

• Create new eating and exercise habits

Easy Tips for Physicians to Successfully Manage Their Type 2 Diabetes Patients’ Weight:

• Don’t be reluctant about discussing the importance of weight loss issues with your patients, but do so in a way that is not blaming, shaming or judgmental

• Refer your patients to weight loss programs and health care professionals in your area who specialize in nutrition and weight management

• Provide your patients with basic tools to enable them to make appropriate lifestyle changes

• Reinforce the importance of setting manageable, achievable goals

• Encourage your patients to be patient with their own efforts and progress; acknowledge with them that weight management is not easy and occasional setbacks are common

• In a collaborative and caring manner, remember to ask your patients how they are doing each and every visit

Posted by dlifenews at 10:12 AM | Comments (6)

Joslin Launches National Study To Explore If Anti-Inflammatory Drug Can Treat Type 2 Diabetes

January 21, 2009 (EurekAlert) - Joslin Diabetes Center scientists are taking groundbreaking research on the role of inflammation in type 2 diabetes to a new level with the launch of a national clinical trial to investigate whether salsalate, an anti-inflammatory drug used for years to manage arthritis pain, can reduce blood glucose levels in people with type 2 diabetes. If successful, the trial could lead one day to an inexpensive way to treat this most common form of diabetes, which has been increasing at epidemic rates in recent years.

About 560 adults with poorly controlled blood glucose levels are being sought to participate for one year in a clinical research study, referred to as Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D). The study is being funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health. The study will be conducted at Joslin in Boston and at about 20 other medical institutions across the nation.

Initial studies by the Joslin group showed that salsalate was effective to lower blood glucose when given for 3 months, leading to the start of this larger trial of longer duration.

"These are very important studies aimed to test whether reducing inflammation can actually be used to treat diabetes," says principal investigator Steven E. Shoelson, M.D., Ph.D., the Helen and Morton Adler Chair and Associate Director of Research at Joslin Diabetes Center and Professor of Medicine at Harvard Medical School. "Given what we are learning about how type 2 diabetes develops, we think this might be getting at an underlying cause. We hope the study shows that targeting inflammation is a safe and inexpensive way to treat type 2 diabetes. We also hope that reducing inflammation decreases risk for coronary heart disease, which is another theory that we will be testing in a separate clinical study in the coming months."

In the United States, nearly 24 million people have diabetes. Type 2 diabetes accounts for about 90 to 95 percent of diagnosed cases, representing nearly 10 percent of the adult population. Type 2 diabetes, previously called adult onset or non-insulin dependent diabetes, is a disorder in which muscle and fat cells do not use insulin properly. Type 2 diabetes is closely linked to obesity and puts people who have the disease at greater risk for complications, including cardiovascular disease, blindness, kidney disease and amputations. People with type 2 diabetes die at rates two- to four-times higher than those who do not have diabetes.

"Sedentary lifestyle and western diet have been associated with obesity and diabetes," says co-principal investigator Allison B. Goldfine, M.D., Director of Clinical Research at Joslin and Associate Professor of Medicine at Harvard Medical School. "The study medication, salsalate, which is chemically similar to aspirin but has fewer side effects, has been used for more than 40 years in people to treat pain associated with arthritis. Recent studies in people show that salsalate also lowers blood glucose, but further testing on long-term efficacy and safety specifically in patients with diabetes needs to be done."

"The outcome of this study has the potential for significant public health benefit," said Myrlene Staten, M.D., NIDDK's Senior Advisor for Diabetes Translational Research. "If salsalate improves the control of type 2 diabetes, we would have an inexpensive addition to our arsenal of drug options."

In previous studies Drs. Shoelson and Goldfine and their collaborators found that inflammation – an immune system response that normally fights infection and promotes healing – plays a major role in the development of insulin resistance and type 2 diabetes. These researchers were the first to show that a major trigger of inflammation – the transcription factor NF-kB – is activated in fat, liver, and other tissues of the body, perhaps providing the "missing link" between obesity and diabetes.

In a real bench-to-bedside victory, the researchers built on these discoveries by conducting clinical trials in patients with diabetes, testing anti-inflammatory salicylates, which inhibit NF-kB, as insulin sensitizers. In these patients, blood glucose and lipid levels substantially decreased, glucose uptake and utilization improved, and liver glucose production decreased. These findings of improved glycemia were recently confirmed when the drug was given for three months to patients with type 2 diabetes, laying the groundwork for the new clinical trial.

Posted by dlife at 10:08 AM | Comments (0)

Adult-Onset Diabetes Slows Mental Functioning In Several Ways, With Deficits Appearing Early

January 05, 2009

January 5, 2009 (EurekAlert) - Adults with diabetes experience a slowdown in several types of mental processing, which appears early in the disease and persists into old age, according to new research. Given the sharp rise in new cases of diabetes, this finding means that more adults may soon be living with mild but lasting deficits in their thought processes.

A full analysis appears in the January issue of Neuropsychology, which is published by the American Psychological Association.

Researchers at Canada's University of Alberta analyzed a cross-section of adults with and without adult-onset Type 2 diabetes, all followed in the Victoria Longitudinal Study. At three-year intervals, this study tracks three independent samples of initially healthy older adults to assess biomedical, health, cognitive and neurocognitive aspects of aging. The Neuropsychology study involved 41 adults with diabetes and 424 adults in good health, between ages 53 and 90.

The research confirmed previous reports that diabetes impairs cognition and added two important findings. First, it teased out the specific domains hurt by diabetes. Second, it revealed that the performance gap was not worse in the older group. Thus, the reductions in executive function and processing speed seem to begin earlier in the disease.

Healthy adults performed significantly better than adults with diabetes on two of the five domains tested: executive functioning, with significant differences across four different tests, and speed, with significant differences or trends across five different tests. There were no significant differences on tests of episodic and semantic memory, verbal fluency, reaction time and perceptual speed.

When researchers divided participants into young-old and old-old, with age 70 as the cutoff, they found the same pattern of cognitive differences between young-old and old-old in the diabetes and control groups. Thus, the researchers concluded, the diabetes-linked cognitive deficits appear early and remain stable.

"Speed and executive functioning are thought to be among the major components of cognitive health," says co-author Roger Dixon, PhD. With Type 2 diabetes a growing concern among adults of all ages, but especially those above age 30, Dixon says that public health programs could check the cognitive status of people with more advanced or severe cases; ensure that diet and medications are effectively employed in all early diagnosed cases; and enact possible cognitive monitoring or training programs for people with diabetes. According to the U.S. Centers for Disease Control and Prevention, new cases of diabetes nearly doubled in the past decade, with nearly one new case for every 100 adults between the years 2005 and 2007.

The normal age-related slowing of thought processes could be exacerbated by diseases such as Type 2 diabetes, says Dixon. But, he continues, "There could be some ways to compensate for these declines, at least early and with proper management." The level of impairment detected, he adds, should not make it hard for people to manage their condition.

Diabetes is a known risk factor for late-life neurodegenerative diseases such as Alzheimer's. Although the deficits detected in the current sample were not clinically significant, they appear (according to subsequent research by the authors) to foreshadow additional deficits. Only further study would reveal whether it's possible to "connect the dots" between mild early deficits in speed and executive function, and later signs of a progressive cognitive impairment.

Posted by dlifenews at 02:37 PM | Comments (1)

ESC Statement On The Control Of Type 2 Diabetes

December 19, 2008

December 19, 2008 (EurekAlert) - A study published by the Journal of the American Medical Association (JAMA) on 16 December 2008 has found that those with type 2 diabetes who had a diet high in low-glycemic foods such as nuts, beans and lentils had greater improvement in glycemic control and risk factors for coronary heart disease than those on a diet with an emphasis on high-cereal fibre.

The study gives further weight to the lifestyle advice currently recommended for the control of diabetes, says Professor Lars Ryden (Karolinska University Hospital, Stockholm, Sweden), ESC Spokesperson for diabetes and cardiovascular disease, who adds: "Treatment of type 2 diabetes should always be initiated with structured life-style advice. This is clearly highlighted in the ESC/EASD Guidelines for diabetes, pre-diabetes and cardiovascular disease. Results from the JAMA study suggest that such advice may be as effective as some drug interventions

"The JAMA study also shows that a well balanced diet will improve not only blood glucose tolerance but also blood lipid levels, which are of great importance in decreasing cardiovascular complications. If drugs are still needed in these circumstances, their dose and number may be lower.

"Subjects with type 2 diabetes should also be aware that it is important to avoid excess weight, and the diet described in the study may help achieve this goal."

Speaking specifically about the study Professor Joep Perk (Oskarshamn District Hospital, Sweden), an ESC spokesperson on the subject of cardiovascular prevention, said that the study was of relatively short duration (six months) in 210 patients; a diet high in low-glycemic foods resulted in a modest decrease in HbA1c levels when compared to a high-cereal fibre diet.

"The main finding of the study – a significant increase of HDL levels and a greater reduction in the LDL/HDL ratio - may provide the rationale for long-term interventional studies. However, in the absence of these studies it is still premature to change the current practice of dietary counseling for type 2 diabetes patients," said Professor Perk.

Posted by dlife at 01:46 PM | Comments (0)

FDA Announces New Recommendations on Evaluating Cardiovascular Risk in Drugs Intended to Treat Type 2 Diabetes

December 17, 2008

December 17, 2008 (FDA) --The U.S. Food and Drug Administration recommended today that manufacturers developing new drugs and biologics for type 2 diabetes provide evidence that the therapy will not increase the risk of such cardiovascular events as a heart attack. The recommendation is part of a new guidance for industry that applies to all diabetes drugs currently under development.

"We need to better understand the safety of new antidiabetic drugs. Therefore, companies should conduct a more thorough examination of their drugs' cardiovascular risks during the product's development stage," said Mary Parks, M.D., director, Division of Metabolism and Endocrinology Products, Center for Drug Evaluation and Research (CDER), FDA. "FDA's guidance outlines the agency's recommendations for doing such an assessment."

More than 23 million people in the United States have been diagnosed with type 2 diabetes or diabetes mellitus, a chronic metabolic disorder characterized by abnormally high blood sugar levels known as hyperglycemia.

Patients with diabetes have a two- to four-times greater risk of heart disease than their non-diabetic counterparts, and none of the currently approved antidiabetic therapies has been convincingly proven to reduce that risk. Because diabetes often requires life-long treatment, prescribers and patients need to know more about whether their antidiabetic therapies put patients at increased risk of heart attack. This is the purpose of today's guidance, which has benefited from the July 2008 recommendation from FDA's Endocrinologic and Metabolic Drugs Advisory Committee.

The guidance, which is effective immediately, defines more robust and adequate design and data collection approaches for Phase 2 and Phase 3 clinical trials than were previously required. Specifically, the guidance recommends that these studies demonstrate that new antidiabetic therapies do not increase cardiovascular risk in comparison with existing therapies -- especially when the drugs are used by patients of advanced age or by those with advanced diabetes or renal impairment.

The FDA also recommends that manufacturers have any cardiovascular events in their clinical trials analyzed by committees of outside cardiologists who are unaware of which patients received the tested products and which were on placebo. Based on these evaluations, the FDA can better ensure that product labeling includes comprehensive information on safety and effectiveness. This will enable prescribers and patients to make better-informed decisions on the management of type 2 diabetes.

The FDA remains confident that currently marketed antidiabetic therapies are safe and effective when used according to approved labeling and advises patients to work with their healthcare professionals to select the most appropriate therapy to achieve adequate blood glucose control. The FDA is continuing to evaluate how today's recommendations will be applied to already approved antidiabetic drugs and expects to release further guidance on this issue in the future.

The FDA's guidance and its ongoing evaluation of this issue supports our approach to drug regulation throughout the product life-cycle, by evaluating a drug's safety before and after its approval," said Janet Woodcock, M.D., director, CDER, FDA.

"Diabetes Mellitus – Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes" is posted on FDA's website at http://www.fda.gov/cder/guidance/8576fnl.pdf. It will be published in the Federal Register on December 19, 2008. In addition, the FDA has provided written notice of the recommendations from this guidance to more than 100 manufacturers who have submitted investigational new drug applications for type 2 diabetes treatment.

Posted by dlifenews at 04:54 PM | Comments (2)

CPAP Improves Sleeping Glucose Levels In Type 2 Diabetes Patients With OSA

December 15, 2008

December 15, 2008 (EurekAlerthttp://www.eurekalert.org/pub_releases/2008-12/aaos-cis121108.php) - A study in the Dec. 15 issue of the Journal of Clinical Sleep Medicine suggests that screening type 2 diabetes patients for obstructive sleep apnea (OSA) and treating those who have OSA with continuous positive airway pressure (CPAP) therapy could improve the management of their hyperglycemia and might favorably influence their long-term prognosis.

Results show that in a group of 20 type 2 diabetics who were mostly obese and were newly diagnosed with OSA, sleeping and nocturnal hyperglycemia were reduced and the sleeping interstitial glucose level was less variable during CPAP treatment. The average glucose level during sleep decreased by approximately 20 mg/dl after an average of 41 days of CPAP. The sleeping glucose also was more stable after treatment, with the median standard deviation decreasing from 20.0 to 13.0 and the mean difference between maximum and minimum values decreasing from 88 to 57.

According to Arthur Dawson, MD, senior consultant in the Division of Chest and Critical Care Medicine and co-director of research at Scripps Clinic Sleep Center in La Jolla, Calif., it is not surprising that many diabetics have sleep apnea since type 2 diabetes and OSA are both conditions that are becoming much more common because of the obesity epidemic.

Dawson said, "The low blood oxygen level and the arousals associated with an apneic event activate the sympathetic nervous system and cause the release of stress hormones, both of which tend to raise the blood glucose. If we could prevent these apneic events with CPAP then we might keep the glucose level lower and more stable through the night."

According to the authors, population surveys, the Wisconsin Sleep Cohort and the Sleep Heart Health Study estimate the prevalence of type 2 diabetes in patients with OSA to be about 15 percent. OSA is associated with increased insulin resistance independent of obesity; 50 percent of patients with OSA have type 2 diabetes or impaired carbohydrate metabolism.

Twenty patients with type 2 diabetes who were on a stable diabetic regime were recruited at the time of their initial consultation with a sleep physician. All participants were newly diagnosed with moderate to severe OSA, and none had any previous experience with CPAP. Glucose level was monitored with a continuous glucose monitoring system (CGMS) over a period of 36 hours, which included a night in a sleep laboratory for evaluation by polysmnography. On the first night of the study, patients' OSA was untreated. A second night of glucose monitoring and sleep recording was done after the participants had been on CPAP therapy for a duration of one-to-three months. No changes were made in participants' diets or medication for diabetes throughout the study.

The authors report that previous studies have shown that variability of the glucose level increases the risk of eye complications and death in type 2 diabetics. Dawson said that the authors believe that recognizing and treating sleep apnea could improve the outlook for diabetics who also suffer from OSA. Researchers involved in this study theorized that by using the CGMS they were able to pick up short-term changes in the glucose level that would not be detected by traditional measurements.

Posted by dlife at 04:03 PM | Comments (1)

Overweight Siblings Of Children With Type 2 Diabetes Likely To Have Abnormal Blood Sugar Levels

December 09, 2008

December 9, 2008 (EurekAlert) - Overweight siblings of children with type 2 diabetes are four times more likely to have abnormal glucose levels compared to other overweight children. Because abnormal glucose levels may indicate risk for diabetes or diabetes itself, these children could benefit from screening tests and diabetes prevention education.

Researchers from The Children's Hospital of Philadelphia published their findings today in the online edition of the Journal of Pediatrics.

"To our knowledge, previous studies have not specifically looked at the risk of abnormal glucose tolerance among siblings of children diagnosed with type 2 diabetes. This group has a unique combination of genetic and environmental risk factors," said Sheela N. Magge, M.D., M.S.C.E., a pediatric endocrinologist at The Children's Hospital of Philadelphia and primary author of the study. "Clinical experience suggests that children with type 2 diabetes often have an obese sibling, which makes siblings an appropriate target for prevention trials."

The study looked at 62 children: 20 obese subjects with a sibling who had type 2 diabetes and a control group of 42 obese children. The groups were similar for age, gender, racial distribution (predominantly African American), pubertal status and body mass index over 95th percentile.

The researchers found that overweight siblings of children with type 2 diabetes had four times greater odds of having abnormal glucose levels (impaired glucose tolerance or type 2 diabetes) than other overweight children. However, investigators found no significant differences in insulin resistance, as measured by the homeostasis model assessment.

Type 2 diabetes is caused by a combination of both genetic and environmental factors. Known risks include obesity, decreased physical activity, race/ethnicity, family history and insulin resistance. Obesity decreases insulin sensitivity, as does puberty, when all adolescents experience a period of relative insulin resistance. In obese adolescents already at risk of developing type 2 diabetes, the increase in insulin resistance during puberty may be enough to unmask disease. Family history is also important; 74 to 100 percent of children with type 2 diabetes have a first- or second-degree relative who also has the condition.

Not all children with a family history of type 2 diabetes, insulin resistance or obesity develop type 2 diabetes, cautions Dr. Magge.

The researchers also add that identifying groups at high risk for type 2 diabetes during childhood, such as obese siblings of children with type 2 diabetes, could help guide screening of obese children for abnormal glucose tolerance by primary care providers. This could also help to identify children who might benefit from participation in future type 2 diabetes prevention studies.

Posted by dlife at 09:36 AM | Comments (0)

Increasing Physical Activity And Limiting Television May Lead To Reduction In Type 2 Diabetes

December 08, 2008

December 8, 2008 (EurekAlert) - Researchers from Boston University's Slone Epidemiology Center have found that reducing time spent watching television and increasing time spent walking briskly or engaged in vigorous physical activity may reduce the incidence of type 2 diabetes in African-American women. These findings appear on-line in the American Journal of Epidemiology.

Type 2 diabetes has reached epidemic proportions in the U.S. and affects an estimated 20.6 million people. African-American women make up a significant percentage of that population. Although previous studies support a role for physical activity in preventing type 2 diabetes, there has been little attention focused on the impact of this factor in the high-risk population of African-American women.

Using data collected through questionnaires in the Black Women's Health Study, (an ongoing prospective follow-up study of African–American women from across the U.S.), the researchers found that vigorous activity was inversely associated with a reduced risk of diabetes. Brisk walking (for five plus hours/week) was also associated with a reduced risk of diabetes, as compared to no walking.

Television watching was positively associated with an increased risk of diabetes. The researchers found the risk of type 2 diabetes was increased among women who spent an appreciable amount of time watching television. This increase was apparent whether or not a woman was physical active.

"Our results confirm that vigorous activity is protective against type 2 diabetes in African-American women," said study author Julie Palmer, a professor of epidemiology at the Slone Epidemiology Center at Boston University. "A key public health finding is that brisk walking reduced risk. That is important because many women don't have the time or place to engage in "vigorous" physical activity, but most women can find time to walk," added Palmer.

Posted by dlife at 09:50 AM | Comments (0)

Why Do Sulfonylureas Fail Amongst People With Type 2 Diabetes?

October 27, 2008

October 27, 2008 (EurekAlert) - Sulfonylurea drugs, such as glibenclamide, are widely used for the treatment of type 2 diabetes. These drugs work by causing pancreatic beta cells to release insulin, which occurs when the drug inhibits ATP-sensitive potassium channels, causing calcium to enter the beta cells which then stimulates release of insulin, and consequently a fall in blood glucose levels. However, long term treatment with sulfonylureas eventually fails, but the mechanism is not known.

In a series of mouse experiments published in this issue of PLoS Medicine, Maria Remedi and Colin Nichols from the Washington University School of Medicine explore the mechanisms underlying this treatment failure, and suggest how that failure might be prevented. Their results show that the failure of treatment is not due to sulfonylurea treatment causing death of the pancreatic beta cells, but rather permanent depolarization of the beta cell potassium channels. These studies also show that in mice treated with slow-release sulfonylureas, failure to release insulin is reversible on removal of drug treatment.

The findings suggest that new approaches to sulfonylurea dosing, for example testing low-doses or pulsed doses, may prevent treatment failure. However, new treatment approaches would need to be evaluated first in animals before progressing to clinical testing.

The implications of this study are discussed in a linked Perspective by Erik Renstrom and colleagues from Lund University.

Posted by dlife at 10:57 AM | Comments (1)

ADA/EASD Statement: Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy

October 22, 2008

October 22, 2008 (Media Statement) - Today the American Diabetes Association and the European Association for the Study of Diabetes published an update to the consensus algorithm for the medical management of type 2 diabetes in Diabetes Care and Diabetologia. Amylin and Lilly believe that it is important for physicians to have this treatment guidance to help them assess the best combination of medical support to treat their diabetes patients. We are pleased that this update takes into account new classes of medications important to the overall treatment of diabetes, including GLP-1 receptor agonists such as BYETTA, the first and only FDA approved treatment in the GLP-1 class.

Type 2 diabetes is a complex metabolic condition, which often requires a combination of treatments to help patients manage the many complications associated with the disease. The updated consensus algorithm includes two tiers of treatment recommendations: “Tier 1” to guide the use of core therapies and “Tier 2” to guide the use of newer medications. The use of a GLP-1 receptor agonist, such as BYETTA, is recommended as part of the “Tier 2” treatment algorithm for patients who need additional help lowering glucose levels following initial treatment with metformin, when weight loss is recommended and when hypoglycemia is of concern. The importance of treating A1C and weight should not be underestimated, as 80-90 percent of patients with type 2 diabetes are overweight or obese. The guidelines note that modest weight loss, on the order of 4 kg, has beneficial effects on glycemia and improves coincident CVD risk factors.

BYETTA differs in chemical structure and glucose-lowering actions from insulin and the commonly used oral agents used to treat diabetes. No other compounds currently available to treat diabetes, such as sulfonylureas, metformin, thiazolidinediones, DPP-4s, or insulin, work in this same way. As the only FDA-approved GLP-1 receptor agonist, BYETTA has consistently shown powerful HbA1c reductions with sustained weight loss and no increased risk of hypoglycemia in combination with metformin and/or TZDs and is an important treatment consideration for patients with type 2 diabetes.

Posted by dlife at 05:22 PM | Comments (4)

Proteins Involved In Blood Vessel Dysfunction In Type 2 Diabetes Are Identified

October 06, 2008

October 6, 2008 (EurekAlert) - According to the American Heart Association, three-fourths of people with diabetes die of some form of heart or blood-vessel disease. Previous studies have shown that cardiac function is compromised and cardiovascular diseases are increased in people with type 2 diabetes. Before vascular diseases develop in diabetics, blood-vessel cell dysfunction occurs. Using precise microscopes, University of Missouri researchers are dissecting coronary microvessels and testing which proteins are responsible for inflammation that causes blood-vessel dysfunction. By identifying the proteins that play important roles in blood-vessel dysfunction, they hope to develop new treatments for blood-vessel dysfunction in people with type 2 diabetes.

"We believe that understanding blood-vessel dysfunction in diabetes is critical because the progression of vascular diseases may be significantly reduced if dysfunction is corrected," said Cuihua Zhang, an investigator in the Dalton Cardiovascular Research Center and associate professor of internal medicine in the MU School of Medicine. "The results of our studies may provide new approaches for the treatment of blood-vessel diseases and disorders in type 2 diabetes, such as the possible use of antibodies that work to stop the proteins responsible for inflammation."

Zhang and other researchers tested their hypothesis that tumor necrosis factor-α (TNF-α), a signaling protein involved in inflammation, was responsible for blood-vessel dysfunction in type 2 diabetes. They observed that diabetic mice had elevated levels of TNF. When diabetic mice lacked TNF, their blood vessels functioned normally. They also observed that advanced glycation end products and their receptors (AGE/RAGE), which are proteins and lipids that are thought to contribute to various blood vessel complications, amplified TNF production in diabetes. In patients with diabetes, AGEs accumulate more quickly than normal in the blood and arteries.

"We found that the overproduction of AGE and RAGE contributes to blood-vessel dysfunction in type 2 diabetes," Zhang said. "Changes in the blood vessels caused by these proteins cause oxidative stress and vascular dysfunction that leads to diseases such as heart disease and stroke."

Posted by dlife at 03:53 PM | Comments (0)

ONGLYZA™ (saxagliptin) With Metformin as Initial Combination Therapy Significantly Lowered A1C and Demonstrated Significant Improvements Across Key Measures of Glucose Control in Treatment Naïve People With Type 2 Diabetes

September 09, 2008

September 9, 2008 (Press Release) - Results from a 24-week Phase III study presented at the 44th European Association for the Study of Diabetes Annual Meeting demonstrated that ONGLYZA™ (saxagliptin), an investigational selective inhibitor with extended binding to the dipeptidyl peptidase-4 (DPP-4) enzyme in development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN), when used in combination with metformin as an initial therapy, produced significant reductions across all key measures of glucose control studied [glycosylated hemoglobin level (A1C), fasting plasma glucose (FPG) and postprandial glucose (PPG)] in treatment naïve people with inadequately controlled type 2 diabetes, compared to monotherapy with saxagliptin or metformin. The initial combination of saxagliptin and metformin was well tolerated over the course of the study, and significantly more people were able to achieve target A1C of less than 7 percent, compared to monotherapy with saxagliptin or metformin.

The companies submitted a New Drug Application to the U.S. Food & Drug Administration (FDA) on June 30, which has been officially filed by the FDA, and a Marketing Authorization Application to the European Medicines Agency (EMEA) on July 1, which has been accepted for review by the Agency. The submissions are based on data from a comprehensive clinical trial program conducted in addition to standard therapies, as well as in treatment naïve patients as a monotherapy. The clinical trial program included studies that evaluated the drug at up to 80 times the proposed usual clinical dose of 5 mg, once daily. The six core Phase III trials assessing the safety and efficacy of saxagliptin involved more than 4,000 patients, including 3,000 who were treated with saxagliptin. The companies have proposed the name ONGLYZA which, if approved by the FDA and the EMEA, will serve as the trade name for saxagliptin.

About the Study
The study was designed to assess saxagliptin as an initial combination therapy with metformin vs. each agent alone. The data represent findings from a 24-week, randomized, double-blind, active-controlled study of 1,306 people with type 2 diabetes (ages 18-77) who were treatment naïve and whose A1C level was greater than or equal to 8 percent and less than or equal to 12 percent. After a one-week placebo lead-in phase, individuals were randomized to one of four separate treatment arms: saxagliptin 5 mg + metformin 500 mg (n=320), saxagliptin 10 mg + metformin 500 mg (n=323), saxagliptin 10 mg + placebo (n=335) or metformin 500 mg + placebo (n=328), given daily. From Week 1 to Week 5, in the saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin and metformin + placebo treatment arms, metformin was up-titrated weekly in 500 mg increments, as tolerated, to a maximum total daily dose of 2,000 mg, based on levels of FPG (a measure of a person’s blood glucose after at least eight hours of fasting).

The primary endpoint of the study was the change from baseline to Week 24 in A1C. The secondary endpoints included the proportion of individuals achieving the American Diabetes Association recommended A1C target of less than 7 percent, the proportion of individuals achieving the International Diabetes Federation recommended A1C target of less than or equal to 6.5 percent and changes from baseline in FPG and PPG, measured during an oral glucose tolerance test [OGTT]).

Study Results
After 24 weeks, individuals in the saxagliptin + metformin treatment arms demonstrated a significant adjusted mean change in A1C from baseline of -2.5 percent for saxagliptin 5 mg + metformin and -2.5 percent for saxagliptin 10 mg + metformin, compared to -1.7 percent for saxagliptin 10 mg + placebo and -2.0 percent for metformin + placebo (p-value less than 0.0001 for both treatment arms).

A greater percentage of individuals treated with saxagliptin in combination with metformin achieved A1C of less than 7 percent: 60.3 percent for saxagliptin 5 mg + metformin and 59.7 percent for saxagliptin 10 mg + metformin, compared to 32.2 percent for saxagliptin 10 mg + placebo and 41.1 percent for metformin + placebo (p-value less than 0.0001 for both treatment arms). A greater percentage of individuals treated with saxagliptin in combination with metformin also achieved A1C of less than or equal to 6.5 percent: 45.3 percent for saxagliptin 5 mg + metformin and 40.6 percent for saxagliptin 10 mg + metformin, compared to 20.3 percent for saxagliptin 10 mg + placebo and 29.0 percent for metformin + placebo (p-value less than or equal to 0.0026 for both treatment arms).

Individuals treated with saxagliptin in combination with metformin demonstrated a significant adjusted mean change in FPG from baseline: -60 mg/dL for saxagliptin 5 mg + metformin and -62 mg/dL for saxagliptin 10 mg + metformin, compared to -31 mg/dL for saxagliptin 10 mg + placebo and -47 mg/dL for metformin + placebo (p-value less than or equal to 0.0002 for both treatment arms). The two saxagliptin + metformin treatment arms also demonstrated significant adjusted mean decreases in PPG from baseline, compared to either monotherapy.
Over 24 weeks, the incidence of adverse events was: 55.3 percent for saxagliptin 5 mg + metformin, 57.3 percent for saxagliptin 10 mg + metformin, 53.4 percent for saxagliptin 10 mg + placebo and 58.5 percent for metformin + placebo. The percentages of the most commonly reported (greater than or equal to 5 percent) adverse events for saxagliptin from the saxagliptin 5 mg + metformin, saxagliptin 10 mg + metformin, saxagliptin 10 mg + placebo and metformin + placebo treatment arms, respectively, were: nasopharyngitis [6.9, 2.5, 4.2, 4.0], headache [7.5, 9.9, 6.3, 5.2], diarrhea [6.9, 9.6, 3.0, 7.3] and hypertension [4.7, 5.3, 4.5, 3.4].

The reported hypoglycemic events were: 3.4 percent for saxagliptin 5 mg + metformin, 5.0 percent for saxagliptin 10 mg + metformin, 1.5 percent for saxagliptin 10 mg + placebo and 4.0 percent for metformin + placebo. The occurrence of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50 mg/dL) was: two cases (0.6 percent) in the saxagliptin 10 mg + metformin group and one case (0.3 percent) in the metformin + placebo monotherapy group, with no cases of confirmed hypoglycemia in the saxagliptin 5 mg + metformin or the saxagliptin 10 mg + placebo groups.

Similar reductions in weight were seen across all treatment groups. Mean change from baseline in body weight at Week 24 was: -1.8 kg for saxagliptin 5 mg + metformin, -1.4 kg for saxagliptin 10 mg + metformin, -1.1 kg for saxagliptin 10 mg + placebo and -1.6 kg for metformin + placebo.

Posted by dlife at 11:44 AM | Comments (1)

ONGLYZA™ (Saxagliptin) Demonstrated Significant Improvements Across Key Measures Of Glucose Control When Added To A Sulfonylurea Or Thiazolidinedione In People With Inadequately Controlled Type 2 Diabetes

September 08, 2008

September 8, 2008 (Press Release) - Results from two 24-week Phase III studies presented at the 44th European Association for the Study of Diabetes Annual Meeting demonstrated that ONGLYZA™ (saxagliptin), an investigational selective inhibitor with extended binding to the dipeptidyl peptidase-4 (DPP-4) enzyme in development by Bristol-Myers Squibb Company (NYSE: BMY) and AstraZeneca (NYSE: AZN), produced significant reductions across all key measures of glucose control studied [glycosylated hemoglobin level (A1C), fasting plasma glucose (FPG) and postprandial glucose (PPG)] when added to a sulfonylurea (SU) or a thiazolidinedione (TZD) in people with inadequately controlled type 2 diabetes, compared to placebo added to either an increased dose of SU or a stable dose of TZD. The addition of saxagliptin to SU or TZD was well tolerated over the course of the studies, and significantly more people were able to achieve target A1C of less than 7 percent versus the comparators.

The companies submitted a New Drug Application to the U.S. Food & Drug Administration (FDA) on June 30, which has been officially filed by the FDA, and a Marketing Authorization Application to the European Medicines Agency (EMEA) on July 1, which has been accepted for review by the Agency. The submissions are based on data from a comprehensive clinical trial program conducted in addition to standard therapies, as well as in treatment naïve patients as a monotherapy. The clinical trial program included studies that evaluated the drug at up to 80 times the proposed usual clinical dose of 5 mg, once daily. The six core Phase III trials assessing the safety and efficacy of saxagliptin involved more than 4,000 patients, including 3,000 who were treated with saxagliptin. The companies have proposed the name ONGLYZA which, if approved by the FDA and the EMEA, will serve as the trade name for saxagliptin.

“A large number of people with type 2 diabetes have difficulty managing their disease, and remain uncontrolled,” said Dr. Priscilla Hollander, Baylor University Medical Center, Director of Diabetes Programs, Dallas, Texas. “Given the growing number of people with diabetes around the world, it is important to investigate new therapeutic options as we fight this chronic disease.”

About the Study:
Saxagliptin Added to Sulfonylurea This study was designed to assess the addition of saxagliptin to a submaximal dose of sulfonylurea vs. increasing the dose of the sulfonylurea. The data represent findings from a 24-week, randomized, double-blind, placebo-controlled, three-arm, parallel-group, multi-center international study of 768 people with type 2 diabetes (ages 18-77) whose A1C level was greater than or equal to 7.5 percent and less than or equal to 10 percent after at least two months on a submaximal dose of a sulfonylurea at enrollment. After a four-week, open-label, lead-in phase, where all individuals received glyburide (GLY) 7.5 mg, individuals were randomized to one of three separate treatment arms: saxagliptin 2.5 mg + GLY 7.5 mg (n=248), saxagliptin 5 mg + GLY 7.5 mg (n=253), or placebo (PBO) + GLY 10 mg (n=267), given daily. In the PBO + GLY 10 mg group, blinded up-titration of GLY was allowed to a maximum total daily dose of 15 mg (UP-GLY). Approximately 92 percent of individuals in the UP-GLY group reached the maximum total daily dose during the study. The primary endpoint of the study was the change from baseline to Week 24 in A1C. The secondary endpoints of the study included changes from baseline to Week 24 in FPG, PPG response, as indicated by PPG area under the curve (AUC) from 0-180 minutes during an oral glucose tolerance test (OGTT), and the proportion of individuals achieving the American Diabetes Association recommended A1C target of less than 7 percent.

Study Results
After 24 weeks, individuals in the saxagliptin + GLY treatment arms demonstrated a significant adjusted mean change in A1C from baseline of -0.5 percent for saxagliptin 2.5 mg + GLY and -0.6 percent for saxagliptin 5 mg + GLY, compared to +0.1 percent for UP-GLY (p-value less than 0.0001 for both treatment arms). Reductions were observed at four weeks, the earliest assessment point in the study. More than twice as many individuals receiving saxagliptin + GLY achieved A1C of less than 7 percent compared to UP-GLY: 22.4 percent for saxagliptin 2.5 mg + GLY and 22.8 percent for saxagliptin 5 mg + GLY, compared to 9.1 percent for UP-GLY (p-value less than 0.0001 for both treatment arms).

Individuals treated with saxagliptin + GLY demonstrated a significant adjusted mean change in FPG from baseline to Week 24: -7.1 mg/dL for saxagliptin 2.5 mg + GLY and -9.7 mg/dL for saxagliptin 5 mg + GLY, compared to +0.7 mg/dL for UP-GLY (p-value less than or equal to 0.0218 for both treatment arms). Reductions were observed at two weeks, the earliest assessment point in the study. The two saxagliptin + GLY treatment arms also demonstrated significant adjusted mean decreases in PPG from baseline to Week 24, compared to UP-GLY (p-value less than 0.0001 for both treatment arms).

Over 24 weeks, the reported hypoglycemic events were: 13.3 percent for saxagliptin 2.5 mg + GLY, 14.6 percent for saxagliptin 5 mg + GLY and 10.1 percent for UP-GLY (p-value equals NS). The occurrence of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50 mg/dL) was: 2.4 percent for saxagliptin 2.5 mg + GLY, 0.8 percent for saxagliptin 5 mg + GLY and 0.7 percent for UP-GLY.

Incidence of adverse events was: 75.0 percent for saxagliptin 2.5 mg + GLY, 72.3 percent for saxagliptin 5 mg + GLY and 76.8 percent for UP-GLY. The percentages of the most commonly reported (greater than or equal to 5 percent) adverse events for the saxagliptin 2.5 mg + GLY, saxagliptin 5 mg + GLY and UP-GLY treatment arms, respectively, were: urinary tract infection [5.2, 10.7, 8.2]; nasopharyngitis [5.6, 5.9, 6.7]; upper respiratory tract infection [4.4, 6.3, 6.7]; influenza [5.2, 4.0, 6.0]; diarrhea [5.6, 4.0, 5.2]; back pain [4.8, 5.9, 4.5]; pain in extremity [4.4, 3.6, 5.6]; headache [7.7, 7.5, 5.6]; cough [5.2, 4.0, 4.9]; and hypertension [3.6, 6.3, 2.2].

About the Study: Saxagliptin Added to Thiazolidinedione
This study was designed to assess the addition of saxagliptin to thiazolidinedione (TZD) vs. the addition of placebo to TZD. The data represent findings from a 24-week, multinational, randomized, placebo-controlled, three-arm, parallel group, double-blind study of 565 people with type 2 diabetes (ages 18-77) whose A1C level was greater than or equal to 7 percent and less than or equal to 10.5 percent and who were receiving stable TZD monotherapy (pioglitazone 30 mg or 45 mg, or rosiglitazone 4 mg or 8 mg, total daily dose) for at least twelve weeks prior to screening. After a two-week lead in period during which all individuals continued on their previous pioglitazone or rosiglitazone dose, individuals were randomized to one of three treatment arms: saxagliptin 2.5 mg (n=195), saxagliptin 5 mg (n=186) or PBO (n=184), given once daily, in addition to continuing on their previously prescribed TZD dose.

The primary endpoint of the study was the change from baseline to Week 24 in A1C. The secondary endpoints of the study included changes from baseline to Week 24 in FPG, PPG response, as indicated by PPG area under the curve (AUC) from 0-180 minutes during an oral glucose tolerance test (OGTT), and the proportion of individuals achieving the ADA recommended A1C target of less than 7 percent.

Study Results
After 24 weeks, individuals in the saxagliptin + TZD treatment arms demonstrated a significant adjusted mean change in A1C from baseline: -0.7 percent for saxagliptin 2.5 mg + TZD and -0.9 percent for saxagliptin 5 mg + TZD, compared to -0.3 percent for PBO + TZD (p-value less than or equal to 0.0007 for both treatment arms). A greater percentage of individuals treated with saxagliptin + TZD achieved an A1C of less than 7 percent at Week 24: 42.2 percent for saxagliptin 2.5 mg + TZD and 41.8 percent for saxagliptin 5 mg + TZD, compared to 25.6 percent for PBO + TZD (p-value less than or equal to 0.0013 for both treatment arms).

Individuals treated with saxagliptin + TZD demonstrated a significant adjusted mean change from baseline in FPG: -14.3 mg/dL for saxagliptin 2.5 mg + TZD and -17.3 mg/dL for saxagliptin 5 mg + TZD, compared to -2.8 mg/dL for PBO + TZD (p-value less than or equal to 0.0053 for both treatment arms). Both saxagliptin + TZD treatment arms also demonstrated significant adjusted mean decreases from baseline in PPG, compared to PBO + TZD (p-value less than 0.0001 for both treatment arms).

One case of confirmed hypoglycemia (symptoms of hypoglycemia with a fingerstick glucose less than or equal to 50 mg/dL) was reported in the saxagliptin 2.5 mg + TZD treatment arm. There were no cases of confirmed hypoglycemia in the saxagliptin 5 mg + TZD or PBO + TZD treatment arms. Reported hypoglycemic events were: 4.1 percent for the saxagliptin 2.5 mg + TZD, 2.7 percent for saxagliptin 5 mg + TZD and 3.8 percent for PBO + TZD.

Over 24 weeks, the incidence of adverse events was: 62.1 percent for saxagliptin 2.5 mg + TZD, 74.2 percent for saxagliptin 5 mg + TZD and 66.8 percent for placebo + TZD. The percentages of the most commonly reported (greater than or equal to 5 percent) adverse events from the saxagliptin 2.5 mg + TZD, saxagliptin 5 mg + TZD and PBO + TZD treatment arms, respectively, were: upper respiratory tract infection [7.7, 9.1, 7.1]; urinary tract infection [3.6, 6.5, 6.5]; nasopharyngitis [3.1, 4.8, 6.0]; arthralgia or joint pain [5.6, 2.7, 2.7]; headache [4.6, 5.4, 3.8]; dizziness [2.6, 3.2, 5.4]; peripheral edema [3.1, 8.1, 4.3]; and hypertension [5.6, 4.3, 4.9].

Posted by dlife at 01:58 PM | Comments (0)

New Once-Weekly Diabetes Drug Formulation Gives Better Blood Sugar Control Than Twice-Daily Regimen

September 07, 2008

September 7, 2008 (EurekAlert) - Using a new formulation of the diabetes drug exenatide given once weekly provides better blood sugar (glycaemic) control and is much more convenient than the current twice-daily regimen. These are the conclusions of an Article published early Online and in an upcoming edition of The Lancet, authored by Dr Daniel Drucker, Mount Sinai Hospital and University of Toronto, Ontario, Canada, and colleagues. The findings are being announced at The European Association for the Study of Diabetes meeting in Rome.

Exenatide improves blood sugar control and gives progressive weight reductions in patients with type 2 diabetes. In this randomised trial, 259 patients completed a 30-week course of either a long-acting release formulation of exenatide 2mg administered once weekly (129 patients), or 10µg exenatide twice a day (130 patients). The patients had a mean weight of 102kg and an average diabetes duration of nearly seven years. The extent of their blood sugar control was monitored by the levels of haemoglobin A1c*(HbA1c) in their blood, which was at a mean of 8.3% before exenatide was given.

The researchers found that patients given exenatide once weekly saw their HbA1c levels fall to a mean of 6.4% (-1.9%), while those given the drug twice daily only fell to 6.8% (-1.5%). More patients given the once weekly formulation (77%) achieved the target HbA1c of 7.0% or less compared with the twice daily regimen (61%); the proportions achieving HbA1c of 6.5% or less or 6.0% or less were similar in both groups. The authors conclude: "Exenatide once weekly resulted in significantly greater improvements in glycaemic control than exetanide given twice a day, with no increased risk of hypoglycaemia and similar reductions in bodyweight."

In an accompanying Comment. Dr André Scheen, University of Liège, Belgium says "Compared with the twice-a-day exenatide regimen, the once-a-week formulation, besides obvious improved ease of use, provided the remarkable advantage of both improved efficacy on glucose control and good gastrointestinal tolerability." He further suggests that management of type 2 diabetes could change substantially as after confirmation and extension of these findings.

Posted by dlife at 09:19 AM | Comments (2)

New Research Suggests Diabetes Transmitted From Parents To Children

August 20, 2008

August 20, 2008 (EurekAlert) - A new study in the September issue of the Journal of Lipid Research suggests an unusual form of inheritance may have a role in the rising rate of diabetes, especially in children and young adults, in the United States.

DNA is the primary mechanism of inheritance; kids get half their genes from mom and half from dad. However, scientists are just starting to understand additional kinds of inheritance like metabolic programming, which occurs when an insult during a critical period of development, either in the womb or soon after birth, triggers permanent changes in metabolism.

In this study, the researchers looked at the effects of a diet high in saturated fat on mice and their offspring. As expected, they found that a high-fat diet induced type 2 diabetes in the adult mice and that this effect was reversed by stopping the diet.

However, if female mice continued a high-fat diet during pregnancy and/or suckling, their offspring also had a greater frequency of diabetes development, even though the offspring were given a moderate-fat diet. These mice were then mated with healthy mice, and the next generation offspring (grandchildren of the original high-fat fed generation) could develop diabetes as well.

In effect, exposing a fetal mouse to high levels of saturated fats can cause it and its offspring to acquire diabetes, even if the mouse goes off the high-fat diet and its young are never directly exposed.

The study used mice so it's not time to warn women to eat differently during pregnancy and breastfeeding but earlier research has shown that this kind of inheritance is at work in humans. For example, there is an increased risk of hypertension and cardiovascular disease in children born of malnourished mothers.

Posted by dlife at 09:30 AM | Comments (1)

Women With Gestational Diabetes At Risk Of Type 2 Diabetes

July 30, 2008

July 29, 2008 (Science Daily) - Women with gestational diabetes are at greater risk of developing type 2 diabetes, with almost 20% of women developing the condition within 9 years of pregnancy, found a large, population-based study of 659,000 women published in the Canadian Medical Association Journal.

The study, conducted by a group of researchers from the University of Toronto, Mount Sinai Hospital and the Institute for Clinical and Evaluative Sciences, looked at 21,823 women diagnosed with gestational diabetes and examined follow up records up to 9 years. They found the rate of diabetes increased rapidly in the first 9 months after delivery, peaking at 9 years.

"In this large, population-based study, we found that diabetes developed within 9 years after the index pregnancy in 18.9% of women with previous gestational diabetes; this rate was much higher than the rate among women without gestational diabetes (2%)," state Dr. Denice Feig and coauthors.

As well, they note that the rate of gestational diabetes in Ontario, the study province, seems to be increasing and is linked to older mothers. Living in low-income neighbourhoods and in urban areas were also risk factors for gestational diabetes. Higher urban statistics "may reflect the large numbers of South and East Asian and black populations living in urban areas, who have a higher risk of type 2 diabetes," postulate Dr. Feig and colleagues.

"The main strength of our study lies in the fact that it was a large population-based study involving more than 21,000 women with gestational diabetes, with up to 9 years of follow-up," state the researchers. "Unlike other studies, it covered a large, well-defined geographic region with a population of 13 million, which allowed us to make a more robust assessment of the risk of type 2 diabetes after gestational diabetes than has been possible in previous studies."

However, the study could not "assess the effect of ethnicity, obesity and level of fasting glucose during pregnancy, risk factors that are clearly associated with the development of diabetes."

"These women may benefit from both preventative interventions and regular screening," conclude the researchers who point out that physicians and policy makers need to counsel and screen these women accordingly.

In a related commentary, Dr. David Simmons of Cambridge University Hospitals NHS Foundation in the UK comments that many women with gestational diabetes become pregnant again, leading to potential risks for the fetus. "Type 2 diabetes in pregnancy, particularly if previously undiagnosed, is associated with poor outcomes, including an increased incidence of fetal loss, malformation and perinatal death." He argues for more investment in prevention and screening programs for at-risk women to protect women and their future children.

Posted by dlife at 10:38 AM | Comments (0)

Study Links Soft Drinks And Fruit Drinks With Risk For Diabetes In African-American Women

July 28, 2008

July 28, 2008 (EurekAlert) - Researchers from Boston University's Slone Epidemiology Center have found that regular consumption of sugar-sweetened soft drinks and fruit drinks is associated with an increased risk for type 2 diabetes in African-American women. These findings appear in the July 28 issue of Archives of Internal Medicine.

Type 2 diabetes, a leading cause of morbidity and mortality in the United States, has increased in incidence in recent years, while the age of diagnosis has dropped. Type 2 diabetes is a particular problem among U.S. black women, as their incidence rate is twice that of U.S. white women.

In questionnaires mailed to participants of the Black Women's Health Study (an ongoing prospective study of 59,000 African-American women from all parts of the U.S.) the researchers obtained information on height, weight, demographic characteristics, medical history, usual diet and other factors. Follow-up questionnaires that requested updated information on lifestyle factors, occurrences of diabetes and other serious illnesses were mailed to participants every two years.

The researchers found 2,713 participants developed diabetes during the first ten years of follow-up in the study. The incidence of type 2 diabetes rose with increasing intake of both sugar-sweetened soft drinks and fruit drinks. Women who consumed two or more soft drinks a day had a 24 percent increase in incidence of relative to women who drank less than one soft drink per month. A similar association was observed for sweetened fruit drinks, with a 31 percent increase observed for two or more servings per day relative to less than one per month.

The researchers note that while there has been increasing public awareness of the adverse health effects of soft drinks, little attention has been given to fruit drinks, which often are marketed as a healthier alternative to soft drinks.

"Fruit drinks were consumed more frequently than soft drinks in our study, and the proportion of total energy intake from fruit drinks in the U.S. population doubled from 1977 to 2001," said lead author Julie Palmer, ScD, a professor of epidemiology at Boston University School of Public Health. "The public should be made aware that these drinks are not a healthy alternative to soft drinks with regard to risk of type 2 diabetes," she added.

Posted by dlife at 09:14 AM | Comments (4)

Newly Published Study Results Showed That Two Mealtime Insulin Dosing Algorithms Were Effective for Patients with Type 2 Diabetes

July 22, 2008

Two Regimens Including Lantus® and Apidra® Resulted in Significant Reductions in A1C in Patients with Type 2 Diabetes, Whatever the Algorithm Used

July 22, 2008 (Sanofi–Aventis Press Release) - Results from the “Adjust to Target in Type 2 Diabetes: Comparison of a Simple Algorithm to Carbohydrate Counting for Adjustment of Mealtime Insulin Glulisine” study, were published in the American Diabetes Association’s (ADA) medical journal, Diabetes Care. This study, using a basal-bolus insulin regimen with Lantus® (insulin glargine [rDNA origin] injection) once daily (basal insulin) and rapid-acting Apidra® (insulin glulisine [rDNA origin] injection) at mealtime (bolus insulin) demonstrated significant reductions in postprandial blood glucose and A1C using two different dosing algorithms.

The 24-week, multicenter, randomized, controlled study compared two algorithms for adjusting mealtime insulin (Apidra®) in 273 intent-to-treat patients with type 2 diabetes. Apidra® and Lantus® were adjusted weekly in both groups based on the previous week’s self-monitored blood glucose (SMBG) results. One group, the “Simplified Algorithm” group, was provided set doses of Apidra® to take before each meal. The second group, the “Carbohydrate Counting” group, was provided an insulin-to-carbohydrate ratio to use for each meal and adjusted their Apidra® dose based on amount of carbohydrate consumed. After 24 weeks, the percentage of patients who achieved A1C<7 percent – the ADA’s recommended target for blood sugar control – while following these two treatment algorithms were 73% and 69% (P=0.70), respectively.

Average A1C levels at week 24 were 6.70 percent in the Simplified Algorithm group and 6.54 percent in the Carb Counting group. The respective mean A1C changes from baseline to 24 weeks were –1.46 percent and –1.59 percent (P=.24). A1C <7.0 percent was achieved by 73 percent (Simplified Algorithm) and 69 percent (Carb Counting) (P=.70); respective values for A1C <6.5 percent were 44.3 percent and 49.5 percent (P=.28). The Simplified Algorithm group had 53 episodes of severe hypoglycemia in 19 patients, and the Carb Counting group had 37 episodes in 19 patients, leading to estimates of 0.89 and 0.67 event/patient-year for the two groups (P=0.58). SMBG < 50 mg/dL with symptoms was slightly but statistically significantly more common in the Carb Counting group than in the Simplified Algorithm group (8.0 vs. 4.9 events/patient-year, P=0.02). 2

“A combination of basal and bolus insulin may be needed to achieve optimal glucose control in type 2 diabetes patients,” explained study author Richard M. Bergenstal, MD, executive director, International Diabetes Center, Park Nicollet Health Services, Minneapolis, MN. “The simplified algorithm investigated in this study allowed patients to start with a fixed dose of Apidra® and then effectively adjust to target based on premeal glucose patterns, or to use carbohydrate counting, which involves a mathematical formula that helps patients match the size of their mealtime insulin dose with the amount of carbohydrates they eat. Having two effective options for managing mealtime insulin doses may increase patients’ and clinicians’ willingness to initiate basal-bolus therapy.”

Throughout the study, SMBG levels were recorded before meals and at bedtime each day, as well as a 7-point blood glucose profile at weeks 2, 6, 12, 18, and 24 (endpoint). Blood glucose values at each visit declined in both arms, and the within-group change from baseline was statistically significant over all daily time points and study visits. By the study’s conclusion, both arms significantly improved fasting plasma glucose (FPG) levels as well, with averages of 112.0 mg/dl in the Simplified Algorithm group and 101.8 mg/dl in the Carb Counting group (P<0.0001 for both groups).

“Type 2 diabetes is a progressive disease that requires treatment adjustments to help manage the potential risks that come with prolonged hyperglycemia,” said Dr. Bergenstal. “The Adjust to Target trial demonstrated that basal-bolus insulin therapy may be an effective option for the many people with type 2 diabetes who are not achieving glycemic targets with their current insulin regimen.”

About the Trial
Study participants were 28-71 years old, had type 2 diabetes for ≥6 months and mean ± SD A1C values of 8.1 ± 0.9% (Simplified Algorithm) and 8.3 ± 0.9% (Carb Counting Algorithm) at screening. They had taken ≥2 insulin injections/day (36 percent on 2 injections, 64 percent on more than 2 injections) ± metformin (one-third were on metformin), for ≥3 months before study entry. Upon entry into the study, 37 percent were using Lantus® and at least one injection of a rapid-acting insulin analog, 36 percent were using a pre-mixed insulin and the remainder were on a combination of various other diabetes treatment regimens.

About Diabetes
Diabetes is a chronic, widespread condition in which the body does not produce or properly use insulin – the hormone needed to transport glucose (sugar) from the blood into the cells of the body for energy. More than 230 million people worldwide are living with the disease and this number is expected to rise to a staggering 350 million within 20 years. It is estimated more than 20 million Americans have diabetes, including an estimated 6.2 million who remain undiagnosed. At the same time, more than 40 percent of those diagnosed are not achieving the blood sugar control target of A1C <7 percent recommended by the American Diabetes Association (ADA). The A1C test measures average blood glucose levels over a two- to three-month period.

About sanofi-aventis
Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT : SAN) and in New York (NYSE : SNY).3

Forward Looking Statements
This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include financial projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions and expectations with respect to future events, operations, products and services, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects,” “anticipates,” “believes,” “intends,” “estimates,” “plans” and similar expressions. Although sanofi-aventis’ management believes that the expectations reflected in such forwardlooking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of sanofi-aventis, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include those discussed or identified in the public filings with the SEC and the AMF made by sanofi-aventis, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward- Looking Statements” in sanofi-aventis’ annual report on Form 20-F for the year ended December 31,
2007. Other than as required by applicable law, sanofi-aventis does not undertake any obligation to update or revise any forward-looking information or statements.

U.S. Media Contacts:
Carrie Melia
Carrie.Melia@sanofi-aventis.com
908-981-6486
US.GLA.08.06.085

Posted by dlifenews at 01:42 PM | Comments (0)

Can Diet Alone Control Type 2 Diabetes? No Evidence Yet

July 16, 2008

July 16, 2008 (Science Daily) - Despite strong evidence that type 2 diabetes can be prevented or at least delayed by a combination of lifestyle changes and good dietary advice, a team of Cochrane Researchers found that there is no indication whether dietary advice alone can prevent the disease.

Type 2 diabetes is very common and the number of people affected is increasing. The disease is linked to obesity, with 80% of individuals who develop the disease being obese. Therefore as the incidence of obesity rises around the world, so too does the incidence of type 2 diabetes. The World Health Organization (WHO) estimates that more than 180 million people worldwide have diabetes. It claims that this number is likely to more than double by 2030.*

When a team of Cochrane Researchers set out to see if dietary advice alone could help a person with type 2 diabetes, they were only able to identify two trials that together involved just 358 people.

"Considering the importance of this disorder, we were disappointed to find such a small amount of relevant data," says lead researcher Lucie Nield, who works in Centre for Food, Physical Activity & Obesity, University of Teesside, Middlesbrough.

The two studies did, however, indicate that dietary advice alone could play an important role. One study randomly assigned people to either a control group or a dietary advice group. After six years 67.7% of people in the control group had diabetes, compared with only 43.8% in the advice group. This was a 33% reduction. In another study 12 months of dietary advice led to significant reductions in many diabetes related factors, such as insulin resistance, fasting C-peptide, fasting proinsulin, fasting blood glucose, fasting triglycerides, and fasting cholesterol and PAI-1.

"These two studies give grounds for believing that dietary advice alone could play an important role in reducing type 2 diabetes, but we do need more well-designed, long-term studies before we can work out the best advice to give," says Nield.

Posted by dlife at 03:01 PM | Comments (5)

Type 2 Diabetes: Culturally-Tailored Education Can Improve Blood Sugar Control

July 15, 2008

July 15, 2008 (EurekAlert) - Using community-based health advocates, delivering information within same-gender groups or adapting dietary and lifestyle advice to fit a particular community's likely diet can help people with type 2 diabetes control their blood sugar levels, certainly for up to six months, following health education. This conclusion was reached by a team of Cochrane Researchers after they considered the data in 11 trials that involved 1,603 people.

Type 2 diabetes is a particular problem for minority ethnic groups who originate from developing countries, but live in upper-middle income or high income countries. These people tend to have low socio-economic status and find that they are faced with many physical, communication and cultural barriers that make it difficult to access healthcare effectively.

The Cochrane Researchers found 11 trials where people had deliberately tried to overcome cultural barriers. In short-term studies, culturally appropriate health education programs led to improved blood-sugar control within 3 months. This benefit was still seen when the 6-month trial periods ended. Knowledge about diabetes and healthy lifestyles also improved over this time period. One-year later, however, the benefits had not been sustained.

"These are important and encouraging results. They show that providing culturally tailored information can help people control their diabetes." says Kamila Hawthorne, who works at the Department of Primary Care and Public Health at the University of Cardiff, UK.

"Diabetes is a chronic condition and complications can develop over many years. We now need to carry out longer term studies with larger groups, all measuring the same results, to discover which type of assistance is most useful and see how to keep the benefits running for longer," says Hawthorne.

Posted by dlife at 02:58 PM | Comments (0)

All Sweeteners Not The Same For Managing Type 2 Diabetes

July 15 , 2008 (Newswise) - Recent research by Kalidas Shetty of the University of Massachusetts Amherst and Lena Galvez Ranilla of the University of San Paolo, Brazil, shows that when it comes to managing Type 2 diabetes, all sweeteners may not be the same. Some sweeteners, including date sugar and less refined, dark brown sugars, showed potential for managing Type 2 diabetes and related complications − information that could help Type 2 diabetics make better dietary choices.

“Depending on their origin and grade of refining, many sweeteners contained significant amounts of antioxidants, which have the potential to control diabetes-linked high blood pressure and heart disease,” says Shetty, who adds that these were in vitro laboratory studies performed outside of living organisms. “Several types of sweeteners also showed an interesting potential to inhibit the action of a key enzyme related to Type 2 diabetes, which is also the target of drugs used to treat this condition.”

Additional members of the research team include food scientist Young-In Kwon of UMass Amherst and Maria Ines Genovese and Franco Maria Lajolo of the University of San Paulo, Brazil. Results were published in the most recent issue of the Journal of Medicinal Food.”

The team started by collecting an exhaustive array of sweeteners, everything from the complete line offered by Domino, to unprocessed, dark brown sugars from Mauritius and Peru. Pure maple syrup, corn syrup-based sweeteners, “natural” sugar products like sucanat and sugars from Asia, India, South America and China rounded out the list.

Extracts of the sweeteners were first analyzed to determine their total content of a group of antioxidants known as phenolic compounds, the same plant chemicals that give red wine and tea their heart-healthy benefits. Testing showed that when it comes to sugar, darker is definitely better. Dark brown sugars contained up to 4,741 micrograms of phenolic compounds per gram, compared to 18 micrograms per gram for white sugar. The highest antioxidant levels were found in the darkest sugars.

Further testing showed that these phenolic compounds had significant antioxidant properties, scavenging harmful free radicals that can damage the delicate machinery of cells. According to Shetty, high blood sugar levels in diabetics can cause the overproduction of these free radicals, contributing to high blood pressure and accelerating the development of heart disease.

Date sugar produced in the United States and dark brown sugars from Peru and Mauritius packed the biggest punch, racking up the highest antioxidant levels and scavenging an impressive 82 to 88 percent of free radicals in laboratory in vitro tests.

Sweeteners were then tested for their ability to inhibit the activity of alpha-glucosidase, an enzyme that moderates blood glucose levels by controlling the passage of sugars from the small intestine. “Diabetes is characterized by a rapid rise in blood glucose levels after meals,” says Shetty. “Inhibiting alpha-glucosidase, which is the target of several drugs used to treat diabetes, can help prevent this spike.”

Most sweeteners derived from sugar cane inhibited alpha-glucosidase action by 26 to 50 percent, including the dark brown sugars and natural sugar products from evaporated cane juice. Date sugar inhibited the enzyme by 75 percent.

Surprisingly, several sweeteners based on corn syrup inhibited alpha-glucosidase levels by 77 to 81 percent, although they contained low levels of phenolic compounds. “This level of inhibition could be due to sugar polymers known as oligosaccharides that are not completely broken down, mimicking the action of certain drugs that inhibit alpha-glucosidase,” says Shetty. “This investigation is continuing.”

Date sugar and sweeteners based on corn syrup also inhibited an enzyme that plays a role in high blood pressure, a common complication of diabetes. According to Shetty, the reason for this is not clear based on current studies.

“Replacing sugars in processed foods and beverages with low calorie and noncaloric sweeteners is one long term strategy for Type 2 diabetics,” says Shetty. “But these results indicate that a strategic choice of dietary sweeteners, especially less refined sugars close to the original nature of the ingredients found in whole plants, also has potential in managing Type 2 diabetes and related complications. This provides a strong rationale for further animal and clinical studies for better diet design.”

Posted by dlife at 10:34 AM | Comments (3)

Potential To Prevent Loss Of Insulin In Type 2 Diabetes

July 14, 2008

July 14, 2008 (Science Daily) - There are two completely different diseases known as diabetes. Type 1 is an autoimmune condition that often starts in childhood or adolescence. Type 2 is a metabolic disorder sometimes associated with lifestyle. In both cases, the insulin-secreting beta cells in the pancreas die, albeit at different rates.

Until now, it was thought that the processes leading to beta cell death were similar in both diseases. Scientists at the Garvan Institute of Medical Research in Sydney have now shown that the causes of cell death are quite different.

In April 2007, Garvan's Associate Professor Trevor Biden and Dr Ross Laybutt published a landmark paper establishing the existence of ER (Endoplasmic Reticulum) stress in people with Type 2 diabetes. The ER is the part of a cell where simple strings of amino acids are structured into three-dimensional proteins which then go on to perform specific tasks in the body. Insulin is one such protein. When the correct re-structuring of proteins is disrupted, beta cells suffer ER stress, and eventually die.

The new study, undertaken by PhD student Mia Akerfeldt, expands our knowledge about ER stress in Type 2 diabetes, while ruling out its importance in Type 1 diabetes. The paper is now online in the international journal Diabetes.

Mia is hopeful that the findings will translate quickly into treatments. "Garvan was first to show that ER stress was present in people with Type 2 diabetes, and that reducing it could slow down beta cell death," she said. "We've not only shown the same thing again, we've identified a potentially useful therapeutic agent."

Project leader Ross Laybutt echoes Mia's optimism. "One interesting aspect of the new study is that we used a "chemical chaperone", an agent that helps the secretory protein, in this case insulin, to form properly. This compound relieved cell death and ER stress in laboratory experiments."

"The compound, known as PBA, is already FDA approved for use in another clinical application. That suggests it could be fast tracked for use in humans to prevent or delay beta cell dysfunction."

"Naturally, we would want to test it on animals before conducting clinical trials on people."

Posted by dlife at 04:10 PM | Comments (1)

Elevated Level of Certain Protein Linked With Risk for Diabetes

July 09, 2008

July 8, 2008 (Newswise) - Having a higher than normal level of fetuin-A, a protein produced in the liver and secreted into the blood stream, is associated with an increased risk of the development of diabetes, according to a study in the July 9 issue of JAMA.

“Type 2 diabetes mellitus has become a global epidemic and the increased prevalence of obesity is a major contributing factor. However, diabetes does not develop in all obese individuals and there is a strong genetic contribution to risk. Despite significant recent advances, mechanisms responsible for individual differences in clinical phenotype remain largely unknown,” the authors write. Previous studies have found an association between higher fetuin-A levels and insulin resistance, but the association with incident type 2 diabetes mellitus is unknown.

Joachim H. Ix, M.D., M.A.S., of the University of California, San Diego, and San Diego Veterans Affairs Healthcare System, and colleagues conducted a study to examine whether higher fetuin-A levels are associated with the occurrence of diabetes in older persons. The study included 406 persons (age 70 to 79 years) without diabetes at the start of the study, and who had fetuin-A levels measured at baseline, and had six years of follow-up. Diabetes developed in 135 participants (10.1 cases/1,000 person-years [the number of individuals in the study times the number of years of follow-up per person]).

Analysis indicated a graded increase in the incidence of diabetes with increased fetuin-A levels. The third of the group with the highest levels had more than twice the incidence rate compared with the lowest third (13.3 vs. 6.5 cases/1,000 person-years). The association was independent of physical activity, inflammatory biomarkers, and other commonly available measures of insulin resistance and was irrespective of sex, race, and obesity status. The association was moderately weakened by adjustment for visceral adiposity (fat accumulation around the abdomen).

“Future studies should evaluate whether the results may generalize to middle-aged individuals in whom the [diabetes] incidence rate is highest. If confirmed in future studies, fetuin-A may ultimately prove useful as a target for therapeutics, and its study may provide novel insights to glucose metabolism in humans,” the authors conclude.

Posted by dlife at 11:29 AM | Comments (0)

The Coming Epidemic of Type 2 Diabetes in Young Adults

July 07, 2008

July 7, 2008 (Newswise) - How will the epidemic of childhood obesity today affect the future health of Americans?

As concern about children’s health grows along with their waistlines, medical experts fear that the childhood obesity epidemic could lead to large numbers of younger adults developing type 2 diabetes, causing serious and lasting health complications for future generations of Americans.

In an article in the July issue of the Archives of Pediatric & Adolescent Medicine, University of Michigan C.S. Mott Children’s Hospital pediatric endocrinologist Joyce Lee, M.D., M.P.H, warns that the most damaging effects of childhood obesity have yet to surface, and will likely result in an epidemic of type 2 diabetes among young adults, leading to a greater number of diabetes complications, and ultimately, lower life expectancy.

“The full impact of the childhood obesity epidemic has yet to be seen because it can take up to 10 years or longer for obese individuals to develop type 2 diabetes,” says Lee, a member of the Child Health Evaluation and Research (CHEAR) Unit at Mott. “Children who are obese today are more likely to develop type 2 diabetes as young adults.”

The longer a person has diabetes, Lee says, the more likely he or she is to develop devastating complications. Young adults with type 2 diabetes are therefore more likely to develop complications such as blindness and kidney failure during their lifetimes, and they have higher rates of diabetes complications and heart disease than older adults with type 2 diabetes.

Plus, babies born to young women with type 2 diabetes are at greater risk for obesity and type 2 diabetes, creating a vicious cycle.

“Recent studies suggest that there have been dramatic increases in type 2 diabetes among individuals in their 20s and 30s, whereas it used to be that individuals developed type 2 diabetes in their late 50s or 60s, “ notes Lee, assistant professor in the Department of Pediatrics and Communicable Diseases at the U-M Medical School. “This may be the first indication of a type 2 diabetes epidemic among young adults who were obese during childhood.”

Given the delayed negative effects of childhood obesity, Lee says that there needs to be a greater overall investment in childhood obesity, to prevent development of type 2 diabetes.

“Our society heavily invests in the treatment and management of chronic diseases like type 2 diabetes for adults. But it spends very little for the prevention and treatment of childhood obesity to stave off the onset of type 2 diabetes,” says Lee.

“If there isn’t a significant investment in obesity prevention and treatment during childhood within schools, communities, and the health care system, recent trends in childhood obesity will likely lead to increases in type 2 diabetes among young adults, resulting in even greater costs to society and the health care system.”

Lee notes that further studies are needed to learn more about how trends in childhood obesity will impact future rates and age at onset of type 2 diabetes.

These studies will help assess the future burden of disease and disability in the population, and to evaluate whether interventions in childhood can successfully prevent individuals from developing type 2 diabetes over their lifetimes.

Posted by dlife at 11:03 AM | Comments (1)

Insulin Analogs No Better than the Real Deal, According to Latest Research

June 25, 2008

June 25, 2008 (Newswise) - Efforts to make diabetes care more manageable, and easier on the patient, have led to the introduction of insulin “analogs” – medicines that act similarly to ordinary insulin, but which are supposed to provide additional benefits. Recent research from Generex Biotechnology, a company focused on advanced insulin delivery and diabetes vaccine research, shows that the advantages of insulin analogs may be illusory. Investigators from the company presented their data at the recently completed Endocrine Society 90th Annual Meeting, held in San Francisco from June 15 through 18. The presentation was co-authored by researchers from the Institute for Endocrinology IEMYR, Quito, Ecuador, and the University of Florida, Gainsville.

The year-long study examined 26 subjects with type 1 diabetes, which is normally treated with “basal” injected injection once or twice a day to provide baseline glycemic control, and additional insulin injections before meals. The control study group received insulin glargine (an insulin analog) once a day as their basal dose, and a faster-acting insulin analog before meals. The treatment group received a non-analog long-acting insulin twice a day as their basal insulin; before meals the they took Oral-lyn™, a liquid formulation of human insulin, developed by Generex, that is absorbed through the lining of the mouth. All subjects were monitored for three standard measures of glycemic control: Hemoglobin A1c and fructosamine levels were recorded every two weeks by investigators, and pre-meal glucose levels were taken by patients themselves. Together, these readings assess the effectiveness of diabetes treatment regimens better than any test alone. Higher readings generally indicate less-effective glucose control.

At the end of the study all three measures were found to be consistently and significantly lower in the group that received the human insulin regimen that included the Oral-lyn product before meals. Oral-lyn uses a formulation that allows insulin to pass through the “buccal” mucosa – the soft tissues lining the inside of the mouth – and into the bloodstream rapidly and safely, without injection. Oral-lyn is delivered to the mouth using Generex’s proprietary RapidMist™ spray device. Unlike inhaled insulin products which have enjoyed limited success, the combination of Oral-lyn insulin and RapidMist delivery technology allows patients to deliver their insulin dose as needed, and do not deposit insulin into the lungs.

People with diabetes, and physicians treating them, have become excited in recent years by insulin analogs due to their rapid window of action. Several studies have also claimed that analogs improve glycemic control. Insulin analogs can cost up to three times as much as insulin, however, which can place serious financial strains on families that pay for their own insulin. Even families with comprehensive drug coverage will find that plans charge a significantly higher co-pay for insulin analogs than for “regular” human insulin.

“Our results clearly show that over the course of a year-long study the advantage of these analogues is equaled or improved upon by the use of Oral-lyn. When Oral-lyn is absorbed through the buccal mucosa its rapid entry into the blood stream mimics and improves upon the rapid acting analogues.” commented Dr. Jaime Guevara, a study author and clinician that has conducted studies for Generex’s Oral-lyn. “Claims that analogs provide superior convenience do have some merit when these agents are compared with insulin injected before meals. However, when compared with Oral-lyn, which is not injected, even those arguments fail to make the case for drugs that cost three times as much as standard insulin.”

Oral-lyn is currently approved in two countries, and is currently undergoing clinical testing for U.S. approval.

For more information, log on to http://www.generex.com

Posted by dlife at 10:28 AM | Comments (1)

Lifestyle Can Alter Gene Activity, Lead To Insulin Resistance

June 19, 2008

June 19, 2008 (EurekAlert) - A Finnish study of identical twins has found that physical inactivity and acquired obesity can impair expression of the genes which help the cells produce energy. The findings suggest that lifestyle, more than heredity, contributes to insulin resistance in people who are obese. Insulin resistance increases the chance of developing diabetes and heart disease.

The study, "Acquired obesity and poor physical fitness impair expression of genes of mitochondrial oxidative phosphorylation in monozygotic twins discordant for obesity," appears in the online edition of the American Journal of Physiology-Endocrinology and Metabolism, published by The American Physiological Society (www.the-aps.org).

The study was carried out by Linda Mustelin and Kirsi Pietiläinen, of Helsinki University Central Hospital and the University of Helsinki; Aila Rissanen, Anssi Sovijärvi and Päivi Piirilä of Helsinki University Central Hospital; Jussi Naukkarinen, Leena Peltonen and Jaakko Kaprio, University of Helsinki and National Public Health Institute; and Hannele Yki-Järvinen of Helsinki University Central Hospital and Minerva Medical Research Institute.

Environment can influence genes

Recent studies have suggested that defects in expression of genes involved in the body's conversion of food to energy, known as mitochondrial oxidative phosphorylation, can lead to insulin resistance. The researchers wanted to know if defects in the expression of these genes are primarily a result of heredity or lifestyle. Because the twins in the study were identical, any differences that were found could be attributed to environmental factors, the researchers reasoned.

Twenty four pairs of identical twins, born in Finland between 1975 and 1979, took part in the study. Fourteen pairs (eight male and six female) were discordant for obesity, that is, one twin was obese, while the other was not. The control group consisted of five male and five female twin pairs who were concordant for weight. Some of the concordant pairs were normal-weight while some pairs were overweight.

The researchers measured whole body insulin sensitivity, body composition and cardiorespiratory fitness. They also obtained a needle biopsy of abdominal subcutaneous fat tissue, although they were unable to obtain this measurement for one of the discordant pairs.

Among the discordant pairs, the study found the obese twin had significantly lower:

* Insulin sensitivity, indicating the body has a harder time using glucose to produce energy.

* Fitness levels, as measured by maximum oxygen uptake and maximum work capacity.

* Transcription levels of genes that help cells convert food to energy (the genes of mitochondrial oxidative phosphorylation). Transcription is a multi-step process in which information in the genes is used to manufacture proteins. Proteins, in turn, direct cell activity. This suggests that the impaired expression of the genes may make it more difficult to lose excess weight, or may make additional weight gain more likely.

Heredity may still play role

"These data suggest that physical inactivity may have contributed to the defects in mitochondrial oxidative phosphorylation described in type 2 diabetic patients and prediabetic subjects," the authors wrote. The authors also noted that, although environment plays a role in how these genes work, there still may be a hereditary component.

"Although we found that the reduced transcript levels of genes encoding mitochondrial oxidative phosphorylation in obesity is influenced by environmental and acquired factors, it does not exclude the possibility that genetic factors contribute to regulation of mitochondrial oxidative metabolism," lead author Linda Mustelin noted.

The next step is to do a clinical study to see if exercise and other lifestyle changes can increase the expression of these genes.

Posted by dlife at 09:03 AM | Comments (0)

Depression and Diabetes: Fellow Travelers, Researchers Say

June 17, 2008

June 17, 2008 (EurekAlert) - Researchers have long known that type-2 diabetes and depression often go hand in hand. However, it's been unclear which condition develops first in patients who end up with both. Now, a new study led by Johns Hopkins doctors suggests that this chicken-and-egg problem has a dual answer: Patients with depression have an increased risk of developing type-2 diabetes, and patients with type-2 diabetes have an increased risk of developing depression.

For the study, published in the June 18 Journal of the American Medical Association, diabetes expert Sherita Hill Golden, M.D., M.H.S., and her colleagues took advantage of data generated by the Multi-Ethnic Study of Atherosclerosis (MESA), which examined risk factors for atherosclerosis, or hardening of the arteries, in an ethnically diverse group of 6,814 men and women between ages 45 to 84. Participants in the MESA study identified themselves when they enrolled as white, black, Hispanic or Chinese.

During MESA, participants made three visits to clinics over the course of three years to be examined for various atherosclerosis risk factors, including type-2 diabetes and symptoms of depression, which could serve as a precursor for full-blown clinical depression.

The study also collected information on other atherosclerosis risk factors, such as participants' body-mass indices, blood pressure, diet and exercise patterns, and smoking habits, as well as information correlated with health in general, such as income and socioeconomic factors.

Mining the data for their own purposes, Golden and her colleagues excluded from their analysis all participants who had high fasting glucose, an indication of diabetes, at the initial clinic visit. They then looked to see whether participants who initially had elevated symptoms of depression, as indicated through a questionnaire, were more likely than those who didn't to develop high fasting glucose at the end of the three-year study period.

Results showed that those with elevated depressive symptoms were 42 percent more likely overall to develop diabetes by the end of the study than those without these symptoms. Moreover, the stronger the symptoms, the higher the risk of diabetes, a "dose response" that lends strength to the findings.

Even when the researchers accounted for such factors as overweight, lack of exercise, and smoking, the risk of developing diabetes was still 34 percent higher for patients with depressive symptoms.

To investigate whether diabetes could lead to depression, Golden and her colleagues used the same pool of MESA information and excluded those who had elevated depressive symptoms at the initial clinic visit. Then, they looked to see whether those who had high fasting glucose—with or without a formal diagnosis of diabetes—were more likely to develop depressive symptoms by the end of the study.

The researchers found that patients treated for diabetes, about 9 percent of the group, were about 54 percent more likely to develop elevated depressive symptoms than those without diabetes.

Surprisingly, those with prediabetes or untreated diabetes were about 25 percent less likely to develop elevated depressive symptoms than people with normal fasting glucose, a finding Golden's team cannot explain at this time.

Golden, an associate professor of medicine and epidemiology at the Johns Hopkins University School of Medicine, speculates that depression may lead patients to develop behaviors that trigger diabetes or make it worse, such as overeating, not exercising or smoking. Similarly, keeping up with the often extensive treatment regimens to care for their diabetes may make patients' depression worse. Understanding how one condition might lead to another could improve treatments for both problems, she says.

"Having both diabetes and depression can make it difficult for patients to get the good clinical outcomes that we like to see for each of these conditions," says Golden. "To make sure that patients with diabetes and depression receive the best care, we wanted to get to the bottom of the connection between these two conditions.

"It's important that doctors be attuned to look for both conditions in patients at risk for either diabetes or depression," Golden adds. "We may want to develop interventions for both treatments, instead of just one or the other."

Posted by dlife at 01:31 PM | Comments (0)

Some Patients May Not Need Insulin For Long-Term Control Of Type 2 Diabetes

June 16, 2008

June 15, 2008 (EurekAlert) - Some patients with type 2 diabetes can control their disease for years yet avoid insulin injections by using multiple classes of oral diabetic medications, a new study found. The results were presented Sunday, June 15, at The Endocrine Society's 90th Annual Meeting in San Francisco.

Findings from the study contradict common beliefs about non-insulin diabetic medications, said principal investigator Arthur Swislocki, MD, of the Veterans Affairs (VA) Northern California Health Care System in Martinez. Oral diabetes medications help control blood glucose, or sugar, levels in people whose bodies still produce some insulin, as is true for many patients with type 2 diabetes.

"Generally, both patients and physicians believe that long-term use of oral diabetic medications is not possible because these drugs lose their effectiveness over time as the patient's pancreas fails," Swislocki said. "Our data suggest that some patients can remain in good glucose control for years using non-insulin, oral diabetic agents."

The study result is good news for people who need medical therapy for type 2 diabetes, according to Swislocki. "They may be able to delay or avoid the use of insulin," he said.

Some patients prefer pills over insulin injections because they are easier to use or because the patient fears needles or getting low blood sugar, as is possible with insulin treatment, he said.

Swislocki and his coworkers studied the VA medical records of 191 veterans (188 men and 3 women) with type 2 diabetes who received treatment beginning in 1992 and received follow-up for 15 consecutive years. Of these patients, 96 began treatment solely with oral drugs. The researchers found that 55 percent of the patients (53 of 96) who started treatment with oral diabetic agents were able to continue using them 15 years later and achieve good blood sugar control. A measure of long-term blood sugar control—hemoglobin A1c—improved from an average of nearly 8 percent to about 7 percent 15 years later in this group.

Of the 96 patients, 45 percent eventually switched to insulin, either alone or in combination with oral drugs. At the beginning of the study, the duration of diabetes was similar between these patients and those who remained on an oral drug regimen. However, the group of patients who stayed on oral medications throughout the study had a lower beginning A1c and were less obese than patients in the other group, the authors reported. They also were more likely to be white. Past studies show minorities have poorer blood sugar control than do whites.

Swislocki said the long-term effectiveness of oral diabetic medications seen in their study may reflect the wider range of oral drugs now available for treating type 2 diabetes, compared with 15 years ago. Therefore, if one class of drugs became less effective, other classes could be added in combination.

The study, however, did not specifically address whether or not oral diabetic drugs lose their effectiveness over a long time, according to Swislocki. Rather, it mainly tracked the prescribing practices of VA primary care providers. "Deductions about drug effectiveness need to be made cautiously," he said.

Posted by dlife at 10:36 AM | Comments (2)

Severe Insulin Resistance may Increase Rate of Pregnancy and Birth Complications

June 15, 2008

June 15, 2008 (Newswise) - Testing pregnant women for insulin resistance with a simple blood test may be a new tool for predicting problems during pregnancy, according to a new study. The results will be presented at The Endocrine Society’s 90th Annual Meeting in San Francisco.

Insulin resistance is a condition in which the body blocks the effects of the hormone insulin. As a result, glucose, or sugar, builds up in the blood, and diabetes can develop. Insulin resistance lies behind the development of gestational diabetes—diabetes that develops during pregnancy—which increases the risk of pregnancy and birth complications. Therefore, the authors aimed to find out whether insulin resistance is linked to poor outcomes in pregnant women and newborns, said the lead author, Weerapan Khovidhunkit, MD, PhD, of Chulalongkorn University, Bangkok, Thailand.

It is standard for pregnant women to get a blood test for gestational diabetes between the 24th and 28th weeks of pregnancy, according to The Hormone Foundation, the public education affiliate of The Endocrine Society. This test is called the glucose challenge test or glucose challenge screening. If this test result is positive, the woman then has an oral glucose tolerance test (OGTT), in which her blood sugar levels are tested 3 hours after she drinks a glucose drink.

“The OGTT is time-consuming,” Khovidhunkit said. “Also, many women cannot tolerate an OGTT due to nausea and vomiting.”

It is possible for women to have high insulin resistance without having gestational diabetes, according to Khovidhunkit. A special test of insulin resistance, called HOMA, is not part of standard pregnancy tests, but it is quick and easy, he said. This test relies on a fasting blood test of glucose and insulin levels.

The authors studied 538 pregnant women who had positive glucose challenge tests and then underwent the OGTT. The researchers also assessed insulin resistance using HOMA. They tracked pregnancy complications, including preeclampsia, a condition involving high blood pressure; excess amniotic fluid (called polyhydramnios); premature rupture of the membranes, in which the woman’s water breaks before she goes into labor; and need for a cesarean section.

Even if women did not have gestational diabetes, those who had the highest degree of insulin resistance (above 2.44) had nearly 1.5 times the rate of pregnancy complications than those with the lowest insulin resistance, the authors found. The most common maternal complication was need for a cesarean section, according to Khovidhunkit.

Similarly, babies born to women in the group that had the highest degree of insulin resistance had a complication rate at birth 1.75 times higher than babies born to women with the lowest insulin resistance. The most common newborn complications were macrosomia—an abnormally large size—as well as low blood sugar (hypoglycemia), the authors reported.

The study tested only pregnant women who were at increased risk of pregnancy complications because they had high blood glucose levels, as shown by a positive glucose challenge test. Therefore, Khovidhunkit said, “Before we can advise pregnant women to undergo this testing, further studies are needed in other patient populations.”

Posted by dlife at 12:24 PM | Comments (0)

Periodontitis Associated With Development of Type 2 Diabetes and Its Complications

June 06, 2008

June 6, 2008 (Marketwire) - Critical links between periodontal (gum) disease and the development of type 2 diabetes, as well as the development and progression of its complications, were reported here today in the first ever symposium presented by dentists to diabetes experts at the American Diabetes Association's Annual Scientific Sessions at its 68th such event.

"One of the many complications of diabetes is a greater risk for periodontal disease," said Maria E. Ryan, DDS, PhD, Professor of Oral Biology and Pathology, and Director of Clinical Research, School of Dental Medicine, Stony Brook University, New York, in a recent interview. "If you have this oral infection and inflammation, as with any infection, it's much more difficult to control blood glucose levels." Intensive periodontitis treatment significantly reduces levels of A1C, a measure of glucose control over the prior two to three months.

These links between oral and systemic health may start even before clinical diabetes begins. "We have found evidence that the severity of periodontal disease is associated with higher levels of insulin resistance, often a precursor of type 2 diabetes, as well as with higher levels of A1C, a measure of poor glycemic control of diabetes," she said.

The importance of these findings were emphasized by her colleague, George W. Taylor, DrPH, DMD, Associate Professor of Dentistry, Schools of Dentistry and Public Health, University of Michigan. "Several recent studies have shown that having periodontal disease makes those with type 2 diabetes more likely to develop worsened glycemic control and puts them at much greater risk of end-stage kidney disease and death," he reported.

"Given the numerous medical studies showing that good glycemic control results in reduced development and progression of diabetes complications, we believe there is the potential that periodontal treatment can provide an increment in diabetes control and subsequently a reduction in the risk for diabetes complications," said Dr. Taylor.

Nearly 21 million Americans have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, and amputation. It is the fifth leading cause of death by disease in the U.S. Type 2 occurs mainly in adults who are overweight and ages 40 and older.

Periodontal (gum) disease is an infection and chronic inflammatory disease of the tissues surrounding and supporting the teeth. It is a major cause of tooth loss in adults. In periodontitis, unremoved plaque hardens into calculus (tartar), gums gradually begin to pull away from the teeth, and pockets form between the teeth and gums. However, people often do not know they have periodontal disease because it is usually painless.

Periodontitis Associated with Insulin Resistance and Diabetes Severity

"In an analysis of the National Health and Nutrition Examination Survey of the U.S. population data from 1988-94, we recently found that people with periodontal disease were twice as likely to have insulin resistance than those without such disease," said Dr. Taylor. This result was found after controlling for other characteristics that would be associated with insulin resistance, such as obesity, lipids, exercise, and other markers of inflammation, such as CRP, and whether or not they had diabetes.

In an unpublished study at the General Clinical Research Center at Stony Brook University, a group of individuals who were by one measure -- RD values (a measure of glucose uptake and insulin sensitivity) -- insulin resistant, and likely had pre-diabetes, also had their oral health assessed. Their degree of insulin resistance directly correlated with the severity of their periodontal disease.

"The inflammation from the oral cavity may be contributing to the insulin resistance in this patient population," said Dr. Ryan.

Also measured in this group were levels of cytokines, such as IL-1 beta, which are pro-inflammatory mediators involved in the long-term diabetes complications. "Genetic testing revealed that 50% of the insulin resistant patients had an IL-1 polymorphism -- in contrast to 20% in the overall population, meaning that they are genetically susceptible to an excessive inflammatory response, and this 50% was the group that had high levels of insulin resistance and more severe periodontal disease," she said.

The presence of the IL-1 polymorphism fits with one theory of how periodontitis worsens glycemic control in type 2 diabetes.

"We think periodontitis may adversely affect glycemic control because the pro-inflammatory chemicals produced by the infection -- such as IL-1-beta, IL-6, and TNF-alpha -- could transfer from the gum tissue into the bloodstream and stimulate cells to become resistant to insulin," said Dr. Taylor. "Then insulin resistance prevents cells in the body from removing glucose from the bloodstream for energy production."

Periodontitis Associated with Diabetes Complications

Dr. Taylor reported on studies at the University of Michigan and elsewhere demonstrating the association between periodontitis and the complications of type 2 diabetes.

"A recent set of observational studies of the Pima Indians in the Southwest, a population with a very high rate of type 2 diabetes, investigated whether those with periodontitis are more likely to develop poorer glycemic control," said Dr. Taylor. "We found that those with periodontitis were more than four times as likely to develop worsened glycemic control after two years of follow-up."

Studies of Pima Indians published by others have shown a higher risk of diabetes complications in those with periodontal disease. For example, one showed that residents of the Gila River Indian Community with severe periodontal disease were at more than three times the risk of death due to diabetic nephropathy or ischemic heart disease than those with no, mild, or moderate periodontal disease over 11 years.

Periodontal Treatment Can Improve Diabetes Control

"Just as periodontal disease makes diabetes worse, the reverse also appears to be true, with improvements in periodontal disease benefiting diabetes control," said Dr. Taylor. "We conducted an NIH-funded, randomized clinical trial in 46 people with type 2 diabetes and, 15 months after routine periodontal treatment, found a statistically significant reduction of 0.67% in A1C levels," said Dr. Taylor.

"We recently published a randomized, placebo-controlled, 30-patient study done at the General Clinical Research Center at Stony Brook University showing that a sub-antimicrobial dose of doxycycline, during and after root planing, as part of a 9-month course of treatment, significantly reduced A1C by 1% and also reduced proteinuria, a marker of diabetic kidney disease, and CRP, a marker of inflammation," said Dr. Ryan. "It also significantly reduced pocket depths associated with periodontitis and enabled gains in clinical attachment, while reducing signs of inflammation, such as bleeding upon probing or brushing." Two confirmatory 3-month studies of this program developed at Stony Brook have been conducted, at Columbia University and Buffalo University with 150 patients, and presented at International Association for Dental Research meetings.

"When glycemia has been difficult to control, the physician might consider asking patients when they last saw their dentist, whether periodontitis has been diagnosed and, if so, whether treatment has been completed," said Dr. Ryan. "A consultation with the dentist may be appropriate, to discuss whether periodontal treatment has been successful or whether a more intensive approach with oral or sub-antimicrobial antibiotics is in order because, just as it is difficult to control diabetes while the patient has an infected leg ulcer, the same applies when there's infection and inflammation of the gums."

Posted by dlife at 02:34 PM | Comments (0)

Long-Term Pesticide Exposure May Increase Risk Of Diabetes

June 04, 2008

June 4, 2008 (EurekAlert) - Licensed pesticide applicators who used chlorinated pesticides on more than 100 days in their lifetime were at greater risk of diabetes, according to researchers from the National Institutes of Health (NIH). The associations between specific pesticides and incident diabetes ranged from a 20 percent to a 200 percent increase in risk, said the scientists with the NIH's National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI).

"The results suggest that pesticides may be a contributing factor for diabetes along with known risk factors such as obesity, lack of exercise and having a family history of diabetes," said Dale Sandler, Ph.D., chief of the Epidemiology Branch at the NIEHS and co-author on the paper. "Although the amount of diabetes explained by pesticides is small, these new findings may extend beyond the pesticide applicators in the study," Sandler said. Some of the pesticides used by these workers are used by the general population, though the strength and formulation may vary. Other insecticides in this study are no longer available on the market, however, these chemicals persist in the environment and measurable levels may still be detectable in the general population and in food products. For example, chlordane, which was used to treat homes for termites, has not been used since 1988, but can remain in treated homes for many decades. More than half of those studied in the National Health and Nutrition Examination Survey in 1999-2002 had measurable evidence of chlordane exposure. "This is not cause for alarm," added Sandler "since there is no evidence of health effects at such very low levels of exposure."

Overall, pesticide applicators in the highest category of lifetime days of use of any pesticide had a small increase in risk for diabetes (17 percent) compared with those in the lowest pesticide use category (0-64 lifetime days). New cases of diabetes were reported by 3.4 percent of those in the lowest pesticide use category compared with 4.6 percent of those in the highest category. Risks were greater when users of specific pesticides were compared with applicators who never applied that chemical. For example, the strongest relationship was found for a chemical called trichlorfon, with an 85 percent increase in risk for frequent and infrequent users and nearly a 250 percent increase for those who used it more than 10 times. In this group, 8.5 percent reported a new diagnosis of diabetes compared with 3.4 percent of those who never used this chemical. Trichlorfon is an organophosphate insecticide classified as a general-use pesticide that is moderately toxic. Previously used to control cockroaches, crickets, bedbugs, fleas, flies and ticks, it is currently used mostly in turf applications, such as maintaining golf courses.

"This is one of the largest studies looking at the potential effects of pesticides on diabetes incidence in adults," said Freya Kamel, Ph.D., a researcher in the intramural program at NIEHS and co-author in the paper appearing in the May issue of the American Journal of Epidemiology. "It clearly shows that cumulative lifetime exposure is important and not just recent exposure," said Kamel. Previous cross-sectional studies have used serum samples to show an association between diabetes and some pesticides.

Diabetes occurs when the body fails to produce enough insulin to regulate blood sugar levels or when tissues stop responding to insulin. Nearly 21 million Americans have diabetes. The cause of diabetes continues to be a mystery, although genetics and environmental factors such as obesity and lack of exercise appear to play roles.

To conduct the study, the researchers analyzed data from more than 30,000 licensed pesticide applicators participating in the Agricultural Health Study, a prospective study following the health history of thousands of pesticide applicators and their spouses in North Carolina and Iowa. The 31,787 applicators in this study included those who completed an enrollment survey about lifetime exposure levels, were free of diabetes at enrollment, and updated their medical records during a five-year follow-up phone interview. Among these, 1,171 reported a diagnosis of diabetes in the follow-up interview. The majority of the study participants were non-Hispanic white men.

Researchers compared the pesticide use and other potential risk factors reported by the 1,171 applicators who developed diabetes since enrolling in the study to those who did not develop diabetes. Among the 50 different pesticides the researchers looked at, they found seven specific pesticides — aldrin, chlordane, heptachlor, dichlorvos, trichlorfon, alachlor and cynazine — that increased the likelihood of diabetes among study participants who had ever been exposed to any of these pesticides, and an even greater risk as cumulative days of lifetime exposure increased.

All seven pesticides are chlorinated compounds, including two herbicides, three organochlorine insecticides and two organophosphate pesticides.

"The fact that all seven of these pesticides are chlorinated provides us with an important clue for further research," said Kamel. Previous studies found that organochlorine insecticides such as chlordane were associated with diabetes or insulin levels. The new study shows that other types of chlorinated pesticides, including some organophosphate insecticides and herbicides, are also associated with diabetes. The researchers also found that study participants who reported mixing herbicides in the military had increased odds of diabetes compared to non-military participants.

Posted by dlife at 09:41 AM | Comments (0)

Anti-inflammatory Medication May Treat Type 2 Diabetes

May 21, 2008

May 21, 2008 (Newswise) — Researchers at the Joslin Diabetes Center who reported earlier this year that an inexpensive, non-steroidal anti-inflammatory drug called salsalate might prevent type 2 diabetes are now reporting that the drug may also be beneficial in the treatment of the disease.

The paper, which appears in the May 2008 issue of the journal Clinical and Translational Science (CTS), reports on three proof-of-concept studies that demonstrate that salsalate, which has been used for decades to treat arthritis, may benefit patients with type 2 diabetes by lowering blood sugar and reducing inflammation.

“These are the first studies showing that potentially safe and tolerable doses of salsalate lower blood sugars and have other favorable effects in patients with type 2 diabetes,” notes Allison B. Goldfine, M.D., Director of Clinical Research at Joslin and Associate Professor at Harvard Medical School, and senior author of the report.

Goldfine was also the lead researcher for an earlier study, published in the February issue of Diabetes Care, which demonstrated that salsalate may prevent type 2 diabetes by lowering blood glucose and reducing inflammation.

Together, these four proof-of-concept studies have led to three large, ongoing multi-center clinical trials that seek to confirm the benefit of targeting inflammation using salsalate to lower glucose in patients with type 2 diabetes or who are at risk for diabetes, or to reduce atherosclerosis in patients with coronary artery disease.

The clinical studies are a direct extension of the findings of study co-author and collaborator Steven Shoelson, M.D., Ph.D., Helen and Morton Adler Chair, Head of the Section of Cellular and Molecular Physiology at Joslin, and Professor at Harvard Medical School. Dr. Shoelson studies the molecular pathogenesis of type 2 diabetes and the role of obesity in promoting diabetes and other metabolic conditions, including atherosclerosis.

It had originally been noted nearly 150 years ago that salicylates could lower blood glucose levels, but this had either been forgotten or ignored. Dr. Shoelson’s laboratory used this as clue to probe potential reasons why obesity promotes disease. They found that the inflammatory pathway regulated by NF-kB is activated in animals with obesity and diabetes. They went on to demonstrate that this pathway could be inhibited using salicylates, thus showing that the effects of obesity are mediated through inflammation. This was not an accepted concept at the time, and is still debated in field.

Studies in animals showed that high doses of salicylates, including aspirin, could be effective, but since these could not be used safely in patients due to the risk of stomach upset and bleeding the researchers considered alternative drugs. Together, Drs. Goldfine and Shoelson opted to study salsalate, which is a salicylate similar to aspirin but that does not cause stomach upset or bleeding.

Shoelson notes that the studies now being reported in CTS provide a ‘smoking gun’ – new evidence that incriminates inflammation as a major pathogenic mediator in type 2 diabetes – as well as a potentially safe new way to treat the disease.

“It is rare to see basic discoveries move from bench to bedside so quickly. This was fueled by at least two things, first the ready availability of a safe drug, and second the environment at the Joslin Diabetes Center which is ideally suited to rapid advancements in clinical discovery,” he said.

Goldfine further opines, “much of the pharmacokinetic and long-term safety data for salsalate is already established, so clinical studies could move forward rapidly.”

“Our findings are potentially very exciting because we show that a medication that treats inflammation may also treat diabetes and related medical conditions,” said Goldfine. “If we can show in the larger clinical trials now underway that it is safe and effective, it means salsalate may be a new way to treat diabetes.”

In the paper out today, two of the studies involved small numbers of patients with type 2 diabetes. One tested salsalate on seven subjects at a dose of 4.5 grams per day, while the other used 3 grams per day on nine subjects. Patients in both groups showed benefits such as reductions in blood sugar between 10 and 20 percent, but improvements were greatest in the group taking the higher dose. Glucose utilization also improved in both groups, although those taking the higher dose showed a 50 percent improvement, compared to 15 percent for those on the lower dose. The studies ran for two weeks each.

Impressive reductions were also seen in circulating levels of triglycerides and free fatty acids, particularly at the higher dose. This is important because patients with diabetes often have elevated lipid levels that potentially contribute to complications of type 2 diabetes.

The third study, a double blind, placebo-controlled trial that ran for four weeks, involved eight patients on the drug and nine on placebo. Study participants on the drug showed improvements similar to those reported in the patients in the other two studies analyzed.

In an accompanying commentary, Barry J. Goldstein, M.D., of the Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College, wrote: “The testing of a commonly used class of drugs, with a well-known safety profile, offers an exciting translational approach that promises to help in the management of glycemia in type 2 diabetes.”

He noted: “A world-wide epidemic of type 2 diabetes is underway that shows no signs of remitting in the next several years. In order to address the basic therapeutic needs of these millions of patients, additional treatment options will need to be made available, especially to have some hope of getting the majority of patients to accepted glucose treatment goals.”

The studies were funded by grants from the National Institutes of Health; fellowships from the William Randolph Hearst Foundation and American Diabetes Association; and the Helen and Morton Adler Chair at Joslin Diabetes Center.

Other researchers participating included Robert Silver, Elizabeth Tatro and Jongsoon Lee at Joslin; Waleed Aldahi of Mubarik Alkabeer University Hospital, Kuwait; and Dongsheng Cai of the University of Wisconsin.

Salsalate Clinical Trials
Dr. Goldfine is the principal investigator of a study that targets inflammation using salsalate in patients with coronary artery disease and metabolic syndrome. The study, called Targeting INflammation using SALsalate or Lifestyle intervention in the Metabolic Syndrome and Cardiovascular Disease (TINSAL-CVD), is funded by The National Heart, Lung and Blood Institute and is currently enrolling patients. It will look at the effects of lifestyle intervention (diet, exercise and omega-3 fatty acid supplement) or salsalate compared to placebo to reduce progression or promote regression of hard and soft coronary artery calcification as assessed by multi-detector CT angiography (MDCTA), a relatively new method to image the coronary arteries. Patients are randomized to lifestyle, salsalate or placebo with images of the coronary arteries at baseline and after 30 months of intervention. Dr. Shoelson is co-PI on the salsalate arm of the trial, while study collaborators Dr. Ernest Schaefer of The Jean Mayer USDA Human Nutrition Center on Aging at Tufts University and Dr. Francine Welty of Beth Israel Deaconess Medical Center (BIDMC) are running the lifestyle intervention arm; Dr. Melvin Clouse of BIDMC is leading the imaging core.

A second study called Targeting Inflammation using SALsalate in Type 2 Diabetes (TINSAL-T2D) headed by Drs. Goldfine and Shoelson is using salsalate in patients with type 2 diabetes to target inflammation and thus lower blood glucose. This study is ongoing and is funded by the National Institute of Diabetes and Digestive and Kidney Diseases.

Another study led by Dr. Goldfine and Dr. Peter Reaven of the Carl T. Hayden VA Medical Center in Phoenix targets inflammation using salsalate in patients with impaired glucose tolerance in order to improve insulin sensitivity. This study, called TINSAL-IGT, is ongoing and is funded by the VA.

Posted by dlifenews at 08:29 AM | Comments (2)

Data from Pooled Analyses Demonstrates Welchol, Combined with Metformin- or Sulfonylurea-Based Therapy, Significantly Lowers Blood Glucose in Adults with Type 2 Diabetes

May 16, 2008

May 16, 2008 (PRNewswire) -- Daiichi Sankyo, Inc. (DSI) announced today that data from two pooled analyses further demonstrate that Welchol(TM) (colesevelam HCl), in combination with metformin- or sulfonylurea- based therapy, significantly lowers blood glucose (as measured by A1C) in patients with type 2 diabetes mellitus who had failed to achieve glycemic control (ADA target of A1C <7%). These findings, presented at the American Association of Clinical Endocrinologists' (AACE) 17th Annual Meeting and Clinical Congress, are the latest in a series of diabetes-related milestones for Welchol. In April, DSI announced that Welchol was added to the American College of Endocrinology (ACE)/AACE "Road Maps to Achieve Glycemic Control in Type 2 Diabetes Mellitus."

The efficacy of Welchol compared to placebo was evaluated in patients receiving metformin-based or sulfonylurea-based therapy (either monotherapy or in combination with other antidiabetes therapy) in two separate pooled analyses of patients from three Welchol pivotal studies.* The addition of Welchol in patients on established metformin-based therapy demonstrated a significant mean A1C reduction of 0.50%, placebo-corrected change from baseline (mean baseline A1C was 8.2% for both Welchol and placebo). In a second pooled analysis, the addition of Welchol in patients on established sulfonylurea-based therapy demonstrated a mean reduction in A1C of 0.53%, placebo-corrected change from baseline (mean baseline A1C was 8.2% and 8.3% for Welchol and placebo, respectively).

"These analyses further demonstrate the potential benefit of adding Welchol to current common diabetes treatment regimens," said Vivian E. Fonseca, Professor of Medicine and Pharmacology and Chief, Section of Endocrinology, Tulane University Health Sciences Center, a principal investigator of the study. "This gives physicians an additional option when it comes to helping their patients lower their A1C levels."

Several mechanisms have been proposed for the glucose-lowering effect of Welchol, including reductions in glucose absorption and effects on glucose metabolism via nuclear receptors in the intestine and/or the liver. The exact mechanism(s) is under investigation and remains to be confirmed.

About the Analyses

A pooled analysis evaluated 696 patients on metformin-based therapy (monotherapy or combination with other antidiabetes agents) who received add- on treatment with Welchol 3.75 g/day (n=355) or placebo (n=341). Efficacy endpoints in this analysis included change from baseline in A1C and fasting plasma glucose (FPG). Lipids and weight were not analyzed in this pooled analysis, however, LDL-C was significantly reduced in each of the primary studies (P<0.001 vs. placebo). Weight did not significantly change with Welchol in any of the primary studies. The addition of Welchol to metformin- based therapy achieved a significant mean reduction in A1C levels of 0.42% while A1C increased by 0.08% in the placebo group, resulting in a placebo- corrected mean change from baseline of -0.50% (P<0.001). Fasting plasma glucose decreased by -4.6 mg/dL in the Welchol group and increased by 11.1 mg/dL in the group treated with placebo, resulting in a mean treatment difference of -15.7 mg/dL (P<0.001). Furthermore, the addition of Welchol to metformin therapy resulted in a significantly higher proportion of patients achieving a mean reduction in A1C of greater than or equal to 0.7% (38.3% vs. 19.4%; P<0.001) or a reduction in FPG greater than or equal to 30 mg/dL (30.1% vs. 22.0%; p=0.015), from baseline to endpoint versus the placebo.

A second pooled analysis evaluated 653 patients on sulfonylurea-based therapy (monotherapy or combination with other antidiabetes agents). Patients received add-on therapy with Welchol 3.75 g/day (n=326) or placebo (n=327). The addition of Welchol resulted in a mean A1C change from baseline of -0.35% (mean baseline A1C 8.2%) compared with placebo which had a mean increase of 0.18% (mean baseline A1C 8.3%), resulting in a mean treatment difference of - 0.53% by study end (P<0.001). Fasting plasma glucose decreased by -1.4 mg/dL in the patients treated with Welchol and increased by 12.2 mg/dL in the placebo group, resulting in a mean treatment difference of -13.6 mg/dL (P<0.001). In addition, significantly more patients in the Welchol treatment group achieved a reduction in A1C greater than or equal to 0.7% (35.0% vs. 16.5%; P<0.001) or FPG greater than or equal to 30 mg/dL (29.1% vs. 21.7%; P=0.029), from baseline to endpoint versus the placebo group.

Welchol Added to AACE Road Maps

Daiichi Sankyo also recently announced that Welchol has been added to the American College of Endocrinology (ACE) and American Association of Clinical Endocrinologist's (AACE) 2008 "Road Maps to Achieve Glycemic Control in Type 2 Diabetes Mellitus". The Road Maps are updated regularly by ACE/AACE to provide physicians with the latest and most comprehensive treatment options for their patients with type 2 diabetes mellitus. Welchol is the first and only therapy approved to treat both type 2 diabetes and high LDL-cholesterol. This is the second major diabetes related milestone for Welchol this year, as Welchol was approved by the FDA for the treatment of type 2 diabetes in January.

"Welchol offers physicians a new treatment option that addresses two cardiovascular risk factors, high LDL-cholesterol and blood glucose in patients with type 2 diabetes," said Sukumar Nagendran, M.D., Senior Director, Diabetes and Metabolism, Daiichi Sankyo, Inc. "Cardiovascular risk factors are always of great concern to physicians treating type 2 diabetes patients, as they are at significantly greater risk for developing cardiovascular disease. The inclusion of Welchol in these Road Maps will enable more physicians to be aware of the potential impact of adding this unique product to their patients' treatment regimen."

It is estimated that half of all Americans have elevated blood cholesterol levels that can negatively impact their health and quality of life.(1) According to the National Healthcare Quality Report, nearly 40 percent of adults with high cholesterol also have type 2 diabetes.(2)

The ADA recommends that patients with type 2 diabetes target an A1C level of <7 percent.(3) A1C is a common test for persistent hyperglycemia ("too much glucose in the blood"). Additionally, the National Cholesterol Education Program (NCEP) recommends that patients with type 2 diabetes keep their cholesterol levels in check and target an LDL-C goal of <100 mg/dL.(4) Despite this recommendation, nearly 40 percent of patients with type 2 diabetes have LDL-cholesterol levels greater than 130 mg/dL.(5)

IMPORTANT INFORMATION ABOUT WELCHOL

Welchol is indicated as an adjunct to diet and exercise to reduce elevated low-density lipoprotein cholesterol (LDL-C) in patients with primary hyperlipidemia (Fredrickson Type IIa) as monotherapy or in combination with an hydroxymethyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor. Welchol is also indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Welchol should not be used for the treatment of type 1 diabetes or for the treatment of diabetic ketoacidosis. It has not been studied in type 2 diabetes as monotherapy or in combination with a dipeptidyl peptidase 4 inhibitor and has not been extensively studied in combination with thiazolidinediones. Welchol has not been studied in Fredrickson Type I, III, IV, and V dyslipidemias.

Welchol is contraindicated in individuals with bowel obstruction, those with serum triglyceride (TG) concentrations of >500 mg/dL, or with a history of hypertriglyceridemia-induced pancreatitis.

The effect of Welchol on cardiovascular morbidity and mortality has not been determined. Welchol can increase serum TG concentrations particularly when used in combination with sulfonylureas or insulin. Caution should be exercised when treating patients with TG levels >300 mg/dL.

Welchol may decrease the absorption of fat-soluble vitamins A, D, E, and K. Patients on vitamin supplements should take their vitamins at least 4 hours prior to Welchol. Caution should be exercised when treating patients with a susceptibility to vitamin K or fat soluble vitamin deficiencies.

Caution should also be exercised when treating patients with gastroparesis, gastrointestinal motility disorders, major gastrointestinal tract surgery, and when treating patients with dysphagia and swallowing disorders.

Welchol reduces gastrointestinal absorption of some drugs. Drugs with a known interaction with colesevelam (glyburide, levothyroxine, and oral contraceptives [ethinyl estradiol, norethindrone]) should be administered at least 4 hours prior to Welchol. Drugs that have not been tested for interaction with colesevelam, especially those with a narrow therapeutic index, should also be administered at least 4 hours prior to Welchol. Alternatively, the physician should monitor drug levels of the co-administered drug.

Primary Hyperlipidemia: In clinical trials, the adverse reactions observed in greater than or equal to 2% of patients -- and more commonly with Welchol than placebo -- regardless of investigator assessment of causality were constipation (11.0% vs. 7.0%), dyspepsia (8.3% vs. 3.5%), nausea (4.2% vs. 3.9%), accidental injury (3.7% vs. 2.7%), asthenia (3.6% vs. 1.9%), pharyngitis (3.2% vs. 1.9%), flu syndrome (3.2% vs. 3.1%), rhinitis (3.2% vs. 3.1%) and myalgia (2.1% vs. 0.4%).

Type 2 Diabetes: In clinical trials, the adverse reactions observed in greater than or equal to 2% of patients -- and more commonly with Welchol than placebo -- regardless of investigator assessment of causality were constipation (8.7% vs. 2.0%), nasopharyngitis (4.1% vs. 3.6%), dyspepsia (3.9% vs. 1.4%), hypoglycemia (3.0% vs. 2.3%), nausea (3.0% vs. 1.4%) and hypertension (2.8% vs. 1.6%).

Post-marketing experience: Due to the voluntary nature of these reports it is not possible to reliably estimate frequency or establish a causal relationship. Increased seizure activity or decreased phenytoin levels have been reported in patients receiving phenytoin concomitantly with Welchol. Reduced International Normalized Ratio (INR) has been reported in patients receiving warfarin concomitantly with Welchol.

Welchol is Pregnancy Category B.

For more information on Welchol, call 877-4-DSPROD (877-437-7763), or go to the Welchol web site at www.Welchol.com.

Posted by dlifenews at 12:03 PM | Comments (0)

How Slow Growth as a Fetus Can Cause Diabetes as an Adult

May 08, 2008

May 8, 2008 (EurekAlert) - Intrauterine growth retardation (IUGR), which results in a baby having a low weight at birth, has been linked to the development of type 2 diabetes in adulthood. It has been suggested that this is because the expression of key genes is altered during fetal development and that this affects disease susceptibility later in life. Evidence to support this hypothesis and indicating that the changes in gene expression might be permanent has now been provided by Rebecca Simmons and colleagues, at the University of Pennsylvania, Philadelphia, using a rat model of IUGR.

Pervious studies using the rat model of IUGR have shown decreased fetal expression of the gene Pdx1, which is critical for the development and function of the cells that become defective in type 2 diabetes (pancreatic beta-cells), and adult onset of diabetes. In this study, expression of Pdx1 was found to be reduced in pancreatic beta-cells throughout life following IUGR. The molecular mechanisms (known as epigenetic mechanisms because they affect gene expression without altering the information in the gene) that reduced Pdx1 expression in pancreatic beta-cells were found to change during development. One mechanism was observed in the fetus, one following birth, and one after the onset of diabetes in adulthood. Of interest, the mechanisms reducing Pdx1 gene expression in the fetus and following birth could be reversed, whereas those reducing Pdx1 gene expression in the adult were irreversible. These data provide new insight into the mechanisms by which diabetes develops in adulthood following IUGR.

Posted by dlife at 12:49 PM | Comments (0)

American Association of Clinical Endocrinologists Endorses National Diabetes Goal

May 07, 2008

May 7, 2008 (AACE Newsroom) - The American Association of Clinical Endocrinologists (AACE) today announced its support for the National Diabetes Goal. The Goal is to help 45% of all Americans at risk for type 2 diabetes know their blood glucose levels and understand what actions to take, by the year 2015.

The National Diabetes Goal was announced in our nation’s capitol, with national leaders in health care, business, government, and education showing their support for the unified goal. The groups hope that this knowledge will help reverse the upward trend in diagnoses of type 2 diabetes.

Survey results released today by Gallup and commissioned by the National Changing Diabetes Project show that, while more than 90% of Americans consider diabetes a serious health issue, and half say they feel personally affected by diabetes, awareness has not yet translated into collective, widespread action.

The National Diabetes Goal has a call to action for every American:
• Find out if you are at risk for type 2 diabetes
• Ask about getting your blood glucose tested during your next doctor’s visit
• Know your blood glucose level and what actions to take

AACE is one of more than 20 organizations who have committed their support to the National Diabetes Goal. Other supporting organizations include: American Academy of Family Physicians, American Association of Colleges of Pharmacy, American Association of Diabetes Educators, American Association of Physician Assistants, American College of Physicians, American College of Clinical Pharmacy, American Diabetes Association, American Medical Group Association, American Optometric Association, Campaign to End Obesity, Center for Health Transformation, Essence Healthcare, Entertainment Industry Foundation, Food Marketing Institute, National Association of Chain Drug Stores, National Association of School Nurses, National Business Coalition on Health, National Minority Quality Forum, National Changing Diabetes Program, Novo Nordisk, and Revolution Health.

An online resource has been setup at www.NationalDiabetesGoal.com that outlines the background and purpose of the goal and provides resources for consumers and stakeholders to respond to the call to action.

Posted by dlife at 02:04 PM | Comments (0)

Researchers Important Markers Of High Risk Of Type 2 Diabetes

April 29, 2008

April 25, 2008 (EurekAlert) - Doctors are aware of a range of risk factors, mostly related to the patients’ family history, overweight, and lifestyle, that contribute to the risk of developing type 2 diabetes. Now researchers at the University of Warwick have found markers that indicate endothelial dysfunction (changes in the cells which line the blood vessels) and sub-clinical systemic inflammation can also help identify a far greater number of people at high risk for future development of type 2 diabetes.

In a study led by Dr Saverio Stranges, Associate Professor of Cardiovascular Epidemiology at Warwick Medical School at the University of Warwick, the team looked at a protein called E-selectin, whose presence is an indication of endothelial dysfunction, white blood cell count and levels of albumin, which are marker for sub-clinical systemic inflammation.

They found high levels of E-selectin and white blood cell count with low levels of serum albumin were clear predictors of high risk for type 2 diabetes. The researchers found that traditional risk factors such as obesity or family history helped identify 65% of all patients who were at high risk of developing type 2diabetes. But when the information from these three markers was added this increased from 65% to 73% which means doctors could be able to spot a greater number of people at risk of type 2 diabetes at an early stage.

The research used data taken from the Western New York Health Study. This was a six-year longitudinal study of diabetes and cardiovascular risk factors among residents of Erie and Niagara Counties, New York.

Dr Stranges said: "High levels of E-selectin and white blood cells with low levels of serum albumin can indicate endothelial dysfunction and sub-clinical systemic inflammation. These findings corroborate the notion that both these conditions play an important role in the development of the disease. Endothelial dysfunction is also regarded as a key event in the development and progression of atherosclerosis. Finding new markers for type 2 diabetes will help us gain a greater understanding of the condition and possibly open up new possibilities for the way we prevent and treat it."

Posted by dlife at 10:30 AM | Comments (0)

100M Pounds a Year Spent on Self-Monitoring in Diabetes That May Increase Anxiety and Depression

April 17, 2008

Research: Efficacy of self-monitoring of blood glucose in patients with newly diagnosed type 2 diabetes: Randomized controlled trial

April 17, 2008 (EurekAlert) - The National Health Service (NHS) in the UK is spending £100 million a year to help people with non-insulin treated type 2 diabetes monitor their own blood sugar levels, but the process is more likely to make them depressed than provide any long-term health benefits, according to a series of articles published ahead of print on bmj.com today.

Globally one in twenty people have diabetes. The majority (85–95%) have type 2 diabetes, in which the body has either stopped making insulin or has difficulty making enough to convert blood sugar into the fuel our bodies need. Cases of type 2 diabetes are on the increase in the UK.

It has been generally acknowledged that self monitoring of blood glucose levels is beneficial for patients who have type 1 diabetes and those with type 2 diabetes who use insulin to treat their condition. However, the majority of people with type 2 diabetes do not use insulin, and it is for this group of people that there has been debate over the effectiveness of self monitoring. Yet, despite a lack of evidence, self monitoring has been widely promoted for this group in clinical practice.

Dr Maurice O’Kane and colleagues from the University of Ulster, report on a randomised controlled trial to assess whether self monitoring has an effect on blood glucose levels and the incidence of hypoglycaemia in people with newly diagnosed type 2 diabetes.

The researchers found no significant effect of self monitoring on blood sugar levels or cases of hypoglycaemia after a year. However, the patients in the self-monitoring group reported higher levels of depression and anxiety.

Evidence suggests that some patients find self monitoring “uncomfortable, intrusive and unpleasant”. And the researchers suggest that the negative feelings reported in the study might be due to the enforced discipline of regular monitoring without any obvious benefit, rather than due to “feelings of powerlessness in the face of high blood glucose readings.”

Self monitoring of blood glucose is the largest single management cost associated with implementing more intensive blood glucose control in the UK, with costs of providing test strips increasing from £85m to £118m between 2001 and 2003. Thus, it is important to establish if self monitoring represents a cost effective use of resources that could otherwise be used to finance other aspects of diabetes care.

In a separate study, Dr Judit Simon and colleagues from the University of Oxford, analysed the cost-effectiveness of helping patients with non-insulin treated type 2 diabetes self monitor their blood glucose levels in addition to standardised usual care, using data from the diabetes glycaemic education and monitoring (DiGEM) trial.

Their analysis confirms that self monitoring of blood glucose is significantly more expensive than the standardised usual care. They found that the additional healthcare costs of self monitoring were about £90 per patient each year. Furthermore, people who self monitored reported a lower quality of life probably owing to significant increases in their levels of anxiety and depression.

The authors say that self monitoring in addition to standardised usual care is unlikely to provide this group of patients with significant lifetime health benefits or be cost effective for the NHS. They conclude: “This study therefore provides no convincing evidence for routinely recommending self monitoring to patients with non-insulin treated type 2 diabetes.”

In an accompanying editorial, Professor Martin Gulliford argues that the £100 million that is spent each year on self monitoring for this group of patients: “Represents a substantial opportunity cost in terms of alternative interventions that might have improved the health of people with diabetes…[such as] more effective disease control measures aimed not at blood glucose but also at blood pressure, cholesterol, smoking, body weight, and physical activity.”

Posted by dlife at 11:45 AM | Comments (11)

How And Where Fat Is Stored Predicts Disease Risk Better Than Weight

April 16, 2008

April 16, 2008 (EurekAlert) - A new study in mice indicates that overeating, rather than the obesity it causes, is the trigger for developing metabolic syndrome, a collection of heath risk factors that increases an individual’s chances of developing insulin resistance, fatty liver, heart disease and type 2 diabetes.

How and where the body stores excess, unused calories appears to matter most when determining a person’s risk of developing metabolic syndrome, researchers at UT Southwestern Medical Center suggest.

“Most people today think that obesity itself causes metabolic syndrome,” said Dr. Roger Unger, professor of internal medicine at UT Southwestern and senior author of the study. “We’re ingrained to think obesity is the cause of all health problems, when in fact it is the spillover of fat into organs other than fat cells that damages these organs, such as the heart and the liver. Depositing fatty molecules in fat cells where they belong actually delays that harmful spillover.”

The study, available online, is to be published in a future issue of the Proceedings of the National Academy of Sciences. It is among the first to suggest that weight gain is an early symptom of pre-metabolic syndrome, rather than a direct cause.

“Obesity delays the onset of metabolic syndrome, but it doesn’t prevent it,” said Dr. Unger, who has investigated diabetes, obesity and insulin resistance for more than 50 years. “People who are obese or overweight are on the road to developing metabolic syndrome unless they stop overeating. Sooner or later, it will happen.”

Currently about 50 million Americans suffer from metabolic syndrome. The exact cause of metabolic syndrome is unknown, but obesity and lack of exercise have been considered to be the primary underlying contributors to its development. Several studies in Dallas have shown that overweight patients with metabolic syndrome have increased fat levels in their liver, heart and pancreas.

Individuals with congenital generalized lipodystrophy – a genetic condition in which people are born with no fat cells in which to store fat – develop metabolic syndrome at an earlier age than people who are obese. They also develop more severe cases of metabolic syndrome earlier than their obese counterparts.

The goal of this study was to determine whether an individual’s capacity to store fat in fat cells plays a role in whether they develop metabolic syndrome and type 2 diabetes and at what point that occurs.

For the study, the researchers compared mice genetically altered to prevent their fat cells from expanding when overfed to mice with no such protections against becoming obese. The normal mice got fat when overfed, but didn’t develop signs of metabolic syndrome until about 7 weeks into the experiment, at about 12 weeks of age.

The mice engineered to remain slim, however, enjoyed no such “pre-diabetic honeymoon period,” the study authors said. Some became seriously ill at 4 to 5 weeks of age and displayed evidence of severe heart problems and marked hyperglycemia by 10 weeks of age, a full 8 weeks before the normal mice displayed even minimal heart problems. The genetically altered mice also suffered devastating damage to heart cells and to the insulin-secreting cells in their pancreas.

“The genetically altered animals were perfectly normal as long as they were on a normal diet and not overfed. But as soon as we put them on a high-calorie diet, they got terribly sick very fast,” said Dr. May-yun Wang, assistant professor of internal medicine at and lead author of the study.

She said the mice engineered to stay slim got sick quicker because the extra calories were not stored in the fat cells, the one place in the body equipped to store fat. Instead, fat was stored in other tissues, mimicking what happens in people with congenital generalized lipodystrophy.

“Recognition of this should encourage physicians and obese patients to pursue more aggressive interventions before they develop metabolic syndrome, rather than after the onset of disease, as is customary,” Dr. Wang said.

The new results complement earlier findings by diabetes researchers at UT Southwestern who investigated why mice genetically engineered to be obese are at no more risk of developing metabolic syndrome than normal mice. The results of that study, which was led by Dr. Philipp Scherer, professor of internal medicine and director of the Touchstone Center for Diabetes Research, also suggested that it’s not the amount of body fat, but where it is stored in the body that appears to matter most to health.

Dr. Unger said the most recent findings, like Dr. Scherer’s, in no way condone obesity.

“It’s best to eat only what you need to replace the energy you burn,” he said. “But, if you eat more than you need, as most Americans do, it’s better to put the surplus calories in fat cells than in the rest of the body because fat cells are designed specifically for fat storage. You won’t be as trim, but you’ll be healthier,” Dr. Unger said.

The study results also imply that any gene that impairs the ability to store fat in the fat cells likely predisposes an individual to metabolic syndrome and type 2 diabetes, Dr. Unger said.

Posted by dlife at 11:37 AM | Comments (1)

Cholesterol, Blood Pressure Control May Reverse Atherosclerosis in Adults With Diabetes

April 08, 2008

April 8, 2008 (EurekAlert) - Aggressively lowering cholesterol and blood pressure levels below current targets in adults with type 2 diabetes may help to prevent – and possibly reverse – hardening of the arteries, according to new research supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. Hardening of the arteries, also known as atherosclerosis, is the number one cause of heart disease and can lead to heart attack, stroke, and death.

The three-year study of 499 participants is the first to compare two treatment targets for LDL (“bad”) cholesterol and systolic blood pressure levels, key risk factors for heart disease, in people with diabetes. Results are published in the April 9 issue of the Journal of the American Medical Association.

“This study provides good news for adults with type 2 diabetes,” said Elizabeth G. Nabel, M.D., NHLBI director. “These patients are two to four times more likely than people without diabetes to die from heart disease. For the first time, we have evidence that aggressively lowering LDL cholesterol and blood pressure can actually reverse damage to the arteries in middle-aged adults with diabetes.”

In the Stop Atherosclerosis in Native Diabetics Study (SANDS), approximately one-half of the participants (247) were asked to lower to standard levels their LDL cholesterol (to 100 milligrams per deciliter) and blood pressure (systolic blood pressure of 130 mmHg or lower), while the other half (252) aimed for more aggressive lowering of LDL cholesterol to 70 mg/dL or lower and of systolic blood pressure to 115 mmHg or lower. All participants were American Indians 40 years or older (average age of 56) who had diabetes, high blood cholesterol, and high blood pressure but no history of heart attack or other evidence of heart disease. The study was conducted at four clinical centers in southwestern Oklahoma; Phoenix, Ariz.; northeastern Arizona; and South Dakota. All participants continued to receive their medical care, including diabetes management, dietary and exercise counseling, and smoking cessation, from their health care providers with the Indian Health Service. Like the NIH, the Indian Health Service is part of the U.S. Department of Health and Human Services.

“American Indians have a high rate of diabetes and cardiovascular disease related to diabetes, but there are few clinical trials that address these issues in this population,” said Barbara V. Howard, Ph.D., of MedStar Research Institute in Hyattsville, Md., lead author of the paper. “These study results provide needed evidence to help develop community-based programs to treat and prevent the epidemic of cardiovascular disease among American Indians. At the same time, we are increasing our understanding of the effects of intensively lowering cholesterol and blood pressure in adults with type 2 diabetes, which might also apply to other populations.”

During the three-year study, participants were examined by study clinicians one month after enrollment, then every three months, to assess their blood cholesterol and blood pressure levels and general well being. Food and Drug Administration-approved blood pressure and cholesterol medications were added and adjusted as needed to help participants achieve their treatment goals. The same medications were available to participants in the standard and the aggressive treatment groups. Participants were also encouraged to follow lifestyle approaches to help meet their blood pressure and cholesterol treatment targets, such as following a heart-healthy eating plan, being physically active, maintaining a healthy weight, and not smoking.

To assess the impact of the treatments on the participants’ cardiovascular health, researchers used ultrasound to measure the thickness of the carotid (neck) artery -- an indication of hardening of the arteries, a leading effect of high blood pressure and cholesterol and an early sign of cardiovascular disease. In addition, ultrasound was also used to measure the size and function of the left ventricle, the heart's main pumping chamber. Enlarged hearts are known to be predictors of increased risk of heart attack and stroke. These measurements were taken at enrollment, at 18 months, and at 36 months, when the study ended.

On average, participants in both groups reached and maintained their target goals for blood cholesterol and blood pressure levels. The numbers of heart attacks and other cardiovascular events were similar between the two groups and lower than expected.

In addition, carotid artery thickness measurements of participants in the aggressive treatment group were significantly lower than those in the standard treatment group. Researchers report that, compared to baseline, carotid artery thickness increased slightly in the standard group and regressed in the aggressive treatment group, indicating a partial reversal of atherosclerosis. Furthermore, although heart size decreased from baseline in both groups, the beneficial change was significantly greater among participants in the aggressive treatment group.

“Many patients with diabetes do not reach their blood pressure and cholesterol goal levels and thus remain at high risk for heart attacks and stroke,” noted Howard. “In our study, participants successfully managed their blood cholesterol and blood pressure to reach their goal levels. Our message to doctors, nurses, and patients is that you can reach your goal levels, and we should work together to help you do that.”

As with any therapy, the benefits and risks must be considered for each patient. In SANDS, participants in the aggressive treatment group on average needed more medications and higher doses than the standard treatment group, and they were slightly more likely to have side effects from blood pressure-lowering medications than those in the standard group. Such adverse effects generally resolved, however, after the medication was changed or the dose reduced. There were no differences in side effects related to cholesterol-lowering drugs between the standard and the aggressive treatment groups.

“These encouraging findings from SANDS suggest that more aggressive blood pressure and cholesterol targets than those currently recommended in patients with diabetes may reduce their future cardiovascular risk,” said Jerome L. Fleg, M.D., NHLBI project officer of the study and a coauthor of the paper. “Longer term followup of this population as well as additional studies in other populations are needed to confirm the benefit and cost-effectiveness of these lower targets.”

Posted by dlife at 02:54 PM | Comments (0)

Red Wine, Tea, May Help Regulate Blood Sugar in Type 2 Diabetics

April 02, 2008

April 2, 2008 (Newswise) — Red wine has been shown to protect people from heart disease, even when they follow a diet high in saturated fat, and the healing powers of tea are becoming the stuff of legend. Now, researchers at the University of Massachusetts Amherst have shown that these beverages may hold promise for regulating the blood sugar of people with type 2 diabetes.

Results have been published in the Journal of Food Biochemistry. Researchers include food scientists Kalidas Shetty, Young-In Kwon and Emmanouil Apostolidis.

“Levels of blood sugar, or blood glucose, rise sharply in patients with type 2 diabetes immediately following a meal,” says Shetty. “Red wine and tea contain natural antioxidants that may slow the passage of glucose through the small intestine and eventually into the bloodstream and prevent this spike, which is an important step in managing this disease.”

One of the main challenges in managing diabetes is keeping blood sugar levels as normal as possible with few major fluctuations, which can prevent the disease from contributing to heart disease and high blood pressure as well as damaging the eyes, kidneys, nerves and blood vessels.

Both red and white wines were tested in the laboratory using in vitro enzyme studies to determine how well they could inhibit the activity of a target enzyme called alpha-glucosidase, responsible for triggering the absorption of glucose by the small intestine. Red wine was the winner, able to inhibit the enzyme by nearly 100 percent. Values for white wine hovered around 20 percent.

This was clearly related to the amount of a specific type of antioxidants, called polyphenolics, found in the wines. “Our testing showed that red wine contains roughly ten times more polyphenolics than white wine,” says Shetty. “Laboratory results suggest that these compounds, found in many plant-based foods, may play a role in inhibiting alpha-glucosidase and slowing the passage of carbohydrates into the bloodstream.”

Alpha-glucosidase is the target for current drugs used to treat type 2 diabetes and the development of new drugs.

The team also tested four kinds of tea, including black, oolong, white and green teas. Water extracts of black tea had the highest effect on inhibiting the activity of
alpha-glucosidase, followed by white tea and oolong tea.

Wine and tea had no effect on a pancreatic enzyme called alpha-amylase that breaks down starch, which could help patients avoid the side effects of medications used to control blood sugar.

“A major drawback of medications that control both enzymes is the bacterial fermentation of undigested carbohydrates, especially starch, in the colon, which can lead to side effects such as flatulence, bloating and diarrhea,” says Shetty. “Tea and wine had no effect on the breakdown of starch by alpha-amylase, which could potentially help patients avoid these side effects.”

Another benefit is that the polyphenolics in wine and tea could also help in protecting the rest of the body from the additional complications of diabetes such as high blood pressure and heart disease. Diabetes places a stress on the entire body by increasing the production of free radicals, including molecules that react with oxygen, which degrade cellular function. Both red wine and tea contain antioxidants with proven health benefits, and have the potential to manage heart disease, high blood pressure and perhaps contribute to the prevention of cancer, which are all linked to free radicals.

“These results provide strong evidence for further studying the use of wine and tea to manage some stages of type 2 diabetes using animal models and clinical studies, and point to the importance of an antioxidant-rich diet as part of an overall management strategy,” says Shetty. “This concept is not new, but we are finding clear cellular targets for the functions of dietary polyphenolics. Using specific beverage combinations could generate a whole food profile that has the potential to manage type 2 diabetes and its complications, especially in the early stages.”

Posted by dlife at 02:24 PM | Comments (23)

Trans Fat: Why It’s Time to Eliminate This Dietary Villain

April 2, 2008 (Newswise) — Trans fats are a cholesterol double whammy. Also known as trans-fatty acids, trans fats raise low-density lipoprotein (LDL or “bad”) cholesterol and lower high-density lipoprotein (HDL or “good”) cholesterol.

Experts consider trans fat the worst type of dietary fat. Trans fat contributes to heart disease by promoting low-grade inflammation in the blood vessels. And, trans fats are associated with a higher risk of developing type 2 diabetes.

The April issue of Mayo Clinic Women’s HealthSource provides information to better understand the health risks posed by trans fats as well as tips to avoid consuming them.

Trans fats are formed when liquid oils are made into solid fats such as shortening and hard margarine. Because of their long shelf life and appealing texture, synthetic trans fats have been favored ingredients in commercially baked goods such as cakes, cookies, crackers and crusts. Commercially fried foods, such as doughnuts and french fries, also often contain trans fats.

The use of trans fats is starting to change. New York City made headlines when it banned trans fats in restaurants. Other cities are considering going trans-fat free. Some food manufacturers are reducing or eliminating trans fats in their products.

But avoiding trans fats still takes diligence. The American Heart Association recommends limiting trans fats to less than 1 percent of daily calories. That’s just 20 calories (2 grams) in a 2,000-calorie per day diet. That amount can easily come from naturally occurring trans-fatty acids in dairy products and meat from cows, goats and sheep.

At the grocery store, product nutrition labels contain trans fat information. However, a product that has less than ½ gram of trans fat can be labeled as zero. Eating modest amounts of these products easily can add up to more than 2 grams of trans fats. Keys words such as “shortening,” “partially hydrogenated” or “hydrogenated” indicate the food contains trans fats even when the chart on the label indicates none. Many restaurants continue to use trans fats for deep-fried foods. Grilled or baked foods are more likely to be trans-fat free.

Posted by dlife at 02:22 PM | Comments (0)

Michigan Tech Researchers Link 11 Genetic Variations to Type 2 Diabetes

April 01, 2008

Doing the math: New statistical methods can pinpoint problem genes

April 1, 2008 (EurekAlert) - Mathematicians at Michigan Technological University have developed powerful new tools for winnowing out the genes behind some of humanity’s most intractable diseases.

With one, they can cast back through generations to pinpoint the genes behind inherited illness. With another, they have isolated 11 variations within genes—called single nucleotide polymorphisms, SNPs or “snips”—associated with type 2 diabetes.

“With chronic, complex diseases like Parkinson’s, diabetes and ALS [Lou Gehrig’s disease], multiple genes are involved,” said Qiuying Sha, an assistant professor of mathematical sciences. “You need a powerful test.”

That test is the Ensemble Learning Approach (ELA), software that can detect a set of SNPs that jointly have a significant effect on a disease.

With complex inherited conditions, including type 2 diabetes, single genes may precipitate the disease on their own, while other genes cause disease when they act together. In the past, finding these gene-gene combinations has been especially unwieldy, because the calculations needed to match up suspect genes among the 500,000 or so in the human genome have been virtually impossible.

ELA sidesteps this problem, first by drastically narrowing the field of potentially dangerous genes, and second, by applying statistical methods to determine which SNPs act on their own and which act in combination. “We thought it was pretty cool,” Sha said.

To test their model on real data, Sha’s team analyzed genes from over 1,000 people in the United Kingdom, half with type 2 diabetes and half without. They identified 11 SNPs that, singly or in pairs, are linked to the disease with a high degree of probability. Their work has been accepted by the journal Genetic Epidemiology and is available online at http://www3.interscience.wiley.com/cgi-bin/abstract/117890704/ABSTRACT .

ELA is used to compare the genetic makeup of unrelated individuals to sort out disease-related genes. The team has also developed another approach, which uses a two-stage association test that incorporates founders’ phenotypes, called TTFP, that can examine the genomes of family members going back generations.

“In the past, researchers have dealt with the nuclear family, parents and children, but this could go back to grandparents, great-grandparents . . . as far back as you want.”

The team has published their findings in the European Journal of Human Genetics. An abstract is available at www.nature.com/ejhg/journal/v15/n11/abs/5201902a.html.

Now that they’ve developed the software, the analysis is relatively simple, says Sha. But getting the genetic data to work on is not. “We don’t have the data sets yet to work with,” she says, clearly frustrated. “That’s the problem with having no medical school.”

Those who do have data sets, however, can use the team’s software to help find the cause—and hopefully, the cures—for a panoply of illnesses. ELA is available in Windows and Linux versions at www.math.mtu.edu/~shuzhang/software.html, and TTFP is available by request.

Posted by dlife at 09:25 AM | Comments (0)

Potential Association of Type 2 Diabetes Genes with Prostate Cancer

March 30, 2008

March 30, 2008 (EurekAlert) - Scientists have identified six new genes which play a role in the development of type 2 diabetes, and among the group is the second gene known to also play a role in prostate cancer.

The new findings bring the total number of genes or genomic regions implicated in diabetes to 16, said Laura Scott, assistant research scientist in the Department of Biostatistics. Researchers from the University of Michigan were one of three teams of scientists in Europe and North America that led the multi-group collaboration. The findings, which were published today in the journal Nature Genetics, provide new insights into the mechanisms which are usually responsible for the control of glucose, or sugar, levels in the blood, and to the derangements that can result in type 2 diabetes, which impacts more than 170 million people worldwide.

One of the newly discovered genes, which goes by the name of JAZF1, contains a separate variant that has recently been shown to play a role in prostate cancer, and is the second gene that appears to play a role in both conditions. The first identified overlap between genes for prostate cancer and type 2 diabetes was with HNF1B, which is also involved in an early onset form of diabetes discovered at U-M in an unrelated study, called Maturity Onset Diabetes of the Young (MODY). In HNF1B, the same variant that is associated with increased risk of diabetes is associated with decreased risk of prostate cancer. In JAZF1, the diabetes and prostate cancer variants reside in different parts of the gene and there is no known relationship between them.

"Some of these genes for type 2 diabetes might be involved in diseases other than prostate cancer, in fact there is already a known overlap with heart disease in another genomic region? Scott said. "We have about 25,000 genes, and we've found a very small number by genome wide studies, so to have the same genomic regions come up in studies of different diseases is actually pretty interesting."

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body's inability to utilize insulin to move blood sugar into the cells for energy. Type 2 diabetes affects nearly 21 million in the United States and the incidence of the disease has skyrocketed in the last 30 years. Diabetes is a major cause of heart disease and stroke, as well as the most common cause of blindness, kidney failure and amputations in U.S. adults.

"The remarkable recent progress in identifying regions of the genome that increase risk to diabetes---from 3 to 16 in only a year---will help us unravel the complex basis diabetes and may suggest new and better tailored methods to prevent or treat this disease.," said U-M's Michael Boehnke, the lead scientist on the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group, one of the three lead groups in the study.

The researchers in this project set out to find differences in the genetic code that contribute to individual differences in susceptibility to disease. Previous efforts from these groups and others identified ten genes contributing to type 2 diabetes risk.

Posted by dlife at 10:16 AM | Comments (0)

A Ton of Bitter Melon Produces Sweet Results for Diabetes

March 26, 2008

March 26, 2008 (EurekAlert) - Scientists have uncovered the therapeutic properties of bitter melon, a vegetable and traditional Chinese medicine, that make it a powerful treatment for Type 2 diabetes.

Teams from the Garvan Institute of Medical Research and the Shanghai Institute of Materia Medica pulped roughly a tonne of fresh bitter melon and extracted four very promising bioactive components. These four compounds all appear to activate the enzyme AMPK, a protein well known for regulating fuel metabolism and enabling glucose uptake. The results are published online today in the international journal Chemistry & Biology.

“We can now understand at a molecular level why bitter melon works as a treatment for diabetes,” said Professor David James, Director of the Diabetes and Obesity Program at Garvan. “By isolating the compounds we believe to be therapeutic, we can investigate how they work together in our cells.”

People with Type 2 diabetes have an impaired ability to convert the sugar in their blood into energy in their muscles. This is partly because they don’t produce enough insulin, and partly because their fat and muscle cells don’t use insulin effectively, a phenomenon known as ‘insulin resistance’.

Exercise activates AMPK in muscle, which in turn mediates the movement of glucose transporters to the cell surface, a very important step in the uptake of glucose from the circulation into tissues in the body. This is a major reason that exercise is recommended as part of the normal treatment program for someone with Type 2 diabetes.

The four compounds isolated in bitter melon perform a very similar action to that of exercise, in that they activate AMPK.

Garvan scientists involved in the project, Drs Jiming Ye and Nigel Turner, both stress that while there are well known diabetes drugs on the market that also activate AMPK, they can have side effects.

“The advantage of bitter melon is that there are no known side effects,” said Dr Ye. “Practitioners of Chinese medicine have used it for hundreds of years to good effect.”

Garvan has a formal collaborative arrangement with the Shanghai Institute of Materia Medica. In addition to continuing to work together on the therapeutic potential of bitter melon, we will be exploring other Chinese medicines.

Professor Yang Ye, from the Shanghai Institute and a specialist in natural products chemistry, isolated the different fractions from bitter melon and identified the compounds of interest.

“Bitter melon was described as “bitter in taste, non-toxic, expelling evil heat, relieving fatigue and illuminating” in the famous Compendium of Materia Medica by Li Shizhen (1518-1593), one of the greatest physicians, pharmacologists and naturalists in China’s history,” said Professor Ye. “It is interesting, now that we have the technology, to analyse why it has been so effective.”

“Some of the compounds we have identified are completely novel. We have elucidated the molecular structures of these compounds and will be working with our colleagues at Garvan to decipher their actions at a molecular level. We assume it’s working through a novel pathway inside cells, and finding that pathway is going to be very interesting.”

Posted by dlife at 01:56 PM | Comments (6)

A Link Between Antidepressants and Type 2 Diabetes

March 25, 2008

March 25, 2008 (EurekAlert) - While analyzing data from Saskatchewan health databases, Lauren Brown, researcher with the U of A’s School of Public Health, found people with a history of depression had a 30 per cent increased risk of type 2 Diabetes.

Brown then studied the medical history of 2,400 people who were diagnosed with depression and were taking antidepressants to determine whether there was a clear correlation between that disease and type 2 Diabetes.

Brown divided the group into four categories: those who took antidepressants that were considered older therapies, patients who were using newer treatments, those using a combination of both an old and new treatments and people who were switching medications.

What she found was the risk of diabetes almost doubled for the patients who were using two types of therapies at the same time, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). Brown says people are usually prescribed multiple medications “if they have severe depression or if they are having a problem finding the right therapy.”

Brown believes these results, and results of previous studies demonstrating an increased risk of type 2 diabetes in people with depression, emphasize the need for regular screening for type 2 diabetes in people with depression, particularly those taking more than one antidepressant. She also encourages diabetes and depression organizations to educate their members about this link.

Posted by dlife at 03:37 PM | Comments (5)

Previously Unrecognized Testosterone Deficiency Common in Men with Type 1 Diabetes

March 25, 2008 (Newswise) - Testosterone deficiency, previously recognized as common in men with type 2 diabetes, is also common in men with type 1 diabetes according to a new study accepted for publication in the Journal of Clinical Endocrinology & Metabolism (JCEM). These findings suggest that there is a direct link between insulin resistance and reduced testosterone levels in men.

“As testosterone deficiency may contribute to impaired performance, mood, and libido, as well as have adverse impact on cardiovascular risk, these findings demonstrate the presence of a significant and unrecognized problem among men with diabetes,” said Dr. Mathis Grossmann of the University of Melbourne in Australia. “Our findings of insulin resistance as a potential determinant of reduced testosterone levels may represent an important avenue for intervention.”

For this study, researchers conducted a survey of 580 men with type 2 diabetes and 69 men with type 1 diabetes. A subgroup of 262 men with type 2 diabetes was then reassessed after six months. Testosterone levels were measured from blood samples using the Access testosterone assay.

Previous population-studies found an association of reduced testosterone levels in men and type 2 diabetes, however this is the first study to demonstrate a similar prevalence in individuals with type 1 diabetes.

This study raises the question of whether testosterone replacement therapy can reduce insulin resistance or symptoms of hypogonadism in men with diabetes. Researchers, however stress that the balance of benefits and risks of such treatment is currently unknown and still to be defined by large and long-term clinical trials. Also, while insulin resistance is associated with testosterone deficiency, there is no evidence that insulin sensitizers are able to elevate testosterone levels in men with diabetes.

Other researchers working on the study include Merlin Thomas, Sianna Panagiotopoulos, Ken Sharpe, Richard MacIsaac, Sophie Clarke, Jeffrey Zajac, and George Jerums of the University of Melbourne in Australia.

A rapid release version of this paper has been published on-line and will appear in the May 2008 issue of JCEM, a publication of The Endocrine Society.

Founded in 1916, The Endocrine Society is the world’s oldest, largest, and most active organization devoted to research on hormones, and the clinical practice of endocrinology. Today, The Endocrine Society’s membership consists of over 14,000 scientists, physicians, educators, nurses and students in more than 80 countries. Together, these members represent all basic, applied, and clinical interests in endocrinology. The Endocrine Society is based in Chevy Chase, Maryland. To learn more about the Society, and the field of endocrinology, visit our web site at http://www.endo-society.org.

Posted by dlife at 10:22 AM | Comments (0)

Scientists Link 11 Genetic Variations to Type 2 Diabetes

March 24, 2008

March 24, 2008 (Newswise) — Mathematicians at Michigan Technological University have developed powerful new tools for winnowing out the genes behind some of humanity’s most intractable diseases.

With one, they can cast back through generations to pinpoint the genes behind inherited illness. With another, they have isolated 11 variations within genes—called single nucleotide polymorphisms, SNPs or “snips”—associated with type 2 diabetes.

“With chronic, complex diseases like Parkinson’s, diabetes and ALS [Lou Gehrig’s disease], multiple genes are involved,” said Qiuying Sha, an assistant professor of mathematical sciences. “You need a powerful test.”

That test is the Ensemble Learning Approach (ELA), software that can detect a set of SNPs that jointly have a significant effect on a disease.

With complex inherited conditions, including type 2 diabetes, single genes may precipitate the disease on their own, while other genes cause disease when they act together. In the past, finding these gene-gene combinations has been especially unwieldy, because the calculations needed to match up suspect genes among the 500,000 or so in the human genome have been virtually impossible.

ELA sidesteps this problem, first by drastically narrowing the field of potentially dangerous genes, and second, by applying statistical methods to determine which SNPs act on their own and which act in combination. “We thought it was pretty cool,” Sha said.

To test their model on real data, Sha’s team analyzed genes from over 1,000 people in the United Kingdom, half with type 2 diabetes and half without. They identified 11 SNPs that, singly or in pairs, are linked to the disease with a high degree of probability. Their work has been accepted by the journal Genetic Epidemiology and is available online at http://www3.interscience.wiley.com/cgi-bin/abstract/117890704/ABSTRACT .

ELA is used to compare the genetic makeup of unrelated individuals to sort out disease-related genes. The team has also developed another approach, which uses a two-stage association test that incorporates founders’ phenotypes, called TTFP, that can examine the genomes of family members going back generations.

“In the past, researchers have dealt with the nuclear family, parents and children, but this could go back to grandparents, great-grandparents . . . as far back as you want.”

The team has published their findings in the European Journal of Human Genetics. An abstract is available at http://www.nature.com/ejhg/journal/v15/n11/abs/5201902a.html .

Now that they’ve developed the software, the analysis is relatively simple, says Sha. But getting the genetic data to work on is not. “We don’t have the data sets yet to work with,” she says, clearly frustrated. “That’s the problem with having no medical school.”

Those who do have data sets, however, can use the team’s software to help find the cause—and hopefully, the cures—for a panoply of illnesses. ELA is available in Windows and Linux versions at http://www.math.mtu.edu/~shuzhang/software.html, and TTFP is available by request.

Other members of Michigan Tech's statistical genetics group are Associate Professor Shuanglin Zhang and postdoctoral scientists Zhaogong Zhang and Tao Feng.

Posted by dlife at 09:42 AM | Comments (0)

Low Levels of PYY Hormone a Very Early Indicator of Type 2 Diabetes

March 10, 2008

March 10, 2008 (EurekAlert) - It may soon be possible to take a simple blood test and predict whether or not someone has low levels of a particular molecule, predisposing them to the development of Type 2 diabetes. If the test is positive, it may then be possible to use preventative treatment, slowing down, or even halting that development.

Such is the hope of scientists and clinicians at Sydney’s Garvan Institute of Medical Research who have shown conclusively that people who produce low levels of the molecule PYY have a higher risk of developing Type 2 diabetes and obesity.

The findings were published online on 4 March in the prestigious International Journal of Obesity.

It is already known that the hormone PYY, which is released from the gut after a meal, creates a feeling of satiety. When PYY is in oversupply, it prevents diet-induced obesity in mice.

Professor Herbert Herzog, Director of Garvan’s Neuroscience Program, and an expert on appetite, says that the new findings are important in that they show a metabolic defect before the presence of any disease or manifestation of weight gain. “We can now see that low PYY levels after eating are a very early predictor of the development of obesity and Type 2 diabetes,” he said.

Professor Lesley Campbell, Director of Diabetes Services at St. Vincent’s Hospital and a senior member of Garvan’s Diabetes and Obesity Clinical Studies group, has been researching genetic factors in the development of Type 2 diabetes for over 10 years. Specifically, her research looks at people before they get the disease, the contributing factors, and the effects of the diabetes.

Professor Campbell has already published findings that insulin resistant people, with a family history of Type 2 diabetes, have low levels of PYY. “In earlier studies we hinted at the fact that before any of the abnormalities of diabetes are present, people already have an abnormality of satiety, marked by the lack of the secretion of this PYY hormone,” she said.

“We now have published that, even earlier in the development of diabetes, people who are not yet insulin resistant show a low secretion of PYY. They have a blunted post-meal secretion of this hormone, making them less likely to feel satiety, and more likely to gain weight.”

Professor Campbell’s research involved elaborate testing of two groups of people, eight in each group, over a period of two years. One group had relatives with Type 2 diabetes, the other group had no family history of the disease. The groups were matched for gender, for age and for adiposity.

“It was most important to match the groups for their fatness,” said Professor Campbell. “The only difference was their relatives. You assume that they are carrying the genetic burden of diabetes, which we already know to be a reality.”

“Low levels of PYY at this very early pre-diabetes stage could be used as a marker, or predictor, that Type 2 diabetes is very likely to develop.”

“As a clinician, I am hopeful that it will be possible to screen extensively in the future, and therefore stem the spread of this debilitating disease.”

Posted by dlife at 02:01 PM | Comments (1)

Chronically Elevated Blood Sugar Levels Disable 'Fasting Switch'

March 06, 2008

March 6, 2008 (EurekAlert) — Continually revved up insulin production, the kind that results from overeating and obesity, slowly dulls the body’s response to insulin. As a result, blood sugar levels start to creep up, setting the stage for diabetes-associated complications such as blindness, stroke and renal failure. To make matters even worse, chronically elevated blood sugar concentrations exacerbate insulin resistance.

The vicious circle gets rolling, researchers at the Salk Institute for Biological Studies discovered, when out-of-control blood sugar levels disable the molecular switch that normally shuts off sugar production in the liver in response to rising levels of insulin.

Their findings, published in the March 7 issue of Science suggest that appropriate inhibitors of the enzymatic pathway that blocks the “sugar-off”-switch might be useful in lowering glucose levels in diabetic individuals and reducing long-term complications associated with the disease.

“The islet cells in the pancreas can compensate with increased insulin production only for so long when confronted with chronic obesity and inactivity,” says Marc Montminy, Ph.D., a professor in the Clayton Foundation Laboratories for Peptide Biology, who led the study. “As a result glucose levels start to rise causing a host of problems.”

Just like a flex-fuel vehicle that can run on either gasoline or ethanol, the human body can switch between different types of fuel: During the day the body mostly burns glucose, and during the night or prolonged fasting, it burns primarily fat. But neither flex-fuel engines nor human brains can run on ethanol or fat alone —a little bit of gasoline or glucose needs to be thrown into the mix to keep either one of them humming.

Three years ago, Montminy discovered a “fasting switch” called CRTC2 (formerly known as TORC2) that flips on glucose production in the liver when blood glucose levels run low during the night. After a meal, the hormone insulin normally shuts down CRTC2 ensuring that blood sugar levels don’t rise too high.

In many patients with type II diabetes, however, CRTC2 no longer responds to rising insulin levels and as a result the liver acts like a sugar factory on overtime, churning out glucose throughout the day, even when blood sugar levels are high. The Salk researchers were interested in the molecular mechanism that leads to the breakdown of the normally tightly regulated feedback loop.

Mice whose livers light up — courtesy of the luciferase gene, which produces the glow in fireflies — as soon as CRTC2 is turned on, led post-doctoral fellow and first author Renaud Dentin, Ph.D., onto the trail of the hexosamine biosynthetic pathway. Activation of the pathway promotes the addition of sugar molecules to proteins, a process also known as O-glycosylation. “It had been known that increases in the concentration of circulating glucose activate the hexosamine biosynthetic pathway,” says Dentin. “But we had no idea that the resulting O-glycosylation would lock CRTC2 in the ‘on’-position.”

Normally, the rise in insulin after a meal activates a liver enzyme called SIK2. The enzyme chemically tags CRTC2 with a phosphate group, marooning the protein outside the cell’s nucleus. Unable to reach the genes involved in gluconeogenesis, CRTC2 is powerless to turn them on and glucose production in the liver ceases.

In the presence of excessive glucose levels, however, the hexosamine biosynthetic pathway is activated and blocks crucial phosporylation sites on CRTC2 by adding sugar molecules instead. CRTC2 can no longer be phosphorylated in response to rising insulin levels and is now free to slip into the nucleus and keep the gluconeogenic program going.

Shutting down the O-glycosylation pathway should then get the body’s own glucose production under control, the researchers reasoned. Just as predicted, glucose tolerance and insulin sensitivity markedly improved in insulin resistant diabetic mice and mice fed a high fat diet — who both suffered from hyperglycemia — when Dentin and his colleagues decreased the activity of the hexosamine biosynthetic pathway in the liver of these animals.

“What I really would like to do is to use the glowing mice to screen for drugs that decrease gluconeogenesis,” says Montminy. “Imagine hyperglycemic mice whose livers light up because CRTC2 is on all the time. When you feed them a drug that inhibits O-glycosylation the light dims and you know you have compound that’s effective in living animals and you know how it works.”

Posted by dlife at 10:45 AM | Comments (1)

Type 2 Diabetes May Be Caused by Intestinal Dysfunction

March 05, 2008

March 5, 2008 (Newswise) — Growing evidence shows that surgery may effectively cure Type 2 diabetes -- an approach that not only may change the way the disease is treated, but that introduces a new way of thinking about diabetes.

A new article -- published in a special supplement to the February issue of Diabetes Care by a leading expert in the emerging field of diabetes surgery -- points to the small bowel as the possible site of critical mechanisms for the development of diabetes.

The study's author, Dr. Francesco Rubino of NewYork-Presbyterian Hospital/Weill Cornell Medical Center, presents scientific evidence on the mechanisms of diabetes control after surgery. Clinical studies have shown that procedures that simply restrict the stomach's size (i.e., gastric banding) improve diabetes only by inducing massive weight loss. By studying diabetes in animals, Dr. Rubino was the first to provide scientific evidence that gastrointestinal bypass operations involving rerouting the gastrointestinal tract (i.e., gastric bypass) can cause diabetes remission independently of any weight loss, and even in subjects that are not obese.

"By answering the question of how diabetes surgery works, we may be answering the question of how diabetes itself works," says Dr. Rubino, who is a professor in the Department of Surgery at Weill Cornell Medical College and chief of gastrointestinal metabolic surgery at NewYork-Presbyterian/Weill Cornell.

Dr. Rubino's prior research has shown that the primary mechanisms by which gastrointestinal bypass procedures control diabetes specifically rely on the bypass of the upper small intestine -- the duodenum and jejunum. This is a key finding that may point to the origins of diabetes.

"When we bypass the duodenum and jejunum, we are bypassing what may be the source of the problem," says Dr. Rubino, who is heading up NewYork-Presbyterian/Weill Cornell's Diabetes Surgery Center.

In fact, it has become increasingly evident that the gastrointestinal tract plays an important role in energy regulation, and that many gut hormones are involved in the regulation of sugar metabolism. "It should not surprise anyone that surgically altering the bowel's anatomy affects the mechanisms that regulate blood sugar levels, eventually influencing diabetes," Dr. Rubino says.

While other gastrointestinal operations may cure diabetes as an effect of changes that improve blood sugar levels, Dr. Rubino's research findings in animals show that procedures based on a bypass of the upper intestine may work instead by reversing abnormalities of blood glucose regulation.

In fact, bypass of the upper small intestine does not improve the ability of the body to regulate blood sugar levels. "When performed in subjects who are not diabetic, the bypass of the upper intestine may even impair the mechanisms that regulate blood levels of glucose," says Dr. Rubino. In striking contrast, when nutrients' passage is diverted from the upper intestine of diabetic patients, diabetes resolves.

This, he explains, implies that the upper intestine of diabetic patients may be the site where an abnormal signal is produced, causing, or at least favoring, the development of the disease.

How exactly the upper intestine is dysfunctional remains to be seen. Dr. Rubino proposes an original explanation known in the scientific community as the "anti-incretin theory."

Incretins are gastrointestinal hormones, produced in response to the transit of nutrients, that boost insulin production. Because an excess of insulin can determine hypoglycemia (extremely low levels of blood sugar) -- a life-threatening condition -- Dr. Rubino speculates that the body has a counter-regulatory mechanism (or "anti-incretin" mechanism), activated by the same passage of nutrients through the upper intestine. The latter mechanism would act to decrease both the secretion and the action of insulin.

"In healthy patients, a correct balance between incretin and anti-incretin factors maintains normal excursions of sugar levels in the bloodstream," he explains. "In some individuals, the duodenum and jejunum may be producing too much of this anti-incretin, thereby reducing insulin secretion and blocking the action of insulin, ultimately resulting in Type 2 diabetes."

Indeed, in Type 2 diabetes, cells are resistant to the action of insulin ("insulin resistance"), while the pancreas is unable to produce enough insulin to overcome the resistance.

After gastrointestinal bypass procedures, the exclusion of the upper small intestine from the transit of nutrients may offset the abnormal production of anti-incretin, thereby resulting in remission of diabetes.

In order to better understand these mechanisms, and help make the potential benefits of diabetes surgery more widely available, Dr. Rubino calls for prioritizing research in diabetes surgery. "Further research on the exact molecular mechanisms of diabetes, surgical control of diabetes and the role played by the bowel in the disease may bring us closer to the cause of diabetes."

Today, most patients with diabetes are not offered a surgical option, and bariatric surgery is recommended only for those with severe obesity (a body mass index, or BMI, of greater than 35kg).

"It has become clear, however, that BMI cut-offs can no longer be used to determine who is an ideal candidate for surgical treatment of diabetes," says Dr. Rubino.

"There is, in fact, growing evidence that diabetes surgery can be effective even for patients who are only slightly obese or just overweight. Clinical trials in this field are therefore a priority as they allow us to compare diabetes surgery to other treatment options in the attempt to understand when the benefits of surgery outweigh its risks. Clinical guidelines for diabetes surgery will certainly be different from those for bariatric surgery, and should not be based only on BMI levels," he notes.

"The lesson we have learned with diabetes surgery is that diabetes is not always a chronic and relentless disease, where the only possible treatment goal is just the control of hyperglycemia and minimization of the risk of complications. Gastrointestinal surgery offers the possibility of complete disease remission. This is a major shift in the way we consider treatment goals for diabetes. It is unprecedented in the history of the disease," adds Dr. Rubino.

Type 2 diabetes, which accounts for 90 to 95 percent of all cases of diabetes, is a growing epidemic that afflicts more than 200 million people worldwide.

At a time when diabetes is growing epidemically worldwide, Dr. Rubino says that finding new treatment strategies is a race against time. "At this point, missing the opportunity that surgery offers is not an option."

In addition to having performed landmark studies in the field of diabetes surgery, Dr. Rubino was the principal organizer of an influential Diabetes Surgery Summit, held in Rome in March 2007. This international consensus conference helped establish the field, making international recommendations for the use of surgery and creating an International Diabetes Surgery Task Force. Dr. Rubino serves as a founding member.

For more information, patients may call (866) NYP-NEWS.

Posted by dlife at 11:12 AM | Comments (2)

Study Shows Cholesterol-lowering Power of Dietitian Visits

March 04, 2008

March 4, 2008 (Newswise) — Worried about your cholesterol? You may want to schedule a few appointments with a registered dietitian, to get some sound advice about how to shape up your eating habits, according to a new national study led by University of Michigan Health System researchers.

Not only are you likely to lower your cholesterol levels, you may be able to avoid having to take cholesterol medication, or having to increase your dose if you’re already taking one. And you’ll probably lose weight in the process, which also helps your heart.

The new results, published in the February issue of the Journal of the American Dietetic Association, are based on data from 377 patients with high cholesterol who were counseled by 52 registered dietitians at 24 sites in 11 states.

In the group of 175 patients who started the study with triglycerides less than 400 milligrams per deciliter of blood (mg/dL), and who had their cholesterol measured before they changed or added medication, 44.6 percent either reduced their levels of “bad” cholesterol by at least 15 percent, or reached their cholesterol goal.

The results reflect progress in approximately eight months, after three or more appointments with a dietitian. But the results add further evidence that medical nutrition therapy, as it is called, can make a big difference in a patient’s life.

All of the R.D.s in the study based their advice to their patients on the latest research-based evidence about eating habits and cholesterol levels available at the time of the study: the American Dietetic Association’s 1998 Medical Nutrition Therapy Hyperlipidemia Protocol.

Since that time, the ADA has updated the clinical guideline based on new research, which means that patients who see an R.D. today may have even more success.

The study was funded by the ADA and its Clinical Nutrition Management Dietetic Practice Group, and based on a framework developed for a pilot project carried out in Michigan by the Michigan Dietetic Association and led by U-M cardiovascular dietitians.

“Everyone knows that nutrition is important for cholesterol management, and that a registered dietitian is the professional most thoroughly trained to help patients choose foods wisely,” says lead author Kathy Rhodes, Ph.D., R.D., manager of Nutrition Services with the U-M Cardiovascular Medicine program at Domino’s Farms and the U-M Cardiovascular Center. “But this is the first national study to show what happens when high-risk patients work with R.D.s to follow nutrition guidelines grounded in the best evidence.”

Key nutrition issues in the 1998 guidelines used in the study include reducing saturated and trans fat and increasing “healthy” fats such as olive oil; increasing soluble and insoluble fiber; eating fish twice a week; increasing fruits and vegetables; regular exercise and healthy weight management. Information about food-label reading and dining out was also included.

Called the Lipid Management Nutrition Outcomes Project or LMNOP, the national study was launched by Rhodes and her U-M colleagues Melvyn Rubenfire, M.D., and Martha Weintraub, MPH, R.D., after the successful completion of the Michigan-wide pilot project. Rubenfire, Weintraub and Christina Biesemeier, M.S., R.D., FADA, of Vanderbilt University are co-authors of the new study.

The study gives us an important “real world” picture of what happens when R.D.s try to implement evidence-based nutrition guidelines in daily practice, Rhodes notes.

Some commercial health insurance plans are beginning to cover appointments with registered dietitians, but many still do not. Only dietitian visits for diabetes or kidney disease are covered by Medicare. It is important for people to check their specific health insurance plan to see whether nutrition is covered, Rhodes says. But even if individuals need to pay for the appointments out of their own pocket, they may find that an R.D.’s advice will pay off in the long run, she says.

To get uniform data, the researchers brought lead R.D.s from each state to U-M for training on the cholesterol and nutrition guidelines, and on the data collection practices used in the study. R.D.s at Veterans Affairs hospitals got their training by phone conferencing. R.D.s then returned to their own practices, trained their colleagues and implemented the ADA guidelines.

The study included only patients between the ages of 25 and 70 years who had high cholesterol levels, or triglyceride levels over 200 mg/dL, and who met other inclusion criteria including no recent changes in their cholesterol medication status. Neither the R.D.s nor their patients were paid to participate in the study.

The “real world” aspect of this study included the disappointing finding that many patients dropped out of nutrition counseling after one or two visits, when three or four sessions with an R.D. is recommended to make and sustain truly effective changes in eating habits. Lack of insurance coverage was a major factor in this dropout rate.

Patients whose doctors changed their cholesterol medication status, either by starting them on a drug for the first time, or increasing their dose before assessing the effect of diet change, were not included in the analysis. But for the 219 patients who didn’t have any change in their medication status, the impact of the R.D. counseling became apparent in the first year after the initial visit.

“Although some patients may already be eating a relatively healthy diet, medical nutrition therapy can increase patient’s knowledge of ‘cardioprotective foods’ and assist them in individualizing the guidelines to fit their preferences and lifestyle,” says Weintraub. A significant number of patients reduced the fat in their diets to less than 30 percent of calories, as recommended for a heart health. Many participants also lost weight and/or increased the number of days each week on which they exercised for 30 minutes or more.

“Often, we see heart patients who are on multiple cholesterol medications but have never seen a dietitian. And even when a patient with high cholesterol does get to see an R.D., their care team may not allow enough time to see how effective diet is before they add additional treatment,” says Rhodes. “We hope that this demonstration of how well cholesterol can be lowered without medication or increases in medication will be very useful for patients and physicians, and perhaps insurers too.”

To learn more about how eating habits can influence cholesterol levels, or to find an R.D., visit the ADA’s web site at http://www.eatright.org. For more on U-M Cardiovascular Medicine and its nutrition services, visit http://www.med.umich.edu/cvc/prevention. Reference: JADA, Vol. 108, No. 2, Feb. 2008.

Posted by dlife at 11:14 AM | Comments (2)

Overweight Hispanic Children Shown To Have Vascular Inflammation

February 27, 2008

February 27, 2008 (Joslin Diabetes Center) — Overweight Hispanic children with normal blood glucose (sugar) levels showed elevated markers for blood vessel inflammation that may predispose them to developing both type 2 diabetes and cardiovascular disease, says a new study led by researchers from the Joslin Diabetes Center.

The study, published in the March issue of Diabetes Care, is the first to focus on Hispanic children, already known to be at high risk for developing type 2 diabetes as a result of both genetic and lifestyle factors.

“Our findings suggest that these children are not only at risk for type 2 diabetes, but also for cardiovascular disease,” said Dr. A. Enrique Caballero, lead investigator.

The study looked at 38 Hispanic children and adolescents, ages 10 through 18. Twenty-one were obese but with normal blood glucose levels, so they had not yet developed diabetes. The rest were considered lean. As a group, the obese subjects had significantly higher percentages of body fat than the lean group and were already showing signs of insulin resistance, meaning the insulin that their bodies produce is not working well and as a consequence their pancreases were being forced to work harder to produce more insulin to maintain normal blood sugar levels.

Overall, the obese group exhibited increased blood markers for subclinical or asymptomatic inflammation of the inner layer of blood vessels. “They are already exhibiting problems with circulation,” said Caballero, Director of the Latino Diabetes Initiative, Clinical Investigator, Staff Endocrinologist and Director, Medical Affairs, Professional Education at Joslin Diabetes Center, as well as an Assistant Professor of Medicine at Harvard Medical School. “There is an inflammatory process going on in the vessels.”

Such problems suggest these children may be at increased risk of developing cardiovascular problems at a young age, he said.

Subclinical vascular inflammation is a key element in the development of cardiovascular disease and is closely associated with insulin resistance. It also predicts the development of type 2 diabetes.

Earlier studies in overweight or obese children and adolescents showed similar vascular abnormalities, but were conducted primarily in non-Hispanic children.

Caballero wanted to study Hispanic children because they had not previously been studied and because they are a high-risk population for type 2 diabetes.

“We have found that overweight Hispanic children and adolescents have elevated markers of endothelial dysfunction and vascular inflammation closely related to excess body fat and increased insulin resistance,” the paper concluded. “This. . . may increase their risk of developing type 2 diabetes and cardiovascular disease, further emphasizing the need for obesity prevention strategies.”

Caballero said such strategies must be culturally appropriate.

“Even if these abnormalities may not be that different than those in Caucasian children, the strategies to prevent heart disease and diabetes need to be culturally oriented,’’ he said. “They need to be tailored to the population.”

Caballero stressed that the findings do not mean that such children will definitely develop type 2 diabetes or cardiovascular problems, but said the idea is to step in early to make sure they don’t.

“The problem is serious enough to warrant attention and a prevention strategy,” he said.

The research was funded by a grant from Sanofi Aventis and a National Institutes of Health grant for general clinical research at Beth Israel Deaconess Medical Center.

In addition to Dr. Caballero, other researchers participating in the study included: Dr. Ludivina Robles-Osorio, Valeria Montagnani, RN, Dr. Geetha Soodini, Dr. Sriurai Porramatikul, Dr. Osama Hamdy and Dr. Edward S. Horton from the Joslin and Kelb Bousquet-Santos and Dr. Antonio C.L. Nobrega from Fluminense Federal University in Brazil.

Posted by dlife at 11:20 AM | Comments (0)

Welchol™ (colesevelam HCl) Receives FDA Approval to Reduce Blood Glucose in

January 18, 2008

First and only medication approved to reduce both A1C and LDL cholesterol

January 18, 2008 (Press Release) – Daiichi Sankyo, Inc., announced today that the United States Food and Drug Administration (FDA) has approved Welchol™ (colesevelam HCl) to improve glycemic control (measured as hemoglobin A1C) in adults with type 2 diabetes mellitus in combination with metformin, sulfonylureas, or insulin, either alone or in combination with other anti-diabetic agents. Welchol is now the first and only medication approved to reduce both glucose levels and low density lipoprotein cholesterol levels (LDL-C). The ADA estimates that 20.8 million people in the United States have diabetes with more than 90 percent of these people having type 2 diabetes.1 Forty percent of patients with type 2 diabetes also have high LDL-cholesterol2. Welchol is a new option that addresses both these chronic health conditions and provides physicians with a unique therapeutic approach for treating patients with type 2 diabetes.

Pivotal data presented at the American Diabetes Association’s (ADA) 67th Annual Scientific Sessions in Chicago in June, 2007 demonstrated that Welchol can lower both A1C and LDL-C levels in patients with type 2 diabetes who were uncontrolled on a metformin-based regimen. Patients in the study were randomly assigned to two groups. The addition of Welchol was compared to the addition of placebo in patients on a metformin-based regimen. The addition of Welchol (n=79) to pre-existing metformin monotherapy achieved a significant mean reduction in A1C levels of 0.47 percent relative to placebo (p<0.0024). Further, the total Welchol treatment group, when treated with either metformin monotherapy or metformin-combination therapy, achieved significantly greater reductions in A1C levels compared to placebo (mean reduction of 0.54%; p<0.001). The study further demonstrated that the total Welchol treatment group achieved significantly lower LDL-C levels compared to the placebo group (mean reduction of 15.9%; p<0.001).

In addition, two other pivotal studies showed similar results in A1C reductions when Welchol was added to either sulfonylurea-based therapy or insulin-based therapy. In patients with type 2 diabetes who were inadequately controlled on sulfonylurea-based therapy the addition of Welchol was shown to have significant reductions in A1C (mean reduction of 0.54%; p<0.001) vs. placebo at week 26. In patients inadequately controlled with insulin, alone or in combination with other anti-diabetic agents, the addition of 2 Welchol was shown to have a significant mean reduction in A1C (mean reduction of 0.50%; p<0.0001) vs. placebo.

"Welchol now offers physicians a treatment option that addresses two major cardiovascular risk factors; elevated LDL cholesterol and blood glucose in patients with type 2 diabetes," said Ronald B. Goldberg, MD, an investigator in the insulin and metformin pivotal studies and Professor of Medicine at the Division of Diabetes and Metabolism and Associate Director of the Diabetes Research Institute at the University of Miami, Miller School of Medicine in Florida. “Cardiovascular risk factors are of great concern because patients with type 2 diabetes have a significantly increased risk of developing cardiovascular disease. Once clinical cardiovascular disease develops, these patients have a poorer prognosis than normoglycemic patients.”

Since 2000, Welchol, a bile acid sequestrant, has been indicated, alone or in combination with a statin, for the reduction of elevated LDL-C in patients with primary hypercholesterolemia. It is different from most other cholesterol-lowering drugs on the market because it is non-systemic, meaning that the body does not absorb it and it is eliminated without traveling to the liver or kidneys. Therefore, Welchol is not expected to have drug interactions via the cytochrome P450 pathway. Systemic medications, which include statins, fibrates and cholesterol absorption inhibitors, are those that are absorbed from the intestine into the bloodstream and travel throughout the body, specifically to the liver and/or kidneys.

Additionally, Welchol has demonstrated beneficial effects on other lipid parameters such as HDL- C and APO-B. Welchol has also been studied in combination with fenofibrate in patients with mixed dyslipidemia (Fredrickson Type IIb), and provided additional LDL-C reductions in these patients when added to a stable fenofibrate regimen. Welchol is not indicated for use in combination with fenofibrate or in the treatment of mixed dyslipidemia or lipid parameters other than LDL-C.

"We are excited by the opportunity to help more patients with chronic conditions reach their recommended health goals,” said Joseph P. Pieroni, President and CEO of Daiichi Sankyo, Inc. “This approval represents an important milestone for our growing U.S. organization and underscores our continued commitment to combating cardiovascular and metabolic diseases.”

People with diabetes face significantly higher risk of developing cardiovascular disease. The ADA recommends that patients with type 2 diabetes target an A1C level of < 7%.4 A1C is a common test for persistent hyperglycemia (“too much glucose in the blood”). Additionally, the National Cholesterol Education Program (NCEP) recommends that patients with type 2 diabetes keep their cholesterol levels in check and target an LDL-C goal of < 100 mg/dL.5 Despite this recommendation, nearly 40 percent of
patients with type 2 diabetes have LDL cholesterol levels greater than 130 mg/dL.

It is estimated that half of all Americans have elevated blood cholesterol levels that can negatively impact their health and quality of life.7 According to the National Healthcare Quality Report, nearly 40 percent of adults with high cholesterol also have type 2 diabetes.

Posted by dlifenews at 02:37 PM | Comments (0)

How Does Insulin Influence Resistin?

January 17, 2008

January 17, 2008 (EurekAlert) - Obesity is a worldwide health problem directly linked to several diseases such as hypertension and type 2 diabetes. Resistin is a cysteine-rich hormone mainly secreted by adipose tissues and may form a biochemical link between obesity and type 2 diabetes.

It has been reported insulin inhibits resistin mRNA level in 3T3-L1, which does not support a role for resistin in insulin resistance. Does resistin play a role in insulin resistance? Is insulin the major regulator of resistin?

A research article to be published on January 7, 2008 in the World Journal of Gastroenterology (volume 14, issue 1) addresses these questions. The research team led by Dr. Guo Xi-Rong studied the resistin action in vitro and resistin secretion. In addition to this, diet-induced obese rats were used to study the relationship between insulin, resistin and insulin resistance.

One result reported by the investigators was resistin expression and secretion was enhanced during 3T3-L1 pre-adipocytes differentiation, insulin inhibits resistin expression and secretion. Insulin does not support a role for resistin in insulin resistance.

The result showed resistin induces cellular insulin resistance in H4IIE hepatocytes and L6 rat myoblasts. Serum resistin negatively correlates to insulin sensitivity, not to serum insulin in diet-induced obesity rats.

The results of this study suggest insulin inhibits resistin secretion and resistin induces insulin sensitivity. In vivo study shows serum resistin correlated to rat insulin sensitivity, so insulin is not the major regulator of resistin. Resistin induced hepatocytes insulin resistance takes part in diet induced insulin resistance.

Posted by dlifenews at 09:40 AM | Comments (0)

Researcher Uncovers Possible Explanation for Ties Between Diabetes, Heart Disease

January 11, 2008

January 11, 2008 (Newswise) — A researcher at the University of Virginia Health System is demonstrating why so many people with diabetes may have heart disease. Assistant Professor of Internal Medicine Dr. Zhenqi Liu has shown that in healthy humans, insulin greatly increases blood flow in heart muscle. His work was recently published in the American Journal of Physiology – Endocrinology and Metabolism.

The study involved 13 healthy volunteers who had fasted overnight experienced a 41 percent increase in microvascular (smallest blood vessels) blood volume in heart tissue after an insulin infusion.

Now, Dr. Liu is conducting trials focused on insulin resistance, a cardinal feature of type 2 diabetes. He is testing the theory that insulin resistance limits circulation in heart muscle in patients with type 2 diabetes and is the major contributor to the development of heart disease in diabetic patients.

"I hope findings from this project will eventually lead to the development of new ways to diagnose and treat diabetes-related cardiac complications," Dr. Liu says.

Posted by dlifenews at 04:43 PM | Comments (0)

Good News! Heart Health Improved with Vitamin E for 40% of Type 2 Diabetics

January 11, 2008 (Newswise) — Vitamin E supplements can significantly reduce the risk of heart attacks and related deaths for type 2 diabetics who carry a particular version of a gene, according to researchers at the Technion-Israel Institute of Technology and Clalit Health Services in Israel.

After 18 months of treatment, people with the haptoglobin (Hp) 2-2 gene who took 400 International Units (IU) of vitamin E daily had more than 50 percent fewer heart attacks, strokes, and related deaths than Hp 2-2 patients who took a placebo pill. 40% of individuals with diabetes carry the Hp 2-2 gene.
The findings were published in the November 21 online edition of the journal Arteriosclerosis, Thrombosis, and Vascular Biology.

Most of the difference came from the reduced number of heart attacks among those taking vitamin E. In the group of 1,434 Hp 2-2 individuals taking part in the study, seven people had a heart attack, compared to 17 who did not take the vitamin. Dr. Andrew Levy, of the Technion Faculty of Medicine, said there were no side effects observed in patients who took vitamin E.

The study suggests that genetic testing for the Hp 2-2 gene “may be useful to identify a large group of diabetes individuals who could potentially derive cardiovascular benefit from a very inexpensive treatment,” Levy said.

The finding is a new answer to an old question: can antioxidant vitamins such as vitamin E help prevent heart disease? Previously, cardiologists routinely prescribed vitamin E for their patients, but the practice has dwindled as several major studies in the past decade showed no heart-protective effects and potential harm from vitamin E mega-doses.

However, Levy and colleagues suspected that there might be one group of patients who could benefit from vitamin E: diabetic individuals with a particular variant of the haptoglobin gene. Haptoglobin is a powerful antioxidant protein that stabilizes the iron-rich red blood cell molecule called hemoglobin, preventing inflammation in the walls of arteries.

There are several versions of the haptoglobin gene. In previous studies, Levy and colleagues showed that Hp 2-2 is an inferior antioxidant compared to its genetic siblings, and that this difference is exaggerated in patients with diabetes. The researchers also discovered that diabetic patients with Hp 2-2 are two-to-three times more likely than other diabetics to suffer a cardiovascular event such as a heart attack.

“This version of the gene does not determine whether or not an individual will develop diabetes but rather whether an individual with diabetes is susceptible to developing the devastating complications associated with diabetes such as heart disease, kidney disease or visual loss,” Levy noted.

A genetic test for Hp 2-2 is commercially available, said Levy, who is also a consultant for Synvista Therapeutics, which owns a patent on the use of Hp testing to predict diabetic complications.

By making a kit, the group hopes to considerably lower the price of testing. According to Levy, the test would cost about $30 and only have to be done once.

Posted by dlifenews at 04:40 PM | Comments (0)

Type 2 Diabetics Require Special Heart Care

January 11, 2008 (Newswise) — The worldwide obesity epidemic is of top concern to Dr. George A. Beller, Professor of Cardiology at the University of Virginia Health System. As he explains it, patients who are obese often have type 2 diabetes, a condition that requires special heart care.

Type 2 diabetes is the most common form of diabetes mellitus. People who have this condition are resistant to their insulin and often develop inflammation in their coronary arteries. Although type 2 diabetes commonly occurs in adults, an increasing number of overweight children and adolescents are also developing it.

Six years ago, Dr. Beller established one of the nation’s first combined Diabetes-Cardiovascular Disease clinics at UVA to care for diabetic patients with suspected or known heart disease. At the clinic, a cardiologist and an endocrinologist who specializes in diabetes use a team-based approach to treat patients.

“About 70 percent of diabetics die from cardiovascular disease,” notes Dr. Beller. “That’s why our clinic acts as if the diabetics we treat already have some degree of heart disease, even if they have never exhibited any signs of it.”

Treatment goals for diabetic patients without heart disease symptoms include reducing their LDL (bad cholesterol) to under 100, which often requires use of cholesterol lowering drugs like statins. “An LDL below 100 is the same level we aim for when treating someone who has had a heart attack,” says Dr. Beller. “We also focus on getting the patient’s systolic blood pressure below 135 and place them on aspirin.”

When treating a diabetic patient with heart disease, cardiologists have to get “extremely aggressive,” Dr. Beller says. “These people have a much greater risk of having a heart attack or dying of heart disease than someone who isn’t diabetic.”

Diagnostic testing is the first step in assessing diabetic patients whose symptoms suggest they may have heart disease. “Many obese type 2 diabetics who have heart disease may experience shortness of breath with exertion rather than chest pain. Such patients need to have stress testing with cardiac nuclear imaging or echocardiography to detect if they have severe blockages in their coronary arteries,” notes Dr. Beller.

When heart disease is detected, cholesterol goals become even more stringent. Treatment plans focus on getting a patient’s LDL under 70 and their HDL (good cholesterol) above 40.

As Dr. Beller notes, a crucial element of treatment is encouraging diabetics to make lifestyle changes that include weight loss and exercise. “Obesity is driving the epidemic of type 2 diabetes, and drugs alone will not solve the problem,” he says. “Obese people who lose just ten percent of their body weight can reverse inflammation of the arteries and reverse many other cardiometabolic abnormalities.”

Posted by dlifenews at 04:37 PM | Comments (0)

Carrot Cake Study on Sugar in Type 2 Diabetes

January 09, 2008

New study adds to new thinking on sugar in the diabetes diet

January 9, 2008 (EurekAlert) - Patients with type 2 diabetes are often advised to cut out sucrose (table sugar) all together. However, in recent years this traditional advice has been questioned by some researchers who suggest that moderate amounts of sugar can be safely consumed as part of the diet of patients with diabetes. Now a new study has been published that is consistent with this revised approach. It showed that patients who increased their daily sugar intake (in the form of carrot cake) but maintained a stable body weight, showed no adverse changes in their blood glucose.

The study was conducted by the Department of Nutrition and Dietetics at London’s Hammersmith Hospital. Three slices of carrot cake were added to the daily diets of nine, overweight type 2 diabetes patients over 24 days (bringing their daily total to 88g or 18 teaspoons of sugar). Consumption of the carrot cake slices was evenly distributed across the day. Several measurements were recorded at the beginning and end of the study, including the patients’ weight, blood sugar (glucose) levels, cholesterol levels, and insulin sensitivity (which is a measure of how well the body responds to the hormone insulin).

Professor Gary Frost, who led the study, explained ‘In this study, the energy intake of these patients was balanced to their body weight, and their sucrose intake was spread evenly over a day. Correspondingly, they did not gain weight or show an increase in blood glucose levels at the end of the study; in addition, their cholesterol levels and insulin sensitivity did not change.’ He added ‘the results of this small, short-term study support other scientific studies, which suggest that there could be more flexibility with sucrose in the diets of patients with type 2 diabetes. There is evidence from other studies (reviewed by Kirk et al 2000) that inclusion of sucrose may help people to lower their fat intake, which in turn may be beneficial to overall health’.

Professor Frost continued ‘This research is in line with the dietary guidelines set by the American Diabetes Association (2007), which state that sucrose does not cause a greater increase in blood glucose levels than an equivalent amount of starch. Therefore sucrose or sucrose-containing foods should be treated similarly to other carbohydrate containing foods by people with diabetes; either substituted for other carbohydrates in the total daily intake, or managed with appropriate diabetes medication.

Posted by dlifenews at 04:35 PM | Comments (8)

Lack of Deep Sleep May Increase Risk of Type 2 Diabetes

January 02, 2008

January 2, 2008 (EurekAlert) - Suppression of slow-wave sleep in healthy young adults significantly decreases their ability to regulate blood-sugar levels and increases the risk of type 2 diabetes, report researchers at the University of Chicago Medical Center in the “Early Edition” of the Proceedings of the National Academy of Science, available online as soon as Dec. 31, 2007.

Deep sleep, also called “slow-wave sleep,” is thought to be the most restorative sleep stage, but its significance for physical well-being has not been demonstrated. This study found that after only three nights of selective slow-wave sleep suppression, young healthy subjects became less sensitive to insulin. Although they needed more insulin to dispose of the same amount of glucose, their insulin secretion did not increase to compensate for the reduced sensitivity, resulting in reduced tolerance to glucose and increased risk for type 2 diabetes. The decrease in insulin sensitivity was comparable to that caused by gaining 20 to 30 pounds.

Previous studies have demonstrated that reduced sleep quantity can impair glucose metabolism and appetite regulation resulting in increased risk of obesity and diabetes. This current study provides the first evidence linking poor sleep quality to increased diabetes risk.

"These findings demonstrate a clear role for slow-wave sleep in maintaining normal glucose control," said the study's lead author, Esra Tasali, MD, assistant professor of medicine at the University of Chicago Medical Center. "A profound decrease in slow-wave sleep had an immediate and significant adverse effect on insulin sensitivity and glucose tolerance."

“Since reduced amounts of deep sleep are typical of aging and of common obesity-related sleep disorders, such as obstructive sleep apnea these results suggest that strategies to improve sleep quality, as well as quantity, may help to prevent or delay the onset of type 2 diabetes in populations at risk,” said Eve Van Cauter, PhD, professor of medicine at the University of Chicago and senior author of the study.

The researchers studied nine lean, healthy volunteers, five men and four women between the ages of 20 and 31. The subjects spent two consecutive nights in the sleep laboratory, where they went to bed at 11 P.M., slept undisturbed but carefully monitored, and got out of bed 8.5 hours later, at 7:30 A.M.

The same subjects were also studied for three consecutive nights during which they followed identical nighttime routines. During this session, however, when their brain waves indicated that they were drifting into slow-wave sleep they were subtly disturbed by sounds administered through speakers beside the bed.

These sounds were loud enough to disrupt deep sleep but not so loud as to cause a full awakening. This technique enabled the researchers to decrease slow-wave sleep by about 90 percent, shifting the subjects from the onset of deep sleep (stage 3 or 4) to a lighter sleep (stage 2) without altering total sleep time.

"Our system proved quite effective," Tasali said. When asked about the sounds the next morning, study subjects vaguely recalled hearing a noise "three or four times," during the night. Some recalled as many as 10 to 15. On average, however, subjects required about 250-300 interventions each night, fewer the first night but more on subsequent nights as "slow-wave pressure," the body's need for deep sleep, accumulated night after night.

"This decrease in slow-wave sleep resembles the changes in sleep patterns caused by 40 years of aging," Tasali said. Young adults spend 80 to 100 minutes per night in slow-wave sleep, while people over age 60 generally have less than 20 minutes. "In this experiment," she said, "we gave people in their 20s the sleep of those in their 60s."

At the end of each study, the researchers gave intravenous glucose (a sugar solution) to each subject, then took blood samples every few minutes to measure the levels of glucose and insulin, the hormone that controls glucose uptake.

They found that when slow-wave sleep was suppressed for only three nights, young healthy subjects became about 25 percent less sensitive to insulin. As insulin sensitivity decreased, subjects needed more insulin to dispose of the same amount of glucose. But for eight of the nine subjects, insulin secretion did not go up to compensate for reduced effects. The result was a 23 percent increase in blood-glucose levels, comparable to older adults with impaired glucose tolerance.

Those with low baseline levels of slow-wave sleep had the lowest levels after having their sleep patterns disrupted and the greatest decrease in insulin sensitivity.

The alarming rise in the prevalence of type 2 diabetes is generally attributed to the epidemic of obesity combined with the aging of the population. "Previous studies from our lab have demonstrated many connections between chronic, partial, sleep deprivation, changes in appetite, metabolic abnormalities, obesity, and diabetes risk," said Van Cauter. "These results solidify those links and add a new wrinkle, the role of poor sleep quality, which is also associated with aging."

"Chronic shallow non-REM sleep, decreased insulin sensitivity and elevated diabetes risk are typical of aging," the authors conclude. "Our findings raise the question of whether age-related changes in sleep quality contribute to the development of these metabolic alterations."

Posted by dlifenews at 10:28 AM | Comments (0)

Smoking Associated With Increased Risk of Diabetes

December 11, 2007

December 11, 2007 (Newswise) — A review of previous studies indicates that people who currently smoke have an increased risk of developing type 2 diabetes, compared with non-smokers, according to an article in the December 12 issue of JAMA.

A number of studies have examined the association between smoking and incidence of glucose abnormalities, and have suggested that smoking could be independently associated with glucose intolerance, impaired fasting glucose and type 2 diabetes, which could make smoking a modifiable risk factor for type 2 diabetes. However, it appears the quality and clinical features of these studies have not been fully assessed regarding this possible association.

Carole Willi, M.D., of the University of Lausanne, Switzerland, and colleagues conducted a systematic review and meta-analysis of studies describing the association between active smoking and the incidence of diabetes or other glucose metabolism irregularities. A search of databases yielded 25 studies, which were published between 1992 and 2006. The number of participants per study ranged from 630 to 709,827, for a total of 1.2 million participants. A total of 45,844 new cases of diabetes were reported during a study follow-up period ranging from 5 to 30 years.

Analysis of the data indicated that active smokers have a 44 percent increased risk of developing type 2 diabetes compared with non-smokers. Further analyses suggested a dose-response relationship between smoking and diabetes, with the association stronger for heavy smokers (20 or more cigarettes/day; 61 percent increased risk) compared with lighter smokers (29 percent increased risk).

The association also was weaker for former smokers (23 percent increased risk) than it was for active smokers.

“… we conclude that the relevant question should no longer be whether this association exists, but rather whether this established association is causal,” the authors write.

They add that observational primary studies cannot prove causality, but that the studies in this review do meet several recommended criteria for causation. “First, there is an appropriate temporal relationship: the cigarette smoking preceded diabetes incidence in all studies. Second, the findings are consistent with a dose-response relationship, with stronger associations for heavy smokers relative to lighter smokers and for active smokers relative to former smokers. … Third, there is theoretical biological plausibility for causality, in that smoking may lead to insulin resistance or inadequate compensatory insulin secretion responses according to several but not all studies.”

“Conversely, there are also possible non-causal explanations for this association. Smoking is often associated with other unhealthy behaviors that favor weight gain and/or diabetes, such as lack of physical activity, poor fruit and vegetable intake, and high alcohol intake,” the researchers write.

“Considering the consistent finding of increased diabetes incidence associated with active cigarette smoking across a large number of studies, we believe that there is no need for further cohort studies to test this hypothesis. However, there is a need for studies that include detailed measurement and adjustment for potential confounding factors such as socioeconomic status, education, and exercise with a goal of establishing whether the association with smoking is causal. We recommend that future studies focus on plausible causal mechanisms or mediating factors such as obesity, lack of physical activity, dietary habits, and stress levels.”

Posted by dlifenews at 09:55 AM | Comments (0)

Monotherapy BYETTA® Showed Significant Improvement in Glucose Control and Weight Loss in Adults with Type 2 Diabetes

December 06, 2007

FDA Submission Planned in First Half of 2008

December 6, 2007 (PRNewswire-FirstCall via COMTEX News Network) -- Amylin Pharmaceuticals, Inc. (Nasdaq: AMLN) and Eli Lilly and Company (NYSE: LLY) today announced study results from a 24-week study of monotherapy, or stand-alone, BYETTA (exenatide) injection taken twice daily in drug-naive patients with type 2 diabetes. Study participants taking 5 mcg or 10 mcg of monotherapy BYETTA twice daily showed significant reductions in A1C (a measure of average blood sugar over 3 months) by 0.7 percentage points and 0.9 percentage points, respectively, from an average baseline A1C ranging from 7.8 to 7.9 percent. In addition, approximately 60 percent of study participants on either 5 mcg or 10 mcg of monotherapy BYETTA at the conclusion of the study had an A1C of 7 percent or less, a common target for good glucose control. The companies plan a regulatory submission to the U.S. Food and Drug Administration (FDA) in the first half of 2008.

In this 24-week, randomized, placebo-controlled study, 232 drug-naive people with type 2 diabetes were treated with monotherapy BYETTA or placebo. More than 85 percent of study participants in the 5 mcg and 10 mcg arms completed the study. Weight loss from baseline was significant and similar to that observed in previous BYETTA studies.

"The American Diabetes Association's (ADA) clinical guidelines for the treatment of patients with type 2 diabetes are to achieve target glucose control, as well as weight loss in overweight or obese patients," said James Malone, M.D., Global Medical Director, Eli Lilly and Company. "These data are robust and are consistent with data from other trials that support the use of BYETTA before starter insulin. If approved for monotherapy, BYETTA may provide an additional treatment option for physicians to consider earlier in the continuum of care."

There was a low incidence of nausea reported in both treatment arms of the study of approximately 3 and 13 percent in the 5 mcg and 10 mcg arms, respectively. There were no instances of severe hypoglycemia in this study. Overall hypoglycemia observed was similar to that seen in studies where BYETTA was used in conjunction with metformin only.

BYETTA -- the first and only FDA-approved incretin mimetic -- was approved in April 2005 and has been used by more than 700,000 patients since its introduction. BYETTA is indicated as an add-on therapy for use twice a day in adults with type 2 diabetes who are unsuccessful at controlling their blood sugar levels using common oral diabetes medications. This study was conducted following receipt of an approvable letter for a monotherapy indication from the FDA in 2005.

Study Design
The 24-week, randomized study included 232 people with type 2 diabetes who were not achieving adequate glucose control using diet and exercise without previous use of antidiabetes agents. Study participants were randomized to receive subcutaneous injections of placebo, 5 mcg exenatide, or 10 mcg exenatide twice daily without taking any oral antidiabetes agents. Patients randomized to 10 mcg exenatide received 5 mcg injections for the first 4 weeks, and increased to 10 mcg injections for the final 20 weeks.

Full study results will be included in future scientific publications.

Posted by dlifenews at 12:26 PM | Comments (3)

Quality-Improvement Initiatives Lead to Progress in Diabetes Care

December 03, 2007

December 3, 2007 (Newswise) — Two major initiatives designed to improve primary care treatment of type 2 diabetes have yielded significant benefits in largely minority, disadvantaged populations, according to a pair of studies in the December issue of Medical Care, published by Lippincott Williams & Wilkins, a part of Wolters Kluwer Health, a leading provider of information and business intelligence for students, professionals, and institutions in medicine, nursing, allied health, pharmacy and the pharmaceutical industry.

One study finds that patients treated at clinics that follow the "Chronic Care Model" have lower rates of diabetes-related coronary artery disease, while another finds that the "Health Disparities Collaboratives" initiative has improved diabetes care at U.S. community health centers.

In both studies, outcomes appeared better when care more closely followed the research-based quality improvement programs. "Patients are better off when we use what we know; the more reliably we use it, the better off they are," writes Dr. Donald M. Berwick of the Institute for Healthcare Improvement, Cambridge, Mass., in an accompanying editorial. "That's the simple, affirming conclusion of both of these papers."

Dr. Michael Parchman and colleagues of the South Texas Veterans Health Care System, San Antonio, evaluated an approach called the Chronic Care Model (CCM), which outlines specific organizational characteristics believed to lead to improved outcomes for patients with chronic diseases such as type 2 diabetes. Using data on diabetic patients treated at twenty Texas primary care clinics, the researchers looked at how closely diabetes care followed the CCM approach, and whether CCM care led to reductions in the risk of coronary heart disease—a major complication of diabetes.

Just fifteen percent of patients in the study met target levels for three critical risk factors: hemoglobin A1c (which measures long-term control of blood sugar levels), blood pressure, and lipid levels (including cholesterol). The overall coronary risk over 10 years was 16.2 percent—nearly one-third of this risk (5.0 percent) could be explained by poor control of risk factors.

At clinics that followed the CCM approach more closely, the percentage of CHD risk explained by poor risk factor control was significantly reduced. For example, at a clinic that closely followed the CCM, just 1.7 percent of CHD risk was explained by poor risk factor control, compared to 5.0 percent at a clinic that only partially followed the CCM approach. "These findings contribute to the growing body of evidence documenting a relationship between how care is provided in primary care clinic settings and patient outcomes," Dr. Parchman and colleagues conclude.

The second study, led by Dr Marshall H. Chin of University of Chicago, evaluated the impact of a Health Resources and Services Administration initiative, the Health Disparities Collaborative (HDC). The goal of the HDC was to institute a quality improvement program for diabetes care for patients treated at community health centers.

Using nationwide data, the researchers found that health centers where staff were trained in the HDC approach achieved significant improvements in several measures of diabetes care, including reductions in hemoglobin A1c level and "bad" cholesterol levels. Centers receiving a more intensive form of the HDC approach had only slightly better improvement. It may be that the "standard" HDC approach is adequate, or that even stronger interventions will be needed to achieve greater improvements.

New approaches to improving care for patients with chronic diseases such as diabetes are urgently needed—particularly in medically "under-served" populations at increased risk of poor health outcomes. However, it can be difficult to translate research-proven management approaches into "real-world" health care settings.

The new studies show that research-based initiatives such as CCM and HDC can improve diabetes care for disadvantaged populations, at both the patient and organizational levels. Dr. Berwick writes, "Both papers seek to build a bridge between two important worlds of endeavor: the world of study and assessment of medical practices, and the world of action to put that knowledge to work on behalf of patients."

Posted by dlifenews at 10:25 AM | Comments (0)

High-Glycemic Index Carbohydrates Associated with Risk for Developing Type 2 Diabetes in Women

November 27, 2007

November 27, 2007 (Eurekalert) – Eating foods high on the glycemic index, which measures the effect of carbohydrates on blood glucose levels, may be associated with the risk for developing type 2 diabetes in Chinese women and in African-American women, according to two studies in the November 26 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. However, eating more cereal fiber may be associated with a reduced risk for type 2 diabetes in African-American women.

Researchers remain uncertain regarding exactly how diet, including carbohydrate intake, affects the development of type 2 diabetes, according to background information in the articles. Studies have revealed that the body absorbs carbohydrates from different foods at different rates. This leads to varying effects on levels of blood glucose and the hormone insulin, which converts glucose into energy. Foods high on the glycemic index, such as rice and other simple carbohydrates, cause a rapid spike and then a drop in blood glucose, whereas high-fiber foods tend to be lower on the glycemic index and have a more gradual effect. Some evidence has linked high–glycemic index foods with the risk of developing type 2 diabetes.

In one study, Supriya Krishnan, D.Sc., of Boston University School of Public Health, and colleagues examined data from 40,078 U.S. black women who filled out a food questionnaire in 1995. The glycemic index and glycemic load—a measure of the amount of carbohydrates from glucose—were calculated. Every two years through 2003, the women answered follow-up questionnaires about their weight, health and other factors.

During eight years of follow-up, 1,938 participants developed type 2 diabetes. Women who ate high–glycemic index foods or a diet with a high glycemic load had a higher risk for diabetes. However, women who ate more fiber from grains (cereal fiber) had a reduced risk; for women with a body mass index (BMI) of less than 25, women who ate about 1.5 grams of fiber per day were 59 percent less likely to develop diabetes than women who ate about 8.3 grams per day.

Because high–glycemic index foods increase blood glucose levels significantly, they increase the body’s demand for insulin, the authors note. This can contribute to problems with the pancreas (which produces insulin) that may eventually lead to diabetes. In addition, high–glycemic index foods can directly decrease the body’s response to insulin by increasing the production of fatty acids after meals.

“Our results indicate that black women can reduce their risk of diabetes by eating a diet that is high in cereal fiber,” the authors write. “Incorporating fiber sources into the diet is relatively easy: a simple change from white bread (two slices provides 1.2 grams of fiber) to whole wheat bread (two slices provides 3.8 grams of fiber) or substituting a cup of raisin bran (5 to 8 grams of fiber) or oatmeal (4 grams of fiber) for a cup of corn chex (0.5 grams of fiber) or rice chex (0.3 grams of fiber) will move a person from a low fiber intake category to a moderate intake category, with a corresponding 10 percent reduction in risk.”

In another study, Raquel Villegas, Ph.D., of Vanderbilt University Medical Center, Nashville, Tenn., and colleagues followed a group of 64,227 Chinese women for an average of five years. During in-person interviews conducted every two years between 2000 and 2004, the researchers collected data on dietary habits, physical activity and other health-related information.

During the study, 1,608 of the women developed diabetes. Women who consumed more carbohydrates overall were more likely to develop diabetes—when they were split into five groups based on carbohydrate intake, those in the group consuming the most (about 337.6 grams per day) had a 28 percent higher risk than those in the group consuming the least (about 263.5 grams per day). Women who ate diets with a higher glycemic index and who ate more staples such as bread, noodles and rice specifically also had an increased risk. Women who ate 300 grams or more of rice per day were 78 percent more likely to develop diabetes than those who ate less than 200 grams per day.

“Given that a large part of the world’s population consumes rice and carbohydrates as the mainstay of their diets, these prospective data linking intake of refined carbohydrates to increased risk of type 2 diabetes mellitus may have substantial implications for public health,” the authors conclude.

Posted by dlifenews at 11:50 AM | Comments (0)

Fat Cells Send Message that Aids Insulin Secretion

November 07, 2007

November 7, 2007 (EurekAlert) - The body's fat cells help the pancreas do its job of secreting insulin, according to research at Washington University School of Medicine in St. Louis. This previously unrecognized process ultimately could lead to new methods to improve glucose metabolism in type 2 diabetic or insulin-resistant people.

In a study using laboratory mice, published in the November 7, 2007 issue of Cell Metabolism, scientists at the School of Medicine report that fat cells release a protein that aids insulin secretion from pancreatic beta cells, which are the sole source of insulin. The protein is an enzyme that the pancreatic cells themselves produce in only minimal amounts. The enzyme works to enhance glucose-stimulated insulin secretion from pancreatic beta cells.

Insulin helps the body process blood sugar (glucose), and those with type 2 diabetes have a deficiency of insulin or a resistance to its effects. More than 7 million people in the U.S. are living with a diagnosis of type 2 diabetes and many more are undiagnosed.

The researchers assert that the enzyme secreted by fat cells, called Nampt, is an important component of the insulin-secretion pathway. "We think this secretion process allows fat cells to communicate with the pancreas and aid its function," says senior author Shin-ichiro Imai, M.D., Ph.D., assistant professor of medicine and of molecular biology and pharmacology. "I suspect this process could be critical for compensating pancreatic beta cell function in the face of increasing insulin resistance."

The association of type 2 diabetes and insulin resistance with obesity suggests there may be limits to the ability of the process to enhance pancreatic function, according to Imai. "It may be that in some obese individuals a threshold has been reached so that this mechanism no longer provides adequate compensation," he says. "But there may be ways to overcome this threshold."

Interestingly, in 2004 Nampt provoked excitement in the scientific community because it was reported to be a newly discovered fat-derived hormone that worked very much like insulin. That study named the enzyme visfatin. The scientists who made this assertion have since retracted their claim.

In the new study, the Washington University researchers contend that Nampt is not an insulin-like hormone. Instead, their investigation shows it's an enzyme that modulates pancreatic function.
"Our work marks a conceptual breakthrough," Imai says. "Nampt synthesizes a compound in the bloodstream, and when that compound reaches the pancreas it stimulates insulin secretion. This is a surprising mechanism by which a circulating metabolite modulates pancreatic function."

Imai says he believes it's possible that the compound produced by Nampt, called NMN for short, could be used to raise insulin secretion from pancreatic cells and thus help improve the way the body handles sugar. Imai and his group are collaborating with clinical researchers at the University to find out how much NMN is in the blood of normal and diabetic or obese patients. They also hope to initiate clinical trials to test NMN as a therapeutic agent in patients with type 2 diabetes or insulin resistance.

Nampt is actually a widespread enzyme and catalyzes such a fundamental process that most cells of the body have an internal form of it. But, studying mice, the researchers saw that Nampt could be secreted from cells — but only from fat cells. And because Nampt levels are low in pancreatic cells, the pancreas depends on the enzyme secreted from fat and its product, NMN, in the blood.

When pancreatic beta cells absorb enough NMN, it stimulates them to secrete insulin. In the bloodstreams of laboratory mice, NMN was measured at a concentration shown to be sufficient to enhance insulin secretion from pancreatic beta cells. No one had previously known that NMN circulated in the bloodstream.

Mice engineered to have just one instead of two copies of the Nampt gene had a mildly impaired ability to metabolize glucose and had a defect in insulin secretion. The researchers showed that NMN restored normal insulin secretion in these mice.

In conjunction with the Office of Technology Management at the University, Imai has patented the use of Nampt and NMN for the prevention and treatment of metabolic complications, such as type 2 diabetes.
Next, the researchers will try to identify the factors that cause secretion of Nampt from fat cells and the mechanisms by which NMN enhances insulin secretion in the pancreas.

Posted by dlifenews at 04:14 PM | Comments (0)

'Tweens' Double Use of Diabetes Drugs

More children taking chronic medications for blood pressure, cholesterol, asthma, depression and diabetes

November 7, 2007 (EurekAlert) – America’s tweens more than doubled their use of type-2 diabetes medications between 2002 and 2005, with girls between 10 and 14 years of age showing a 166 percent increase. The likely cause: Obesity, which is closely associated with Type 2 diabetes.

The finding is included in a study of chronic medication use in children 5 to 19 reported Wednesday, Nov. 7 at the annual meeting of the American Public Health Association by researchers from the Saint Louis University School of Medicine and School of Public Health and pharmacy benefit manager Express Scripts. In addition to diabetes, utilization patterns for blood pressure, cholesterol, asthma and depression medications were also examined.

“Across every chronic medication class we examined over this four year period of time, children’s use increased, with varying patterns of growth across males and females and age groups,” said Emily R. Cox, Ph.D., RPh, senior director of research at Express Scripts.

For example, the number of males between 15 and 19 using a blood pressure drug increased by 15.4 percent even as the number of females in the age group taking the drugs, called antihypertensives, declined by 1.6 percent.

On the other hand, the number of females between 15 and 19 taking an anti-depressant increased by 6.8 percent while, for males in the same age group, utilization declined slightly.

This increase in anti-depressant use among 15 to 19 year old girls was a striking exception to decreases for boys and girls 5 to 9 and boys 10 to 19. It also occurred despite a Public Health Advisory released by the Food and Drug Administration in October 2003, regarding anti-depressant use by children. Among all children, the prevalence of antidepressant use had been increasing prior to the advisory after which it decreased.

With asthma, children age 5 to 9 accounted for the largest increase in the use of controller medication among the three age groups at 67.3 percent as compared to 38.8 percent for the 10 to 14 age group and 34.7 percent for the 15 to 19 age group.

“This may be explained by concerns over long-term side effects of these medications in children and/or greater physician office visits, and therefore greater likelihood of prescribing,” explained Donna R. Halloran, M.D., MSPH, assistant professor of pediatrics at Saint Louis University School of Medicine.

“Overall, these patterns could reflect changing prescribing behaviors by physicians (anti-hypertensives), increases in the risk factors for chronic diseases (type-2 antidiabetics, antihyperlipidemics), increased office visit rates and therefore screening rates – particularly for females – or trends toward greater use of drug therapy as the preferred mode of treating children with chronic conditions,” observed Sharon M. Homan, Ph.D., professor of community health at Saint Louis University School of Public Health.

Posted by dlifenews at 02:24 PM | Comments (0)

UCSD Researchers Discover Inflammation, Not Obesity, Cause of Insulin Resistance

November 06, 2007

Findings may have important potential for new drug discoveries in fight against Type 2 diabetes

November 6, 2007 (UCSD News) - Researchers at the University of California, San Diego (UCSD) School of Medicine have discovered that inflammation provoked by immune cells called macrophages leads to insulin resistance and Type 2 diabetes. Their discovery may pave the way to novel drug development to fight the epidemic of Type 2 diabetes associated with obesity, the most prevalent metabolic disease worldwide.

In recent years, it has been theorized that chronic, low-grade tissue inflammation related to obesity contributes to insulin resistance, the major cause of Type 2 diabetes. In research done in mouse models, the UCSD scientists proved that, by disabling the macrophage inflammatory pathway, insulin resistance and the resultant Type 2 diabetes can be prevented.

The findings of the research team, led by principle investigators Michael Karin, Ph.D., Professor of Pharmacology in UCSD’s Laboratory of Gene Regulation and Signal Transduction, and Jerrold Olefsky, Distinguished Professor of Medicine and Associate Dean for Scientific Affairs, will be published as the feature article of the November 7 issue of Cell Metabolism. Co-first authors of the paper are Giovanni Solinas, UCSD Department of Pharmacology and Cristian Vilcu, UCSD Division of Endocrinology and Metabolism.

“Our research shows that insulin resistance can be disassociated from the increase in body fat associated with obesity,” said Olefsky.

Macrophages, found in white blood cells in the bone marrow, are key players in the immune response. When these immune cells get into tissues, such as adipose (fat) or liver tissue, they release cytokines, which are chemical messenger molecules used by immune and nerve cells to communicate. These cytokines cause the neighboring liver, muscle or fat cells to become insulin resistant, which in turn can lead to Type 2 diabetes.

The UCSD research team showed that the macrophage is the cause of this cascade of events by knocking out a key component of the inflammatory pathway in the macrophage, JNK1, in a mouse model. This was done through a procedure called adoptive bone marrow transfer, which resulted in the knockout of JNK1 in cells derived from the bone marrow, including macrophages.

With this procedure, bone marrow was transplanted from a global JNK1 knockout mouse (lacking JNK1 in all cell types) into a normal mouse that had been irradiated to kill off its endogenous bone marrow. This resulted in a chimeric mouse in which all tissues were normal except the bone marrow, which is where macrophages originate. As a control, the scientists used normal, wild-type mice as well as mice lacking JNK1 in all cell types. These control mice were also subjected to irradiation and bone marrow transfer.

The mice were all fed a high-fat diet. In regular, wild-type mice, this diet would normally result in obesity, leading to inflammation, insulin resistance and mild Type 2 diabetes. The chimeric mice, lacking JNK1 in bone marrow-derived cells, did become obese; however, they showed a striking absence of insulin resistance – a pre-condition that can lead to development of Type 2 diabetes.

“If we can block or disarm this macrophage inflammatory pathway in humans, we could interrupt the cascade that leads to insulin resistance and diabetes,” said Olefsky. “A small molecule compound to block JNK1 could prove a potent insulin-sensitizing, anti-diabetic agent.”

The research also proved that obesity without inflammation does not result in insulin resistance. Olefsky explained that when an animal or a human being becomes obese, they develop steatosis, or increased fat in the liver. The steatosis leads to liver inflammation and hepatic insulin resistance.

The chimeric mice did develop fatty livers, but not inflammation. “Their livers remained normal in terms of insulin sensitivity,” said Olefsky, adding that this shows that insulin resistance can also be disassociated from fatty liver.

“We aren’t suggesting that obesity is healthy, but indications are promising that, by blocking the macrophage pathway, scientists may find a way to prevent the Type 2 diabetes now linked to obesity and fatty livers,” Olefsky said.

Additional contributors include Jun-Li Luo, Willscott Naugler and Sergei Grivennikov, UCSD Department of Pharmacology; Jaap G. Neels, and Gautam K. Bandyopadhyay, UCSD Division of Endocrinology and Metabolism; Anthony Wynshaw-Boris, UCSD Departments of Pediatrics and Medicine; and Miriam Scadeng, UCSD Department of Radiology.

This research was supported by National Institutes of Health grants ES004151, ES006376, DK033651 and DK074868. Additional funding was provided by a fellowship from the Swiss National Science Foundation, a University of California Discovery Grant and Mentor-Based Postdoctoral Fellowships from the American Diabetes Association. Michael Karin is an American Cancer Society Research Professor.

Posted by dlifenews at 02:28 PM | Comments (0)

Genetic 'Roadblock' Hoped to Inspire Future Type 2 Diabetes Research

October 02, 2007

October 2, 2007 (EurekAlert) – A team of Mount Sinai Hospital researchers has found that a “genetic roadblock” identified in a recent study could pave the way toward novel treatments for type 2 diabetes.

In the study, researchers from the Samuel Lunenfeld Research Institute of Mount Sinai Hospital found the first genetic evidence that the elimination of the gene for glycogen synthase kinase-3 (GSK-3) in mice sensitizes the animals to insulin.

Insulin is a hormone that helps control sugar (glucose) levels in the blood. In people with type 2 diabetes, the pancreas does not produce enough insulin, or it is not properly used. As a result, sugar accumulates in the blood rather than being absorbed, stored or burned for energy. The study found that by eliminating GSK-3 in mouse models, more sugar became stored in the liver in response to increased insulin sensitivity, indicating that insulin had become more effective.

The study from the laboratory of Dr. Jim Woodgett, Director of the Lunenfeld, and the first scientist to isolate the GSK-3 genes in 1990, made the cover of the October 3 edition of Cell Metabolism.

“We created a ‘genetic roadblock’ by knocking out this particular gene and this made the mice far more efficient in their ability to use insulin to regulate their blood-sugar levels,” said Dr. Woodgett. “Research creates the best medicine and while potential human treatments are likely still years down the road, this study provides strong evidence that chemical inhibitors of this enzyme will be useful for increasing the effective potency of insulin.“

The study was co-authored by Drs. Katrina MacAulay and Bradley Doble. Dr. MacAulay was inspired to become a medical researcher specializing in diabetes because her sister, Ailsa MacAulay, suffers from this disease.

“I hope our findings will inspire other researchers around the world to develop treatments that will reduce symptoms of this epidemic disease as well as its associated complications, such as heart disease, liver disease or limb amputation,” said Dr. MacAulay.

Currently, more than two million people in Canada suffer from diabetes. It is one of the fastest growing diseases in the country with more than 60,000 new cases diagnosed each year.

Type 2 diabetes makes up about 90 per cent of all cases, with most evidence suggesting that it could be prevented or delayed by maintaining a healthy lifestyle.

“With this research, another piece in the puzzle has been put in place. It advances our understanding of how the complex mechanisms activated by insulin work. Understanding the details of this picture is central to developing new drugs that can help people with diabetes control their blood sugar,” says Dr. Diane T. Finegood, Scientific Director of the CIHR-Institute of Nutrition, Metabolism and Diabetes.

Posted by dlifenews at 04:50 PM | Comments (0)

Novo Nordisk and the International Diabetes Federation Join Forces in the Fight Against Childhood Diabetes

September 18, 2007

September 18, 2007 (Press Release) - Novo Nordisk and the International Diabetes Federation (IDF) today presented a global overview of the diabetes burden among children and adolescents. The Diabetes Youth Charter, an expert review into existing data and global trends in the area of childhood diabetes, highlights that children are in poor control of their diabetes, and that there is a burning need for addressing their special needs to add quality and years to their lives.

The Charter looks at epidemiology, organisation and delivery of care, as well as the psychosocial and the socio-economic impact of diabetes and provides a solid platform for strategies to improve the care and prevention of diabetes.

The Charter highlights that childhood diabetes is growing alarmingly worldwide. Over 70,000 children develop type 1 diabetes every year and the incidence is rising at a rate of 3% per year, with more children under the age of four being diagnosed.[1]

The publication stresses that while not enough data is available, it is now recognised that type 2 diabetes in children and adolescents is also on the rise and affects children in both developed and developing countries. For instance, Western Australia had an increase of 27% in the incidence of type 2 diabetes in young people between 1990 and 2002, and also Japan has experienced the same development with a more than 30-fold increase over the past 20 years. Both increases are believed to be a result of overweight and increasing obesity rates.[2]

As the rate of childhood diabetes is going up, the Charter provides a picture that much could be done to prevent complications of diabetes. Not just in countries with limited access to care, but also in many developed countries. For instance, of children with type 1 diabetes studied in France, only one in seven were at the American Diabetes Association (ADA) target of mean glucose levels under 7%. Since the risk of complications is linked to glycaemic control, stricter control is recommended. The complications of diabetes can be very severe, leading to early onset of cardiovascular disease and premature death.

“More has to be done to diagnose diabetes in children in a timely manner and give them adequate diabetes care. However, for many children, particularly in the less-developed world, the diagnosis of diabetes is still a death sentence. The family simply does not have money to allow their child to be treated with insulin and thereby save the child’s life. Even in the developed countries, children with diabetes in poor control live 10–20 years shorter than their peers,” says Dr Henk-Jan Aanstoot, chair of the Diabetes Youth Charter.

The Charter highlights a number of actions to promote better outcomes in childhood diabetes:

• Type 2 diabetes can be prevented in children through lifestyle changes, including better nutrition and physical exercise.

• Early detection, intensive treatment and improved care strategies may prevent complications and add years to life. Diabetes self-management education for every child and their family is necessary to achieve appropriate regulation of the disease.

• The changing epidemiological patterns in type 1 and type 2 diabetes among children create major knowledge gaps concerning the impact of diabetes and how to manage it. We need to understand the epidemiology better to facilitate effective treatment and care strategies and optimal resource allocation and organisation.

• While there is great variation in the availability of insulin around the world, some of the least developed countries have managed to provide a basic standard of care. Fiji and Azerbaijan are examples of countries that have succeeded in providing insulin to every child requiring it. Partnerships should be established to help the world’s least developed countries develop sustainable solutions for treating children with diabetes.

Lise Kingo, executive vice president of Novo Nordisk, stated “Novo Nordisk will explore how some of our existing programmes can be fine-tuned and strengthened to better reflect the challenges presented in the Youth Charter. Specifically, we are working to create and test a new model for sustainable diabetes care and insulin delivery for children in the developing world. Starting in 2008, we will test the new model in a few countries, one of them being Tanzania. This endeavour will be done in close collaboration with our international and local partners.”

With the Charter, Novo Nordisk and IDF seek to motivate healthcare systems around the world to do more for children and adolescents living with diabetes, by securing access to medicine and treatment, but also by educating the people around each child to facilitate successful management of the condition.

IDF President Martin Silink stressed that “access to diabetes care, especially for children and adolescents, is a human right which should no longer be ignored. Action must be taken now to prevent the needless deaths of children in both developed and less-developed nations. Governments should prioritise childhood diabetes on a par with HIV/AIDS, tuberculosis and malaria”.

The Diabetes Youth Charter (The Global Burden of Youth Diabetes: Perspectives and Potential) has been prepared by some of the world’s leading paediatric diabetologists. The launch of the Diabetes Youth Charter follows the recent adoption of the UN Resolution on diabetes (Resolution 61/225) and supports the World Diabetes Day (WDD) theme for 2007 and 2008, ‘Diabetes in Children and Adolescents’. The first UN-observed WDD will be this year on 14 November.

The full version of the Diabetes Youth Charter is available online: blackwell-synergy.com/toc/pdi/8/s8.
For more information, please contact Markela Dedopoulos, PR & Media liaison manager at Novo Nordisk, mded@novonordisk.com, +45 3079 4137.

Posted by dlifenews at 03:37 PM | Comments (0)

One-Year Data Showed Investigational Use of Initial Combination Therapy with JANUVIA™ (sitagliptin) and Metformin Significantly Improved Blood Sugar Control in Patients with Type 2 Diabetes Compared to Metformin Alone

Data Also Showed that Initial Combination Therapy with JANUVIA and Metformin Led to Significant Improvement in Markers of Beta Cell Function in Patients with Type 2 Diabetes

• Up to 67 percent of patients with type 2 diabetes who continued past 24 weeks in this study achieved A1C of less than seven percent with investigational use of sitagliptin and metformin as initial combination therapy, compared to 44 percent on metformin alone at 54 weeks

• In a subgroup analysis of patients grouped by severity of starting baseline A1C, mean response to treatment with JANUVIA (sitagliptin) 50 mg and metformin 1000 mg twice daily was larger for patients with higher baseline A1C

• A separate study in healthy adults showed a four-fold increase in active GLP-1 concentrations following a meal when JANUVIA and metformin were used together (p<0.001) compared with placebo

September 18, 2007 (Business Wire)--Data presented at the 43rd Annual Meeting of the European Association for the Study of Diabetes (EASD) demonstrated that, when used investigationally as initial therapy in combination with metformin, JANUVIA™ (sitagliptin) provided significant and sustained improvement in blood sugar control compared to metformin alone and was generally well tolerated over a one-year period. Since metformin is administered twice daily, in this study sitagliptin was given as 50 mg twice daily to allow for co-administration of the two treatments. The approved dose for JANUVIA is 100 mg once daily.

JANUVIA is a selective, once-daily dipeptidyl peptidase-4 (DPP-4) inhibitor that enhances a natural body system, called the incretin system, which helps to regulate glucose by affecting the beta cells and alpha cells in the pancreas. JANUVIA is the first and only DPP-4 inhibitor to be approved and marketed in the United States for patients with type 2 diabetes. JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes mellitus. JANUVIA is also indicated to improve glycemic control, in combination with metformin or a thiazolidinedione (TZD), in patients with type 2 diabetes when the single agent alone plus diet and exercise do not provide adequate glycemic control. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, as it would not be effective in these settings. There are no contraindications for JANUVIA.

The study demonstrated a mean A1C reduction from baseline of 1.8 percent in patients treated with the initial combination of sitagliptin 50 mg/metformin 1000 mg twice daily for up to 54 weeks (n=153). Additionally, mean A1C reductions from baseline were 1.4 percent in patients treated with sitagliptin 50 mg/metformin 500 mg twice daily (n=147), 1.3 percent in patients treated with metformin 1000 mg twice daily (n=134), 1.0 percent in patients treated with metformin 500 mg twice daily (n=117), and 0.8 percent in patients treated with sitagliptin 100 mg once daily (n=106).

After completing an initial 24-week placebo-controlled phase (n=1091), 748 patients with a mean baseline A1C of 8.7 percent continued for an additional 30 weeks on their previously assigned active therapies: sitagliptin 50 mg/metformin 1000 mg twice daily (n=157); sitagliptin 50 mg/metformin 500 mg twice daily (n=148); metformin 1000 mg twice daily (n=137); metformin 500 mg twice daily (n=122); and sitagliptin 100 mg once-daily (n=106).

The aim of this 54-week study was to assess the longer term efficacy and safety of initial combination therapy with sitagliptin and metformin in patients with type 2 diabetes with inadequate glycemic control (A1C of 7.5 percent to 11 percent) on diet and exercise. The study found that 67 percent of patients who continued past 24 weeks in this study achieved an A1C goal of less than seven percent on sitagliptin 50 mg/metformin 1000 mg twice daily compared to 44 percent on metformin 1000 mg twice daily alone. Further, 48 percent of patients treated with sitagliptin 50 mg/metformin 500 mg twice daily, 25 percent of patients treated with metformin 500 mg twice daily, and 23 percent of patients treated with sitagliptin 100 mg once daily reached the target A1C goal.

A patient’s starting level of A1C is an important predictive factor of the magnitude of A1C reduction in response to anti-hyperglycemic therapy. In a subgroup analysis of patients grouped by severity of A1C at baseline, treatment with sitagliptin 50 mg/metformin 1000 mg twice daily demonstrated larger mean A1C reductions from baseline with higher baseline A1C. A mean reduction of 3.1 percent was seen in patients with baseline A1C of 10 percent or more (n=17), while reductions of 2.2 percent, 1.7 percent, and 1.0 percent were seen with baseline A1C values of ≥9 to <10 percent, ≥8 to <9 percent, and less than 8 percent, respectively.

"Initial therapy with one agent is often unsuccessful at getting patients to blood sugar goals. Many patients may require initial combination therapy, and this study provides important and useful information about the use of sitagliptin and metformin, in addition to diet and exercise, in order to achieve and maintain blood sugar control," said John Amatruda, M.D., vice president, clinical research, Merck & Co., Inc. "This study examines the clinical effect of initial combination therapy with JANUVIA and metformin over one year."

Investigational use of JANUVIA (sitagliptin) and metformin as initial combination therapy led to improvement in markers of beta cell function in patients with type 2 diabetes
The effects of sitagliptin and metformin on beta cell function were examined in patients with type 2 diabetes who participated in the 24-week, placebo-controlled phase of the above investigational study, in which 1,091 patients were randomized in a balanced manner to receive one of six treatments. Pancreatic islet beta cell function determines the ability of the body to produce insulin and suppress glucagon, hormones which play a central role in the regulation of blood sugar levels. Of the 1,091 patients randomized, a subset of 500 patients underwent frequently-sampled meal tolerance tests. Beta cell function was measured using a computer model-based evaluation. Parameters of beta cell function from this model allowed for the estimation of the insulin secretion rate (ISR) and the characterization of the ISR into static (beta cell responsiveness to above-basal glucose following a meal) and dynamic (beta cell responsiveness to the rate of increase in above-basal glucose following a meal) components.

After 24 weeks, the changes in static and dynamic beta cell responsiveness and insulin sensitivity were increased across all active treatments relative to placebo, and appeared to be increased in an approximately additive fashion with co-administration with sitagliptin and high dose metformin in comparison to each as monotherapy. The results of the beta cell modeling analysis showed that initial combination therapy with sitagliptin and metformin resulted in a 49 percent increase in measured change in static beta cell responsiveness compared with metformin alone (20.1, sitagliptin 50 mg/metformin 1000 mg twice daily vs. 13.5, metformin 1000 mg twice daily). Further, the initial combination therapy with sitagliptin and metformin resulted in a 114 percent increase in measured change in dynamic beta cell responsiveness compared with metformin alone (151.0, sitagliptin 50 mg/metformin 1000 mg twice daily vs. 70.7, metformin 1000 mg twice daily).

JANUVIA (sitagliptin) and metformin together increase active GLP-1 levels in healthy adults by more than four-fold compared to placebo
Data from a separate pharmacologic study suggest that the different mechanisms of action of sitagliptin and metformin, when used in combination in healthy adults, may have a complementary effect on levels of glucagon-like peptide-1 (GLP-1), another hormone that is an important regulator of blood sugar levels. This aspect of the mechanism of action of metformin used in combination with sitagliptin was previously unknown. GLP-1 acts, in part, by enhancing insulin production and secretion by the pancreatic beta cell.

A randomized, placebo-controlled, double-blind, crossover study was conducted in 16 healthy adults to assess the potential complementary effects of sitagliptin and metformin on GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). In each 2-day treatment period, subjects received one of four treatments: sitagliptin, metformin, the co-administration of sitagliptin and metformin, or placebo.

In this study, sitagliptin and metformin, when taken separately, increased overall, post-meal, active GLP-1 levels by 1.95- and 1.76-fold, respectively (p<0.001), compared with placebo. When administered together, sitagliptin and metformin increased active GLP-1 levels by 4.12-fold (p<0.001) compared with placebo. In contrast to active GLP-1 levels that were increased by both drugs, the levels of total GLP-1 (which includes both active and inactive GLP-1) were increased by metformin only and not by sitagliptin. Active GIP concentrations increased with sitagliptin, but were unchanged with metformin. Measurement of the enzymatic activity of DPP-4 in this study demonstrated that sitagliptin, but not metformin, inhibited DPP-4 activity. These observations are consistent with the effect of sitagliptin to raise active GLP-1 levels by reducing its clearance, and suggest that metformin acts in a different manner to increase active GLP-1 levels.

GLP-1 plays an important role in regulating the body’s blood sugar levels. When food is consumed, GLP-1 is released by the gastrointestinal tract to stimulate the pancreatic beta cells to secrete insulin, a hormone that helps the body to use glucose for energy. GLP-1 also suppresses the release of glucagon from the pancreatic alpha cells, which, in turn, signals the liver to reduce its production of sugar.

Dosing of JANUVIA
The recommended dose of JANUVIA is 100 mg once daily, with or without food, for all approved indications. No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency or in patients with mild renal insufficiency (CrCl ≥50 mL/min). To achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, lower dosages are recommended in patients with moderate and severe renal insufficiency as well as in end-stage renal disease (ESRD) patients requiring hemodialysis. For patients with moderate renal insufficiency (CrCl ≥30 to <50 mL/min), the dose of JANUVIA is 50 mg once daily. For those with severe renal insufficiency (CrCl <30 mL/min) or with ESRD requiring dialysis, the dose of JANUVIA is 25 mg once daily. Because there is a need for dosage adjustment based upon renal function, assessment of renal function is recommended prior to initiation of JANUVIA and periodically thereafter.

Selected cautionary information for JANUVIA
Because JANUVIA is renally eliminated, and to achieve plasma concentrations of JANUVIA similar to those in patients with normal renal function, a dosage adjustment is recommended in patients with moderate renal insufficiency and in patients with severe renal insufficiency or with ESRD requiring hemodialysis or peritoneal dialysis. Safety and effectiveness of JANUVIA in pediatric patients have not been established. There are no adequate and well-controlled studies in pregnant women. JANUVIA should be used during pregnancy only if clearly needed. Caution should be exercised when JANUVIA is administered to a nursing woman. In clinical trials, JANUVIA demonstrated an overall incidence of side effects comparable to placebo. The most common side effects reported with JANUVIA (≥5 percent and higher than placebo) were stuffy or runny nose and sore throat, upper respiratory infection, and headache.

Expanding clinical development program for sitagliptin family
Merck’s clinical development program for sitagliptin is robust and continues to expand with 49 studies completed or underway and five more studies set to begin this year. There have been more than 9,400 patients in the Company’s clinical studies, with about 6,000 of these patients being treated with sitagliptin. Additionally, about 2,300 patients have been treated with sitagliptin for more than a year and of these 400 patients have been treated for at least two years.

About Merck
Merck & Co., Inc. is a global research-driven pharmaceutical company dedicated to putting patients first. Established in 1891, Merck currently discovers, develops, manufactures and markets vaccines and medicines to address unmet medical needs. The Company devotes extensive efforts to increase access to medicines through far-reaching programs that not only donate Merck medicines but help deliver them to the people who need them. Merck also publishes unbiased health information as a not-for-profit service. For more information, visit www.merck.com.

Forward-looking statement
This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management's current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck's business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck's Form 10-K for the year ended Dec. 31, 2006, and in its periodic reports on Form 10-Q and Form 8-K, which the Company incorporates by reference.

Posted by dlifenews at 03:16 PM | Comments (0)

Mutations in the Insulin Gene Can Cause Neonatal Diabetes

September 11, 2007

September 11, 2007 (EurekAlert) - Mutations in the insulin gene can cause permanent neonatal diabetes, an unusual form of diabetes that affects very young children and results in lifelong dependence on insulin injections, report researchers from the University of Chicago and Peninsula University (Exeter, UK) in Sept. 18, 2007, issue of the Proceedings of the National Academy of Sciences, published early online.

Although abnormal insulin has been associated with milder cases of type 2 diabetes since the discovery of "insulin Chicago" in 1979, this is the first time that an insulin mutation has been connected to severe diabetes with onset early in life.

The researchers describe 10 mutations, found in 21 patients from 16 families. They suspect that the mutations alter the way insulin folds during its synthesis. They suggest that these improperly folded proteins interfere with other cellular processes in ways that eventually kill the cells that produce insulin.

"This is a novel and potentially treatable cause of diabetes in infants," said study author Louis Philipson, MD, PhD, professor of medicine at the University of Chicago. "It's exciting because each of these patients has one normal insulin gene as well as one mutated gene. If we could detect the disease early enough and somehow silence the abnormal gene, or just protect insulin-producing cells from the damage caused by misfolding, we might be able to preserve or restore the patient's own insulin production."

The effort to learn more about possible genetic causes of neonatal diabetes followed a flurry of publicity last September. Philipson and colleagues at the University of Chicago -- using a protocol developed by co-author Andrew Hattersley, MD, Professor of Molecular Medicine at Peninsula University -- were able to wean a young diabetes patient with a known, treatable mutation in an ion channel protein essential for insulin secretion, off of insulin. This was one of the first such cases in the United States.

Media coverage of that case and outreach by the Juvenile Diabetes Research Foundation stimulated parents of other children diagnosed as infants with type-1 diabetes to contact one of the two centers to request genetic testing. Testing at the University of Chicago uncovered more than a dozen patients with the same treatable mutation.

The publicity also brought calls from the families of more than 70 patients who had been diagnosed with diabetes at less than one year of age but who, as it turned out, did not have a known mutation.

In one family with four affected individuals, tests for known mutations were negative. A combination of linkage studies and candidate-gene testing, however, traced the problem to an abnormal insulin gene.

Further tests identified a total of 10 different insulin-gene mutations in patients from 15 other families.

All ten are "missense" mutations; they code for a different amino acid than the one normally found at that position. Such mutations can prevent a protein from folding into its customary shape.

Dysfunctional proteins are usually dismantled by the endoplasmic reticulum, an organelle that can detect misfolded proteins and degrade them. Prolonged demands on this system, however, can cause chronic endoplasmic reticulum stress that can lead eventually to cell death.

The authors postulate that misfolded insulin and its precursors could induce prolonged ER stress, causing the insulin-producing pancreatic beta cells to die.

Treatments aimed at reducing ER stress "might result in better beta cell survival," they suggest. "This could partially ameliorate the diabetic state if secretion resulting from the normal insulin allele could be better preserved."

"Insulin mutations are an important cause of neonatal diabetes," say the authors, accounting for about 20 percent of cases of this rare disorder. Most cases tied to insulin mutation were diagnosed in the first six months of life, with an average age at diagnosis of only 13 weeks. Three of the cases were diagnosed between 6 months and one year after birth.

Neonatal diabetes is considered a genetic disorder by many, said Philipson. Mutations in known genes explain 50 to 60 percent of cases and research teams in the US and Europe are trying to identify a genetic cause of diabetes in the remaining patients.

Even though neonatal diabetes is a rare disease, identification of genes causing it has lead to important knowledge about pancreatic development and function, as well as to more precise diagnosis and improved management of patients.

In 2001, Graeme Bell, PhD, the Louis Block Distinguished Service Professor of Medicine and Human Genetics at the University of Chicago and a co-author of this paper, discovered one of the first gene defects associated with neonatal diabetes, mutation of the gene for glucokinase, an enzyme that helps regulate blood-sugar levels. Bell also discovered several genes that cause other forms of monogenic diabetes and the first gene associated with Type 2 diabetes.

In 1979, co-author Donald Steiner, MD, the A.N. Pritzker Professor in Biochemistry & Molecular Biology and a member of the Howard Hughes Medical Institute at the University of Chicago, was a member of the team that discovered the first mutant insulin, known as "insulin Chicago."

Posted by dlifenews at 04:42 PM | Comments (0)

Patients with Diabetes Need Better Advice About Home Glucose Monitoring

September 04, 2007

Self monitoring of blood glucose in type 2 diabetes: longitudinal qualitative study of patients' perspectives BMJ Online First

September 4, 2007 (EurekAlert) - A new study published on bmj.com today calls for better advice about home blood glucose monitoring for patients with non-insulin dependent (type 2) diabetes.

Type 2 diabetes usually develops in people over 40, especially when the person is overweight. In most cases, insulin injections are not needed. Instead, a combination of dietary measures, weight reduction, and oral medication controls the condition.

Some experts believe that daily self monitoring helps to control blood glucose levels and it is often recommended. But others believe that self monitoring is complex and inconvenient and can lead to feelings of frustration and guilt. As such, there is still no firm agreement about the role and value of self monitoring for patients with type 2 diabetes.

So Dr Elizabeth Peel and colleagues interviewed 18 patients with newly diagnosed type 2 diabetes over four years to explore their views about self monitoring over time.

They found that self monitoring decreased over time, and those who did continue monitoring did so less frequently. Some patients expressed uncertainty about the meaning of the test results and how to act on them, while others found self monitoring to be reassuring.

How to act on high readings was a consistent problem.

Most patients also voiced concerns about the value health professionals placed on their readings. Doctors generally appeared to show little interest in patients’ test results after the initial phase, leading some patients to see self monitoring as not very important or even pointless.

Interestingly, some patients continued to self monitor despite lack of guidance and the perceived disinterest from health professionals.

Clinical uncertainty about the role of self monitoring in patients with type 2 diabetes is mirrored in patients’ own accounts, say the authors. Patients tended not to act on their self monitoring results, in part because of a lack of education and dialogue about the appropriate response to readings.

They urge health professionals to be explicit about whether and when such patients should self monitor and how they should interpret and act upon the results, especially high readings.

Posted by dlifenews at 02:10 PM | Comments (1)

UIC Studies Aspirin-Like Treatment for Type 2 Diabetes

August 27, 2007

August 27, 2007 (Newswise) — The University of Illinois at Chicago is one of 16 sites in the United States taking part in the first large-scale study to test a promising approach to lowering blood glucose levels in adults with type 2 diabetes.

The clinical trial will investigate whether a common anti-inflammatory drug known as salsalate, used to manage arthritis pain, can reduce blood glucose levels in people with type 2, or adult onset, diabetes. The study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, part of the National Institutes of Health.

Nearly 21 million people in the United States have diabetes. Type 2 diabetes accounts for about 90 percent to 95 percent of diagnosed cases and is closely linked to obesity, cardiovascular disease, blindness, kidney disease and amputations. People with type 2 diabetes die at rates two to four times higher than those who do not have diabetes.

Recent research suggests that chronic inflammation may be involved in the development of insulin resistance and type 2 diabetes, says Theodore Mazzone, professor of medicine at UIC and principal investigator of the clinical trial at that site.

"By targeting the underlying cause, we hope to determine if reducing inflammation, and thereby lowering blood glucose levels, is a safe and cost-effective treatment for diabetes," Mazzone said. "If this drug treatment is successful, we may also be able to reduce a person's risk of developing associated health problems, such as elevated cholesterol levels and coronary artery disease."

Salsalate is chemically similar to aspirin and has been used for more than 40 years to treat pain associated with arthritis, according to the researchers.

About 800 adults with poorly controlled blood glucose levels are being sought to participate in the three-year, multi-center study.

Researchers are seeking adults ages 18 to 75 whose glucose levels are not well controlled and who do not take insulin. Eligible participants may use no medication or take up to two oral medications to control their diabetes.

During the study, participants will be randomized to receive either salsalate or a placebo and will receive all medication and treatments related to the study free of charge. Participants will also be compensated for time and travel. For more information about the study, call Felecia Gilet at (312) 355-4442.

For more information about UIC, visit http://www.uic.edu

Posted by dlifenews at 05:24 PM | Comments (0)

Determining Therapeutic Effects of Cinnamon Proves Elusive

August 23, 2007

August 23, 2007 (Newswise) — For most of us, cinnamon is associated with baked goods or hot apple cider. Few realize this spice, from a small evergreen tree native to Sri Lanka and Southern India, dates back to biblical times. Fewer still are aware that both common and cassia cinnamon have been observed to have pharmacological and clinical effects.

Based on pre-clinical and clinical data, common and cassia cinnamon are well known for their medicinal properties in the treatment of type 2 diabetes. In animal studies, both common and cassia cinnamon have been shown to reduce blood glucose following a glucose tolerance test, with cassia was found to be superior to common cinnamon. It has also been proposed that the antioxidant properties of common and cassia cinnamon may influence diabetic complications. In humans, three randomized controlled trials have been conducted on cassia and its effects on fasting glucose, glycosylated hemoglobin (HA1c) and lipid profile markers.

To further understand the activity of the spice, a team of naturopathic physicians and scientists decided to systematically review the scientific literature for evidence of safety, efficacy and pharmacological activity of common and cassia cinnamon. The researcher team is comprised of Jean-Jacques Dugoua ND, Dugald Seely, BSc, ND, Dan Perri, MD, Kieran Cooley, ND, Taryn Forelli, ND, Edward Mills, Ph.D., and Gideon Koren, MD, whose study is entitled “From Type 2 Diabetes to Antioxidant Activity, The Safety And Efficacy Of Common (Cinnamomum Verum, C. Zeylanicum) And Cassia (Cinnamomum Aromaticum) Cinnamon Bark – A Systematic Review.” Dr. Dugoua will discuss his team’s findings at the 22nd annual meting of the American Association of Naturopathic Physicians (AANP; www.Naturopathic.org). The conference will be held at the Palm Springs Convention Center, Palm Springs, CA, August 22-25, 2007.

Methodology
The researcher team identified all existing relevant pre-clinical and clinical medical literature that provided information regarding the safety, efficacy and pharmacology of common and cassia cinnamon. The databases they reviewed included MedLine, Old Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Cochrane Data, Allied and Complementary Medicine (AMED), EMBASE, and AltHealthWatch. This was in addition to individual searchers of the relevant review papers and reference lists of original research publications that were conducted by the research team. To evaluate toxicology, adverse effects and pharmacology, animal and in vitro studies were also included in the search.

Results
The highlights of the findings included the following:
* Eight studies involving humans involving the therapeutic efficacy of common and cassia cinnamon were found. One pharmacological study on antioxidant activity and seven clinical studies on various medical conditions were reported in the scientific literature, including three studies involving type 2 diabetes, and one each addressing Helicobacter pylori infection, activation of the olfactory cortex of the brain, oral candidiasis (fungal infection) in HIV, and chronic salmonellosis (bacterial infection found in individuals with compromised immune systems).

* Common and cassia cinnamon had been investigated in animal studies for their anti-diabetic properties. Cassia cinnamon, however, had been the subject of three clinical trials while common cinnamon remained unstudied in humans.

* Based on strong scientific evidence from two of three randomized clinical trials reviewed, cassia cinnamon demonstrated a therapeutic effect in reducing fasting blood glucose by 10.3 percent; the third clinical trial did not observe this effect. Cassia cinnamon, however, did not have an effect at lowering glycosylated hemoglobin.

* One randomized clinical trial reported that cassia cinnamon lowered total cholesterol, LDL cholesterol and triglycerides; the other two trials, however, did not observe this effect. There was scientific evidence that at least one species of cinnamon was not effective at eradicating H. pylori infection. Common cinnamon showed weak to very weak evidence of efficacy in treating oral candidiasis in HIV patients and chronic salmonellosis.

Conclusions
According to Dr. Dugoua, the lead researcher, “The studies we reviewed offered mixed results with therapeutic efficacy being demonstrated in some research efforts and not in others. This literature review has given us a clear road map for further research regarding the healing effects of cinnamon, a spice that continues to have a reputation for providing flavor and medicinal treatments.”

Posted by dlifenews at 04:11 PM | Comments (1)

Scientists Show that Mitochondrial DNA Variants are Linked to Risk Factors for Type 2 Diabetes

August 13, 2007

August 13, 2007 (EurekAlert) – Today, researchers report for the first time that genetic variants in mitochondria—energy-producing structures harboring DNA that are inherited only from the mother—are directly linked to metabolic markers for type 2 diabetes. The study, which highlights the role of mitochondrial genome variation in the pathogenesis of common diseases, is published online in Genome Research (www.genome.org).

According to the Centers for Disease Control, 7% of the U.S. population has diabetes, and 90-95% of those cases are classified as type 2 diabetes. Type 2 diabetes is caused by external factors such as diet and exercise, and is influenced by several genes. While most of the genes known to be involved in diabetes susceptibility are located in the nuclear genome, a recent study estimated that more than 20% of type 2 diabetes cases may involve mutations in the mitochondrial genome.
In the study published today, the scientists compared two different rat strains; the strains possessed virtually identical nuclear genomes but different mitochondrial genomes. This eliminated any complicating effects due to environmental factors or variation in the nuclear genome. Any differences observed between the two rat strains could be attributed to variation in the mitochondria.

When comparing the two rat strains, the researchers found that the two strains exhibited significant differences related to energy metabolism and storage. One rat strain exhibited impaired glucose tolerance, reduced muscle glycogen synthesis, decreased skeletal muscle ATP (energy) levels, and decreased activity of an energy-producing enzyme called cytochrome c oxidase, when compared to the second rat strain. These metabolic characteristics are typical of diabetic individuals.
The researchers then obtained DNA sequences from mitochondria of both rat strains, and found DNA variants in genes that encode for proteins involved in energy production. Thus, for the first time, they were able to directly link inherited variation in the mitochondrial genome to metabolic markers for type 2 diabetes.

“Our study highlights the role of mitochondrial DNA variation in common genetic diseases,” says Dr. Theodore Kurtz, the lead investigator on the project. “In addition, the animal models developed in this study will open the door for future studies in which the effects of mitochondrial genome variation can be investigated on fixed nuclear genetic backgrounds.”

Posted by dlifenews at 12:07 PM | Comments (0)

Identifying the Mechanism Behind a Genetic Susceptibility to Type 2 Diabetes

August 02, 2007

August 2, 2007 (EurekAlert) - Type 2 diabetes is reaching epidemic proportions in the developed world. Determining if and how certain genes predispose individuals to type 2 diabetes is likely to lead to the development of new treatment strategies for individuals with the disease.

In a study appearing in the August issue of the Journal of Clinical Investigation Valeriya Lyssenko and colleagues from Lund University in Sweden show that certain variants of the gene TCF7L2 make individuals more susceptible to type 2 diabetes. The susceptibility variants were associated with increased expression of TCF7L2 in pancreatic islet cells and decreased islet cell secretion of insulin. Consistent with this, ectopic overexpression of TCF7L2 in human islet cells decreased insulin secretion in response to exposure to glucose.

This study identifies TCF7L2 type 2 diabetes susceptibility variants and provides a mechanism by which these genetic variants might cause susceptibility to the disease. As discussed by the authors and in the accompanying commentary by Andrew Hattersley from Peninsula Medical School in the United Kingdom, future studies are likely to investigate the potential for manipulating the signaling pathways controlled by TCF7L2 for the development of new therapeutics for type 2 diabetes.

Posted by dlifenews at 08:22 AM | Comments (0)

Rosiglitazone For Type 2 Diabetes -- Concern Over Side Effects

July 19, 2007

The latest findings from the Cochrane Library

July 19, 2007 (EurekAlert) - New studies are needed to assess the trade-offs between potential benefits and potential harms when rosiglitazone is used by people with type 2 diabetes.

This Cochrane Systematic Review analysed data from 18 trials that involved a total of 8432 people and found no evidence that rosiglitazone led to better patient outcomes when compared with other therapies. Diabetic control (as measured by levels of HbA1c) was no better in patients given rosiglitazone when compared to other antidiabetic drugs. Patient oriented outcomes such as mortality, diabetes related morbidity, or quality of life were not addressed in most studies.

In addition to confirming the known risk of edema (people taking the treatment are at twice the risk of developing this condition) and an increase in body weight up to 5.0 kg, the authors found evidence from one large study indicating increased cardiovascular risk and an enhanced risk in women of having broken bones.

In people with type 2 diabetes, their body has a reduced ability to cause cells to remove glucose from the blood. The resulting high levels of blood-glucose can cause considerable damage especially to the eyes, nerves and kidneys. Rosiglitazone is one of a range of drugs that increase cell’s sensitivity to insulin and therefore may restore some of the normal function.

“Unfortunately, the published studies where people have taken rosiglitazone for at least 24 weeks do not give relevant data about issues like mortality, morbidity, and changes in health-related quality of life,” says lead author Associate Professor Bernd Richter, who works at the Department of General Practice, in Duesseldorf.

“Studies on patient-oriented outcomes are urgently needed, although it is questionable whether new studies with rosiglitazone will be ethical given the fact that less dangerous therapeutic alternatives exist,” says Richter.

Posted by dlifenews at 04:48 PM | Comments (0)

Adult Type 2 Diabetes -- Poor Information on Diet, but Exercise Seems Good

July 18, 2007

July 18, 2007 (EurekAlert) - There are no high quality data to assess how well dietary treatments for type 2 diabetes work in people who have just been told they have the disease, but there is evidence that taking on exercise seems to be one way of improving blood sugar levels, according to the findings of a Cochrane Systematic Review.

Type 2 diabetes leaves a person at danger of having elevated levels of sugar (glucose) in their blood. This high sugar content then causes damage to blood vessels, which in turn harms many organs including the eyes, nerves, kidneys and heart.

When people are first diagnosed with this disease they are given dietary advice in the hope that this will enable them to take more control over the level of sugar in their blood. However, after searching published scientific literature, a team of Cochrane Researchers was unable to find high quality data that showed whether dietary advice did indeed alter the risk of developing long-term complications, affect overall quality of life or the likelihood of dying.

“We did find 36 published articles that reported work from 18 different trials which included a total of 1467 people with type 2 diabetes, but only a minority of these trials examined hard clinical endpoints such as death or vascular disease, and those that did offered no details; most talked about factors that are easier to measure such as weight or blood sugar control,” says lead researcher Nield, a researcher at the University of Teesside in Middlesbrough, UK.

The team did, however, find data suggesting that if people with type 2 diabetes increase the amount of exercise as an adjunct to dietary advice they do, then they can see an improvement in their blood sugar levels after six and twelve months.

“There is an urgent need for well-designed and well-reported studies which examine a range of interventions and see how they influence many of the features that are important in type 2 diabetes,” says Lucie Nield.

The researchers point out that there is some good news, in that one promising study is already underway.

Posted by dlifenews at 04:58 PM | Comments (0)

While Most Diabetes Drugs Provide Similar Glucose Control, Some Offer Important Advantages, New Review Shows

July 16, 2007

July 16, 2007 (AHRQ) - Most oral medications prescribed for type 2 diabetes are similarly effective for reducing blood glucose, but the drug metformin is less likely to cause weight gain and may be more likely than other treatments to decrease so-called bad cholesterol, according to a report funded by the Department of Health & Human Services's (HHS) Agency for Healthcare Research and Quality (AHRQ). A version of the analysis was posted today in the online version of Annals of Internal Medicine.

The federally funded analysis is based on scientific evidence found in 216 published studies. The report summarizes the effectiveness, risks, and estimated costs for 10 drugs: acarbose (sold as Precose), glimepiride (Amaryl), glipizide (Glucotrol), glyburide (Micronase, DiaBeta, Glynase PresTab), metformin (Glucophage, Riomet, Fortamet), miglitol (Glyset), nateglinide (Starlix), pioglitazone (Actos), repaglinide (Prandin), and rosiglitazone (Avandia).

Type 2 diabetes is an increasingly common chronic disease that occurs in people who have difficulty converting glucose (a sugar) into energy. Blood glucose levels are high either because their cells are resistant to insulin (a hormone that helps convert glucose into energy) or because their pancreas does not produce enough insulin. Diabetes can cause severe problems with the heart, eyes, kidneys, and nerves. Obesity increases the risks of developing type 2 diabetes. From 1980 through 2005, the number of Americans diagnosed with diabetes soared from 5.6 million to 15.8 million.

"As more people are diagnosed with type 2 diabetes and with the growing array of treatment choices, this is a landmark review," said AHRQ Director Carolyn M. Clancy, M.D. "This summary of scientific evidence is not only an important tool for clinicians and patients seeking the most appropriate therapy, but it also points out in what areas we need more research to confront this disease."

As new classes of oral diabetes medications have become available, patients and clinicians have faced a growing list of treatment options. Earlier scientific reviews have highlighted some differences between medications, but AHRQ's new analysis is the first to summarize evidence on the effectiveness and adverse events for all approved oral medications commonly used in the United States for type 2 diabetes.

Diabetes patients typically are monitored with tests that check the percentage of hemoglobin A1c (HbA1c) in their blood. Checking for HbA1c is a more reliable indicator of chronic high blood sugar than checking blood glucose itself. According to the AHRQ review, most diabetes drugs offer about a one point absolute reduction in HbA1c. In those cases, for example, a diabetes patient's HbA1c might drop from 8 to 7 (with 5 being normal in patients who don't have diabetes). Nateglinide, acarbose, and miglitol lower HbA1c by about half that much. Combining diabetes medications, evidence shows, often works better at reducing HbA1c.

AHRQ's analysis of published studies, completed by the Agency's Johns Hopkins University Evidence-based Practice Center in Baltimore, also concluded:

Metformin and acarbose do not increase weight among diabetes patients. Other diabetes drugs (glimepiride, glipizide, glyburide, pioglitazone, repaglinide, and rosiglitazone) have been shown to increase weight by an average of 2 pounds to 11 pounds.

Blood levels of low-density lipoprotein, which is known as "bad cholesterol" because it may amplify risks of heart attack and stroke, consistently decrease (by about 10 milligrams per deciliter) in patients taking metformin and increase (by similar amounts) in patients taking rosiglitazone and pioglitazone.

Pioglitazone and rosiglitazone cause a small but significant increase in high-density lipoprotein, often called "good cholesterol" because it promotes the breakdown and removal of cholesterol from the body.

Glimepiride, glipizide, glyburide, and repaglinide are associated with hypoglycemia (when blood glucose levels go too low) more than other diabetes drugs.

Metformin and acarbose are generally more likely than other diabetes medications to cause gastrointestinal problems such as diarrhea. Patients who used metformin alone were more likely to experience problems than those using the drug at a lower dose in combination with glimepiride, glipizide, glyburide, pioglitazone, or rosiglitazone.

Patients who take pioglitazone and rosiglitazone have a greater risk of congestive heart failure compared with those who take metformin, glimepiride, glipizide, or glyburide. While one recent analysis raised the possibility that rosiglitazone may also increase heart attack risks, authors of the AHRQ analysis concluded that current evidence is not sufficient to make a meaningful assessment.

More, longer studies are needed to understand the impact of oral diabetes drugs on patients' quality of life and whether long-term use causes adverse side effects or reduces important complications of diabetes such as heart disease and kidney disease. Additional research is needed to study interactions between the drugs and to compare therapeutic combinations of the drugs, according to the report.

The report released today, Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults with Type 2 Diabetes, is the newest analysis from AHRQ's Effective Health Care program, authorized by the Medicare Prescription Drug, Improvement and Modernization Act. That program represents an important federal effort to compare alternative treatments for health conditions and make the findings public. The program is intended to help patients, doctors, nurses, and others choose the most effective treatments. Information can be found at http://www.effectivehealthcare.ahrq.gov.

For more information, please contact AHRQ Public Affairs: (301) 427-1855 or (301) 427-1998.

Posted by dlifenews at 10:07 AM | Comments (1)

Class of Medications May Offer Alternative Option for Treating Type 2 Diabetes

July 11, 2007

July 11, 2007 (EurekAlert) - A review of previous studies indicates that use of a class of medications known as “incretin-based therapy”, which act via certain pathways that affect glucose metabolism may provide modest effectiveness and favorable weight change outcomes for the treatment of type 2 diabetes and may represent an alternative to other hypoglycemic therapies, according to an article in the July 11 issue of JAMA.

Current therapies for type 2 diabetes are often limited by adverse effects such as weight gain or hypoglycemia (low blood sugar). A more recent class of treatment to address these issues is incretin therapy, which involves glucose-stimulated insulin secretion by intestinally derived peptides, which are released in the presence of glucose or nutrients in the gut, according to background information in the article. In October 2006 the Food and Drug Administration approved the first oral incretin enhancer, sitagliptin, a selective DPP4 inhibitor (a class of oral hypoglycemics), for use as monotherapy or in combination with other medications. The effectiveness of this class of medications in managing type 2 diabetes is not well understood.

Renee E. Amori, M.D., of Tufts-New England Medical Center, Boston, and colleagues conducted a meta-analysis of 29 studies to assess the effectiveness and safety of incretin-based therapy (GLP-1 analogues and DPP4 inhibitors) in nonpregnant adults with type 2 diabetes.

“Our analysis of randomized controlled trials showed that incretin-based therapy with GLP-1 analogues or DPP4 inhibitors in adults with type 2 diabetes is moderately effective in improving glycemia, with greater reductions in postprandial [after a meal] glycemia and favorable (GLP-1 analogues) or neutral (DPP4 inhibitors) effects on weight. Glucagon [a hormone secreted by the pancreas]-like peptide 1 analogues were associated with gastrointestinal adverse effects, while DPP4 inhibitors had a slightly increased risk of infection (nasopharyngitis [inflammation of the nasal passages] and urinary tract infection) and headache,” the authors write.

“Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes with modest efficacy and a favorable weight change profile,” they write. “Individuals with mild diabetes, suggesting an adequate pancreatic beta cell reserve, who are at risk of hypoglycemic sequelae and in need of weight loss may benefit from this new class. However, these new classes of hypoglycemic agents will need continued evaluation both in long-term efficacy and safety controlled trials and in clinical practice to assess their effectiveness and safety profile to determine their role among the many available and well-established therapies for type 2 diabetes.”

Posted by dlifenews at 10:57 AM | Comments (0)

Boosting Key Milk Nutrients May Help Lower Type 2 Diabetes Risk

July 10, 2007

New research finds combination of calcium and vitamin D may offer protection against type 2 diabetes

July 10, 2007 (EurekAlert) – Most Americans fail to get the calcium and vitamin D they need, but this shortfall could be affecting more than their bones. It may, at least in part, be one reason behind the epidemic of type 2 diabetes, suggests new research conducted at Tufts University. Drinking more milk – a leading source of calcium and vitamin D in the American diet – could help decrease the risk of type 2 diabetes by nearly 15 percent, according to the new meta-analysis and review published in the Journal of Clinical Endocrinology & Metabolism (1).

In the thorough analysis of previously published studies, the researchers found chronically low levels of vitamin D were linked to as high as 46 percent greater risk of type 2 diabetes. Yet boosting vitamin D alone would likely have little effect in healthy adults. Instead, the researchers suggested that a combination of vitamin D and calcium, like that found in milk, would have the greatest potential to help prevent diabetes, especially among those at highest risk for the disease.

Examining the intake of milk and milk products specifically, the researchers found there was nearly a 15 percent lower risk for type 2 diabetes among individuals with the highest dairy intake (3-5 servings per day) compared to those getting less than 1 ½ servings each day.

Most of the studies assessed were observational and the limited number of intervention trials makes definitive conclusions difficult, yet the Tufts researchers suggest calcium and vitamin D may affect the body’s ability to produce or utilize insulin, the hormone the body makes to process sugar that is impaired in those with diabetes and pre-diabetes.

Beside calcium and vitamin D, milk is the primary beverage source of magnesium, which a second meta-analysis found may also reduce the risk of type 2 diabetes (2). The analysis concludes that for every 100 milligram increase in magnesium up to the recommended dietary intake, the risk of developing type 2 diabetes decreased by 15 percent.

Type 2 diabetes and insulin resistance syndrome (or pre-diabetes) affect a staggering 75 million Americans and death rates from diabetes have increased nearly 45 percent over the past 20 years, elevating the importance of finding new ways to treat and prevent this deadly disease.

Milk is a primary source of calcium and vitamin D in the American diet. In fact, government reports indicate that more than 70 percent of the calcium in our nation’s food supply comes from milk and milk products. Additionally, milk is one of the few food sources of vitamin D, which is fast emerging as a “super nutrient.”

The recommended three servings of lowfat or fat-free milk provides 900 mg of calcium, 300 IU of vitamin D and 80 mg of magnesium daily.

Posted by dlifenews at 10:53 AM | Comments (0)

Early Indicator of Kidney Disease May Also Predict Risk of Pre-Diabetes

July 03, 2007

July 3, 2007 (EurekAlert) -- A blood component called cystatin C, used to test for early-stage kidney impairment, also may be a very early marker for those at risk of developing a condition known as pre-diabetes, a study conducted by researchers at the University at Buffalo has shown. Pre-diabetes is diagnosed when the amount of glucose in the bloodstream begins to rise and remain above normal, an indication that glucose is not being absorbed properly by cells.

An estimated 54 million people Americans have been diagnosed with pre-diabetes, which, if not arrested, often develops into full-blown Type 2 diabetes, a serious chronic disease linked to heart disease, stroke, kidney failure, blindness and nerve damage.

UB researchers report in the July 2007 issue of Diabetes Care that high levels of cystatin C were associated with a three-fold risk of progression to pre-diabetes in their study population.

“It’s important to identify people at risk of pre-diabetes very early, because you can prevent this condition from developing by making changes in diet and lifestyle,” said Richard P. Donahue, Ph.D., first author on the study.

“If further studies support our finding, testing for cystatin C could become an important part of a standard physical examination. Preventive measures could be in place before glucose intolerance has a chance to develop and take its toll.”

Donahue is an associate professor of social and preventive medicine in the UB School of Public Health and Health Professions.

The cystatin C investigation is based on the Western New York Health Study, conducted between 1996 and 2001, in which researchers collected baseline information on a number of health indicators, including fasting glucose, in a randomly selected cohort of healthy Erie and Niagara county residents.
The first follow-up to the baseline study took place between 2001 and 2004 and involved 1,455 of the original participants, all of whom had no known heart or kidney disease. Information on health indicators were collected once again. Analysis determined that 91 people who had normal glucose levels in 1996 had developed pre-diabetes since then.

Levels of cystatin C then were measured in the blood samples taken at baseline of these 91 and were compared to cystatin C levels in samples from 273 participants from the original cohort who had not developed pre-diabetes.

Results showed a direct link between those with the highest levels of cystatin C and the development of pre-diabetes, said Donahue. The association didn’t change when factors that traditionally are related to development of diabetes such as weight, amount of blood glucose at baseline, smoking history, high blood pressure or alcohol use were considered, he noted.

“Pre-clinical signs of renal impairment may occur before or coincident with pre-diabetes,” Donahue said. “These findings may suggest that those who have pre-diabetes also should be screened for early signs of kidney impairment, which itself is a major chronic illness and cause of much morbidity and mortality.”

Posted by dlifenews at 02:00 PM | Comments (0)

Inhaled Insulin for Type 2 Diabetes Shows Mixed Results

July 02, 2007

July 2, 2007 (Newswise) — Inhaled insulin, taken before meals, can improve blood glucose control for people with type 2 diabetes who have not had good results with short-acting injected insulin that is taken in addition to the baseline insulin administered throughout the day and night, according to a new review of the body of published research.

People who use insulin to manage their type 2 diabetes typically have to take extra insulin at mealtimes to regulate the glucose response to food. They can use short-acting injected insulin or inhaled insulin.
The review examined several clinical issues surrounding the use of inhaled insulin by patients with type 2 diabetes. It looked at how inhaled insulin compares to injected insulin as a mealtime insulin supplement for patients who are already using injected insulin daily.

The report also compared use of inhaled insulin by type 2 diabetes patients who had not previously taken insulin in any form. Inhaled insulin was compared to the effectiveness of oral antidiabetic drugs used alone and to antidiabetic drugs used with inhaled insulin.

In patients with type 2 diabetes, inhaled insulin worked as well as short-acting injected insulin to control blood glucose over three months, according to the review. However, inhaled insulin users had more trouble controlling low blood glucose — hypoglycemia —a common complication of diabetes medication.

“Insulin is associated with hypoglycemia,” said John Buse, M.D., president-elect of the American Diabetes Association. “That is its most common and potentially serious complication in all of its formulations.”
Among patients who had not previously taken insulin in any form, inhaled insulin alone was more effective than oral diabetes medication at controlling blood glucose levels at the three-month follow-up.

When patients took oral medication plus inhaled insulin, higher rates of hypoglycemia occurred.

The Windows on Medical Technology report is published by ECRI Institute, an independent nonprofit health services research agency that researches the best approaches to improving patient care. The institute produces systematic reviews on medical devices, drugs, biotechnologies, procedures, and health services.

Jonathan Treadwell, Ph.D., senior research analyst at ECRI Institute, led a team of investigators who analyzed eight studies encompassing 1,881 patients with type 2 diabetes to make the comparisons between inhaled insulin, injected insulin, and oral medication regimens.

Despite some positive findings, the authors write, “the evidence regarding inhaled insulin for patients with type 2 diabetes is still insufficient to answer many key clinical questions” such as patient satisfaction, inhaled insulin’s effect on other complications of diabetes, on weight gain, and very importantly, the long-term effects on lung function.

“One detail to note about inhaled insulin — the dosing is not as precise as with injections because specific increments in doses are not as precise,” Treadwell said. He added that companies who are developing inhaled insulin are working on more dose-tailored devices.

Type 2 diabetes occurs when glucose remains in the blood instead of being transported to cells as it is supposed to be. There is no cure, but the disorder can often be controlled with medication and lifestyle modifications. When these changes are insufficient to control diabetes, oral medication and sometimes insulin become necessary.

Insulin can be delivered through needle syringes, insulin pens, jet injectors and external infusion pumps. If uncontrolled, diabetes can lead to heart disease, blindness, kidney failure, nerve damage, poor circulation, amputation of limbs, and ultimately result in death.

The U.S. Food and Drug Administration first approved inhaled insulin to treat diabetes in 2006. However, inhaled insulin is contraindicated for patients who have smoked in the last six months, have lung disease, are younger than age 18 or are experiencing a bout of low-blood sugar.

Its convenience makes inhaled insulin an attractive option, although it may not be the right medication for every diabetes patient who needs insulin.

“Advantage: it is inhaled; disadvantage: it is inhaled,” Buse said. “It’s all about perspective. So if there is someone who just will not take an injection, then inhaled insulin is a big advantage.”

“There are six to seven classes of pills that could theoretically be tried first,” Buse said. “It is a fairly personal decision whether it is more convenient to use insulin in vial-and-syringe, in a pen or in an inhaler.”

According to the American Diabetes Association it is unclear if delivering insulin through the lungs could result in long-term respiratory problems.

“This is the reason for resistance by doctors and patients to inhaled insulin — long-term lung damage,” Treadwell said. “It’s a valid concern since it is suspected that people with diabetes already have lung problems — the concern is that this form of administration would exacerbate these problems.”

“It’s too early to say if inhaled insulin could be used to the extent that injected insulin is — our review only covered six month follow-up because that’s the only data currently available. The question is: Could it provide long-term glucose control without damaging effects?” Treadwell said.

ECRI is a nonprofit international health services research agency that provides information and technical assistance to the health care community.

Treadwell J, et al. Inhaled insulin for the treatment of type 2 diabetes. Windows on Medical Technology July 2007 Issue No. 146.

Posted by dlifenews at 05:20 PM | Comments (1)

Demonstrated Saxagliptin Added to Metformin Improved Glycemic Control in Subjects with Type 2 Diabetes Compared to Metformin Alone

June 27, 2007

June 27, 2007 (PRNewswire-FirstCall) -- Phase III data presented this week at the annual meeting of the American Diabetes Association demonstrated that saxagliptin, an inhibitor of dipeptidyl-peptidase-4 (DPP-4) in development by Bristol-Myers Squibb Company and AstraZeneca , in combination with metformin, exhibited a statistically significant improvement in glycemic control in subjects with Type 2 diabetes compared to metformin alone through 24 weeks of treatment. This was the first time that Phase III data for saxagliptin have been presented in a scientific setting.

A group of 743 subjects (ages 18-77) with Type 2 diabetes whose hemoglobin A1C level was within the range of greater than or equal to 7 percent or less than or equal to 10 percent and on a stable metformin dose alone (1500 to 2550 mg/day) were randomized 1:1:1:1 to add-on saxagliptin 2.5 mg, 5 mg, 10 mg, or placebo once daily. The primary endpoint of the study was the change from baseline in hemoglobin A1C levels. After 24 weeks, the subjects receiving saxagliptin+metformin demonstrated statistically significant decreases in hemoglobin A1C levels compared to placebo+metformin: -0.73 percent, -0.83 percent, and -0.72 percent at the 2.5 mg, 5 mg and 10 mg doses, respectively (p-value at all dosage levels less than 0.0001 vs. placebo+metformin).

Saxagliptin+metformin also statistically significantly reduced fasting plasma glucose (secondary endpoint) as compared to placebo+metformin: -16 mg/dL, -23 mg/dL, and -22 mg/dL for saxagliptin 2.5 mg, 5 mg and 10 mg, respectively (p-value at all dosage levels less than 0.0001 vs.

placebo+metformin). The percentage of subjects with hemoglobin A1C less than 7 percent at Week 24 (secondary endpoint) was 17 percent for placebo+metformin and 37 percent, 44 percent and 44 percent for the 2.5 mg, 5 mg and 10 mg doses of saxagliptin respectively (p-value at all dosage levels less than 0.0001 vs. placebo+metformin).

In this study, the number of subjects with investigator-reported hypoglycemia, with or without confirmation, were: 9 on placebo+metformin, and 15, 10 and 7, for 2.5 mg, 5 mg, and 10 mg on saxagliptin+metformin, respectively. There was one subject with confirmed hypoglycemia in each of the four arms (as measured by blood glucose less than or equal to 50 mg/dL with symptoms). The most common adverse events seen in more than 5 percent of subjects randomized to either placebo+metformin or saxagliptin+metformin (all doses combined) were: nasopharyngitis 7.8% vs. 8.7 %, headache 7.3% vs. 8.0%, diarrhea 11.2% vs. 7.1%, upper respiratory infection 5.0% vs. 6.6%, influenza 7.3% vs. 6.0%, and urinary tract infection 4.5% vs. 5.1%.

Phase I Studies Also Presented at 2007 American Diabetes Association Annual Meeting
In the presentation "Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Once-Daily Oral Doses of Saxagliptin for 2 Weeks in Type 2 diabetic and Healthy Subjects" by David Boulton, Ph.D., Principal Scientist, Bristol-Myers Squibb, results from two Phase I studies were reported. Study 1 was conducted in subjects with Type 2 diabetes; Study 2 was conducted in healthy subjects. Both studies were placebo-controlled, randomized, double-blind, sequential, multiple ascending dose studies. The primary objective of these two studies was to assess the safety and tolerability profiles of multiple daily oral doses of saxagliptin in subjects with Type 2 diabetes and in healthy subjects.

Study 1 consisted of 40 subjects (ages 18-70) who had been diagnosed with Type 2 diabetes for less than 10 years, had hemoglobin A1C in the range of 6.5 to 9.5 percent, and fasting plasma glucose in the range 125-250 mg/dL. Participants were randomized to receive 2.5, 5, 15, 30, or 50 mg of saxagliptin or matched placebo once-daily for 14 days (3 saxagliptin, 1 placebo ratio, n=8 subjects/dose panel).

Study 2 consisted of 50 healthy subjects (ages 18-45) who were randomized to receive 40, 100, 150, 200, 300 or 400 mg saxagliptin or matching placebo once daily for 14 days. Within each panel, 6 subjects received 100, 150, 200, 300 or 400 mg saxagliptin, 2 subjects received 40 mg saxagliptin and 2 subjects received matching placebo.

In both studies, there were no deaths or serious adverse events. Additionally, no adverse events of hypoglycemia were reported by investigators. In Study 2, one participant experienced an adverse event (mild rash), which resulted in discontinuation from the study while taking 200 mg of saxagliptin once daily.

Posted by dlifenews at 04:02 PM | Comments (0)

Investigational DPP-4 Inhibitor Demonstrated Efficacy in Reducing Glucose Levels

June 25, 2007

June 25, 2007 (Newswise) — Alogliptin, a highly selective dipeptidyl peptidase-IV (DPP-4) inhibitor under investigation for the treatment of type 2 diabetes, demonstrated efficacy in reducing glucose levels throughout the day, in an early phase clinical study. Safety results for this multi-dose study showed that alogliptin was well tolerated in patients with type 2 diabetes, with an incidence of hypoglycemia similar to placebo. No serious adverse event was reported, and no dose-limiting toxicity was observed over the entire dose range of 25 to 400 mg. The data were announced during a poster presentation at the 67th Scientific Sessions of the American Diabetes Association (ADA) meeting in Chicago.

"These are encouraging early results for alogliptin as a potential new type 2 diabetes treatment to help manage glucose levels throughout the day,” said Qais A. Mekki, MD, PhD, vice president, Clinical Science at Takeda Global Research & Development, Inc. “Alogliptin is a reflection of Takeda’s commitment to finding innovative options to help patients manage their type 2 diabetes.”

Alogliptin Study Design
This was a randomized, double-blind, placebo-controlled, parallel-group, multi-dose study conducted in multiple centers. Subjects were patients with type 2 diabetes who were either newly diagnosed or treated with diet and exercise alone for the previous three months and were between the ages of 18 and 75 years.

The objectives of the study were to assess the uptake, utilization and metabolism, as well as the tolerability, of alogliptin after multiple-dose administration to patients with type 2 diabetes. The primary efficacy endpoint was change in mean 4-hour postprandial plasma glucose levels from Baseline (Day -1) to Day 14. Secondary efficacy endpoints included change in mean 4-hour postprandial insulin levels; fasting plasma levels of C-peptide, fructosamine, and glycosylated hemoglobin (A1C); and incidence of hyperglycemia (blood glucose ≥200 mg/dL).

Fifty-five patients were assigned to receive alogliptin 25 (n=15), 100 (n=14), or 400 mg (n=15), or placebo (n=11) once daily for 14 days. Patients received three standardized meals a day and a snack after dosing on Days -1 (Baseline), 1 and 14. Blood and urine samples were collected through 24 hours after Day 1 and through 48 hours after Day 14.

Alogliptin Study Results
On Day 14, statistically significant decreases from Baseline in mean 4-hour plasma glucose levels were observed for 25, 100, and 400 mg doses, after each of three meals. These reductions were compared to those achieved by placebo:

o Breakfast: -39.9, -48.6, and -68.3 mg/dL, respectively
o Lunch: -30.5, -46.0, and -38.4 mg/dL, respectively
o Dinner: -35.1, -54.7, and -46.1 mg/dL, respectively

Alogliptin demonstrated rapid and sustained inhibition of plasma DPP-4 activity, across all doses:
o On Days 1 and 14, mean peak inhibition of plasma DPP-4 activity ranged from 93.8% to 98.9% across all alogliptin doses; median time to peak inhibition ranged from 1.0 to 2.5 hours.

o At 24 hours and 72 hours after Day 14, mean inhibition ranged from 81.8% to 96.7% and from 66.3% to 81.6%, respectively, across all alogliptin doses.

Secondary endpoint results showed that mean fasting fructosamine levels were significantly decreased from Baseline to Day 15 for the alogliptin 100 and 400 mg groups, compared to placebo, suggesting greater glucose control. There were no statistically significant differences in mean 4-hour postprandial insulin concentrations, hyperglycemia, or mean C-peptide concentrations in the alogliptin or placebo groups.

Alogliptin was well tolerated at all doses, with no patient discontinuation due to adverse events (AEs), and no serious AEs identified among patients through the duration of the study. In addition, there was a low incidence of hypoglycemia similar to placebo.

About Alogliptin
Alogliptin, initially referred to as SYR-322, is a highly selective and potent DPP-4 inhibitor and is under investigation for the treatment of type 2 diabetes. Alogliptin was designed by Takeda to selectively inhibit DPP-4 and not other closely related proteins that are associated with other biologic activity. In in vitro studies, alogliptin has been shown to be 10,000-fold more selective for DPP-4 over other closely related proteins.

DPP-4 inhibitors are a new class of oral agents for the treatment of type 2 diabetes that block the degradation of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide), known as incretins, which are normally released in the digestive tract in response to food, and mediate glucose-dependent insulin secretion. GLP-1 also suppresses pancreatic glucagon secretion and subsequent liver glucose production, slows gastric motility and elicits satiety, a feeling of fullness. In type 2 diabetes, GLP-1 levels are decreased and the insulinotropic response to GIP is reduced, contributing to high blood sugar. DPP-4 inhibitors have displayed a weight-neutral profile along with a risk of low blood sugar similar to placebo due to their glucose-dependent mechanism of action.
Discovered by Takeda San Diego, Inc., alogliptin is being developed by Takeda Global Research & Development and is currently in Phase 3 clinical studies.

Posted by dlifenews at 10:40 AM | Comments (0)

Byetta Study Showed Sustained Blood Glucose Control Over Three Years in People with Type 2 Diabetes

June 25, 2007 (PRNewswire-FirstCall) -- Amylin Pharmaceuticals, Inc. and Eli Lilly and Company today announced three- year, open-label study results that showed treatment with BYETTA(R) (exenatide) injection was associated with sustained blood sugar control and progressive weight loss in people with type 2 diabetes. These findings were presented at the 67th Annual Scientific Sessions of the American Diabetes Association (ADA) in Chicago.

In this open-label extension study, 217 people with type 2 diabetes not achieving adequate blood sugar control on oral medication alone (metformin and/or sulfonylurea) were treated with BYETTA (10 mcg) in addition to their oral medication(s) for three years. Study participants treated with BYETTA and oral medication(s) showed sustained reductions in blood sugar as measured by A1C, a test that measures average blood sugar levels over approximately three months, and fasting blood glucose levels (-1.0 +/- 0.1 percent and -23.5 +/- 3.8 mg/dL, respectively).(1) After three years of BYETTA treatment, 46 percent of study participants achieved the American Diabetes Association's recommended target A1C of 7 percent and 30 percent of participants achieved an A1C of 6.5 percent.(2) Weight loss from baseline was progressive, with participants losing on average 11.68 +/- 0.88 lbs at three years. In addition, one in four patients lost an average of 28.66 lbs.

Pancreatic beta cells (beta-cells) are responsible for producing insulin, a hormone that helps the body convert glucose (blood sugar) into energy.(3) Type 2 diabetes develops when the pancreas does not produce enough insulin for the body to adequately regulate blood sugar levels, or the body is unable to use the insulin efficiently. In this study, BYETTA treatment was assessed for improvements in pancreatic beta-cell function in a subset of 92 study participants. HOMA-B (Homeostasis Model Assessment), a measure of pancreatic beta-cell function, improved by 17 percent from baseline over three years.

"Type 2 diabetes is associated with impaired insulin production in the pancreas that progressively deteriorates over time," said John Buse, Chief of the Division of General Medicine and Clinical Epidemiology at the University of North Carolina School of Medicine in Chapel Hill, NC. "Although currently BYETTA is not indicated to improve beta cell function, these study findings suggest that long-term BYETTA treatment may help improve insulin production, a root cause of the condition, and help people with type 2 diabetes better control their blood sugar levels."

BYETTA was generally well-tolerated in this study, and side effects were consistent with those seen in previous studies. In clinical trials and post- approval adverse event reports, the most common side effect is mild-to- moderate nausea, which affects fewer than half of patients and usually decreases over time.

BYETTA is indicated for use as an adjunctive therapy for people with type 2 diabetes who are not achieving blood sugar control using metformin, a sulfonylurea, or a thiazolidinedione. Over three million prescriptions have been written in the U.S. since being approved by the Food and Drug Administration (FDA) in 2005. For more information, visit www.BYETTA.com.

Posted by dlifenews at 09:48 AM | Comments (1)

Penn Researchers Find Potential New Target for Type 2 Diabetes

June 09, 2007

Implications for treating impaired fat metabolism in obese diabetics

June 9, 2007 (EurekAlert) - Philadelphia - Researchers at the University of Pennsylvania School of Medicine have discovered a potential new target for treating type 2 diabetes, according to a new study that appeared online this week in Nature. The target is a protein, along with its molecular partner, that regulates fat metabolism.

"Over the last 10 years, we have begun to understand the importance of fat metabolism in diabetes," notes lead author Morris J. Birnbaum, MD, PhD, the Willard and Rhoda Ware Professor of Diabetes and Metabolic Diseases at Penn and an Investigator of the Howard Hughes Medical Institute. "Type 2 diabetics are at a higher risk for cardiovascular disease because they also have disorders in fat metabolism as a result of obesity and abnormal insulin action." Birnbaum is also the Associate Director of the Type 2 Diabetes Unit for Penn's Institute for Diabetes, Obesity, and Metabolism.

When a person eats a meal, the pancreas usually responds by secreting insulin that signals the liver to stop making glucose and burning fat. When a type 2 diabetic eats a meal, insulin cannot stop the manufacture of glucose in the liver, but it can stop the burning of fat stores. This gives the diabetic person a "double whammy": fatty acids accumulate from food and from the liver. Consequently, more fat is deposited in tissues and obesity worsens.

Until now there was no clear connection between insulin and the control of fat metabolism. This study shows that when insulin is present, as it is after a meal, the protein Akt2/PKB adds a phosphate group to its molecular partner PGC-1Ą. When this happens, PGC-1Ą cannot activate the genes needed for fat metabolism.

The findings suggest that if a drug could induce Akt2/PKB to add the phosphate group (phosphorylation) to PGC-1Ą, then the liver of a diabetic might be "fooled" into stopping the oxidation of fat stores. "Muscle and fat tissue also burn fat stores, and we are currently investigating whether PGC-1Ą and Akt2/PKB have the same role in those tissues," says Birnbaum.

The researchers also found that insulin-stimulated phosphorylation of PGC-1Ą was blunted in mice that had non-functional Akt2/PKB. Finally, they showed that livers with too much PGC-1Ą or with PGC-1Ą that could not be phosphorylated put out many copies of the genes for fat metabolism. Each approach pointed to the same conclusion: PGC-1Ą had phosphate groups added to it by Akt2/PKB in the presence of insulin and this prevented the turning on of genes that make fat.

There are currently no drugs that target PGC-1Ą and Akt2/PKB. "We hope that drug companies will look for new ways to modify fat metabolism in type 2 diabetics using these possible targets," says Birnbaum.

Posted by dlifenews at 12:44 PM | Comments (0)

Massachusetts Residents May Participate in a Research Study To See if the Aspirin Family of Drugs Can Improve Type 2 Diabetes Management

May 07, 2007

May 7, 2007 (Joslin) -- Are you one of the estimated 360,000 people with type 2 diabetes in the Commonwealth of Massachusetts? If so, you may be eligible to participate in a clinical trial at Joslin Diabetes Center investigating whether salsalate, an anti-inflammatory drug used for years to manage arthritis pain, can reduce blood glucose levels in people with type 2 diabetes.

Massachusetts follows the national trend of diabetes. Approximately 6 out of 100 people in the Commonwealth have been diagnosed with diabetes, and 20 out of every 100 deaths are diabetes-related. Clinical trials are a critical way to explore better treatment and management programs that can reduce the complications caused by diabetes, such as heart attacks and strokes. This study will examine if salsalate, which is chemically similar to aspirin but has fewer side effects, can significantly reduce high levels of blood glucose and lead to an inexpensive yet effective treatment path for people with type 2 diabetes. Salsalate has been used for more than 40 years to treat pain associated with arthritis.

Participants in this study will make seven to eight visits to Joslin Diabetes Center over the course of 21 weeks. Each visit will be an hour or less, including an exam and lab work. Participants will be provided at no charge with a glucose monitor and trial medication (either the study drug or a placebo, a pill with no active medication). Parking is free for each visit, and participants will receive monetary compensation for each study visit completed. During the study, participants will continue to see their personal physician for all of their healthcare needs.

The ideal candidates will be adults diagnosed with type 2 diabetes who are between the ages of 18 and 75, who are not on insulin and whose glucose levels are not in good control. Other criteria will be reviewed during the screening process for the study.

If you are interested in participating in this study, referred to as Targeting Inflammation with Salsalate in Type 2 Diabetes (TINSAL-T2D), please contact Elizabeth Tatro at 617-735-1940. For more information on Joslin, call 1-800-JOSLIN-1 or visit http://www.joslin.org/

For more information about the study, please contact Allison B. Goldfine, M.D., via phone at 617-732-2643 or via e-mail at Allison.Goldfine@joslin.harvard.edu or visit the clinical research part of Joslin's Web site: http://www.joslinresearch.org/PINET/ClinicalDetail.asp?clinicalSectionID=3

Posted by dlifenews at 02:29 PM | Comments (0)

Alzheimer's, Parkinson's, Type 2 Diabetes Similar at Molecular Level

May 01, 2007

Protein analysis may offer new therapeutic route

May 1, 2007 (EurekAlert) - Alzheimer's disease, Parkinson's disease, type 2 diabetes, the human version of mad cow disease, and other degenerative diseases are more closely related at the molecular level than scientists realized, a team reports this week in an advanced online publication of the journal Nature.

While still preliminary, the research, could help scientists develop tools for diagnosing such diseases, and potentially for treating them through "structure-based drug design," said David Eisenberg, a UCLA chemist and molecular biologist who is part of the research team.

The researchers studied the harmful rope-like structures known as amyloid fibrils--linked protein molecules that form in the brain. The fibrils contain a stack of water-tight "molecular zippers."

"With each disease, a different protein transforms into amyloid fibrils, but all of these diseases are similar at the molecular level," Eisenberg said.

If the molecular zipper is universal in amyloid fibrils, as Eisenberg believes, is it possible to pry open the zipper or prevent its formation?

Eisenberg's research team used X-ray analysis and a sophisticated computer algorithm to study proteins known to be associated with human diseases. When the computer said a protein will form an amyloid fibril, it almost always did. And one team member is experimenting with various compounds to break up the fibrils.

"Structural analysis of micro-crystals of proteins is an example of how basic research can have a profound impact on our understanding of health, biotechnology and other practical issues," said Parag Chitnis, program director in National Science Foundation's (NSF) Division of Molecular and Cellular Biosciences.

Posted by dlifenews at 09:39 AM | Comments (0)

Landmark Study Highlights Complex Genetic Risk Factors Behind Type 2 Diabetes

April 27, 2007

April 27, 2007 (EurekAlert) - A UK collaboration of scientists has identified three new genes that predispose individuals to develop type 2 diabetes, bringing scientists a step closer towards understanding what causes this complex disease.

The study, jointly led by researchers at the University of Oxford and the Peninsula Medical School, Exeter, and forming part of the Wellcome Trust Case Control Consortium looked at over 2 billion pieces of genetic data and 6,000 people with type 2 diabetes and 8,000 controls to track down these three genes. In addition, they confirmed the link between the disease and a further two previously-identified genes.

The findings, published online today in the journal Science, bring the total number of genes known to be involved in type 2 diabetes to nine, including the FTO gene reported by the same UK group two weeks ago. The FTO gene influences individual risk of type 2 diabetes through its effect on weight and obesity.

Type 2 diabetes occurs as a result of a failure of the body to produce enough insulin to maintain normal levels of glucose (sugar) in the blood. This failure is usually compounded by a reduction in the capacity of the insulin released to work properly in tissues such as muscle and fat (known as insulin resistance). It is a major cause of heart disease and stroke, as well as blindness and kidney failure.

There are currently around 200 million people who have type 2 diabetes worldwide, yet its underlying cause is poorly understood, limiting both treatment and prevention. Lifestyle factors, such as poor diet and lack of exercise have been known for some time to increase risk of developing the disease, but scientists are becoming increasingly aware of the role played by genetics.

For each of the three genes described in the paper, the researchers have found that there are two common "versions", one of which is associated with an increased risk of developing type 2 diabetes, and the other with reduced risk. Each high-risk version increases the risk of type 2 diabetes by between 10 and 20 percent. All are common in the general population.

"This research helps us to understand that, for most people at least, an individual’s risk of developing diabetes as they get older is influenced by a number of genes, as well as by their environment," says Professor Mark McCarthy from the University of Oxford, one of the lead authors of the paper. "Clearly, the more 'high risk' alleles a person inherits, the higher the likelihood that they will go on to develop diabetes."

The exact role of the genes that have been implicated by these studies is still uncertain. However, two of them appear to be involved in the development, function and regeneration of insulin-producing beta cells, found within the pancreas. This finding is likely to help to answer a long-standing controversy in the diabetes field concerning the extent to which a reduced number of pancreatic beta-cells (as opposed to reduced function) contributes to the development of diabetes.

"We now have significantly more pieces to the jigsaw that will help us understand the mechanisms behind type 2 diabetes," says Professor Andrew Hattersley of the Peninsula Medical School, also a lead author on the paper. "Each piece of new knowledge takes us a step closer towards a future with improved prevention and treatment of this very significant condition."

The first important clues to the identities of these genes came from a genome-wide analysis conducted in 2,000 people with type 2 diabetes and 3,000 controls as part of the Wellcome Trust Case Control Consortium2. The Consortium is one of the biggest projects ever undertaken to identify the genetic variations that predispose people to or protect them from major diseases.

Professor Peter Donnelly of the University of Oxford, who heads the consortium said: "This landmark study reveals the power of the strategy that the Wellcome Trust Case Control Consortium has adopted to study diabetes and several other common diseases. It is clear that these and other findings which the Consortium will shortly be reporting will have a major impact on our understanding of the mechanisms behind many diseases of global importance."

These initial findings were then confirmed by studying a further 9,000 samples from the UK (the majority of them from the Dundee area collected by researchers from the Ninewells Hospital and Medical School.

The research has been conducted in close collaboration with two other groups from the US and Scandinavia, who were undertaking similar research studies in samples from Sweden and Finland. Their results, which have also identified the same three genes, are published today alongside the UK study. In a unique collaboration, these three international groups chose to combine forces rather than compete, resulting in the largest ever collaborative study of type 2 diabetes, involving over 32,000 subjects.

"The extraordinary achievements of this research project have only been made possible through the unique international collaboration," says Dr Mark Walport, Director the Wellcome Trust, which funded the UK study. "By sharing data and working together, the researchers have made significant progress in understanding the genetics underlying type 2 diabetes in a very short time."

Iain Frame, Research Manager at Diabetes UK, said: "Diabetes UK welcomes these exciting findings. It’s important to remember that Type 2 diabetes is a genetic condition and not just associated with lifestyle factors. This discovery will help us get closer to unravelling the genetics of the condition. If we can understand more about the genetics we can make real progress towards the prevention and treatment of Type 2 diabetes.

"Diabetes UK funded the original collection of samples at the beginning of this study. It is thanks to the collaborative efforts of Diabetes UK, a number of excellent researchers and the Wellcome Trust that this discovery has been possible."

Posted by dlifenews at 03:44 PM | Comments (0)

U of M-led Study Identifies New Genetic Risk Factors for Type 2 Diabetes

April 27, 2007 (EurekAlert) - Ten genetic variants associated with type 2 diabetes, a disease which impacts more than 170 million people worldwide, have been identified or confirmed by a U.S.-Finnish team led by scientists at the University of Michigan School of Public Health.

The discoveries could lead to the development of new drugs for diabetes, permit more effective targeting of drug and behavioral therapies, and help scientists and physicians better predict who will develop diabetes, said Michael Boehnke, the Richard G. Cornell Collegiate Professor of Biostatistics at the U-M School of Public Health.

Boehnke is the lead scientist on the Finland-United States Investigation of Non-Insulin-Dependent Diabetes Mellitus Genetics (FUSION) study group, which collaborated with two other groups of scientists to conduct the most comprehensive study to date of genetic risk factors for type 2 diabetes.

"Until recently we knew very little about the genetic architecture of type 2 diabetes," said Boehnke, adding that diabetes has been called 'the geneticist's nightmare' because there are so many behavioral and environmental factors---in addition to genes---that are risk factors for the disease. "This is certainly not the complete genetic architecture for diabetes, but we have come a long way in better understanding the genetic basis for this disease."

The groups identified at least four new genetic factors associated with increased risk of diabetes and confirmed the existence of another six. The findings of the three groups, published simultaneously today in the online edition of the journal Science, boost to at least 10 the number of genes confidently associated with increased susceptibility to type 2 diabetes.

"One of the nicest aspects of this study has been the collaboration between the three groups," Scott said. "Most of these variants would have taken substantially longer to identify if each group had proceeded independently."

Type 2 diabetes is characterized by high levels of blood sugar, caused by the body's inability to utilize insulin to move blood sugar into the cells for energy. Type 2 diabetes affects nearly 21 million in the United States and the incidence of the disease has skyrocketed in the last 30 years. Diabetes is a major cause of heart disease and stroke, as well as the most common cause of blindness, kidney failure and amputations in U.S. adults.

"By identifying these genes, we are identifying potential loci for drug action and suggesting classes of compounds that might be useful to help develop drugs to treat diabetes," Boehnke said.

In the study, researchers used a relatively new strategy known as a genome-wide association study, Boehnke said. Researchers began by scanning the genomes of more than 2,300 Finnish by typing more than 300,000 strategically selected markers of genetic variation. About half of the participants had type 2 diabetes and the other half had normal blood glucose levels.

To validate their findings, the researchers compared their initial findings with results from genome-wide studies of 3,000 Swedish and Finnish participants carried out by the Diabetes Genetics Initiative and 5,000 British participants done by the Wellcome Trust Case Control Consortium and UK Type 2 Diabetes Consortium. After identifying promising leads through this approach, the three research teams jointly replicated their findings by testing more focused sets of genetic markers in additional groups totaling more than 22,000 people from Finland, Sweden, Poland, the United States and the United Kingdom. All told, more than 32,000 people were tested for the study, making it one of the largest genome-wide association and follow-up efforts conducted to date.

"This achievement represents a major milestone in our battle against diabetes. It will accelerate efforts to understand the genetic risk factors for this disease, as well as explore how these genetic factors interact with each other and with lifestyle factors," said Elias A. Zerhouni, director of the National Institutes of Health. "Such research is opening the door to the era of personalized medicine. Our current one-size-fits-all approach will soon give way to more individualized strategies based on each person's unique genetic make-up."

The newly identified diabetes-associated variations lie in or near:

IGF2BP2. This gene codes for a protein called insulin-like growth factor 2 mRNA binding protein 2. Insulin-like growth factor 2 is thought to play a role in regulating insulin action.

CDKAL1. This gene codes for a protein called CDK5 regulatory subunit associated protein1-like1. The protein may affect the activity of the cyclin dependent kinase 5 (CDK5) protein, which stimulates insulin production and may influence other processes in the pancreas's insulin-producing cells, known as beta cells. In addition, excessive activity of CDK5 in the pancreas may lead to the degeneration of beta cells.

CDKN2A and CDKN2B. The proteins produced by these two genes inhibit the activity of cyclin-dependent protein kinases, including one that has been shown to influence the growth of beta cells in mice. Interestingly, these genes have been heavily studied for their role in cancer, but their contribution to diabetes comes as a complete surprise.

Chromosome 11. One intriguing association is located in a region of chromosome 11 not known to contain any genes. Researchers speculate that the variant sequences may regulate the activity of genes located elsewhere in the genome, but more work is needed to determine the exact relationships to pathways involved in type 2 diabetes.

The diabetes-associated genetic variants that were confidently confirmed by the new research are: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11 and FTO.

Posted by dlifenews at 03:41 PM | Comments (0)

Report Reveals Estimated High Prevalence and Heavy Cost of Type 2 Diabetes Complications

April 10, 2007

April 10, 2007 (EurekAlert) – A first-of-its-kind report looking at the prevalence and cost of type 2 diabetes complications shows that an estimated three out of five people (57.9 percent) with type 2 diabetes have at least one of the other serious health problems commonly associated with the disease, and that these health problems are taking a heavy financial toll on the United States. In 2006, the nation spent an estimated $22.9 billion on direct medical costs related to diabetes complications.*

The new report, titled State of Diabetes Complications in America, also shows that estimated annual healthcare costs for a person with type 2 diabetes complications are about three times higher than that of the average American without diagnosed diabetes. These complications, which can include heart disease, stroke, eye damage, chronic kidney disease and foot problems that can lead to amputations, cost a person with type 2 diabetes almost $10,000 each year.* People with diabetes complications pay nearly $1,600 out of their own pockets for costs that are not reimbursed by insurance, such as co-payments and deductibles.* This amount is significant, considering that according to the National Health Interview Survey, an estimated 40 percent of adults with diabetes reported a family income of less than $35,000 per year in 2005.

Results from the report were released today at the American Association of Clinical Endocrinologists' (AACE) 16th Annual Meeting and Clinical Congress, by AACE in partnership with the members of a diabetes complications consortium: the Amputee Coalition of America, Mended Hearts, the National Federation of the Blind and the National Kidney Foundation, and supported by GlaxoSmithKline.

The State of Diabetes Complications in America is an analysis of national health and economic data specific to type 2 diabetes complications, and was developed as a follow-up to a 2005 AACE study showing that two out of three Americans with type 2 diabetes analyzed in a study had elevated blood sugar levels, which can lead to diabetes complications.

Many people with type 2 diabetes develop more than one health complication associated with the disease. The new report shows that an estimated one out of three people (33.3 percent) with the disease has one other serious health problem; one out of ten people (10.3 percent) with the disease has two other serious health problems; one out of 15 people (6.7 percent) with the disease has three other serious health problems; one out of 13 people (7.6 percent) has four or more other serious health problems.

"The report makes it clear that we have a major national issue when it comes to diabetes management, and that urgent action is needed," said Daniel Einhorn, MD, FACE, and Secretary of the Board of Directors of AACE. "People with type 2 diabetes need to achieve and maintain good blood glucose levels over time to improve their chances of reducing the risk of these serious complications."

The State of Diabetes Complications in America report synthesizes data from two large national studies to examine the issue of diabetes-related complications in the United States. Data on the prevalence of diabetes-related complications were derived from the National Health and Nutrition Examination Survey (NHANES) and combined with economic data from the Medical Expenditure Panel Survey (MEPS).

The report estimates that in people with diabetes, there are specific health problems that are more prevalent than in people with normal blood sugar levels. The prevalence of macrovascular problems, or those related to the heart and large blood vessels, in people with diabetes vs. people with normal blood sugar levels is as follows:

• Congestive heart failure occurs in 7.9 percent of people with diagnosed diabetes vs. 1.1 percent of people without diabetes

• Heart attack occurs in 9.8 percent of people with diabetes vs. 1.8 percent without diabetes

• Coronary heart disease occurs in 9.1 percent of people with diabetes vs. 2.1 percent without diabetes

• Stroke occurs in 6.6 percent of people with diabetes vs. 1.8 percent without diabetes

In terms of microvascular complications, which relate to small blood vessels, the prevalence is as follows:

• Chronic kidney disease (1) occurs in 27.8 percent of people with diabetes vs. 6.1 percent without diabetes

• Foot problems such as foot/toe amputation, foot lesions and numbness in the feet occur in 22.8 percent of people with diabetes vs. 10 percent without diabetes

• Eye damage (2) occurs in 18.9 percent of people with diabetes (figures for eye damage in people without diabetes are not available in NHANES)

While type 2 diabetes is closely tied to the development of these complications, it is possible that some people may have developed these health problems independent of their diabetes, due to family history or other underlying medical conditions.

"Beyond the impact on quality of life, health complications from type 2 diabetes also contribute to substantial national and individual healthcare costs," said Willard G. Manning, PhD, Professor, Harris School of Public Policy Studies at the University of Chicago. "My hope is that the report will call attention to the issue of diabetes-related complications and bring about change in the way we manage type 2 diabetes to help reduce both the physical and financial burdens."

Regarding annual healthcare costs for people with type 2 diabetes, heart attack is the most costly complication, at $14,150 per person, followed by chronic kidney disease (3) ($9,002); congestive heart failure ($7,932); stroke ($7,806); coronary heart disease ($6,062); foot problems (4) ($4,687); and eye damage (5) ($1,785).*

"As great as these financial burdens are, this is a conservative estimate, as it only includes direct medical costs," adds Manning. "Costs attributed to lost employment or productivity, premature death and disability have not been included, and if we factor in those costs, the overall burden would be far greater."

Posted by dlife at 11:46 AM | Comments (1)

Better Diabetes Awareness Doesn’t Equal Better Habits for Some African-Americans

April 03, 2007

April 3, 2007 (Newswise) — African-Americans who have family members with diabetes are more aware of the disease’s risk factors — but that awareness may not lead to a healthier lifestyle.

The type 2 diabetes epidemic disproportionately affects African-Americans, so researchers wanted to see whether having a family member with the disease had any influence on a person’s awareness or behavior. Their findings appear in the May issue of the American Journal of Public Health.

The study evaluated 1,122 African-American adults, living in Raleigh and Greensboro, N.C. None of the participants were diagnosed with diabetes; however, 36 percent reported that an immediate family member had the disease.
Participants where shown a seven-item list and asked whether any of the factors increase a person’s risk of developing diabetes. All seven items on the list are risk factors for diabetes — minority race or ethnicity, overweight, family history of diabetes, sedentary lifestyle, older age, high-calorie diet and diabetes during pregnancy.

Among the participants with a family history of diabetes, nearly 60 percent had a better- than-average awareness of the diabetes risk factors. About 47 percent of the participants with no family history demonstrated such awareness.

Yet, this awareness didn’t necessarily translate into healthy behavior.

“We hypothesized that persons with a family history would be more aware of risk factors for diabetes, however, we were surprised that they were not more likely to engage in more of the healthy behaviors compared to persons without a family a history,” said study co-author Tiffany Gary, Ph.D., of the Johns Hopkins Bloomberg School of Public Health.

More than 75 percent of the participants were aware that being overweight increases the risk of diabetes. But, of the 65 percent who were overweight, only 32 percent were trying to lose weight.

“Some reasons for this difference could be that people may not be aware of national standards used to define overweight and obesity,” Gary said. “Furthermore, it has been shown in several studies that there may be a greater acceptance of a heavier body size among African-Americans.”

So, what more can be done to raise awareness that being overweight can lead to dangerous health consequences?

“One approach would be to improve awareness of health risks associated with being overweight or obese and accurate perceptions of defining overweight and obesity,” Gary said. “This could be accomplished by national campaigns, community activism and policy approaches.”

Kate Lorig, R.N., a professor at Stanford University’s Patient Education Research Center said people who are overweight are “definitely aware that being overweight is unhealthy, but may not be able to name a specific risk.”

“Education is part of the answer,” Lorig said. “But what we really have to do is make it environmentally and educationally appealing to change behaviors, not just for diabetes, but for most chronic health conditions.”

The authors did find two areas of significant behavior difference. African-Americans with a family history of diabetes were more likely (26.9 percent vs. 20.4 percent) to eat five or more servings of fruits and vegetables daily and to have had a diabetes screening test (74.6 percent vs. 61.2 percent).

Posted by dlife at 04:02 PM | Comments (0)

FDA Approves JANUMET™ for Type 2 Diabetes

April 02, 2007

WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck & Co., Inc. announced today that the U.S. Food and Drug Administration (FDA) approved JANUMET™, the first and only tablet combining a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin (also known as JANUVIA™), and metformin for the treatment of type 2 diabetes.

JANUMET has been approved, as an adjunct to diet and exercise, to improve blood sugar (glucose) control in adult patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone, or in patients already being treated with the combination of sitagliptin and metformin. JANUMET should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

The FDA approved JANUMET based upon clinical data including sitagliptin plus metformin as separate tablets. A clinical bioequivalence study has demonstrated the equivalence between JANUMET and sitagliptin plus metformin as separate tablets.

"JANUMET is the latest advance in Merck's longstanding commitment to developing effective medicines for type 2 diabetes," said Adam Schechter, president, United States Human Health, Merck & Co., Inc. "With JANUMET and JANUVIA, Merck now has a growing family of products that provides physicians with important treatment options for patients with type 2 diabetes."

JANUMET delivers proven efficacy

A 24-week, randomized, double-blind, placebo-controlled study with 701 patients with mildly to moderately elevated A1C levels (mean baseline 8.0 percent) inadequately controlled on metformin, showed that patients taking JANUMET2 (n=453) experienced significant additional mean placebo-subtracted reductions in A1C of 0.7 percent beyond that achieved by patients who continued on metformin alone (n=224) (p<0.001). In the study, more than twice as many patients on JANUMET (213 of 453 patients, or 47 percent) reached the American Diabetes Association's A1C goal of <7 percent compared with patients on metformin alone (41 of 224 patients, or 18 percent) (p<0.001).

JANUMET combines two agents with proven ability to deliver significant improvements in glycemic control: metformin, a commonly used effective glucose-lowering agent, and sitagliptin, a DPP-4 inhibitor that provides significant A1C lowering as monotherapy and as add-on therapy to metformin or thiazolidinediones (TZDs) based on clinical trials. JANUMET, like metformin, is dosed twice daily with meals. Consistent with the labeling for metformin alone, the labeling for JANUMET contains a boxed warning for lactic acidosis, a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with JANUMET.

"Physicians use several different medications in combination to address the multiple defects associated with type 2 diabetes, however, less than half of patients achieve and maintain their goal A1C levels," said Nir Barzilai, M.D., professor of Medicine and Molecular Genetics, director of the Institute for Aging Research, Albert Einstein College of Medicine. "JANUMET is an important new treatment option for many patients who need more than one therapy to control their type 2 diabetes because it addresses all three key defects of type 2 diabetes for improved glycemic control."

Patients treated with JANUMET experienced weight loss comparable to metformin alone, with no increased risk of hypoglycemia, edema, or GI disturbances beyond metformin alone

As clinicians select agents to add to the treatment regimens of patients with uncontrolled type 2 diabetes, it is important to consider issues such as weight gain, hypoglycemia, edema, and gastrointestinal disturbances.

In a 24-week study, mean body weight decreased 1.5 lb (n=399) in patients taking JANUMET, similar to patients taking metformin alone (1.3 lb decrease; n=169). There was no increased risk of hypoglycemia in patients treated with JANUMET (1.3 percent vs. metformin alone, 2.1 percent) and no increased risk of edema in patients treated with JANUMET (0.9 percent vs. metformin alone, 1.3 percent). In addition, there was no significant increase in the risk of overall gastrointestinal adverse reactions in patients treated with JANUMET (11.6 percent vs. metformin alone, 9.7 percent). Specific gastrointestinal adverse reactions included diarrhea (JANUMET, 2.4 percent vs. metformin alone, 2.5 percent), abdominal pain (JANUMET, 2.2 percent vs. metformin alone, 3.8 percent), nausea (JANUMET, 1.3 percent vs. metformin alone, 0.8 percent), and vomiting (JANUMET, 1.1 percent vs. metformin alone, 0.8 percent). The most common adverse experience in sitagliptin monotherapy reported regardless of investigator assessment of causality in ≥5 percent of patients and more commonly than in patients given placebo was nasopharyngitis.

Clinicians should be mindful that hypoglycemia could occur when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents (such as sulfonylureas and insulin) or ethanol. Elderly, debilitated, or malnourished patients and those with adrenal or pituitary insufficiency or alcohol intoxication are particularly susceptible to hypoglycemic effects.

By incorporating the novel mechanism of DPP-4 inhibition, JANUMET uniquely addresses the three key defects of type 2 diabetes

With the two active components, sitagliptin and metformin, JANUMET has a comprehensive mechanism of action that targets all three key defects of type 2 diabetes for improved glycemic control: diminished insulin release, uncontrolled production of glucose, and insulin resistance.

The sitagliptin component in JANUMET address two of the three key defects that cause poor glucose control: diminished insulin release due to beta-cell dysfunction and uncontrolled production of glucose by the liver due to alpha-cell and beta-cell dysfunction. By inhibiting the DPP-4 enzyme, sitagliptin significantly increases the levels of active incretin hormones, increasing the synthesis and release of insulin from the pancreatic beta cells and decreasing the release of glucagon from the pancreatic alpha cells.

JANUMET also contains metformin, which addresses the other key defect: insulin resistance. Metformin improves insulin sensitivity by increasing uptake and utilization of glucose by the muscles and tissues of the body. Metformin also decreases hepatic glucose production in a manner that is complementary to sitagliptin.

JANUMET provides powerful A1C lowering through combined reductions of both post-prandial glucose and fasting plasma glucose

JANUMET has been demonstrated to provide 24-hour glucose response - at mealtimes, between meals and overnight. In a 24-week, placebo-controlled study of patients with inadequate glycemic control on metformin alone, JANUMET significantly reduced post prandial, or post-meal, glucose (PPG) levels beyond metformin alone by a mean of 51 mg/dL in patients with a mean baseline 2-hour PPG of 275 mg/dL (n=387, p<0.001) and fasting plasma glucose levels (FPG) beyond metformin alone by a mean of 25 mg/dL in patients with a mean baseline FPG of 170 mg/dL (n=454, p<0.001).

Indications and contraindications for JANUMET

JANUMET is indicated, as an adjunct to diet and exercise, to improve glycemic control in adult patients with type 2 diabetes who are not adequately controlled on metformin or sitagliptin alone or in patients already being treated with the combination of sitagliptin and metformin. Consistent with the labeling for metformin alone, JANUMET is contraindicated in patients with renal disease, renal dysfunction, or abnormal creatinine clearance; and acute or chronic metabolic acidosis, including diabetic ketoacidosis. JANUMET should not be used in patients with type 1 diabetes.

Flexible dosing of JANUMET

JANUMET should be given twice daily with meals, with gradual dose escalation as needed to reduce the gastrointestinal (GI) side effects due to metformin. In this formulation, the dose of sitagliptin remains constant (100 mg daily) and is combined with the two most widely prescribed doses of metformin (1000 mg daily or 2000 mg daily). The recommended starting dose of JANUMET for patients not on prior metformin therapy and for those not adequately controlled on sitagliptin is 50 mg sitagliptin and 500 mg metformin twice-daily with meals. For patients already receiving metformin therapy, the starting dose should be based on the patient’s current metformin regimen. The total daily dose should not exceed 100 mg sitagliptin and 2000 mg metformin.

Metformin and sitagliptin are known to be substantially excreted by the kidney. The risk of metformin accumulation and lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels above the upper limit of normal for their age should not receive JANUMET. In the elderly, JANUMET should be carefully titrated to establish the minimum dose for adequate glycemic effect, because aging can be associated with reduced renal function. Any dose adjustment should be based on a careful assessment of renal function. Before initiation of therapy with JANUMET and at least annually thereafter, renal function should be assessed and verified as normal.

Pricing and availability of JANUMET

The price of twice-daily JANUMET will be $4.86 per day. JANUMET will be broadly available in pharmacies in the near future.

Selected cautionary information for JANUMET

JANUMET should be avoided in patients with evidence of hepatic disease. Before initiation of therapy with JANUMET and at least annually thereafter, renal function should be assessed and verified as normal. Patients should be warned against excessive alcohol intake while receiving JANUMET. Patients may require discontinuation of JANUMET and temporary use of insulin during periods of stress and decreased intake of fluids and food such as may occur with fever, trauma, infection or surgery. Patients previously controlled on JANUMET who develop laboratory abnormalities or clinical illness should be evaluated promptly for evidence of ketoacidosis or lactic acidosis. The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). When lactic acidosis occurs, it is fatal in approximately 50 percent of cases.

Posted by dlife at 10:39 AM | Comments (0)

Type 2 Diabetes Present in Jamaican Youth

March 30, 2007

March 30, 2007 (Newswise) — New research indicates that a significant number of Jamaican adolescents and young adults are being diagnosed with type 2 diabetes, a disease once seen almost exclusively in middle aged and elderly adults. These findings will be presented at the American Association of Clinical Endocrinologists (AACE) Sixteenth Annual Meeting and Clinical Congress which will be held April 11-15 at the Washington State Convention & Trade Center in Seattle.

“Type 2 diabetes at this age can be considered an indicator of obesity in a society. This research helps confirm that the ‘obesity epidemic’ is not just an American problem,” Marshall Tulloch-Reid, MBBS, DSc, FACE, the study’s author said. “It is becoming a significant public health challenge in the developing world.”

In America, adolescents diagnosed with type 2 diabetes are generally between ten and 19 years old, obese, have a family history of type 2 diabetes, and are insulin resistant. Because there is no golden rule to differentiate the types of childhood diabetes, Dr. Tulloch-Reid’s research is significant as he presents criteria that can be used to identify patients who may have type 2 diabetes. It is the first profile of youth onset type 2 diabetes from the English Speaking Caribbean.

As more adolescents become obese at an earlier age, they are at an increased risk of developing type 2 diabetes. According to Tulloch-Reid, “Surveys in Jamaica show that nearly 19 percent of adolescents are considered obese. One in five diabetic youth in this study was diagnosed with type 2 diabetes.”

This original research is being presented by Dr. Tulloch-Reid, along with colleagues from The University of the West Indies and the Kingston Public Hospital.

This study will be featured as part of a poster session held during the Sixteenth Annual Meeting and Clinical Congress. Members of the press are invited to attend on Thursday, April 12 and Friday, April 13 from 9:00 a.m. to 9:45 a.m. The preview session will be located at the Convention Center Exhibit Hall 4E in Seattle. Dr. Tulloch-Reid will be available in the media room to discuss his findings on Friday, April 13, from 10:00 a.m. to 11:00 a.m.

Posted by dlife at 03:03 PM | Comments (0)

Soy Nut Consumption Reduces Markers of Inflammation

March 28, 2007

March 28, 2007 (PRNewswire) Eating soy nuts instead of red meat decreases some markers of inflammation and improves endothelial function in postmenopausal women with a collection of cardiometabolic risk factors, a new study by researchers at Isfahan University of Medical Sciences in Iran and the Harvard School of Public Health found. In previous studies by the same group, subjects who ate soy nuts also showed improvements in their lipid profiles, suggesting that soy may improve cardiac health among a subgroup of women.

Previous research has looked at the effect of soy on inflammatory markers and endothelial function in the general population, but this was the first study to look more narrowly at how eating soy nuts (versus soy protein) would specifically affect postmenopausal women who already had a number of metabolic abnormalities. Consuming soy protein did not produce the same benefits, the researchers found.

Women (and men) who have certain cardiometabolic risk factors (abdominal obesity, high blood pressure, high cholesterol and insulin resistance) are at high risk for type 2 diabetes and for heart disease, the number one killer of people with diabetes. Studies have shown that lifestyle changes, such as losing moderate amounts of weight and increasing physical activity, can substantially reduce the chances of developing diabetes for people who already have these risk factors.

"A well-balanced meal plan should be part of any program designed to lose weight or improve overall health. This study shows that adding soy nuts to your diet -- and eating less red meat -- could be an important part of that meal plan," said lead researcher Dr. Leila Azadbakht, at the Isfahan University of Medical Sciences Department of Nutrition in Iran.

Soy is also often used as an alternative or adjunct to hormone replacement therapy in postmenopausal women. The researchers note that the mechanisms by which soy affects the inflammatory state may be related to the effects of soy phytoestrogens, which mimic hormone replacement therapy. However, more research needs to be done to understand the mechanisms through which soy affects inflammation and endothelial function. It is also unclear whether other groups of postmenopausal women would benefit as much as those participating in this study who had a number of high risk factors for diabetes and heart disease.

Posted by dlife at 09:18 AM | Comments (0)

Diabetes Linked to Higher Parkinson's Risk

March 28, 2007 (PRNewswire) -- People who have type 2 diabetes are more likely to develop Parkinson's disease as they age, though researchers are uncertain what accounts for the link between the two diseases, according to a new study being published in the April issue of Diabetes Care.

The study, by researchers in Finland, is the first large prospective study to find type 2 diabetes to be a risk factor for Parkinson's disease, a movement disorder characterized by muscle rigidity and tremors.

According to the authors, people with type 2 diabetes are 83 percent more likely to be diagnosed with Parkinson's than people in the general population. The study found the association between the two diseases existed for both men and women, independently of other confounding factors.

"Diabetes might increase the risk of Parkinson's disease partly through excess body weight," the researchers hypothesized, since their work showed that excess body weight was also associated with an elevated risk of Parkinson's disease. However, they concluded that more research needed to be done to fully understand the mechanisms behind this link.

Posted by dlife at 09:15 AM | Comments (2)

Periodontal Diseases May Aggravate Pre-Diabetic Characteristics

March 14, 2007

March 14, 2007 (EurekAlert) - Periodontal diseases may contribute to the progression to pre-diabetes, according to a new study that appears in the March issue of the Journal of Periodontology.

Pre-diabetes is a condition in which blood glucose levels are higher than normal, but not high enough to be diagnosed as diabetes. The American Diabetes Association estimates 54 million people in the United States have pre-diabetes, and a significant portion of those people will develop Type 2 diabetes within 10 years.

Researchers from Denmark investigated if having periodontal diseases can influence pre-diabetes and contribute to the progression of diabetes. They found that having periodontal disease can cause someone to develop pre-diabetic characteristics, and probably disturb the glucose regulation of a non-diabetic who has pre-diabetic characteristics, contributing to the progression of Type 2 diabetes. The study, conducted with rat models known to exhibit pre-diabetes characteristics, is believed to be the first to evaluate the relationship between periodontitis and pre-diabetes.

"This study found that having periodontal diseases can alter the metabolic conditions which would probably lead to the progression to pre-diabetic characteristics and Type 2 diabetes," said Dr. Carla Pontes Andersen, Department of Periodontology at the University of Copenhagen.

"We have known that people with diabetes are more susceptible to periodontal diseases and have more severe disease," said Dr. Preston D. Miller, Jr., President of the American Academy of Periodontology.

"This breakthrough research shows having periodontal disease may aggravate pre-diabetes which is a precursor for diabetes. These findings underscore the importance of taking good care of your teeth and gums: it may be a simple way to prevent diabetes, or to prevent the progression of diabetes."

Posted by dlife at 10:39 AM | Comments (0)

MUHC led Research Identifies Risk Factor Genes for Type 2 Diabetes

February 11, 2007

February 11, 2007 (MUHC News) - A new study led by researchers at the McGill University Health Centre (MUHC) has identified four genes that increase the risk of developing type 2 diabetes. This form of diabetes is the most common worldwide and affects nearly 2 million Canadians. In recent years, the prevalence of Type 2 diabetes has increased rapidly. This genetic discovery may help stem this rise.

This genetic study, published today in the journal Nature, was led by MUHC endocrinologist Dr. Rob Sladek at the McGill University and Genome Quebec Innovation Centre together with Dr. Co