Study Links Depression To Higher Death Rate From All Causes Among Medicare Beneficiaries With Diabetes

September 30, 2008 (Press Release) - In a large group of Medicare beneficiaries with diabetes, depression was associated with a higher death rate from all causes during a two-year study period. The findings are published in the October 2008 Journal of General Internal Medicine.

Lead author Dr. Wayne Katon, professor of psychiatry and behavioral sciences at the University of Washington (UW), noted that previous research indicates that depression and diabetes is a potentially lethal mix among young to middle-aged patients. Depression also puts patients at greater risk of complications from their diabetes. This more recent study suggests that depression is also a risk factor for mortality in older patients with diabetes. Most Medicare beneficiaries, like the ones in this study, are over age 65. The mean age of the participants was 75.6 years.

The study tracked 10,704 Medicare beneficiaries with diabetes who were enrolled in a disease management program in Florida. They were surveyed at the start of the study with a health assessment questionnaire. Evidence of depression among members of the group came from physician diagnosis, patient reports of having a prescription for an antidepressant in the year before the survey, or patient answers to a brief screening test. For the next two years, the research team recorded the death and cause of death of participants through bi-monthly checks of Medicare claims and eligibility files, or from phone calls with the participants' families.

The research team found that patients with both diabetes and depression had an increased risk of about 36 percent to 38 percent of dying from any cause during the two-year follow-up. Participants with a physician diagnosis of depression were significantly younger than their cohorts, more likely to be female, had more severe medical illness, were less likely to be African-American, and more likely to be Hispanic. These variables were controlled for in the analysis of increased risk. A total of 12.1 percent of participants who had both disorders died during that period. Among those without depression, 10.4 percent died.

Participants who had been treated with one or more antidepressant medications in the year before the study had a 24 percent increased risk of mortality, compared to non-depressed participants. According to the study authors, those patients may have been treated with antidepressants because their depressive symptoms were more severe and persistent than those of more mildly depressed patients who weren't prescribed antidepressants.

There was no difference in the rate of cardiovascular or cerebrovascular events between those treated with antidepressants and those who had no indication of depression.

"Rates of mortality from vascular disease may be decreasing in recent years among patients with diabetes due to more aggressive treatment of high blood pressure, cholesterol, and glucose levels," the researchers surmised, "as well as widespread use of preventative medications such as aspirin and beta blockers."

According to the authors, there may be several reasons why depression worsens chronic diseases such as diabetes. Depression has been associated with inadequate self-care and harmful habits like smoking or overeating. Depression is also associated with nervous system and endocrine system problems, and with inflammatory markers.

The authors noted their study's limitations: the participants were from one geographic region of the United States, and the follow-up period was relatively short. Defining depression in part by physician diagnosis and treatment, they added, may have selected for participants with more severe illness. The study was also not able to obtain information on education, income, weight, smoking habits, physical activity, or compliance in taking medication.

In addition to Katon, the researchers included Drs. Ming-Yu Fan and Jurgen Unutzer from the UW, Dr. Jennifer Taylor from Green River Health in Tampa, Fl.; Dr. Harold Pincus from Columbia University and the Rand Corporation; and Michael Schoenbaum from the National Institutes of Health (NIH) in Bethesda, Md.

Grants from the National Institute of Mental Health of the NIH funded the study.

Posted by dlife at 05:16 PM | Comments (0)

Scientists Discover Why A Mother's High-Fat Diet Contributes To Obesity In Her Children

September 30, 2008 (EurekAlert) - New research published online in The FASEB Journal (http://www.fasebj.org) suggests that pregnant women should think twice about high-fat foods. In a study from the University of Cincinnati and the Medical College of Georgia, scientists found that female mice fed high fat diets were more likely to have oversized offspring (a risk factor for overweight and obesity) because fat causes the placenta to go into "overdrive" by providing too many nutrients to the fetus. This information also suggests that the reverse may be true as well—high fat diets may help prevent undersized babies.

"Our model may one day lead to dietary recommendations for mothers who are entering pregnancy overweight or obese," said Helen N. Jones, Ph.D., first author of the study. "We hope this research will ultimately help reduce the number of babies suffering from birth injuries, decrease C-section rates, and lower the risk of babies becoming overweight or obese later in life."

To reach their conclusion, the researchers fed one group of mice a normal diet and another group a higher fat diet for eight weeks. Then the mice were mated. At the end of each mouse's pregnancy the offspring were delivered by c-section and weighed along with their placentas. The scientists then took blood from the mothers and measured the ability of the placenta to transport nutrients to the babies.

"It's no secret that big women tend to have big babies," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but now we know that there's more at play than genetics. Cutting back on fatty foods during pregnancy might decrease the chance of having a baby that becomes overweight in the future."

According to the U.S. Centers for Disease Control and Prevention, about one-third of adult men and women, and 16.3 percent of children and youth in the United States are obese. Obesity increases the risk of many diseases and health conditions, including: hypertension, osteoarthritis (breakdown of cartilage and its underlying bone in a joint), dyslipidemia (high total cholesterol, high levels of triglycerides), type 2 diabetes, coronary heart disease, stroke, gallbladder disease, sleep apnea and respiratory problems, and some cancers.

Posted by dlife at 11:50 AM | Comments (0)

Candesartan can increase regression of retinopathy in type 2 diabetes

September 25, 2008 (EurekAlert) - Treatment with candesartan can increase regression of retinopathy in type 2 diabetes and reduce incidence of retinopathy in type 1 diabetes. These are among the conclusions of the DIRECT studies, published early Online and in an upcoming edition of The Lancet.

Diabetic retinopathy is a leading cause of blindness in people of working age. In the first of the two Articles, Professor Nish Chaturvedi, National Heart and Lung Institute, Imperial College Healthcare NHS Trust, London, UK, and colleagues, examine the effect of candesartan on incidence and progression of retinopathy in type 1 diabetes. Two randomised controlled trials formed this part of the study - DIRECT-Prevent 1 for patients without existing retinopathy and DIRECT-Protect 1 for patients already with the condition. In DIRECT-Prevent 1, 711 patients received candesartan and 710 placebo; and the researchers found that the incidence of retinopathy was 18% lower for patients given candersartan, a result with borderline statistical significance. In DIRECT-Protect 1, 951 patients received candesartan and 954 placebo, with no statistically significant difference overall in retinopathy progression between the two groups. However, further analysis revealed that risk of retinopathy progression by three or more steps on the EDTRS scale* was 35% lower for candesartan patients compared with placebo. And a patient's final 'stage' of retinopathy after the four-year long trial was more likely to have improved with candesartan compared with placebo in both DIRECT-Prevent 1 (by 16%) and in DIRECT-Protect 1 (by 12%). The authors conclude: "Although candesartan reduces the incidence of retinopathy, we did not see a beneficial effect on retinopathy progression."

In the second Article, Professor Anne Sjølie, Odense University Hospital, Denmark, and colleagues, report the DIRECT-Protect 2 study — a randomised controlled trial to analyse the effect of candesartan on both slowing progression and inducing regression of retinopathy in patients with type 2 diabetes. The trial looked at 1905 patients with mild to moderately severe retinopathy, 951 received candesartan 16mg once per day (doubled to 32mg after one month) and 954 placebo. The researchers found that 17% of candesartan patients and 19% on placebo had progression of retinopathy by three or more steps on the ETDRS scale - a non-statistically significant risk reduction of 13% for candesartan patients. Regression (defined as a 3-step improvement or a persistent 2-step improvement confirmed in 2 consecutive visits on the ETDRS scale) was increased by 34% in the candesartan group compared with placebo. Finally, patients in the candesartan group were 17% more likely than placebo to experience an overall change towards less severe retinopathy by the end of the trial. The authors conclude: "These results suggest that treatment with candesartan in type 2 diabetic patients with mild to moderate retinopathy could induce improvement of retinopathy."

In an accompanying Comment, Dr Paul Mitchell, Centre for Vision Research, University of Sydney, Australia, and Dr Tien Y Wong, Centre for Eye Research Australia, University of Melbourne, Australia, and Singapore National University, say: "Clearly, prevention of retinopathy development and progression, or induction of its regression, could have widespread benefits both on the eye and the systemic health of people with diabetes. The DIRECT trials' conclusions that candesartan reduces retinopathy development in type 1 diabetes and benefits its evolution in type 2 are therefore justified, with some caveats."

Posted by dlife at 03:33 PM | Comments (0)

For Insulin Sensitive Overweight Patients, 1 Session Of Exercise Improves Metabolic Health

September 25, 2008 (EurekAlert) - One out of every three Americans is obese. These individuals are at greater risk for additional diseases, since obesity leads to other health problems, such as diabetes.

Obesity-related complications are associated with an abnormal fat metabolism in the muscle. As a result, accumulated fat by-products inside the muscle affect insulin resistance. To avoid the build up of fat by-products, fat must either be oxidized (burned, as in exercise) or stored (as benign fat) in muscle.

A team of researchers has examined the effect of exercise on fat accumulation in a new study involving five obese women. In one session the women overate and did not exercise; in a follow-on session they overate and did exercise. The researchers found that:

* the body's fat-burning oxidation rate was reduced after one day of overeating;

* conversely, just one session of exercise increased the rate of fat-burning oxidation; and

* exercise increased the amount of fat that would eventually be stored in the muscle.

The findings indicate that even one bout of exercise helps to reduce the fat by-products inside the muscle, which affects the insulin sensitivity. The findings also suggest that a single session of exercise "steers" muscle fat towards oxidation, thereby avoiding the accumulation of fat by-products.

The study was conducted by Andrea Cornford, Minghua Li, Simon Schenk, Matthew Harber and Jeffrey Horowitz, Division of Kinesiology, University of Michigan, Ann Arbor. Their research is entitled "Alteration in Lipid Metabolism After One Day of Overeating Are Reversed by a Single Session of Exercise." They will present their findings at a meeting sponsored by the American Physiological Society (APS; www.The-APS.org). The conference, The Integrative Biology of Exercise V, will be held September 24-27, 2008 in Hilton Head, SC.

Study Summary

The aim of the study was to assess changes in fatty acid (FA) metabolism in response to acute overeating and exercise. Five obese women performed three separate two-day trials in which they consumed (1) a weight-maintaining diet [Control]; (2) a hypercaloric diet (700 calories above normal); and (3) the same hypercaloric diet, but exercised to the point where they expended the 700 excess calories.

The morning after each trial, researchers measured whole-body FA oxidation [FAO] and calculated non-oxidative FA disposal as the difference between FA uptake and FAO.

A muscle biopsy was performed to measure the presences of triglycerides that are involved in fat storage.

The morning after the trials, the researchers observed that overeating suppressed fatty acid oxidation below the control levels, while exercising increased oxidation. Non-oxidative FA disposal was the same in each trial and a direct correlation between FA uptake and muscle GPAT activity were found.

Conclusions

According to Andrea Cornford, a member of the research team, "Exercise decreases everyone's insulin resistance and therefore reduces the chances of developing diseases such as type 2 diabetes. This study shows that even a single bout of exercise helps obese individuals increase their body's fat-burning rate and improve their metabolic health."

Posted by dlife at 03:31 PM | Comments (0)

Discovery Offers New Understanding Of Diabetes Drug Target

September 25, 2008 (EurekAlert) - Scientists at the University of Leicester have published findings about a new advance in the study of major diabetes drug target.

The advance - described by the researchers as 'very significant' - could lead to new drugs being developed to target a protein that plays a critical role in controlling the way the body breaks down sugar.

Professor John Schwabe and his team from the University of Leicester Department of Biochemistry (together with teams from Japan and Hungary) have been studying the protein, PPAR gamma. PPAR gamma is a major drug target for the treatment of type 2 diabetes. Although it was known how drugs are able to activate this protein, until this study, using the sophisticated technique of X-ray Crystallography, it was not clear how PPAR gamma is naturally activated in the body.

X-ray Crystallography is the principal method by which the detailed 3- dimensional structures of molecules - especially the molecules of living systems - have been discovered. It is achieved by firing X-rays at the target and creating its structures by analysing how the x-rays scatter into many different directions.

Through this method, the Leicester team have shown how PPAR gamma binds to eight different fatty acids, derived in part from what we eat. They found that many of these acids joined irreversibly with the protein and led to its long term activation. They have also shown that sometimes two fatty acids bind simultaneously, which might mean that PPAR gamma could be targeted by a mixture of drugs.

Professor John Schwabe, who led the Leicester project with his team, including Dr Toshimasa Itoh and Dr Louise Fairall, said: "The finding that natural activators for PPAR gamma couple irreversibly to the PPAR gamma receptor dramatically changes our understanding of how this receptor is activated.

"It may also allow for the design of novel pharmaceuticals that give longer term activation of PPAR gamma, at lower doses, without some of the side effects of the current generation of drugs."

Professor Schwabe said: "PPAR gamma is a critical player in the increasingly prevalent metabolic disease of type 2 diabetes which affects more than 180 million people worldwide (World Health Organisisation) and in the UK alone costs the NHS £9.6 million every day.

"PPARgamma is activated by two widely prescribed anti-diabetic insulin- sensitising drugs, Actos and Avandia. However the identity of the natural activators for PPAR gamma has remained unclear.

"Our breakthrough is important because it reveals for the first time that how this protein is activated by naturally-occuring fatty acids. This knowledge will help in the design of future novel pharmaceutical agents."

Posted by dlife at 03:29 PM | Comments (0)

American Diabetes Association Celebrates Historic Victory for Americans with Disabilities

September 25, 2008 (Press Release) - The American Diabetes Association applauds President George W. Bush for signing the Americans with Disabilities Act Amendments Act (ADA-AA) into law today. In recent weeks, both houses of Congress passed this landmark civil rights legislation. Enacted in 1990, the Americans with Disabilities Act promised to be a vital means of protecting the interests of people who are treated unfairly because of their diabetes. However, a series of Supreme Court decisions severely narrowed who is covered by the law and many individuals with diabetes have found themselves no longer covered by the act. The ADA-AA takes critical steps to restore the 1990 law to its original intent to include such individuals among those protected from discrimination.

"Today, we celebrate this act becoming law and we applaud the Bush Administration and Congress for taking this critical step toward protecting the civil rights of Americans with disabilities," said R. Stewart Perry, Chair of the Board, American Diabetes Association. "This is a historic victory for Americans with chronic illnesses like diabetes who will once again be covered by this law, and is a triumph for all individuals with disabilities who want to work and will now be able to fulfill their potential. Today, we proudly usher in a new era for hardworking Americans with disabilities."

Posted by dlife at 03:12 PM | Comments (1)

Discovery May Help Diabetic Gastric Problem

September 25, 2008 (Newswire) - Mayo Clinic researchers have found what may provide a solution to one of the more troubling complications of diabetes -- delayed gastric emptying or gastroparesis. The researchers showed in animal models that a red blood cell derivative increases production of a key molecule, normalizing the digestive process. The findings appear in the current online issue of the journal Gastroenterology (http://www.gastrojournal.org/).

Gastroparesis occurs when the stomach retains food for longer periods. When that food eventually passes into the small intestine, insulin is released. Because the passage of food out of the stomach becomes unpredictable, maintaining a proper blood glucose level -- critical for controlling diabetes -- also becomes difficult. Gastroparesis can cause pain, nausea, vomiting, stomach spasms and weight loss due to inadequate absorption of nutrients. The abnormally high blood glucose levels cause chemical changes in nerves and in pacemaker cells which regulate digestive processes in the gut, and damage blood vessels that carry oxygen and nutrients to cells.

“If these data are confirmed in humans, it may point toward a treatment for this difficult problem,” says Gianrico Farrugia, M.D., Mayo Clinic gastroenterologist and senior author on the study. “Our goal is to normalize gastric emptying and therefore improve a patient’s quality of life and glucose control.”

Science Behind the Findings

Previous studies in animals and humans showed that two aspects of gastroparesis were: 1) loss of Kit, a marker for interstitial cells of Cajal (ICC), and 2) loss of expression of neuronal nitric oxide synthase (nNOS). ICC cells produce electrical signals that regulate muscle contraction in the digestive tract. nNOS generates nitric oxide, which transmits nerve impulses in the digestive tract. Both are important for normal functioning but can be depleted by oxidative stress (an imbalance in ionic charges at the molecular level), a problem common in diabetes that also can lead to heart and kidney damage.

The research team decided to test a molecule known to protect cells against oxidative injury -- heme oxygenase-1 (HO1). The team measured gastric emptying in a set of diabetic mice and then looked at expression of HO1. Results showed that production of HO1 was lost in all mice with gastroparesis and nNOS expression was decreased. When the team induced HO1 production by introducing hemin, a red blood derivative, gastric emptying returned to normal and Kit and nNOS expression were restored, despite the diabetes. The team says that future research should target the HO1 pathway as a means of reversing the affects of diabetic gastroparesis.

Others researchers were Kyoung Moo Choi, Ph.D.; Simon Gibbons, Ph.D.; Tien Hguyen; Gary Stoltz; Matthew Lurken; Tamas Ordog, M.D.; and Joseph Szurszewski, Ph.D., all of Mayo Clinic. The research was funded by the National Institutes of Health.

Posted by dlife at 10:21 AM | Comments (0)

Liraglutide Improves Glucose Control And Increases Weight Loss In Type 2 Diabetes Patients

September 24, 2008 (EurekAlert) - Liraglutide, a new treatment for type 2 diabetes, improves blood glucose control compared with a conventional oral treatment glimepiride. Patients given liraglutide injections also recorded increases in weight loss and decreases in blood pressure. These are the conclusions of an Article published early Online and in an upcoming edition of The Lancet, written by Dr Alan Garber, Baylor College of Medicine, Houston, TX, USA, and colleagues.

In this randomised-controlled phase III trial, 746 patients with early type 2 diabetes were assigned to once daily liraglutide 1.2mg, (251 patients) or 1.8mg (247 patients) or glimepiride 8mg (248 patients) for one year. The primary outcome was the change in proportion of glycosylated haemoglobin* (HbA1c). Patients in the three groups had a mean HbA1c of 8.3-8.4% at baseline. The researchers found that HbA1c decreased by 0.51% in the glimepiride group, while in the liraglutide 1.2mg group the reduction was 0.84% and in the liraglutide 1.8mg group it was 1.14%. Proportions of patients achieving HbA1c of both less than 7.0% and less than 6.5% (two internationally accepted targets) were higher for both liraglutide group patients than for glimepiride patients, in both patients who had been receiving treatment before and those who were treatment naive. Five patients in the liraglutide 1.2mg, one in the 1.8mg group and none in the glimepiride group discontinued treatment because of vomiting.

Further, the researchers found that participants in the liraglutide groups lost weight (around 2kg) while those in the glimepiride group gained weight (1kg), when adjusted for the effects of nausea. Systolic blood pressure fell by 0.7 mm Hg in the glimepiride group, compared with 2.1mg Hg in the liraglutide 1.2mg group and 3.6mm Hg in the liraglutide 1.8 mg group. These blood pressure results were only statistically significant for the liraglutide 1.8 mg group versus glimepiride.

The authors conclude: "Treatment with liraglutide as monotherapy provided better glycaemic control for 52-weeks than did glimepiride, a traditional first-line therapy for type 2 diabetes mellitus, in participants previously treated with either diet and exercise or oral antidiabetic monotherapy. Liraglutide improved glycaemic control with a low rate of hypoglycaemia...On the basis of these results, we conclude that liraglutide is safe and effective as initial pharmacological therapy for type 2 diabetes mellitus and has advantages over other drugs used in monotherapy, such as greater reductions in weight, the number of hypoglycaemic events, and systolic blood pressure."

In an accompanying Comment, Dr Sten Madsbad, Hvidovre Hosptial and University of Copenhagen, Denmark, says that treatments such as liraglutide offer new options in the treatment of type 2 diabetes, but adds that their final role "remains to be clarified, after carefully conducted long-term trials with cardiovascular endpoints and safety data."

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

Weight Loss Surgery May Be Associated with Bone Loss

September 23, 2008 Newswise — Weight loss surgery may be linked to deficiencies in calcium and vitamin D and bone loss, according to a new study accepted for publication in The Endocrine Society’s Journal of Clinical Endocrinology & Metabolism (JCEM).

With the growing epidemic of obesity, many people are opting for surgical procedures to help promote weight loss. While these procedures result in significant and sustained weight loss and reverse many of the complications of obesity, this new study shows there may be harmful effects on calcium and bone metabolism.

“Our research shows that deficiencies of calcium and vitamin D absorption occur following gastric bypass surgery,” said Dr. Shonni J. Silverberg, professor of medicine at Columbia University College of Physicians & Surgeons in New York, N.Y., and coauthor of the study. “When analyzing hip bone density, we found that those who lost the most weight also lost the most bone.”

In this study, researchers evaluated 23 morbidly obese men and women who underwent gastric bypass surgery. Dr. Silverberg and her colleagues measured serum calcium, vitamin D, and parathyroid hormone levels before surgery and at three, six, and twelve months after surgery. Researchers also measured bone mineral density before and after surgery using dual-energy x-ray absorptiometry (DXA). One year after weight loss surgery, patients had lost an average of 99 pounds and had significant declines in hip bone mineral density (both total hip and femoral neck measurements).

“The calcium and vitamin D deficiencies may be due to the alterations in the gastrointestinal tract that take place during these procedures,” said Dr. Silverberg. “These deficiencies may be restored if the amount of calcium and vitamin D supplementation is increased appropriately.”

The findings from this study highlight the importance of assessing calcium sufficiency and skeletal health in the increasing numbers of individuals undergoing these procedures, said Dr. Silverberg. She adds that further studies are needed to discover how these findings relate to bone quality and fracture risk.

Other researchers working on the study include J. Fleischer, E.M. Stein, M. Della Badia, D.J. McMahon, M. Bessler, N. Restuccia, and L. Olivero-Rivera of Columbia University College of Physicians in New York, N.Y.

The article “The Decline in Hip Bone Density Following Gastric Bypass Surgery is Associated with Extent of Weight Loss,” will appear in the October issue of JCEM.

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 dlifenews at 11:50 AM | Comments (0)

'Friendly' Bacteria Protect Against Type 1 Diabetes, Yale Researchers Find

September 21, 2008 (EurekAlert) - In a dramatic illustration of the potential for microbes to prevent disease, researchers at Yale University and the University of Chicago showed that mice exposed to common stomach bacteria were protected against the development of Type I diabetes.

The findings, reported in the journal Nature, support the so-called "hygiene hypothesis" – the theory that a lack of exposure to parasites, bacteria and viruses in the developed world may lead to increased risk of diseases like allergies, asthma, and other disorders of the immune system. The results also suggest that exposure to some forms of bacteria might actually help prevent onset of Type I diabetes, an autoimmune disease in which the patient's immune system launches an attack on cells in the pancreas that produce insulin.

The root causes of autoimmune disease have been the subject of intensive investigation by scientists around the world.

In the past decade, it has become evident that the environment plays a role in the development of some overly robust immune system responses. For instance, people in less-developed parts of the world have a low rate of allergy, but when they move to developed countries the rate increases dramatically. Scientists have also noted the same phenomenon in their labs. Non-obese diabetic (NOD) mice develop the disease at different rates after natural breeding, depending upon the environment where they are kept. Previous research has shown that NOD mice exposed to killed (i.e., non-active) strains of tuberculosis or other disease-causing bacteria are protected against the development of Type I diabetes. This suggests that the rapid "innate" immune response that normally protects us from infections can influence the onset of Type 1 diabetes.

In the Nature paper, teams led by Li Wen at Yale and Alexander V. Chervonsky at the University of Chicago showed that NOD mice deficient in innate immunity were protected from diabetes in normal conditions. However, if they were raised in a germ-free environment, lacking "friendly'' gut bacteria, the mice developed severe diabetes. NOD mice exposed to harmless bacteria normally found in the human intestine were significantly less likely to develop diabetes, they reported.

"Understanding how gut bacteria work on the immune system to influence whether diabetes and other autoimmune diseases occurs is very important," Li said. "This understanding may allow us to design ways to target the immune system through altering the balance of friendly gut bacteria and protect against diabetes."

Posted by dlife at 10:54 AM | Comments (0)

Type 1 Diabetes May Result From Good Genes Behaving Badly

September 19. 2008 (EurekAlert) - WHAT: New research from Stanford University scientists suggests that type 1 diabetes, an autoimmune disease that develops in children and young adults, may not be due to bad genes but rather to good genes behaving badly.

Because type 1 diabetes typically runs in families, scientists have looked for inborn genetic errors or gene variants passed on from generation to generation. Although this search has failed to find a single type 1 diabetes gene, many candidate type 1 diabetes susceptibility genes have been identified. These susceptibility genes, located in a region known as the major histocompatibility complex (MHC), help the body distinguish its own cells and tissues from those that are foreign.

Studies in identical twins, however, reveal that the situation is more complicated: often one twin develops type 1 diabetes while the other twin remains disease-free. This pattern of good luck/bad luck led researchers at Stanford to examine whether genetically at-risk individuals respond differently to environmental stimuli. In some cases, the immune system will respond in a benign fashion, while in other cases it will begin an inflammatory response that can ultimately lead to diabetes. The critical difference between health and disease might thus reside not in an individual's genetic blueprint but in how those genes are "expressed"--that is, how the translation of genetic information into proteins or RNA is switched on and off.

In a study supported by the National Institute of Allergy and Infectious Diseases, (NIAID) part of the National Institutes of Health, the Stanford team, led by C. Garrison Fathman, M.D., studied differences in gene expression between two groups of mice. The first group, non-obese diabetic mice, spontaneously develop type 1 diabetes. The second group, mice genetically identical to the first group except for their MHC genes, do not develop the disease. The researchers looked at gene expression in three different tissues in the diabetic and non-diabetic mice at separate times after birth. In the first few weeks of life, they found an explosion of changes in gene expression in the pancreatic lymph nodes, spleen and circulating blood cells of the diabetic mice compared with those in the non-diabetic mice. At 8 weeks, this activity had quieted down. But several weeks later, when the mice were 12 weeks old, a second explosion of changes in gene expression occurred in the diabetic mice in all three tissues examined: pancreatic lymph nodes, spleen and blood cells.

According to Dr. Fathman, the results suggest that type 1 diabetes may not result from genetic mutations but from differences in how normal genes and gene variants are turned on and off during disease progression. In addition to identifying altered genes that may indicate potential avenues for therapeutic or preventive treatments, the authors also found patterns of coordinated gene expression that may prove useful as biomarkers of disease onset or progression.

Posted by dlife at 10:51 AM | Comments (0)

High Blood Pressure Takes Big Toll On Small Filtering Units Of The Kidney

September 19, 2008 (EurekAlert) - Take a kidney out of the body and it still knows how to filter toxins from the blood.

But all bets are off in the face of high blood pressure.

"How does the kidney know how to do it and why does it break in hypertension?" says Dr. Edward W. Inscho, physiologist in the Medical College of Georgia Schools of Medicine and Graduate Studies.

The kidneys filter about 200 quarts of plasma daily, eliminating about two quarts of waste product and extra water as urine, according to the National Institute of Diabetes and Digestive and Kidney Diseases. But the complete physiology remains a mystery.

He challenged colleagues to fill in important blanks in how this process works normally and how to make it work better in disease during the Sept. 19 Lewis K. Dahl Memorial Lecture at the 62nd High Blood Pressure Research Conference and Workshop in Atlanta.

One thing is clear: Hypertension takes a serious toll on the kidneys and damaged kidneys worsen hypertension. Dr. Inscho believes the kidneys' million hard-working filters, or glomeruli, are direct victims of high pressure. His research focuses on the minute arteries, or arterioles, that feed blood into each of them. These afferent arterioles are responsible for keeping blood pressure at a comfortable 60 mmHg inside glomeruli. At a healthy blood pressure of 120/80 mmHg, blood enters the artery at a mean pressure of 100 mmHg, but higher pressures mean the arterioles must work even harder to reach the 60 mmHg target. They seem up to the task at least initially, contracting to make it harder for blood to pass and reducing pressure in the process. "We want to know how it does that," Dr. Inscho says as he watches the near instantaneous contraction.

He thinks he may at least know the messenger. The first reaction to high pressure actually is for the small vessel to stretch. That stretch prompts smooth muscle cells on the vessel wall to release ATP, a common molecule known as an energy source but also gaining acceptance as an extracellular messenger, he theorizes. "It's an action-reaction kind of event."

When he puts ATP on the vessel it rapidly constricts; when he blocks the ATP receptor it won't. Unfortunately ATP works best in the face of normal pressures: constricting pressure about 25 percent as opposed to 2-3 percent when it's high. Still there are plenty of questions. Whether ATP is really released by the initial stretching is a critical one, he says. Whether ATP really comes from smooth muscle cells is another.

University of Southern California researcher Dr. Janos Peti-Peterdi thinks high pressures tugging the tethers connecting smooth muscle cells to others in the blood vessel wall may really be what releases ATP, a theory Dr. Inscho presented during the Sept. 19 meeting. It may be that hypertension changes the attachment of those tethers so they don't respond and the blood vessel can't either.

"We are trying to figure out how all this fits together," says Dr. Inscho. Figuring out the critical steps of this "amazingly elegant, amazingly precise and very complicated" process will lead to better understanding of what gets corrupted by diseases such as hypertension and diabetes and maybe how to stop kidney destruction.

As scientists are finding with many diseases, Dr. Inscho says inflammation likely plays a big role. "We know we can make these animals hypertensive, treat them with anti-inflammatories and prevent this whole process from occurring," he says of glomeruli destruction. "I think that's pretty exciting, but we don't know exactly how we are doing that." Blood pressure is not affected, just the negative impact on the kidneys. Inflammation, he notes, is likely well-intended but ultimately ends up thickening blood vessel walls and hampering flexibility.

Posted by dlife at 10:49 AM | Comments (0)

Drinking Chamomile Tea May Help Fight Complications Of Diabetes

September 16, 2008 (Science Daily) - Drinking chamomile tea daily with meals may help prevent the complications of diabetes, which include loss of vision, nerve damage, and kidney damage, researchers in Japan and the United Kingdom are reporting.

The findings could lead to the development of a new chamomile-based drug for type 2 diabetes, which is at epidemic levels in this country and spreading worldwide, they note. Their study appears in the Sept. 10 issue of the ACS' Journal of Agricultural and Food Chemistry, a bi-weekly publication.

In the new study, Atsushi Kato and colleagues point out that chamomile, also known as manzanilla, has been used for years as a medicinal cure-all to treat a variety of medical problems including stress, colds, and menstrual cramps. Scientists recently proposed that the herbal tea might also be beneficial for fighting diabetes, but the theory hasn't been scientifically tested until now.

To find out, the researchers fed chamomile extract to a group of diabetic rats for 21 days and compared the results to a group of control animals on a normal diet. The chamomile-supplemented animals showed a significant decrease in blood glucose levels compared with the controls, they say. The extract also showed significant inhibition of both ALR2 enzymes and sorbitol, whose elevated levels are associated with increased diabetic complications, the scientists say.

Posted by dlife at 11:31 AM | Comments (0)

Higher Urinary Levels Of Commonly Used Chemical, BPA, Linked With Cardiovascular Disease, Diabetes

September 16, 2007 (EurekAlert) - Higher levels of urinary Bisphenol A (BPA), a chemical compound commonly used in plastic packaging for food and beverages, is associated with cardiovascular disease, type 2 diabetes and liver-enzyme abnormalities, according to a study in the September 17 issue of JAMA. This study is being released early to coincide with a Food and Drug Administration (FDA) hearing on BPA.

BPA is one of the world's highest production–volume chemicals, with more than two million metric tons produced worldwide in 2003 and annual increase in demand of 6 percent to 10 percent annually, according to background information in the article. It is used in plastics in many consumer products. "Widespread and continuous exposure to BPA, primarily through food but also through drinking water, dental sealants, dermal exposure, and inhalation of household dusts, is evident from the presence of detectable levels of BPA in more than 90 percent of the U.S. population," the authors write. Evidence of adverse effects in animals has created concern over low-level chronic exposures in humans, but there is little data of sufficient statistical power to detect low-dose effects. This is the first study of associations with BPA levels in a large population, and it explores "normal" levels of BPA exposure.

David Melzer, M.B., Ph.D., of Peninsula Medical School, Exeter, U.K., and colleagues examined associations between urinary BPA concentrations and the health status of adults, using data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004. The survey included 1,455 adults, age 18 through 74 years, with measured urinary BPA concentrations.

The researchers found that average BPA concentrations, adjusted for age and sex, appeared higher in those who reported diagnoses of cardiovascular diseases and diabetes. A 1-Standard Deviation (SD) increase in BPA concentration was associated with a 39 percent increased odds of cardiovascular disease (angina, coronary heart disease, or heart attack combined) and diabetes.

When dividing BPA concentrations into quartiles, participants in the highest BPA concentration quartile had nearly three times the odds of cardiovascular disease compared with those in the lowest quartile. Similarly, those in the highest BPA concentration quartile had 2.4 times the odds of diabetes compared with those in the lowest quartile.

In addition, higher BPA concentrations were associated with clinically abnormal concentrations for three liver enzymes. No associations with other diagnoses were observed.

"Using data representative of the adult U.S. population, we found that higher urinary concentrations of BPA were associated with an increased prevalence of cardiovascular disease, diabetes, and liver-enzyme abnormalities. These findings add to the evidence suggesting adverse effects of low-dose BPA in animals. Independent replication and follow-up studies are needed to confirm these findings and to provide evidence on whether the associations are causal," the authors conclude. "Given the substantial negative effects on adult health that may be associated with increased BPA concentrations and also given the potential for reducing human exposure, our findings deserve scientific follow-up."

Posted by dlife at 09:44 AM | Comments (0)

Study Identifies Factors Associated With Poor Weight Loss After Gastric Bypass Surgery

September 15, 2008 (EurekAlert) - Individuals with diabetes and those whose stomach pouches are larger appear less likely to successfully lose weight after gastric bypass surgery, according to a report in the September issue of Archives of Surgery, one of the JAMA/Archives journals.

Roux-en-Y gastric bypass surgery is the most common bariatric procedure in North America, according to background information in the article. During the procedure, surgeons create a smaller stomach pouch that restricts food intake and bypasses large sections of the digestive system. "When performed in high-volume centers and with a low rate of complications, gastric bypass provides sustained and meaningful weight loss, significant improvement in quality of life, improvement or resolution of obesity-associated comorbidities and extended life span," the authors write. "However, 5 percent to 15 percent of patients do not lose weight successfully, despite perceived precise surgical technique and regular follow-up."

Guilherme M. Campos, M.D., and colleagues at the University of California, San Francisco, examined data from 361 patients who underwent gastric bypass at one institution between 2003 and 2006. Poor weight loss was defined as losing 40 percent or less of excess body weight after 12 months and good weight loss as losing more than 40 percent of excess weight.

Twelve-month follow-up data were available for 310 of the patients, who had an average body mass index (BMI) of 52 before surgery. At follow-up, they had an average BMI of 34 and had lost an average of 60 percent of their excess body weight. A total of 38 patients (12.3 percent) had poor weight loss. After adjusting for other related factors, diabetes and having a larger size of the stomach pouch after gastric bypass surgery were independently associated with poor weight loss.

Individuals with diabetes may take insulin or other drugs that stimulate the production of fat and cholesterol, the authors note. "Other factors that may lead to weight gain in patients with diabetes include a 'protective' increase in caloric intake to treat episodes of hypoglycemia [low blood sugar], reduction of urinary glucose losses and sodium and water retention that are a direct effect of insulin on the distal tubule in the kidney," the authors write.

The restriction on dietary intake imposed by a small stomach pouch is one of the most important aspects of gastric bypass surgery, they note. Surveys suggest that many surgeons estimate pouch size using anatomical landmarks rather than using a sizing balloon. "As the use of gastric bypass continues to grow, we believe it is critical to stress the importance of and to teach the creation of the small gastric pouch and to better standardize the technique used for pouch creation," the authors write.

"We conclude that gastric bypass provides good or excellent weight loss for most patients," they continue. "However, diabetes mellitus and larger pouch size are independently associated with poor weight loss after gastric bypass. Changes in the use of diabetes medications may reduce the risk of poor weight loss among diabetics undergoing gastric bypass. Detailed attention to the creation of a small gastric pouch is essential for achieving the best results."

Posted by dlife at 11:05 AM | Comments (1)

American Diabetes Association Lauds U.S. Senate for Passing Landmark Legislation for Americans with Disabilities

September 11, 2008 (ADA) - The American Diabetes Association (ADA) applauds the U.S. Senate today, for passing S. 3406, the Americans with Disabilities Act Amendments Act, landmark legislation designed to protect Americans with disabilities from discrimination. This legislation, cosponsored by more than 70 Members of the Senate, is aimed at protecting the rights of Americans with diabetes and other serious illnesses who face discrimination. If signed into law, the act will be restored to its original intent to ensure that Americans with disabilities like chronic illnesses such as diabetes are protected from discrimination.

“We applaud the U.S. Senate for passing S. 3406, the Americans with Disabilities Act Amendments Act and we appreciate and recognize the leadership of Senators Tom Harkin (D-IA), Orrin Hatch (R- UT), Edward Kennedy, (D- Mass), Arlen Specter (R-PA) and Senate Leadership for moving this critical legislation forward," said Dan Kohrman, Chair of the American Diabetes Association’s Legal Advocacy Subcommittee. “The Senate’s support for this landmark civil rights bill illustrates its strong commitment to protecting hardworking, qualified individuals from unwarranted discrimination," said Kohrman. “Not only will these amendments restore the act to its original intent, the measure will restore dignity to the many Americans with disabilities who want to work but have been punished by a law that was narrowly interpreted."

The American Diabetes Association partnered with other disability rights organizations and members of the business community to work with Congress towards passage of this historic legislation. Now that the bill has pg 2 / U.S. Senate passes landmark legislation to protect Americans with Disabilities passed the Senate, the American Diabetes Association and community partners will work to see the bill signed into law this fall.

The American Diabetes Association is leading the fight against the deadly consequences of diabetes and fighting for those affected by diabetes. 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. For more information please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit www.diabetes.org. Information from both these sources is available in English and Spanish.

Posted by dlife at 03:46 PM | Comments (0)

Levemir® Demonstrates A 24-Hour Duration Of Action And Significant Weight Loss In Obese Patients – New Studies Announced

September 10, 2008 (Press Release) - Data released today at the European Association for the Study of Diabetes (EASD) Annual Meeting concludes that Levemir® (insulin detemir [rDNA origin] injection) is a once-daily treatment for diabetes patients after demonstrating a 24-hour duration of action in both type 1 and type 2 diabetes.1,2 Results from two other studies announced today reveal that Levemir® can lead to significant weight loss for insulin-naïve patients with type 2 diabetes3, and provides a similar blood glucose response as glargine with no significant difference in daily average consumption (DACON) or diabetes-related pharmacy costs4.

Once-daily Levemir® demonstrates 24-hour duration of action

The randomised, double-blind study by Bock et al1 demonstrates that once-daily Levemir® is effective over a 24-hour period (mean duration 23.3 hours) in type 1 diabetes patients and has a more consistent duration of action compared to insulin glargine1. This reflects other published research in which patients with type 2 diabetes achieve 24-hour glycaemic control with once-daily Levemir®.5
Weight benefit beyond glycaemic control

In another study presented today, a subset analysis of the PREDICTIVE™ study3, it was shown that insulin-naïve patients with type 2 diabetes and a BMI >35 kg/m2 experienced an average weight loss of up to -3.46 kg after 52 weeks of Levemir® treatment3.

“This data confirms that Levemir® provides a significant weight benefit for overweight or obese patients who are being initiated into insulin treatment. This weight advantage is important because weight gain is a common barrier to insulin initiation,” said Professor Helene Hanaire, Hospital Rangueil, Toulouse, France. “This weight advantage combined with the efficacy and convenience of Levemir®, which can be taken once daily, makes it a good option for overweight or obese diabetes patients who need to take insulin.”
Levemir® shows similar daily average consumption versus glargine

A retrospective analysis of insulin-naïve patients with type 2 diabetes enrolled in a major US health plan compared daily average consumption (DACON) of and glycaemic control with the insulins Levemir® and glargine, along with associated medical costs. Results showed that there was no difference in HbA1c values between Levemir® and insulin glargine cohorts, and no significant difference in DACON4.
About Levemir® (insulin detemir [rDNA origin] injection)

Levemir® (insulin detemir [rDNA origin] injection) is a long-acting modern insulin (insulin analogue) indicated for once- or twice-daily subcutaneous administration for the treatment of adults and children with type 1 diabetes mellitus and adult patients with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycaemia. Levemir® has a relatively flat action profile with up to 24-hour duration of action. It can be added to oral antidiabetic agents, or used in combination with rapid-acting insulin. Levemir® is available in FlexPen®, a prefilled insulin pen for easy, discreet dosing, and in vials. The dose should be taken in the evening, at dinner or before bedtime. Levemir® has been available for use in Europe since March 2004 and is currently approved in more than 50 countries worldwide.

Prescribing information for Levemir® is available by contacting Novo Nordisk or
visiting novonordisk.com.

Levemir® and FlexPen® are registered trademarks of Novo Nordisk A/S.

Posted by dlife at 09:02 AM | 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 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)

Dance To The Music: Learning And Exercising At YMCA Can Prevent Diabetes

September 9, 2008 (EurekAlert) - Community-based exercise organizations, such as the YMCA, are an effective tool in the fight against diabetes, according to a study by Indiana University School of Medicine researchers in the October 2008 issue of the American Journal of Preventive Medicine.

More than 60 million Americans have pre-diabetes, and most of them are unaware. Adults with pre-diabetes are at more than 10 times the normal risk for developing diabetes and at twice the risk for heart attack or stroke. Reaching this growing population is a concern for diabetes educators and physicians.

"Previous studies, such as the highly regarded national Diabetes Prevention Program, have shown that structured diet and physical exercise can significantly reduce the progression of pre-diabetes to diabetes. But these trials involved major lifestyle changes that are difficult to translate into large-scale, community-level programs. In our study we were able to train lay people in the community to deliver the program at the YMCA, an environment accessible to many people with pre-diabetes, to help them sustain lifestyle changes," said the study's principal author, Ronald Ackermann, M.D., M.P.H., IU School of Medicine assistant professor of medicine and an affiliated scientist of the Regenstrief Institute.

With more than 2,500 facilities serving more than 10,000 inner-city, suburban and rural communities nationwide and a long history of implementing successful health promotion programs, the YMCA is in a unique position to reach persons with pre-diabetes, according to Dr. Ackermann. In this study, 92 individuals were enrolled in two groups. The intervention group received a core curriculum involving 16 classroom-style meetings focused on building knowledge and skills for goal setting, self-monitoring and problem-solving. The control group was offered standard diabetes-prevention advice.

At the 4-6-month follow-up visit, body weight had decreased by 6 percent in the intervention participants and by 2 percent in the control participants. This was equal to a mean weight loss of 12.5 pounds for intervention participants and 4 pounds for the group that received the standard information. The difference in the amount of weight lost is a clinically meaningful and significant difference, as was the change in total cholesterol concentration, according to Dr. Ackermann. These differences persisted at the 12-14 month follow-up visits.

"This is the first study to demonstrate that the YMCA is a promising vehicle for the dissemination of the DPP lifestyle intervention into the community. In the DPP, a 5 percent weight loss was associated with a 58 percent reduction in risk of developing diabetes. In our pilot study, people at high risk for developing diabetes achieved and maintained a mean 6 percent reduction in baseline body weight and significant reductions in total cholesterol," he noted.

The study concludes, "By lowering the cost of and expanding the accessibility to diabetes-prevention services, the YMCA may serve not only to increase the number of individuals with pre-diabetes who have access to and can pay for evidence-based diabetes prevention; it may also provide a compelling model for health-plan reimbursement. This provides yet another compelling reason to develop and test novel strategies that link community-based program delivery with existing clinical services that could help to identify and activate more adults with pre-diabetes."

Posted by dlife at 09:18 AM | Comments (0)

Receptor Activation Protects Retina From Diabetes Destruction

September 9, 2008 (EurekAlert) - Diabetes can make the beautifully stratified retina look like over-fried bacon.

A drug known for it pain-relieving power and believed to stimulate memory appears to prevent this retinal damage that leads to vision loss, researchers say.

"The effects of this drug on retinal health are phenomenal," says Dr. Sylvia Smith, retinal cell biologist and co-director of the Vision Discovery Institute in the Medical College of Georgia School of Medicine. She's comparing retinal images from a diabetic mouse model treated with (+)- pentazocine to one that wasn't. Even to the untrained eye, the differences are dramatic.

The findings, published in the September issue of Investigative Ophthalmology & Visual Science, suggest such compounds that bind with the sigma receptor in the eye may be good treatments for the top two causes of vision loss: diabetic retinopathy and glaucoma.

Sigma receptors are ubiquitous in the body, but their role and what naturally activates them are unknowns. Recent research suggests sigma receptors help protect cells from stress by ensuring an adequate level of the properly folded proteins they need for normal function. Dr. Smith and others have shown that sigma receptors are located within the endoplasmic reticulum of cells, which controls protein synthesis and regulates calcium levels. When needed, the receptors appear to chaperone these proteins to the cell powerhouse, or mitochondria. Dr. Smith suspects sigma receptors help manage this hotbed of cell stress. In fact, sigma receptor binding with pentazocine increases with cellular stress.

This cell protection role could help explain the resilience of the retina, which receives light and transforms it to a neural impulse that goes to the brain. The retina can tolerate regular insults, such as the light or high blood sugar, and still function for years. In the case of diabetic retinopathy for example, nerve cell damage and death are gradual, eventually spurring new blood vessels in an apparent attempt to get more blood and oxygen to dying cells. Instead, blood vessel proliferation results in further vision loss.

Dr. Smith' lab is collaborating with other MCG investigators to breed mice without a sigma receptor to better understand the receptor's role and whether regular treatment with the drug has a similar dramatic impact on other animal models of retinal disease. "We need to know if we just hit it lucky with the Akita mouse or do we have something that could be of widespread benefit."

Interestingly, pentazocine's binding with sigma receptors didn't impact insulin levels. "It does not solve that problem of diabetes; however our findings do suggest that just because you are hyperglycemic does not mean you will have diabetic retinopathy," Dr. Smith says.

Her lab's studies of sigma receptors' potential to protect against diabetes' blinding cascade are pioneering but sigma receptors have become a hot topic. Scientists are exploring their potential to treat problems from Alzheimer's to brain tumors to depression. As of early September, there were 2,700 papers on sigma receptors in the literature, Dr. Smith says.

Posted by dlife at 09:14 AM | Comments (0)

Significant Improvement In Glycaemic Control Observed With NovoMix® 30 In Type 2 Diabetes Patients New To Insulin

September 9, 2008 (Press Release) - New data from IMPROVE™ - the largest ever observational study in diabetes – announced today at the European Association for the Study of Diabetes (EASD) Annual Meeting, have shown that treatment with premixed modern insulin NovoMix® 30 resulted in a significant 2.4 percentage point reduction in HbA1c levels in insulin-naïve patients.1 In patients who had previously received no pharmaceutical therapy, the improvement was even more pronounced, with a reduction of 3.2 percentage points.

This data, from a subgroup of 30,171 patients from the IMPROVE™ study, also confirmed that NovoMix® 30 achieved this significant improvement in glycaemic control without compromising safety - only 0.1% of patients reported major hypoglycaemia1.

Professor Kawamori of the Juntendo University School of Medicine in Tokyo, and lead investigator of the IMPROVE™ study in Japan, said the results were impressive. “They confirm that the vast majority of poorly controlled patients who are new to insulin can rely on a simple twice-daily injection of NovoMix® 30 to reduce their HbA1c to acceptable levels and subsequently improve their quality of life by a significant degree.”
Scale of poor diabetes control revealed

However, baseline data from IMPROVE™, published for the first time in this month’s International Journal of Clinical Practice2, highlights the damaging levels of HbA1c that many patients are allowed to reach before being treated with insulin.

In total, just over half of all patients in the study had an HbA1c of over 9% when they were enrolled, with the average HbA1c standing at 9.4%. This is significantly higher than the international target guidelines of =6.5% or <7%.3,4

Looking at the data per country, Japanese patients had the highest levels of HbA1c at the start of the study on average, and Japan also had the highest proportion of patients with HbA1c over 9%. This was closely followed by Russia, China and India, representing some of the nations with the highest prevalence of diabetes in the world.5

Reflecting the poor levels of glycaemic control, the highest levels of microvascular complications were seen in Japan, Russia, Greece and Italy, with over two thirds of Russian patients already showing signs of damage to their eyes. Macrovascular complications were evident in over half the Polish and Russian patients with 41% and 37% already showing signs of coronary heart disease, respectively.

“These high rates of micro- and macrovascular complications translate into a major healthcare burden worldwide. It confirms the widely held concerns about the continued delayed initiation of therapy, particularly insulin, in clinical practice,” said Professor Paul Valensi, Department of Endocrinology-Diabetology-Nutrition at the Paris Nord University in France and lead investigator of the IMPROVE™ study.

Posted by dlife at 09:04 AM | Comments (0)

JDRF-Funded Clinical Trial Demonstrates Continuous Glucose Monitoring Improves Blood Sugar Control

Study findings presented at the European Association for the Study of Diabetes meeting and reported in the New England Journal of Medicine indicate CGM can help type 1 diabetes patients lower HbA1c levels, better control diabetes

September 8, 2008 (EurekAlert) - Patients with type 1 diabetes who used continuous glucose monitoring (CGM) devices to help manage their disease experienced significant improvements in blood sugar control, according to initial results of a major multicenter clinical trial funded by the Juvenile Diabetes Research Foundation. Results from the study were presented today during the European Association for the Study of Diabetes (EASD) annual meeting in Rome, and portions of the data will be published in the October 2 issue of the New England Journal of Medicine, available on line today at nejm.org.

The CGM study is a randomized, controlled trial involving 322 patients spanning the age range of 8 to 72 years at 10 sites, which included academic, community, and managed care based practices at the Atlanta Diabetes Associates, the Joslin Diabetes Center, Kaiser Permanente Southern California, Nemours Children's Clinic - Jacksonville, FL, the Lucile Packard Children's Hospital at Stanford University, the Barbara Davis Center for Childhood Diabetes at the University of Colorado Denver, the University of Iowa, the University of Washington, and Yale University, and coordinated by the Jaeb Center for Health Research in Tampa, Florida. Patients were assigned to either CGM or a control group using standard blood sugar monitoring and were followed for 26 weeks to assess effects on blood sugar control, principally assessed by measurement of the HbA1c level. At enrollment into the study, patients had HbA1c levels of 7-to-10% (the goal for adults with type 1 diabetes generally is a level below 7% and for children and adolescents below 7.5-8%). Three age groups were analyzed separately: 8 to 14 years of age, 15 to 24 years of age, and 25 years of age or older.

Improvements in blood sugar control were greatest for CGM patients 25 years of age or older, whose HbA1c levels decreased (improved) during the study by an average of 0.53% compared with control patients (p<0.001); improvements in secondary measurements were also significantly greater in CGM patients, including the percentage of patients able to achieve an HbA1c level below 7%, or a 10% relative or 0.5% absolute drop in HbA1c. The improvement in HbA1c occurred without an increase in hypoglycemia (low blood sugar), which is the worry when attempting to tighten glucose control. In children aged 8-14 years old, the average decrease in HbA1c was not significantly different in the CGM and control groups; however, those in the CGM group were more likely to lower their HbA1c by at least 10% and achieve HbA1c levels below 7% compared with the control group. Fifteen-to-24-year-old CGM patients, as a group did not experience significant improvements in glucose control compared with the control group.

CGM use varied with age, averaging at least six days a week over the course of the trial in 83% of the patients 25 years and older, but dropping off to 30% of the 15 to 24 year olds and 50% of the 8 to 14 year olds (for whom CGM use typically involved their parents' assistance). Although the study was not specifically designed to assess the effect of frequency of CGM use on HbA1c, an analysis presented at EASD suggested that patients within all three age groups, including teens and young adults, who used the device at least six days a week had substantially lower HbA1c levels after six months compared with patients who used CGM less than six days a week.

"These results are very important, because they show that continuous glucose monitors are more than simply devices of convenience for people with diabetes – they are tools that can substantially improve blood sugar control when used regularly," said Dr. Aaron Kowalski, Program Director for Metabolic Control at JDRF. "Based on the findings of previous studies, better control of glucose levels over the long term can be expected to translate to a lower risk of complications for people with Type 1 diabetes.

The lower levels of regular CGM use among children and teenagers observed in this study underscore the importance of continued research into a closed-loop artificial pancreas – a device that uses CGM data to administer appropriate doses of insulin through a pump without the need for involvement of the patient or for young children their parents."

Posted by dlife at 04:32 PM | Comments (0)

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 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)

Nine Out Of 10 Children With Diabetes Lack Support At School

September 8, 2008 (Press Release) - Novo Nordisk, together with the International Society for Pediatric and Adolescent Diabetes (ISPAD), today presented the results from the largest international survey exploring the psychosocial aspects of childhood diabetes. The DAWN Youth (Diabetes, Attitudes, Wishes and Needs) survey draws an alarming portrait of the various challenges that children with diabetes face at school:

Six out of 10 children with diabetes do not manage their diabetes successfully in school (according to their physicians)

Nine out of 10 cannot rely on a school nurse to assist them with their diabetes during school

Indications are that children with diabetes drop out of school earlier than others.

In addition, the survey highlights the lack of awareness and appropriate measures taken such as available school nurses or school staff to answer to the needs of children with diabetes in a school environment. And the consequences of poor diabetes management are frightening: if the blood sugar level is too high or too low the child can feel ill, lose concentration or in worst case, suffer from an insulin shock. Poorly regulated diabetes can, in the long run, lead to severe complications to the heart or kidneys. All this can easily be prevented by good and proper diabetes care and support.

“The situation for children with diabetes in school today is unacceptable. The risks that children face due to poor support in school environments are serious and life-threatening. The DAWN Youth survey results indeed highlight the importance of dealing with the problems of diabetes in relation to children. The conditions for children with diabetes in school can only be changed when parents, school staff and healthcare providers work together – each taking their part of the responsibility,” says Professor Thomas Danne, secretary general of ISPAD.
Need for unified action

Diabetes is one of the most common chronic diseases in childhood and can strike children at any age. Today, more than 200 children a day develop diabetes and the disease poses a severe burden for these children and their families as it affects them physically, mentally and socially. Therefore, children with diabetes need permanent attention from their families and surroundings.

“It is very important to involve families and the education system, starting from primary school. An example for all: we should replace automatic snack vendors with the option of eating fruit and vegetables. We can summarise this lifestyle in a slogan, so that it is easier to understand for children: more sport and nature, less snacks,” declares Italian Senator Emanuela Baio, secretary of the Senate President’s Committee and member of the Parliamentary Committee for Children.

Drawing on coordinated research and advocacy across countries, a variety of initiatives are being facilitated via the DAWN Youth initiative to promote access to adequate education and psychosocial support to families affected by diabetes worldwide. For example, the US DAWN Youth has given substantial support to the training aspects of the American Diabetes Association’s ‘Safe at School’ programme. The programme offers advocacy training for school nurses, school policymakers, educators, parents and other advocates on challenges and strategies in school diabetes care.

“Novo Nordisk strongly believes that all children with diabetes have a right to equal access to education as well as a safe environment at school. Novo Nordisk will continue supporting initiatives that highlight conditions of children with diabetes, raise childhood diabetes awareness and continue to give children with diabetes and their parents a voice,” says Lise Kingo, executive vice president and chief of staffs at Novo Nordisk.

About the DAWN Youth survey
The DAWN Youth survey was carried out in 2007–2008 in order to gather information on diabetes and its influence on the lives of children and young people with diabetes. Schools have been one of the focus areas in the survey. The respondents in the survey were young people with diabetes, parents or caregivers of at least one child with diabetes, and healthcare professionals. 9,200 respondents from 13 different countries participated in the survey.

For more information and background about the DAWN Youth initiative please visit dawnyouth.com.

Posted by dlife at 09:00 AM | Comments (0)

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

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)

“Healthy” Individuals May Be at Risk for Heart Disease

September 5, 2008 (EurekAlert) - In the face of a growing obesity epidemic in the United States, researchers at Wake Forest University Baptist Medical Center have new study results that indicate that how much fat a person has is not as important as where that fat is located when assessing risk for cardiovascular events and metabolic disease.

“We are facing an obesity epidemic, which obviously affects many things – metabolic abnormalities, cardiovascular disease, etc.,” said Jingzhong Ding, M.D., lead researcher and an assistant professor of gerontology. “Now we are finding out that where the fat is distributed is of high importance.”

The findings of the study, funded by the National Heart, Lung and Blood Institute and the National Institutes of Health, will appear in the September issue of the American Journal of Clinical Nutrition, a publication of the American Society for Nutrition.

For the study, researchers used cardiac and CT scans to measure multiple fat depots in 398 white and black participants from Forsyth County, N.C., ages 47-86. They found that the amount of fat a person had deposited around organs and in between muscles (nonsubcutaneous fat) had a direct correlation to the amount of hard, calcified plaque they had. Calcified plaque itself is not considered risky, but it is associated with the development of atherosclerosis, or the presence of less stable, fatty deposits in the blood vessels that can lead to heart attack and stroke.

“Our hypothesis was that this kind of fat is quite different from subcutaneous fat, or fat just below the skin,” Ding said. “Subcutaneous fat may not be as bad as having fat deposited around organs and in between muscles.”

Last month, Ding published results of a similar study showing that fat deposited around the heart (pericardial fat) is associated with calcified plaque in the arteries and therefore may be worse than having a high BMI or a thick waist.

“For the previous study, our hypothesis was that pericardial fat released inflammatory cytokines and free fatty acids directly into the coronary arteries, leading to endothelial dysfunction, which initiates atherosclerosis,” Ding said.

Ding is continuing long-term studies to investigate whether individuals with excessive fat deposited in and around organs and muscles may be at higher risk of cardiovascular disease and cardiac events regardless of overall body fat.

“We know that even thin people could have excessive non-subcutaneous fat,” Ding said. “If this hypothesis is confirmed, we should look for ways to specifically target the non-subcutaneous fat depot.”

Co-researchers were Stephen B. Kritchevsky, Ph.D., Fang-Chi Hsu, Ph.D., Gregory L. Burke, M.D., and J. Jeffrey Carr, M.D., all of Wake Forest; Tamara B. Harris, M.D., of the National Institute on Aging; Robert C. Detrano, M.D., Ph.D., of the Los Angeles Biomedical Research Institute; Moyses Szklo, M.D., Dr. P.H., of the Johns Hopkins Bloomberg School of Public Health; Michael H. Criqui, M.D., and Matthew Allison, M.D., both of the University of California’s Department of Family and Preventative Medicine; Pamela Ouyang, M.B.B.S., of Johns Hopkins University School of Medicine; and Elizabeth R. Brown, Sc.D., of the University of Washington.

Wake Forest University Baptist Medical Center (www.wfubmc.edu) is an academic health system comprised of North Carolina Baptist Hospital, Brenner Children’s Hospital, Wake Forest University Physicians, and Wake Forest University Health Sciences, which operates the university’s School of Medicine and Piedmont Triad Research Park. The system comprises 1,154 acute care, rehabilitation and long-term care beds and has been ranked as one of “America’s Best Hospitals” by U.S. News & World Report since 1993. Wake Forest Baptist is ranked 32nd in the nation by America’s Top Doctors for the number of its doctors considered best by their peers. The institution ranks in the top third in funding by the National Institutes of Health and fourth in the Southeast in revenues from its licensed intellectual property.

Posted by dlife at 10:18 AM | Comments (0)

Bisphenol A Linked to Metabolic Syndrome in Humans

September 4, 2008 (UC Healthnews) - New research from the University of Cincinnati (UC) implicates the primary chemical used to produce hard plastics—bisphenol A (BPA)—as a risk factor for the metabolic syndrome and its consequences.

In a laboratory study, using fresh human fat tissues, the UC team found that BPA suppresses a key hormone, adiponectin, which is responsible for regulating insulin sensitivity in the body and puts people at a substantially higher risk for metabolic syndrome.

Metabolic syndrome is a combination of risk factors that include lower responsiveness to insulin and higher blood levels of sugar and lipids. According to the American Heart Association, about 25 percent of Americans have metabolic syndrome. Left untreated, the disorder can lead to life-threatening health problems such as coronary artery disease, stroke and type 2 diabetes.

Nira Ben-Jonathan, PhD, and her team are the first to report scientific evidence on the health effects of BPA at environmentally relevant doses equal to “average” human exposure. Previous studies have primarily focused on animal studies and high doses of BPA.

They report their findings in the Aug. 14, 2008, online edition of the journal Environmental Health Perspectives. This scientific data comes just before a key Federal Drug Administration meeting about the safety of the chemical in consumer products scheduled for Sept. 16, 2008.

“People have serious concerns about the potential health effects of BPA. As the scientific evidence continues to mount against the chemical, it should be given serious attention to minimize future harm,” says Ben-Jonathan, a professor of cancer and cell biology at UC who has studied BPA for more than 10 years.

“Experimenting with human tissue is the closest we can come to testing the effects of BPA in humans. It’s a very exciting breakthrough because epidemiological studies looking at BPA effects on humans are difficult since most people have already been exposed to it,” she adds.

Scientists estimate that over 80 percent of people tested have measurable BPA in their bloodstream. The UC study was designed to mimic a realistic human exposure (between 0.1 and 10 nanomolar) so that