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

May 08, 2008

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

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

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

American Association of Clinical Endocrinologists Endorses National Diabetes Goal

May 07, 2008

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

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

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

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

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

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

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

Researchers Important Markers Of High Risk Of Type 2 Diabetes

April 29, 2008

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

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

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

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

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

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

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

April 17, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

April 16, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

April 08, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

April 02, 2008

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

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

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

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

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

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

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

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

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

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

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

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

Posted by dlife at 02:24 PM | Comments (22)

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

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

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

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

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

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

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

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

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

Michigan Tech Researchers Link 11 Genetic Variations to Type 2 Diabetes

April 01, 2008

Doing the math: New statistical methods can pinpoint problem genes

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

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

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

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

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

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

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

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

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

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

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

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

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

Potential Association of Type 2 Diabetes Genes with Prostate Cancer

March 30, 2008

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

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

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

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

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

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

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

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

A Ton of Bitter Melon Produces Sweet Results for Diabetes

March 26, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

A Link Between Antidepressants and Type 2 Diabetes

March 25, 2008

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

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

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

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

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

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

Previously Unrecognized Testosterone Deficiency Common in Men with Type 1 Diabetes

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

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

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

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

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

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

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

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

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

Scientists Link 11 Genetic Variations to Type 2 Diabetes

March 24, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

March 10, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

Chronically Elevated Blood Sugar Levels Disable 'Fasting Switch'

March 06, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

Type 2 Diabetes May Be Caused by Intestinal Dysfunction

March 05, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Study Shows Cholesterol-lowering Power of Dietitian Visits

March 04, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Overweight Hispanic Children Shown To Have Vascular Inflammation

February 27, 2008

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

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

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

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

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

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

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

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

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

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

Caballero said such strategies must be culturally appropriate.

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

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

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

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

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

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

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

January 18, 2008

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

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

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

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

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

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

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

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

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

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

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

How Does Insulin Influence Resistin?

January 17, 2008

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

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

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

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

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

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

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

Researcher Uncovers Possible Explanation for Ties Between Diabetes, Heart Disease

January 11, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

By making a kit, the group hopes to considerably lower the price of testing. According to Levy, the test would cost about $30 and only have to be done once.

Posted by dlifenews at 04:40 PM | Comments (0)

Type 2 Diabetics Require Special Heart Care

January 11, 2008 (Newswise) — The worldwide obesity epidemic is of top concern to Dr. George A. Beller, Professor of Cardiology at the University of Virginia Health System. As he explains it, patients who are obese often have type 2 diabetes, a condition that requires special heart care.

Type 2 diabetes is the most common form of diabetes mellitus. People who have this condition are resistant to their insulin and often develop inflammation in their coronary arteries. Although type 2 diabetes commonly occurs in adults, an increasing number of overweight children and adolescents are also developing it.

Six years ago, Dr. Beller established one of the nation’s first combined Diabetes-Cardiovascular Disease clinics at UVA to care for diabetic patients with suspected or known heart disease. At the clinic, a cardiologist and an endocrinologist who specializes in diabetes use a team-based approach to treat patients.

“About 70 percent of diabetics die from cardiovascular disease,” notes Dr. Beller. “That’s why our clinic acts as if the diabetics we treat already have some degree of heart disease, even if they have never exhibited any signs of it.”

Treatment goals for diabetic patients without heart disease symptoms include reducing their LDL (bad cholesterol) to under 100, which often requires use of cholesterol lowering drugs like statins. “An LDL below 100 is the same level we aim for when treating someone who has had a heart attack,” says Dr. Beller. “We also focus on getting the patient’s systolic blood pressure below 135 and place them on aspirin.”

When treating a diabetic patient with heart disease, cardiologists have to get “extremely aggressive,” Dr. Beller says. “These people have a much greater risk of having a heart attack or dying of heart disease than someone who isn’t diabetic.”

Diagnostic testing is the first step in assessing diabetic patients whose symptoms suggest they may have heart disease. “Many obese type 2 diabetics who have heart disease may experience shortness of breath with exertion rather than chest pain. Such patients need to have stress testing with cardiac nuclear imaging or echocardiography to detect if they have severe blockages in their coronary arteries,” notes Dr. Beller.

When heart disease is detected, cholesterol goals become even more stringent. Treatment plans focus on getting a patient’s LDL under 70 and their HDL (good cholesterol) above 40.

As Dr. Beller notes, a crucial element of treatment is encouraging diabetics to make lifestyle changes that include weight loss and exercise. “Obesity is driving the epidemic of type 2 diabetes, and drugs alone will not solve the problem,” he says. “Obese people who lose just ten percent of their body weight can reverse inflammation of the arteries and reverse many other cardiometabolic abnormalities.”

Posted by dlifenews at 04:37 PM | Comments (0)

Carrot Cake Study on Sugar in Type 2 Diabetes

January 09, 2008

New study adds to new thinking on sugar in the diabetes diet

January 9, 2008 (EurekAlert) - Patients with type 2 diabetes are often advised to cut out sucrose (table sugar) all together. However, in recent years this traditional advice has been questioned by some researchers who suggest that moderate amounts of sugar can be safely consumed as part of the diet of patients with diabetes. Now a new study has been published that is consistent with this revised approach. It showed that patients who increased their daily sugar intake (in the form of carrot cake) but maintained a stable body weight, showed no adverse changes in their blood glucose.

The study was conducted by the Department of Nutrition and Dietetics at London’s Hammersmith Hospital. Three slices of carrot cake were added to the daily diets of nine, overweight type 2 diabetes patients over 24 days (bringing their daily total to 88g or 18 teaspoons of sugar). Consumption of the carrot cake slices was evenly distributed across the day. Several measurements were recorded at the beginning and end of the study, including the patients’ weight, blood sugar (glucose) levels, cholesterol levels, and insulin sensitivity (which is a measure of how well the body responds to the hormone insulin).

Professor Gary Frost, who led the study, explained ‘In this study, the energy intake of these patients was balanced to their body weight, and their sucrose intake was spread evenly over a day. Correspondingly, they did not gain weight or show an increase in blood glucose levels at the end of the study; in addition, their cholesterol levels and insulin sensitivity did not change.’ He added ‘the results of this small, short-term study support other scientific studies, which suggest that there could be more flexibility with sucrose in the diets of patients with type 2 diabetes. There is evidence from other studies (reviewed by Kirk et al 2000) that inclusion of sucrose may help people to lower their fat intake, which in turn may be beneficial to overall health’.

Professor Frost continued ‘This research is in line with the dietary guidelines set by the American Diabetes Association (2007), which state that sucrose does not cause a greater increase in blood glucose levels than an equivalent amount of starch. Therefore sucrose or sucrose-containing foods should be treated similarly to other carbohydrate containing foods by people with diabetes; either substituted for other carbohydrates in the total daily intake, or managed with appropriate diabetes medication.

Posted by dlifenews at 04:35 PM | Comments (8)

Lack of Deep Sleep May Increase Risk of Type 2 Diabetes

January 02, 2008

January 2, 2008 (EurekAlert) - Suppression of slow-wave sleep in healthy young adults significantly decreases their ability to regulate blood-sugar levels and increases the risk of type 2 diabetes, report researchers at the University of Chicago Medical Center in the “Early Edition” of the Proceedings of the National Academy of Science, available online as soon as Dec. 31, 2007.

Deep sleep, also called “slow-wave sleep,” is thought to be the most restorative sleep stage, but its significance for physical well-being has not been demonstrated. This study found that after only three nights of selective slow-wave sleep suppression, young healthy subjects became less sensitive to insulin. Although they needed more insulin to dispose of the same amount of glucose, their insulin secretion did not increase to compensate for the reduced sensitivity, resulting in reduced tolerance to glucose and increased risk for type 2 diabetes. The decrease in insulin sensitivity was comparable to that caused by gaining 20 to 30 pounds.

Previous studies have demonstrated that reduced sleep quantity can impair glucose metabolism and appetite regulation resulting in increased risk of obesity and diabetes. This current study provides the first evidence linking poor sleep quality to increased diabetes risk.

"These findings demonstrate a clear role for slow-wave sleep in maintaining normal glucose control," said the study's lead author, Esra Tasali, MD, assistant professor of medicine at the University of Chicago Medical Center. "A profound decrease in slow-wave sleep had an immediate and significant adverse effect on insulin sensitivity and glucose tolerance."

“Since reduced amounts of deep sleep are typical of aging and of common obesity-related sleep disorders, such as obstructive sleep apnea these results suggest that strategies to improve sleep quality, as well as quantity, may help to prevent or delay the onset of type 2 diabetes in populations at risk,” said Eve Van Cauter, PhD, professor of medicine at the University of Chicago and senior author of the study.

The researchers studied nine lean, healthy volunteers, five men and four women between the ages of 20 and 31. The subjects spent two consecutive nights in the sleep laboratory, where they went to bed at 11 P.M., slept undisturbed but carefully monitored, and got out of bed 8.5 hours later, at 7:30 A.M.

The same subjects were also studied for three consecutive nights during which they followed identical nighttime routines. During this session, however, when their brain waves indicated that they were drifting into slow-wave sleep they were subtly disturbed by sounds administered through speakers beside the bed.

These sounds were loud enough to disrupt deep sleep but not so loud as to cause a full awakening. This technique enabled the researchers to decrease slow-wave sleep by about 90 percent, shifting the subjects from the onset of deep sleep (stage 3 or 4) to a lighter sleep (stage 2) without altering total sleep time.

"Our system proved quite effective," Tasali said. When asked about the sounds the next morning, study subjects vaguely recalled hearing a noise "three or four times," during the night. Some recalled as many as 10 to 15. On average, however, subjects required about 250-300 interventions each night, fewer the first night but more on subsequent nights as "slow-wave pressure," the body's need for deep sleep, accumulated night after night.

"This decrease in slow-wave sleep resembles the changes in sleep patterns caused by 40 years of aging," Tasali said. Young adults spend 80 to 100 minutes per night in slow-wave sleep, while people over age 60 generally have less than 20 minutes. "In this experiment," she said, "we gave people in their 20s the sleep of those in their 60s."

At the end of each study, the researchers gave intravenous glucose (a sugar solution) to each subject, then took blood samples every few minutes to measure the levels of glucose and insulin, the hormone that controls glucose uptake.

They found that when slow-wave sleep was suppressed for only three nights, young healthy subjects became about 25 percent less sensitive to insulin. As insulin sensitivity decreased, subjects needed more insulin to dispose of the same amount of glucose. But for eight of the nine subjects, insulin secretion did not go up to compensate for reduced effects. The result was a 23 percent increase in blood-glucose levels, comparable to older adults with impaired glucose tolerance.

Those with low baseline levels of slow-wave sleep had the lowest levels after having their sleep patterns disrupted and the greatest decrease in insulin sensitivity.

The alarming rise in the prevalence of type 2 diabetes is generally attributed to the epidemic of obesity combined with the aging of the population. "Previous studies from our lab have demonstrated many connections between chronic, partial, sleep deprivation, changes in appetite, metabolic abnormalities, obesity, and diabetes risk," said Van Cauter. "These results solidify those links and add a new wrinkle, the role of poor sleep quality, which is also associated with aging."

"Chronic shallow non-REM sleep, decreased insulin sensitivity and elevated diabetes risk are typical of aging," the authors conclude. "Our findings raise the question of whether age-related changes in sleep quality contribute to the development of these metabolic alterations."

Posted by dlifenews at 10:28 AM | Comments (0)

Smoking Associated With Increased Risk of Diabetes

December 11, 2007

December 11, 2007 (Newswise) — A review of previous studies indicates that people who currently smoke have an increased risk of developing type 2 diabetes, compared with non-smokers, according to an article in the December 12 issue of JAMA.

A number of studies have examined the association between smoking and incidence of glucose abnormalities, and have suggested that smoking could be independently associated with glucose intolerance, impaired fasting glucose and type 2 diabetes, which could make smoking a modifiable risk factor for type 2 diabetes. However, it appears the quality and clinical features of these studies have not been fully assessed regarding this possible association.

Carole Willi, M.D., of the University of Lausanne, Switzerland, and colleagues conducted a systematic review and meta-analysis of studies describing the association between active smoking and the incidence of diabetes or other glucose metabolism irregularities. A search of databases yielded 25 studies, which were published between 1992 and 2006. The number of participants per study ranged from 630 to 709,827, for a total of 1.2 million participants. A total of 45,844 new cases of diabetes were reported during a study follow-up period ranging from 5 to 30 years.

Analysis of the data indicated that active smokers have a 44 percent increased risk of developing type 2 diabetes compared with non-smokers. Further analyses suggested a dose-response relationship between smoking and diabetes, with the association stronger for heavy smokers (20 or more cigarettes/day; 61 percent increased risk) compared with lighter smokers (29 percent increased risk).

The association also was weaker for former smokers (23 percent increased risk) than it was for active smokers.

“… we conclude that the relevant question should no longer be whether this association exists, but rather whether this established association is causal,” the authors write.

They add that observational primary studies cannot prove causality, but that the studies in this review do meet several recommended criteria for causation. “First, there is an appropriate temporal relationship: the cigarette smoking preceded diabetes incidence in all studies. Second, the findings are consistent with a dose-response relationship, with stronger associations for heavy smokers relative to lighter smokers and for active smokers relative to former smokers. … Third, there is theoretical biological plausibi