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)

Not All Fat Created Equal

May 06, 2008

May 6, 2008 (EurekAlert) - It has long been known that type 2 diabetes is linked to obesity, particularly fat inside the belly. Now, researchers at the Joslin Diabetes Center have found that fat from other areas of the body can actually reduce insulin resistance and improve insulin sensitivity.

In a study published in the May issue of Cell Metabolism, a team lead by C. Ronald Kahn, M.D. found that subcutaneous fat -- fat found below the skin, usually in the hips and thighs -- is associated with reduced insulin levels and improved insulin sensitivity.

“This points to a new opportunity to find substances made by subcutaneous fat that may actually be good for glucose metabolism,’’ said Dr. Kahn, Head of the Joslin Research Section on Obesity and Hormone Action and the Mary K. Iacocca Professor of Medicine at Harvard Medical School. “If we can identify how subcutaneous fat does this, we will have a big clue as to where to look for these substances.”

Kahn noted that obesity in the abdominal or visceral area -- the classic “beer belly” or “apple” shape -- increases the risk of diabetes and mortality, and said it has been thought that obesity in subcutaneous areas -- the “pear” shape -- might decrease such risks.

“We started out to answer the basic question of whether fat inside the belly is bad for you because of where it is located, or is abdominal fat itself different from fat in other places,” said Kahn, an internationally recognized researcher in diabetes and metabolism.

To test if the differences were due to anatomic location or intrinsic properties of the fat deposits themselves, transplantations were performed in mice. The researchers found that when subcutaneous fat was transplanted into the abdominal area, there was a decrease in body weight, fat mass, glucose and insulin levels and an improvement in insulin sensitivity. By contrast, transplantation of abdominal fat into either the abdominal or subcutaneous area had no effect.

The paper concludes that subcutaneous fat is intrinsically different from visceral fat and may produce substances that can improve glucose metabolism.

“The surprising thing was that it wasn’t where the fat was located,” Kahn said. “It was the kind of fat that was the most important variable. Even more surprising, it wasn’t that abdominal fat was exerting negative effects, but that subcutaneous fat was producing a good effect. Animals with more subcutaneous fat didn’t gain as much weight as they aged, had better insulin sensitivity, lower insulin levels and were improved all around.”

Earlier studies in humans had shown that removal of subcutaneous fat by liposuction does not result in improvement of any aspect of metabolic syndrome, a collection of medical problems related to insulin resistance, but none had focused on possible good effects of this subcutaneous fat. However, one human study did show that obese individuals with high levels of both intra-abdominal and subcutaneous fat were more insulin sensitive than those with only high levels of intra-abdominal fat.

In addition, Kahn noted that a class of diabetes drugs called thiazoladines may cause patients to gain weight in the subcutaneous area, yet also improve insulin sensitivity.

Kahn said it is possible that subcutaneous fat may be producing certain hormones, known as adipokines, which produce beneficial effects on metabolism. These effects may offset the negative effects produced by abdominal fat.

The next step is to identify how subcutaneous fat produces these substances that improve metabolism and then find the substances themselves with the idea of creating a drug that can do the same thing.

“We’re already trying to identify through the use of proteomics what is coming out of the different fat cells,” Kahn said.

Posted by dlife at 09:48 AM | Comments (0)

Blocked Brain Enzyme Decreases Appetite and Promotes Weight Loss

May 6, 2008 (EurekAlert) - Imagine being able to tone down appetite and promote weight loss, while improving the body’s ability to handle blood sugar levels.

That’s just what Tony Means, PhD, and his team at the Duke University Medical Center were able to do when they blocked a brain enzyme, CaMKK2, in mice.

“We believe we have identified an important drug development target that could potentially turn into a metabolic triple play: appetite control, weight loss and blood sugar management,“ said Means, who is the Nanaline H. Duke Professor and Chairman of Pharmacology and Cancer Biology.

For many years, scientists have been identifying and testing every step of the appetite stimulation and suppression pathways in search of a target. Such research is considered critical to finding ways for people to better control their weight and minimize their risk of developing diabetes, heart disease and other health conditions.

Activation of the enzyme CaMKK2 is just one step in the appetite stimulation pathway located in the hypothalamus section of the brain. An empty stomach releases the hormone ghrelin, which launches a cascade of signals that ultimately results in increased appetite.

Means and colleagues believed that CaMKK2 in the ghrelin pathway might be a likely candidate for study, because it activates AMPK, an enzyme that stimulates animals to eat and gain weight. They tested their theory in several ways, the results of which are published in the May issue of Cell Metabolism. The work was funded by NIH grants, as well as by the Australian Research Council, National Heart Foundation, and the National Health and Medical Research Council of Australia.

First they blocked CaMKK2 in mice with a specialized molecule inhibitor and then measured food intake. These mice ate significantly less food than untreated mice during the six days in which they were evaluated, and also lost body weight, which led the scientists to think they might be on to something.

Next they studied a group of mice that normally do not make CaMKK2 and found that the molecule inhibitor did not change feeding behavior or reduce weight. “The fact that blocking CaMKK2 worked in normal mice to make them eat less and lose weight, but not in mice missing the enzyme, provides compelling evidence that CaMKK2 signaling is a requirement for appetite control,” Means said.

They also studied both normal mice and mice missing CaMKK2 to learn how these types responded to low-fat and high-fat diets. After nearly 30 weeks on the specific diets, the normal mice on the high-fat diet became diabetic – they were unable to respond to insulin and weren’t able to manage blood sugar levels well. In contrast, the normal mice on a low-fat diet stayed healthy.

In mice missing CaMKK2, the scientists found that they stayed healthy regardless of whether they were on a low-fat or high-fat diet. The CAMKK2-negative mice apparently were protected from changes that lead to diabetes in a high-fat diet.

“Remarkably, we find that blocking CaMKK2 in the brain prevents the deposits of fat in liver and skeletal muscle that are characteristic of obese, diabetic patients,” Means said. “We find this very exciting and are trying to understand the mechanism responsible for this protective effect, as well as to identify more potent drugs to inhibit CaMKK2.”

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

Studies Test New Approaches to Islet Transplantation

May 01, 2008

May 1, 2008 (NIH) - Researchers from 11 medical centers in the United States, Canada, Sweden, and Norway have begun testing new approaches to transplanting clusters of insulin-producing islets in adults with difficult-to-control type 1 diabetes. The clinical studies, funded by the National Institutes of Health (NIH), will determine whether changes to current methods of islet transplantation lead to improved, long-lasting control of blood glucose with fewer side effects.

In islet transplantation, clusters of islets are extracted from a donor pancreas and infused into the recipient's liver. In a successful transplant, the islets become embedded in the liver and begin producing insulin.

"A major goal of the NIH research program in type 1 diabetes is to develop therapies that replace the insulin-producing cells destroyed by the autoimmune process," said NIH Director Elias A. Zerhouni, M.D. "These studies, which build on advances in immunology and transplantation research, may open the door to more widespread use of islet transplantation for patients with severe type 1 diabetes."

About 5 percent to 10 percent of the nearly 21 million people with diabetes have type 1, formerly known as juvenile onset diabetes or insulin-dependent diabetes. In type 1 diabetes, a person's own immune cells attack and destroy pancreatic beta cells, which produce the hormone insulin needed for survival. Beta cells, along with several other types of cells that work together to balance blood glucose, reside in islets, also known as islets of Langerhans, in the pancreas. Three or more insulin injections a day or treatment with an insulin pump are often needed to maintain blood glucose control, but most people with type 1 diabetes still develop complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys. Despite steady improvements in managing the disease, type 1 diabetes cuts lives short by about 15 years, with early deaths due mainly to heart attacks and strokes.

In 2000, a research team led by Dr. James Shapiro at the University of Alberta in Edmonton, Canada, reported sustained insulin independence in seven patients transplanted with islets from two to four donor pancreases and treated with an immunosuppressive regimen that omitted glucocorticoids, thought to be toxic to islets. In the next few years, other researchers replicated the "Edmonton protocol," and most centers adopted this approach to islet transplantation.

The protocol greatly benefits some patients with severe type 1 diabetes, but two or more infusions of islets are usually needed, and the islets tend to lose their insulin-producing function over time. Participating in an islet transplant study is appropriate for people with severe hypoglycemia (dangerously low levels of blood sugar) and for those with type 1 diabetes who have had a kidney transplant to treat kidney failure, a complication of diabetes.

Since the Edmonton advance, scientists have been working to lengthen the survival of donor islets and reduce the side effects — such as anemia, nerve and kidney damage, and vulnerability to infection — of drugs that prevent the body's destruction of donor islets. In the new studies, the researchers will culture islets before transplantation to enhance their viability. They will also compare specific anti-rejection drugs for the ability to maximize islet survival while reducing toxicity. As the procedure becomes safer and new sources of beta cells become available, more people are likely to benefit.

The researchers are conducting pilot, or phase 1/2, studies of experimental agents as well as phase 3 studies that modify the Edmonton protocol. If the phase 3 studies succeed in safely controlling blood glucose levels, the investigators may ask the Food and Drug Administration to approve the procedure for people with poorly controlled type 1 diabetes. (For information about the phases of clinical trials, see http://www.fda.gov/fdac/features/2003/503_trial.html.)

"If these approaches are successful in prolonging islet function with less drug toxicity, type 1 diabetes patients with severe problems controlling their blood glucose may have another treatment option for controlling their diabetes," said study chair Dr. Camillo Ricordi of the University of Miami.

The studies are enrolling individuals with type 1 diabetes who have serious difficulty controlling their blood glucose despite intensive medical therapy and who suffer from episodes of severe hypoglycemia (dangerously low levels of blood glucose). Also eligible are patients with severe hypoglycemia and hypoglycemia unawareness, who cannot sense a drop in blood glucose and may lose consciousness without warning. In addition, researchers are accepting type 1 diabetes patients who have had a kidney transplant and are already taking immunosuppressive drugs. For more information about the studies, call 1-877-IsletStudy (1-877-475-387-8839) or see http://www.citisletstudy.org/index.html.

The following researchers are conducting the studies:

* Dr. Camillo Ricordi, study chair
University of Miami
* Dr. Christian Larsen
Emory University, Atlanta
* Dr. Dixon Kaufman
Northwestern University, Chicago
* Dr. Bernhard Hering
University of Minnesota, Minneapolis
* Dr. Ali Naji
University of Pennsylvania, Philadelphia
* Dr. Peter Stock
University of California, San Francisco
* Dr. James Shapiro
University of Alberta, Edmonton, Canada
* Dr. Jose Oberholzer
University of Illinois at Chicago
* Dr. Aksel Foss
University Hospital Rikshospitalet, Oslo, Norway
* Dr. Olle Korsgren
Uppsala University Hospital, Uppsala, Sweden
* Dr. Annika Tibell
Karolinska University Hospital, Stockholm, Sweden

Dr. William Clarke oversees the Consortium's Data Coordinating Center at the University of Iowa.

Posted by dlife at 10:39 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)

Statins Shown to Lower Blood Pressure

April 14, 2008

April 14, 2008 (EurekAlert) - A large, randomized drug trial has shown for the first time that statin drugs result in a modest, but significant, reduction in blood pressure. These effects may contribute to the reduced risk of stroke and cardiovascular events reported for patients on statins, according to lead investigator Beatrice Golomb, M.D., Ph.D., associate professor of medicine at the University of California, San Diego School of Medicine and director of UC San Diego’s Statin Study.

The results of the double-blind, placebo-controlled study of 973 men and women in Southern California will be published in the April 14 edition of the journal Archives of Internal Medicine.

“Statins, of course, are known to lower LDL cholesterol levels, but lower LDL cholesterol levels are not generally linked to lower occurrence of stroke,” said Golomb. “However, lower blood pressure is strongly related to lower stroke risk, and these findings provide one means by which statins may reduce rates of stroke and other cardiovascular events in patients.”

Study participants had no known cardiovascular disease or diabetes. Equal numbers of participants were either given 20 milligrams of simvastatin, 40 milligrams of pravastatin or a placebo daily for six months. Reductions in both systolic and diastolic blood pressure readings occurred in patients taking both simvastatin and pravastatin, two forms of statin drugs.

“We found that statins lower both systolic and diastolic blood pressure, and that the effect extends to patients with pre-hypertension, those with normal blood pressure and persons not on blood-pressure lowering medications,” said Golomb. “While reductions in blood pressure with statins were measurable as early as one month into the trial, the lowered blood pressure was significant at six months.”

Posted by dlife at 01:44 PM | Comments (0)

People With Diabetes May Have All Natural Citrus Supplement

April 09, 2008

KGK Synergize Inc. presents Diabetinol, test results

April 9, 2008 (EurekAlert) - Two new studies presented at the Experimental Biology Annual Meeting suggest that an all-natural dietary supplement made from citrus may help people with type 2 diabetes lower their blood glucose numbers after a meal and their LDL-cholesterol levels.

Mal Evans, DVM, MSc, PhD, KGK Synergize Inc’s Scientific Director, said, “Our scientifically validated testing has consistently shown that Diabetinol™ improves blood glucose numbers. This time we saw a sizeable change in glucose intolerance in just a short time. This is good news for many of the 21 million Americans with diabetes. Tighter blood sugar control may mean less diabetic complications like nerve pain and kidney disease. And, that could mean less disability and expense from complications and associated medications and certainly less stress for the patient.

“Although there were no statistically significant changes in fasting blood glucose levels in either group, the Diabetinol™-treated subjects demonstrated an excellent favorable downward trend in their hemoglobin A1C levels. These results suggest that when administered to people with type 2 diabetes over a longer treatment period, Diabetinol™ significantly improves glucose tolerance or the blood glucose numbers following a meal.

“Additionally, the Diabetinol™-treated group showed improvements in LDL-cholesterol levels. An elevated LDL-cholesterol level is a risk factor for heart disease, and having type 2 diabetes increases an individual’s risk for developing heart disease two to four times. In fact, sixty-five percent of deaths from diabetes are related to cardiovascular causes such as heart attack and stroke,” said Evans.

Hemoglobin A1C is an indicator of average blood glucose control over two to three months and is correlated to an individual’s risk of developing diabetic complications such as diseases of the eye, kidney and nerves.

In a pilot study, twenty adults with diabetes who were taking oral diabetes medications were randomly assigned to receive either Diabetinol™ or a placebo twice per day for three months. Each subject had mildly to moderately elevated cholesterol levels at the start of the study as well.

After 84 days, the group receiving Diabetinol™ showed a significant 19 percent reduction in glucose intolerance measured as peak changes in blood glucose over the four hours of a standard oral glucose challenge. The placebo group showed no significant improvements in glucose intolerance. A standard glucose challenge involves ingesting 100 grams of glucose and having blood glucose measurements after 30 minutes and hourly for four hours. Neither the investigators nor the volunteers knew who was receiving the Diabetinol™ or the placebo.

The number of Americans with diabetes has been increasing as obesity rates continue to rise. At least 90% of Americans with diabetes have type 2 diabetes. In type 2 diabetes, the body either produces too little insulin or the cells do not respond properly to the insulin and leave the cells starved for energy while raising the blood glucose level.

Earlier animal studies led researchers to test Diabetinol in humans. Twelve hamsters were treated with a special high-fructose diet to induce diabetes-like symptoms including increased blood glucose, insulin, cholesterol and triglyceride levels. Half of the animals were then given Diabetinol™ for 42 days. The other six hamsters were given no anti-diabetic treatment. At the end of the study, the Diabetinol™-treated animals showed improvements in each blood glucose, insulin, and cholesterol and triglyceride levels.

Taken together, these studies suggest that Diabetinol™ may help lower blood glucose levels and be beneficial in lowering the risks of heart disease and diabetic complications in people with type 2 diabetes.

An additional six-month study is underway to evaluate Diabetinol™ treatment in a larger sample of people with type 2 diabetes.

Posted by dlife at 09:47 AM | Comments (1)

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)

Crestor Outcomes Study JUPITER Closes Early Due To Unequivocal Evidence Of Benefit

March 31, 2008

March 31, 2008 (Press Release) - AstraZeneca today announced it has decided to stop the CRESTOR JUPITER clinical study early based on a recommendation from an Independent Data Monitoring Board and the JUPITER Steering Committee, which met on March 29, 2008. The study will be stopped early because there is unequivocal evidence of a reduction in cardiovascular morbidity and mortality amongst patients who received CRESTOR when compared to placebo.

JUPITER (Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin) was designed to determine if treating patients with no evidence of pre-existing cardiovascular disease and low to normal LDL-C but elevated C-reactive protein (CRP) with CRESTOR 20mg once daily would reduce major cardiovascular events. CRP is a recognized marker of inflammation and is associated with an increased risk of atherosclerotic cardiovascular events.

The JUPITER study team has initiated activities to close this large multi-centre study. Over 15,000 trial participants will be scheduled by their investigator for final assessments at over 1,200 sites in 26 countries. Data from these visits will be collected and reviewed to allow a full and complete analysis and final results of the study will be published once the analysis is complete.

JUPITER is one study from the global research initiative known as the GALAXY programme, which has now recruited more than 64,000 patients from 55 countries worldwide, to investigate the impact of CRESTOR on cardiovascular risk reduction and patient outcomes.

Posted by dlife at 03:22 PM | Comments (1)

Once-Daily Basal Insulin Glargine vs. Thrice-Daily Prandial

March 27, 2008

Insulin glargine as good at controlling blood sugar as insulin lispro but simpler and more liked by patients

March 27, 2008 (EurekAlert) - The use of insulin glargine, (a single injection of daily insulin) is as effective at controlling blood sugar for people with diabetes as insulin lispro (which has to be injected up to three times a day), and is associated with increased satisfaction among users. These are the conclusions of authors of an Article published in this week’s edition of The Lancet.

The use of insulin glargine, (a single injection of daily insulin) is as effective at controlling blood sugar for people with diabetes as insulin lispro (which has to be injected up to three times a day), and is associated with increased satisfaction among users. These are the conclusions of authors of an Article published in this week’s edition of The Lancet.

Controlling blood sugar can help people with diabetes avoid the occurrence of microvascular events (eg, retinopathy) and, to a lesser extent, macrovascular complications. Blood sugar control is measured using the concentration of haemoglobin A1c in the blood, and concentrations less than 7% (optimally less than 6.5%) can substantially reduce the risk of these complications. The amount of haemoglobin A1c is directly related to the amount of sugar in the blood.

Professor Reinhard G Bretzel, Justus-Liebig-Universität Giessen, Germany, and colleagues did the APOLLO study, a 44-week trial of 418 patients with type 2 diabetes in 69 study sites across Europe and Australia. All patients had diabetes that was not adequately controlled by oral hypoglycaemic drugs, and were randomly assigned to either insulin glargine injected once daily at the same time every day (205 individuals), or to insulin lispro injected three times per day (210).

The investigators found that both groups achieved similar reductions in haemoglobin A1c, with the average decrease in the insulin glargine group -1.7% (from 8.7% to 7.0%); in the insulin lispro group the average decrease was -1.9% (from 8.7% to 6.8%).

The authors conclude: “A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A1c. We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro.”

Posted by dlife at 10:13 AM | Comments (0)

Reduced Lung Capacity Accelerates with Diabetes

March 26, 2008

March 26, 2008 (Newswise) — People who have diabetes encounter a faster loss of lung capacity than those who do not have diabetes, a finding that may have implications for the potential use of inhaled insulin, according to a study appearing in the April issue of Diabetes Care.

The April issue also contains a consensus statement from the American Diabetes Association and American College of Cardiology Foundation emphasizing the need for more aggressive goals in controlling lipids to reduce cardiometabolic risk. In particular, the paper focuses for the first time on the need to test for and treat high levels of a protein called apolipoprotein B (ApoB), a more direct measure of the number of LDL particles that lead to plaques that cause heart disease (atherosclerosis). This is based on evidence that levels of ApoB are a better indicator of heart disease risk than total cholesterol or LDL (“bad cholesterol”).

Reduced Lung Capacity in People with Diabetes

The lung research, part of a larger investigation known as the Atherosclerosis Risk in Communities (ARIC) study, confirmed previous suggestions that the lung is a target organ for diabetic injury and that lung abnormalities accelerate once diabetes takes hold. Previous research by the same authors established that decreased lung capacity precedes and may predict a diagnosis of diabetes. The new study is accompanied by an editorial that concludes that diminished lung function may contribute to diabetes morbidity and mortality.

Specifically, the study found that people with type 2 diabetes experienced a more rapid decline in forced vital capacity, the measure of how well the lungs fill with air, than people who did not have diabetes. Though all people experience a decline in forced vital capacity as they age, people with diabetes appear to undergo a more rapid loss that appears before the diabetes diagnosis and accelerates after the disease sets in.

This could be because high blood sugar levels stiffen the lung tissue, or because the fat tissue in the chest and abdomen may confine the lungs more in people with diabetes, explained the researchers. They concluded the study with advice to clinicians to “pay heightened attention to pulmonary function in their patients with type 2 diabetes.”

“Think of the lung as a crime victim who unwittingly abets the perpetrator to hasten the demise of the host,” wrote Dr. Connie Hsia, of the University of Texas Southwestern Medical Center’s Department of Internal Medicine, in an editorial accompanying the study. She suggested that the loss of pulmonary function could add

to diabetic morbidity and mortality, and raised concerns about the potential use of inhaled insulin, since it may “trigger or exacerbate pulmonary dysfunction.”

Recently, makers of inhaled insulin have pulled their products from the market because of poor sales or halted product investigations, though several companies continue to explore this type of insulin delivery.

“Manufacturers of inhaled insulin should find these data useful as they study potential long-term effects of their product on lung function,” said Dr. Fred Brancati, one of the lead researchers on the study. “The results suggest that doctors and patients should keep an eye on the literature about diabetes and the lung down the road, since there’s a stronger connection than we previously thought.”

Consensus Statement Urges Greater Lipid Control

The ADA-American College of Cardiology (ACC) paper highlights a new consensus suggesting that, in people who exhibit cardiometabolic risk factors (such as insulin resistance, hypertension, overweight/obesity, or a family history of premature heart disease), a certain protein called apolipoprotein B (apo B) may better predict the risk of heart disease than LDL cholesterol levels, long used as one measurement of good heart health. A panel of diabetes and heart experts agreed that LDL (“bad”) cholesterol was still an important risk factor, but that after LDL cholesterol levels were brought under control, ApoB (a measure of the number of LDL particles in the blood that cause hardening of the arteries) should also be tested and treated to target levels in people at high risk.

The statement emphasizes the need to examine all factors for heart disease, to continue to focus on lifestyle interventions to reduce the risk for type 2 diabetes and heart disease, and to more aggressively control all lipids. The paper also urged health care providers to look at a person’s lifetime risk for heart disease, rather than just at short-term risks.

Diabetes Care, published by the American Diabetes Association, is the leading peer-reviewed journal of clinical research into the nation’s fifth leading cause of death by disease. Diabetes also is a leading cause of heart disease and stroke, as well as the leading cause of adult blindness, kidney failure, and non-traumatic amputations. For more information about diabetes, visit the American Diabetes Association Web site http://www.diabetes.org or call 1-800-DIABETES (1-800-342-2383).

Posted by dlife at 09:28 AM | Comments (2)

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)

NYU Dental Researchers Find Evidence of Periodontal Disease Leading to Gestational Diabetes

The findings, published in the April 2008 issue of the Journal of Dental Research, underscore how important it is for expectant mothers to maintain good oral health

March 24, 2008 (EurekAlert) - A study by a New York University dental research team has discovered evidence that pregnant women with periodontal (gum) disease are more likely to develop gestational diabetes mellitus than pregnant women with healthy gums.

The study, led by Dr. Ananda P. Dasanayake, a professor of epidemiology & health promotion at the NYU College of Dentistry, followed 256 women at New York’s Bellevue Hospital Center through their first six months of pregnancy. Twenty-two women developed gestational diabetes. Those women had significantly higher levels of periodontal bacteria and inflammation than the other women in the study.

The findings, published in the April 2008 issue of the Journal of Dental Research, underscore how important it is for expectant mothers to maintain good oral health.

“In addition to its potential role in preterm delivery, evidence that gum disease may also contribute to gestational diabetes suggests that women should see a dentist if they plan to get pregnant, and after becoming pregnant,” says Dasanayake. “Treating gum disease during pregnancy has been shown to be safe and effective in improving women’s oral health and minimizing potential risks.”

“In the future,” he added, “we can expect to see more research on the link between these two conditions involving other high risk groups, such as Asian and Native American women.”

Gestational diabetes is characterized by an inability to transport glucose -- the main source of fuel for the body -- to the cells during pregnancy. The condition usually disappears when the pregnancy ends, but women who have had gestational diabetes are at a greater risk of developing the most common form of diabetes, known as Type 2 diabetes, later in life. Hispanics, Asians, and Native Americans are at the highest risk for developing gestational diabetes. Eighty percent of the women in the NYU study were Hispanic.

Inflammation associated with periodontal disease is believed to play a role in the onset of gestational diabetes, perhaps by interfering with the normal functioning of insulin, the hormone that regulates glucose metabolism.

Posted by dlife at 09:16 AM | Comments (0)

Grape Skin Compound Fights The Complications Of Diabetes

March 20, 2008

March 20, 2008 (Science Daily) - Research carried out by scientists at the Peninsula Medical School in the South West of England has found that resveratrol, a compound present naturally in grape skin, can protect against the cellular damage to blood vessels caused by high production of glucose in diabetes, according to a recently published paper in the science journal "Diabetes, Obesity and Metabolism."

The elevated levels of glucose that circulate in the blood of patients with diabetes causes micro- and macrovascular complications by damaging mitochondria, the tiny power plants within cells responsible for generating energy. When they are damaged they can leak electrons and make highly damaging 'free radicals'.

Complications that can result when this happen include nephropathy (kidney disease), heart disease and retinopathy (which if left untreated can lead to blindness).

Resveratrol stops the damage by helping cells make protective enzymes to prevent the leakage of electrons and the production of toxic 'free radicals'.

As well as being naturally present in grape skins, resveratrol is also present in seeds, peanuts and red wine.

Dr. Matt Whiteman, Principal Investigator and Senior Lecturer at the Institute of Biomedical and Clinical Science, Peninsula Medical School, commented: "Resveratrol's antioxidant effects in the test tube are well documented but our research shows the link between high levels of glucose, its damaging effect on cell structure, and the ability of resveratrol of protect against and mend that damage."

He added: "Resveratrol or related compounds could be used to block the damaging effect of glucose which in turn might fight the often life threatening complications that accompany diabetes. It could well be the basis of effective diet-based therapies for the prevention of vascular damage caused by hyperglycaemia in the future."

Posted by dlife at 02:27 PM | Comments (14)

Joslin Researchers Discover New Effect For Insulin

March 20, 2008 (EurekAlert) - Researchers at the Joslin Diabetes Center have shown that insulin has a previously unknown effect that plays a role in aging and lifespan, a finding that could ultimately provide a mechanism for gene manipulations that could help people live longer and healthier lives.

The paper, published in the March 21st issue of Cell, reports that insulin inhibits a master gene regulator protein known as SKN-1, and that increased SKN-1 activity increases lifespan. SKN-1 controls what is called the Phase 2 detoxification pathway, a network of genes that defends cells and tissue against oxidative stress – damage caused by elevated levels of free radicals (byproducts of metabolism) – and various environmental toxins. The new finding was demonstrated in experiments on the digestive system of C. elegans, a microscopic worm often used as a model organism.

“We’ve found something new that insulin does and it has to be considered when we think about how insulin is affecting our cells and bodies,” said Dr. T. Keith Blackwell, senior investigator at Joslin and author of the paper. “This has implications for basic biology since under some circumstances insulin may reduce defense against the damaging effects of oxidative stress more than we realize.”

The idea down the line is that fine-tuning the activity of SKN-1 may lead to increased resistance to chronic diseases and influence longevity, he said. The work could be important as it relates to diabetes and the many problems associated with the disease, particularly vascular and renal complications.

But, today’s finding may be most important for what it teaches about aging in general, he said.

“The major implication is that we have found something new that affects lifespan and aging, and an important new effect that insulin and/or a related hormone called insulin-like growth factor-1 may have in some tissues,” said Blackwell. “The implications go far beyond diabetes.”

It has been known since the 1990s that insulin inhibits a gene regulator protein known as FOXO, important in diabetes metabolism, tumor suppression and stem cell maintenance. FOXO controls a number of genes, including many involved in stress resistance. Studies in C. elegans showed that reduced insulin signaling boosted activity of a FOXO protein known as DAF-16, leading to greater stress resistance and longer life.

The new work places SKN-1 alongside FOXO as a second master gene regulator that is inhibited by insulin signaling and adds to the body of knowledge about insulin and its effects on gene pathways, stress resistance and aging. According to the paper, insulin’s effect on SKN-1 occurs independently of its effect on DAF-16.

“You can manipulate the expression of SKN-1 and the worms live longer,” said Blackwell, an Associate Professor of Pathology at Harvard Medical School and faculty member at the Harvard Stem Cell Institute.

The experiments will have to be repeated in mammals, where insulin and insulin-like growth factor-1 have a complex array of effects in different tissues. But, according to Blackwell, other findings in the C. elegans model have generally turned out to be applicable to mice and humans.

Blackwell’s lab at Joslin is focusing on mechanisms of free radical resistance and aging, and on gene regulation mechanisms in C. elegans stem cells with the idea of using this knowledge towards reprogramming human stem cells into insulin-producing cells.

Posted by dlife at 11:52 AM | Comments (0)

Uric Acid May Provide Early Clues to Diabetic Kidney Disease

March 17, 2008

March 17, 2008 (Newswise) — For patients with type 1 diabetes, increased levels of uric acid in the blood may be an early sign of diabetic kidney disease—appearing before any significant change in urine albumin level, the standard screening test, reports a study in the May 2008 issue of the Clinical Journal of the American Society of Nephrology.

The results raise the possibility that treatments to reduce uric acid might slow the decline of renal function in patients with diabetes. "Thus we have the hope of having a means to thwart the loss of kidney function while function is still in a relatively preserved stage," comments Dr. Elizabeth T. Rosolowsky of Joslin Diabetes Center, Boston.

The researchers measured serum uric acid concentration in 675 patients with type 1 diabetes. On screening tests, 311 patients had small amounts of the protein albumin in the urine. This result—called microalbuminuria—is generally regarded as a harbinger of kidney function loss in diabetic kidney disease (nephropathy). The other 364 patients had normal urine albumin levels.

None of the patients had higher levels of albumin (albuminuria) representing more advanced diabetic nephropathy. Nevertheless, one in five had some impairment of kidney function on a standard test, the glomerular filtration rate. "Our research showed that loss of kidney function takes place even in the absence of albuminuria in patients with type 1 diabetes," says Dr. Rosolowsky.

In contrast, the serum uric acid level was consistently related to kidney function—the higher the uric acid, the lower the kidney function. "The serum concentration of uric acid in these patients varied in a manner consistent with its having played a role in this early loss of kidney function," according to Dr. Rosolowsky.

Urine albumin is commonly measured to identify patients with type 1 diabetes at risk of developing nephropathy. "Historically, it was believed that the start of kidney function loss happened only when the amount of leakage of albumin into the urine had reached a certain level," Dr. Rosolowsky explains. "However, recent studies by our group have suggested that kidney function loss may start much earlier in some patients with type 1 diabetes." Other studies have suggested that increased serum uric acid levels are associated with loss of kidney function, and may even be a causative factor.

If higher uric acid levels do contribute to loss of kidney function, then the findings may offer a new approach to treating diabetic kidney disease. "The serum uric acid concentration is modifiable by drugs or by decreasing the intake of dietary protein, the main source of uric acid," says Dr. Rosolowsky. "If follow-up studies, already underway, demonstrate that serum uric acid concentration predicts the course of early decline in kidney function, then clinical trials would be justified to test whether modifying serum uric acid concentration also modifies the course of renal function decline in type 1 diabetic patients with high normoalbuminuria or microalbuminuria."

The American Society of Nephrology (ASN) is a not-for-profit organization of 11,000 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases. ASN publishes the Journal of the American Society of Nephrology (JASN), the Clinical Journal of the American Society of Nephrology (CJASN), and the Nephrology Self-Assessment Program (NephSAP).

Posted by dlife at 03:51 PM | Comments (0)

Blood Vessel Protein Reverses Macular Degeneration, Diabetic Retinopathy in Mice

March 16, 2008

March 16, 2008 (EurekAlert) - Two major eye diseases and leading causes of blindness—age-related macular degeneration and diabetic retinopathy—can be reversed or even prevented by drugs that activate a protein found in blood vessel cells, researchers at the University of Utah School of Medicine and several other institutions have announced in a new study.

Damage from both diseases was prevented and even reversed when the protein, Robo4, was activated in mice models that simulate age-related macular degeneration (AMD) and diabetic retinopathy, according to Dean Y. Li, M.D., Ph.D., senior author of the study published March 16 in Nature Medicine online.

Robo4 treated and prevented the diseases by inhibiting abnormal blood vessel growth and by stabilizing blood vessels to prevent leakage. Abnormal blood vessel growth and leakage are two primary factors in both age-related macular degeneration (AMD) and diabetic retinopathy. But the study’s ramifications go beyond eye diseases.

Serious infections such as SARS (Severe Acute Respiratory Syndrome), for example, kill people when an infection destabilizes blood vessels, allowing fluids to leak into the lungs. Tumors hijack blood vessel growth to feed on nutrients and grow. Although this study did not prove Robo4 would treat those diseases, Li believes it merits investigation.

“Many diseases are caused by injury or inflammation destabilizing blood vessels and causing them to leak fluid into adjacent tissues as well,” said Li, professor of internal medicine and an investigator with the University’s Program in Human Molecular Biology and Genetics. “We found a natural pathway – the Robo4 pathway – that counterattacks this by stabilizing blood vessels.”

“This discovery has significant implications for developing drugs that activate Robo4 to treat AMD and diabetic retinopathy,” said Kang Zhang, M.D., Ph.D., associate professor of ophthalmology and visual sciences at the University of Utah’s John A. Moran Eye Center and an investigator with the University’s Program in Human Molecular Biology and Genetics. Li and Zhang’s laboratories closely collaborated on the research, using the same animal models of AMD and diabetic retinopathy that are required for drug development. The collaboration means the time required to test the approach in people could be shortened, perhaps by years. Nonetheless, both Zhang and Li caution that getting new drugs to market still would take a number of years.

Randall J. Olson, M.D., director of the University’s John A. Moran Eye Center and professor and chair of ophthalmology and visual sciences, called Li’s finding historic.

“This is a major breakthrough in an area where the advances have been minimal,” Olson said. “We are excited about taking this opening and moving the frontier forward with real hope for patients who have but few, often disappointing, options.”

The discovery is a prime example of basic science research yielding a discovery with direct clinical applications, according to Hemin Chin, Ph.D., director of ocular genetics program at the National Eye Institute. “Given that vascular eye diseases, such as age related macular degeneration and diabetic retinopathy, are the number one cause of vision loss in the United States, the identification of new signaling pathways that prevent abnormal vessel growth and leakage in the eye represents a major scientific advancement,” said Chin.

Blood vessel growth (angiogenesis) is critical in human development and as a response to injury or disease. In earlier research, Li had shown that a family of proteins, netrins, induce blood vessel and nerve growth in mice, a discovery with important ramifications for potential therapies to help people with too few blood vessels. But when the body grows new blood vessels at the wrong time or place, these blood vessels are often unstable and weak, which causes them to leak and potentially lead to diseases such as macular degeneration and diabetic retinopathy.

In 2003, Li’s laboratory cloned Robo4 and showed it served the opposite function of netrins by inhibiting blood vessel growth and the destabilization that causes leakage. Robo4 is found only in cells in the interior surface of blood vessels and is activated by a protein called Slit. After being activated, Robo4 initiates a chain of biochemical events to stabilize blood vessels and prevent uncontrolled growth.

“Everything in biology has a yin (negative) and a yang (positive), and in the previous paper on netrins we brought attention to a new signaling pathway that induces vessels and nerves to grow,” Li said. “Robo4 is the yin to that process, preventing new vessel growth by stabilizing the integrity of mature blood vessels.”

Age-related macular degeneration is the most common cause of legal blindness in people age 65 or older and is expected to become an increasingly common and costly health issue as the number of older people in United States increases. Diabetic retinopathy is the most common cause of legal blindness in working-age Americans. Currently, there are an estimated 21 million people with diabetes.

Posted by dlife at 01:51 PM | Comments (6)

Study in Circulation Research Details How Diabetes Drives Atherosclerosis

March 14, 2008

Mechanisms suggest new way to treat heart disease among diabetics

March 14, 2008 (EurekAlert) - Researchers have discovered how diabetes, by driving inflammation and slowing blood flow, dramatically accelerates atherosclerosis, according to research to be published in the March 14 edition of the journal Circulation Research.

Experts once believed that atherosclerosis, or hardening of the arteries, developed when too much cholesterol clogged arteries with fatty deposits called plaques. When blood vessels became completely blocked, heart attacks and strokes occurred. Today most agree that the reaction of the body's immune system to fatty build-up, more than the build-up itself, creates heart attack risk. Immune cells traveling with the blood mistake fatty deposits for intruders, akin to bacteria, home in on them, and attack. This causes inflammation that makes plaques more likely to swell, rupture and cut off blood flow.

Making matters worse, nearly 21 million Americans have diabetes, a disease where patients’ cells cannot efficiently take in dietary sugar, causing it to build up in the blood. In part because diabetes increases atherosclerosis-related inflammation, diabetic patients are twice as likely to have a heart attack or stroke.

Past work has shown that high blood sugar has two effects on cells lining blood vessels as part of atheroslerosis. First, it increases the production of free radicals, highly reactive molecules that tear about sensitive cell components like DNA, causing premature cell death (apoptosis). This process also reduces the availability of nitric oxide (NO), which would otherwise enable blood vessels to relax and blood flow to increase. In contrast to diabetes, exercise and good diet bring about faster blood flow through blood vessels. The force created by fast, steady blood flow as it drags along blood vessel walls has been shown by recent studies to protect arteries from atherosclerosis. Physical force has emerged recently as a key player in bodily function, capable of kicking off biochemical processes (e.g. weightlifting thickens bone).

“Inflammation is blood vessels is one of the main drivers of atherosclerosis, and diabetes makes it much worse,” said Jun-ichi Abe, M.D., Ph.D., associate professor with the Aab Cardiovascular Research Center at the University of Rochester Medical Center, and a study author. “Our study argues that a pathway surrounding a key signaling enzyme both protects the heart in normal cases, and is sabotaged by the chemicals produced in diabetes. We believe we have found a new therapeutic target for the treatment of diabetes-related damage to blood vessels.”

How Diabetes Does It

In people without diabetes, fast blood flow triggers an enzyme called extracellular signal-regulated kinase 5 (ERK-5). ERK5 in turn signals endothelial nitric oxide synthase (eNOS) to produce more nitric oxide and dilate blood vessels. It also activates Kruppel-like factor 2 (KLF2) and peroxisome proliferator-activated receptor-g (PPARg), both of which block the ability of pro-inflammatory immune cells to home in on and adhere to diseased portions of blood vessels.

Past studies had shown diabetes to worsen atherosclerosis, but its exact link to related inflammation had remained unclear. The current results provides the first mechanistic description of how diabetes takes away the ability of fast blood flow force to protect blood vessels, arguing that it does so by interfering with ERK5 and its signaling partners.

Abe’s team showed that molecules called advanced glycation end products (AGEs), produced in greater levels by patients with diabetes, interfere with ERK5 cardioprotection. Glycation reactions cause the release of oxidizing side products like hydrogen peroxide (H202) that drive free radical production, inflammation and cell damage in many diseases.

Researchers found that AGEs and H202 sabotage ERK5 by encouraging the attachment to it of a small ubiquitin-related modifier (SUMO), a protein tag used by cells to fine-tune their control over proteins. In normal function, a cell may extend a protein’s lifespan, or send it from one part of the cell to another, by attaching a SUMO tag. In the current study, researchers found that AGEs and H202 induced ERK5-SUMOylation as part of disease. In addition, the team found that ERK5-SUMOylation was increased in the aortas of diabetic mice.

Along with Abe, Chang-Hoon Woo, Tetsuro Shishido and Carolyn McClain contributed to the work within the Aab Cardiovascular Research Center. Jae Hyang Lim and Jian-Dong Li within the Department of Microbiology & Immunology at the Medical Center contributed expertise, along with Jay Yang, professor of Anesthesiology at Columbia University. This work is supported by grants from the America Heart Association and the National Institutes of Health.

“Our experiments found that taking away the “SUMO tag” from ERK protects blood vessels against diabetes,” Abe said. “We believe that the SUMOylation of ERK turns off ‘good’ genes that are important in countering atherosclerosis. In the next phase, we will be looking for drug candidates that can turn on ERK5 as diabetes attempts to shut it down.”

Posted by dlife at 10:18 AM | Comments (1)

Diabetes Ten City Challenge Collaborative Model

March 13, 2008

March 13, 2008 (PR Newswire) - Interim results show that participants in the Diabetes Ten
City Challenge (DTCC) improved across all key clinical and patient satisfaction indicators in the
early stages of the program, the American Pharmacists Association (APhA) Foundation
announced today.

Initial data show a positive trend in controlling diabetes, the chronic disease that affects 21 million
Americans and costs the U.S. more than $174 billion annually. The final DTCC report, due out in
2009, will include cost-savings data for DTCC employers.

The Diabetes Ten City Challenge (DTCC) is an employer-based diabetes self-management
program conducted by APhA Foundation with support from GlaxoSmithKline. Since it was
launched in October 2005, 31 employers in ten cities have joined forces with hundreds of
pharmacists to help more than 1,000 people manage their diabetes.

Through the DTCC, employers establish a voluntary health benefit for employees, dependents and
retirees with diabetes, and waive co-payments for diabetes medications and supplies if they work
with a pharmacist “coach” to manage their condition in collaboration with their doctors and diabetes
educators. The DTCC is modeled after other highly successful APhA programs that have proven
to improve overall health, reduce absenteeism, shorten hospital stays and reduce health care
costs.

“The results to date prove that this collaborative-practice model is effective for managing diabetes
and replicable in diverse locations and employers,” said William M. Ellis, CEO of the APhA
Foundation and co-author of a peer-reviewed article on the results published in the March/April
issue of the Journal of the American Pharmacists Association (JAPhA). “In years of experience
with this model we have seen that when you have positive clinical outcomes and increased patient
satisfaction in the early stages, the economic benefits follow.”

Key Findings

The report released today analyzed aggregate data on 914 DTCC participants who were in the
program at least three months as of September 30, 2007. It documented clinical improvements in
all the recognized standards for diabetes care, including:

• Decreases in laboratory measures (mean) for hemoglobin A1C (a laboratory test showing the
patient’s average blood sugar control over the previous two to three months), LDL cholesterol
and blood pressure over the initial year of the program
• Increases in the number of participants with current influenza vaccinations, foot examinations
and eye examinations
• 21% increase in the number of participants achieving the American Diabetes Association goal
of A1c level <7.0
• Increase from 43.8% to 57.7% in participants achieving nationally recognized National
Cholesterol Education Program goals for LDL cholesterol
• 15.7% increase in the number of people achieving recognized goals for systolic blood
pressure

Other Key Data

• The number of DTCC participants who felt their overall diabetes care was “very good to
excellent” increased from 39% to 87%
• More than 97% of participants reported being “very satisfied” or “satisfied” with diabetes care
provided by DTCC pharmacists
• The number of participants with self-management goals to control their diabetes also
increased significantly over the course of the program: the number of people with nutrition
goals increased from 22% to 66%; the number of people with weight goals increased from
23% to 64%; and the number of participants with exercise goals increased from 24% to 72%

“The data show significant improvement in all clinical and diabetes care indicators measured,” said
Toni Fera, PharmD, principal author of an article on the results appearing in the March/April issue
of the Journal of the American Pharmacists Association. “These results are consistent with data
from past projects where similar clinical improvements translated to annual savings to employers in
total direct medical costs for participants."

"Chronic diseases like diabetes are threatening the stability of our healthcare system," said
GlaxoSmithKline President of U.S. Pharmaceuticals, Chris Viehbacher. "By focusing on patients
and helping them to better understand and self-manage their condition, we can improve their
health and lower costs. GSK is proud to support the Diabetes Ten City Challenge because it is a
model that works and can be replicated.”

How the DTCC Model Works

The APhA Foundation contracts with employers, helps establish local pharmacist networks and
provides software and data analysis for the DTCC. Employers offer the voluntary employee benefit
and compensate pharmacists for the care provided. Participating pharmacists, who are specially
trained in diabetes care, educate participants on diabetes, diet and nutrition. These “pharmacist
coaches” meet with participants regularly to help them track key diabetes indicators and manage
their diabetes by eating right, exercising regularly, visiting their doctors and taking medications as
prescribed.

Physicians are informed of participants’ enrollment and are encouraged to share individual patient
care plans with the pharmacist, who reinforces those plans in personal meetings. Pharmacists
communicate with physicians after every visit and refer patients to other health care providers as
needed for additional care or education.

Expanding the DTCC Model for all Chronic Diseases

An additional 50 employers and 1,300 employees are using the DTCC model through the APhA
Foundation’s HealthMapRx™ to manage many chronic diseases, such as diabetes and
cardiovascular disease.

“The Diabetes Ten City Challenge provides an opportunity to transform health care delivery in
local communities and drive fundamental change in the U.S. health care system,” Ellis said. “Our
overall goal is to make this model as widely available as possible and encourage employers to
invest in helping their employees manage all chronic conditions. Our nation’s health care system
is broken – we need more programs that are an investment in wellness rather than an expense for
sickness.”

About the APhA Foundation (www.aphafoundation.org)

The American Pharmacists Association (APhA) Foundation, headquartered in Washington, D.C., is
a non-profit organization affiliated with the American Pharmacists Association, the national
professional society of pharmacists in the United States.

The APhA Foundation has expertise in designing programs that seek to create a new medication
use system in the U.S. where patients, pharmacists, physicians and other health care providers
collaborate to dramatically improve the cost and quality of consumer health outcomes through the
safe and effective use of medications.

Posted by dlife at 02:06 PM | Comments (0)

Extra vitamin D in Early Childhood Cuts Adult Diabetes Risk

Vitamin D supplementation in early childhood and risk of type 1 diabetes: a systematic review and meta-analysis

March 13, 2008 (EurekAlert) - Vitamin D supplements in early childhood may ward off the development of type 1 diabetes in later life, reveals a research review published ahead of print in the Archives of Disease in Childhood.

Type 1 diabetes is an autoimmune disorder, in which insulin producing beta cells in the pancreas are destroyed by the body’s own immune system, starting in early infancy. The disease is most common among people of European descent, with around 2 million Europeans and North Americans affected.

Its incidence is rising at roughly 3% a year, and it is estimated that new cases will have risen 40% between 2000 and 2010.

A trawl of published evidence on vitamin D supplementation in children produced five suitable studies, the pooled data from which were re-analysed.

The results showed that children given additional vitamin D were around 30% less likely to develop type 1 diabetes compared with those not given the supplement.

And the higher and the more regular the dose, the lower was the likelihood of developing the disease, the evidence suggested.

Levels of vitamin D, and sunlight, from which the body manufactures the vitamin, have been implicated in the risks of developing various autoimmune disorders, including multiple sclerosis and rheumatoid arthritis.

And there is a striking difference in the incidence of type 1 diabetes according to latitude and levels of sunlight exposure, with a child in Finland 400 times more likely to develop the disease than a child in Venezuela, say the authors.

Further evidence of vitamin D’s role comes from the fact that pancreatic beta cells and immune cells carry receptors or docking bays for the active forms of the vitamin.

Posted by dlife at 10:16 AM | Comments (1)

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 BM