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January 28, 2011, 8:06 PM CT

Root cause of blood vessel damage in diabetes

Root cause of blood vessel damage in diabetes
Blood flow was interrupted in a vessel in normal mice (above) and in FASTie mice (below). After a few weeks, the normal mice formed new blood vessels to restore blood flow, but FASTie mice without fatty acid synthase did not.

Semenkovich lab, Washington University School of Medicine
A key mechanism that appears to contribute to blood vessel damage in people with diabetes has been identified by scientists at Washington University School of Medicine in St. Louis.

Blood vessel problems are a common diabetes complication. A number of of the nearly 26 million Americans with the disease face the prospect of amputations, heart attack, stroke and vision loss because of damaged vessels.

Reporting in the Journal of Biological Chemistry, the Washington University scientists say studies in mice show that the damage appears to involve two enzymes, fatty acid synthase (FAS) and nitric oxide synthase (NOS), that interact in the cells that line blood vessel walls.

"We already knew that in diabetes there's a defect in the endothelial cells that line the blood vessels," says first author Xiaochao Wei, PhD. "People with diabetes also have depressed levels of fatty acid synthase. But this is the first time we've been able to link those observations together".

Wei is a postdoctoral research scholar in the lab of Clay F. Semenkovich, MD, the Herbert S. Gasser Professor of Medicine, professor of cell biology and physiology and chief of the Division of Endocrinology, Metabolism and Lipid Research.

Wei studied mice that had been genetically engineered to make FAS in all of their tissues except the endothelial cells that line blood vessels. These so-called FASTie mice experienced problems in the vessels that were similar to those seen in animals with diabetes.........

Posted by: JoAnn      Read more         Source


November 30, 2010, 7:58 AM CT

Moderate alcohol consumption lowers the risk of metabolic diseases

Moderate alcohol consumption lowers the risk of metabolic diseases
With the emergence of an epidemic of obesity and type 2 diabetes (DM) throughout the world, the association of lifestyle habits that may affect the risk of metabolic diseases is particularly important. Most prospective studies have shown that moderate drinkers tend to have about 30% lower risk of developing late onset diabetes than do non-drinkers, and moderate drinkers also tend to be at lower risk of developing metabolic syndrome (MS). A cross-sectional analysis of 6172 subjects age 35 -75 in Switzerland related varying levels of alcohol intake to the presence of DM, MS, and an index of insulin resistance (HOMA-IR).

Alcohol consumption was categorized as non-drinkers (0), low-risk (1󈝹 drinks a week), medium-to-high-risk (14󈞎) and very-high-risk (= 35) drinkers. 73% of participants consumed alcohol, 16% were medium-to-high-risk drinkers and 2% very-high risk drinkers.

Study findings: In multivariate analysis, the prevalence of the metabolic syndrome, diabetes and mean HOMA-IR decreased with low-risk drinking and increased with high-risk drinking. Adjusted prevalence of the metabolic syndrome was 24% in non-drinkers, 19% in low-risk, 20% in medium-to-high-risk and 29% in very-high-risk drinkers. Adjusted prevalence of diabetes was 6.0% in non-drinkers, 3.6% in low-risk, 3.8% in medium-to-high-risk and 6.7% in very-high-risk drinkers. These relationships did not differ as per beverage types.........

Posted by: JoAnn      Read more         Source


October 12, 2010, 7:30 AM CT

Insulin resistance and stroke risk

Insulin resistance and stroke risk
Insulin resistance, a condition in which insulin produced by the body becomes less effective in reducing blood glucose levels, may be linked to an increased risk of stroke in individuals without diabetes, as per a report in the recent issue of Archives of Neurology, one of the JAMA/Archives journals.

Insulin resistance originates from several factors, including genetics, a sedentary lifestyle and obesity, as per background information in the article. The condition contributes significantly to the risk of cardiovascular disease, but whether it predicts ischemic stroke (interruption in blood flow to the brain due to a blood clot or another artery blockage) is still a matter of debate.

One widely used tool to estimate insulin sensitivity is the homeostasis model evaluation (HOMA), calculated using fasting blood glucose and fasting insulin levels. Tatjana Rundek, M.D., Ph.D., of Miller School of Medicine, University of Miami, and his colleagues assessed insulin resistance using HOMA for 1,509 non-diabetic participants in the Northern Manhattan Study, a study assessing stroke risk, incidence and prognosis in a multi-ethnic urban community. Participants were followed for an average of 8.5 years.

During the follow-up period, vascular events occurred in 180 participants, including 46 who had fatal or non-fatal ischemic strokes, 45 who had fatal or non-fatal heart attacks and 121 who died of vascular causes. Individuals in the top one-fourth (quartile) of HOMA index had an increased risk of stroke in comparison to those in the other three quartiles of the HOMA index. Adjusting for established cardiovascular risk factorsincluding glucose level, obesity and metabolic syndromedid not diminish the association. The relationship between insulin resistance and the risk of first stroke was stronger in men than women but did not vary by racial or ethnic group.........

Posted by: JoAnn      Read more         Source


October 5, 2010, 7:13 AM CT

Promise for Type 1 diabetes treatment

Promise for Type 1 diabetes treatment
A research team from the University of British Columbia and the Child & Family Research Institute (CFRI) at BC Children's Hospital has identified the role of a type of T cell in type 1 diabetes that may lead to new therapy options for young patients.

Also known as juvenile diabetes, type 1 diabetes is an autoimmune disease primarily affecting children and young adults. In patients with type 1 diabetes, the body attacks itself by destroying insulin-producing cells in the pancreas that regulate glucose, or blood sugar.

Led by Rusung Tan, a Pathology professor in the UBC Faculty of Medicine and co-head of the Immunity in Health and Disease research cluster at CFRI, the research team has identified the increased presence of Th17 cells, a type of T cell discovered in 2005, in children newly diagnosed with type 1 diabetes.

"T cells are white blood cells and key members of the immune system that control infections," says Tan, who is also a member of the Department of Pathology & Laboratory Medicine at BC Children's Hospital and a senior scholar of the Michael Smith Foundation for Health Research. "In healthy individuals, Th17 cells provide a strong defence against bacteria and viruses by guiding the immune system to strongly attack infected targets within our bodies".........

Posted by: JoAnn      Read more         Source


July 13, 2010, 7:21 AM CT

New Approach For Diabetes Therapy

New Approach For Diabetes Therapy
Nutrition experts at Oregon State University have essentially "cured" laboratory mice of mild, diet-induced diabetes by stimulating the production of a particular enzyme.

The findings could offer a new approach to diabetes treatment, experts say, particularly if a drug could be identified that would do the same thing, which in this case was accomplished with genetic manipulation.

Increased levels of this enzyme, called fatty acid elongase-5, restored normal function to diseased livers in mice, restored normal levels of blood glucose and insulin, and effectively corrected the risk factors incurred with diet-induced diabetes.

"This effect was fairly remarkable and not anticipated," said Donald Jump, a professor of nutrition and exercise sciences at Oregon State, where he is an expert on lipid metabolism and principal investigator with OSU's Linus Pauling Institute.

"It doesn't provide a treatment yet, but could be fairly important if we can find a drug to raise levels of this enzyme," Jump said. "There are already some drugs on the market that do this to a point, and further research in the field would be merited".

The studies were done on a family of enzymes called "fatty acid elongases," which have been known of for decades. Humans get essential fatty acids that they cannot naturally make from certain foods in their diet. These essential fatty acids are converted to longer and more unsaturated fatty acids. The fatty acid end products of these reactions are important for managing metabolism, inflammation, cognitive function, cardiovascular health, reproduction, vision and other metabolic roles.........

Posted by: JoAnn      Read more         Source


June 28, 2010, 7:46 AM CT

Can too much HDL be harmful?

Can too much HDL be harmful?
Elevated blood levels of high-density lipoprotein (HDL) or "good" cholesterol, typically thought to protect against heart disease, may do the opposite in women with type 1 diabetes, as per a University of Pittsburgh Graduate School of Public Health study being presented at the 70th Scientific Sessions of the American Diabetes Association.

The study, abstract number 0098-OR, included 658 men and women enrolled in the Pittsburgh Epidemiology of Diabetes Complications Study, a long-term prospective examination of childhood onset type 1 diabetes that began in 1986. Participants were diagnosed with type 1 diabetes between 1950 and 1980.

HDL cholesterol is known as "good" cholesterol because it helps prevent arteries from becoming clogged. High levels of HDL cholesterol, over 60 milligrams per deciliter (mg/dL), generally protect against heart disease, while low levels (less than 40 mg/dL for men and less than 50 mg/dL for women) increase risk.

Study scientists found the occurence rate of heart disease increased in both men and women with diabetes who had lower levels of HDL below 47.5 mg/dL. For men, as levels of HDL increased, their occurence rate of heart disease decreased. The same was found for women, except in those with very high levels of HDL (over 80 mg/dL) whose occurence rate of heart disease increased substantially. Study authors were unable to draw a meaningful comparison to male participants since only a few had HDL over 80 mg/dL.........

Posted by: Daniel      Read more         Source


June 16, 2010, 7:21 AM CT

Linking diabetes and cancer

Linking diabetes and cancer
A new consensus statement of experts assembled by the American Diabetes Association and the American Cancer Society reviews emerging evidence that suggests cancer incidence is linked to diabetes as well as certain diabetes risk factors and therapys. The new report reviews the state of science concerning the association between diabetes and cancer incidence/prognosis; risk factors common to both diseases; possible biologic links between diabetes and cancer risk; and whether diabetes therapys influence the risk of cancer or cancer prognosis. In addition, the report outlines key unanswered questions for future research.

Diabetes and cancer are common diseases that have a tremendous impact on health worldwide. Epidemiologic evidence suggests that people with diabetes are at a significantly higher risk of a number of forms of cancer. Type 2 diabetes and cancer share a number of risk factors, but potential biologic links between the two diseases are not completely understood. Moreover, evidence from findings based on observation suggests that some medications used to treat hyperglycemia are linked to either an increased or reduced risk of cancer. Against this backdrop, the American Diabetes Association and the American Cancer Society convened a consensus development conference in December 2009. After a series of scientific presentations by experts in the field, the writing group independently developed a consensus report to address important questions: Is there a meaningful association between diabetes and cancer incidence or prognosis? What risk factors are common to both cancer and diabetes? What are possible biologic links between diabetes and cancer risk? And do diabetes therapys influence cancer risk or cancer prognosis?.........

Posted by: Janet      Read more         Source


February 5, 2010, 7:54 AM CT

Possible source of beta cell destruction

Possible source of beta cell destruction
Doctors at Eastern Virginia Medical School's Strelitz Diabetes Center have been stalking the culprit responsible for Type 1 diabetes. Now, they are one step closer.

Members of a research team at the center, led by Jerry Nadler, MD, professor and chair of internal medicine and director of the center, have been studying the role of the enzyme 12-Lipoxygenase (12-LO) in the development of Type 1 diabetes. They hope that targeting this enzyme will hold the key to a cure.

Dr. Nadler and several research colleagues in the EVMS Department of Internal Medicine, including Kaiwen Ma, PhD, research instructor; Swarup K. Chakrabarti, PhD, research assistant professor; and David A. Taylor-Fishwick, PhD, associate professor, recently published their findings in the recent issue of The Journal of Clinical Endocrinology and Metabolism

Type 1 diabetes is a chronic condition that develops when the pancreas stops generating enough insulin to maintain normal levels of glucose (sugar) in the blood. Insulin moves sugar from the bloodstream to cells so that it can be used to generate energy. In Type 1 diabetes, a person's immune system attacks the insulin-producing beta cells, found only in the pancreas. When the beta cells die, the body no longer can produce enough insulin to regulate blood-glucose levels, and this can lead to serious health complications, even death, without therapy.........

Posted by: JoAnn      Read more         Source


August 6, 2009, 11:29 PM CT

Noninsulin-producing alpha cells in the pancreas

Noninsulin-producing alpha cells in the pancreas
In findings that add to the prospects of regenerating insulin-producing cells in people with type 1 diabetes, scientists in Europe -- co-funded by the Juvenile Diabetes Research Foundation -- have shown that insulin-producing beta cells can be derived from non-insulin-producing cells in the pancreas.

In results of a study published recently in the journal Cell, the researchers, led by Patrick Collombat of the Max-Planck Institute for Biophysical Chemistry in Gera number of and Ahmed Mansouri of the University of Gttingen in Gera number of, in collaboration with scientists at the JDRF Center for Beta Cell Therapy in Diabetes in Brussels, discovered in mice that new insulin-producing beta cells can be generated from alpha cells in the islets of the pancreas by modifying the expression of a specific gene (Pax4) in alpha cells. (Alpha cells generate the hormone glucagon in response to low blood sugar to restore normal blood sugar levels.) They also discovered that the alpha cells that give rise to new beta cells originate from progenitor cells in the pancreas. The newly formed beta cells result in better glucose control and prolonged survival of younger mice with diabetes.

In type 1 diabetes, the immune system attacks beta cells, stopping a person's pancreas from producing insulin, the hormone that enables people to get energy from glucose. One pathway towards a cure for type 1 diabetes appears to be to restore insulin production through regeneration of insulin-producing beta cells within a person's body, an alternative to transplanting functional beta cells from a donor.........

Posted by: JoAnn      Read more         Source


May 19, 2009, 5:21 AM CT

Triglycerides implicated in diabetes nerve loss

Triglycerides implicated in diabetes nerve loss
A common blood test for triglycerides a well-known cardiovascular disease risk factor may also for the first time allow doctors to predict which patients with diabetes are more likely to develop the serious, common complication of neuropathy.

In a study now online in the journal Diabetes, University of Michigan and Wayne State University scientists analyzed data from 427 diabetes patients with neuropathy, a condition in which nerves are damaged or lost with resulting numbness, tingling and pain, often in the hands, arms, legs and feet. The data revealed that if a patient had elevated triglycerides, he or she was significantly more likely to experience worsening neuropathy over a period of one year. Other factors, such as higher levels of other fats in the blood or of blood glucose, did not turn out to be significant. The study will appear in print in the journal's July issue.

"In our study, elevated serum triglycerides were the most accurate at predicting nerve fiber loss, in comparison to all other measures," says Kelli A. Sullivan, Ph.D., co-first author of the study and an assistant research professor in neurology at the U-M Medical School.

"These results set the stage for clinicians to be able to address lowering lipid counts with their diabetes patients with neuropathy as vigilantly as they pursue glucose control," says Eva L. Feldman, M.D., Ph.D., senior author of the study and the Russell N. DeJong Professor of Neurology at the U-M Medical School.........

Posted by: JoAnn      Read more         Source


May 11, 2009, 9:31 PM CT

How high glucose damages blood vessels

How high glucose damages blood vessels
New evidence of how the elevated glucose levels that occur in diabetes damage blood vessels may lead to novel strategies for blocking the destruction, Medical College of Georgia scientists say.

They found a decreased ability of blood vessels to relax resulted from increased activity of a natural mechanism for altering protein form and function, says Dr. Rita C.Tostes, physiologist in the MCG School of Medicine.

The scientists suspect increased modification of proteins by a glucose-derived molecule is a player in vascular problems linked to hypertension, stroke and obesity as well.

One aftermath of high glucose levels is low levels of the powerful vasodilator nitric oxide in blood vessels, a shortfall that increases the risk of hypertension and eventual narrowing of the vessels, scientists reported at the American Society of High blood pressure 24th Annual Scientific Program in San Francisco during a joint session with the Council for High Blood Pressure.

"We know diabetes is a major risk factor for cardiovascular disease and we think this is one of the reasons," Dr. Tostes says.

Diabetes increases the risk of cardiovascular disease such as heart disease and stroke, even when glucose, or blood sugar, levels are under control. In fact, about 75 percent of people with diabetes die from some form of heart or blood vessel disease, as per the American Heart Association.........

Posted by: JoAnn      Read more         Source


March 19, 2009, 6:13 AM CT

A step closer to understanding how to control high blood sugar

A step closer to understanding how to control high blood sugar
Researchers are closer to understanding which proteins help control blood sugar, or glucose, during and after exercise. This understanding could lead to new drug therapies or more effective exercise to prevent Type 2 diabetes and other health problems linked to having high blood sugar.

Insulin resistance happens when insulin produced by the body doesn't properly stimulate the transport of glucose into the cells for energy. Too much glucose in the bloodstream can cause a host of medical problems, including Type 2 diabetes, said Gregory Cartee, professor at the University of Michigan School of Kinesiology.

Insulin and muscle contractions are the two most important stimuli to increase glucose transport into muscle cells. Cells then use the glucose for energy. However, researchers aren't entirely sure how this works.

Cartee and colleague Katsuhiko Funai, a graduate student researcher in kinesiology, looked at how two different proteins thought to beimportant in stimulating glucose transport react to two different enzymes also correlation to glucose transport. The goal of the study was to understand the contribution of the two proteins, AS160 and TBC1D1, in skeletal muscle stimulated by insulin.

"We're trying to rule out or rule in which proteins are important with exercise," Cartee said.........

Posted by: JoAnn      Read more         Source


February 16, 2009, 9:49 PM CT

Insulin analogues or Insulin?

Insulin analogues or Insulin?
Insulin analogues are modified human insulins developed to address the limitations of human insulins which do not always respond to increased blood glucose levels in the same way as insulin that is naturally secreted by the body.

A comprehensive systematic review by Sumeet Singh and his colleagues http://www.cmaj.ca/press/pg385.pdf. looked at outcomes linked to the use of rapid- and long-acting insulin analogues in adult and childhood type 1 and type 2 diabetes as well as gestational diabetes.

"Our results suggest that differences between conventional insulins and insulin analogues are minimal in the management of type 1, type 2 and gestational diabetes," write Mr. Singh and coauthors. They suggest that insulin analogues appears to be useful for some patients with problematic hypoglycemia.

In a companion research study http://www.cmaj.ca/press/pg400.pdf looking at cost-effectiveness of insulin analogues, CADTH scientists observed that the routine use of long-acting insulin analogues in adults with type 1 or type 2 diabetes or use of rapid-acting analogues in patients with type 2 diabetes is not likely to be economically viable in a health care system with finite resources.

However, for adults with type 1 diabetes, rapid-acting insulin analogues can make sense as they appear to be cost-effective over human insulin.........

Posted by: JoAnn      Read more


January 12, 2009, 11:49 PM CT

Diabetes dementia and brain injuries

Diabetes dementia and brain injuries
Patients with dementia and diabetes appear to display a different pattern of injuries in their brains than patients with dementia but without diabetes, as per an article posted online today that will appear in the March print issue of Archives of Neurology, one of the JAMA/Archives journals.

"The association between diabetes mellitus and increased risk for dementia in the elderly is well documented," the authors write as background information in the article. Several possible mechanisms have been proposed for this association, including the direct effects of high blood glucose and insulin, the build-up of beta-amyloid plaques in the brain and the effects of diabetes-related vascular disease on blood vessels in the brain.

Joshua A. Sonnen, M.D., of the University of Washington, Seattle, and his colleagues studied 196 individuals who were part of the Adult Changes in Thought Study, a community-based investigation of dementia. After the participants died, their brains were autopsied and their cases were divided into four groups based on clinical information: those with diabetes and dementia, those with diabetes but not dementia, those with dementia but not diabetes and those without either disease.

In the 125 patients without dementia, neuropathological and biochemical factors did not differ based on diabetes status. However, among the 71 with dementia, two patterns of injury emerged based on whether the patients had diabetes and received diabetes therapy. Those without diabetes had larger amounts of beta-amyloid buildup and greater free radical damage, whereas those with diabetes had more microvascular infarcts (microscopic injury to small blood vessels in the brain known as arterioles) and more inflammation in neural tissue. This pattern was correlation to diabetes therapy, in that patients with dementia receiving therapy for diabetes had more microvascular infarcts, and untreated diabetic patients with dementia had beta-amyloid build-up similar to non-diabetic patients with dementia.........

Posted by: JoAnn      Read more         Source


January 5, 2009, 11:22 PM CT

Controlling diabetes with Low carbohydrate diet

Controlling diabetes with Low carbohydrate diet
In a six-month comparison of low-carb diets, one that encourages eating carbohydrates with the lowest-possible rating on the glycemic index leads to greater improvement in blood sugar control, as per Duke University Medical Center researchers.

Patients who followed the no-glycemic diet experienced more frequent reductions, and in some cases elimination, of their need for medicine to control type 2 diabetes, as per main author Eric Westman, MD, director of Duke's Lifestyle Medicine Program. The findings are published online in Nutrition and Metabolism

"Low glycemic diets are good, but our work shows a no-glycemic diet is even better at improving blood sugar control," he says. "We found you can get a three-fold improvement in type 2 diabetes as evidenced by a standard test of the amount of sugar in the blood. That's an important distinction because as a doctor who is faced with the choice of drugs or diet, I want a strong diet that's shown to improve type 2 diabetes and minimize medicine use".

Eight-four volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate ketogenic diet (less than 20 grams of carbs/day) or a low-glycemic, reduced calorie diet (500 calories/day). Both groups attended group meetings, had nutritional supplementation and an exercise regimen.........

Posted by: JoAnn      Read more         Source


December 11, 2008, 5:17 AM CT

Type 1 diabetes and celiac disease linked

Type 1 diabetes and celiac disease linked
Type 1 (juvenile) diabetes and celiac disease appear to share a common genetic origin, researchers at the University of Cambridge and Barts and The London School of Medicine and Dentistry, have confirmed.

Their findings, which are reported in this week's edition of the New England Journal (NEJM), identified seven chromosome regions which are shared between the two diseases. The research suggests that type 1 diabetes and celiac disease may be caused by common underlying mechanisms such as autoimmunity-related tissue damage and intolerance to dietary antigens (foreign substances which prompt an immune response).

Type 1 diabetes is an autoimmune disorder which causes the body to attack the beta cells of the pancreas, limiting its ability to produce the insulin necessary to regulate blood sugar levels. Celiac disease, also an autoimmune disorder, attacks the small intestine and is triggered by the consumption of gluten (a protein found in wheat, barley and rye) and cereals. The development and anatomy of the small intestine and pancreas are closely related, and the gut immune system shares connections with pancreatic lymph nodes, which have been associated with an inflammation of the pancreas and the destruction of beta cells.

In order to assess the genetic similarities and differences between the two inflammatory disorders, the scientists obtained 9339 control samples, 8064 samples from people with type 1 diabetes and 2560 samples from individuals with celiac disease. They found a total of seven loci (regions of a chromosome) were shared between the two.........

Posted by: JoAnn      Read more         Source

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Type-2 Diabetes
Type-2 diabetes is the most common form of diabetes, accounting for 90% of cases diabetes. This disease affects nearly 17 million Americans and is the seventh leading cause of death in the United States. Even though 17 million Americans have type-2 diabetes only half of these people are aware that they have diabetes. The death rate in patients with diabetes may be up to 11 times higher than in persons without the disease. The occurrence of diabetes in persons 45 to 64 years of age is 7 percent, but the proportion increases significantly in persons 65 years of age or older. Type-2 diabetes accounts for more than 90% of all diabetes worldwide.

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