February 5, 2010, 7:54 AM CT
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 MetabolismType 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.........
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August 6, 2009, 11:29 PM CT
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.........
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May 19, 2009, 5:21 AM CT
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.........
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May 11, 2009, 9:31 PM CT
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.........
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March 19, 2009, 6:13 AM CT
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.........
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February 16, 2009, 9:49 PM CT
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.........
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January 12, 2009, 11:49 PM CT
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.........
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January 5, 2009, 11:22 PM CT
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.........
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December 11, 2008, 5:17 AM CT
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.........
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November 19, 2008, 8:24 PM CT
More Data On Key Genes In Diabetes
One of the most reliable indicators to predict that a person will develop type 2 diabetes is the presence of insulin resistance. Insulin is produced in the pancreas and is the hormone responsible for ensuring that glucose reaches several tissues and organs in the body, such as muscles. Typically insulin resistance is characterized by the lack of tissue response to insulin and is counteracted by a greater production of insulin by the pancreas. When the pancreas does not have the capacity to produce the amount of insulin mandatory for tissues to receive glucose, glucose in blood increases to pathological levels and the individual goes from being insulin-resistant to suffering type 2 diabetes. Eventhough it is unclear what makes people develop insulin resistance, several studies report that resistant subjects show functional alterations in mitochondria. These intracellular organelles are responsible for transforming glucose into energy that the cell will then use to perform several functions. A study performed by the researcher Marc Liesa, a member of Antoni Zorzano's lab at the Institute for Research in Biomedicine (IRB Barcelona), describes a new control pathway of a gene responsible for mitochrondrial fusion, a process that contributes to the correct function of these organelles. This pathway could therefore be a key component in the development of insulin resistance. The results of this study have been reported in the scientific journal PloS One.........
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October 31, 2008, 5:15 AM CT
Type-1 diabetes not so much bad genes
Investigators combing the genome in the hope of finding genetic variants responsible for triggering early-onset diabetes may be looking in the wrong place, new research at the Stanford University School of Medicine suggests.
Early-onset diabetes, also known as type-1 diabetes, is an autoimmune disease, caused when the immune system attacks and destroys insulin-producing cells in a person's pancreas.
What triggers that immune response apparently has less to do with having a distinct set of gene variants than how the behavior of genes may differ in people with the disease. That is the finding of a study reported in the recent issue of Clinical Immunology, by Garry Fathman, MD, professor of immunology and rheumatology, and colleagues.
The paper builds upon the knowledge that particular immune-system-related gene variants confer type-1 diabetes susceptibility. A number of people have those genes, but only a fraction actually develop the disease. This has led a number of researchers to conduct exhaustive searches of the genome for other elusive genes that, when defective, may predispose someone to type-1 diabetes. Fathman suggests they may be on the wrong track.
Fathman explained it this way: "Take a pair of identical twins, with one having type-1 diabetes. Eventhough both have precisely the same genes, roughly half the time the other twin doesn't get the disease." The same holds true for other autoimmune diseases such as multiple sclerosis and rheumatoid arthritis, he added.........
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October 23, 2008, 9:24 PM CT
Green tea may delay onset of type 1 diabetes
A powerful antioxidant in green tea may prevent or delay the onset of type 1 diabetes, Medical College of Georgia scientists say.
Scientists were testing EGCG, green tea's predominant antioxidant, in a laboratory mouse with type 1 diabetes and primary Sjogren's syndrome, which damages moisture-producing glands, causing dry mouth and eyes.
"Our study focused on Sjogren's syndrome, so learning that EGCG also can prevent and delay insulin-dependent type 1 diabetes was a big surprise," says Dr. Stephen Hsu, molecular/cell biologist in the School of Dentistry.
They found it also worked well in their original disease focus.
In the mouse, EGCG reduced the severity and delayed onset of salivary gland damage linked to Sjogren's syndrome, which has no known cure.
"EGCG modulates several important genes, so it suppresses the abnormality at the molecular level in the salivary gland. It also significantly lowered the serum autoantibodies, reducing the severity of Sjogren's syndrome-like symptoms," Dr. Hsu says. Autoantibodies are antibodies the body makes against itself.
Both type 1 diabetes and Sjogren's syndrome are autoimmune diseases, which cause the body to attack itself. Autoimmune disorders are the third most common group of diseases in the United States and affect about 8 percent of the population, says Dr. Hsu. Sjogren's syndrome can occur alone or secondary to another autoimmune disease, such as lupus, rheumatoid arthritis or type 1 diabetes.........
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October 14, 2008, 7:52 PM CT
Researchers continue to find genes for type 1 diabetes
Genetics scientists have identified two novel gene locations that raise the risk of type 1 diabetes. As they continue to reveal pieces of the complicated genetic puzzle for this disease, the scientists expect to improve predictive tests and devise preventive strategies.
"As we add to our knowledge of the biology of type 1 diabetes and better understand details of the disease's genetic risk, we will be able to develop better diagnostic tests that meaningfully predict who will develop diabetes," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia.
The study appeared online Oct. 7 in
Diabetes, the journal of the American Diabetes Association. Hakonarson's co-leader in the study was Constantin Polychronakos, M.D., director of Pediatric Endocrinology at McGill University in Montreal.
Type 1 diabetes, formerly called juvenile diabetes, commonly begins in childhood, when the body's immune system malfunctions and destroys insulin-producing beta cells in the pancreas. Without insulin, blood sugar levels run out of control and can impair blood flow and damage the eyes, nerves and kidneys. It is second only to asthma as the most common chronic disease in American children. Patients are dependent for life on insulin injections or insulin medications.........
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June 10, 2008, 9:15 PM CT
Unique drug combination for Type I diabetes
Promising results from a study that tested a new approach for reversing Type 1 diabetes are being presented this week at the American Diabetes Association's 68th Annual Scientific Session in San Francisco.
The study tested the combination of Lisofylline (LSF), a drug that is being developed to halt immune damage to insulin producing cells, and Islet Neogenesis Associated Protein peptide (INGAP), a drug based on a naturally occurring protein produced by the pancreas. (ADA abstract number: 1620-P Unique Drug Combination for Reversal of Type 1 Diabetes, by Tersey, Carter, Kropf, Rosenberg, Nadler, available online at http://scientificsessions.diabetes.org).
The study was conducted at the University of Virginia by a team of researchers led by Jerry L. Nadler, M.D. Currently Director of Endocrinology and Metabolism at the University of Virginia, Nadler will join the faculty at Eastern Virginia Medical School (EVMS) in July as chair of the Department of Internal Medicine and head of the EVMS Strelitz Diabetes Center.
INGAP was discovered in 1997 at the EVMS Strelitz Diabetes Center by Aaron I. Vinik, M.D., Ph.D., Professor of Internal Medicine and the Strelitz Center's Director of Research.
Diabetes is caused by the body's inability to produce or process insulin, a hormone that cells need to convert food into energy. Uncontrolled diabetes causes serious complications throughout the body, including cardiovascular disease, blindness, kidney failure, and nerve disease. Type 1 diabetes is an autoimmune disease, caused when the body's own immune system mistakenly attacks and destroys the insulin-producing cells of the pancreas. This damage was once believed to be irreversible, however, new evidence suggests that the pancreas has an innate ability to repair and regenerate the insulin-producing cells. In Type 1 diabetes, however, the pancreas' ability to self-repair cannot keep pace against the autoimmune response that is causing the diabetes.........
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May 26, 2008, 8:05 PM CT
Natural compounds in cocoa and type 2 diabetes
Cocoa
Researchers have observed that consuming cocoa flavanols naturally occurring compounds in cocoa may offer a benefit to those affected by type-2 diabetes.
Consuming a cocoa flavanol-rich beverage daily may have the potential to positively impact the blood vessel dysfunction linked to diabetes, suggests a first-of-its-kind study recently reported in the Journal of the American College of Cardiology by an international group of scientists. Study participants who regularly consumed a cocoa flavanol-rich beverage made using the Mars, Incorporated Cocoapro process experienced a 30 percent improvement in measured vessel function at the completion of a 30-day trial.
Poor blood vessel function is recognized as an early stage in the development process of cardiovascular diseases such as atherosclerosis. For more than 20 million Americans living with diabetes, these vascular impairments can eventually lead to heart disease and stroke, the cause of death for two-thirds of those who suffer from diabetes. Despite good diabetes control and medical therapy, adults with the disease often continue to experience vascular dysfunction. This has led researchers on a search for novel medical or nutritional options to improve the health and quality of life for people with diabetes.........
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May 8, 2008, 9:14 PM CT
How slow growth as a fetus can cause diabetes as an adult
Intrauterine growth retardation (IUGR), which results in a baby having a low weight at birth, has been associated with the development of type 2 diabetes in adulthood. It has been suggested that this is because the expression of key genes is altered during fetal development and that this affects disease susceptibility during the later part of life. Evidence to support this hypothesis and indicating that the changes in gene expression might be permanent has now been provided by Rebecca Simmons and his colleagues, at the University of Pennsylvania, Philadelphia, using a rat model of IUGR.
Pervious studies using the rat model of IUGR have shown decreased fetal expression of the gene Pdx1, which is critical for the development and function of the cells that become defective in type 2 diabetes (pancreatic beta-cells), and adult onset of diabetes. In this study, expression of Pdx1 was found to be reduced in pancreatic beta-cells throughout life following IUGR. The molecular mechanisms (known as epigenetic mechanisms because they affect gene expression without altering the information in the gene) that reduced Pdx1 expression in pancreatic beta-cells were found to change during development. One mechanism was observed in the fetus, one following birth, and one after the onset of diabetes in adulthood. Of interest, the mechanisms reducing Pdx1 gene expression in the fetus and following birth could be reversed, whereas those reducing Pdx1 gene expression in the adult were irreversible. These data provide new insight into the mechanisms by which diabetes develops in adulthood following IUGR.........
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April 29, 2008, 8:29 PM CT
Benefits of drug therapy for diabetic eye disease
Diabetes retina
A JDRF collaboration between Johns Hopkins scientists and Genentech has shown that a drug for the therapy of diabetic eye disease haccording toformed better in clinical trials than the current standard therapy using laser surgery.
These findings, representing the six-month end-point evaluation of the READ-2 clinical trial coordinated by The Johns Hopkins University, were presented Monday at the 2008 Annual Meeting of The Association for Research in Vision and Ophthalmology, in Fort Lauderdale, Florida.
As per Barbara Araneo, Ph.D., director of the complications program at JDRF, These are very encouraging results, showing that drugs we have been testing in human clinical trials can be effective in slowing or stopping the effects of eye disease brought on by diabetes.
The multi-center READ-2 Study (Ranibizumab for Edema of the mAcula in Diabetes), which began in December 2006, was designed to test the long-term safety and effectiveness of injections of the drug ranibizumab in patients with diabetic macular edema, a condition characterized by swelling of the central portion of the retina, or macula, at the back of the eye. In addition, the trial sought to determine the comparative efficacy of ranibizumab versus conventional therapy laser photocoagulation treatment or both together.........
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November 7, 2007, 9:25 PM CT
'Tweens' double use of diabetes drugs
Diabetic pills
Americas tweens more than doubled their use of type-2 diabetes medications between 2002 and 2005, with girls between 10 and 14 years of age showing a 166 percent increase. The likely cause: Obesity, which is closely linked to Type 2 diabetes.
The finding is included in a study of chronic medicine use in children 5 to 19 reported Wednesday, Nov. 7 at the annual meeting of the American Public Health Association by scientists from the Saint Louis University School of Medicine and School of Public Health and pharmacy benefit manager Express Scripts. In addition to diabetes, utilization patterns for blood pressure, cholesterol, asthma and depression medications were also examined.
Across every chronic medicine class we examined over this four year period of time, childrens use increased, with varying patterns of growth across males and females and age groups, said Emily R. Cox, Ph.D., RPh, senior director of research at Express Scripts.
For example, the number of males between 15 and 19 using a blood pressure drug increased by 15.4 percent even as the number of females in the age group taking the drugs, called antihypertensives, declined by 1.6 percent.
Conversely, the number of females between 15 and 19 taking an anti-depressant increased by 6.8 percent while, for males in the same age group, utilization declined slightly.........
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July 17, 2007, 10:44 PM CT
Adult type 2 diabetes : exercise seems good
There are no high quality data to assess how well dietary therapys for type 2 diabetes work in people who have just been told they have the disease, but there is evidence that taking on exercise seems to be one way of improving blood sugar levels, as per the findings of a Cochrane Systematic Review.
Type 2 diabetes leaves a person at danger of having elevated levels of sugar (glucose) in their blood. This high sugar content then causes damage to blood vessels, which in turn harms a number of organs including the eyes, nerves, kidneys and heart.
When people are first diagnosed with this disease they are given dietary advice in the hope that this will enable them to take more control over the level of sugar in their blood. However, after searching published scientific literature, a team of Cochrane Scientists was unable to find high quality data that showed whether dietary advice did indeed alter the risk of developing long-term complications, affect overall quality of life or the likelihood of dying.
We did find 36 published articles that reported work from 18 different trials which included a total of 1467 people with type 2 diabetes, but only a minority of these trials examined hard clinical endpoints such as death or vascular disease, and those that did offered no details; most talked about factors that are easier to measure such as weight or blood sugar control, says lead researcher Nield, a researcher at the University of Teesside in Middlesbrough, UK.........
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