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)

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)

Discovery Leads to Earlier Diagnosis of Type 1 Diabetes

April 16, 2008

April 16, 2008 (PRNewswire) - Researchers at Children's Research Institute, located in Milwaukee, recently made significant discoveries in juvenile diabetes diagnosis. Led by Martin Hessner, PhD, associate, professor, Medical College of Wisconsin, the research team applied a new approach, finding that type 1 diabetes patients during the honeymoon phase create a unique genomic fingerprint.

The research team used a new type of blood test that identifies inflammation associated with type 1 diabetes though a unique genomic fingerprint. Remarkably, this fingerprint is evident years prior to disease onset. This discovery offers insight into the pathways responsible for type 1 diabetes. This fingerprint will be useful in identifying at-risk children earlier in the disease process. This offers hope for earlier treatment and even delay or prevention of full-blown diabetes. The Journal of Immunology recently published this research.

This research was accomplished through the Max McGee National Research Center for Juvenile Diabetes, established by football legend Max McGee. Diabetes is prevalent in the McGee family. Max's brother fought diabetes in his lifetime, and today, the McGees' son, Dallas, lives every day with this life-threatening disease. The late McGee, who died last October, co-founded the center to find a cure not only for his son, but for all people living with type 1 diabetes.

The center is one of few in the world studying the role of genetics in childhood diabetes. While diabetes is prevalent in some families, like the McGees, only 10 percent of newly diagnosed cases occur in families here that history exists. The Diabetes Program at Children's Hospital of Wisconsin is one of the largest in the country, serving more than 1,700 children with type 1 and type 2 diabetes and their families.

Posted by dlife at 02:56 PM | Comments (0)

Experimental Treatment for Type 1 Diabetes Patients Shows Promise

April 10, 2008

April 9, 2008 (Newswise) - New research monitoring the effects of Islet cell transplantation resulted in near-normal metabolic control and decreased hypoglycemia. This research will be presented at the American Association of Clinical Endocrinologists (AACE) 17th Annual Meeting & Clinical Congress, on Friday, May 16th, at the Walt Disney World Dolphin Resort in Orlando.

During the 18 month study, physicians used Continuous Glucose Monitoring Systems to monitor the effects of the islet cell transplant procedure on patients with type 1 diabetes. The results were intriguing.

“Our findings suggest that the majority of patients with Type 1 diabetes who have received an islet transplant benefit from near normal metabolic control, with fewer and shorter episodes of hypoglycemia,” said Lisa Gorn, DO, the study’s primary author. “These patients also spent longer periods of time in normoglycemia overall.

At the 2008 AACE Annual Meeting diabetes will be taking center stage. A special symposium titled “Clinical Trials Targeting Glycemia: What Do We Expect to Learn?” will consider the impact of glucose control through studies including ACCORD, ADVANCE, VADT, and others. Related sessions of interest include “Insulin Resistance and Atherosclerosis: The Missing Link,” and “Hypoglycemia: The Limiting Factor in the Glycemic Management of Diabetes.”

Posted by dlife at 09:53 AM | Comments (2)

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

April 08, 2008

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

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

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

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

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

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

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

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

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

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

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

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

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

Extra vitamin D in Early Childhood Cuts Adult Diabetes Risk

March 13, 2008

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)

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)

Deficient Regulators in the Immune System Responsible for Type 1 Diabetes

January 25, 2008

January 25, 2008 (EurekAlert) - The main regulators of the immune system, called CD4+Treg cells, are thought to be highly involved in a large range of immune diseases. The gradual reduction in their regulating capacity seems to play a critical role in the onset of type 1 diabetes, as demonstrated in the latest study by Dr. Ciriaco Piccirillo, a researcher in the Department of Microbiology and Immunology at the Research Institute of the McGill University Health Centre and the principal investigator for this project. This study was published this month in the journal Diabetes.

The immune system needs to be regulated so that it attacks only the site of an inflammation and focuses its attack on pathogens rather than on the body tissues, causing an autoimmune disease.

In a healthy patient, CD4+Treg cells deactivate any T lymphocytes, a type of immune cell, that are misprogrammed and could attack the body. Dr Piccirillo’s research indicates that in type 1 diabetic patients this control mechanism may be deficient, thereby allowing the misprogrammed T lymphocytes to proliferate and gain the ability to destroy the insulin-producing cells of the pancreas. This leads to type 1 diabetes.

“We have been able to demonstrate this in mice with type 1 diabetes, and other genetic studies have shown that this same mechanism is applicable to humans,” explained Dr. Piccirillo. Dr Piccirillo is an assistant professor at the McGill University, and the Canada Research Chair in Regulatory Lymphocytes of the Immune System. “Furthermore, the predominant role of nTreg cells leads us to believe that they are also involved in other autoimmune pathologies. Finding this common denominator among diseases that were previously thought to be unrelated is a very promising avenue for future study”, he adds.

Although the mechanism of action of CD4+Treg cells has not yet been completely unravelled, the scientific community generally accepts that this mechanism is of crucial importance to the entire immune system. Major fundamental and applied research efforts are currently being directed down this path and aim to clarify the role of CD4+Treg cells in order to develop innovative cellular therapies that could restore immune stability in patients.

“The eventual hope is to treat the cause of type 1 diabetes and other autoimmune diseases and not just their symptoms, as we do today”, says Dr Piccirillo.

Posted by dlifenews at 10:44 AM | Comments (1)

Vitamin A Suppresses Type 1 Diabetes in Animal Study

December 28, 2007

December 28, 2007 (USDA) - Pumpkin pie, sweet potatoes and many other holiday favorites are rich in vitamin A, a nutrient essential for good health. Now a study by Agricultural Research Service (ARS) nutrition scientists has shown, for the first time, that high levels of vitamin A can suppress development of type 1 diabetes in laboratory mice prone to that disease.

Type 1 diabetes, which affects more than 750,000 Americans, occurs when the immune system mistakenly attacks and destroys the pancreas' insulin-producing beta cells. Scientists already know that vitamin A and antioxidants—such as those in the freeze-dried grape powder also tested in the study—can regulate the immune system.

However, apparently no one had shown the suppressive effect of either vitamin A or grape powder on type 1 diabetes in either lab mice or humans, according to ARS physiologist Charles B. Stephensen.
He collaborated with molecular biologist Susan J. Zunino for the investigation, conducted in their laboratories at the ARS Western Human Nutrition Research Center in Davis, Calif. They reported their findings earlier this year in the Journal of Nutrition.

Blood sugar levels of the 45 mice in the experiment were taken regularly to determine onset of diabetes. At about seven months, only 25 percent of those mice eating a high-vitamin-A feed, and 33 percent of those eating grape-powder-enriched feed, had developed type 1 diabetes, while 71 percent of those on non-enriched feed had became diabetic.

Differences in levels of a protein called tumor necrosis factor-alpha, or TNF-alpha, linked in other studies to type 1 diabetes, were notable. TNF-alpha production by immune cells of mice fed the vitamin A- or grape-powder-enriched feed was significantly lower than that in cells of mice fed standard feed.
The study is part of ongoing research at the nutrition center to discover more about the potential of vitamin A and other nutrients to help prevent diabetes, cancer, asthma and other diseases of the immune system.

ARS, the U.S. Department of Agriculture's chief scientific research agency, and the National Institutes of Health of the U.S. Department of Health and Human Services funded the research.

Posted by dlifenews at 01:59 PM | Comments (1)

Cancer and Arthritis Therapy May be Promising Treatment for Diabetes

December 19, 2007

December 19, 2007 (EurekAlert) - An antibody used to treat certain cancers and rheumatoid arthritis appears to greatly delay type 1 diabetes in mice, Yale School of Medicine researchers report in the Journal of Clinical Investigation.

“Even better, the beneficial effects of the antibody continue to be observed long after the antibody is no longer administered,” the researchers said.

The antibody, rituximab (anti-CD20), depletes B cells. Experimental evidence in mutant mice indicates that B cells play a role in autoimmune diseases by interacting with T cells of the immune system. It is T cells that destroy insulin-producing cells directly in the pancreas, leading to type 1 diabetes.

“Our paper shows, for the first time, that after successful B cell depletion, regulatory cells emerge that can continue to suppress the inflammatory and autoimmune response even after the B cells return,” said Li Wen, senior research scientist in the division of endocrinology. “Even more strikingly, we found that these regulatory cells include both B and T cells.”

To determine if B cell depletion would work as a therapy for type 1 diabetes, Wen and her colleague at Yale, Mark Shlomchik, M.D., professor of laboratory medicine and immunobiology, developed a mouse model. They engineered mice that were predisposed to diabetes and had the human version of CD20, the molecule rituximab targets, on the surface of their B cells.

The researchers tested a mouse version of the drug to deplete B cells in mice either before diabetes onset, or within days of diagnosis with diabetes. The drug treatment significantly delayed diabetes onset in pre-diabetic mice. This translated to a 10- to 15-week delay in developing diabetes compared to mice given a “sham” treatment. The equivalent period for humans would be approximately 10 to 15 years. Of the 14 mice that already had diabetes, five stopped needing insulin for two to five months while all the sham-treated mice remained diabetic.

“These studies suggest that B cells can have dual roles in diabetes and possibly other autoimmune diseases. The B cells might promote disease initially, but after being reconstituted following initial depletion with rituximab, they actually block further disease,” Shlomchik added. “This means that multiple rounds of medication to deplete the B cells might not be necessary or even advisable.”

Posted by dlifenews at 11:38 AM | Comments (0)

Team Uncovers Gene’s Role in Type 1 Diabetes

November 07, 2007

November 7, 2007 (Newswise) — Researchers at the University of Virginia Health System have identified an enzyme thought to be an important instigator of the inner-body conflict that causes Type 1 diabetes. A chronic condition that affects nearly three million American children and adults, Type 1 diabetes is more severe than Type 2. Type 1 diabetes, also called autoimmune diabetes, arises when the body’s infection-fighting white blood cells start destroying the beta-cells that produce insulin in the pancreas.

To shed light on how this conflict begins, UVa researchers focused on a single gene, 12/15-lipoxygenase (12/15-LO). This gene leads to the production of the enzyme, which appears to have an important role in the activation of white blood cells in the pancreas.

Researchers developed non-obese diabetic female mice to serve as a model of Type 1 diabetes. After turning off the 12/15-LO gene in study mice, they discovered that these mice without the enzyme were 97 percent less likely to develop diabetes than mice that had normal levels of it, according to the study, published online in the journal Diabetes (to be published in print in February 2008).

“This research is exciting because it advances our knowledge of a new gene that is involved in causing Type 1 diabetes and could pave the way for new treatments to prevent or reverse this increasingly prevalent disease,” said Dr. Jerry L. Nadler, who is chief of the UVa Division of Endocrinology and Metabolism.

UVa researchers also discovered that study mice that did not have the 12/15-LO gene and remained non-diabetic demonstrated better glucose tolerance than non-diabetic NOD mice that were matched for age. (Worse glucose tolerance is an indication of having a pre-diabetes condition). The same group of study mice also had improved beta cell mass and less severe insulitis than their non-diabetic NOD counterparts.

Insulitis is a change in the islet cells that includes a high-fluid volume and too many white blood cells. While white blood cells normally help to fight off infections, they can cause damage over time when they infiltrate the islet cells of the pancreas.

“Our findings have two practical implications,” said co-author Marcia McDuffie, professor of Microbiology at UVa. “First, they help us to understand the complicated process that produces self-destructive white blood cells. This knowledge may be useful in predicting which children may be at risk for developing Type 1 diabetes before significant damage has occurred in the islets. Second, we may be able to design drugs targeting this enzyme that may help to prevent Type 1 diabetes in people at risk for the disease and also to prevent recurrence of disease in transplanted islets.”

Type 1 diabetes requires insulin injections, because the body cannot produce insulin on its own.

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

Consumption of Omega-3 Fatty Acids Associated with Decreased Risk of Type 1 Diabetes

September 25, 2007

September 25, 2007 (EurekAlert) - Preliminary research suggests that in children at increased risk for type 1 diabetes, dietary intake of omega-3 fatty acids was associated with a reduced risk of pancreatic islet autoimmunity, which is linked to the development of diabetes, according to an article in the Sept. 26 issue of JAMA.

“Type 1 diabetes mellitus is an autoimmune disease that is characterized by the destruction of insulin-producing beta cells in the pancreatic islets. Although it is not yet known what initiates the autoimmune process, it is likely that both genetic background and environmental factors contribute to the disease process,” the authors write. Certain dietary factors have been associated with the onset of type 1 diabetes as well as the autoimmune process that leads to the disease.

Jill M. Norris, M.P.H., Ph.D., of the University of Colorado at Denver and Health Sciences Center, Denver, and colleagues examined whether consumption of omega-3 and omega-6 fatty acids are associated with the development of pancreatic islet autoimmunity (IA; development of antibodies against the cells in pancreas that produce insulin) in children. The study, conducted between 1994 and 2006, included 1,770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA (human leukocyte antigen) genotype or having a sibling or parent with type 1 diabetes. The average age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. Fish is the primary source of marine polyunsaturated fatty acids. Childhood diet was measured using a food frequency questionnaire (FFQ).

A case-cohort study (n = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (outer portion of the red blood cell) was examined.

Fifty-eight children became positive for IA during follow-up. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and total omega-6 fatty acid intake, total omega-3 fatty acid intake was inversely associated with IA risk (a 55 percent reduced risk). The association was strengthened when the definition of the outcome was limited to those positive for two or more autoantibodies. In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was associated with a 37 percent decreased risk of IA.

“Our study suggests that higher consumption of total omega-3 fatty acids, which was reported on the FFQ, is associated with a lower risk of IA in children at increased genetic risk of type 1 diabetes,” the researchers write.

Posted by dlifenews at 11:45 AM | Comments (0)

Reducing Inflammation Plays Key Role in Type 1 Diabetes Therapy

August 01, 2007

August 1, 2007 (Eurekalert) -- Researchers at Beth Israel Deaconess Medical Center (BIDMC) have found that a triple combination therapy consisting of both tolerance-inducing and anti-inflammatory properties is successful in abolishing adverse autoimmunity against insulin-producing cells in a mouse model of Type 1 diabetes.

The findings, which appear in the Online Early Edition of the Proceedings of the National Academy of Sciences (PNAS) this week, offer a possible new prototype for therapies to restore normal blood glucose levels in diabetes patients and suggest a previously unrecognized role for inflammation in the disease.

“Type 1 diabetes is known to develop as a consequence of autoimmune destruction of insulin-producing pancreatic beta cells,” explains senior author Terry Strom, MD, Director of the Transplantation Research Center at BIDMC and Professor of Medicine at Harvard Medical School. “But in addition to the long-recognized role of T-cell-dependent immune-system-mediated islet destruction, this work reveals for the first time that a form of inflammation in fat and muscle [is also acting to] prevent insulin from disposing blood glucose into tissues that require glucose.”

Formerly known as juvenile-onset or insulin-dependent diabetes, Type 1 diabetes develops when the body’s immune cells attack and destroy its own pancreatic beta cells. Without beta cells, the body is unable to produce insulin, a hormone needed to convert glucose into energy. To prevent the development of serious complications, more than 21 million individuals with Type 1 diabetes – primarily children and young adults – must receive as many as three injections of insulin each day.

Previous attempts to treat existing Type 1 diabetes were primarily focused on restoring immune tolerance, which in healthy individuals is achieved when immune system cells “turn off” so as not to overreact and attack one’s own cells. In individuals with Type 1 diabetes, the process of immune tolerance fails to work properly, thereby permitting the self-destruction of the body’s beta cells.

But lead author Maria Koulmanda, MSc, PhD, director of Non-Human Primate Research in BIDMC’s Transplantation Research Center, wondered if there might also be a role for inflammation in the disease process.

“We knew that in cases of type 2 [non-insulin dependent] diabetes, a form of inflammation in muscle and fat prevents insulin from triggering the transfer of glucose from the blood into important insulin-sensitive tissues,” explains Koulmanda, who is also Assistant Professor of Surgery at HMS. “We thought that in addition to autoimmune destruction of insulin-producing cells, there might also be inflammation-induced insulin resistance [in type 1 diabetes.]”

To test this hypothesis, the authors administered a “cocktail” of three separate agents (rapamycin plus agonist IL-2- and antagonist-type, mutant IL-15-related Ig fusion proteins) in a NOD (non-obese diabetes) mouse model of type 1 diabetes. The therapy regimen, which included two novel immunoglobulin-fusion proteins, was aimed at both increasing tolerance and decreasing inflammation.

As predicted, following two to four weeks of treatment, the mice that had received the triple therapy maintained normal levels of blood sugar. In contrast, the control group of diabetic mice did not survive, despite receiving insulin.

The authors then conducted a molecular analysis which confirmed that the treatment had eliminated insulin resistance and relieved inflammation in the animals’ fat and muscle tissues.

“Although the treatment halted the progressive loss of insulin producing cells, the restoration of normal blood glucose levels actually was the result of inflammation being ablated in fat and muscle cells,” explains Strom. “By blocking the inflammation, we were able to restore the animals’ abilities to respond to insulin.”

“Our findings are very promising,” adds Koulmanda. “Type 1 diabetes is a serious disease requiring that children and young adults take insulin two to three times a day.”

And, she adds, despite this arduous therapy, insulin treatment does not prevent the occurrence of serious late-arising complications, including kidney failure, blindness and widespread cardiovascular disease.

“In clinical practice, it is not currently possible to identify when and if an individual will develop type 1 diabetes,” says Koulmanda. “Therefore, it is urgent to identify treatments that can restore normal blood glucose levels in patients with new-onset diabetes before insulin-producing cells are totally destroyed. We hope that our findings offer new hope in the long search for a cure of type 1 diabetes.”

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

Rapid-Acting Insulin Analogues in Diabetes Mellitus Type 1 -- Superiority Not Proven

July 18, 2007

High-quality long-term studies are lacking -- Not all studies have been fully published

July 18, 2007 (EurekAlert) - There is currently no evidence available of a superiority of rapid-acting insulin analogues over human insulin in the treatment of adult patients with diabetes mellitus type 1. The evidential value and design of studies available so far are inadequate and do not allow conclusions regarding most patient-relevant therapy goals, such as the reduction in long-term complications or overall mortality. Due to the lack of data, the benefit of rapid-acting insulin analogues in children and adolescents is unclear. Although one of the manufacturers conducted long-term comparative studies in this group of patients, it is withholding some of the results. This is the result of the final report of the Institute for Quality and Efficiency in Health Care (IQWiG) which was published in June 2007 and for which an English-language summary is now available.

The German Federal Joint Committee commissioned IQWiG to compare the benefit of rapid-acting insulin analogues versus human insulin, as well as to compare the benefit of various rapid-acting insulin analogues with each other. IQWiG assessed all 3 rapid-acting insulin analogues approved in Germany: insulin aspart (tradename in Germany: Novorapid), insulin lispro (tradenames in Germany: Humalog, Liprolog), and insulin glulisine (tradename in Germany: Apidra).

Effects determinable after 6 months at the earliest
The literature search retrieved a total of 9 published comparative studies, in which patients were observed for at least 24 weeks. Only studies with this minimum duration were included, as they give patients sufficient time to adjust to the new medication, and to observe the treatment effects under stable application. Eight of these studies compared either insulin aspart or insulin lispro with human insulin; no such study was available for glulisine. The only study available that compared two analogues referred to glulisine and lispro.

No long-term studies on insulin pump therapy available
Regarding insulin pump therapy, no study lasting at least 24 weeks was available. Therefore, it remains unclear whether patients would benefit and which advantage patients would have by using this form of administration. The same applies to children and adolescents, as only fully published short-term studies are available in this population so far. The company Novo Nordisk sponsored 2 completed long-term studies in children and adolescents. However, to date, both studies have only been partially published. In contrast to the manufacturers Sanofi and Lilly, Novo Nordisk was not prepared to provide the information needed for the report.

Studies not blinded
The conclusions of the 9 studies included in the evaluation are only of limited robustness. None of the studies was blinded, i.e. both the patient and the physician knew which type of insulin was being injected. Without blinding, there is a danger that patients, knowing their type of insulin, behave differently, which would subsequently lead to a bias in the results of the study. Moreover, inconsistent statements on important issues, which could not be clarified, were often made in the study documents.

No conclusions on important therapy goals possible
Even though patients have been treated with insulin analogues for 10 years, it is still unclear as to how these types of insulin affect long-term complications of diabetes type 1, mortality, and the necessity of hospital admissions. Regarding the reduction in blood glucose levels (measured by means of HbA1c), patients treated with insulin aspart had, on average, lower levels. However, these statistical differences were so small that an effect on patients’ health is not to be expected. Insulin lispro may prevent nocturnal hypoglycaemia better than insulin glulisine. The only study that compared these insulin analogues provided first indications, but no reliable evidence.

Rules of a fair comparison violated
In some studies, patients treated with insulin analogues assessed their quality of life as higher and were more satisfied with treatment than patients who injected human insulin. IQWiG did not evaluate this finding as evidence of an additional benefit of insulin analogues, as it was not based on a fair comparison: In the human insulin group, patients were requested to adhere to a fixed injection-meal interval; this was not the case in the insulin analogue group. It is therefore unclear whether the larger treatment satisfaction was caused by the drug class itself, or by the different forms of application prescribed by physicians.

The role of rapid-acting insulin analogues in the treatment of diabetes type 2 was assessed in a separate commission; the relevant final report had already been published by IQWiG in December 2005. This report also came to the conclusion that evidence of an additional benefit of insulin analogues has yet to be provided.

Posted by dlifenews at 04:54 PM | Comments (0)

Gene Discovered for Type 1 Diabetes in Children

July 16, 2007

July 16, 2007 (Newswise) — Pediatrics researchers at The Children’s Hospital of Philadelphia and McGill University in Montreal have identified a gene variant that raises a child’s risk for type 1 diabetes, formerly called juvenile diabetes. As investigators continue to pinpoint genes contributing to diabetes, they have their eyes on providing a scientific basis for designing better treatments and preventive measures for the disease.

The research adds a new gene and new knowledge to the four genes previously discovered for type 1 diabetes, in which the immune system destroys insulin-producing beta cells in the pancreas and makes patients dependent on frequent insulin injections to keep the body’s blood sugar under control. As the project continues, the study team expects to identify additional genes (perhaps as many as 15 or 20) thought to interact with each other in the disease.

The study appeared July 15 in an advance online letter in the journal Nature.

“The genotyping technology we now have available has revolutionized the way we can ask and answer research questions,” said the study’s lead author, Hakon Hakonarson, M.D., Ph.D., the director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia. “Unlike the previous technology, which was quite limited and dealt largely with relatively rare gene variants, we can now detect common genetic variants that are important in large numbers of individuals, and begin to understand how multiple genes interact in complex diseases such as diabetes.”

In the discovery phase of the study, the investigators examined the genomes of 1,046 children with type 1 diabetes. These DNA samples came from patients and families followed in pediatric diabetes clinics in Philadelphia and four Canadian cities. Specifically, the researchers compared the genomes of 563 patients with type 1 diabetes with those of 1,146 matched control subjects. Those results were combined with those obtained from an independent analysis of 483 family trios, in which the genomes of a child with the disease and both parents were examined.

The researchers confirmed the four previously identified locations for genes contributing to type 1 diabetes, but also uncovered a new type 1 diabetes locus on chromosome 16, occupied by a gene called KIAA0350. The team then replicated this discovery in yet another independent cohort of 1,333 children with the disease from the Type 1 Diabetes Genetics Consortium, which includes children of European descent in Europe, North America and Australia, as well as in 390 additional type 1 diabetes family trios from Canada.

Constantin Polychronakos, M.D., director of Pediatric Endocrinology at McGill University and senior author of the study, said that better knowledge of genes that predispose to type 1 diabetes may later enable physicians to screen newborns to predict those at high risk for the disease.

The gene implicated in the current research, KIAA0350, is known to be active almost exclusively in immune cells. Although scientists do not currently know the exact function of the protein the gene encodes, other research has predicted that it produces a protein called C-type lectin that is located on the surface of immune cells and binds to groups of sugars in the body.

“The role of KIAA0350 needs to be investigated,” said Hakonarson. “However, a special cell type called a natural killer (NK) cell expresses this gene abundantly, although at different levels based on these gene variants. Our hypothesis is that a special mutation in KIAA0350 may influence the sugar binding of the protein, and trigger an autoimmune response that activates these NK cells in such a way that they attack and destroy the islet cells in the pancreas, resulting in type 1 diabetes. A particular version of the gene protects against this inappropriate autoimmune response, while a different version of the gene makes it more likely to happen. ”

Although much research remains to be done, better understanding of the disease process may guide doctors to new and improved therapies. “If we know the gene pathways that give rise to type 1 diabetes, we hope to intervene early in life with targeted drugs or cell therapies to prevent the disease from developing,” said Polychronakos.

The current research used a technique called genome-wide association, in which highly automated analytic equipment rapidly scans each patient’s DNA for more than half a million genetic markers. It was performed at the Center for Applied Genomics at Children’s Hospital. The Center’s tools spell out a patient’s genotype—the specific pattern of variations among an individual’s 30,000 genes. Established in the summer of 2006, the center is taking on one of the largest genotyping projects in the world, and is the largest one dedicated to genetic analysis of childhood diseases.

“This study is the first one that our center has published on a gene associated with a complex childhood disease, but we have many projects under way and several other papers in press,” said Hakonarson. “Our goal at the Center is to discover the major disease-causing variants and genes that influence complex pediatric diseases, thus providing a scientific foundation that is based in biology for translating those discoveries into successful treatments.”

Among its current projects, the Center’s investigators are focused on identifying genes involved in pediatric asthma, allergy, obesity, attention-deficit hyperactivity disorder, autism, inflammatory bowel disease, hypertension, juvenile rheumatoid arthritis and the pediatric cancer neuroblastoma. The Center recently contributed 4,000 DNA samples to an industry-hosted database that serves as a free repository of control samples for researchers seeking gene variations in diseases.

Financial support for the study came from Genome Canada through the Ontario Genomics Institute, the Juvenile Diabetes Research Foundation and The Children’s Hospital of Philadelphia. Hakonarson’s and Polychronakos’ co-authors were affiliated with the University of Pennsylvania School of Medicine, the University of Manitoba, the Children’s Hospital of Eastern Ontario, the University of Ottawa, and Markham-Stoufville Hospital of Markham, Ontario.

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 430-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

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

Study Estimates 15,000 Children and Teens Diagnosed with Type 1 Diabetes Annually

June 29, 2007

June 29, 2007 (Newswise) — Approximately 15,000 children and adolescents in the United States are diagnosed with type 1 diabetes, and about 3,700 youth are diagnosed with type 2 diabetes annually, according to estimates from a major national study called SEARCH for Diabetes in Youth.

SEARCH, a multi-center study of childhood diabetes in racially and ethnically diverse populations, is the largest surveillance effort of diabetes among youth under the age of 20 conducted in the United States to date. The study covers 10 locations across the country where about 5.5 million children live.

In a report in the June 26, 2007, issue of the Journal of the American Medical Association (JAMA), study investigators identified 2,435 youth who were diagnosed with type 1 and type 2 diabetes in 2002 and 2003. The estimated overall incidence of diabetes in youth is 24.3 per 100,000 per year.

“The number of youth with newly diagnosed diabetes varies across major U.S. racial and ethnic groups as well as across age groups,” said lead author Dana Dabelea, MD, PhD, an associate professor of preventive medicine at the University of Colorado at Denver and Health Sciences Center’s School of Medicine, and SEARCH principal investigator (PI) for the Colorado site.

In children under the age of 10, most had type 1 diabetes, previously known as insulin-dependent diabetes, regardless of their race or ethnicity. Even among older youth ages 10-14, type 1 diabetes was frequent among non-Hispanic white (32.0 per 100,000 per year), African-American (19.2 per 100,000) and Hispanic adolescents (19.2 per 100,000 per year), but was much less common among Asian Pacific Islander (8.3 per 100, 000 per year) and American Indian youth (7.1 per 100,000 per year). In all age groups, the highest rates of type 1 diabetes were observed in non-Hispanic white boys and girls.

SEARCH estimates of type 1 diabetes incidence are higher than the incidence of insulin-dependent diabetes mellitus reported by previous U.S. childhood diabetes registries. Type 1 diabetes is an autoimmune disease in which a person’s own immune cells attack and destroy the beta cells of the pancreas, which produce the hormone insulin needed for survival. Researchers believe that the disease arises from a combination of susceptibility genes and an environmental trigger or triggers, such as an infectious agent or dietary component, that have not yet been identified.

The study also found that newly diagnosed type 2 diabetes was extremely rare in children under age 10 and gradually increased with age. Among minority adolescents and young adults 15-19 years of age high rates were documented among American Indian (49.4 per 100,000 per year), Asian-Pacific Islander (22.7 per 100,000 per years), African American (19.4 per 100,000 per year) and Hispanic (17.0 per 100,000 per year) youth. Although still relatively infrequent, type 2 diabetes was, nevertheless, present among non-Hispanic white youth 15-19 years of age (5.6 per 100,000 per year).

The incidence of type 2 diabetes in youth is consistent with the increasing rates of type 2 diabetes in adults. In both adults and children, this form of diabetes is closely linked to obesity, physical inactivity and a family history of type 2 diabetes.

“Reports of increasing incidence of both type 1 and type 2 diabetes in youth have been among the most concerning aspects of the evolving diabetes epidemic,” said Ann Albright, PhD, and director of the CDC’s Division of Diabetes Translation. “The SEARCH study has provided a clear picture of diabetes burden among youth of all US major racial/ethnic groups. These estimates are essential to ultimately design and implement public health efforts to prevent type 1 diabetes, once prevention strategies are identified, and type 2 diabetes, and to reduce the risk for both acute and chronic complications of diabetes in youth.”

“Information on the rates of diabetes in children is critical to developing policies to keep today’s and tomorrow’s youth healthy,” said Barbara Linder, MD, PhD, of the NIDDK. “The control, and ultimately the cure and prevention, of diabetes are particularly important in children because the risk of complications increases with disease duration. Fortunately, new therapies are allowing children with diabetes to have improved outcomes.”

The study investigators will continue to track the incidence of diabetes in youth in all of the various population groups through 2009.

“Continuing this surveillance effort is essential to document temporal trends in the incidence of diabetes among various racial and ethnic groups and accurately assess the future health care burden of diabetes and its complications in the U.S. pediatric and young adult population,” said Dabelea.

The study was funded by the Division of Diabetes Translation at the Centers for Disease Control and Prevention (CDC) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), a part of the National Institutes of Health (NIH). It involves six clinical centers in the states of California (Jean Lawrence, ScD; PI), Colorado (Dana Dabelea, MD, PhD, PI, study vice-chairperson), Hawaii (Beatriz Rodriguez, MD, PI), Ohio (Lawrence Dolan, MD, PI), South Carolina (Elizabeth Mayer-Davis, PhD, PI, study chairperson) and Washington (Catherine Pihoker, MD, PI). The central laboratory for the study is the Northwest Lipid Research Laboratories in Seattle, Wash. (Santica Marcovina, PhD, PI). The coordinating center is at the Division of Public Health Sciences at Wake Forest University School of Medicine (Ronny Bell, PhD, PI).

The School of Medicine faculty work to advance science and improve care as the physicians, educators and scientists at University of Colorado Hospital, The Children’s Hospital, Denver Health, National Jewish Medical and Research Center and the Veterans Administration Medical Center. The School is part of the University of Colorado at Denver and Health Sciences Center, one of three universities in the University of Colorado system.

Posted by dlifenews at 05:07 PM | Comments (0)

Cord Blood May Preserve Insulin Levels in Children With Type 1 Diabetes

June 27, 2007

June 27, 2007 (EurekAlert) -- Umbilical cord blood may safely preserve insulin production in children newly diagnosed with type 1 diabetes, according to findings from a small national pilot study presented Monday (June 25) at the American Diabetes Association’s 67th Scientific Sessions in Chicago.

University of Florida researchers sought to determine whether it is feasible to use a patient’s own cord blood stem cells to neutralize the body’s autoimmune attack on the pancreas and help restore the organ’s ability to make insulin, which regulates how the body uses sugar and other nutrients for energy.

“This is the first attempt at using cord blood as a potential therapy for type 1 diabetes. We hope these cells can either lessen the immune system’s attack on the pancreas or possibly introduce stem cells that can differentiate into insulin-producing cells,” said pediatric endocrinologist Dr. Michael Haller, an assistant professor of medicine at UF’s College of Medicine.

“While this is a relatively small study we can confidently say this is safe, and we have seen metabolic and immunologic changes to suggest there may be benefit,” Haller said. “It’s not curing diabetes, but this is a first step to help us learn more and get us moving in the right direction.”

Researchers got the idea in part from a patient’s father who had read that scientists elsewhere were able to reverse diabetes in mice by taking bone marrow from one animal and infusing it into its identical sibling without using chemotherapy or radiation therapy. And in the lab, scientists have been able to coax stem cells isolated from cord blood into making insulin. The man asked UF researchers whether giving a patient his or her own cord blood could have a similarly positive effect.

“We thought this was a very reasonable question and would be a safe approach as long as we refrained from using chemotherapy, radiation therapy or manipulating the cells. Since there are a lot more people out there who are banking cord blood than there were five years ago, we felt this approach would become increasingly attractive,” Haller said.
A decade ago less than 1 percent of Americans were banking cord blood; today, that figure has grown to about 4 percent and is rising, Haller said. Cord blood is rich with cells that help regulate the immune system but until now has typically been used to restore a patient’s immune system after treatments for leukemia or lymphoma.

UF researchers identified children recently diagnosed with type 1 diabetes whose families banked their umbilical cord blood at birth. Most were still producing a small amount of insulin. The researchers then gave seven patients ages 2 to 7 intravenous infusions of stem cells isolated from their own cord blood. (They have since treated an additional four children.) The patients were evaluated for the next two years to measure how much insulin they were making on their own and to assess blood sugar levels and the function of key immune system cells.

In the first six months, they required significantly less insulin -- on average 0.45 versus 0.69 units of insulin per kilogram per day -- and maintained better control of blood sugar levels than children of comparable age with type 1 diabetes who were randomly selected from the clinic population. The researchers also noted that the children who received cord blood infusions had higher levels of regulatory immune cells in their blood six months after the infusion, on average 9 percent of the total cell volume compared with 7.21 percent at the time of infusion.

“This isn’t a cure-all. We think that giving these cells is essentially providing some immunotherapy and downregulating the autoimmunity these patients have,” Haller said. “Realistically, we hope to protect what’s left of their insulin-production for an extended period of time. We think the immune regulation hypothesis is more likely than the hypothesis that stem cells are forming insulin producing cells on their own.”

The idea would be to intervene and repair any early damage during the “honeymoon period” many patients enjoy -- the first several months after diagnosis during which insulin needs are minimal, he added.

“Our group’s concept is that we won’t be able to cure diabetes without a combination therapy approach,” Haller said. “It’s naïve to think that with one agent we’re going to reverse a very complicated disease like type 1 diabetes. We probably need to go at it with multiple drugs to attack the various facets of the disease. Curing type 1 diabetes may require a similar approach to treating AIDS or cancer. The care of patients with these complex diseases did not markedly improve until combination therapies were administered. I suspect it will be the same with diabetes.”

The Juvenile Diabetes Research Foundation and the National Institutes of Health funded the study, with support from UF’s Clinical Research Center. UF researchers next plan to enroll up to 23 patients who will receive cord blood infusions. They also will seek to improve on the small metabolic and immunologic advantages they’ve noted so far, possibly by testing the addition of one of the many drugs currently being used in other type 1 diabetes trials.

“We need to decide which agent will work well when combined with the cord blood,” Haller said. “Right now we are not manipulating the cells. We are simply infusing the cord blood. In addition to adding other drugs, we may need to see if we can take the key cells from cord blood and safely manipulate them to improve on our findings.”

The application of human cord blood in the treatment of type 1 diabetes is of extreme importance, said Colin P. McGuckin, a professor of regenerative medicine at Britain’s University of Newcastle upon Tyne Medical School.

“The work carried out in the University of Florida has led the field in showing that cord blood contains cells which can quieten the immune system attack on the patient’s pancreas,” McGuckin said. “We know that cord blood contains very specialized cells which are there to stop rejection of the placenta of the child to the mother during pregnancy, and these are likely to be the ones which are useful for treatment in type 1 diabetes. Together with our work, showing that beta cells producing insulin can be formed using cord blood, we are on track to help diabetes patients in the future. The first step, though, has to be quietening the immune system attack, and this is why the work in Gainesville is so important.”

Posted by dlifenews at 04:07 PM | Comments (2)

First Use of Cord Blood to Alter Course of Type 1 Diabetes

June 25, 2007

June 25, 2007 (PRNewswire-USNewswire) -- In a small pilot study, transfusion of stored, autologous (i.e. the person's own), umbilical cord blood into a group of children newly diagnosed with type 1 diabetes appears to have reduced their disease severity, possibly re-setting the immune system and slowing the destruction of their insulin-producing cells, according to a report presented today at the American Diabetes Association's 67th Annual Scientific Sessions.

"After only six months, it is too early to tell how long the children will benefit from this therapy, but early signs indicate that it may have helped enhance blood glucose control and management," said Michael J. Haller, MD, Assistant Professor of Pediatric Endocrinology at the University of Florida College of Medicine and lead author of the study, in a recent interview.

"But more important than the potential benefit in these children, this first use of cord blood in diabetes will help us focus on what it is in the cord blood that yielded the benefit," he said. "We then hope to isolate and grow that cell type to develop therapies for a larger pool of people, not just those who have stored cord blood." He discussed how such a cellular therapy might be one component of a future immune-modulating "cocktail."

Nearly 21 million Americans have diabetes, a group of serious diseases characterized by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, and amputations. It is the fifth leading cause of death by disease in the U.S.

Type 1 diabetes is an immune-mediated disease that involves a failure of the body's immune system to recognize cells -- its "self" -- as non- threatening (called a failure of "tolerance"), leading to progressive destruction of the insulin-producing beta cells in the pancreas. Type 1 diabetes usually strikes children and young adults, although disease-onset can occur at any age.

STUDY METHODOLOGY AND RESULTS
The researchers recruited seven young (age 2 to 7 years at the time of infusion) children with type 1 diabetes who had their own stored cord blood and infused them with it. This group was matched with 13 randomly selected youngsters of similar age and diabetes duration who had been intensively treated with insulin and served as a control group.

A1C tests and total daily insulin use from diagnosis to six months after infusion were compared. (A1C is a measure of blood glucose control over a two- to three-month period.)

The children who received cord blood transfusions had lower average A1Cs, i.e. 7% vs. 8.04% in the intensively treated control group receiving insulin therapy alone. Children who had cord blood transfusions also required much lower average total daily insulin than the control group, 0.45 vs. 0.69 units of insulin per kilogram per day, respectively.

Over the six-month period there was little change in the stimulated C-peptide values of the group, indicating that they may have had retention of endogenous insulin production longer than expected for young children.

"Because of the cord blood infusion, these youngsters may retain endogenous insulin production for a longer period," said Dr. Haller. "Therefore, they may be at lower risk for diabetes complications over the length of their lifetime, as was demonstrated by the groundbreaking Diabetes Control and Complications Trial."

No adverse events associated with the transfusions were observed.

CONCLUSIONS
"Our preliminary data showing lower A1Cs, lower average insulin requirements, and possible preservation of C-peptide suggest a beneficial effect of autologous umbilical cord transfusion in youngsters with recent onset type 1 diabetes," said Dr. Haller. "Considerable research today is seeking to delay complete beta cell loss, and this may be one effective approach for children who have their own cord blood, who are newly diagnosed with type 1, and who enter clinical trials."

However, he emphasized that it would be costly and inefficient for everyone to save their cord blood as a possible type 1 therapy. Therefore, the goal is to determine the factor in the cord blood that is yielding the benefit.

POSSIBLE MECHANISMS
Desmond A. Schatz, MD, Professor and Associate Chairman of Pediatrics at the University of Florida College of Medicine and senior author of the study, posited three potential mechanisms for the results in a recent interview.

"While cord blood contains stem cells capable of differentiating into insulin-producing cells, and infused cells could have stimulated islets to regenerate, it is most likely that infused regulatory T cells, known to be able to induce autoimmune tolerance, may have prompted a type of immune regulation," he said.

"We think that cord blood is a very rich source of these regulatory T cells, and there was a measurable increase in these cells in patient's blood through six months after the infusion," said Dr. Schatz. "While we have not followed the participants long enough to determine how long these benefits will last, the improvement in blood glucose control appears to be related to the infusion of these cord blood cells." The youngsters will continue to be followed long term.

While this study does not confirm a specific advantage for any particular type of cell therapy, it argues strongly in favor of expanded studies to better characterize any source of regulatory T cells (also known as T regs) that may eventually be used in type 1 diabetes.

"Transfusing the cord blood may provide a bolus of T regs, a type of immune cell that can keep the immune system from attacking the pancreas," said Dr. Haller. Based on the changes observed at six months, the researchers think the T regs may restrain the immune system.

"The idea of restoring tolerance is the holy grail of autoimmune research, and would make it possible to arrest and perhaps even prevent the development of diabetes," he explained. "Our theory is that T regs are one of the key factors yielding benefit in cord blood," he explained. "Eventually we might be able to take T regs out of cord blood in order to have a source from which to grow more."

"The type 1 diabetes disease process may be altered with T regs plus a mild immunosuppressive or other immunomodulating drug or additional cell therapy, which is called 'cocktail therapy,' in a manner similar to the breakthroughs made in treating HIV and cancer," said Dr. Haller.

"We feel a cautious optimism for a role for cellular therapies in altering the natural history of type 1 as it relates to ameliorating the disease or preventing the disease, likely in combination with other agents," said Dr. Schatz.

An editorial in the Journal of the American Medical Association in April 2007 on another approach to cellular therapy to interdict type 1 diabetes noted that umbilical cord cells are one of the many sources of such cells under consideration, as well as T-regulatory lymphocytes, embryonic or adult stem cells, and dendritic cells. The editorialist suggested that, "Research in this field is likely to explode in the next few years... " and that "The time may indeed be coming for starting to reverse and prevent type 1."(1)

Co-authors with Drs. Haller and Schatz were Mark Atkinson, PhD; Hilla-Lee Viener, BS; Todd Brusko, PhD; Clive Wasserfall, MS; Kieran McGrail, BS; Susan Staba, MD; and Chris Cogle, MD, all of the University of Florida College of Medicine.

The American Diabetes Association is the nation's leading voluntary health organization supporting diabetes research, information and advocacy. Founded in 1940, the Association has offices in every region of the country, providing services to hundreds of communities. For more information, please call the American Diabetes Association at 1-800-DIABETES (1-800-342-2383) or visit http://www.diabetes.org. Information from both these sources is available in English and Spanish.

Posted by dlifenews at 09:52 AM | Comments (0)

Novel Delivery Method of Insulin Gene to Combat Juvenile Diabetes Developed

June 04, 2007

June 1, 2007 (Newswise) — A safer method to deliver the insulin gene to diabetes patients using nanoparticles, was presented today at the 10th Annual Meeting of the American Society of Gene Therapy (ASGT) in Seattle.

Type 1 or juvenile diabetes is caused by autoimmune destruction of the insulin producing pancreatic β-cells. As a result of the loss of insulin, blood sugar levels rise too high, causing damage to fine blood vessels and nerve endings leading to debilitating symptoms. As a result patients become dependent upon daily insulin injections to survive. However, it is virtually impossible to match the sugar content of each meal with the optimal dose of insulin – the cumulative ‘mistakes’ severely reduce both the quality and length of life.

Recreating appropriately regulated internal insulin secretion in surrogate cells (i.e. non-β-cells) in individuals with diabetes is an attractive approach to cure this disease. A major hurdle with this approach has been replicating automatic insulin secretion that is tuned to the body’s requirements.

Dr. Anthony Cheung and his colleagues at enGene, Inc., Vancouver, aim to develop an approach to restore the meal-responsive insulin production and release capability in individuals with diabetes, thereby eliminating the need for insulin injections while also improving control of blood sugar levels.

They intend to achieve this by inducing specific cells of the gut to take over production of insulin. The team previously reported that gut K-cells can be induced with the insulin gene to produce insulin in response to meal ingestion in a pattern comparable to normal insulin production from the pancreas.

In order to translate this technology to clinical use, the team developed a novel method to deliver the insulin gene to the target K-cells in the gut using nanoparticles. The nanoparticles contain a component called chitosan that provides protection to the insulin gene while in the gut as well as an integrase to insert the insulin gene into the patient’s gut cells.

Gene delivery by these nanoparticles is expected to be safer and less immunogenic than more commonly used virus-based agents. In the preclinical testing reported in this conference, a single administration of the nanoparticles induced the production of insulin in the recipients for over 130 days. Moreover, the insulin production was responsive to meals.

Work is currently underway to support an Investigational New Drug filing with the FDA, anticipated by late 2008 or early 2009, after which the team plans to test these nanoparticles in individuals suffering from diabetes.

Posted by dlifenews at 11:13 AM | Comments (0)

Study Tests Oral Insulin to Prevent Type 1 Diabetes

June 01, 2007

GAINESVILLE, Fla., June 1, 2007 (Eurekalert)— University of Florida researchers have begun a clinical study of oral insulin to prevent or delay type 1 diabetes in people at risk for the disease.

The UF Health Science Center and Shands at UF are among 14 centers in the United States working with affiliate sites and participating physicians in Type 1 Diabetes TrialNet, a research group dedicated to the understanding, prevention and early treatment of type 1 diabetes.

“This is a unique opportunity to attempt to prevent the disease in relatives at risk for type 1 diabetes,” said Desmond Schatz, M.D., medical director of UF’s Diabetes Center of Excellence and principal investigator with the UF TrialNet Clinical Center. “The intervention may also offer hope for delaying the onset of the disease.”

An estimated 1 to 2 million people with the disease have type 1 diabetes, which occurs when white blood cells vital to the body’s defenses against infectious diseases attack insulin-producing beta cells in the pancreas. The insulin these cells produce regulates how the body uses and stores sugar and other food nutrients for energy.

Research has shown the pancreas is resilient and more than half its insulin-producing beta cells must be irreversibly destroyed before an individual develops symptoms of the disease, which can take months or even years to occur.

That long period prior to the onset of symptoms provides an opportunity for interventions aimed at preventing the disease’s development, Schatz said.

In the study, University of Florida researchers are testing whether an insulin capsule taken by mouth once a day can prevent or delay type 1 diabetes in a specific group of people at risk for the disease.

An earlier trial suggested that oral insulin might delay type 1 diabetes for about four years in some people with islet cell autoantibodies in their blood. The presence of these autoantibodies alerts physicians to the destruction of insulin-producing cells up to 10 years before symptoms set in and indicates an individual is at greater risk of developing the disease.

For a person with high-risk genes and all three autoantibodies, the risk of developing diabetes in the next five years is greater than 50 percent, Schatz said.

“We hope that learning about the underlying immune events that set the stage for diabetes will help us identify ways to rein in the autoimmune attack on beta cells,” he said.

Animal studies have also suggested that insulin taken orally might even prevent type 1 diabetes. Some scientists think that introducing insulin via the digestive tract induces tolerance, a quieting of the immune system.

First- and second-degree relatives of people with type 1 diabetes who may be at risk are initially being screened through TrialNet’s natural history study, which is examining the immune and metabolic events that precede diabetes symptoms. Screening involves a simple blood test. Individuals enrolled in the natural history study are closely monitored for diabetes development and may be eligible to participate in the oral insulin trial or future studies that try to arrest the autoimmune process.

To lower blood sugar levels once diabetes occurs, patients need three or more insulin injections a day or treatment with an insulin pump. To prevent complications, they must regularly monitor their blood glucose, striving for a range that is as close to normal as possible.

Other diabetes studies under way at UF include a trial aimed at preserving insulin production in people recently diagnosed with type 1 diabetes, who often still have a supply of functioning beta cells. If these remaining beta cells can be protected with the help of insulin injections, more patients would be able to tightly control their blood glucose, preventing or delaying damage to the eyes, nerves, kidneys, heart and blood vessels.

Another TrialNet study seeks to turn off the body’s attack on beta cells with rituximab, a monoclonal antibody that binds to and temporarily destroys a class of immune cells. The rituximab trial is recruiting patients with type 1 diabetes diagnosed within the previous three months. Also under way is a study testing whether a combination of two drugs approved by the FDA to prevent rejection after an organ transplant can slow or arrest the autoimmunity of type 1 diabetes.

Lastly, the Environmental Determinants of Diabetes in the Young, or TEDDY, study aims to discover the genes and environmental exposures that may cause type 1 diabetes through a newborn screening program. Babies found to be at a high risk of developing the disease may enroll in TEDDY II and will be tracked over time to examine environmental risk factors.

Posted by dlifenews at 04:51 PM | Comments (0)

Glucosamine-like Supplement Inhibits Multiple Sclerosis, Type 1 Diabetes

May 14, 2007

EurekAlertMay 14, 2007 (EurekAlert) — A glucosamine-like dietary supplement has been found to suppress the damaging autoimmune response seen in multiple sclerosis and type-1 diabetes mellitus, according to University of California, Irvine health sciences researchers.

In studies on mice, Dr. Michael Demetriou and colleagues with the UC Irvine Center for Immunology found that N-acetylglucosamine (GlcNAc), which is similar but more effective than the widely available glucosamine, inhibited the growth and function of abnormal T-cells that incorrectly direct the immune system to attack specific tissues in the body, such as brain myelin in MS and insulin-producing cells of the pancreas in diabetes. Study results appear on the online version of the Journal of Biological Chemistry.

“This finding shows the potential of using a dietary supplement to help treat autoimmune diseases,” said Demetriou, an assistant professor of neurology, and microbiology and molecular genetics. “Most importantly, we understand how this sugar-based supplement inhibits the cells that attack the body, making metabolic therapy a rational approach to prevent or treat these debilitating diseases.”

The UC Irvine study defines how metabolic therapy with the sugar GlcNAc and other related nutrients modifies the growth and autoimmune activitiy of T-cells. Virtually all proteins on the surface of cells, including T-cells, are modified with complex sugars of variable lengths and composition. Recent studies have shown that changes in these sugars are often associated with T-cell hyperactivity and autoimmune disease.

In mouse models of both MS and type 1 diabetes, Demetriou and colleages found that GlcNAc prevented this hyperactivity and autoimmune response by increasing sugar modifications to the T-cell proteins. This therapy normalized T-cell function and prevented development of paralysis in MS and high blood glucose levels in type 1 diabetes.

This study comes on the heels of others showing the potential of GlcNAc in humans. One previous clinical study reported that 8 of 12 children with treatment-resistant autoimmune inflammatory bowel disease improved significantly following two years of treatment with GlcNAc. No significant adverse side effects were noted.

“Together, these findings identify metabolic therapy using dietary supplements such as GlcNAc as potential treatments for autoimmune diseases.” Demetriou said. “Excitement for this treatment strategy stems from the novel mechanism for affecting T-cell function and autoimmunity and the availability and simplicity of its use. However, additional studies in humans will be required to assess the full potential of this therapeutic approach.”

Autoimmune diseases such as MS and type 1 diabetes mellitus result from poorly understood interactions between inherited genetic risk and environmental exposure. MS results in neurological dysfunction, while uncontrolled blood glucose in type 1 diabetes can lead to damage of multiple organs.

Posted by dlifenews at 10:50 AM | Comments (0)

National Joslin-Led Study Shows Tight Blood Glucose Control in People with Type 1 Diabetes Does Not Impact Cognitive Ability

May 03, 2007

JoslinMay 2, 2007 (Joslin) - A study led by researchers at Joslin Diabetes Center provides good news for patients with type 1 diabetes who want to maintain tight blood glucose control and thus significantly reduce their risk of developing the devastating complications of the disease--heart disease, kidney failure, eye disease and blindness, and nerve damage. The study, which is part of the Epidemiology of Diabetes Interventions and Complications study (EDIC) funded by the National Institutes of Health (NIH), will be published in the May 3, 2007, issue of the New England Journal of Medicine.

The EDIC is a follow-up study of the Diabetes Control and Complications Trial (DCCT), a large NIH-funded study that compared intensive management of blood glucose to conventional control in people with type 1 diabetes. The study's findings established the effectiveness of tight blood glucose control in dramatically slowing the onset and progression of diabetes complications. However, intensive control increased episodes of severe hypoglycemia--abnormally low blood glucose levels that can cause confusion, irrational behavior, convulsions and unconsciousness--that is associated with tight control. After following participants for 12 more years, the researchers have shown that multiple episodes of severe hypoglycemia do not lead to long-term loss of cognitive ability. They cautioned, however, that further study is needed to determine whether hypoglycemic episodes in young children have any lasting cognitive effects, since the youngest DCCT participants were 13 years old at the beginning of the study.

"The EDIC study provides further support for the safety of intensive diabetes therapy and the benefits of maintaining good glycemic control," says the study's principal investigator, Alan M. Jacobson, M.D., head of Joslin's Behavioral and Mental Health Research Section and Professor of Psychiatry at Harvard Medical School. Preliminary findings from the EDIC study were presented at the June 2006 Scientific Sessions of the American Diabetes Association. "While acute episodes of hypoglycemia can impair thinking and can even be life-threatening, type 1 diabetes patients do not have to worry that such episodes will impair their long-term abilities to perceive, reason and remember."

"Hypoglycemia is a serious, frightening experience," said Catherine Cowie, Ph.D., who oversees EDIC for the NIH. "However, given the importance of intensive blood glucose control in preventing the complications of diabetes, it is tremendously heartening to know that such episodes have no long-term cognitive effects in the age groups studied in the DCCT/EDIC."

The DCCT findings confirmed Dr. Elliott P. Joslin's theory on the benefits of tight diabetes control in reducing diabetes complications. The DCCT investigators examined 1,441 subjects, ages 13 to 39, with type 1 diabetes. About half of the group received intensive therapy with either an insulin pump or three or more daily insulin injections. The remaining subjects received conventional therapy of one to two insulin injections daily. During the study, the patients' A1C readings, which reflect average blood glucose levels over several months, differed between the two groups by about 2 percentage points (7.1 percent for the intensive therapy group vs. 9.0 percent for the conventional). At the study's conclusion in 1993, researchers reported that the group receiving intensive therapy experienced 76 percent less eye disease, 50 percent less kidney disease, and 60 percent less nerve disease. As a result of their findings, intensive therapy was recommended for all subjects taking part in the trial.

But the DCCT also showed that tight control comes at a cost: patients who received intensive therapy were three times as likely to experience hypoglycemic episodes severe enough to require the assistance of another person than patients who were on conventional therapy. This finding raised the fear that, although tight control may lower the risk of developing serious diabetes complications, it might also lead to a long-term loss of cognitive ability.

At the start of the DCCT, in order to evaluate the potential impact of diabetes treatment and recurrent hypoglycemic episodes on cognitive ability, all patients were given a comprehensive battery of cognitive tests. These tools analyzed abilities in eight domains: problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency and motor speed. When these tests were repeated during the DCCT on an average of 6.5 years after its start, no adverse effects were observed that were associated with either treatment type or with the number of severe hypoglycemic episodes experienced.

Although these findings were encouraging, the researchers recognized the need for longer-term follow-up to determine if the increase in hypoglycemic episodes would affect cognitive ability over time. Furthermore, a longer-term study would allow them to examine whether the added effect of increasing age and duration of the disease might also contribute to a decline in cognitive ability.

To answer these questions, Dr. Jacobson and his colleagues at 28 other medical centers around the country examined 1,144 participants from the original DCCT trial: 588 patients who had received intensive therapy, and 556 patients who received conventional therapy. Tracking for hypoglycemic comas or seizures over the 12-year period following the DCCT, 889 patients reported no such events; 246 reported from one to five events; and nine patients reported more than five.

"While it is most gratifying to find little evidence of a direct effect of moderately severe hypoglycemia on intelligence, diabetic patients still need to avoid hypoglycemia because very low blood sugar levels can trigger a temporary reduction in their ability to pay attention and react quickly, which may, in turn, lead to serious injuries," said Christopher Ryan, Ph.D., Professor of Psychiatry, Psychology, and Health & Community Systems at the University of Pittsburgh School of Medicine.

The researchers evaluated all of the patients using the same neuropsychological tests administered during the DCCT trial. Adjusting for age, sex, years of education, length of follow-up, and the number of cognitive tests taken, the researchers found no change in any of the eight areas examined. Higher A1C readings among patients--which indicate less, not tighter, control--were associated with a modest decline in motor speed and psychomotor efficiency, but no other cognitive domain was affected.

"The DCCT/EDIC is a study of the complications of type 1 diabetes that is entering its 23rd year and will continue through 2016. The study has been heralded for the high rate of ascertainment and the quality of the data," said Patricia A. Cleary, M.S., who is the director of the data coordinating center for DCCT/EDIC at the Biostatistics Center of The George Washington University.

Others collaborating with Dr. Jacobson in this study included: Amanda Burwood, Katie Weinger, Ed.D., R.N., and Gail Musen, Ph.D., of Joslin; Barbara Waberski, M.S., of George Washington University's Biostatistics Center; Meg Bayless, R.N., of the University of Iowa; William Dahms, M.D., of Case Western Reserve University; Nancy Silvers, R.N., of the University of Pittsburgh Medical Center; and Judy Harth, R.N., of the University of Western Ontario. The study was supported by grants from the National Institute of Diabetes and Digestive Kidney Diseases and the General Clinical Research Centers Program of the National Center for Research Resources.

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

Study suggests use of stem cell transplantation is beneficial treatment of type 1 diabetes

April 11, 2007

April 11, 2007 (EurekAlert) A therapy that includes stem cell transplantation induced extended insulin independence in patients with type 1 diabetes mellitus, according to a preliminary study in the April 11 issue of JAMA.

Type 1 diabetes mellitus (DM) results from a cell-mediated autoimmune attack against pancreatic beta cells. At the time of clinical diagnosis, approximately 60 percent to 80 percent of the beta-cell mass has been destroyed, according to background information in the article. Beta-cell preservation has been shown to be an important target in the management of type 1 DM and in the prevention of its related complications.

Julio C. Voltarelli, M.D., Ph.D., of the University of São Paulo, Ribeirão Preto, Brazil, in collaboration with Richard Burt, M.D., of the Northwestern University Feinberg School of Medicine, Chicago, and colleagues conducted a study to examine the effect of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) to preserve beta-cell function in 15 newly diagnosed patients with type 1 DM. AHST, which uses a patient's own blood stem cells, involves the removal and treatment of the stem cells, and their return to the patient by intravenous injection.

During a 7 to 36-month follow-up, 14 patients became insulin-free (one for 35 months, four for at least 21 months, seven for at least six months; and two with late response were insulin-free for one and five months, respectively). Among those, one patient resumed insulin use one year after AHST. The only severe adverse effects were pneumonia in one patient and endocrine dysfunction in two others.

"This is, to our knowledge, the first report of high-dose immunosuppression followed by autologous nonmyeloablative hematopoietic stem cell transplantation for human type 1 DM. Very encouraging results were obtained in a small number of patients with early-onset disease. Ninety-three percent of patients achieved different periods of insulin independence and treatment-related toxicity was low, with no mortality. Further follow-up is necessary to confirm the duration of insulin independence and the mechanisms of action of the procedure. In addition, randomized controlled trials and further biological studies are necessary to confirm the role of this treatment in changing the natural history of type 1 DM and to evaluate the contribution of hematopoietic stem cells to this change," the authors conclude.

Related: Nancy Peolsi interview

Posted by dlifenews at 08:45 AM | Comments (3)

Dramatic Increase of Type 1 Diabetes in Under-Fives

March 16, 2007

March 16, 2007 (Diabetes UK) - Researchers are calling for more work into the reasons behind a big increase of young children with type 1 diabetes.

A new study, announced today at Diabetes UK’s Annual Professional Conference, has discovered that the number of under-fives with type 1 diabetes has increased five-fold over 20 years.

While the largest rise of the condition was seen in children under five years old, type 1 diabetes in under-15s almost doubled during the study. There was a 2.3 per cent increase in the number of children diagnosed with type 1 diabetes each year.

“This project has produced some very interesting results," said Simon O’Neill, Director of Care, Information and Advocacy Services at Diabetes UK.

“The evidence of a steep rise of type 1 diabetes found in the under-fives indicates that the peak age for diagnosis of the condition in the UK is becoming younger. While 10- to 14-year-olds remain the largest group for diagnosis, the rise in cases found in children under five is worrying.”

Professor Polly Bingley from Bristol University added: “The incidence of childhood Type 1 diabetes has been shown to be increasing all over Europe, particularly in the very young.

“The increase is too steep to be put down to genetic factors, so it must be due to changes in our environment. This could either mean that we are being exposed to something new, or that we now have reduced exposure to something that was previously controlling our immune responses. We now need to work to identify what these changes might be.”

The results come from researchers at the University of Bristol who were funded by Diabetes UK. The study looked at Oxford’s population of 2.6m people between 1985 and 2004.

Posted by dlife at 08:27 AM | Comments (1)

Study Tests Oral Insulin to Prevent Type 1 Diabetes

January 31, 2007

January 31, 2007 (NIDDK) - Researchers have begun a clinical study of oral insulin to prevent or delay type 1 diabetes in at-risk people, the National Institutes of Health (NIH) announced today. Type 1 Diabetes TrialNet, an NIH-funded network of researchers dedicated to the understanding, prevention, and early treatment of type 1 diabetes, is conducting the study in more than 100 medical centers across the United States, Canada, Europe, and Australia.

"Our goal is to prevent type 1 diabetes or to delay it as long as possible. If diabetes can be delayed, even for several years, those at risk will be spared the difficult challenges of controlling glucose and the development of complications for that much longer," said TrialNet study chair Jay Skyler, M.D., of the University of Miami.

In the study, researchers are testing whether an insulin capsule taken by mouth once a day can prevent or delay diabetes in a specific group of people at risk for type 1 diabetes. An earlier trial suggested that oral insulin might delay type 1 diabetes for about four years in some people with autoantibodies to insulin in their blood. Animal studies have also suggested that insulin taken orally may prevent type 1 diabetes. Some scientists think that introducing insulin via the digestive tract induces tolerance, or a quieting of the immune system. Insulin taken orally has no side effects because the digestive system breaks it down quickly. To lower blood glucose, insulin must be injected or administered by an insulin pump.

In type 1 diabetes, a person's own immune cells destroy the beta cells of the pancreas. Beta cells sense blood glucose and produce the hormone insulin, which regulates glucose and converts it to energy. The immune attack on beta cells begins well before a person develops diabetes and continues long after the disease is diagnosed. In the early stages of autoimmunity, up to 10 years before diabetes is diagnosed, autoantibodies may appear in the blood. These autoantibodies to glutamate decarboxylase (GAD), IA-2, and to insulin