Diabetes :: Plan Will Guide NIH Research in Type 1 Diabetes

The National Institutes of Health (NIH) has released a long range plan that will help to guide research in type 1 diabetes for the next decade. Advances and Emerging Opportunities in Type 1 Diabetes Research: A Strategic Plan identifies goals and objectives to exploit recent scientific advances in combating this autoimmune form of diabetes.

About 5 to 10 percent of the nearly 21 million people with diabetes have type 1, formerly known as juvenile onset diabetes or insulin-dependent diabetes. In this form of diabetes, immune cells attack and destroy pancreatic beta cells, which produce the critical hormone insulin needed for survival. Type 1 diabetes tends to arise in children and young adults, who need three or more insulin injections a day or treatment with an insulin pump to maintain blood glucose control. To prevent complications they must regularly monitor their blood glucose, striving for a range that is as close to normal as possible. The constant challenge of managing the disease poses a serious burden for patients and their families.

Type 1 diabetes cuts lives short by about 15 years, with early deaths due mainly to heart attacks and strokes. However, research has made dramatic progress in extending life expectancy for people with this disease. A recent study found that 20 percent of people born in the 1950?s died within 20 years of a type 1 diabetes diagnosis, and 30 percent died within 25 years of diagnosis. For people born between 1975 and 1980, however, 3.5 percent died within 20 years of diagnosis, and 7 percent died within 25 years.

?Research has greatly improved the length and quality of life of people with type 1 diabetes, and it has lowered the risk of developing certain serious complications, such as retinopathy and kidney failure. However, many challenges remain in combating this complex autoimmune disease. The NIH Strategic Plan sets forth a cogent, multifaceted approach to future research that soundly addresses these challenges,? said NIH Director Elias A. Zerhouni, M.D.

The Plan describes scientific advances resulting from type 1 diabetes research and outlines specific objectives to further the following goals:

1. Identify the genetic and environmental causes of type 1 diabetes
Both genetic susceptibility and one or more environmental triggers contribute to the development of type 1 diabetes. Genes that confer varying degrees of risk have been identified, but researchers continue to search for others. Finding all the genes will boost the ability to predict who is at risk and foster prevention efforts. Because many people with high-risk genes don?t develop type 1 diabetes, scientists believe environmental factors ? perhaps toxins, infectious agents, or components of the diet ? also play a role. Several groups, including the International Type 1 Diabetes Genetics Consortium and The Environmental Determinants of Diabetes in the Young (TEDDY), are working to identify all the genetic and environmental factors that lead to diabetes. The outcome of their work could have enormous benefits, such as a preventive vaccine against an infectious trigger or a dietary change that averts autoimmunity and diabetes onset.

2. Prevent or reverse type 1 diabetes
Researchers have made great strides in understanding, detecting, and monitoring autoimmunity and now have better tools to study the early stages of type 1 diabetes. Testing for genetic susceptibility and autoantibodies, they can identify who is at high, moderate, and low risk for developing type 1 diabetes. They also have a better grasp of the immune events that lead to the destruction of beta cells. Several studies now point to insulin itself as the target of immune cells. Clinical trial groups, including the Type 1 Diabetes TrialNet and the Immune Tolerance Network, are currently testing ways to modulate the immune system to prevent type 1 diabetes and to arrest the autoimmune attack in people with newly diagnosed diabetes, who still have some functioning beta cells.

3. Develop cell replacement therapy
Since 2000, when researchers at the University of Alberta in Edmonton, Canada, pioneered a new method for transplanting islets, or clusters of beta cells, researchers have been steadily refining the procedure for people with severe complications from type 1 diabetes. Islet transplantation improves glucose control and alleviates hypoglycemia unawareness, which afflicts some people with longstanding type 1 diabetes. However, the side effects of immunosuppressive drugs, which prevent the body?s rejection of donor islets, have limited the procedure to people with hypoglycemia unawareness or those already taking immunosuppressive drugs after a kidney transplant. Researchers seek to overcome the remaining barriers to islet transplantation by:

developing methods to produce an unlimited supply of islets
improving ways to harvest islets
reducing complications of islet transplantation, and
testing ways to prevent recurrent autoimmunity and the immune rejection of donor islets.
To address the inadequate supply of donor islets, the Beta Cell Biology Consortium is exploring beta cell development and regeneration with the goal of growing unlimited numbers of beta cells. Other projects include a registry that tracks the outcomes of islet transplants and a research group that is testing ways to induce immune tolerance in non-human primate models of kidney and islet transplantation.

4. Prevent or reduce hypoglycemia in type 1 diabetes
Major clinical studies have clearly shown that intensive glucose control dramatically delays or prevents the eye, nerve, kidney, and heart complications of type 1 diabetes. The main barrier to tight control is hypoglycemia, which occurs when insulin causes blood glucose to fall too low. Some patients with difficult-to-control diabetes cannot sense falling blood glucose and lose consciousness without warning. Recently approved continuous glucose monitors developed with NIH support are helping patients control their glucose levels more easily. This revolutionary technology is the first step in the path to develop an artificial pancreas. Current studies are also focusing on how the brain senses hypoglycemia and controlling hypoglycemia through behavioral therapy.

5. Prevent or reduce the complications of type 1 diabetes
Together, diabetes and high blood pressure account for 72 percent of all new cases of kidney failure. After 20 years of annual increases from 5 to 10 percent, rates for new kidney failure cases have leveled off. The most encouraging trend is in diabetes, where rates for new cases in whites under age 40 are the lowest in 20 years. Improved control of glucose and blood pressure and the use of anti-hypertensive drugs called ACE inhibitors and ARBs prevent or delay kidney failure. With good care, fewer than 10 percent of people with diabetes now develop kidney failure.

Scientists have made great progress in preventing and treating the eye damage of diabetes. With laser treatment and vitrectomy, blindness has been reduced by 90 percent in patients with severe diabetic retinopathy. NIH researchers discovered that a protein called vascular endothelial growth factor (VEGF) spurs the development of abnormal blood vessels that invade the retina to cause blindness. NIH-sponsored clinical studies are now testing drugs that control the development of new blood vessel growth in the eye.

Advances in understanding how high blood glucose causes damage to cells and tissues have led to several promising drugs that are ready for testing in clinical trials to treat and prevent complications. The Strategic Plan stresses the need to further clarify these pathways by studying the role of genetic factors and applying the tools of systems biology.

6. Attract new talent and apply new technologies to research on type 1 diabetes
Engaging talented scientists from diverse disciplines is critical to the success and future of diabetes research. The NIH is vigorously pursuing this goal in different ways, e.g., by encouraging interdisciplinary collaboration, creating incentives that reward research innovation and collaboration, and attracting and training new diabetes investigators.

By employing powerful new technologies, researchers are poised to solve the most vexing problems of type 1 diabetes research. It is well known, for example, that patients have already lost most of their beta cells by the time type 1 diabetes is diagnosed. Having a way to measure the actual number of beta cells would greatly help researchers in their quest to develop new therapies. State-of-the-art diagnostic tools, such as magnetic resonance imaging (MRI) and positron emission tomography (PET), are giving hope that beta cell mass can be assessed in real time to judge the effects of promising therapies. Imaging technologies are also being applied to better understand the brain?s response to hypoglycemia.

Do NOT follow this link or you will be banned from the site!