Diabetes Symptom

Prevention of Diabetes

Researchers continue to search for the cause or causes of diabetes and ways to prevent and cure the disorder. Scientists are looking for genes that may be involved in type 1 or type 2 diabetes. Some genetic markers for type 1 diabetes have been identified, and it is now possible to screen relatives of people with type 1 diabetes to see if they are at risk.
Type 1 Diabetes

The Diabetes Prevention Trial–Type 1 (DPT-1) identified relatives at risk for developing type 1 diabetes and investigated two ways to delay or prevent type 1 diabetes. Neither low-dose insulin injections nor an oral form of insulin were successful in delaying or preventing type 1 diabetes in people at risk.

The DPT-1 was funded by the NIDDK, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, and the National Center for Research Resources within the National Institutes of Health as well as the American Diabetes Association and the Juvenile Diabetes Research Foundation International.

Researchers are working on a way to help people with type 1 diabetes live without daily injections of insulin. In an experimental procedure called islet transplantation, islets are taken from a donor pancreas and transferred into another person. Once implanted, the beta cells in these islets begin to make and release insulin.

Scientists have made many advances in islet transplantation in recent years. Since reporting their findings in the June 2000 issue of the New England Journal of Medicine, researchers at the University of Alberta in Edmonton, Canada, have continued to use a procedure called the Edmonton protocol to transplant pancreatic islets into people with type 1 diabetes. A multicenter clinical trial of the Edmonton protocol for islet transplantation is currently under way, and results will be announced in several years. According to the International Islet Transplant Registry, as of June 2003, about 50 percent of the patients have remained insulin-free for up to 1 year after receiving a transplant. A clinical trial of the Edmonton protocol is also being conducted by the Immune Tolerance Network, funded by the National Institutes of Health and the Juvenile Diabetes Research Foundation International.

The goal of islet transplantation is to infuse enough islets to control the blood glucose level without insulin injections. For an average-sized person (70 kg), a typical transplant requires about 1 million islets, extracted from two donor pancreases. Because good control of blood glucose can slow or prevent the progression of complications associated with diabetes, such as nerve or eye damage, a successful transplant may reduce the risk of these complications. But a transplant recipient will need to take immunosuppressive drugs that stop the immune system from rejecting the transplanted islets.

Researchers are trying to find new approaches that will allow successful transplantation without the use of immunosuppressive drugs, thus eliminating the side effects that may accompany their long-term use. These drugs have significant side effects and their long-term effects are still not known. Immediate side effects of immunosuppressive drugs may include mouth sores and gastrointestinal problems, such as stomach upset or diarrhea. Patients may also have increased blood cholesterol levels, decreased white blood cell counts, decreased kidney function, and increased susceptibility to bacterial and viral infections. Taking immunosuppressive drugs increases the risk of tumors and cancer as well.

Researchers do not fully know what long-term effects this procedure may have. Also, although the early results of the Edmonton protocol are very encouraging, more research is needed to answer questions about how long the islets will survive and how often the transplantation procedure will be successful.

A major obstacle to widespread use of islet transplantation will be the shortage of islet cells. The supply available from deceased donors will be enough for only a small percentage of those with type 1 diabetes. However, researchers are pursuing avenues for alternative sources, such as creating islet cells from other types of cells. New technologies could then be employed to grow islet cells in the laboratory.
Type 2 Diabetes

In 1996, NIDDK launched its Diabetes Prevention Program (DPP). The goal of this research effort was to learn how to prevent or delay type 2 diabetes in people with impaired glucose tolerance (IGT), a strong risk factor for type 2 diabetes.

The findings of the DPP, which were released in August 2001, showed that people at high risk for type 2 diabetes could sharply lower their chances of developing the disease through diet and exercise. In addition, treatment with the oral diabetes drug metformin also reduced diabetes risk, though less dramatically.

Participants randomly assigned to intensive lifestyle intervention reduced their risk of getting type 2 diabetes by 58 percent. On average, this group maintained their physical activity at 30 minutes per day, usually with walking or other moderate intensity exercise, and lost 5 to 7 percent of their body weight. Participants randomized to treatment with metformin reduced their risk of getting type 2 diabetes by 31 percent.

Of the 3,234 participants enrolled in the DPP, 45 percent were from minority groups that suffer disproportionately from type 2 diabetes: African Americans, Hispanic Americans, Asian Americans and Pacific Islanders, and American Indians. The trial also recruited other groups known to be at higher risk for type 2 diabetes, including individuals age 60 and older, women with a history of gestational diabetes, and people with a first-degree relative with type 2 diabetes.
Prevention and Treatment of Cardiovascular Disease

The National Institutes of Health is studying the best strategies to prevent and treat cardiovascular disease (CVD) in people with diabetes in three trials: Look AHEAD, ACCORD, and BARI 2D. These studies are all joint efforts of the National Institute of Diabetes and Digestive and Kidney Diseases and the National Heart, Lung, and Blood Institute.

The Look AHEAD: Action for Health in Diabetes study will be the largest clinical trial to date to examine the long-term health effects of voluntary weight loss. This multi-center, randomized clinical trial will examine the consequences of a lifestyle intervention designed to achieve and maintain weight loss over the long term through decreased caloric intake and increased exercise. Look AHEAD will focus on the disease most associated with overweight and obesity, type 2 diabetes, and on the outcome that causes the greatest morbidity and mortality, cardiovascular disease.

The Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, a randomized multi-center trial, is being undertaken by the NIH to study three key approaches to preventing major cardiovascular events in individuals with type 2 diabetes. The primary outcome that ACCORD will measure is the first occurrence of a major cardiovascular disease event, specifically heart attack, stroke, or cardiovascular death. In addition, the study will investigate the impact of the treatment strategies on other cardiovascular outcomes; total mortality; limb amputation; eye, kidney, or nerve disease; health-related quality of life; and cost-effectiveness.

The Bypass Angioplasty Revascularization Investigation in Type 2 Diabetics Trial (BARI 2D), a 5-year, multi-center clinical trial, will compare medical versus early surgical management of patients with type 2 diabetes who also have coronary artery disease and stable angina or ischemia. At the same time, BARI 2D is studying the effect of two different strategies to control blood glucose–providing insulin versus increasing the sensitivity of the body to insulin–on risk of cardiovascular mortality and morbidity.

A complete listing of clinical research studies can be found at http://ClinicalTrials.gov

Several new drugs have been developed to treat type 2 diabetes. By using the oral diabetes medications now available, many people can control blood glucose levels without insulin injections. Studies are under way to determine how best to use these drugs to manage type 2 diabetes.