Insulin Injections Fail To Prevent Type 1 Diabetes; Separate Prevention Trial Tests Benefit Of Oral Insulin

“Animal studies and a small pilot study in people had suggested that insulin injections could prevent type 1 diabetes, but science mandates that such observations be tested with carefully designed clinical trials,” said study chair Dr. Jay S. Skyler of the University of Miami. “Now we’ve learned that insulin injections, given in the way tested in this trial and in people at high risk of developing type 1 diabetes, do not delay or prevent type 1 diabetes. But from this study we’ve also learned a great deal about the natural history of type 1 diabetes and the immune markers that identify at-risk individuals. This knowledge will be extremely valuable for future prevention efforts.”

A total of 339 people took part in the trial comparing insulin injections and close observation in high-risk people whose ability to make insulin was below normal though they were not yet diabetic. Half the participants were randomized to receive low-dose insulin injections twice a day under the skin and, once a year, a 4-day course of low-dose, continuous intravenous insulin. The other half received no treatment but were closely observed throughout the trial, which began in 1995. Participants’ ages ranged from 4 to 45 years old, with a median age of 11 years.

After 5 years of observation, nearly 60 percent of high-risk people developed type 1 diabetes, a rate of diabetes onset that was virtually identical in both groups. In the majority of people who developed the disease, diabetes onset was detected during routine testing before symptoms developed, a benefit to participants. Patients receiving insulin injections had no significant adverse reactions.

To identify people at risk, researchers screened nearly 90,000 relatives of people with type 1 diabetes for islet cell antibodies (ICAs), one marker of risk. About 3.5 percent of screened relatives had ICAs in their blood, making them eligible for participation in the study. Further genetic, immunologic, and metabolic tests helped researchers identify high-risk individuals. Among these high-risk individuals, 11.5 percent developed diabetes before they could begin the study.

“We’re disappointed, but we’re not discouraged by the results of the insulin injection trial,” said Dr. Judith Fradkin, director of the Division of Diabetes, Endocrinology, and Metabolic Diseases in the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). “This study has taught us a great deal about type 1 diabetes and how to predict onset in people at risk. We’re still looking for a way to stop the disease process in its tracks, and we’re hoping that oral insulin or other prevention approaches being tested in upcoming clinical trials will provide the answers.”

The insulin injection trial is part of the Diabetes Prevention Trial-Type 1 (DPT-1), which is also testing whether insulin taken by mouth can prevent or delay type 1 diabetes in people with a lower (25 to 50 percent) risk of developing diabetes in 5 years. The oral insulin trial is based on a different scientific rationale and targets people who have evidence of autoimmunity but no loss of ability to produce insulin. In contrast to insulin injections, which rest the insulin-producing cells, oral insulin has no effect on blood glucose. Oral insulin is thought to stimulate a protective immune response to counteract the destructive response that causes type 1 diabetes. The oral insulin trial is currently recruiting participants. (See Type 1 Diabetes Prevention Trials:Q & A)

The DPT-1 is 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.

About 16 million Americans have diabetes. Of these, 5 to 10 percent or up to 1 million people have type 1 diabetes, an autoimmune disease that destroys the insulin-producing cells of the pancreas. Formerly known as juvenile onset or insulin-dependent diabetes, type 1 diabetes develops when the body’s immune system destroys pancreatic beta cells, the only cells in the body that make the hormone insulin, which regulates blood glucose. This form of diabetes usually strikes children and young adults, who need several insulin injections a day or an insulin pump to survive.

Type 2 diabetes, which accounts for up to 95 percent of diabetes cases in the United States, is most common in adults over age 40. Affecting about 6 percent of the U.S. population, it is strongly associated with obesity (more than 80 percent of people with type 2 diabetes are overweight), inactivity, family history of diabetes, and racial or ethnic background. A major clinical trial, the Diabetes Prevention Program, will determine whether lifestyle intervention with diet and exercise or treatment with the diabetes drug metformin can prevent the development of type 2 diabetes in people at risk. This trial is no longer recruiting patients.