Effects of oral insulin in relatives of patients with type 1 diabetes: The Diabetes Prevention Trial--Type 1.

OBJECTIVE This randomized, double-masked, placebo-controlled clinical trial tested whether oral insulin administration could delay or prevent type 1 diabetes in nondiabetic relatives at risk for diabetes. RESEARCH DESIGN AND METHODS We screened 103,391 first- and second-degree relatives of patients with type 1 diabetes and analyzed 97,273 samples for islet cell antibodies. A total of 3,483 were antibody positive; 2,523 underwent genetic, immunological, and metabolic staging to quantify risk of developing diabetes; 388 had a 5-year risk projection of 26-50%; and 372 (median age 10.25 years) were randomly assigned to oral insulin (7.5 mg/day) or placebo. Oral glucose tolerance tests were performed every 6 months. The median follow-up was 4.3 years, and the primary end point was diagnosis of diabetes. RESULTS Diabetes was diagnosed in 44 oral insulin and 53 placebo subjects. Annualized rate of diabetes was similar in both groups: 6.4% with oral insulin and 8.2% with placebo (hazard ratio 0.764, P = 0.189). In a hypothesis-generating analysis of a subgroup with insulin autoantibody (IAA) levels confirmed (on two occasions) > or =80 nU/ml (n = 263), there was the suggestion of benefit: annualized diabetes rate 6.2% with oral insulin and 10.4% with placebo (0.566, P = 0.015). CONCLUSIONS It is possible to identify individuals at high risk for type 1 diabetes and to enroll them in a large, multisite, randomized, controlled clinical trial. However, oral insulin did not delay or prevent type 1 diabetes. Further studies are needed to explore the potential role of oral insulin in delaying diabetes in relatives similar to those in the subgroup with higher IAA levels.