Immunologic Issues in Type 1 Diabetes

This is the second in a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions held in Philadelphia, PA, in June 2001. It covers topics related to immunity and type 1 diabetes.

Jay Skyler, Miami, FL, presented the results of the parenteral substudy arm of the Diabetes Prevention Trial for Type 1 Diabetes (DPT-1), in which relatives of patients with type 1 diabetes, whose risk of type 1 diabetes is 10- to 20-fold greater than that of the general population, were screened for islet cell antibodies (ICAs) and enrolled in a study of insulin administration if they showed high risk of developing diabetes. Animal studies in female nonobese diabetic (NOD) mice have shown this to be an effective treatment, and in the early 1990s, Keller et al. (1) reported a pilot study of 12 individuals with a predicted risk of diabetes; 5 subjects were treated with insulin and 7 subjects declined treatment. By 2.5 years, all of those who declined treatment had developed diabetes; at 5 years, only half of the intervention group had the disease.

The DPT-1 was initiated in 1993. Screening began in February 1994 and randomization began in January 1995; 339 subjects were enrolled, with follow-up ending 13 April 2001. Screening of 89,827 relatives, with 84,228 samples analyzed, showed that 3,152 (3.7%) were ICA positive. A total of 2,103 subjects were staged, 535 having low first-phase insulin response. Of 372 subjects who were eligible for randomization, 339 were randomized. Skyler pointed out that 354 of the 3,152 ICA-positive individuals had actually already developed diabetes, with 156 identified before further testing. The projected annual event rate was 21%, and the actual finding was of 15.1% developing diabetes (in addition to those developing diabetes before randomization). Of the patients who developed diabetes, 60% were sibs, 25% …