DELAY OF TYPE-I DIABETES IN HIGH-RISK, FIRST DEGREE RELATIVES BY PARENTERAL ANTIGEN ADMINISTRATION - THE SCHWABING INSULIN PROPHYLAXIS PILOT TRIAL

The Schwabing Insulin Prophylaxis Trial is a randomised, controlled pi lot study designed to examine whether insulin therapy can delay or pre vent the clinical onset of Type I diabetes in high risk first degree r elatives of people with the disease. First degree relatives of patient s with Type I diabetes, who were aged 4 years or more, had an islet ce ll antibody (ICA) value more than 20 Junevile Diabetes Foundation Unit s (JDF-U), a reduced first phase insulin response (FPI) to an i.v gluc ose tolerance test less than the 5th centile, and a normal oral glucos e tolerance test were eligible for the trial. Between January 1989 and October 1995, 1736 relatives of patients with Type I diabetes were sc reened for ICA. We identified 64 cases (3.7 %) with ICA values more th an 20 JDF-U, Of ICA positive relatives, 17 (27%) had a low FPI and wer e eligible for enrolment. Of these 14 agreed to participate, of whom 7 were randomised to the treatment group and 7 to the control group, In the treatment group, human insulin was administered i.v. by continuou s infusion for 7 days, followed by daily s.c. injections for 6 months. Intravenous insulin infusions were repeated every 12 months. In the t reatment group 3 of the 7 individuals (follow-up from time of eligibil ity: 2.3 to 7.1 years) and in the control group 6 of the 7 untreated i ndividuals (1.7 to 7.1 years developed clinical diabetes. Life table a nalysis showed that clinical onset of Type I diabetes was delayed in i nsulin-treated subjects compared with control subjects (means +/- SEM diabetes-free survival: 5.0 +/- 0.9 years vs 2.3 +/- 0.7 years, p < 0. 03). Insulin levels after i.v. glucose increased in the first year of intervention therapy. Titres of ICA, and antibodies to glutamic acid d ecarboxylase, and tyrosine phosphatase-like protein IA2 remained uncha nged. These data suggest that insulin prophylaxis can delay the onset of overt diabetes in high risk relatives. This is encouraging in view of I) the continuing American Diabetes Prevention Trial, which is curr ently testing the effect of parenteral insulin in a large nation-wide study and 2) the initiation of pilot trials to determine whether new a ntigen-specific intervention is more effective in delaying the clinica l onset of Type I diabetes.