PREDICTION OF THE COURSE OF PRE-TYPE-1 DIABETES

To increase knowledge on the predictability of the onset of insulin-dependent diabetes mellitus (IDDM; type I), we followed 38 subjects < 18 years of age who had positive results on two or more islet-cell antibody tests and one identical twin who had positive results on one islet-cell antibody test. All 39 patients had longitudinal intravenous glucose tolerance tests to determine the first-phase insulin response (FPIR). Insulin dependence has developed in 10 untreated subjects < 18 years of age. Of the 10 subjects, insulin dependence developed in eight a mean of 4.6 months after their FPIR fell to < 30-mu-U/ml and a mean of 14 months after it fell to < 46-mu-U/ml. Nine of the untreated subjects had an FPIR < 67-mu-U/ml on at least two occasions and became insulin dependent a mean of 19 months after the value first fell below this level (95% confidence limit = 66.4% to 100%). All but one of the 10 subjects in whom IDDM developed initially had islet-cell antibody levels of > 80 JDF units. Insulin autoantibody values at onset were available for 9 of the 10 subjects and were positive (> 39 nU/ml) in six. We conclude that the combination of positive results on two islet-cell antibody tests and two diminished FPIRs (< 67-mu-U/ml) in subjects less than 18 years of age reliably predicts the onset of IDDM. These data should permit intervention studies to be planned.