EARLY AND LATE INSULIN-RESPONSE AS PREDICTORS OF NIDDM IN PIMA-INDIANS WITH IMPAIRED GLUCOSE-TOLERANCE

Risk factors predicting deterioration to diabetes mellitus were examin ed in 181 subjects with impaired glucose tolerance. Fifty-seven subjec ts had impaired glucose tolerance on one occasion followed by normal g lucose tolerance at a repeat oral glucose tolerance test, and 124 subj ects had impaired glucose tolerance on two successive oral glucose tol erance tests. Subjects were followed for a median period of 5.0 years (range 1.0-17.2). The age- and sex-adjusted cumulative incidence of di abetes at 10 years of follow-up was higher in subjects who had impaire d glucose tolerance on both tests (70%) than in those whose glucose to lerance was normal at the repeat test (53%), [rate ratio (RR) = 1.6, 9 5% confidence intervals (CI) = 1.0-2.5]. Proportional hazards analyses were used to identify baseline risk factors (measured at the repeat o ral glucose tolerance test) for subsequent diabetes, and incidence rat e ratios were calculated for the 90th percentile compared with the 10t h percentile of each continuous variable for the whole group. In all s ubjects, in separate models, higher body mass index [RR = 2.0, 95% CI = 2.2-9.9], high fasting serum insulin concentrations [RR = 2.4, 95% C I = 1.4-4.2], and low early insulin response [RR = 0.5, 95% CI = 0.3-0 .8] 30 min after a glucose load were significant predictors for deteri oration to diabetes. In a multivariate analysis which controlled for a ge and sex, 120-min post-load glucose, fasting insulin and late insuli n response predicted diabetes. In subgroup analyses the predictors of diabetes were generally similar in subjects who had impaired glucose t olerance at only one test and those who had impaired glucose tolerance on both tests. These findings suggest that in those subjects with imp aired glucose tolerance whose glucose tolerance has returned to normal , the risk of subsequent diabetes is high. Insulin resistance, impaire d early insulin response, or both, are predictive of subsequent develo pment of diabetes in Pima Indians with impaired glucose tolerance.