Absence of an Acute Insulin Response Predicts Onset of Type 2 Diabetes in a Caucasian Population with Impaired Glucose Tolerance

Context: In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes mellitus (T2DM). However, few studies have used criterion standard measures to asses the predictive value of impaired insulin secretion and insulin resistance for the conversion to T2DM in a Caucasian IGT population. Objectives: The objective of the study was to determine the predictive value of measures of insulin secretion and insulin resistance derived from a hyperglycemic clamp, including the disposition index, for the development of T2DM in a Caucasian IGT population. Design, Setting, and Participants: The population-based Hoorn IGT study consisted of 101 Dutch IGT subjects (aged < 75 yr), with mean 2-h plasma glucose values, of two separate oral glucose tolerance tests, between 8.6 and 11.1 mmol/liter. A hyperglycemic clamp at baseline was performed to assess first-phase and second-phase insulin secretion and insulin sensitivity. During follow-up, conversion to T2DM was assessed by means of 6-monthly fasting glucose levels and yearly oral glucose tolerance tests. Results: The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex, and body mass index was 5.74 [95% confidence interval (CI) 2.60–12.67] for absence of first insulin peak, 1.58 (95% CI 0.60–4.17) for lowest vs. highest tertile of insulin sensitivity, and 1.78 (95% CI 0.65–4.88) for lowest vs. highest tertile of the disposition index. Conclusions: In these Caucasian persons with IGT, the absence of the first insulin peak was the strongest predictor of T2DM.