Context. In persons with impaired glucose tolerance (IGT), both impaired insulin secretion and insulin resistance contribute to the conversion to type 2 diabetes (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. 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 years), with mean two-hour plasma glucose values, of two separate oral glucose tolerance tests (OGTTs), between 8.6 and 11.1 mmol/l. 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 six-monthly fasting glucose levels and yearly OGTTs.

Results. The cumulative incidence of T2DM was 34.7%. Hazard ratio for T2DM development adjusted for age, sex and BMI 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 versus highest tertile of insulin sensitivity and 1.78 (95% CI, 0.65-4.88) for lowest versus 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.