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.

A study of the effects of acarbose on glucose metabolism in patients predisposed to developing diabetes: the Dutch acarbose intervention study in persons with impaired glucose tolerance (DAISI).

BACKGROUND: We hypothesized that acarbose would delay conversion from impaired glucose tolerance (IGT) to type 2 diabetes by alleviating postprandial hyperglycaemia. Our study's main objective was to investigate the effect of acarbose in IGT-persons on their 2-h plasma glucose level and beta-cell function. SUBJECTS AND METHODS: The study included a random sample of 45-70-year-old residents of Hoorn, Netherlands, with mean fasting plasma glucose < 7.8 mmol/L and mean 2-h plasma glucose of 8.6-11.1 mmol/L (measured by two successive oral glucose tolerance tests). After a qualification period, participants were randomized to acarbose treatment or placebo. Insulin secretion and insulin sensitivity were measured by hyperglycaemic clamp. After a 3-year treatment, analyses were performed of both the intention-to-treat and the per-protocol groups. RESULTS: Of the 12 093 residents who received postal invitations, 118 participants were randomized. The mean difference of the post-load plasma glucose after 3 years, was - 1.16 mmol/L (95% CI: - 2.03; - 0.17). The absolute risk reduction for diabetes was 6% (95% CI: - 9; 21). No effect was seen on insulin secretion and insulin sensitivity. CONCLUSIONS: In patients with IGT, treatment with acarbose was associated with beneficial effects on 2-h plasma glucose levels but not with improvement of beta-cell function.