Insulin secretion and its determinants in the progression of impaired glucose tolerance to type 2 diabetes in impaired glucose-tolerant individuals: The Finnish diabetes prevention study

Abstract

OBJECTIVE - We investigated the effect of early-phase insulin secretion on the incidence of type 2 diabetes in individuals with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). We examined how a lifestyle intervention affected early-phase insulin secretion (ratio of total insulin area under the curve [AUC] and total glucose AUC [AIGR] from 0 to 30 min) during a 4-year follow-up intervention trial and whether AIGR 0-30 response was modified by insulin sensitivity (IS) and obesity. RESEARCH DESIGN AND METHODS - A total of 443 participants with IGT originally randomized to a lifestyle intervention or control group were studied. IS and AIGR 0-30 were estimated from an oral tolerance glucose test administered annually during the 4-year followup trial and were related to the risk of diabetes onset over a 6-year follow-up. RESULTS - Lifestyle intervention resulted in higher IS (P = 0.02) and lower unadjusted AIGR 0-30 (P = 0.08) during the 4-year follow-up. A higher IS and a lower BMI during the follow-up were associated with a lower unadjusted AIGR 0-30 during the follow-up, independently of study group (P < 0.001). A greater increase in IS on the median cutoff point of a 0.69 increase was associated with higher IS-adjusted AIGR 0-30 during the follow-up (P = 0.002). In multivariate models, IS and IS-adjusted AIGR 0-30 were both inversely associated with diabetes incidence (P < 0.001). Participants who progressed to type 2 diabetes were more obese and had lower IS and Matsuda IS index-AIGR 0-30 than nonprogressors. CONCLUSIONS - Our results indicate that the reduction in the risk of developing type 2 diabetes after lifestyle intervention is related to the improvement of IS along with weight loss. Improved IS may also have beneficial effects on preservation of β-cell function. © 2012 by the American Diabetes Association.