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

Vanessa D F de Mello, Jaana Lindström, Johan Eriksson, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi, Jouko Sundvall, Markku Laakso, Jaakko Tuomilehto, Matti Uusitupa, Vanessa D F de Mello, Jaana Lindström, Johan Eriksson, Pirjo Ilanne-Parikka, Sirkka Keinänen-Kiukaanniemi, Jouko Sundvall, Markku Laakso, Jaakko Tuomilehto, Matti Uusitupa

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 follow-up 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.

Trial registration: ClinicalTrials.gov NCT00518167.

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Source: PubMed

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