Abstract

Objective: Impaired insulin secretion (IIS) and insulin resistance (IR) are the two main mechanisms for type 2 diabetes (T2D), but IIS has been reported to contribute to incident T2D more than IR in Asian populations. However, we assumed that the impact of IR on the incident T2D was being greater in the recent Japanese population, because the burden of obesity increased. Herein, we addressed the magnitude of the contribution of IIS and IR to the development of T2D in a Japanese community. Methods: In 2007, a total of 2,108 residents aged 40-79 years (participation rate 77.1%) without diabetes at baseline underwent health examination including 75g OGTT, insulinogenic index (IGI), and HOMA-IR. Subjects were divided into 4 groups according to the presence or absence of IIS (IGI ≤ 0.4) and IR (1.6 ≤ HOMA-IR) and were followed-up prospectively for a median of 6.9 years. A Cox’s proportional hazards model was used to estimate the hazard ratios and 95% confidential intervals (CIs) for incident T2D with adjustment for confounders. The population attributable fraction (PAF) for the development of diabetes due to IS, IR and their combination were calculated. Result: At baseline, the proportions of subjects with neither of IIS nor IR, isolated IIS, isolated IR, and both IIS and IR were 45.5%, 21.0%, 28.7%, and 4.8%, respectively. During follow-up period, 273 subjects developed T2D. The risk of incident T2D was 5.3 (95% CI 3.6-7.9) times higher in subjects with isolated IIS, 4.1 (2.8-6.2) times higher in subjects with isolated IR, and 13.5 (8.5-21.5) times higher in subjects with both IIS and IR than subjects with neither of IIS nor IR. The PAFs on the excess risk of T2D among subjects with isolated IIS, isolated IR and both IIS and IR were 25.8%, 29.1%, and 15.9%, respectively. Conclusion: Our finding suggests that IIS and IR contributed equally to the development of T2D in the recent general Japanese population. Disclosure M. Yoshinari: None. Y. Hirakawa: None. J. Hata: None. M. Higashioka: None. T. Honda: None. D. Yoshida: None. N. Mukai: None. U. Nakamura: None. T. Kitazono: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.

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