Insulin resistance and the development of cardiovascular disease in a Japanese community: The Hisayama study

Aims: Although several surrogate measures of insulin resistance have been proposed, their associations with cardiovascular disease (CVD) have not been evaluated sufficiently. Methods: A total of 2,356 community-dwelling Japanese individuals aged 40 to 79 years who underwent a 75 g oral glucose tolerance test were followed up for 14 years. The status of insulin resistance was estimated by using the Matsuda index or homeostasis model assessment of insulin resistance (HOMA-IR). Results: During follow-up, 260 subjects developed CVD. The age-and sex-adjusted hazard ratios of CVD significantly decreased with an increasing Matsuda index and rose with increasing HOMA-IR levels (both p for trend <0.05). After adjustment for age, sex, serum total cholesterol, electrocardiogram abnormalities, proteinuria, smoking habits, alcohol intake, and regular exercise, the risk of CVD was significantly lower in the third to fifth quintiles of the Matsuda index and higher in the fifth quintile of HOMA-IR values compared with the first quintile of the corresponding index (Matsuda index Q3: hazard ratio (HR) = 0.59 [95% confidence interval 0.40-0.87]; Q4: HR = 0.66 [0.45-0.97]; and Q5: HR = 0.67 [0.47-0.97]; HOMA-IR Q5: HR = 1.55 [1.05-2.29]); however, these associations were attenuated after further adjustment for the metabolic syndrome status. In regard to CVD subtypes, the risks for stroke and coronary heart disease significantly decreased with an increasing Matsuda index, while elevated HOMA-IR levels were a significant risk factor for stroke, but not for coronary heart disease. Conclusion: Our findings suggest that insulin resistance significantly increases the risk of incident CVD through metabolic syndrome in Japanese.