Endothelial-Dependent Vasodilation and Incidence of Type 2 Diabetes in a Population of Healthy Postmenopausal Women

Abstract

OBJECTIVE—Both postmenopausal state and diabetes are associated with endothelial dysfunction and are well-known risk factors for atherosclerosis. However, the relationship of endothelium-dependent vasodilation and diabetes has never been prospectively evaluated. This study provided the opportunity to assess the association between endothelial vasodilation function and the incidence of diabetes in a cohort of apparently healthy postmenopausal women. RESEARCH DESIGN AND METHODS—We conducted a prospective cohort study that began in 1997 with 840 apparently healthy, nonobese, postmenopausal women, aged 53 ± 6 years, initially with normal glucose tolerance at the oral glucose tolerance test. All participants were followed up for a mean period of 3.9 ± 0.7 years (range 0.5–6.9). Endothelial function was measured as flow-mediated dilation (FMD) of the brachial artery, using high-resolution ultrasound. RESULTS—There were no significant differences in demographic, blood pressure, and biochemical profiles among each tertile group at baseline or at follow-up review. During follow-up, 102 women developed type 2 diabetes. The adjusted relative risk (RR) for women with FMD ≤4.3 (lowest tertile) was 5.87 (95% CI 4.34–8.10) versus women with FMD ≥5.6 (highest tertile reference). Each 1-unit decrease of FMD was associated with a significant 32% (22–48%) increase in the multiple-adjusted RR of incident diabetes. CONCLUSIONS—These prospective data indicate a significant increase in the RR of diabetes with each unit decrease of FMD. This could suggest that an impaired endothelial function may play a fundamental role in diabetogenesis in postmenopausal women.