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 Ϯ 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 Ϯ 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 Յ4.3 (lowest tertile) was 5.87 (95% CI 4.34 -8.10) versus women with FMD Ն5.6 (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. Diabetes Care 28:702-707, 2005P ostmenopause is a physiological condition known to be associated with endothelial dysfunction. It is due to a lack of estrogen that is typical in this phase of a woman's life (1,2). There is considerable evidence that the impairment of endothelial function is a predicting factor in the development of atherosclerosis (3).Type 2 diabetes represents a very important public health problem in all industrialized countries, mainly in the U.S. (4,5), that involves conspicuous cardiovascular consequences and high costs in terms of mortality, morbidity, and financial resources (6). Endothelial dysfunction is a very frequent occurrence among diabetic patients (7-10).Because endothelial dysfunction is also present in nondiabetic postmenopausal women (1,2), it is not clear whether endothelial dysfunction is a consequence or rather the cause of diabetes, thus preceding its onset. Although there are both references relating to the fact that endothelial dysfunction may precede insulin resistance (11,12) and unique recent work concerning the relationship between the spillover markers of endothelial dysfunction and incident diabetes (13), a clear relationship between endothelium-dependent vasodilation and diabetes has, to our knowledge, never been demonstrated. This study provided the opportunity to prospectively assess the association between endothelial vasodi...

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