Endothelial dysfunction potentially interacts with impaired glucose metabolism to increase cardiovascular risk.

Abstract

See related article, pp 1299–1305 The term endothelial dysfunction generally refers to a maladapted endothelial phenotype characterized by reduced nitric oxide (NO) bioavailability, increased oxidative stress, elevated expression of proinflammatory and prothrombotic factors, and reduced endothelial-derived vasodilation.1 Hyperglycemia, insulin resistance, dyslipidemia, hyperuricemia, increased dietary fructose, and fat are conditions that predispose endothelial dysfunction, an early precursor to increased vascular and cardiac stiffness and atherosclerosis, all risk factors for hypertension, myocardial infarction, stroke, limb ischemia, and heart failure. Thus, endothelial dysfunction is an important risk factor for cardiovascular disease (CVD)–related morbidity and mortality.2 Recently, cross-sectional studies suggested that endothelial dysfunction also independently predicts the incidence of type 2 diabetes mellitus (T2D). For example, a prospective study of the children and spouses of children from the original Framingham Heart Study cohort found that high levels of endothelial cell (EC)–derived Willebrand factor increased the risk of developing T2D independent of other risk factors for diabetes mellitus, including obesity, abnormal glucose metabolism, and inflammation.3 Similarly, in a large, prospective, nested case–control study from an ethnically diverse cohort of US postmenopausal women (Women’s Health Initiative Observational Study), higher levels of circulating E-selectin and intercellular adhesion molecule-1 were consistently associated with increased risk of developing T2D.4 …