ABSTRACT
Pinkney et al. (1997) fi rst put forth the hypothesis that endothelial dysfunction is a common antecedent of the insulin resistance/metabolic syndrome and is intrinsically related to many of its key clinical features. Several biological mechanisms have subsequently been proposed to explain the complex and reciprocal relationships between endothelial dysfunction and insulin resistance (shown in Fig. 1). Briefl y, endothelial dysfunction could directly promote the development and progression of insulin resistance. Alternatively, impaired insulin action may also directly exacerbate endothelial dysfunction. Several studies in non-diabetic individuals have suggested that mildly impaired fasting glucose levels (though within the normoglycemic range) accelerate the impairment of endothelial function via adverse eff ects on oxidative stress, formation of advanced glycation end products, and elevated levels of free fatty acids (Pinkney et al. 1997, Kim et al. 2006).
