Dysfunction of the endothelial cell monolayer leads to increased vascular tone and permeability and a prothrombotic environment. Type 2 diabetes is a state of insulin resistance, hyperglycaemia and dyslipidaemia characterised by high cardiovascular risk and accelerated atherosclerosis. Many mechanisms by which hyperglycaemia can result in endothelial dysfunction have now been identified. However, the presence of endothelial dysfunction in normoglycaemic first-degree relatives and insulin resistant subjects is less well understood and less readily explained by `confounding' variables. We suggest that insulin's effects on glucose transport in classical target tissues and nitric oxide production in the endothelium are fundamentally linked at a molecular level. It is expected that greater understanding of these underlying mechanisms will lead to novel approaches to prevention of cardiovascular disease in both diabetic and non-diabetic subjects.
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