Dyslipidaemia, inflammation and endothelial dysfunction in diabetes mellitus

Abstract

Endothelial dysfunction is an early event in atherogenesis and precedes the thickening of the intima and the formation of atherosclerotic plaques. Endothelial dysfunction has also been implicated in the pathogenesis of both micro- and macroangiopathy in diabetes and has been consistently demonstrated in patients with type 1 and type 2 diabetes mellitus. Markers of endothelial dysfunction (e.g. von Willebrand factor, vascular cell adhesion molecules) are elevated in patients with diabetes mellitus, and vasodilation mediated by endothelium-derived nitric oxide is impaired. The aetiology of endothelial dysfunction in diabetes is complex and it has been shown that more than one mechanism is involved. We and others have demonstrated that diabetic dyslipidaemia plays a significant role. The increase in the concentration of small, dense LDL, enhanced susceptibility of LDL to oxidation and exaggerated postprandial lipidaemia found in patients with type 2 diabetes mellitus are associated with impairment of endothelium-dependent vasodilation. We have shown that treatment with atorvastatin improves, but does not completely normalize, endothelial function in patients with type 2 diabetes. In addition to lowering LDL cholesterol, atorvastatin also lowers C-reactive protein (CRP) levels. The magnitude of reduction in CRP correlates with the degree of improvement in endothelium-dependent vasodilation, suggesting that chronic, low-grade inflammation may also be involved in causing endothelial dysfunction. Chronic inflammation is associated with activation of the endothelium and both dyslipidaemia and advanced glycation end products are important triggers for inflammation in diabetes mellitus. Hence, dyslipidaemia, chronic low-grade inflammation and endothelial dysfunction are interrelated and contribute to high cardiovascular risk in subjects with diabetes.