HMG CoA Reductase Inhibitors

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Large clinical trials have determined that hydroxymethylglutaryl-coenzyme A reductase inhibitors ("statins") significantly reduce cardiovascular morbidity and mortality. Furthermore, lipid-lowering therapy has been shown to improve endothelial function in several studies (204,205). Attempts to ameliorate the impaired endothelium-dependent vascular relaxation that occurs in diabetic patients with dyslipidemia are few and the results mixed. Impaired endothelium-dependent vasodilation in patients with type 2 DM with dyslipidemia has been reported to improve with fibrate therapy (206) (which lowers the serum triglyceride level) but not with simvastatin (206,207).


The normal endothelium plays an important role in the prevention of atherosclerosis and microvascular disease. DM is an important cause of both macro- and microvascular disease. Animal and clinical studies have demonstrated a decrease in endothelium-de-pendent vasodilation in both type 1 and type 2 DM. Possible mechanisms include abnormalities in signal transduction, reduced synthesis of NO, accelerated inactivation of NO, or production of vasoconstrictor prostanoids, probably through the relative increase of oxygen-derived free radicals (Table 1). The mediators of this abnormality include hyperinsulinemia, insulin resistance, or hyperglycemia. Improved glucose control, supplementation with either tetrahydrobiopterin, L-arginine, or vitamin C, or the addition of ACE inhibitors have been shown to improve endothelial function. Further research is required to determine whether restoring endothelial function in patients with either type 1 or type 2 diabetes will translate into an overall reduction in diabetic vascular disease.


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