Aggressive lipid lowering does not improve endothelial function in type 2 diabetes - The Diabetes Atorvastatin Lipid Intervention (DALI) study: a randomized, double-blind, placebo-controlled trial

OBJECTIVE - Endothelial dysfunction is considered an important early marker of atherosclerosis and cardiovascular risk and is currently used as a surrogate end point for cardiovascular at risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might he an effective method to improve endothelial function in these patients. RESEARCH DESIGN AND METHODS - A randomized, double-blind, placebo-controlled trial was completed to study the effect of 30 weeks' administration of atorvastatin 10 rug and 80 rug on endothelial function, as assessed by B-mode ultrasound of the brachial artery, in 133 patients with type 2 diabetes without a history of cardiovascular disease. RESULTS- patients with diabetes and diabetic dyslipidemia had considerable endothelium-dependent and endothelium-independent dysfunction; mean flow-mediated vasodilation (SD) was 3.16% (3.56), and mean response on sublingual nitroglycerin was 6.58% (6.04). Despite su stantia owering of all atherogenic lipid parameters, no improvement of endotheliumdependent vasodilatation was found (P > 0.8). CONCLUSIONS - We observed considerable baseline endothelium-dependent and endothelium-independent dysfunction in patients with diabetes and diabetic dyslipidemia without a history of cardiovascular disease. Aggressive lipid lowering by administration of atorvastatin, resulting in substantial improvement of the lipid profile, did not reverse endothelial dysfunction.