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

Diabetes Care. 2002 Jul;25(7):1211-6. doi: 10.2337/diacare.25.7.1211.

Abstract

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 risk in clinical trials. Type 2 diabetic patients show a characteristic dyslipidemia. Aggressive lipid lowering might be 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 mg and 80 mg 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 substantial lowering of all atherogenic lipid parameters, no improvement of endothelium-dependent 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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents / therapeutic use*
  • Atorvastatin
  • Blood Flow Velocity
  • Blood Pressure
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Double-Blind Method
  • Endothelium, Vascular / physiopathology*
  • Female
  • Heptanoic Acids / therapeutic use*
  • Humans
  • Hyperlipidemias / drug therapy*
  • Hypertension / epidemiology
  • Lipids / blood
  • Male
  • Middle Aged
  • Placebos
  • Pyrroles / therapeutic use*
  • Smoking
  • Vasodilation

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Lipids
  • Placebos
  • Pyrroles
  • Atorvastatin