title: 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.
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.
  
  
  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.
authors.affiliation: Julius Center for General Practice and Patient Oriented Research and Department of Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Francine V
authors.initials: FV
authors.lastname: van Venrooij
authors.forename: Marcel A
authors.initials: MA
authors.lastname: van de Ree
authors.forename: Michiel L
authors.initials: ML
authors.lastname: Bots
authors.forename: Ronald P
authors.initials: RP
authors.lastname: Stolk
authors.forename: Menno V
authors.initials: MV
authors.lastname: Huisman
authors.forename: J D
authors.initials: JD
authors.lastname: Banga
mesh_terms: D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000069059:Atorvastatin; D001783:Blood Flow Velocity; D001794:Blood Pressure; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D006973:Hypertension / Q000453:epidemiology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011758:Pyrroles / Q000627:therapeutic use*; D012907:Smoking; D014664:Vasodilation
chemical_list: D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D008055:Lipids; D010919:Placebos; D011758:Pyrroles; D000069059:Atorvastatin