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
- Francine V. van Venrooij, MD, MSc, PhD12,
- Marcel A. van de Ree, MD, PhD3,
- Michiel L. Bots, MD, PhD1,
- Ronald P. Stolk, MD, PhD1,
- Menno V. Huisman, MD, PhD3,
- J. D. Banga, MD, PhD2 and
- on behalf of the DALI Study Group
- 1Julius Center for General Practice and Patient Oriented Research, University Medical Center Utrecht, Utrecht, the Netherlands
- 2Department of Internal Medicine, University Medical Center Utrecht, Utrecht, the Netherlands
- 3Department of General Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
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.
- A10, atorvastatin 10 mg
- A80, atorvastatin 80 mg
- DALI, Diabetes Atorvastatin Lipid Intervention
- FMD, flow-mediated vasodilation
- NTG, nitroglycerin
Footnotes
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Address correspondence and reprint requests to M. L. Bots, MD, PhD, Julius Center for General Practice and Patient Oriented Research, University Medical Center Utrecht, P.O. Box 85500, 3508 GA Utrecht, the Netherlands. E-mail: M.L.Bots{at}jc.azu.nl.
Received for publication 16 July 2001 and accepted in revised form 25 February 2002.
The laboratory of F.V.V., M.A.V., M.L.B., R.P.S., M.V.H., and J.D.B. has received funds from Pfizer to conduct studies on atorvastatin to treat patients with type 2 diabetes.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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