The Effect of Statin Therapy on Endothelial Function in Type 2 Diabetes Without Manifest Cardiovascular Disease

  1. Edith D. Beishuizen, MD1,
  2. Jouke T. Tamsma, MD, PHD1,
  3. J. Wouter Jukema, MD, PHD2,
  4. Marcel A. van de Ree, MD, PHD3,
  5. J. Carel M. van der Vijver, MD, PHD4,
  6. A. Edo Meinders, MD, PHD1 and
  7. Menno V. Huisman, MD, PHD1
  1. 1Department of General Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands
  2. 2Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands
  3. 3Department of Internal Medicine, Diakonessenhuis, Utrecht, the Netherlands
  4. 4Department of Internal Medicine, Leyenburg Hospital, the Hague, the Netherlands
  1. Address correspondence and reprint requests to E.D. Beishuizen, Department of General Internal Medicine, C1-R41, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, Netherlands. E-mail: e.d.beishuizen{at}lumc.nl

Abstract

OBJECTIVE—Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes and is preceded by endothelial dysfunction. Flow-mediated dilation (FMD) is a noninvasive technique for measuring endothelial dysfunction. We aimed to determine the effect of long-term statin therapy versus placebo on FMD in patients with type 2 diabetes without manifest CVD.

RESEARCH DESIGN AND METHODS—A randomized, placebo-controlled, double-blind trial was performed with 250 type 2 diabetic patients. Patients were given 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, the 0.4 mg cerivastatin was replaced by 20 mg simvastatin, without deblinding the study. The primary end point was the change in FMD, measured by B-mode ultrasound, after 2 years.

RESULTS—Determinants of baseline FMD were diabetes duration, common carotid intima-media thickness, and brachial artery diameter. FMD at baseline was 1.51% in the placebo group and 1.66% in the statin group and did not change significantly after 2 years.

CONCLUSIONS—The 2-year statin therapy had no effect on FMD in type 2 diabetes. Statin-induced improvement of cardiovascular risk in patients with type 2 diabetes may be mediated through mechanisms other than increased nitric oxide availability.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted April 10, 2005.
    • Received December 2, 2004.
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  1. doi: 10.2337/diacare.28.7.1668 Diabetes Care July 2005 vol. 28 no. 7 1668-1674
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