Meta-analysis of the effects of statin therapy on endothelial function in patients with diabetes mellitus

Atherosclerosis. 2012 Jul;223(1):78-85. doi: 10.1016/j.atherosclerosis.2012.01.031. Epub 2012 Jan 23.


Background: Controversies exist among trials reporting the effects of statins on endothelial dysfunction in patients with diabetes mellitus (DM). Therefore, we performed a meta-analysis to determine whether statin therapy could improve endothelial dysfunction in patients with DM.

Methods: PubMed, Cochrane and Embase were searched for randomized controlled trials of statins. Only trials reporting changes in flow-mediated dilatation (FMD) were included in this analysis. A meta-analysis was performed to assess the relationship between statin therapy and improvements in endothelial dysfunction. Meta-regression and subgroup analyses were done to identify sources of heterogeneity.

Results: Ten statin studies (845 patients) were included in this analysis. Statin therapy significantly improved FMD in patients with DM [weighted mean difference (WMD): 0.94%; 95% CI: 0.38%, 1.5%; P<0.001]. Although heterogeneity among trials was found (I(2): 67%), no significant publication bias was detected. Subgroup analyses showed that patients did not benefit from statin therapy if their body mass index (BMI) was>27.6 kg/m(2) (four trials; I(2): 0%; WMD: 0.11%; 95% CI: -0.47%, 0.70%; P=0.70). However, FMD was significantly improved among patients with BMI ≤27.6 kg/m(2) (five trials; I(2): 14%; WMD: 1.52%; 95% CI: 1.19%, 1.85%; P<0.001). Type 1 diabetes, younger age, lower baseline blood lipid levels and blood pressure were all associated with improvements in FMD. The meta-regression analysis yielded similar results.

Conclusion: Statins significantly improved the FMD only in patients with better endothelial functions. The use of FMD in evaluating therapeutic outcomes should be careful in populations at high risk.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / diagnostic imaging
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / drug therapy*
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / physiopathology
  • Endothelium, Vascular / diagnostic imaging
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Male
  • Middle Aged
  • Recovery of Function
  • Risk Assessment
  • Risk Factors
  • Treatment Outcome
  • Ultrasonography
  • Vasodilation / drug effects*


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors