HMG-CoA reductase inhibitor, simvastatin improves reverse cholesterol transport in type 2 diabetic patients with hyperlipidemia

J Atheroscler Thromb. 2008 Feb;15(1):20-5. doi: 10.5551/jat.e512. Epub 2008 Feb 9.


Aim: ApoA-I and HDL promote cellular cholesterol efflux in the early stages of the reverse cholesterol transport (RCT) pathway. A low plasma HDL-C level is characteristic of atherogenic dyslipidemia in patients with type 2 diabetes. We evaluated plasma lipid levels and the expression of factors related to RCT in type 2 diabetic patients, and the effects of an HMG-CoA reductase inhibitor, simvastatin, were studied.

Methods: Messenger RNA (mRNA) expression in circulating mononuclear cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR), focusing on the following factors: liver X receptor alpha (LXR alpha), ATP-binding cassette A1 (ABCA1), scavenger receptor class B type 1 (SR-B1), apolipoprotein E (ApoE), apolipoprotein A-1 (ApoA-1), caveolin, and cholesterol ester transfer protein (CETP). Type 2 diabetic subjects (n=29) were divided into three subgroups: patients with normolipidemia (DM group, n=11), patients with untreated hyperlipidemia (DMHL group, n=10), and those with hyperlipidemia treated with simvastatin 5-10mg/day (DMST group, n=8). The control group (CNT group) included seven healthy volunteers.

Results: Simvastatin treatment significantly increased plasma levels of ApoA-I compared to the other three groups. Simvastatin treatment improved the expression of mRNA for LXRalpha, ABCA1, and ApoA-I compared with DMHL or control groups.

Conclusion: Our data suggest that RCT may be reduced in type 2 diabetic patients with hyperlipidemia, and simvastatin may be able to improve reverse cholesterol transport for this population of diabetic patients.

MeSH terms

  • Aged
  • Apolipoprotein A-I / blood
  • Cholesterol / blood*
  • Cholesterol, HDL / blood*
  • Diabetes Mellitus, Type 2 / blood*
  • Female
  • Gene Expression
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hyperlipidemias / drug therapy*
  • Male
  • Middle Aged
  • Simvastatin / pharmacology*


  • Apolipoprotein A-I
  • Cholesterol, HDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol
  • Simvastatin