Role of simvastatin as an immunomodulator in type 2 diabetes.
OBJECTIVE
To test the hypothesis that simvastatin reduces the levels of circulating immune complexes (ICs) containing modified lipoproteins (mLDLs; mLDL-ICs), which may represent an additional mechanism for the reduced incidence of cardiovascular events in patients treated with simvastatin.


METHODS
A total of 26 patients with type 2 diabetes and triglyceride levels <400 mg/dl who were not receiving lipid-lowering medications or CYP 3A4 inhibitors were enrolled in the study. After 2 weeks on a lipid-lowering diet and exercise, the patients were started on simvastatin 20 mg/day. The dose of simvastatin was adjusted until the levels of LDL cholesterol were < or =100 mg/dl. Blood was collected at baseline, 3 and 6 months after LDL cholesterol levels reached target, and 3 months after stopping simvastatin to measure advanced glycation end product LDL and oxidized LDL antibodies, mLDL-IC, intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), E-selectin, metalloproteinase-1 (MMP-1), lipid profile, liver function tests, creatinine kinase, glucose, and HbA(1c).


RESULTS
Twenty-one patients completed the study. Their HbA(1c) remained within 1% of baseline levels. There was a highly significant decrease in mLDL-IC levels after 3 and 6 months of treatment with simvastatin, with a return to near baseline levels after discontinuation.


CONCLUSIONS
Simvastatin significantly reduced the concentration of mLDL-IC, probably as a consequence of both a decrease in the formation of mLDL and to a reduction in the titers of mLDL antibodies. This effect is likely to have a beneficial impact in the inflammatory reaction associated with atherosclerosis.
Lopes-Virella
Maria F
MF
Department of Medicine, Medical University of South Carolina, and Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, South Carolina 29425, USA. virellam@musc.edu
Mironova
Marina
M
Stephan
Elias
E
Durazo-Arvizu
Ramon
R
Virella
Gabriel
G
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000368:Aged; D000936:Antigen-Antibody Complex / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D019821:Simvastatin / Q000627:therapeutic use*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D000936:Antigen-Antibody Complex; D006442:Glycated Hemoglobin; D008074:Lipoproteins; D019821:Simvastatin