SIMVASTATIN APOB TURNOVER IN DIABETES

The class of cholesterol-lowering agents called HMCGCoA reductase inhibitors (statins) have had a dramatic impact on our potential to safely and effectively lower blood levels of low density lipoprotein cholesterol (LDL-C). Simvastatin is a very potent and effective member of this class of statins that has been used to treat several million patients world wide. The highest approved dose of simvastatin, 40mg/day, can lower LDL-C about 40-45% and reduce triglyceride levels about 10-15%. Simvastatin has modest effects on high density lipoprotein cholesterol (HDL-C); treatment with 40mg/day of simvastatin raised HDL-C about 5-8% Patients with non-insulin dependent diabetes mellitus (NIDDM) have a 2-4 fold increase in rates of coronary artery disease (CAD)and mortality compared to nondiabetics. NIDDM patients typically have a dsylipidemia that is characterized by higher plasma triglyceride levels. Plasma LDL cholesterol levels are not typically increased compared to non-diabetics, but risk for CAD increases as LDL rises. Treatment of diabetic dyslipidemia has often required two drugs, a statin to lower LDL-C and a second drug, either niacin or Lopid, targeted a triglycerides and HDL-C. These drug combinations raise the risk of adverse effects. Recently, doses of standard simvastatin greater than 40mg/day, and the highest approved dose of atorvastatin were shown to be efficacious at lowering triglycerides (25-35%), raising the potential to treat diabetic dyslipidemia with one drug. It is important, however, to delineate the mechanism underlying this dual lipid-lowering action of high dose statins. That is the aim of this study.