Effect of treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor on fasting and postprandial plasma lipoproteins and cholesteryl ester transfer activity in patients with NIDDM

Diabetes. 1995 Apr;44(4):460-5. doi: 10.2337/diab.44.4.460.

Abstract

Patients with non-insulin-dependent diabetes mellitus (NIDDM) have a greater risk of developing coronary heart disease than would be expected from a similar degree of hyperlipidemia in nondiabetic populations. Accelerated transfer of cholesteryl esters (CET) from high-density lipoprotein (HDL) to low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL), a process that is associated with atherosclerosis, may be a possible explanation for this. CET, plasma lipoprotein concentration, and mass in the fasting and postprandial state have been examined in 31 hyperlipidemic patients with NIDDM before and after 8 weeks of treatment with the hydroxymethylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitor pravastatin in a double-blind, placebo-controlled, parallel group study. Body mass index, glycemic control, and blood pressure remained unaltered during the study period. Compared with placebo, pravastatin decreased fasting serum cholesterol (P < 0.001) and LDL cholesterol (P < 0.002) levels. The high basal CET (34.4 +/- 13.1 nmol.ml-1.h-1) was decreased significantly by pravastatin treatment (27.5 +/- 13.7 nmol.ml-1.h-1, P = 0.013). There was a fall in the total cholesterol, free cholesterol, and phospholipid content of the Sf 0-12, 20-60, and 60-400 lipoproteins (all P = 0.001). Lecithin: cholesterol acyl transferase activity was not altered. The postprandial increase in VLDL cholesterol 5 h after a standardized mixed meal was attenuated after pravastatin treatment (P = 0.011). Inhibition of hepatic cholesterol synthesis with an HMG-CoA reductase inhibitor in hyperlipidemic patients with NIDDM decreased serum cholesterol content of triglyceride-rich lipoprotein, thereby decreasing the transfer of cholesteryl ester from HDL to LDL and VLDL.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carrier Proteins / metabolism*
  • Cholesterol Ester Transfer Proteins
  • Cholesterol Esters / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism*
  • Double-Blind Method
  • Fasting
  • Glycoproteins*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors*
  • Lipoproteins / blood*
  • Middle Aged
  • Phosphatidylcholine-Sterol O-Acyltransferase / metabolism
  • Pravastatin / pharmacology*
  • Pravastatin / therapeutic use

Substances

  • CETP protein, human
  • Carrier Proteins
  • Cholesterol Ester Transfer Proteins
  • Cholesterol Esters
  • Glycoproteins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins
  • Phosphatidylcholine-Sterol O-Acyltransferase
  • Pravastatin