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.
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
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Deepak Bhatnagar, Paul N Durrington, Sudesh Kumar, Michael I Mackness, John Dean, Andrew J M Boulton; 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 1 April 1995; 44 (4): 460–465. https://doi.org/10.2337/diab.44.4.460
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