Ezetimibe beneficially influences fasting and postprandial triglyceride-rich lipoproteins in type 2 diabetes

Introduction: Type 2 diabetes is associated with atherogenic abnormalities of postprandial triglyceride-rich lipoproteins. This study evaluated whether ezetimibe, by inhibiting intestinal cholesterol absorption, influences chylomicrons and VLDL particles at fasting and after a standard meal. Methods: By a double blind cross-over design 15 subjects with type 2 diabetes and hypercholesterolaemia followed in random order a 6-week treatment with ezetimibe 10 mg + simvastatin 20 mg (EZE + S) or placebo + simvastatin 20 mg (P + S) and, after a 6-week wash-out period, crossed over to the other treatment (NCT00699023). At the end of each period lipids, apoB-48, and apoB-100 concentrations in plasma and lipoprotein fractions (separated by discontinuous density gradient ultracentrifugation) were determined before and over 6 h following a high-fat test meal. Results: Compared with P + S, EZE + S induced, (a) beside a greater decrease in LDL cholesterol, (b) a significant decrease in chylomicron lipid content both at fasting and postprandially (4.4 +/- 2.7 vs. 8.3 +/- 8.7 mg/dl x 6 h total AUC for cholesterol, p < 0.05; 18 +/- 12 vs. 29 +/- 24 mg/dl triglyceride concentrations at 6 h, p < 0.05), (c) a significant decrease in chylomicron postprandial apoB-48 (0.03 +/- 0.03 vs. 0.09 +/- 0.08 mg/l at 4 h, p < 0.05), and (d) significant fasting and postprandial decreases in the cholesterol content of VLDL, IDL, and LDL, as shown by the significant reduction of the cholesterol/triglyceride ratio in these lipoproteins. Conclusions: A 6-week treatment with ezetimibe and simvastatin, compared to simvastatin alone, positively influences lipoprotein profile both at fasting and postprandially in type 2 diabetic patients by favouring the production of cholesterol-poor chylomicrons and VLDL particles that have less atherogenic potential. (C) 2011 Elsevier Ireland Ltd. All rights reserved.