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ABSORPTION, DISTRIBUTION, METABOLISM, AND EXCRETION

Effect of Atorvastatin on Apolipoprotein B100 Containing Lipoprotein Metabolism in Type-2 Diabetes

Centre de Recherche en Nutrition Humaine, Institut National de la Santé et de la Recherche Médicale U539-Hôtel Dieu, Nantes, France (K.O., T.M., Y.Z., M.K.); Division of Clinical Nutrition, School of Medicine of Ribeirão Preto, São Paolo, Brazil (J.S.M.); Clinique d'Endocrinologie-Nutrition, Hôtel Dieu, Nantes, France (M.K., B.C.); and Pfizer Pharmaceutical Group Paris, Paris, France (H.L.)

Seven hypertriglyceridemic patients with type-2 diabetes were treated with atorvastatin (40 mg/day) for 2 months. Kinetics of apolipoprotein B100 (apoB100)-containing lipoproteins were determined before and after atorvastatin treatment and compared with data obtained in five normolipidemic volunteers. ApoB100 metabolism was studied using stable isotopes and multicompartmental modeling. Compared with normolipidemic obese subjects, type-2 diabetic patients had a higher apoB100 concentration in very low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), and low-density lipoproteins (LDL) (P < 0.005). Kinetic analysis showed an increase in the total apoB100 production rate (P < 0.005) related to VLDL apoB100 overproduction (P < 0.005). Patients were also characterized by a lower fractional catabolic rate (FCR) in VLDL (not significant) or IDL (P < 0.005) mainly related to a decrease in VLDL and IDL delipidation rate (P < 0.005). Catabolism of LDL was also lower in diabetic patients (P < 0.05). Atorvastatin treatment significantly decreased plasma triglycerides (P < 0.05), total and LDL cholesterol (P < 0.05), apoB100 in LDL, IDL, and VLDL (P < 0.05). Treatment significantly decreased total apoB100 production rate (P < 0.05), but only for VLDL (P < 0.05). Treatment normalized FCR in IDL and LDL (P < 0.05). We concluded that atorvastatin improved lipid abnormalities in type-2 diabetic patients not only by increasing the clearance of apoB100-containing lipoproteins but also by decreasing VLDL production.

Address correspondence to: Khadija Ouguerram, Centre de Recherche en Nutrition Humaine, INSERM U539-Hôtel Dieu, France. E-mail: khadija.ouguerram{at}sante.univ-nantes.fr

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