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Journal of Lipid Research, Vol. 50, 1209-1215, June 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes

Bruno Vergès^1,*,, Emmanuel Florentin, Sabine Baillot-Rudoni^*, Jean-Michel Petit^*,, Marie Claude Brindisi^*, Jean-Paul Pais de Barros, Laurent Lagrost, Philippe Gambert and Laurence Duvillard

^* Service Endocrinologie, Diabétologie et Maladies Métaboliques, Centre Hospitalier Universitaire de Dijon, 21033 Dijon, France
INSERM CRI 866, Faculté de Médecine, 21033 Dijon, France

Published, JLR Papers in Press, January 22, 2009.

This study was supported by a grant from AstraZeneca.

¹ To whom correspondence should be addressed. e-mail: bruno.verges{at}chu-dijon.fr

Catabolism of HDL particles is accelerated in type 2 diabetes, leading to a reduction in plasma residence time, which may be detrimental. Rosuvastatin is the most powerful statin to reduce LDL-cholesterol, but its effects on HDL metabolism in type 2 diabetes remain unknown. We performed a randomized double-blind cross-over trial of 6-week treatment period with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes. An in vivo kinetic study of HDL-apolipoprotein A-I (apoA-I) with ¹³C leucine was performed at the end of each treatment period. Moreover, a similar kinetic study was carried out in eight nondiabetic normolipidemic controls. Rosuvastatin significantly reduced plasma LDL-cholesterol (–51%), triglycerides (TGs) (–38%), and HDL-TG (–23%). HDL-apoA-I fractional catabolic rate (FCR) was decreased by rosuvastatin (0.25 ± 0.06 vs. 0.32 ± 0.07 pool/day, P = 0.011), leading to an increase in plasma HDL-apoA-I residence time (4.21 ± 1.02 vs. 3.30 ± 0.73 day, P = 0.011). Treatment with rosuvastatin was associated with a concomitant reduction of HDL-apoA-I production rate. The decrease in HDL-apoA-I FCR, induced by rosuvastatin, was correlated with the reduction of plasma TGs and HDL-TG. HDL apoA-I FCR and production rate values in diabetic patients on rosuvastatin were not different from those found in controls. Rosuvastatin is responsible for a 22% reduction of HDL-apoA-I FCR and restores to normal the increased HDL turnover observed in type 2 diabetes. These kinetic modifications may have beneficial effects by increasing HDL plasma residence time.

Supplementary key words HDL-cholesterol • kinetic • statin

Abbreviations: apoA-I, apolipoprotein A-I; CETP, cholesteryl ester transfer protein; FCR, fractional catabolic rate; FSR, fractional synthetic rate; PR, production rate; TG, triglyceride

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