Rosuvastatin 20 mg restores normal HDL-apoA-I kinetics in type 2 diabetes.
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 (13)C 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.
Vergès
Bruno
B
Service Endocrinologie, Diabétologie et Maladies Métaboliques, Centre Hospitalier Universitaire de Dijon, 21033 Dijon, France. bruno.verges@chu-dijon.fr
Florentin
Emmanuel
E
Baillot-Rudoni
Sabine
S
Petit
Jean-Michel
JM
Brindisi
Marie Claude
MC
Pais de Barros
Jean-Paul
JP
Lagrost
Laurent
L
Gambert
Philippe
P
Duvillard
Laurence
L
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood
D016632:Apolipoprotein A-I; D001786:Blood Glucose; D002247:Carbon Isotopes; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; C034396:HDL-triglyceride; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008075:Lipoproteins, HDL; D011743:Pyrimidines; D013449:Sulfonamides; D014280:Triglycerides; D000068718:Rosuvastatin Calcium