Effects of 20 mg rosuvastatin on VLDL1-, VLDL2-, IDL- and LDL-ApoB kinetics in type 2 diabetes.
OBJECTIVE
In addition to its efficacy in reducing LDL-cholesterol, rosuvastatin has been shown to significantly decrease plasma triacylglycerol. The use of rosuvastatin may be beneficial in patients with type 2 diabetes, who usually have increased triacylglycerol levels. However, its effects on the metabolism of triacylglycerol-rich lipoproteins in type 2 diabetic patients remains unknown.


METHODS
We performed a randomised double-blind crossover trial of 6-week treatment with placebo or rosuvastatin 20 mg in eight patients with type 2 diabetes who were being treated with oral glucose-lowering agents. In each patient, an in vivo kinetic study of apolipoprotein B (ApoB)-containing lipoproteins with [13C]leucine was performed at the end of each treatment period. A central randomisation centre used computer-generated tables to allocate treatments. Participants, caregivers and those assessing the outcomes were blinded to group assignment.


RESULTS
Rosuvastatin 20 mg significantly reduced plasma LDL-cholesterol, triacylglycerol and total ApoB. It also significantly reduced ApoB pool sizes of larger triacylglycerol-rich VLDL particles (VLDL1; p = 0.011), smaller VLDL particles (VLDL2; p = 0.011), intermediate density lipoprotein (IDL; p = 0.011) and LDL (p = 0.011). This reduction was associated with a significant increase in the total fractional catabolic rate of VLDL1-ApoB (6.70 +/- 3.24 vs 4.52 +/- 2.34 pool/day, p = 0.049), VLDL2-ApoB (8.72 +/- 3.37 vs 5.36 +/- 2.64, p = 0.011), IDL-ApoB (7.06 +/- 1.68 vs 4.21 +/- 1.51, p = 0.011) and LDL-ApoB (1.02 +/- 0.27 vs 0.59 +/- 0.13, p = 0.011). Rosuvastatin did not change the production rates of VLDL2-, IDL- or LDL-, but did reduce VLDL1-ApoB production rate (12.4 +/- 4.5 vs 19.5 +/- 8.4 mg kg(-1) day(-1), p = 0.035). No side effects of rosuvastatin were observed during the study.


CONCLUSIONS
In type 2 diabetic patients rosuvastatin 20 mg not only induces a significant increase of LDL-ApoB catabolism (73%), but also has favourable effects on the catabolism of triacylglycerol-rich lipoproteins, e.g. a significant increase in the catabolism of VLDL1-ApoB (48%), VLDL2-ApoB (63%) and IDL-ApoB (68%), and a reduction in the production rate of VLDL1-ApoB (-36%). The effects of rosuvastatin on the metabolism of triacylglycerol-rich lipoproteins may be beneficial for prevention of atherosclerosis in type 2 diabetic patients.
Service Endocrinologie, Diabétologie et Maladies métaboliques, Centre Hospitalier Universitaire de Dijon, Hôpital du Bocage, Dijon, BP 77908, 21079, France. bruno.verges@chu-dijon.fr
B
B
Vergès
E
E
Florentin
S
S
Baillot-Rudoni
S
S
Monier
J M
JM
Petit
D
D
Rageot
P
P
Gambert
L
L
Duvillard
D001055:Apolipoproteins B / Q000097:blood* / Q000187:drug effects; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007700:Kinetics; D053419:Lipoproteins, IDL / Q000097:blood* / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000097:blood* / Q000187:drug effects; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D001055:Apolipoproteins B; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053419:Lipoproteins, IDL; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium