Effects of 20 mg rosuvastatin on VLDL1-, VLDL2-, IDL- and LDL-ApoB kinetics in type 2 diabetes

Abstract

Aims/hypothesis: 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/interpretation: 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. Trial registration: ClinicalTrials.gov NCT00658463 Funding: This study was supported by a grant from AstraZeneca. © 2008 Springer-Verlag.