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

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.