Journal Article

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

Monier, S, Gambert, P, Duvillard, L, Petit, J. M, Rageot, D, Vergès, B, Florentin, E, Baillot-Rudoni, S

2008

Overview

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.

• Publisher: Berlin/Heidelberg : Springer-Verlag,Springer-Verlag,Springer,Springer Nature B.V
• Subject: ApoB / apolipoprotein B / Apolipoproteins / Apolipoproteins B / Apolipoproteins B - blood / Apolipoproteins B - drug effects / Biological and medical sciences / blood / Cardiovascular disease / Cholesterol / Cross-Over Studies / Diabetes / Diabetes Mellitus, Type 2 / Diabetes Mellitus, Type 2 - drug therapy / Diabetes. Impaired glucose tolerance / Double-Blind Method / drug effects / drug therapy / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Etiopathogenesis. Screening. Investigations. Target tissue resistance / Female / Fluorobenzenes / Fluorobenzenes - therapeutic use / Glucose / Human Physiology / Humans / Hydroxymethylglutaryl-CoA Reductase Inhibitors / Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use / Internal Medicine / Kinetic / Kinetics / LDL-cholesterol / Lipids / Lipoproteins, IDL / Lipoproteins, IDL - blood / Lipoproteins, IDL - drug effects / Lipoproteins, LDL / Lipoproteins, LDL - blood / Lipoproteins, LDL - drug effects / Lipoproteins, VLDL / Lipoproteins, VLDL - blood / Lipoproteins, VLDL - drug effects / Low density lipoprotein / Male / Medical sciences / Medicine / Medicine & Public Health / Metabolic Diseases / Metabolic disorders / Middle Aged / Placebos / Plasma / Pyrimidines / Pyrimidines - therapeutic use / Rosuvastatin / Rosuvastatin Calcium / Statin / Statins / Substance abuse treatment / Sulfonamides / Sulfonamides - therapeutic use / therapeutic use / Triacylglycerol