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Effects of rosiglitazone and pioglitazone on lipoprotein metabolism in patients with Type 2 diabetes and normal lipids
Authors:A L Brackenridge  N Jackson  W Jefferson  M Stolinski  F Shojaee‐Moradie  R Hovorka  A M Umpleby  D Russell‐Jones
Institution:1. Centre for Diabetes, Endocrinology and Research, Royal Surrey County Hospital, Guildford, Surrey;2. Diabetes and Endocrinology, Postgraduate Medical School, University of Surrey, Guildford, Surrey;3. Beta Cell Development and Function Group, Division of Reproduction and Endocrinology, School of Biomedical and Health Sciences, Kings College London, London;4. Diabetes Modelling Group, Department of Paediatrics, University of Cambridge, Cambridge, UK
Abstract:Aims Previous studies have suggested that plasma lipids are affected differently by the peroxisome proliferators‐activated receptor (PPAR)‐γ agonists pioglitazone and rosiglitazone. The aim of this study was to perform a quantitative lipoprotein turnover study to determine the effects of PPAR‐γ agonists on lipoprotein metabolism. Methods Twenty‐four subjects with Type 2 diabetes treated with diet and/or metformin were randomized in a double‐blind study to receive 30 mg pioglitazone, 8 mg rosiglitazone or placebo once daily for 3 months. Before and after treatment, absolute secretion rate (ASR) and fractional catabolic rate (FCR) of very low‐density lipoprotein (VLDL), intermediate‐density lipoprotein (IDL) and low‐density lipoprotein (LDL) apolipoprotein B100 were measured with a 10‐h infusion of 1‐13C leucine. Results There was a significant decrease in glycated haemoglobin (HbA1c) and non‐esterified fatty acids with pioglitazone (P = 0.01; P = 0.02) and rosiglitazone (P = 0.04; P = 0.003), respectively, but no change in plasma triglyceride or high‐density lipoprotein (HDL) cholesterol. Following rosiglitazone, there was a significant reduction in VLDL apolipoprotein B100 (apoB) ASR (P = 0.01) compared with baseline, a decrease in VLDL triglyceride/apoB (P = 0.01), an increase in LDL2 cholesterol (P = 0.02) and a decrease in LDL3 cholesterol (P = 0.02). There was a decrease in VLDL triglyceride/apoB (P = 0.04) in the pioglitazone group. There was no significant difference in change in VLDL ASR or FCR among the three groups. Conclusions In patients with Type 2 diabetes and normal lipids, treatment with rosiglitazone or pioglitazone had no significant effect on lipoprotein metabolism compared with placebo.
Keywords:intermediate density lipoprotein  low‐density lipoprotein  non‐esterified fatty acid  peroxisome proliferators‐activated receptor‐γ  agonist  Type   2 diabetes  very low‐density lipoprotein
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