Effects of rosiglitazone and pioglitazone on lipoprotein metabolism in patients with Type 2 diabetes and normal lipids.
OBJECTIVE
Previous studies have suggested that plasma lipids are affected differently by the peroxisome proliferators-activated receptor (PPAR)-gamma agonists pioglitazone and rosiglitazone. The aim of this study was to perform a quantitative lipoprotein turnover study to determine the effects of PPAR-gamma 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 (HbA(1c)) 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.
Brackenridge
A L
AL
Centre for Diabetes, Endocrinology and Research, Royal Surrey County Hospital, Guildford, Surrey GU2 7XX, UK.
Jackson
N
N
Jefferson
W
W
Stolinski
M
M
Shojaee-Moradie
F
F
Hovorka
R
R
Umpleby
A M
AM
Russell-Jones
D
D
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008074:Lipoproteins / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos; D000077154:Rosiglitazone; D018709:Statistics, Nonparametric; D045162:Thiazolidinediones / Q000627:therapeutic use*
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008074:Lipoproteins; D000077205:Pioglitazone; D010919:Placebos; D000077154:Rosiglitazone; D045162:Thiazolidinediones