Pioglitazone decreases plasma cholesteryl ester transfer protein mass, associated with a decrease in hepatic triglyceride content, in patients with type 2 diabetes.
OBJECTIVE
Thiazolidinediones reduce hepatic steatosis and increase HDL cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride content is associated with a decrease in plasma cholesteryl ester transfer protein (CETP) mass and an increase in HDL levels. Therefore, the aim of the present study was to assess the effects of pioglitazone on CETP mass in patients with type 2 diabetes.


METHODS
We included 78 men with type 2 diabetes (aged 56.5 +/- 0.6 years; HbA1c 7.1 +/- 0.1%) who were randomly assigned to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebo, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL cholesterol levels and CETP mass were measured, and hepatic triglyceride content was assessed by proton magnetic resonance spectroscopy. RESULTS Pioglitazone decreased hepatic triglyceride content (5.9 [interquartile range 2.6-17.4] versus 4.1 [1.9-12.3]%, P < 0.05), decreased plasma CETP mass (2.33 +/- 0.10 vs. 2.06 +/- 0.10 microg/ml, P < 0.05), and increased plasma HDL cholesterol level (1.22 +/- 0.05 vs. 1.34 +/- 0.05 mmol/l, P < 0.05). Metformin did not significantly change any of these parameters.


CONCLUSIONS
A decrease in hepatic triglyceride content by pioglitazone is accompanied by a decrease in plasma CETP mass and associated with an increase in HDL cholesterol levels. These results in patients with type 2 diabetes fully confirm recent findings in mice.
Jonker
Jacqueline T
JT
Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, the Netherlands. j.t.jonker@lumc.nl
Wang
Yanan
Y
de Haan
Willeke
W
Diamant
Michaela
M
Rijzewijk
Luuk J
LJ
van der Meer
Rutger W
RW
Lamb
Hildo J
HJ
Tamsma
Jouke T
JT
de Roos
Albert
A
Romijn
Johannes A
JA
Rensen
Patrick C N
PC
Smit
Johannes W A
JW
D053299:Apolipoprotein B-100 / Q000097:blood; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004359:Drug Therapy, Combination; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D008875:Middle Aged; D000077205:Pioglitazone; D010919:Placebos; D011446:Prospective Studies; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D045162:Thiazolidinediones / Q000008:administration & dosage*; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
D053299:Apolipoprotein B-100; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D010919:Placebos; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D014280:Triglycerides; C057619:glimepiride; D008687:Metformin; D002784:Cholesterol; D000077205:Pioglitazone