Science

Pioglitazone decreases plasma CETP mass in type 2 diabetics

Last Updated: 2010-03-18 10:21:27 -0400 (Reuters Health)

NEW YORK (Reuters Health) - In men with type 2 diabetes, pioglitazone induces a decrease in hepatic triglyceride content that's accompanied by a decrease of cholesteryl ester transfer protein (CETP) in plasma and an increase in high density lipoprotein (HDL) cholesterol, researchers from the Netherlands report.

Dr. Jacqueline T. Jonker, of Leiden University Medical Center, and colleagues examined the effects of pioglitazone on plasma CETP mass in 78 men with type 2 diabetes mellitus (mean age 56.5 years) and a mean hemoglobin (Hb)A1c of 7.1%. The researchers randomized the men to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day); all subjects also took glimepiride.

Overall, 34 men in the pioglitazone group and 37 in the metformin group completed the study. Plasma HDL-cholesterol levels and CETP mass were measured at baseline and after 24 weeks of treatment. In addition, triglyceride content in the liver was assessed by proton magnetic resonance spectroscopy.

In a February 11th online paper in Diabetes Care, the researchers report that pioglitazone decreased hepatic triglyceride content from 5.9% at baseline to 4.1% at 24 week (p < 0.05) and plasma CETP mass from 2.33 to 2.06 mcg/mL (p < 0.05); pioglitazone also increased plasma HDL-cholesterol levels from 1.22 to 1.34 mM (p < 0.05).

Metformin did not produce any significant change in any of these parameters.

At 24 weeks, changes in plasma CETP mass and in hepatic triglyceride content were correlated in the pioglitazone group (r = 0.34, p < 0.05). No such association was observed in the metformin group.

"These findings are in full concordance with our recent studies in APOE*3-Leiden.CETP mice, which showed that classical lipid-lowering drugs concurrently lowered hepatic lipid content and decreased hepatic CETP mRNA expression, resulting in a decreased plasma CETP mass," the researchers said.

"Given the generally observed inverse relationship between plasma triglycerides and HDL-cholesterol found in epidemiological studies, a decrease in plasma triglycerides only might induce an increase in HDL-cholesterol," the authors wrote. "However, in the present study the decrease in plasma triglycerides was not different between the groups and plasma HDL-cholesterol only increased in the pioglitazone group, indicating another mechanism may be responsible for eliciting the difference, i.e., the reduction in CETP."

Diabetes Care 2010.