Pioglitazone Decreases Plasma CETP Mass, Associated With A Decrease In Hepatic Triglyceride Content, In Patients With Type 2 Diabetes Mellitus

Abstract

Objective: Thiazolidinediones reduce hepatic steatosis and increase high-density lipoprotein (HDL)-cholesterol levels. In mice with human-like lipoprotein metabolism (APOE*3-Leiden.CETP transgenic mice), a decrease in hepatic triglyceride (TG) 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 mellitus. Research Design and Methods: We included 78 men with type 2 diabetes mellitus (age 56.5+/-0.6 years; HbA1c 7.1+/-0.1%) who were randomized to treatment with pioglitazone (30 mg/day) or metformin (2000 mg/day) and matching placebos, in addition to glimepiride. At baseline and after 24 weeks of treatment plasma HDL-cholesterol levels and CETP mass were measured and hepatic TG content was assessed by proton magnetic resonance spectroscopy. Results: Pioglitazone decreased hepatic TG content (5.9 (2.6-17.4) vs. 4.1 (1.9-12.3)%, P<0.05), decreased plasma CETP mass (2.33+/-0.10 vs. 2.06+/-0.10 mug/mL, P<0.05) and increased plasma HDL-cholesterol levels (1.22+/-0.05 vs. 1.34+/-0.05 mM, P<0.05). Metformin did not significantly change any of these parameters. Conclusions: A decrease in hepatic TG 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 mellitus fully confirm recent findings in mice.