» Articles » PMID: 20150294

Pioglitazone Decreases Plasma Cholesteryl Ester Transfer Protein Mass, Associated with a Decrease in Hepatic Triglyceride Content, in Patients with Type 2 Diabetes

Abstract

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.

Research Design And 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.

Citing Articles

Metabolite profiles of diabetes mellitus and response to intervention in anti-hyperglycemic drugs.

Liu Y, Wang D, Liu Y Front Endocrinol (Lausanne). 2023; 14:1237934.

PMID: 38027178 PMC: 10644798. DOI: 10.3389/fendo.2023.1237934.


Comparative efficacy of glucose-lowering drugs on liver steatosis as assessed by means of magnetic resonance imaging in patients with type 2 diabetes mellitus: systematic review and network meta-analysis.

Malandris K, Papandreou S, Avgerinos I, Karagiannis T, Paschos P, Michailidis T Hormones (Athens). 2023; 22(4):655-664.

PMID: 37770761 PMC: 10651545. DOI: 10.1007/s42000-023-00493-z.


Hepatic triglyceride content does not affect circulating CETP: lessons from a liraglutide intervention trial and a population-based cohort.

van Eyk H, Blauw L, Bizino M, Wang Y, Willems van Dijk K, de Mutsert R Sci Rep. 2019; 9(1):9996.

PMID: 31292457 PMC: 6620358. DOI: 10.1038/s41598-019-45593-2.


A Drug Screen using Human iPSC-Derived Hepatocyte-like Cells Reveals Cardiac Glycosides as a Potential Treatment for Hypercholesterolemia.

Cayo M, Mallanna S, Di Furio F, Jing R, Tolliver L, Bures M Cell Stem Cell. 2017; 20(4):478-489.e5.

PMID: 28388428 PMC: 5385853. DOI: 10.1016/j.stem.2017.01.011.


Serum CETP status is independently associated with reduction rates in LDL-C in pitavastatin-treated diabetic patients and possible involvement of LXR in its association.

Shimada A, Kimura H, Oida K, Kanehara H, Bando Y, Sakamoto S Lipids Health Dis. 2016; 15:57.

PMID: 26984517 PMC: 4794860. DOI: 10.1186/s12944-016-0223-6.


References
1.
Juvet L, Andresen S, Schuster G, Dalen K, Tobin K, Hollung K . On the role of liver X receptors in lipid accumulation in adipocytes. Mol Endocrinol. 2003; 17(2):172-82. DOI: 10.1210/me.2001-0210. View

2.
Luo Y, Tall A . Sterol upregulation of human CETP expression in vitro and in transgenic mice by an LXR element. J Clin Invest. 2000; 105(4):513-20. PMC: 289164. DOI: 10.1172/JCI8573. View

3.
van der Hoogt C, de Haan W, Westerterp M, Hoekstra M, Dallinga-Thie G, Romijn J . Fenofibrate increases HDL-cholesterol by reducing cholesteryl ester transfer protein expression. J Lipid Res. 2007; 48(8):1763-71. DOI: 10.1194/jlr.M700108-JLR200. View

4.
Targher G, Arcaro G . Non-alcoholic fatty liver disease and increased risk of cardiovascular disease. Atherosclerosis. 2006; 191(2):235-40. DOI: 10.1016/j.atherosclerosis.2006.08.021. View

5.
Toledo F, Sniderman A, Kelley D . Influence of hepatic steatosis (fatty liver) on severity and composition of dyslipidemia in type 2 diabetes. Diabetes Care. 2006; 29(8):1845-50. DOI: 10.2337/dc06-0455. View