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Horm Metab Res 2009; 41(3): 202-206
DOI: 10.1055/s-0028-1104592
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Changes in Insulin Resistance and Cardiovascular Risk Induced by PPARγ Activation have no Impact on RBP4 Plasma Concentrations in Nondiabetic Patients

A. Pfützner 1 , 2 , T. Schöndorf 1 , 3 , M. Hanefeld 4 , G. Lübben 5 , P. H. Kann 1 , 6 , E. Karagiannis 5 , B. Wilhelm 1 , T. Forst 1 , 7
  • 1Institute for Clinical Research and Development, Mainz, Germany
  • 2University Medical Center, Cologne, Germany
  • 3University of Applied Sciences, Rheinbach, Germany
  • 4GWT, Dresden, Germany
  • 5TAKEDA Pharma GmbH, Aachen, Germany
  • 6Phillipps University, Department of Endocrinology and Metabolism, Marburg, Germany
  • 7Johannes Gutenberg University, Department of Endocrinology and Metabolism, Mainz, Germany
Further Information

Publication History

received 13.11.2007

accepted 10.07.2008

Publication Date:
17 February 2009 (online)

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Abstract

Retinol binding protein 4 (RBP4) has recently been suggested as a good biomarker for insulin resistance and the metabolic syndrome. With this study, we wanted to investigate the effect of pioglitazone (PIO) and simvastatin (SIMVA) on insulin resistance and RBP4 plasma concentrations in nondiabetic patients with metabolic syndrome and increased risk for cardiovascular complications. The prospective, parallel, randomized, double-blind clinical trial was performed with 125 nondiabetic patients with increased cardiovascular risk (78 females, 47 males, age (mean±STD): 58.6±7.8 years, BMI: 30.8±4.2 kg/m2). They were randomized to either receive PIO (45 mg)+placebo, SIMVA (40 mg)+placebo, or PIO+SIMVA for 3 months. Key outcome measures were the HOMAIR-Score, an oral glucose tolerance test, adiponectin, hsCRP, and RBP4 at baseline and endpoint. No correlation could be detected between the HOMAIR values or the impaired fasting glucose tolerance status and RBP-4. Treatment with PIO alone or in combination with SIMVA resulted in a significant improvement of the HOMAIR-Score and the adiponectin values, while no change in HOMAIR and a decrease in adiponectin (p<0.05) were observed with SIMVA monotherapy. Reductions of hsCRP were seen in all three treatment arms (p<0.001). No changes of the plasma RBP4 concentrations were observed in any of the treatment groups (PIO: 35.6±7.2/36.3±8.7 ng/ml, PIO+SIMVA: 36.5±10.8/36.5±8 ng/ml, SIMVA: 36.1±8.1/36.6±11.1 ng/ml, all n.s. vs. baseline). Despite a partial or comprehensive improvement in insulin resistance and/or cardiovascular risk indicators in all treatment arms, no change in RBP4-levels could be observed. The regulation of RBP4 expression and secretion occurs through biochemical pathways independent from those influenced by pioglitazone or simvastatin.

Key words

metabolic syndrome - retinol binding protein 4 - cardiovascular risk

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Correspondence

A. PfütznerMD, PhD 

Professor of Applied Clinical Research

Institute for Clinical Research and Development

Parcusstraße 8

55116 Mainz

Germany

Phone: +49/6131/576 36 13

Fax: +49/6131/576 36 11

Email: thomasf@ikfe.de

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