title: Changes in insulin resistance and cardiovascular risk induced by PPARgamma activation have no impact on RBP4 plasma concentrations in nondiabetic patients.
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/m (2)). 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 HOMA (IR)-Score, an oral glucose tolerance test, adiponectin, hsCRP, and RBP4 at baseline and endpoint. No correlation could be detected between the HOMA (IR) 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 HOMA (IR)-Score and the adiponectin values, while no change in HOMA (IR) 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.
authors.affiliation: Institute for Clinical Research and Development, Mainz, Germany. thomasf@ikfe.de
authors.forename: A
authors.initials: A
authors.lastname: Pfützner
authors.forename: T
authors.initials: T
authors.lastname: Schöndorf
authors.forename: M
authors.initials: M
authors.lastname: Hanefeld
authors.forename: G
authors.initials: G
authors.lastname: Lübben
authors.forename: P H
authors.initials: PH
authors.lastname: Kann
authors.forename: E
authors.initials: E
authors.lastname: Karagiannis
authors.forename: B
authors.initials: B
authors.lastname: Wilhelm
authors.forename: T
authors.initials: T
authors.lastname: Forst
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D004311:Double-Blind Method; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance / Q000502:physiology*; D047495:PPAR gamma / Q000494:pharmacology*; D000077205:Pioglitazone; D012016:Reference Values; D054839:Retinol-Binding Proteins, Plasma / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D019821:Simvastatin / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D047495:PPAR gamma; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D045162:Thiazolidinediones; D019821:Simvastatin; D000077205:Pioglitazone