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- Title
Influence of a Treatment with Pioglitazone or Simvastatin on Retinol Binding Protein 4 in Patients with Normoglycemic Insulin Resistance.
- Authors
Schöndorf, Thomas; Hanefeld, Markolf; Lübben, Georg; Karagiannis, Efstrathios; Köhler, Carsta; Kann, Peter H.; Wilhelm, Birgit; Forst, Thomas; Pfützner, Andreas
- Abstract
Retinol binding protein 4 (RBP4) has been identified as a laboratory marker for insulin resistance and the metabolic syndrome. We investigated the effect of pioglitazone (PIO) and simvastatin (SIMVA) on insulin resistance and RBP4 plasma concentrations in non-diabetic patients with metabolic syndrome and increased risk for cardiovascular complications in a prospective, parallel, randomized, double-blind clinical trial with 125 non-diabetic patients with increased cardiovascular risk (78 female, 47 male, age(mean±STD): 58.6±7.8 years, BMI: 30.8±4.2 kg/m²). They were treated with PIO(45 mg)+placebo, SIMVA(40 mg)+placebo, or PIO+SIMVA for 3 months. Observation parameters at baseline and endpoint included the HOMA[sub IR]-Score, an oral glucose tolerance test, adiponectin, hsCRP and RBP4. At baseline, 87% of the patients had insulin resistance and 17% showed impaired glucose tolerance in the OGTT, but no correlation could be detected between the HOMA[sub IR] values or the impaired fasting glucose tolerance status and RBP-4 levels at baseline or endpoint. Treatment with PIO alone or in combination with SIMVA resulted in a significant improvement of the HOMA[sub IR]--Score (PIO baseline: 3.3±2.2/endpoint: 2.4±1.0, p<0.05; PIO+SIMVA: 3.9±2.2/2.8±1.2, p<0.05) and the adiponectin values, while no change in HOMA[sub IR] (3.5±2.7/3.6±1.6, n.s.) and a further decrease in adiponectin (p<0.05) was observed with SIMVA mono-therapy. Reductions of hsCRP were seen in all three treatment arms (p<0.001). No changes of the plasma RBP4 concentrations were observed at endpoint 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±8.0 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. Further research is required to understand the role of RBP4 in metabolic syndrome development. In any case, the regulation of RBP4 expression and secretion occurs through biochemical pathways independent from those influenced by pioglitazone or simvastatin
- Subjects
PHARMACODYNAMICS; HYPOGLYCEMIC agents; INSULIN resistance; VITAMIN A; CARRIER proteins; METABOLIC syndrome
- Publication
Diabetes, 2007, Vol 56, pA163
- ISSN
0012-1797
- Publication type
Article