High circulating levels of RBP4 and mRNA levels of aP2, PGC-1alpha and UCP-2 predict improvement in insulin sensitivity following pioglitazone treatment of drug-naïve type 2 diabetic subjects.

Abstract

CONTEXT: High levels of circulating retinol-binding protein 4 (RBP4) and baseline expression of adipogenic genes correlate with subsequent improvement in insulin sensitivity following Thiazolidinedione (TZD) treatment. OBJECTIVE: The aim was to identify baseline characteristics and early changes related to TZD treatment that could predict a good treatment response. DESIGN: Subjects were examined with oral glucose tolerance test, intravenous glucose tolerance test, hyperinsulinaemic euglycaemic clamp, body composition and standard blood sampling at baseline and after 4 and 12 weeks treatment. Subcutaneous adipose tissue biopsies were taken from the abdominal region at baseline, after 3 days and 4 weeks treatment to examine the gene expression profile. SETTING: Research laboratory in a University hospital. PARTICIPANTS: Ten newly diagnosed and previously untreated type 2 diabetic subjects were treated with pioglitazone for 3 months. MAIN OUTCOME MEASURES: Baseline characteristics and early changes related to TZD treatment that could predict the response after 3 months. RESULTS: Pioglitazone improved insulin sensitivity after 4 weeks combined with lower glucose and insulin levels without any change in BMI. It was accompanied by lower circulating resistin and plasminogen activator inhibitor-1 levels rapidly increased levels of circulating total and high molecular weight adiponectin as well as adiponectin and adipocyte fatty acid-binding protein (aP2) mRNA expression in the adipose tissue. High levels of circulating RBP4 at baseline and adipose tissue expression of aP2, proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1alpha) and uncoupling protein 2 (UCP-2) predicted a good treatment response measured as improvement in insulin-stimulated whole-body glucose uptake after 3 months. CONCLUSIONS: Circulating levels of RBP4 as an index of insulin sensitivity and mRNA levels of adipogenic genes correlate with the subsequent improvement in insulin sensitivity following TZD treatment.