Effects of Pioglitazone on Visceral Fat Metabolic Activity in Impaired Glucose Tolerance or Type 2 Diabetes Mellitus

Context: Excess visceral fat is associated with chronic systemic inflammation and cardiovascular complications. Pioglitazone has been reported to variably influence visceral fat volume; however, its effect on metabolic activity of the visceral fat remains uncharacterized. Objective: The aim of this study was to assess the effects of pioglitazone on glucose metabolism of fat tissue by using F-18-fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography imaging. Design, Setting, and Participants: FDG-PET and computed tomography imaging were performed in 56 patients with impaired glucose tolerance or type 2 diabetes mellitus; lipid and glycemic profiles and inflammatory biomarkers were obtained in all patients. These patients were randomized to treatment with either pioglitazone or glimepiride for 16 weeks. Main Outcome Measures: The metabolic activity of the visceral fat tissues as assessed by FDG uptake was expressed as a target-to-background ratio (TBR) of blood-normalized standardized uptake value. Results: The study was completed in 32 pioglitazone-treated and 21 glimepiride-treated patients (40 men and 13 women; mean age, 67.7 +/- 8.1 y; body mass index, 25.0 +/- 3.6 kg/m(2); glycated hemoglobin, 6.78 +/- 0.70%). Both treatments were well-tolerated and comparably improved glycemic control. At baseline, visceral fat exhibited a higher TBR value than subcutaneous fat (0.55 +/- 0.14 vs 0.30 +/- 0.07, P < .001). Pioglitazone, but not glimepiride, significantly decreased the visceral fat volume (130.5 +/- 53.0 to 122.1 +/- 51.0 cm(2), P = .013) and TBR values (0.57 +/- 0.16 to 0.50 +/- 0.11, P = .007). Neither pioglitazone nor glimepiride treatment showed any effect on the volume or TBR values of subcutaneous fat. After 16 weeks of treatment with pioglitazone, reduction in visceral fat TBR was correlated to the increase in high-density lipoprotein cholesterol levels. Conclusions: Our study indicated that pioglitazone decreased the visceral fat volume and its metabolic activity in patients with impaired glucose tolerance or type 2 diabetes mellitus. The beneficial effects of pioglitazone on visceral fat may be independent of its glucose-lowering effect.