Rosiglitazone improves insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus

Rosiglitazone (RSG) is known to be an agonist for the peroxisome proliferator-activated receptor-γ (PPARγ) and promotes differentiation of pre-adipocytes into adipocytes. Leptin is highly correlated with adiposity, while the activation of PPARγ is known to inhibit Lep gene expression and leptin release. This study was performed to evaluate the relationship between changes in circulating leptin levels, insulin sensitivity and regional adiposity after RSG treatment. Two hundred fifty-one type 2 diabetic patients (176 men and 75 women) who had been treated with sulfonylurea and/or metformin received 4 mg of RSG daily, in addition to the previous medications. Before and after RSG treatment (average duration 5.6 ± 0.9 months), indices of insulin resistance, metabolic parameters, and serum leptin and adiponectin levels were measured. Abdominal subcutaneous fat thickness (SFT_max) and visceral fat thickness were measured by sonography. After RSG treatment, HOMA-IR index decreased significantly (2.82 ± 1.94 vs. 2.01 ± 1.58), while BMI and SFT_max increased, and leptin (4.72 ± 3.77 vs. 5.69 ± 4.30 ng/ml) and adiponectin levels (7.54 ± 10.20 vs. 12.89 ± 10.13 μg/ml) increased. The increase in serum leptin correlated with an increase in SFT_max (r = 0.511, p < 0.001) and with a reduction in HOMA-IR (r = -0.368, p < 0.001). The correlation of Δleptin with ΔHOMA-IR and with ΔSFT_max was higher in females and among insulin-resistant subjects. In conclusion, RSG improves the insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus, which is related to an increase in subcutaneous adiposity.