Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance

ObjectiveTo determine the potential effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance and probe into the possible mechanisms.Research design and methodsTwenty-two subjects were treated with pioglitazone 30 mg/day for 4 months. At baseline and after treatment, each subject underwent an IVGTT. The acute insulin response (AIRg), the glucose disappearance rates (coefficients K) and the ratio of Δinsulin/Δglucose (ΔI/ΔG) were calculated according to IVGTT results. Hyperglycemic clamp study was conducted to determine the second-phase insulin response, insulin sensitivity index (ISI) and glucose infusion rate (GIR). Euglycemic–hyperinsulinemic clamp study was made to measure the glucose disposal rate (GDR). Plasma glucose, free fatty acids (FFAs), serum insulin and proinsulin levels were measured.ResultsAIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and ΔI/ΔG increased (P < 0.05). The second-phase insulin response and GIR were both demonstrated marked increments (P < 0.01 and P < 0.01, respectively). Pioglitazone therapy also resulted in improvement of ISI value (P < 0.05). And the increment of GDR during the euglycemic–hyperinsulinemic clamp was also significant (P < 0.01). Furthermore, a decrease in fasting proinsulin level was observed (P < 0.001). And plasma glucose, FFAs and serum insulin levels all declined. The increase of ΔI1/ΔG1 was positively correlated with the improvement of GDR (r = 0.536, P = 0.089). And a positive relationship was observed between the change in the second-phase insulin response and change in K value (r = 0.682, P = 0.021).ConclusionsShort-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance.