Effects of pioglitazone on beta-cell function in metabolic syndrome patients with impaired glucose tolerance |
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Authors: | Jin Juying Yu Yerong Yu Honglin Wang Chun Zhang Xiangxun |
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Institution: | Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, 37 GuoXue Rd, Chengdu, Sichuan 610041, PR China. |
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Abstract: | OBJECTIVE: To 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 METHODS: Twenty-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 Deltainsulin/Deltaglucose (DeltaI/DeltaG) 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. RESULTS: AIRg unchanged (P = 0.25) after treatment, whereas the values of coefficients K (P < 0.01) and DeltaI/DeltaG 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 DeltaI1/DeltaG1 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). CONCLUSIONS: Short-term pioglitazone therapy improved beta-cell dysfunction, the mechanism might involve the attenuation of insulin resistance. |
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