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


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.
Jin
Juying
J
Division of Endocrinology and Metabolism, West China Hospital of Sichuan University, 37 GuoXue Rd, Chengdu, Sichuan 610041, PR China.
Yu
Yerong
Y
Yu
Honglin
H
Wang
Chun
C
Zhang
Xiangxun
X
D000328:Adult; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone