Effect of Troglitazone on Insulin Sensitivity and Pancreatic β-Cell Function in Women at High Risk for NIDDM
Effect of Troglitazone on Insulin Sensitivity and Pancreatic β-Cell Function in Women at High Risk for NIDDM
复制标题
曲格列酮对 NIDDM 高危女性胰岛素敏感性和胰腺 β 细胞功能的影响
作者：
K. Berkowitz;R. Peters;S. Kjos;J. Goico;A. Marroquin;M. E. Dunn;A. Xiang;S. Azen;T. Buchanan
我们进行了一项随机安慰剂对照研究，以确定噻唑烷二酮化合物曲格列酮对42名患有糖耐量减低（IGT）和妊娠期糖尿病（GDM）病史的拉丁美洲女性的全身胰岛素敏感性（SI）、胰腺β细胞功能和葡萄糖耐量的影响，这些特征在5年内发生NIDDM的风险为80%。在基线口服（OGTT）和静脉内（IVGTT）葡萄糖耐量试验后，受试者被分配每天服用安慰剂或200或400 mg曲格列酮，持续12周（每个治疗组14例受试者）。在治疗的第12周期间重复OGTT和IVGTT。5例受试者因个人原因未能完成试验，其余受试者的药物依从性平均为90%，无一例发生严重不良事件。通过IVGTT结果的最小模型分析计算的SI，在安慰剂给药12周期间仅变化4 ± 14%，但在200和400 mg曲格列酮治疗期间分别比基础值增加40 ± 22和88 ± 22%（组间P = 0.01）。曲格列酮给药还与IVGTT期间总胰岛素面积的剂量依赖性减少相关，具有高度显著性（P < 0.001），与OGTT期间的减少相关，接近统计学显著性（P = 0.09）。所有组的葡萄糖耐量均略有改善，但各组之间的变化幅度无显著差异，无论是评估12周时继续表现IGT的受试者人数（各组之间P = 0.64），OGTT期间总葡萄糖面积的变化（P = 0.58），还是IVGTT期间葡萄糖消失率分数的变化（P = 0.28）。在接受曲格列酮治疗的女性中，SI的最大改善发生在基线测试期间具有最高舒张压和最佳IVGTT胰岛素反应的女性中。我们的研究结果表明，曲格列酮改善全身胰岛素敏感性和降低循环胰岛素浓度的妇女与先前的GDM谁是在非常高的风险NIDDM。尽管胰岛素敏感性改善，但葡萄糖耐量没有改善，这可能是β细胞缺陷的一种表现，这种缺陷使妇女易患NIDDM。在我们的高危患者中，对曲格列酮的总体反应模式表明，该药是一种理想的药物，可用于测试改善胰岛素抵抗是否可延迟或预防β细胞储备有限的女性糖尿病。
We conducted a randomized placebo-controlled study to determine the effects of the thiazolidinedione compound troglitazone on whole-body insulin sensitivity (SI), pancreatic β-cell function, and glucose tolerance in 42 Latino women with impaired glucose tolerance (IGT) and a history of gestational diabetes mellitus (GDM), characteristics that carry an 80% risk of developing NIDDM within 5 years. After baseline oral (OGTT) and intravenous (IVGTT) glucose tolerance testing, subjects were assigned to take placebo or 200 or 400 mg troglitazone daily for 12 weeks (14 subjects per treatment group). An OGTT and IVGTT were repeated during the 12th week of treatment. Five subjects failed to complete the trial for personal reasons, and medication compliance averaged 90% in the remaining subjects, none of whom experienced a serious adverse event. SI, calculated by minimal model analysis of IVGTT results, changed by only 4 ± 14% during 12 weeks of placebo administration, but increased 40 ± 22 and 88 ± 22% above basal during treatment with 200 and 400 mg troglitazone, respectively (P = 0.01 among groups). Troglitazone administration was also associated with a dose-dependent reduction in the total insulin area during IVGTTs, which was highly significant (P < 0.001), and with a reduction during OGTTs, which approached statistical significance (P = 0.09). Glucose tolerance improved slightly in all groups, but the magnitude of change did not differ significantly among groups, whether it was assessed as the number of subjects who continued to manifest IGT at 12 weeks (P = 0.64 among groups), the change in total glucose area during OGTTs (P = 0.58), or the change in fractional glucose disappearance rates during IVGTTs (P = 0.28). Among the women who received troglitazone, the greatest improvement in SI occurred in the women who had the highest diastolic blood pressures and the best IVGTT insulin responses during baseline testing. Our findings indicate that troglitazone improved whole-body insulin sensitivity and lowered circulating insulin concentrations in women with prior GDM who are at very high risk for NIDDM. The lack of improvement in glucose tolerance despite improved insulin sensitivity may be a manifestation of the β-cell defect that predisposes the women to NIDDM. The overall pattern of response to troglitazone in our high-risk patients indicates that the drug is an ideal agent with which to test whether the amelioration of insulin resistance can delay or prevent diabetes in women with limited β-cell reserve.
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影响因子：
15.9
作者：
BERGMAN, RN;PHILLIPS, LS;COBELLI, C
通讯作者：
COBELLI, C
肥胖行为治疗的长期随访：男性和女性体重恢复模式。
影响因子：
4.9
作者：
Kramer,FM;Jeffery,RW;Forster,JL;Snell,MK
通讯作者：
Snell,MK
影响因子：
--
作者：
HUGHES, VA;FIATARONE, MA;EVANS, WJ
通讯作者：
EVANS, WJ
影响因子：
158.5
作者：
NOLAN, JJ;LUDVIK, B;OLEFSKY, J
通讯作者：
OLEFSKY, J