Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study.
Changes in insulin sensitivity in response to troglitazone do not differ between subjects with and without the common, functional Pro12Ala peroxisome proliferator-activated receptor-gamma2 gene variant: results from the Troglitazone in Prevention of Diabetes (TRIPOD) study.
复制标题
曲格列酮对胰岛素敏感性的变化在有或没有常见功能性 Pro12Ala 过氧化物酶体增殖物激活受体-gamma2 基因变异的受试者之间没有差异：来自曲格列酮预防糖尿病 (TRIPOD) 研究的结果。
作者：
S. Snitker;R. Watanabe;Ifeanyi Ani;A. Xiang;A. Marroquin;C. Ochoa;J. Goico;A. Shuldiner;T. Buchanan
目的
我们检测了在曲格列酮预防糖尿病（TRIPOD）研究中，参与噻唑烷二酮（TZD）作用的过氧化物酶体增殖物激活受体（PPAR）-γ核受体的Pro 12 Ala变体是否导致曲格列酮未能增加既往妊娠期糖尿病的非糖尿病西班牙裔女性的胰岛素敏感性。
研究设计和方法
93名被分配到曲格列酮组的女性在随机分组时和接受400 mg/天曲格列酮治疗3个月后进行静脉葡萄糖耐量试验，并对PPAR-gamma基因的Pro 12 Ala变体进行基因分型。根据曲格列酮治疗前3个月期间最小模型胰岛素敏感性（S（i））的变化，将受试者分为三分位数。
结果
S（i）反应的底部、中部和顶部三分位数的S（i）平均变化分别为-0.21 +/- 0.57、0.91 +/- 0.26和2.58 +/- 1.32 min（-1）/microU/ml。10（-4）。Ala/-基因型的频率分别为30，22和26%，在相同的三个三分位数（P = 0.77）。按基因型进行的表型分析显示，Pro/Pro组和Ala/-组之间的基线S（i）分别只有很小的差异，（2.76 +/- 0.19 vs. 2.33 +/- 0.33 x 10（-4）min（-1）per microU/ml; P = 0.27），曲格列酮治疗3个月后S（i）的变化（1.19 +/- 0.17 vs. 0.93 +/- 0.30; P = 0.46），以及中位随访30个月期间糖尿病的累积发病率（13 vs. 17%; P = 0.66）。
结论
在2型糖尿病高风险的西班牙裔年轻女性中，PPAR-gamma受体基因的Pro 12 Ala变体不能解释约1/3的受试者在接受400 mg/天剂量的曲格列酮治疗时胰岛素敏感性增加失败的原因。
OBJECTIVE
We have tested whether the Pro12Ala variant of the peroxisome proliferator-activated receptor (PPAR)-gamma nuclear receptor involved in thiazolidinedione (TZD) action accounted for the failure of troglitazone to increase insulin sensitivity in nondiabetic Hispanic women with previous gestational diabetes treated in the Troglitazone in Prevention of Diabetes (TRIPOD) study.
RESEARCH DESIGN AND METHODS
Ninety-three women assigned to troglitazone had intravenous glucose tolerance tests at randomization and after 3 months of treatment with troglitazone, 400 mg/day, and were genotyped for the Pro12Ala variant of the PPAR-gamma gene. Subjects were divided into tertiles based on their change in minimal model insulin sensitivity (S(i)) during the first 3 months of troglitazone treatment.
RESULTS
The mean changes in S(i) in the bottom, middle, and top tertiles of S(i) response were -0.21 +/- 0.57, 0.91 +/- 0.26, and 2.58 +/- 1.32 min(-1) per microU/ml. 10(-4), respectively. Frequencies of the Ala/- genotype were 30, 22, and 26% in the same three tertiles (P = 0.77). Analysis of phenotypes by genotype revealed only small differences between the Pro/Pro and Ala/- groups, respectively, in baseline S(i) (2.76 +/- 0.19 vs. 2.33 +/- 0.33 x 10(-4) min(-1) per microU/ml; P = 0.27), the change in S(i) after 3 months of troglitazone treatment (1.19 +/- 0.17 vs. 0.93 +/- 0.30; P = 0.46), and the cumulative incidence of diabetes during a median follow-up of 30 months (13 vs. 17%; P = 0.66).
CONCLUSIONS
Among young Hispanic women at high risk for type 2 diabetes, the Pro12Ala variant of the PPAR-gamma receptor gene did not explain the failure of approximately 1/3 of subjects to increase their insulin sensitivity when placed on troglitazone at a dose of 400 mg/day.
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