TCF7L2 polymorphism, weight loss and proinsulin:insulin ratio in the diabetes prevention program.
TCF7L2 polymorphism, weight loss and proinsulin:insulin ratio in the diabetes prevention program.
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DOI：
10.1371/journal.pone.0021518
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Diabetes Prevention Program Research Group
中科院分区：
文献类型：
--
作者：
McCaffery JM;Jablonski KA;Franks PW;Dagogo-Jack S;Wing RR;Knowler WC;Delahanty L;Dabelea D;Hamman R;Shuldiner AR;Florez JC;Diabetes Prevention Program Research Group
TCF7L2 变异与 2 型糖尿病、体重指数 (BMI) 以及胰岛素原加工和胰岛素分泌缺陷有关。在这里，我们试图测试这些影响在高危个体中是否明显，并修改治疗反应。我们在糖尿病预防计划 (DPP) 的 2.5 年随访参与者 (N = 2,994) 中检查了 TCF7L2 rs7903146 变异在预测减肥抵抗或胰岛素原加工缺乏改善方面的潜在作用，DPP 是一项旨在预防或延缓高危成人糖尿病的随机对照试验。我们观察到 rs7903146 基因型的体重减轻程度没有差异。然而，rs7903146 的 T 等位基因（导致较高的糖尿病风险）与基线时较高的空腹胰岛素原 (P<0.001)、较高的基线胰岛素原∶胰岛素比值 (p<0.0001) 以及中位随访 2.5 年中胰岛素原∶胰岛素比值升高相关 (P = 0.003)。不同治疗组的效果相当。 TCF7L2 基因型对减肥能力缺乏影响，但在 DPP 过程中对胰岛素原：胰岛素比率存在一致的影响，这表明该位点的高风险基因型携带者可以成功减肥以对抗糖尿病风险，尽管胰岛素产生持续不足。
TCF7L2 variants have been associated with type 2 diabetes, body mass index (BMI), and deficits in proinsulin processing and insulin secretion. Here we sought to test whether these effects were apparent in high-risk individuals and modify treatment responses. We examined the potential role of the TCF7L2 rs7903146 variant in predicting resistance to weight loss or a lack of improvement of proinsulin processing during 2.5-years of follow-up participants (N = 2,994) from the Diabetes Prevention Program (DPP), a randomized controlled trial designed to prevent or delay diabetes in high-risk adults. We observed no difference in the degree of weight loss by rs7903146 genotypes. However, the T allele (conferring higher risk of diabetes) at rs7903146 was associated with higher fasting proinsulin at baseline (P<0.001), higher baseline proinsulin∶insulin ratio (p<0.0001) and increased proinsulin∶insulin ratio over a median of 2.5 years of follow-up (P = 0.003). Effects were comparable across treatment arms. The combination of a lack of impact of the TCF7L2 genotypes on the ability to lose weight, but the presence of a consistent effect on the proinsulin∶insulin ratio over the course of DPP, suggests that high-risk genotype carriers at this locus can successfully lose weight to counter diabetes risk despite persistent deficits in insulin production.
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影响因子：
7.7
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