Association of type 2 diabetes susceptibility loci with one-year weight loss in the look AHEAD clinical trial.
Association of type 2 diabetes susceptibility loci with one-year weight loss in the look AHEAD clinical trial.
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DOI：
10.1038/oby.2012.11
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发表时间：
2012-08
期刊：
影响因子：
6.9
通讯作者：
Huggins, Gondon S.
中科院分区：
文献类型：
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作者：
Peter, Inga;McCaffery, Jeanne M.;Kelley-Hedgepeth, Alyson;Hakonarson, Hakon;Reis, Steven;Wagenknecht, Lynne E.;Kopin, Alan S.;Huggins, Gondon S.
生活方式干预对于预防和治疗2型糖尿病(T2D)的重要性已经被药物治疗的有限益处所强调。我们试图确定导致T2D风险的基因变异是否改变了肥胖和T2D患者对强化生活方式干预(ILI)的体重和腰围的反应。Look Advance(糖尿病健康行动)是一项随机临床试验，比较了ILI和对照条件对患有T2D的超重成年人心血管疾病风险的影响。我们分析了3,903名参与者中17个T2D易感基因上/附近的28个单核苷酸多态(SNPs)。我们通过评估与非糖尿病社区为基础的队列(N=1,016)相比，T2D易感基因是否过度表达来确定队列的遗传学特征。在基线和干预1年后，我们评估了个体变异和综合遗传风险评分(GRS)与人体测量特征的相关性。展望未来，受试者携带的T2D易感等位基因比对照人群更多。在基线水平，TCF7L2风险等位基因和最高GRS与较低的BMI和腰围相关。在JAZF1、MTNR1B、IRS1和JAZF1的1年腰围变化以及JAZF1的BMI中检测到了名义上显著的干预效应。最高的GRS与1岁时腰围的减少程度更大相关，尽管GRS的变化差异很小。这项研究表明，与T2D风险相关的遗传负担不会破坏生活方式干预的效果，并表明存在与T2D易感基因不同的额外基因组区域，这些区域可能会增强或减轻体重减轻。
The importance of lifestyle intervention for the prevention and treatment of type 2 diabetes (T2D) has been underscored by the limited benefit of pharmacologic therapies. We sought to determine whether genetic variants that contribute to T2D risk modify the response of weight and waist circumference to an intensive lifestyle intervention (ILI) in patients with obesity and T2D. Look AHEAD (Action for Health in Diabetes) is a randomized clinical trial comparing an ILI with a control condition on the risk of cardiovascular disease in overweight adults with T2D. We analyzed 28 single-nucleotide polymorphisms (SNPs) at/near 17 T2D-susceptibility genes in 3,903 consented participants. We genetically characterized the cohort by assessing whether T2D-susceptibility loci were overrepresented compared with a nondiabetic community-based cohort (N = 1,016). We evaluated the association of individual variants and a composite genetic risk score (GRS) with anthropometric traits at baseline and after 1-year of intervention. Look AHEAD subjects carried more T2D-susceptibility alleles than the control population. At baseline, TCF7L2 risk alleles and the highest GRS were associated with lower BMI and waist circumference. Nominally significant genotype-by-intervention interactions were detected for 1-year change in waist circumference with JAZF1, MTNR1B, and IRS1, and BMI with JAZF1. Highest GRS was associated with a greater reduction in waist circumference at year 1, although the variance in change attributable to the GRS was small. This study shows that the genetic burden associated with T2D risk does not undermine the effect of lifestyle intervention and suggests the existence of additional genomic regions, distinct from the T2D-susceptibility loci, which may enhance or mitigate weight loss.
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影响因子：
158.5
作者：
Knowler, WC;Barrett-Connor, E;Nathan, DM
通讯作者：
Nathan, DM
影响因子：
7.7
作者：
Takeuchi F;Serizawa M;Yamamoto K;Fujisawa T;Nakashima E;Ohnaka K;Ikegami H;Sugiyama T;Katsuya T;Miyagishi M;Nakashima N;Nawata H;Nakamura J;Kono S;Takayanagi R;Kato N
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Kato N
影响因子：
5.8
作者：
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通讯作者：
Laakso, M
影响因子：
158.5
作者：
Florez, Jose C.;Jablonski, Kathleen A.;Altshuler, David
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Altshuler, David
新的遗传基因座涉及禁食葡萄糖稳态及其对2型糖尿病风险的影响。
影响因子：
30.8
作者：
通讯作者：
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