Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Circulation. 2011 Aug 2;124(5):563-71. doi: 10.1161/CIRCULATIONAHA.111.025767. Epub 2011 Jul 11.
Common genetic variants in the insulin receptor substrate 1 (IRS1) gene have been recently associated with insulin resistance and hyperinsulinemia. We examined whether the best-associated variant modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets in Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
We genotyped IRS1 rs2943641 in 738 overweight adults (61% were women) who were randomly assigned to 1 of 4 diets varying in macronutrient contents for 2 years. We assessed the progress in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and weight loss by genotypes. At 6 months, participants with the risk-conferring CC genotype had greater decreases in insulin (P=0.009), HOMA-IR (P=0.015), and weight loss (P=0.018) than those without this genotype in the highest-carbohydrate diet group whereas an opposite genotype effect on changes in insulin and HOMA-IR (P≤0.05) was observed in participants assigned to the lowest-carbohydrate diet group. No significant differences were observed across genotypes in the other 2 diet groups. The tests for genotype by intervention interactions were all significant (P<0.05). At 2 years, the genotype effect on changes in insulin and HOMA-IR remained significant in the highest-carbohydrate diet group (P<0.05). The highest carbohydrate diet led to a greater improvement of insulin and HOMA-IR (P for genotype-time interaction ≤0.009) in participants with the CC genotype than those without this genotype across 2-year intervention.
Individuals with the IRS1 rs2943641 CC genotype might obtain more benefits in weight loss and improvement of insulin resistance than those without this genotype by choosing a high-carbohydrate and low-fat diet.
http:www.clinicaltrials.gov. Unique identifier: NCT00072995.
胰岛素受体底物 1（IRS1）基因中的常见遗传变异最近与胰岛素抵抗和高胰岛素血症有关。我们研究了最佳相关变异是否会改变预防超重使用新型饮食策略（POUNDS LOST）试验中对减肥饮食的长期胰岛素抵抗和体重变化。
我们对 738 名超重成年人（61%为女性）进行了 IRS1 rs2943641 基因分型，这些成年人被随机分配到 4 种不同宏量营养素含量的饮食组中，为期 2 年。我们根据基因型评估了空腹胰岛素、稳态模型评估的胰岛素抵抗（HOMA-IR）和体重减轻的进展。在 6 个月时，在最高碳水化合物饮食组中，具有风险赋予 CC 基因型的参与者胰岛素（P=0.009）、HOMA-IR（P=0.015）和体重减轻（P=0.018）的降幅大于没有这种基因型的参与者，而在最低碳水化合物饮食组中，对胰岛素和 HOMA-IR 的变化有相反的基因型效应（P≤0.05）。在其他 2 个饮食组中，不同基因型之间没有观察到显著差异。基因型与干预的相互作用检验均具有统计学意义（P<0.05）。在 2 年时，在最高碳水化合物饮食组中，基因型对胰岛素和 HOMA-IR 的变化仍有显著影响（P<0.05）。在最高碳水化合物饮食组中，与没有该基因型的参与者相比，CC 基因型的参与者在 2 年的干预过程中，胰岛素和 HOMA-IR 的改善更大（基因型-时间交互作用的 P 值≤0.009）。
通过选择高碳水化合物和低脂肪饮食，IRS1 rs2943641 CC 基因型的个体可能比没有该基因型的个体在减肥和改善胰岛素抵抗方面获得更多益处。
