Medicine Service, Department of Veterans Affairs Eastern Colorado Healthcare System, Aurora, Colorado, USA.
Division of Hospital Medicine, University of Colorado School of Medicine, Aurora, Colorado, USA.
Diabetes Obes Metab. 2021 Apr;23(4):1030-1040. doi: 10.1111/dom.14309. Epub 2021 Jan 29.
To test whether diabetes genetic risk modifies the association of successful lifestyle changes with incident diabetes.
We studied 823 individuals randomized to the intensive lifestyle intervention (ILS) arm of the Diabetes Prevention Programme who were diabetes-free 1 year after enrolment. We tested additive and multiplicative interactions of a 67-variant diabetes genetic risk score (GRS) with achievement of three ILS goals at 1 year (≥7% weight loss, ≥150 min/wk of moderate leisure-time physical activity, and/or a goal for self-reported total fat intake) on the primary outcome of incident diabetes over 3 years of follow-up.
A lower GRS and achieving each or all three ILS goals were each associated with lower incidence of diabetes (all P < 0.05). Additive interactions were significant between the GRS and achievement of the weight loss goal (P < 0.001), physical activity goal (P = 0.02), and all three ILS goals (P < 0.001) for diabetes risk. Achievement of all three ILS goals was associated with 1.8 (95% CI 0.3, 3.4), 3.1 (95% CI 1.5, 4.7), and 3.9 (95% CI 1.6, 6.2) fewer diabetes cases/100-person-years in the first, second and third GRS tertiles (P < 0.001 for trend). Multiplicative interactions between the GRS and ILS goal achievement were significant for the diet goal (P < 0.001), but not for weight loss (P = 0.18) or physical activity (P = 0.62) goals.
Genetic risk may identify high-risk subgroups for whom successful lifestyle modification is associated with greater absolute reduction in the risk of incident diabetes.
检验糖尿病遗传风险是否会改变成功的生活方式改变与新发糖尿病之间的关联。
我们研究了 823 名参加糖尿病预防计划（Diabetes Prevention Programme）的个体，他们在入组 1 年后无糖尿病。我们在 3 年的随访中测试了 67 个变异的糖尿病遗传风险评分（GRS）与 1 年内实现三个生活方式干预目标（ILS）的加性和乘法交互作用，ILS 目标包括：体重减轻≥7%，中等休闲时间体力活动≥150 分钟/周，和/或自我报告的总脂肪摄入量目标。主要结局是新发糖尿病的发生率。
较低的 GRS 和实现每个或所有三个 ILS 目标均与较低的糖尿病发病率相关（均 P < 0.05）。GRS 与体重减轻目标（P < 0.001）、体力活动目标（P = 0.02）和所有三个 ILS 目标（P < 0.001）之间存在显著的加性交互作用。实现所有三个 ILS 目标与第一、第二和第三 GRS 三分位数的每 100 人年新发糖尿病病例数减少 1.8（95%CI 0.3，3.4）、3.1（95%CI 1.5，4.7）和 3.9（95%CI 1.6，6.2）有关（趋势 P < 0.001）。GRS 与 ILS 目标实现之间的乘法交互作用在饮食目标上具有显著意义（P < 0.001），但在体重减轻（P = 0.18）或体力活动（P = 0.62）目标上无显著意义。
遗传风险可能确定高危亚组，对于这些亚组，成功的生活方式改变与新发糖尿病风险的绝对降低相关。
