Coronary artery disease (CAD) is more frequent among individuals with dysglycemia. Preventive interventions for diabetes can improve cardiometabolic risk factors (CRFs), but it is unclear whether the benefits on CRFs are similar for individuals at different genetic risk for CAD. We built a 201-variant polygenic risk score (PRS) for CAD and tested for interaction with diabetes prevention strategies on 1-year changes in CRFs in 2,658 Diabetes Prevention Program (DPP) participants. We also examined whether separate lifestyle behaviors interact with PRS and affect changes in CRFs in each intervention group. Participants in both the lifestyle and metformin interventions had greater improvement in the majority of recognized CRFs compared with placebo (P < 0.001) irrespective of CAD genetic risk (Pinteraction > 0.05). We detected nominal significant interactions between PRS and dietary quality and physical activity on 1-year change in BMI, fasting glucose, triglycerides, and HDL cholesterol in individuals randomized to metformin or placebo, but none of them achieved the multiple-testing correction for significance. This study confirms that diabetes preventive interventions improve CRFs regardless of CAD genetic risk and delivers hypothesis-generating data on the varying benefit of increasing physical activity and improving diet on intermediate cardiovascular risk factors depending on individual CAD genetic risk profile.

中文翻译：

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2 型糖尿病预防策略与冠状动脉疾病遗传决定因素对心脏代谢危险因素的相互作用

冠状动脉疾病 (CAD) 在血糖异常患者中更为常见。糖尿病的预防性干预措施可以改善心脏代谢危险因素 (CRF)，但尚不清楚 CRF 的益处对于具有不同 CAD 遗传风险的个体是否相似。我们建立了 201 种 CAD 多基因风险评分 (PRS)，并在 2,658 名糖尿病预防计划 (DPP) 参与者的 CRF 的 1 年变化中测试了与糖尿病预防策略的相互作用。我们还研究了不同的生活方式行为是否与 PRS 相互作用并影响每个干预组中 CRF 的变化。与安慰剂相比，生活方式和二甲双胍干预的参与者在大多数公认的 CRF 方面都有更大的改善 (P < 0.001)，无论 CAD 遗传风险如何 (Pinteraction > 0.05)。我们发现，在随机服用二甲双胍或安慰剂的个体中，PRS 与饮食质量和身体活动之间的 BMI、空腹血糖、甘油三酯和 HDL 胆固醇的 1 年变化之间存在名义上的显着相互作用，但没有一个人实现了显着性的多重测试校正。这项研究证实，无论 CAD 遗传风险如何，糖尿病预防干预措施都能改善 CRF，并根据个人 CAD 遗传风险状况，提供关于增加体力活动和改善饮食对中等心血管危险因素的不同益处的假设生成数据。