Objectives To evaluate the individual and combined associations of five modifiable risk factors with risk of type 2 diabetes among women with a history of gestational diabetes mellitus and examine whether these associations differ by obesity and genetic predisposition to type 2 diabetes. Design Prospective cohort study. Setting Nurses’ Health Study II, US. Participants 4275 women with a history of gestational diabetes mellitus, with repeated measurements of weight and lifestyle factors and followed up between 1991 and 2009. Main outcome measure Self-reported, clinically diagnosed type 2 diabetes. Five modifiable risk factors were assessed, including not being overweight or obese (body mass index <25.0), high quality diet (top two fifths of the modified Alternate Healthy Eating Index), regular exercise (≥150 min/week of moderate intensity or ≥75 min/week of vigorous intensity), moderate alcohol consumption (5.0-14.9 g/day), and no current smoking. Genetic susceptibility for type 2 diabetes was characterised by a genetic risk score based on 59 single nucleotide polymorphisms associated with type 2 diabetes in a subset of participants (n=1372). Results Over a median 27.9 years of follow-up, 924 women developed type 2 diabetes. Compared with participants who did not have optimal levels of any of the risk factors for the development of type 2 diabetes, those who had optimal levels of all five factors had >90% lower risk of the disorder. Hazard ratios of type 2 diabetes for those with one, two, three, four, and five optimal levels of modifiable factors compared with none was 0.94 (95% confidence interval 0.59 to 1.49), 0.61 (0.38 to 0.96), 0.32 (0.20 to 0.51), 0.15 (0.09 to 0.26), and 0.08 (0.03 to 0.23), respectively (Ptrend<0.001). The inverse association of the number of optimal modifiable factors with risk of type 2 diabetes was seen even in participants who were overweight/obese or with higher genetic susceptibility (Ptrend<0.001). Among women with body mass index ≥25 (n=2227), the hazard ratio for achieving optimal levels of all the other four risk factors was 0.40 (95% confidence interval 0.18 to 0.91). Among women with higher genetic susceptibility, the hazard ratio of developing type 2 diabetes for having four optimal factors was 0.11 (0.04 to 0.29); in the group with optimal levels of all five factors, no type 2 diabetes events were observed. Conclusions Among women with a history of gestational diabetes mellitus, each additional optimal modifiable factor was associated with an incrementally lower risk of type 2 diabetes. These associations were seen even among individuals who were overweight/obese or were at greater genetic susceptibility. Analytical code used for the present analysis might be made available on a case-by-case basis with approval from the senior author of this manuscript. Data described in the manuscript will not be made publicly available. Further information including the procedures for obtaining and accessing data from the Nurses’ Health Studies II is described online (; email nhsaccess{at}channing.harvard.edu).

中文翻译：

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有妊娠糖尿病史的个体可改变的危险因素和 2 型糖尿病的长期风险：前瞻性队列研究

目的 在有妊娠糖尿病病史的女性中，评估五个可改变的危险因素与 2 型糖尿病风险的单独和联合关联，并检查这些关联是否因肥胖和 2 型糖尿病的遗传易感性而不同。设计前瞻性队列研究。设置护士健康研究 II，美国。参与者 4275 名有妊娠糖尿病病史的妇女，在 1991 年至 2009 年间对体重和生活方式因素进行了重复测量，并进行了随访。主要结果测量 自我报告的临床诊断的 2 型糖尿病。评估了五个可改变的风险因素，包括不超重或肥胖（体重指数 <25.0）、高质量饮食（改良替代健康饮食指数的前五分之二）、定期锻炼（≥150 分钟/周中等强度或≥75 分钟/周剧烈强度），适度饮酒（5.0-14.9 克/天），并且目前不吸烟。2 型糖尿病的遗传易感性以遗传风险评分为特征，该评分基于参与者子集 (n=1372) 中与 2 型糖尿病相关的 59 个单核苷酸多态性。结果 在平均 27.9 年的随访中，924 名女性患上了 2 型糖尿病。与没有达到 2 型糖尿病发展的任何危险因素的最佳水平的参与者相比，所有五个因素都处于最佳水平的参与者患该病症的风险降低了 90% 以上。具有 1、2、3、4 和 5 个最佳可修改因素水平的人与没有的人相比，2 型糖尿病的风险比为 0.94（95% 置信区间 0.59 至 1.49）、0.61（0. 38 至 0.96)、0.32（0.20 至 0.51）、0.15（0.09 至 0.26）和 0.08（0.03 至 0.23）（Ptrend<0.001）。即使在超重/肥胖或具有较高遗传易感性的参与者中，也可以看到最佳可修改因素的数量与 2 型糖尿病风险呈负相关（Ptrend <0.001）。在体重指数≥25 (n=2227) 的女性中，所有其他四个风险因素达到最佳水平的风险比为 0.40（95% 置信区间为 0.18 至 0.91）。在具有较高遗传易感性的女性中，具有四个最佳因素的患 2 型糖尿病的风险比为 0.11（0.04 至 0.29）；在所有五个因素均达到最佳水平的组中，未观察到 2 型糖尿病事件。结论 在有妊娠糖尿病病史的女性中，每个额外的最佳可修改因素都与逐渐降低的 2 型糖尿病风险相关。即使在超重/肥胖或遗传易感性更高的个体中也能看到这些关联。经本手稿高级作者批准，可根据具体情况提供用于本分析的分析代码。手稿中描述的数据不会公开。在线描述了更多信息，包括从护士健康研究 II 中获取和访问数据的程序（经本手稿高级作者批准，可根据具体情况提供用于本分析的分析代码。手稿中描述的数据不会公开。在线描述了更多信息，包括从护士健康研究 II 中获取和访问数据的程序（经本手稿高级作者批准，可根据具体情况提供用于本分析的分析代码。手稿中描述的数据不会公开。在线描述了更多信息，包括从护士健康研究 II 中获取和访问数据的程序（; 电子邮件 nhsaccess{at}channing.harvard.edu）。