Diabetologia. 2013 Jan;56(1):60-9. doi: 10.1007/s00125-012-2715-x. Epub 2012 Sep 28.
AIMS/HYPOTHESIS: Although a family history of type 2 diabetes is a strong risk factor for the disease, the factors mediating this excess risk are poorly understood. In the InterAct case-cohort study, we investigated the association between a family history of diabetes among different family members and the incidence of type 2 diabetes, as well as the extent to which genetic, anthropometric and lifestyle risk factors mediated this association.
A total of 13,869 individuals (including 6,168 incident cases of type 2 diabetes) had family history data available, and 6,887 individuals had complete data on all mediators. Country-specific Prentice-weighted Cox models were fitted within country, and HRs were combined using random effects meta-analysis. Lifestyle and anthropometric measurements were performed at baseline, and a genetic risk score comprising 35 polymorphisms associated with type 2 diabetes was created.
A family history of type 2 diabetes was associated with a higher incidence of the condition (HR 2.72, 95% CI 2.48, 2.99). Adjustment for established risk factors including BMI and waist circumference only modestly attenuated this association (HR 2.44, 95% CI 2.03, 2.95); the genetic score alone explained only 2% of the family history-associated risk of type 2 diabetes. The greatest risk of type 2 diabetes was observed in those with a biparental history of type 2 diabetes (HR 5.14, 95% CI 3.74, 7.07) and those whose parents had been diagnosed with diabetes at a younger age (<50 years; HR 4.69, 95% CI 3.35, 6.58), an effect largely confined to a maternal family history.
CONCLUSIONS/INTERPRETATION: Prominent lifestyle, anthropometric and genetic risk factors explained only a marginal proportion of the excess risk associated with family history, highlighting the fact that family history remains a strong, independent and easily assessed risk factor for type 2 diabetes. Discovering factors that will explain the association of family history with type 2 diabetes risk will provide important insight into the aetiology of type 2 diabetes.
目的/假设：虽然 2 型糖尿病家族史是该病的一个强烈危险因素，但介导这种风险增加的因素仍知之甚少。在 InterAct 病例-对照研究中，我们调查了不同家庭成员的糖尿病家族史与 2 型糖尿病发病之间的关系，以及遗传、人体测量和生活方式危险因素在多大程度上介导了这种关联。
共有 13869 人（包括 6168 例 2 型糖尿病新发病例）有家族史数据，6887 人有所有中介物的完整数据。在国内进行了特定国家的 Prentice 加权 Cox 模型拟合，并使用随机效应荟萃分析对 HR 进行了合并。生活方式和人体测量在基线时进行，创建了一个包含 35 个与 2 型糖尿病相关的多态性的遗传风险评分。
2 型糖尿病家族史与该疾病的发病率较高相关（HR 2.72，95%CI 2.48，2.99）。调整包括 BMI 和腰围在内的既定危险因素仅适度减弱了这种关联（HR 2.44，95%CI 2.03，2.95）；遗传评分单独仅解释了 2%的 2 型糖尿病家族史相关风险。在有双亲 2 型糖尿病家族史的个体（HR 5.14，95%CI 3.74，7.07）和父母在较年轻时（<50 岁）被诊断患有糖尿病的个体（HR 4.69，95%CI 3.35，6.58）中，2 型糖尿病的风险最高，这种效应主要局限于母系家族史。
结论/解释：突出的生活方式、人体测量和遗传危险因素仅解释了与家族史相关的额外风险的一小部分，这突出表明家族史仍然是 2 型糖尿病的一个强烈、独立且易于评估的危险因素。发现解释家族史与 2 型糖尿病风险关联的因素将为 2 型糖尿病的病因学提供重要的见解。
