AIMS/HYPOTHESIS Type 1 and type 2 diabetes differ with respect to pathophysiological factors such as beta cell function, insulin resistance and phenotypic appearance, but there may be overlap between the two forms of diabetes. However, there are relatively few prospective studies that have characterised the relationship between autoimmunity and incident diabetes. We investigated associations of antibodies against the 65 kDa isoform of GAD (GAD65) with type 1 diabetes and type 2 diabetes genetic risk scores and incident diabetes in adults in European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a case-cohort study nested in the EPIC cohort. METHODS GAD65 antibodies were analysed in EPIC participants (over 40 years of age and free of known diabetes at baseline) by radioligand binding assay in a random subcohort (n = 15,802) and in incident diabetes cases (n = 11,981). Type 1 diabetes and type 2 diabetes genetic risk scores were calculated. Associations between GAD65 antibodies and incident diabetes were estimated using Prentice-weighted Cox regression. RESULTS GAD65 antibody positivity at baseline was associated with development of diabetes during a median follow-up time of 10.9 years (HR for GAD65 antibody positive vs negative 1.78; 95% CI 1.43, 2.20) after adjustment for sex, centre, physical activity, smoking status and education. The genetic risk score for type 1 diabetes but not type 2 diabetes was associated with GAD65 antibody positivity in both the subcohort (OR per SD genetic risk 1.24; 95% CI 1.03, 1.50) and incident cases (OR 1.97; 95% CI 1.72, 2.26) after adjusting for age and sex. The risk of incident diabetes in those in the top tertile of the type 1 diabetes genetic risk score who were also GAD65 antibody positive was 3.23 (95% CI 2.10, 4.97) compared with all other individuals, suggesting that 1.8% of incident diabetes in adults was attributable to this combination of risk factors. CONCLUSIONS/INTERPRETATION Our study indicates that incident diabetes in adults has an element of autoimmune aetiology. Thus, there might be a reason to re-evaluate the present subclassification of diabetes in adulthood.

中文翻译：

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自身免疫在40岁以后的糖尿病发作中起作用。

目的/假设1型和2型糖尿病在病理生理因素（例如β细胞功能，胰岛素抵抗和表型出现）方面有所不同，但两种形式的糖尿病之间可能存在重叠。但是，很少有前瞻性研究描述自身免疫性疾病与糖尿病的关系。我们在一项针对案例研究的欧洲癌症与营养前瞻性调查（EPIC）-InterAct中调查了针对成人的1型糖尿病，2型糖尿病遗传风险评分和事件性糖尿病的针对65kDa GAD亚型（GAD65）的抗体的关联嵌套在EPIC队列中。方法在随机分组（n = 15）中，通过放射性配体结合测定法对EPIC参与者（40岁以上且基线无已知糖尿病）中的GAD65抗体进行了分析。802）和糖尿病患者（n = 11,981）。计算1型糖尿病和2型糖尿病的遗传风险评分。使用Prentice加权Cox回归估计了GAD65抗体与糖尿病的相关性。结果在对性别，中枢，身体活动，吸烟进行了调整后，中位随访时间为10.9年（GAD65抗体阳性vs阴性1.78； HR 95％CI 1.43，2.20），基线时GAD65抗体阳性与糖尿病的发展有关。地位和教育。1型糖尿病而非2型糖尿病的遗传风险评分与亚人群（根据SD遗传风险的OR为1.24； 95％CI为1.03，1.50）和事件病例（OR为1.97； 95％CI 1.72， 2.26）。与所有其他个体相比，GAD65抗体呈阳性的1型糖尿病遗传风险评分最高的三分位人群中发生糖尿病的风险为3.23（95％CI 2.10，4.97）归因于风险因素的这种组合。结论/解释我们的研究表明，成年人中发生的糖尿病具有自身免疫病因的要素。因此，可能有理由重新评估目前在成年期糖尿病中的亚类。结论/解释我们的研究表明，成年人中发生的糖尿病具有自身免疫病因的要素。因此，可能有理由重新评估目前在成年期糖尿病中的亚类。结论/解释我们的研究表明，成年人中发生的糖尿病具有自身免疫病因的要素。因此，可能有理由重新评估目前在成年期糖尿病中的亚类。