Aims/hypothesis

Accumulated data suggest that infections in early life contribute to the development of type 1 diabetes. Using data from the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), we set out to assess whether children who later developed diabetes-related autoantibodies and/or clinical type 1 diabetes had different exposure to infections early in life compared with those who did not.

Methods

A cohort of 2159 children with an affected first-degree relative and HLA-conferred susceptibility to type 1 diabetes were recruited between 2002 and 2007 and followed until 2017. Infections were registered prospectively. The relationship between infections in the first year of life and the development of autoantibodies or clinical type 1 diabetes was analysed using univariable and multivariable Cox regression models. As this study was exploratory, no adjustment was made for multiple comparisons.

Results

Adjusting for HLA, sex, breastfeeding duration and birth order, those who had seven or more infections during their first year of life were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.028, HR 9.166 [95% CI 1.277, 65.81]) compared with those who had no infections. Those who had their first viral infection aged between 6 and 12 months were less likely to develop at least one positive type 1 diabetes-related antibody (p=0.043, HR 0.828 [95% CI 0.690, 0.994]) or multiple antibodies (p=0.0351, HR 0.664 [95% CI 0.453, 0.972]). Those who had ever had an unspecified bacterial infection were more likely to develop at least one positive type 1 diabetes-related autoantibody (p=0.013, HR 1.412 [95% CI 1.075, 1.854]), to develop multiple antibodies (p=0.037, HR 1.652 [95% CI 1.030, 2.649]) and to develop clinical type 1 diabetes (p=0.011, HR 2.066 [95% CI 1.182, 3.613]).

Conclusions/interpretation

We found weak support for the assumption that viral infections early in life may initiate the autoimmune process or later development of type 1 diabetes. In contrast, certain bacterial infections appeared to increase the risk of both multiple autoantibodies and clinical type 1 diabetes.

Graphical abstract

中文翻译：

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生命第一年的感染以及高危个体中 β 细胞自身免疫和临床 1 型糖尿病的发展：TRIGR 队列

目标/假设

累积的数据表明，生命早期的感染会导致 1 型糖尿病的发展。使用减少遗传风险中的 IDDM 试验 (TRIGR) 中的数据，我们着手评估后来出现糖尿病相关自身抗体和/或临床 1 型糖尿病的儿童与那些患有糖尿病的儿童相比，在生命早期是否有不同的感染暴露没有。

方法

在 2002 年至 2007 年期间招募了 2159 名具有受影响的一级亲属和 HLA 赋予的 1 型糖尿病易感性的儿童队列，并随访至 2017 年。感染是前瞻性登记的。使用单变量和多变量 Cox 回归模型分析出生后第一年感染与自身抗体或临床 1 型糖尿病的发展之间的关系。由于这项研究是探索性的，因此没有对多重比较进行调整。

结果

调整 HLA、性别、母乳喂养持续时间和出生顺序后，那些在出生后第一年感染过七次或更多次的人更有可能产生至少一种阳性 1 型糖尿病相关自身抗体（p = 0.028，HR 9.166 [95% CI 1.277, 65.81]) 与未感染者相比。首次病毒感染年龄在 6 至 12 个月之间的人不太可能产生至少一种阳性 1 型糖尿病相关抗体（p = 0.043，HR 0.828 [95% CI 0.690，0.994]）或多种抗体（p = 0.0351，HR 0.664 [95% CI 0.453，0.972]）。那些曾经有过不明细菌感染的人更有可能发展出至少一种阳性 1 型糖尿病相关自身抗体 ( p=0.013, HR 1.412 [95% CI 1.075, 1.854]), 发展多种抗体 ( p =0.037, HR 1.652 [95% CI 1.030, 2.649]) 和发展为临床 1 型糖尿病 ( p =0.011, HR 2.066 [ 95% CI 1.182, 3.613])。

结论/解释

我们发现生命早期的病毒感染可能引发自身免疫过程或 1 型糖尿病的后期发展这一假设的支持薄弱。相反，某些细菌感染似乎会增加多种自身抗体和临床 1 型糖尿病的风险。

图形概要