To use islet autoantibody titers to improve the estimation of future type 1 diabetes risk in children.

Prospective cohort studies in Finland, Germany, Sweden, and the U.S. followed 24,662 children at increased genetic or familial risk to develop islet autoimmunity and diabetes. For 1,604 children with confirmed positivity, titers of autoantibodies against insulin (IAA), GAD antibodies (GADA), and insulinoma-associated antigen 2 (IA-2A) were harmonized for diabetes risk analyses.

Survival analysis from time of confirmed positivity revealed markedly different 5-year diabetes risks associated with IAA (n = 909), GADA (n = 1076), and IA-2A (n = 714), when stratified by quartiles of titer, ranging from 19% (GADA 1st quartile) to 60% (IA-2A 4th quartile). The minimum titer associated with a maximum difference in 5-year risk differed for each autoantibody, corresponding to the 58.6th, 52.4th, and 10.2nd percentile of children specifically positive for each of IAA, GADA, and IA-2A, respectively. Using these autoantibody type-specific titer thresholds in the 1,481 children with all autoantibodies tested, the 5-year risk conferred by single (n = 954) and multiple (n = 527) autoantibodies could be stratified from 6 to 75% (P < 0.0001). The thresholds effectively identified children with a ≥50% 5-year risk when considering age-specific autoantibody screening (57–65% positive predictive value and 56–74% sensitivity for ages 1–5 years). Multivariable analysis confirmed the significance of associations between the three autoantibody titers and diabetes risk, informing a childhood risk surveillance strategy.

This study defined islet autoantibody type-specific titer thresholds that significantly improved type 1 diabetes risk stratification in children.

使用胰岛自身抗体滴度来提高对儿童未来 1 型糖尿病风险的估计。

在芬兰、德国、瑞典和美国开展的前瞻性队列研究追踪了 24,662 名患胰岛自身免疫病和糖尿病的遗传或家族风险增加的儿童。对于 1,604 名确诊为阳性的儿童，针对胰岛素 (IAA)、GAD 抗体 (GADA) 和胰岛素瘤相关抗原 2 (IA-2A) 的自身抗体滴度进行了糖尿病风险分析。

从确诊阳性开始的生存分析显示，当按滴度的四分位数分层时，与 IAA ( n = 909)、GADA ( n = 1076) 和 IA-2A ( n = 714)相关的 5 年糖尿病风险显着不同，范围从19%（GADA 第一个四分位数）到 60%（IA-2A 第四个四分位数）。与 5 年风险最大差异相关的最小滴度因每种自身抗体而异，分别对应于 IAA、GADA 和 IA-2A 中每一种特异性阳性儿童的第 58.6、52.4 和 10.2 个百分位数。在测试了所有自身抗体的 1,481 名儿童中使用这些自身抗体类型特异性滴度阈值，单一 ( n = 954) 和多重 ( n= 527) 自身抗体可以从 6% 到 75% 分层 ( P < 0.0001)。在考虑特定年龄的自身抗体筛查时，这些阈值有效地识别出 5 年风险≥50% 的儿童（1-5 岁的阳性预测值为 57-65%，敏感性为 56-74%）。多变量分析证实了三种自身抗体滴度与糖尿病风险之间关联的重要性，为儿童风险监测策略提供了信息。

该研究定义了胰岛自身抗体类型特异性滴度阈值，可显着改善儿童 1 型糖尿病风险分层。