The goal of the TEDDY (The Environmental Determinants of Diabetes in the Young) study is to elucidate factors leading to the initiation of islet autoimmunity (first primary outcome) and those related to progression to type 1 diabetes mellitus (T1DM; second primary outcome). This Review outlines the key findings so far, particularly related to the first primary outcome. The background, history and organization of the study are discussed. Recruitment and follow-up (from age 4 months to 15 years) of 8,667 children showed high retention and compliance. End points of the presence of autoantibodies against insulin, GAD65, IA-2 and ZnT8 revealed the HLA-associated early appearance of insulin autoantibodies (1–3 years of age) and the later appearance of GAD65 autoantibodies. Competing autoantibodies against tissue transglutaminase (marking coeliac disease autoimmunity) also appeared early (2–4 years). Genetic and environmental factors, including enterovirus infection and gastroenteritis, support mechanistic differences underlying one phenotype of autoimmunity against insulin and another against GAD65. Infant growth and both probiotics and high protein intake affect the two phenotypes differently, as do serious life events during pregnancy. As the end of the TEDDY sampling phase is approaching, major omics approaches are in progress to further dissect the mechanisms that might explain the two possible endotypes of T1DM.

TEDDY（年轻人糖尿病的环境决定因素）研究的目标是阐明导致胰岛自身免疫开始的因素（第一主要结果）和与进展为 1 型糖尿病相关的因素（T1DM;第二主要结果）。本综述概述了迄今为止的主要发现，特别是与第一个主要结局相关的结果。讨论了研究的背景、历史和组织。对 8,667 名儿童的招募和随访 （从 4 个月到 15 岁） 显示出很高的保留率和依从性。针对胰岛素、GAD65、IA-2 和 ZnT8 的自身抗体存在的终点揭示了胰岛素自身抗体（1-3 岁）与 HLA 相关的早期出现和 GAD65 自身抗体的后期出现。针对组织转谷氨酰胺酶的竞争性自身抗体 （标记乳糜泻自身免疫） 也出现在早期 （2-4 岁）。遗传和环境因素，包括肠道病毒感染和胃肠炎，支持一种针对胰岛素的自身免疫表型和另一种针对 GAD65 的自身免疫表型的机制差异。婴儿生长以及益生菌和高蛋白质摄入量对这两种表型的影响不同，怀孕期间的严重生活事件也是如此。随着 TEDDY 采样阶段的结束，主要的组学方法正在进行中，以进一步剖析可能解释 T1DM 两种可能内型的机制。