AIMS/HYPOTHESIS Prognostic factors and characteristics of children diagnosed with type 1 diabetes before 6 years of age were compared with those diagnosed at 6-13 years of age in the TEDDY study. METHODS Genetically high-risk children (n = 8502) were followed from birth for a median of 9.9 years; 328 (3.9%) were diagnosed with type 1 diabetes. Cox proportional hazard model was used to assess the association of prognostic factors with the risk of type 1 diabetes in the two age groups. RESULTS Children in the younger group tended to develop autoantibodies earlier than those in the older group did (mean age 1.5 vs 3.5 years), especially insulin autoantibodies (IAA), which developed earlier than GAD autoantibodies (GADA). Children in the younger group also progressed to diabetes more rapidly than the children in the older group did (mean duration 1.9 vs 5.4 years). Children with autoantibodies first appearing against insulinoma antigen-2 (IA-2A) were found only in the older group. The significant diabetes risk associated with the country of origin in the younger group was no longer significant in the older group. Conversely, the diabetes risk associated with HLA genotypes was statistically significant also in the older group. Initial seroconversion after and before 2 years of age was associated with decreased risk for diabetes diagnosis in children positive for multiple autoantibodies, but the diabetes risk did not decrease further with increasing age if initial seroconversion occurred after age 2. Diabetes risk associated with the minor alleles of rs1004446 (INS) was decreased in both the younger and older groups compared with other genotypes (HR 0.67). Diabetes risk was significantly increased with the minor alleles of rs2476601 (PTPN22) (HR 2.04 and 1.72), rs428595 (PPIL2) (HR 2.13 and 2.10), rs113306148 (PLEKHA1) (HR 2.34 and 2.21) and rs73043122 (RNASET2) (HR 2.31 and 2.54) (HR values represent the younger and older groups, respectively). CONCLUSIONS/INTERPRETATIONS Diabetes at an early age is likely to be preceded by IAA autoantibodies and is a more aggressive form of the disease. Among older children, once multiple autoantibodies have been observed there does not seem to be any association between progression to diabetes and the age of the child or family history. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00279318.

中文翻译：

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TEDDY 队列研究中被诊断为 1 型糖尿病的儿童在 6 岁之前与之后的特征。

目的/假设 TEDDY 研究中将 6 岁前诊断为 1 型糖尿病的儿童与 6-13 岁时诊断的儿童的预后因素和特征进行了比较。方法 对遗传高危儿童 (n = 8502) 从出生起进行中位随访 9.9 年；328 人 (3.9%) 被诊断患有 1 型糖尿病。Cox比例风险模型用于评估两个年龄组中预后因素与1型糖尿病风险的关联。结果 年轻组的儿童往往比年长组的儿童更早产生自身抗体（平均年龄 1.5 岁 vs 3.5 岁），尤其是胰岛素自身抗体 (IAA)，它比 GAD 自身抗体 (GADA) 更早产生。年龄较小组的儿童发展为糖尿病的速度也比年龄较大组的儿童更快（平均病程 1.9 年 vs 5.4 年）。首次出现抗胰岛素瘤抗原 2 (IA-2A) 自身抗体的儿童仅在老年组中发现。在年轻群体中，与原籍国相关的显着糖尿病风险在老年群体中不再显着。相反，与 HLA 基因型相关的糖尿病风险在老年组中也具有统计学意义。2岁前后的初始血清转化与多种自身抗体阳性儿童的糖尿病诊断风险降低相关，但如果初始血清转化发生在2岁之后，则糖尿病风险不会随着年龄的增加而进一步降低。 糖尿病风险与次要等位基因相关与其他基因型相比，年轻组和老年组的 rs1004446 (INS) 均下降 (HR 0.67)。rs2476601 (PTPN22) (HR 2.04和1.72)、rs428595 (PPIL2) (HR 2.13和2.10)、rs113306148 (PLEKHA1) (HR 2.34和2.21)和rs73043122 (RNASET2) (HR)的次要等位基因显着增加糖尿病风险。 2.31和 2.54）（HR 值分别代表年轻组和老年组）。结论/解释 早期糖尿病可能先于 IAA 自身抗体出现，并且是一种更具侵袭性的疾病形式。在年龄较大的儿童中，一旦观察到多种自身抗体，糖尿病进展与儿童年龄或家族史之间似乎就没有任何关联。试验注册 ClinicalTrials.gov 标识符：NCT00279318。