在 TEDDY 队列研究中，6 岁前和 6 岁后被诊断为 1 型糖尿病的儿童的特征。
Characteristics of children diagnosed with type 1 diabetes before vs after 6 years of age in the TEDDY cohort study.
机构信息
Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmo, Sweden.
出版信息
Diabetologia. 2021 Oct;64(10):2247-2257. doi: 10.1007/s00125-021-05514-3. Epub 2021 Jul 22.
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.
目的/假设：本研究旨在比较 TEDDY 研究中，6 岁以下和 6-13 岁确诊 1 型糖尿病儿童的预后因素和特征。
方法
对 8502 名遗传高危儿童进行中位时间为 9.9 年的随访；其中 328 名（3.9%）被诊断为 1 型糖尿病。使用 Cox 比例风险模型评估两组中预后因素与 1 型糖尿病风险的相关性。
结果
与年长组相比，年幼组儿童更倾向于更早出现自身抗体（平均年龄 1.5 岁 vs. 3.5 岁），尤其是胰岛素自身抗体（IAA），其出现早于谷氨酸脱羧酶自身抗体（GADA）。年幼组儿童也比年长组儿童更快进展为糖尿病（平均病程 1.9 岁 vs. 5.4 岁）。只有年长组儿童存在最初针对胰岛瘤抗原-2（IA-2A）的自身抗体。年幼组中与原籍国相关的显著糖尿病风险在年长组中不再显著。相反，与 HLA 基因型相关的糖尿病风险在年长组中也具有统计学意义。2 岁之前或之后初次血清转换与多发性自身抗体阳性儿童的糖尿病诊断风险降低相关，但如果初次血清转换发生在 2 岁之后，糖尿病风险不会进一步降低。与其他基因型相比，rs1004446（INS）的次要等位基因（HR 0.67）与年轻和年长组的糖尿病风险降低相关。与 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 2.31 和 2.54）的次要等位基因相关的糖尿病风险显著增加（HR 值分别代表年轻和年长组）。
结论/解释：早期发生的糖尿病可能先出现 IAA 自身抗体，且疾病更具侵袭性。在年长儿童中，一旦观察到多种自身抗体，儿童年龄或家族史与进展为糖尿病之间似乎没有任何关联。
试验注册
ClinicalTrials.gov 标识符：NCT00279318。
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