OBJECTIVE The Environmental Determinants of Diabetes in the Young (TEDDY) study is uniquely capable of investigating age-specific differences associated with type 1 diabetes. Because age is a primary driver of heterogeneity in type 1 diabetes, we sought to characterize by age metabolic derangements prior to diagnosis and clinical features associated with diabetic ketoacidosis (DKA). RESEARCH DESIGN AND METHODS The 379 TEDDY children who developed type 1 diabetes were grouped by age at onset (0-4, 5-9, and 10-14 years; n = 142, 151, and 86, respectively) with comparisons of autoantibody profiles, HLAs, family history of diabetes, presence of DKA, symptomatology at onset, and adherence to TEDDY protocol. Time-varying analysis compared those with oral glucose tolerance test data with TEDDY children who did not progress to diabetes. RESULTS Increasing fasting glucose (hazard ratio [HR] 1.09 [95% CI 1.04-1.14]; P = 0.0003), stimulated glucose (HR 1.50 [1.42-1.59]; P < 0.0001), fasting insulin (HR 0.89 [0.83-0.95]; P = 0.0009), and glucose-to-insulin ratio (HR 1.29 [1.16-1.43]; P < 0.0001) were associated with risk of progression to type 1 diabetes. Younger children had fewer autoantibodies with more symptoms at diagnosis. Twenty-three children (6.1%) had DKA at onset, only 1 (0.97%) of 103 with and 22 (8.0%) of 276 children without a first-degree relative (FDR) with type 1 diabetes (P = 0.008). Children with DKA were more likely to be nonadherent to study protocol (P = 0.047), with longer duration between their last TEDDY evaluation and diagnosis (median 10.2 vs. 2.0 months without DKA; P < 0.001). CONCLUSIONS DKA at onset in TEDDY is uncommon, especially for FDRs. For those without familial risk, metabolic monitoring continues to provide a primary benefit of reduced DKA but requires regular follow-up. Clinical and laboratory features vary by age at onset, adding to the heterogeneity of type 1 diabetes.

中文翻译：

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TEDDY 研究中诊断为 1 型糖尿病的儿童 DKA 发病率和年龄特异性临床特征的异质性。


目的 青少年糖尿病环境决定因素 (TEDDY) 研究具有独特的能力，能够调查与 1 型糖尿病相关的年龄特异性差异。由于年龄是 1 型糖尿病异质性的主要驱动因素，因此我们试图在诊断前描述年龄代谢紊乱以及与糖尿病酮症酸中毒 (DKA) 相关的临床特征。研究设计和方法 将 379 名患有 1 型糖尿病的 TEDDY 儿童按发病年龄（0-4、5-9 和 10-14 岁；分别为 142、151 和 86）分组，并比较自身抗体谱、HLA、糖尿病家族史、DKA 的存在、发病时的症状以及对 TEDDY 方案的遵守。时变分析将那些接受口服葡萄糖耐量测试数据的儿童与未进展为糖尿病的 TEDDY 儿童进行了比较。结果 空腹血糖升高（风险比 [HR] 1.09 [95% CI 1.04-1.14]；P = 0.0003）、刺激血糖（HR 1.50 [1.42-1.59]；P < 0.0001）、空腹胰岛素（HR 0.89 [0.83- 0.95]；P = 0.0009）和葡萄糖与胰岛素比率（HR 1.29 [1.16-1.43]；P < 0.0001）与进展为 1 型糖尿病的风险相关。年龄较小的儿童在诊断时自身抗体较少，症状较多。 23 名儿童 (6.1%) 发病时患有 DKA，103 名儿童中只有 1 名 (0.97%) 患有 1 型糖尿病，276 名没有一级亲属 (FDR) 的儿童中只有 22 名 (8.0%) 患有 1 型糖尿病 (P = 0.008)。患有 DKA 的儿童更有可能不遵守研究方案 (P = 0.047)，最后一次 TEDDY 评估和诊断之间的持续时间较长（中位 10.2 个月与无 DKA 的 2.0 个月；P < 0.001）。结论 TEDDY 中发病时 DKA 并不常见，尤其是对于 FDR 而言。 对于那些没有家族风险的人来说，代谢监测仍然是减少 DKA 的主要益处，但需要定期随访。临床和实验室特征因发病年龄而异，增加了 1 型糖尿病的异质性。