AIMS/HYPOTHESIS Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. METHODS Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1-49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. RESULTS Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. CONCLUSIONS/INTERPRETATION Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.

中文翻译：

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筛选后具有多种自身抗体的个体进展为 1 型糖尿病的风险差异很大。

目的/假设 产生多种自身抗体 (mAb) 的幼儿患 1 型糖尿病的风险非常高。我们评估了通过筛查检测到单克隆抗体的人群是否也处于非常高的风险中，以及风险如何根据年龄、自身抗体类型和代谢状态而变化。方法 1 型糖尿病 TrialNet Pathway to Prevention 参与者（n = 1815；年龄，12.35 ± 9.39 岁；范围，1-49 岁）被分析。根据年龄、自身抗体类型/数量（胰岛素自身抗体 [IAA]、谷氨酸脱羧酶自身抗体 [GADA]、胰岛素瘤相关抗原 2 自身抗体 [IA-2A] 或锌转运蛋白 8 自身抗体 [ZnT8A]）评估 1 型糖尿病风险和 Index60（空腹 C 肽、60 分钟葡萄糖和 60 分钟 C 肽的综合测量值）。Cox 回归和累积发生率曲线用于该队列研究。结果 年龄与 mAb 患者的 1 型糖尿病风险呈负相关 (HR 0.97 [95% CI 0.96, 0.99])。在具有 2 种自身抗体的参与者中，具有 GADA 的参与者发生 1 型糖尿病的风险较低 (HR 0.35 [95% CI 0.22, 0.57])，而具有 IA-2A 的参与者具有较高的风险 (HR 2.82 [95% CI 1.76, 4.51])。患有 IAA 和 GADA 的人 5 年内患 1 型糖尿病的风险仅为 17%。Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) 的风险显着低于 Index60 值 ≥1.0 的风险。在 12% (225/1815) ≥12.0 岁且 GADA 阳性、IA-2A 阴性且 Index60 <1.0 的人群中，1 型糖尿病的 5 年风险为 8%。结论/解释 1 型糖尿病风险因年龄、筛选 mAb 的个体的自身抗体类型和代谢状态。相当一部分使用 mAb 的年龄较大的儿童和成人在 5 年时进展为 1 型糖尿病的风险似乎较低。有了这些知识，1 型糖尿病预防的临床试验可以更好地针对那些最有可能进展的人。