AIMS/HYPOTHESIS Methods to identify individuals at highest risk for type 1 diabetes are essential for the successful implementation of disease-modifying interventions. Simple metabolic measures are needed to help stratify autoantibody-positive (Aab+) individuals who are at risk of developing type 1 diabetes. HOMA2-B is a validated mathematical tool commonly used to estimate beta cell function in type 2 diabetes using fasting glucose and insulin. The utility of HOMA2-B in association with type 1 diabetes progression has not been tested. METHODS Baseline HOMA2-B values from single-Aab+ (n = 2652; mean age, 21.1 ± 14.0 years) and multiple-Aab+ (n = 3794; mean age, 14.5 ± 11.2 years) individuals enrolled in the TrialNet Pathway to Prevention study were compared. Cox proportional hazard models were used to determine associations between HOMA2-B tertiles and time to progression to type 1 diabetes, with adjustments for age, sex, HLA status and BMI z score. Receiver operating characteristic (ROC) analysis was used to test the association of HOMA2-B with type 1 diabetes development in 1, 2, 5 and 10 years. RESULTS At study entry, HOMA2-B values were higher in single- compared with multiple-Aab+ Pathway to Prevention participants (91.1 ± 44.5 vs 83.9 ± 38.9; p < 0.001). Single- and multiple-Aab+ individuals in the lowest HOMA2-B tertile had a higher risk and faster rate of progression to type 1 diabetes. For progression to type 1 diabetes within 1 year, area under the ROC curve (AUC-ROC) was 0.685, 0.666 and 0.680 for all Aab+, single-Aab+ and multiple-Aab+ individuals, respectively. When correlation between HOMA2-B and type 1 diabetes risk was assessed in combination with additional factors known to influence type 1 diabetes progression (insulin sensitivity, age and HLA status), AUC-ROC was highest for the single-Aab+ group's risk of progression at 2 years (AUC-ROC 0.723 [95% CI 0.652, 0.794]). CONCLUSIONS/INTERPRETATION These data suggest that HOMA2-B may have utility as a single-time-point measurement to stratify risk of type 1 diabetes development in Aab+ individuals.

中文翻译：

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HOMA2-B 加强了 TrialNet Pathway to Prevention 参与者对 1 型糖尿病风险的评估。

目的/假设 确定 1 型糖尿病风险最高的个体的方法对于成功实施疾病缓解干预措施至关重要。需要简单的代谢测量来帮助对有患 1 型糖尿病风险的自身抗体阳性 (Aab+) 个体进行分层。HOMA2-B 是一种经过验证的数学工具，通常用于使用空腹血糖和胰岛素来估计 2 型糖尿病患者的 β 细胞功能。HOMA2-B 与 1 型糖尿病进展相关的效用尚未经过测试。方法 参加 TrialNet 预防途径研究的单 Aab+（n = 2652；平均年龄 21.1 ± 14.0 岁）和多 Aab+（n = 3794；平均年龄 14.5 ± 11.2 岁）个体的基线 HOMA2-B 值是比较的。Cox 比例风险模型用于确定 HOMA2-B 三分位数与进展为 1 型糖尿病的时间之间的关联，并针对年龄、性别、HLA 状态和 BMI z 评分进行了调整。接受者操作特征 (ROC) 分析用于检验 HOMA2-B 在 1、2、5 和 10 年内与 1 型糖尿病发展的关联。结果 在研究开始时，与多重 Aab+ 预防途径参与者相比，单一 Aab+ 预防参与者的 HOMA2-B 值更高（91.1 ± 44.5 对比 83.9 ± 38.9；p < 0.001）。最低 HOMA2-B 三分位数中的单个和多个 Aab+ 个体具有更高的风险和更快的进展为 1 型糖尿病的速度。对于在 1 年内进展为 1 型糖尿病，所有 Aab+、单个 Aab+ 和多个 Aab+ 个体的 ROC 曲线下面积 (AUC-ROC) 分别为 0.685、0.666 和 0.680。当结合已知影响 1 型糖尿病进展的其他因素（胰岛素敏感性、年龄和 HLA 状态）评估 HOMA2-B 与 1 型糖尿病风险之间的相关性时，单 Aab+ 组进展风险的 AUC-ROC 最高2 年（AUC-ROC 0.723 [95% CI 0.652, 0.794]）。结论/解释 这些数据表明，HOMA2-B 可能具有作为单一时间点测量的效用，可用于对 Aab+ 个体发生 1 型糖尿病的风险进行分层。