Predictors of Transitions From GADA as the Initial Autoantibody to Multiple Autoantibodies of Type 1 Diabetes in Children at Risk by a Dynamic Prediction Model.

IF 5.6 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Pediatric Diabetes Pub Date : 2025-09-16 eCollection Date: 2025-01-01 DOI:10.1155/pedi/8845330

Lu You, Falastin Salami, Roy Tamura, Carina Törn, Kendra Vehik, William A Hagopian, Marian J Rewers, Richard A McIndoe, Jorma Toppari, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Åke Lernmark

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Abstract

Objective: To design a dynamic prediction model for estimating the time of progression from a single glutamic acid decarboxylase autoantibody (GADA) to multiple islet autoantibodies and type 1 diabetes in children, exploring different longitudinally measured risk variables. Research Design and Methods: GADA-positive children (n = 379) participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study were followed for the appearance of additional autoantibodies against either insulin autoantibody (IAA), insulinoma-like 2 autoantibody (IA-2A), or zinc transporter 8 antibody (ZnT8A) and type 1 diabetes. A dynamic prediction model was designed, including trajectories of longitudinal risk variables, autoantibody titers, and metabolic variables (C-peptide, glucose, and HbA1c) together with time-invariant variables (gender, age at GADA positivity, and high-risk HLA genotypes). Results: Transition risk from GADA to multiple autoantibodies was increased by lower age (p < 0.001) and by increased GADA titers during follow-up (p < 0.001), and was less likely in children with HLA DQ2/X but not DQ2/8 (p=0.004). The transition risk from multiple autoantibodies without IA-2A to IA-2A positivity was associated with increased levels of 2 h glucose following oral glucose tolerance test (OGTT) (p < 0.001) and increased ZnT8A titers (p < 0.001). Increasing HbA1c (p < 0.001) and GADA titers (p < 0.001) were associated with an increased risk of transition from GADA only to type 1 diabetes; while increasing HbA1c (p < 0.001) was associated with the transition from multiple autoantibodies to type 1 diabetes. Risk of transition from multiple autoantibodies, including IA-2A to type 1 diabetes was also associated with 2 h glucose level (p < 0.001). Conclusion: The dynamic prediction model presented an individual time-specific risk of transition from a single GADA to multiple autoantibodies and type 1 diabetes.

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动态预测模型预测儿童1型糖尿病从GADA作为初始自身抗体到多种自身抗体的转变

目的：设计儿童从单一谷氨酸脱羧酶自身抗体（GADA）到多种胰岛自身抗体与1型糖尿病进展时间的动态预测模型，探讨不同纵向测量的危险变量。研究设计和方法：参加青少年糖尿病环境决定因素（TEDDY）研究的gada阳性儿童（n = 379）被跟踪观察胰岛素自身抗体（IAA）、胰岛素瘤样2自身抗体（IA-2A）或锌转运蛋白8抗体（ZnT8A）和1型糖尿病的额外自身抗体的出现。设计了一个动态预测模型，包括纵向风险变量、自身抗体滴度、代谢变量（c肽、葡萄糖和HbA1c）以及时不变变量（性别、GADA阳性年龄和高危HLA基因型）的轨迹。结果：从GADA转变为多种自身抗体的风险随着年龄的降低而增加（p < 0.001），随着随访期间GADA滴度的增加而增加（p < 0.001），并且在HLA DQ2/X的儿童中不太可能，但DQ2/8的儿童中不可能（p=0.004）。从无IA-2A的多种自身抗体到IA-2A阳性的转变风险与口服葡萄糖耐量试验（OGTT）后2 h葡萄糖水平升高（p < 0.001）和ZnT8A滴度升高（p < 0.001）相关。HbA1c升高（p < 0.001）和GADA滴度升高（p < 0.001）与单纯GADA向1型糖尿病转变的风险增加相关；而HbA1c升高（p < 0.001）与多种自身抗体向1型糖尿病的转变有关。从多种自身抗体（包括IA-2A）转变为1型糖尿病的风险也与2小时血糖水平相关（p < 0.001）。结论：动态预测模型显示了个体从单一GADA向多种自身抗体和1型糖尿病转变的时间特异性风险。

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来源期刊

Pediatric Diabetes 医学-内分泌学与代谢

CiteScore

6.60

自引率

14.70%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Pediatric Diabetes is a bi-monthly journal devoted to disseminating new knowledge relating to the epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes in childhood and adolescence. The aim of the journal is to become the leading vehicle for international dissemination of research and practice relating to diabetes in youth. Papers are considered for publication based on the rigor of scientific approach, novelty, and importance for understanding mechanisms involved in the epidemiology and etiology of this disease, especially its molecular, biochemical and physiological aspects. Work relating to the clinical presentation, course, management and outcome of diabetes, including its physical and emotional sequelae, is considered. In vitro studies using animal or human tissues, whole animal and clinical studies in humans are also considered. The journal reviews full-length papers, preliminary communications with important new information, clinical reports, and reviews of major topics. Invited editorials, commentaries, and perspectives are a regular feature. The editors, based in the USA, Europe, and Australasia, maintain regular communications to assure rapid turnaround time of submitted manuscripts.