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.
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
{"title":"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.","authors":"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","doi":"10.1155/pedi/8845330","DOIUrl":null,"url":null,"abstract":"<p><p><b>Objective:</b> 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. <b>Research Design and Methods:</b> GADA-positive children (<i>n</i> = 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). <b>Results:</b> Transition risk from GADA to multiple autoantibodies was increased by lower age (<i>p</i> < 0.001) and by increased GADA titers during follow-up (<i>p</i> < 0.001), and was less likely in children with HLA DQ2/X but not DQ2/8 (<i>p</i>=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) (<i>p</i> < 0.001) and increased ZnT8A titers (<i>p</i> < 0.001). Increasing HbA1c (<i>p</i> < 0.001) and GADA titers (<i>p</i> < 0.001) were associated with an increased risk of transition from GADA only to type 1 diabetes; while increasing HbA1c (<i>p</i> < 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 (<i>p</i> < 0.001). <b>Conclusion:</b> The dynamic prediction model presented an individual time-specific risk of transition from a single GADA to multiple autoantibodies and type 1 diabetes.</p>","PeriodicalId":19797,"journal":{"name":"Pediatric Diabetes","volume":"2025 ","pages":"8845330"},"PeriodicalIF":5.6000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12457058/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/pedi/8845330","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
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.
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.