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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

You, Lu ; Salami, Falastin LU ; Tamura, Roy ; Törn, Carina LU ; Vehik, Kendra LU ; Hagopian, William A. ; Rewers, Marian J. ; McIndoe, Richard A. ; Toppari, Jorma and Ziegler, Anette G. , et al. (2025) In Pediatric Diabetes p.1-11
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,... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
children, dynamic statistical modeling, GADA, risk prediction, type 1 diabetes
in
Pediatric Diabetes
article number
8845330
pages
1 - 11
publisher
John Wiley & Sons Inc.
external identifiers
  • scopus:105016400274
  • pmid:40994736
ISSN
1399-543X
DOI
10.1155/pedi/8845330
language
English
LU publication?
yes
additional info
Publisher Copyright: Copyright © 2025 Lu You et al. Pediatric Diabetes published by John Wiley & Sons Ltd.
id
07a0a129-2f81-4baa-860d-1a94b2ce9355
date added to LUP
2025-09-25 10:35:49
date last changed
2025-10-14 10:38:13
@article{07a0a129-2f81-4baa-860d-1a94b2ce9355,
  abstract     = {{<p>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 &lt; 0.001) and by increased GADA titers during follow-up (p &lt; 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 &lt; 0.001) and increased ZnT8A titers (p &lt; 0.001). Increasing HbA1c (p &lt; 0.001) and GADA titers (p &lt; 0.001) were associated with an increased risk of transition from GADA only to type 1 diabetes; while increasing HbA1c (p &lt; 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 &lt; 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.</p>}},
  author       = {{You, Lu and Salami, Falastin and Tamura, Roy and Törn, Carina and Vehik, Kendra and Hagopian, William A. and Rewers, Marian J. and McIndoe, Richard A. and Toppari, Jorma and Ziegler, Anette G. and Akolkar, Beena and Krischer, Jeffrey P. and Lernmark, Åke}},
  issn         = {{1399-543X}},
  keywords     = {{children; dynamic statistical modeling; GADA; risk prediction; type 1 diabetes}},
  language     = {{eng}},
  pages        = {{1--11}},
  publisher    = {{John Wiley & Sons Inc.}},
  series       = {{Pediatric Diabetes}},
  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}},
  url          = {{http://dx.doi.org/10.1155/pedi/8845330}},
  doi          = {{10.1155/pedi/8845330}},
  year         = {{2025}},
}