University of Oulu

Salami, F, Tamura, R, You, L, et al. HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children. Pediatr Diabetes. 2022; 23( 8): 1586- 1593. doi:10.1111/pedi.13413

HbA1c as a time predictive biomarker for an additional islet autoantibody and type 1 diabetes in seroconverted TEDDY children

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Author: Salami, Falastin1; Tamura, Roy2; You, Lu2;
Organizations: 1Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital, Malmö, Sweden
2Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA
3Department of Pediatrics, Skåne University Hospital, Malmö, Sweden
4Department of Pediatrics, Kristianstad Hospital, Kristianstad, Sweden
5Helmholtz Zentrum München, Institute of Diabetes Research, German Research Center for Environmental Health, Munich-Neuherberg, Germany
6Forschergruppe Diabetes, Technical University Munich at Klinikum Rechts der Isar, Munich, Germany
7Department of Pediatrics, Turku University Hospital, and Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, and Centre for Population Health Research, University of Turku, Turku, Finland
8Department of Pediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu and Oulu University Hospital, Oulu, Finland
9Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, Colorado, USA
10Department of Pediatrics, College of Medicine, University of Florida Diabetes Institute, Gainesville, Florida, USA
11Diabetes Programs Division, Pacific Northwest Research Institute, Seattle, Washington, USA
12Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, USA
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.3 MB)
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Language: English
Published: John Wiley & Sons, 2022
Publish Date: 2023-01-20


Objective: Increased level of glycated hemoglobin (HbA1c) is associated with type 1 diabetes onset that in turn is preceded by one to several autoantibodies against the pancreatic islet beta cell autoantigens; insulin (IA), glutamic acid decarboxylase (GAD), islet antigen-2 (IA-2) and zinc transporter 8 (ZnT8). The risk for type 1 diabetes diagnosis increases by autoantibody number. Biomarkers predicting the development of a second or a subsequent autoantibody and type 1 diabetes are needed to predict disease stages and improve secondary prevention trials. This study aimed to investigate whether HbA1c possibly predicts the progression from first to a subsequent autoantibody or type 1 diabetes in healthy children participating in the Environmental Determinants of Diabetes in the Young (TEDDY) study.

Research Design and Methods: A joint model was designed to assess the association of longitudinal HbA1c levels with the development of first (insulin or GAD autoantibodies) to a second, second to third, third to fourth autoantibody or type 1 diabetes in healthy children prospectively followed from birth until 15 years of age.

Results: It was found that increased levels of HbA1c were associated with a higher risk of type 1 diabetes (HR 1.82, 95% CI [1.57–2.10], p < 0.001) regardless of first appearing autoantibody, autoantibody number or type. A decrease in HbA1c levels was associated with the development of IA-2A as a second autoantibody following GADA (HR 0.85, 95% CI [0.75, 0.97], p = 0.017) and a fourth autoantibody following GADA, IAA and ZnT8A (HR 0.90, 95% CI [0.82, 0.99], p = 0.036). HbA1c trajectory analyses showed a significant increase of HbA1c over time (p < 0.001) and that the increase is more rapid as the number of autoantibodies increased from one to three (p < 0.001).

Conclusion: In conclusion, increased HbA1c is a reliable time predictive marker for type 1 diabetes onset. The increased rate of increase of HbA1c from first to third autoantibody and the decrease in HbA1c predicting the development of IA-2A are novel findings proving the link between HbA1c and the appearance of autoantibodies.

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Series: Pediatric diabetes
ISSN: 1399-543X
ISSN-E: 1399-5448
ISSN-L: 1399-543X
Volume: 23
Issue: 8
Pages: 1586 - 1593
DOI: 10.1111/pedi.13413
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: Centers for Disease Control and Prevention (CDC); Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); Juvenile Diabetes Research Foundation United States of America; National Institute of Allergy and Infectious Diseases (NIAID); NIH/NCATS Clinical and Translational Science Awards; University of Colorado, Grant/Award Number: UL1 TR002535; University of Florida, Grant/Award Number: UL1 TR000064; National Institute of Environmental Health Sciences (NIEHS); National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Grant/Award Numbers: HHSN267200700014C, U01 DK128847, U01 DK124166, UC4 DK117483, UC4 DK112243, UC4 DK106955, UC4 DK100238, UC4 DK95300, UC4 DK63836, UC4 DK63863, UC4 DK63865, UC4 DK63821, UC4 DK63861, UC4 DK63829, U01 DK63790, U01 DK63836, U01 DK63863, U01 DK63865, U01 DK63821, U01 DK63861, U01 DK63829
Copyright information: © 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.