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Reversion of β-Cell Autoimmunity Changes Risk of Type 1 Diabetes: TEDDY Study
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OBJECTIVE: β-Cell autoantibodies are a feature of the preclinical phase of type 1 diabetes. Here, we asked how frequently they revert in a cohort of children at risk for type 1 diabetes and whether reversion has any effect on type 1 diabetes risk. RESEARCH DESIGN AND METHODS: Children were up to 10 years of age and screened more than once for insulin autoantibody, GAD antibody, and insulinoma antigen-2 antibodies. Persistent autoantibody was defined as an autoantibody present on two or more consecutive visits and confirmed in two reference laboratories. Reversion was defined as two or more consecutive negative visits after persistence. Time-dependent Cox regression was used to examine how reversion modified the risk of development of multiple autoantibodies and type 1 diabetes. RESULTS: Reversion was relatively frequent for autoantibodies to GAD65 (19%) and insulin (29%), but was largely restricted to children who had single autoantibodies (24%) and rare in children who had developed multiple autoantibodies (<1%). Most (85%) reversion of single autoantibodies occurred within 2 years of seroconversion. Reversion was associated with HLA genotype, age, and decreasing titer. Children who reverted from single autoantibodies to autoantibody negative had, from birth, a risk for type 1 diabetes of 0.14 per 100 person-years; children who never developed autoantibodies, 0.06 per 100 person-years; and, children who remained single-autoantibody positive, 1.8 per 100 person-years. CONCLUSIONS: Type 1 diabetes risk remained high in children who had developed multiple β-cell autoantibodies even when individual autoantibodies reverted. We suggest that monitoring children with single autoantibodies for at least 1 year after seroconversion is beneficial for stratification of type 1 diabetes risk.
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“In several cohort studies, up to 50% of children with only a single autoantibody revert to being islet autoantibody negative during follow-up (79,80).”
From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [80]
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Metadata
- Authors
- Vehik, K., Lynch, K. F., Schatz, D. A., Akolkar, B., Hagopian, W., Rewers, M., She, J.-X., Simell, O., Toppari, J., Ziegler, A.-G., Lernmark, Å., Bonifacio, E., Krischer, J. P., & the TEDDY Study Group
- Affiliations
- University of South Florida (US)
- University of Florida (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Pacific Northwest Research Institute (US)
- University of Colorado Health (US)
- Augusta University (US)
- Turku University Hospital (FI)
- TUM Klinikum (DE)
- Lund University (SE)
- German Center for Diabetes Research (DE)
- Corresponding author
- Vehik, Kendra
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2016-06-16
- Volume
- 39
- Issue
- 9
- Pages
- 1535-1542
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC5001144
- OpenAlex
- W2438883383
- Cited by
- 103
- References
- 27
- Citations by year
- 2026: 15 · 2025: 14 · 2024: 17 · 2023: 10 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 5
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Care (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Site cant be reached (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK-63829, U01-DK-63861, U01-DK-63821, U01-DK-63865, U01-DK-63863, U01-DK-63836, U01-DK-63790, Contract No. HHSN267200700014C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- type 1 diabetes, islet autoimmunity, insulin autoantibodies, GAD65 antibodies, preclinical type 1 diabetes, type 1 diabetes risk, seroconversion, HLA genotypes, vulnerable children, TEDDY study
- MeSH terms
- Seroconversion, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Genotype, Glutamate Decarboxylase, Humans, Insulin, Insulin Antibodies, Male, Prospective Studies, Risk Factors, Autoimmunity, Risk Assessment, Insulin-Secreting Cells, Receptor-Like Protein Tyrosine Phosphatases, Class 8
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