The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study
Open accessAbstract
Aims/hypothesis Islet autoantibodies, in addition to elevated blood glucose, define type 1 diabetes. These autoantibodies are detectable for a variable period of time before diabetes onset. Thus, the occurrence of islet autoantibodies is associated with the beginning of the disease process. The age at, and order in, which autoantibodies appear may be associated with different genetic backgrounds or environmental exposures, or both. Methods Infants with HLA-DR high-risk genotypes (DR3/4, DR4/4, DR4/8 and DR3/3) were enrolled and prospectively followed with standardised autoantibody assessments quarterly throughout the first 4 years of life and then semi-annually thereafter. Results Autoantibodies appeared in 549/8,503 (6.5%) children during 34,091 person-years of follow-up. Autoantibodies at 3 (0.1%) and 6 (0.2%) months of age were rare. Of the 549, 43.7% had islet autoantibodies to insulin (IAA) only, 37.7% had glutamic acid decarboxylase autoantibodies (GADA) only, 13.8% had both GADA and IAA only, 1.6% had insulinoma antigen-2 only and 3.1% had other combinations. The incidence of IAA only peaked within the first year of life and declined over the following 5 years, but GADA only increased until the second year and remained relatively constant. GADA only were more common than IAA only in HLA-DR3/3 children but less common in HLA-DR4/8 children. Conclusions/interpretation Islet autoantibodies can occur very early in life and the order of appearance was related to HLA-DR-DQ genotype.
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Birth cohort studies describe a wide range but a surprising peak incidence of islet autoantibody development at 9 months of age, particularly focused on insulin autoimmunity.
“In addition, birth cohort studies have shed light on the timing of autoantibody development, describing a wide range but a surprising peak incidence of islet autoantibody development at 9 months of age62, particularly focused on insulin autoimmunity.”
From 100 years of insulin: celebrating the past, present and future of diabetes therapy (2021) · cites this paper as [62]
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- Authors
- the TEDDY Study Group, Krischer, J. P., Lynch, K. F., Schatz, D. A., Ilonen, J., Lernmark, Å., Hagopian, W. A., Rewers, M. J., She, J.-X., Simell, O. G., Toppari, J., Ziegler, A.-G., Akolkar, B., & Bonifacio, E.
- Affiliations
- University of South Florida (US)
- University of Turku (FI)
- Pacific Northwest Research Institute (US)
- Augusta University (US)
- Turku University Hospital (FI)
- TUM Klinikum (DE)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- Center for Regenerative Therapies Dresden (DE)
- Corresponding author
- Krischer, Jeffrey P.
- ORCID
- Venue
- Diabetologia
- Published
- 2015-02-10
- Volume
- 58
- Issue
- 5
- Pages
- 980-987
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC4393776
- OpenAlex
- W2051883261
- Cited by
- 444
- References
- 3
- Citations by year
- 2026: 33 · 2025: 42 · 2024: 40 · 2023: 44 · 2022: 37 · 2021: 45 · 2020: 39 · 2019: 30 · 2018: 45 · 2017: 39 · 2016: 35 · 2015: 14 · 2012: 1
- FWCI
- 30.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Site cant be reached (submittedVersion)
- PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
- Funders
- National Institutes of Health (UL1TR001427, UL1TR000064, UL1TR001082)
- Centers for Disease Control and Prevention
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK063861, HHSN267200700014C, U01 DK63865, U01DK063863, UC4DK095300, UC4DK100238, UC4DK063821, UC4DK063836, U01DK063836, UC4DK63829, UC4DK63836, UC4 DK63865, U01DK63836, U01-DK-63821, U01DK063861, U01DK063865, UC4 DK63821, UC4-DK-63863, U01DK63829, UC4DK95300, UC4-DK-63861, U01DK63861, U01-DK-63790, UC4DK063863, U01 DK63863, UC4DK063829, UC4DK063865, U01DK063821, U01DK063829, U01DK063790)
- National Institute of Environmental Health Sciences
- National Institute of Child Health and Human Development
- National Center for Advancing Translational Sciences
- 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 autoantibodies, insulin autoantibodies, glutamic acid decarboxylase antibodies, TEDDY study
- MeSH terms
- Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Genotype, HLA-DQ Antigens, Humans, Insulin, Islets of Langerhans, Male, Genetic Predisposition to Disease
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