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Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes
Open accessAbstract
Aims/hypothesis Seroconversion to islet autoantibodies precedes type 1 diabetes. This study aimed to identify periods of high seroconversion incidence, which could be targeted for mechanistic and therapeutic studies. Methods Incidence of islet autoantibodies was calculated in 1,650 genetically at-risk children followed with measurements of islet autoantibodies and thyroid autoantibodies at age 9 months and 2, 5, 8, 11, 14 and 17 years. Peak incidence periods were confirmed in a second cohort of 150 children followed until age 6 years with three-monthly samples up to age 3 years. Results Islet autoantibody incidence (per 1,000 person-years) was 18.5 until age 9 months, 21 from 9 months to 2 years and <10 for intervals after age 2 years. The second cohort confirmed peak incidence around age 9 months and demonstrated an absence of seroconversion before this age. Seroconversion to insulin autoantibodies occurred earlier than other autoantibodies (p<0.01 against glutamic acid decarboxylase [GAD]-, insulinoma-associated protein 2 [IA-2]- and zinc transporter 8 [ZnT8]-autoantibodies). Early peak seroconversion incidence was most evident in children with high-risk HLA DR3/4-DQ8 or DR4/4-DQ8 genotypes. Conclusion The age period 9 months to 2 years is associated with a high incidence of activation of type 1 diabetes associated autoimmunity in genetically at-risk children and should be targeted for effective primary prevention strategies.
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“These autoantibodies can appear as early as 6 months of age, with a peak incidence before 2 years of age in genetically susceptible individuals;66 thus, they are present months to years before symptomatic onset.”
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Self-citation
Metadata
- Authors
- the BABYDIAB-BABYDIET Study Group, Ziegler, A.-G., & Bonifacio, E.
- Affiliations
- Helmholtz Munich (DE)
- Corresponding author
- Ziegler, A.-G.
- Venue
- Diabetologia
- Published
- 2012-01-31
- Volume
- 55
- Issue
- 7
- Pages
- 1937-1943
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2030685032
- Cited by
- 264
- References
- 30
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 21 · 2023: 24 · 2022: 14 · 2021: 18 · 2020: 10 · 2019: 14 · 2018: 27 · 2017: 13 · 2016: 32 · 2015: 27 · 2014: 15 · 2013: 18 · 2012: 5
- FWCI
- 12.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- mediaTUM (Technical University of Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- European Commission (202013)
- Deutsche Forschungsgemeinschaft (FZ 111, /14-1)
- Bundesministerium für Bildung und Forschung (FKZ 01GI0805‐07, FKZ 01GI0805, 01GI0805, 01GI0805-07)
- Helmholtz Zentrum München
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pancreatic function and diabetes
- Keywords
- type 1 diabetes, islet autoantibodies, seroconversion, insulin autoantibodies, glutamic acid decarboxylase antibodies, IA-2 autoantibodies, ZnT8 autoantibodies, thyroid autoantibodies, primary prevention
- MeSH terms
- Adolescent, Autoantibodies, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Genotype, Germany, HLA-D Antigens, Humans, Infant, Longitudinal Studies, Male, Prediabetic State, Cohort Studies, Incidence, Polymerase Chain Reaction, Child of Impaired Parents, Age of Onset, Disease Progression, Genetic Predisposition to Disease
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