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; thus, they are present months to years before symptomatic onset.
“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.”
From Type 1 diabetes (2014) · cites this paper as [66]
The Results and Discussion report peak autoantibody incidence from 9 months to 2 years in genetically at-risk children. The claim that autoantibodies can appear as early as 6 months is not established by this study: the Discussion reports no seroconversion at 3 or 6 months in the BABYDIET cohort, while cautioning that its size cannot rule out occurrence then. The citation precedes the sentence’s concluding inference about symptomatic onset, so that inference is not part of the attributed claim. (LLM, conf=0.88)
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Self-citationWinkler, C., Haupt, F., Heigermoser, M., Zapardiel‐Gonzalo, J., Ohli, J., Faure, T., Kalideri, E., Hommel, A., Delivani, P., Berner, R., et al. (2019) · Pediatric Diabetes · doi:10.1111/pedi.12870 · Cited by 62 · see citing works
Self-citationCoxsackievirus and Type 1 Diabetes: Diabetogenic Mechanisms and Implications for Prevention
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Early infant feeding and risk of developing islet autoimmunity and type 1 diabetes
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Self-citationBonifacio, E. E., Weiß, A., Winkler, C., Hippich, M., Rewers, M., Toppari, J., Lernmark, Å., She, J., Hagopian, W., Krischer, J. P., et al. (2021) · Diabetes Care · doi:10.2337/dc20-2122 · Cited by 54 · see citing works
Self-citationElevations in blood glucose before and after the appearance of islet autoantibodies in children
Warncke, K., Weiß, A., Achenbach, P., Berge, T. V. D., Berner, R., Casteels, K., Groele, L., Hatzikotoulas, K., Hommel, A., Kordonouri, O., et al. (2022) · Journal of Clinical Investigation · doi:10.1172/jci162123 · Cited by 53 · see citing works
Self-citationReduced β-cell function in early preclinical type 1 diabetes
Koskinen, M. K., Helminen, O., Matomäki, J., Aspholm, S., Mykkänen, J., Mäkinen, M., Simell, V., Vähä-Mäkilä, M., Simell, T. T., Ilonen, J., et al. (2015) · European Journal of Endocrinology · doi:10.1530/eje-15-0674 · Cited by 49 · see citing works
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Self-citationGeneral population screening for type 1 diabetes
Insel, R. A., Dunne, J. L., & Ziegler, A. (2015) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000173 · Cited by 48 · see citing works
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Meropol, S. B., & Edwards, A. (2015) · Birth Defects Research Part C Embryo Today Reviews · doi:10.1002/bdrc.21114 · Cited by 47 · see citing works
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Screening for T1D risk to reduce DKA is not economically viable
Meehan, C., Fout, B. T., Ashcraft, J., Schatz, D., & Haller, M. J. (2015) · Pediatric Diabetes · doi:10.1111/pedi.12313 · Cited by 45 · see citing works
Tetraspanin 7 autoantibodies in type 1 diabetes
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Common ground: shared risk factors for type 1 diabetes and celiac disease
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Kindt, A. S. D., Fuerst, R., Knoop, J., Laimighofer, M., Telieps, T., Hippich, M., Wörheide, M. A., Wahl, S., Wilson, R., Sedlmeier, E., et al. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.11.008 · Cited by 36 · see citing works
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Peptide serum markers in islet autoantibody-positive children
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Characterising the age-dependent effects of risk factors on type 1 diabetes progression
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Frohnert, B. I., Webb‐Robertson, B., Bramer, L., Reehl, S., Waugh, K., Steck, A. K., Norris, J. M., & Rewers, M. (2019) · Diabetes · doi:10.2337/db18-1263 · Cited by 33 · see citing works
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Understanding Islet Autoantibodies in Prediction of Type 1 Diabetes
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Sex as a determinant of type 1 diabetes at diagnosis
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Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus
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The crucial role of early-life gut microbiota in the development of type 1 diabetes
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Lessons and gaps in the prediction and prevention of type 1 diabetes
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Early childhood CMV infection may decelerate the progression to clinical type 1 diabetes
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Self-citation
- 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 › Surgery › 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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