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Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk
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Aims/hypothesis The aim of the study was to investigate the timing of the appearance of autoantibodies associated with type 1 diabetes between birth and puberty, the natural fate of these autoantibodies and the predictive power of autoantibody concentrations for early progression to clinical diabetes. Methods Children were recruited to the Type 1 Diabetes Prediction and Prevention Project, an ongoing study based on HLA-conferred genetic risk. Autoantibodies against islet cells, insulin, GAD65 and islet antigen 2 were analysed at 3-12 month intervals, starting from birth. Results During the follow-up, 1,320 children (18.4% of the cohort of 7,165 children) were autoantibody positive in at least one sample. Altogether, 184 autoantibody-positive children progressed to type 1 diabetes. Seroconversion occurred at an early age in the progressors (median 1.5 years), among whom 118 (64%) and 150 (82%) seroconverted to autoantibody positivity before the age of 2 and 3 years, respectively. The incidence of seroconversion peaked at 1 year of age. Compared with other autoantibody-positive children, the median autoantibody levels were already markedly higher 3 to 6 months after the seroconversion in children who later progressed to diabetes. Conclusions/interpretation Early initiation of autoimmunity and rapid increases in autoantibody titres strongly predict progression to overt diabetes before puberty, emphasising the importance of early life events in the development of type 1 diabetes.
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“IAA concentration correlates with the rate of progression to overt type 1 diabetes in children followed from birth.67,68”
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Metadata
- Authors
- Parikka, V., Näntö-Salonen, K., Saarinen, M., Simell, T., Ilonen, J., Hyöty, H., Veijola, R., Knip, M., & Simell, O.
- Affiliations
- Turku University Hospital (FI)
- University of Turku (FI)
- Tampere University (FI)
- Oulu University Hospital (FI)
- University of Helsinki (FI)
- Corresponding author
- Parikka, V.
- Venue
- Diabetologia
- Published
- 2012-03-23
- Volume
- 55
- Issue
- 7
- Pages
- 1926-1936
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W2049204060
- Cited by
- 235
- References
- 43
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 19 · 2022: 14 · 2021: 21 · 2020: 8 · 2019: 16 · 2018: 14 · 2017: 17 · 2016: 25 · 2015: 25 · 2014: 21 · 2013: 16 · 2012: 7
- FWCI
- 13.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Juvenile Diabetes Research Foundation International (4‐1998‐274, 4‐1999‐731, 68292, 4-1998-274, 4-1999-731, 4-2001-435, 4‐2001‐435)
- European Commission (BMH4‐CT98‐3314, 4-1998-274, 4-1999-731, 68292, 4-2001-435)
- Academy of Finland (114666, 68292)
- Suomen Kulttuurirahasto
- Tekes (4-1998-274, 68292, 4-1999-731, 4-2001-435)
- Päivikki ja Sakari Sohlbergin Säätiö (68292, 4-1998-274, 4-2001-435, 4-1999-731)
- Signe ja Ane Gyllenbergin Säätiö (4-1999-731, 4-2001-435, 4-1998-274, 68292)
- Emil Aaltosen Säätiö
- Lastentautien Tutkimussäätiö (BMH4- CT98-3314, 4-2001-435, 68292, 4-1998-274, 4-1999-731)
- Fonds Spéciaux de Recherche
- Varsinais-Suomen Rahasto
- 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, autoantibodies, seroconversion, prepubertal onset, islet autoimmunity, GAD65, insulin autoantibodies, disease progression prediction, autoantibody titres, early life events
- MeSH terms
- Autoantibodies, Child, Preschool, Diabetes Mellitus, Type 1, Disease Susceptibility, Female, Finland, HLA Antigens, Humans, Infant, Infant, Newborn, Male, Prediabetic State, Predictive Value of Tests, Pregnancy, Biomarkers, Age of Onset, Disease Progression
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