Natural History of β-Cell Autoimmunity in Young Children with Increased Genetic Susceptibility to Type 1 Diabetes Recruited from the General Population
Abstract
The aim of this study was to evaluate the frequency and predictive value of diabetes-associated autoantibodies, such as islet cell antibodies (ICA) and autoantibodies to insulin (IAA), GAD65 (GADA), and the IA-2 molecule (IA-2A) in genetically susceptible children from the general population during the first 2 yr of life. Of 12,170 newborn infants, 1,005 with increased genetic risk of type 1 diabetes (high risk, human leukocyte antigen DQB1*02/*0302; moderate risk, DQB1*0302/x, where x = other than *02, *0301, or *0602) were monitored for ICA, IAA, GADA, and IA-2A at 3- to 6-month intervals from birth up to a minimum age of 2 yr. In addition, all 15 genetically susceptible children from the general population who had participated in regular immunological follow-up and developed clinical type 1 diabetes by the end of April 2000 were analyzed for the development of autoantibodies. Among 1,005 children, 63 (6.3%) tested positive for at least one autoantibody, 31 for ICA (3.1%), 48 for IAA (4.8%), 23 for GADA (2.3%), and 13 for IA-2A (1.3%) at least once by the age of 2 yr. Both ICA and IAA identified 95% [95% confidence interval (CI), 77.2-99.9%] of those who tested persistently positive for multiple (> or = 2) antibodies at the age of 2 yr, GADA identified 86% (CI, 65.1-97.1%), and IA-2A identified 55% (CI, 32.2-75.6%). Close to half of the antibody-positive children (29 of 63) reverted back to antibody negativity. Autoantibodies disappeared more often among those who tested positive for IAA than among those who tested positive for other autoantibodies (P < or = 0.021). Among the 15 children who developed type 1 diabetes, the disease sensitivity of ICA was 80% (CI, 51.9-95.7%), that of IAA was 93% (CI, 68.0-99.8%), that of GADA was 60% (CI, 32.3-83.7%), and that of IA-2A was 40% (CI, 16.3-67.7%). These results suggest that IAA are characterized by high sensitivity, early appearance, and high frequency of transient antibody positivity, whereas ICA detected with a thoroughly standardized assay appear to be more specific for the screening of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes in the Finnish population, which has the highest incidence of type 1 diabetes in the world.
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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.
“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 [79]
The Inverse seroconversions section reports that 29 of 63 antibody-positive children (46%) became antibody-negative during follow-up, and all 29 had tested positive for only one autoantibody. The 46% figure uses all antibody-positive children as its denominator, not children with only a single autoantibody, so it does not establish the claimed rate for that subgroup. The paper also reports its own cohort and discusses other studies, rather than establishing a 50% rate across several cohorts. (LLM, conf=0.84)
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Research works printed but not linked: 2
- Leslie RDG, Elliott RB 1994 Perspectives in diabetes: early environmental events as a cause of IDDM-evidence and implications. Diabetes 43:843-850 4578 J Clin Endocrinol Metab, October 2002, 87(10):4572-4579 Kimpima ¨ki et al. • -Cell Autoimmunity in Young Children
- Greenbaum C, Palmer JP, Kuglin B, Kolb H 1992 Insulin autoantibodies measured by radioimmunoassay methodology are more related to insulin- dependent diabetes mellitus than those measured with enzyme-linked im- munosorbent assay: results of the Fourth International Workshop on the Stan- dardization of Insulin Autoantibody Measurement. J Clin Endocrinol Metab 74:1040 -1044
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Self-citationSigns of β-Cell Autoimmunity in Nondiabetic Schoolchildren
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- Authors
- Kimpimäki, T., Kulmala, P., Savola, K., Kupila, A., Korhonen, S., Simell, T., Ilonen, J., Simell, O., & Knip, M.
- Affiliations
- Diabetes Tutkimussaatio (FI)
- University of Turku (FI)
- University of Helsinki (FI)
- Corresponding author
- Knip, M.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2002-10
- Volume
- 87
- Issue
- 10
- Pages
- 4572-4579
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2090742005
- Cited by
- 146
- References
- 0
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 6 · 2020: 4 · 2019: 8 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 4.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- 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, islet cell antibodies, insulin autoantibodies, GAD65 antibodies, IA-2 autoantibodies, genetic susceptibility, HLA-DQB1, infants, autoantibody persistence, disease prediction, natural history (disease), disease specificity
- MeSH terms
- Aging, Autoantibodies, Diabetes Mellitus, Type 1, Glutamate Decarboxylase, Humans, Infant, Insulin Antibodies, Islets of Langerhans, Isoenzymes, Autoimmunity, Genetic Predisposition to Disease
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