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The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening
Open accessAbstract
Aims/hypothesis Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs ( n = 1815; age, 12.35 ± 9.39 years; range, 1–49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress.
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“The presence of multiple islet autoantibodies (IAA, GADA, IA-2A/IA-2bA, or ZnT8A) is associated with a risk of type 1 diabetes of >90% (408,422,423).”
From Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus (2023) · cites this paper as [422]
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Metadata
- Authors
- Jacobsen, L. M., Bocchino, L., Evans-Molina, C., DiMeglio, L., Goland, R., Wilson, D. M., Atkinson, M. A., Aye, T., Russell, W. E., Wentworth, J. M., Boulware, D., Geyer, S., & Sosenko, J. M.
- Affiliations
- University of Florida Health (US)
- University of South Florida (US)
- Indiana University Indianapolis (US)
- Columbia University Irving Medical Center (US)
- Stanford Medicine (US)
- Vanderbilt University Medical Center (US)
- The Royal Melbourne Hospital (AU)
- University of Miami (US)
- Corresponding author
- Jacobsen, Laura M.
- ORCID
- Venue
- Diabetologia
- Published
- 2019-11-25
- Volume
- 63
- Issue
- 3
- Pages
- 588-596
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC7229995
- OpenAlex
- W2989794873
- Semantic Scholar
- 2d90c1dba261fa6bccc29d5b520df39827c2c14a
- Cited by
- 133
- References
- 35
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 25 · 2023: 25 · 2022: 14 · 2021: 14 · 2020: 6
- FWCI
- 5.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Minerva Access (University of Melbourne) (submittedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- TrialNet is supported by NIH and JDRF (U01 DK107013, U01 DK107014, UC4 DK106993, JDRF)
- 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
- multiple autoantibodies, disease progression risk, autoantibody detection, insulin autoantibodies, glutamic acid decarboxylase antibodies, IA-2 autoantibodies, zinc transporter 8 autoantibodies, C-peptide, age as risk factor, young children, TrialNet
- MeSH terms
- Adolescent, Adult, Autoantibodies, Autoimmune Diseases, Child, Child, Preschool, Diabetes Mellitus, Type 1, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Individuality, Infant, Male, Mass Screening, Middle Aged, Monitoring, Physiologic, Prediabetic State, Prognosis, Risk Factors, Cohort Studies, Disease Progression, Genetic Predisposition to Disease, Young Adult
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