The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants
Open accessAbstract
AIMS: The Environmental Determinants of Diabetes in the Young (TEDDY) study seeks to identify environmental factors influencing the development of type 1 diabetes (T1D) using intensive follow-up of children at elevated genetic risk. This study requires a cost-effective yet accurate screening strategy to identify the high-risk cohort. METHODS: The TEDDY cohort was identified through newborn screening using human leukocyte antigen (HLA) class II genes based on criteria established with pre-TEDDY data. HLA typing was completed at six international centers using different genotyping methods that can achieve >98% accuracy. RESULTS: TEDDY developed separate inclusion criteria for the general population (GP) and first-degree relatives (FDRs) of T1D patients. The FDR eligibility includes nine haplogenotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4b, DR4/1, DR4/13, DR4/9, and DR3/9) for broad HLA diversity, whereas the GP eligibility includes only the first four haplogenotypes with DRB1*0403 as an exclusion allele. TEDDY has screened 414 714 GP infants, of which 19 906 (4.8%) were eligible, whereas 1415 of the 6333 screened FDR infants (22.2%) were eligible. High-resolution confirmation testing of the eligible subjects indicated that the low-cost and low-resolution genotyping techniques employed at the screening centers yielded an accuracy of 99%. There were considerable variations in eligibility rates among the centers for GP (3.5-7.4%) and FDR (19-32%) subjects. The eligibility rates among US ethnic groups were 0.9, 1.3, 5.0, and 6.9% for Asians, Black, Caucasians, and Hispanics, respectively. CONCLUSIONS: Different low-cost and low-resolution genotyping methods are useful for the efficient and accurate identification of a high-risk cohort for follow-up based on the TEDDY HLA inclusion criteria.
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Measuring islet autoantibodies in relatives of those with type 1 diabetes, in children from the general population, or in children from the general population with high genetic risk can identify many individuals who will develop type 1 diabetes.
“Multiple studies indicate that measuring islet autoantibodies in relatives of those with type 1 diabetes (45), in children from the general population (71,72), or in children from the general population with high genetic risk (73) can identify many individuals who will develop type 1 diabetes.”
From 2. Diagnosis and classification of diabetes: standards of care in diabetes-2025 (2025) · cites this paper as [73]
The Introduction (page unavailable) says TEDDY used genetic screening to identify infants at increased risk and then monitored them for islet autoantibodies and type 1 diabetes. The Discussion (page unavailable) describes HLA-based risk stratification in general-population and first-degree-relative groups. Neither passage establishes that measuring autoantibodies identifies many children who will later develop type 1 diabetes. (LLM, conf=0.84)
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Self-citation
- Authors
- Hagopian, W. A., Erlich, H., Lernmark, Å., Rewers, M., Ziegler, A. G., Simell, O., Akolkar, B., Vogt, R., Blair, A., Ilonen, J., Krischer, J., She, J., & the TEDDY Study Group
- Affiliations
- Pacific Northwest Research Institute (US)
- Lund University (SE)
- University of Colorado Health (US)
- Technical University of Munich (DE)
- University of Turku (FI)
- National Institutes of Health (US)
- Centers for Disease Control and Prevention (US)
- University of South Florida (US)
- Corresponding author
- Hagopian, William A
- ORCID
- Venue
- Pediatric Diabetes
- Publisher
- Wiley
- Published
- 2011-05-12
- Volume
- 12
- Issue
- 8
- Pages
- 733-743
- ISSN
- 1399-543X (ISSN-L)
- PMC
- PMC3315186
- OpenAlex
- W2129044010
- Cited by
- 260
- References
- 2
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 14 · 2023: 11 · 2022: 18 · 2021: 27 · 2020: 11 · 2019: 13 · 2018: 17 · 2017: 23 · 2016: 18 · 2015: 22 · 2014: 18 · 2013: 19 · 2012: 14
- FWCI
- 11.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Pediatric Diabetes (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Technische Universität Dresden
- Karl-Franzens-Universität Graz
- Centers for Disease Control and Prevention (HHSN267200700014C)
- National Institute of Allergy and Infectious Diseases (HHSN267200700014C)
- National Institute of Diabetes and Digestive and Kidney Diseases (UC4DK063861, HHSN267200700014C, U01DK063863, DK-63865, UC4DK095300, UC4DK063821, DK-63821, DK 63790, U01DK063861, DK63863, U01DK063865, DK63861, DK63836, UC4DK063829, UC4DK063865, U01DK063821, U01DK063829, U01DK063790, DK-63829)
- National Institute of Environmental Health Sciences (HHSN267200700014C)
- National Institute of Child Health and Human Development (HHSN267200700014C)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 1 diabetes, TEDDY study, HLA-DRB1*0403, newborn screening, first-degree relatives, genetic risk screening, genotyping accuracy
- MeSH terms
- Diabetes Mellitus, Type 1, Environment, Genotype, Haplotypes, HLA-DR Antigens, Humans, Infant, Infant, Newborn, Quality Control, Risk, Cohort Studies, Neonatal Screening, Genetic Predisposition to Disease
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