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Heterogeneity of Type I diabetes: analysis of monozygotic twins in Great Britain and the United States
Open accessAbstract
Aims To determine the risk, hazard rate and factors affecting progression to diabetes in monozygotic twins of patients with Type I (insulin-dependent) diabetes mellitus.Methods Prospective analysis was done of two cohorts of non-diabetic monozygotic twins of patients with Type I diabetes from Great Britain (n = 134) and the United States (n = 53).Results The diabetes-free survival analysis was similar between both cohorts (p = 0.6). The combined survival analysis (n = 187, median follow-up = 17.7 years, range = 0.01-57) at 40 years of discordance estimated a 39% probability of diabetes for the initially discordant twin. Survival analysis with left truncation of data estimated that probability to be 50%. For twins who became concordant (n = 47), the median discordance time was 4.2 years (range 0.4 to 39), exceeding 15 years in 23.4%. Twins of probands diagnosed at 24 years of age or younger had a 38% probability of diabetes by 30 years of discordance, compared with 6% for twins of probands diagnosed after 24 years of age (p = 0.004). The twins of probands diagnosed before 15 years of age had the highest diabetes hazard rate in the first discordance year, decreasing thereafter. By survival analysis, diabetes risk was higher in twins who were heterozygous for DR3-DQ2 and DR4-DQ8 than in twins with neither DR3-DQ2 nor DR4-DQ8 (p < 0.05).Conclusion/interpretation Monozygotic twins of patients with Type I diabetes from two different countries had similar rates of progression to diabetes. Whereas most twins did not develop diabetes, 25% of the twins who progressed did so after more than 14 years of discordance. An age-related heterogeneity was observed, with higher progression to diabetes for twins of patients diagnosed at a younger age.
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“Evidence suggests that, compared with childhood-onset T1DM, adult-onset (ages ≥18 years) disease has a lower frequency of high-risk HLA types54, lower concordance rates in twins55, more protective genotypes56, lower genetic risk scores57 and lower overall genetic load (with minor differences in HLA class II gene associations)56.”
From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [55]
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“Monozygotic twins have a concordance rate of > 60% if followed long enough47 whereas dizygotic twins have a concordance rate of 6% to 10%.”
From Epidemiology of type 1 diabetes (2010) · cites this paper as [47]
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Metadata
- Authors
- Redondo, M. J., Yu, L., Hawa, M., Mackenzie, T., Pyke, D. A., Eisenbarth, G. S., & Leslie, R. D. G.
- Affiliations
- University of Colorado Health (US)
- St Bartholomew's Hospital (GB)
- University of Colorado Denver (US)
- Venue
- Diabetologia
- Published
- 2001-03-09
- Volume
- 44
- Issue
- 3
- Pages
- 354-362
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W1985484102
- Cited by
- 322
- References
- 27
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 16 · 2022: 8 · 2021: 15 · 2020: 15 · 2019: 14 · 2018: 15 · 2017: 14 · 2016: 13 · 2015: 13 · 2014: 8 · 2013: 15 · 2012: 9
- FWCI
- 8.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 32083-16)
- 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, monozygotic twins, discordant twins, disease progression, diabetes risk, age at diagnosis, HLA-DR3-DQ2, HLA-DR4-DQ8, HLA heterozygosity, twin concordance
- MeSH terms
- Adolescent, Adult, Aged, Child, Child, Preschool, Diabetes Mellitus, Type 1, Diseases in Twins, Female, United Kingdom, Histocompatibility Testing, Humans, Infant, Male, Middle Aged, Polymorphism, Genetic, Time Factors, Twins, Monozygotic, United States, Proportional Hazards Models, Age of Onset, Disease-Free Survival, Microsatellite Repeats
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