The rising incidence of childhood type 1 diabetes and reduced contribution of high-risk HLA haplotypes
Open accessAbstract
The incidence of childhood type 1 diabetes has risen over the past 50 years. We compared the frequency of HLA class II haplotypes in 194 patients diagnosed more than 50 years ago and 582 age-matched and sex-matched individuals diagnosed between 1985 and 2002. The proportion of high-risk susceptibility genotypes was increased in the earlier cohort (p=0.003), especially in those diagnosed at age 5 years or younger, which is consistent with the hypothesis that the rise of type 1 diabetes is due to a major environmental effect.
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Genetic predisposition seems to be less of a factor now than it was in the past as a prerequisite for developing type 1 diabetes.
“Finally, genetic predisposition seems to be less of a factor now than it was in the past as a prerequisite for developing type 1 diabetes.23,24”
From Type 1 diabetes (2014) · cites this paper as [23]
Recent studies show that environmental factors have a stronger effect on individuals with lower-risk genotypes than on those at higher genetic risk.
“Furthermore, they note recent studies17–19 demonstrate environmental factors have a stronger effect on individuals with lower risk genotypes as compared to those at higher risk genetically.”
From Epidemiology of type 1 diabetes (2010) · cites this paper as [19]
Reports suggest a recent temporal trend of fewer high-risk HLA genotypes in youth diagnosed with type 1 diabetes, suggesting an increased influence of environmental factors during recent decades.
“A number of reports suggest a recent temporal trend of fewer high-risk HLA genotypes in youth diagnosed with T1D, suggesting an increased influence of environmental factors in the development of T1D during the past few decades19,44,45.”
From Epidemiology of type 1 diabetes (2010) · cites this paper as [19]
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Hänninen, A. L. M., Nurmela, R., Maksimow, M., Heino, J., Jalkanen, S., & Kurts, C. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.060142 · Cited by 52 · see citing works
Autoimmunity and the pathogenesis of type 1 diabetes
Csorba, T. R., Lyon, A. W., & Hollenberg, M. D. (2010) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408361003787171 · Cited by 52 · see citing works
Diabetes: 1 and 2, or one and the same? Progress with the accelerator hypothesis
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Type 1 diabetes mellitus and multiple sclerosis: common etiological features
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Self-citationHigher abundance of enterovirus A species in the gut of children with islet autoimmunity
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Causes of early-onset type 1 diabetes: toward data-driven environmental approaches
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Is the Risk and Nature of CVD the Same in Type 1 and Type 2 Diabetes?
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- Authors
- Gillespie, K. M., Bain, S. C., Barnett, A. H., Bingley, P. J., Christie, M. R., Gill, G. V., & Gale, E. A.
- Affiliations
- University of Bristol (GB)
- Heartlands Hospital (GB)
- King's College Hospital (GB)
- University of Liverpool (GB)
- Corresponding author
- Gale, Edwin AM
- Venue
- The Lancet
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 364
- Issue
- 9446
- Pages
- 1699-1700
- ISSN
- 0099-5355 (ISSN-L)
- 0140-6736
- OpenAlex
- W2097150236
- Cited by
- 304
- References
- 9
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 7 · 2021: 11 · 2020: 8 · 2019: 10 · 2018: 11 · 2017: 16 · 2016: 11 · 2015: 15 · 2014: 18 · 2013: 18 · 2012: 20
- FWCI
- 7.65
- Type
- journal article
- Language
- en
- Open access
- green
- figshare.com
- Licence
- Locations
- The Lancet (publishedVersion)
- PubMed (publishedVersion)
- Lincoln Repository (University of Lincoln) (acceptedVersion)
- Figshare (submittedVersion, cc-by)
- Research Portal (King's College London) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Diabetes UK
- 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 in children, incidence trends, HLA class II haplotypes, HLA-DQ, HLA-DR, genetic susceptibility, environmental factors, age of onset, genetic epidemiology
- MeSH terms
- Adolescent, Histocompatibility Antigens Class II, Child, Child, Preschool, Diabetes Mellitus, Type 1, Genotype, Haplotypes, HLA-DQ Antigens, HLA-DR Antigens, Humans, Risk, Incidence, Age of Onset, Genetic Predisposition to Disease, HLA-DRB1 Chains, HLA-DQ alpha-Chains, HLA-DQ beta-Chains
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