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Cited by 41Diabetes and associated disordersGenetic Associations and EpidemiologyDiabetes Management and Research

Type 1 diabetes in Africa: an immunogenetic study in the Amhara of North-West Ethiopia

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Balcha, Shitaye A., Demisse, Abayneh G., Mishra, Rajashree, Vartak, Tanwi, Cousminer, Diana L., Hodge, Kenyaita M., Voight, Benjamin F., Lorenz, Kim +10 more·2020·Diabetologia
DOI 10.1007/s00125-020-05229-xPMC PMC7476916
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Abstract

Aims/hypothesis: We aimed to characterise the immunogenic background of insulin-dependent diabetes in a resource-poor rural African community. The study was initiated because reports of low autoantibody prevalence and phenotypic differences from European-origin cases with type 1 diabetes have raised doubts as to the role of autoimmunity in this and similar populations. Methods: A study of consecutive, unselected cases of recently diagnosed, insulin-dependent diabetes ( n = 236, ≤35 years) and control participants ( n = 200) was carried out in the ethnic Amhara of rural North-West Ethiopia. We assessed their demographic and socioeconomic characteristics, and measured non-fasting C-peptide, diabetes-associated autoantibodies and HLA-DRB1 alleles. Leveraging genome-wide genotyping, we performed both a principal component analysis and, given the relatively modest sample size, a provisional genome-wide association study. Type 1 diabetes genetic risk scores were calculated to compare their genetic background with known European type 1 diabetes determinants. Results: Patients presented with stunted growth and low BMI, and were insulin sensitive; only 15.3% had diabetes onset at ≤15 years. C-peptide levels were low but not absent. With clinical diabetes onset at ≤15, 16–25 and 26–35 years, 86.1%, 59.7% and 50.0% were autoantibody positive, respectively. Most had autoantibodies to GAD (GADA) as a single antibody; the prevalence of positivity for autoantibodies to IA-2 (IA-2A) and ZnT8 (ZnT8A) was low in all age groups. Principal component analysis showed that the Amhara genomes were distinct from modern European and other African genomes. HLA-DRB1*03:01 ( p = 0.0014) and HLA-DRB1*04 ( p = 0.0001) were positively associated with this form of diabetes, while HLA-DRB1*15 was protective ( p < 0.0001). The mean type 1 diabetes genetic risk score (derived from European data) was higher in patients than control participants ( p = 1.60 × 10 −7 ). Interestingly, despite the modest sample size, autoantibody-positive patients revealed evidence of association with SNPs in the well-characterised MHC region, already known to explain half of type 1 diabetes heritability in Europeans. Conclusions/interpretation: The majority of patients with insulin-dependent diabetes in rural North-West Ethiopia have the immunogenetic characteristics of autoimmune type 1 diabetes. Phenotypic differences between type 1 diabetes in rural North-West Ethiopia and the industrialised world remain unexplained.

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  • The prevalence of several autoantibodies associated with type 1 diabetes mellitus tends to decrease with increasing age at diagnosis, but glutamic acid decarboxylase antibody remains the dominant autoantibody in adult-onset type 1 diabetes mellitus regardless of ethnicity.

    “Although the prevalence of several autoantibodies associated with T1DM tends to decrease with increasing age at diagnosis61, GADA remains the dominant autoantibody in adult-onset T1DM regardless of ethnicity62–64.”

    From The epidemiology of type 1 diabetes mellitus in older adults (2025) · cites this paper as [63]

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Authors
Balcha, S. A., Demisse, A. G., Mishra, R., Vartak, T., Cousminer, D. L., Hodge, K. M., Voight, B. F., Lorenz, K., Schwartz, S., Jerram, S. T., Gamper, A., Holmes, A., Wilson, H. F., Williams, A. J. K., Grant, S. F. A., Leslie, R. D., Phillips, D. I. W., & Trimble, E. R.
Affiliations
  • University of Gondar (ET)
  • Children's Hospital of Philadelphia (US)
  • Queen Mary University of London (GB)
  • University of Pennsylvania (US)
  • Main Line Health (US)
  • Health Education England (GB)
  • Avon and Wiltshire Mental Health Partnership NHS Trust (GB)
  • Southmead Hospital (GB)
  • Southampton General Hospital (GB)
  • Queen's University Belfast (GB)
Corresponding author
Trimble, Elisabeth R.
ORCID
Venue
Diabetologia
Publisher
Springer Science and Business Media LLC
Published
2020-07-23
Volume
63
Issue
10
Pages
2158-2168
ISSN
  • 0012-186X (ISSN-L)
  • 1432-0428
DOI
10.1007/s00125-020-05229-x
PMC
PMC7476916
OpenAlex
W3044203149
Cited by
41
References
5
Citations by year
2026: 5 · 2025: 13 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 7
FWCI
2.49
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetologia (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Portal (Queen's University Belfast) (publishedVersion, cc-by)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Explore Bristol Research (acceptedVersion, cc-by)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by)
Funders
  • Association of Physicians of Great Britain and Ireland (?)
  • British Diabetic Twin Trust (?)
  • NIH (NIH 1 K((HD099330-01)
  • Type 1 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
Amhara, HLA-DRB1, autoantibodies, glutamic acid decarboxylase antibodies, C-peptide, polygenic risk score, MHC region, genetic ancestry, autoimmunity, growth arrest, age of onset, HLA-DRB1*0301, HLA-DRB1*15
MeSH terms
Zinc Transporter 8, Adolescent, Adult, Autoantibodies, C-Peptide, Child, Diabetes Mellitus, Type 1, Ethiopia, Female, Humans, Male, Age of Onset, Principal Component Analysis, Black People, Genome-Wide Association Study, Young Adult, HLA-DRB1 Chains

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