Autoantibodies and HLA class II DR-DQ genotypes in Ugandan children and adolescents with type 1 diabetes mellitus
The aims were to determine the prevalence of autoantibodies in type 1 diabetes mellitus (T1DM) and further to investigate the human leukocyte antigen (HLA) class II DR-DQ genotypes associated with T1DM in Ugandan children and adolescents. Cross-sectional data were collected between January and December 2015 from 85 recently detected T1DM children and adolescents and 79 age-matched healthy controls. We measured serum concentrations of C-peptide, vitamin D, insulin autoantibodies (IAA), zinc transporter family member 8 antibodies (ZnT8-Ab), and glutamic acid decarboxylase autoantibodies (GADA). HLA-DBR1 and HLA-DQB1 typing was performed on EDTA-anticoagulated blood samples. The t test, chi-square test, and univariate logistic test were performed and multivariate logistic regression model fitted to identify associated factors of T1DM. Positive IAA and ZnT8-Ab were significantly higher in T1DM than in controls. GADA showed no difference between TIDM and controls. HLA-DQB1*02, unadjusted odds ratio (UOR) 4.2 (95% CI 1.4–12.7), and HLA-DBR1*04, adjusted odds ratio (AOR) 30.6 (95% CI 5.7–161.7), were significantly associated with T1DM. IAA and ZnT8-Ab are the likely significant positive antibodies in Ugandan children and adolescents with T1DM. The T1DM was associated with HLA-DQB1*02 and HLA-DBR1*04 (HLA-DR3 and HLA-DR4) genotypes.
KeywordsType 1 diabetes Autoantibodies HLA class II Uganda
We would like to acknowledge the contribution of Dr. William Omale, Arua Regional Hospital, for his assistance in organizing the type 1 diabetes clinic in Arua Regional Hospital, Uganda. We also like to thank MBN Clinical Laboratory and St. Francis Hospital, Nsambya, for the kind assistance in handling the laboratory samples and analysis. We thank the World Diabetes Foundation (WDF) and Novo Nordisk Changing Diabetes in Children (CDiC) for funding the type 1 diabetes clinics in Uganda. We wish to thank all the health workers and parents involved in the type 1 diabetes clinics in Uganda.
All the authors, SKB, RW, TPW, and CN, contributed to the design, data collection, data analysis, and writing of the manuscript. All authors: read and approved the final manuscript.
This study was supported by a grant from the Africa Field Epidemiology Network (AFENET). The funds were towards the laboratory costs. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all individual participants included in the study: children aged 8–17 years assented to participate, with parents of children below age of 18 years giving the informed consent. Participants above the age of 18 years were eligible and gave informed consent to participate.
Ethical approval was obtained from St. Francis Hospital, Nsambya and Mulago Hospital Institutional Review Boards/Review Ethical Committees; both of which are accredited by the Uganda National Council of Science and Technology (UNCST). All procedures performed in this study were in accordance with the ethical standards of UNCST and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 5.International Diabetes Federation. IDF diabetes atlas, Seventh edn (Brussels 2015).Google Scholar
- 9.Cook AR. Notes on the diseases met with in Uganda, Central Africa. J Trop Med. 1901;4:175–8.Google Scholar
- 11.World Health Organization. Global report on diabetes. Geneva: World Health Organization; 2016.Google Scholar
- 20.Kantarova D, Vrlik M, Buc M. Genetic determination and immunopathogenesis of type 1 diabetes mellitus in humans. Acta Med Mart. 2012;12:19–31.Google Scholar
- 32.Asanghanwa M, et al. Clinical and biological characteristics of diabetic patients under age 40 in Cameroon: relation to autoantibody status and comparison with Belgian patients. DRCP. 2014;103:97–105.Google Scholar
- 47.Mendivil CO, Toloza FJK, Ricardo-Silgado ML, Morales-Alvarez MC, Mantilla-Rivas JO, Pinzón-Cortés JA, et al. Antibodies against glutamic acid decarboxylase and indices of insulin resistance and insulin secretion in nondiabetic adults: a cross-sectional study. Diabetes Metab Syndr Obes. 2017;10:179–85.CrossRefPubMedPubMedCentralGoogle Scholar
- 49.Lutale, J.J., Thordarson, H., Holm, P.I., Eide, G.E. & Vetvik, K. Islet cell autoantibodies in African patients with type 1 and type 2 diabetes in Dar es Salaam Tanzania: a cross sectional study. J Autoimmune Dis 4, 4 (2007).Google Scholar