Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Sudan

Pediatr Diabetes. 2021 Aug;22(5):749-757. doi: 10.1111/pedi.13209. Epub 2021 Apr 20.

Abstract

Objective: To further understand clinical and biochemical features, and HLA-DRB1 genotypes, in new cases of diabetes in Sudanese children and adolescents.

Research design and methods: Demographic characteristics, clinical information, and biochemical parameters (blood glucose, HbA1c, C-peptide, autoantibodies against glutamic acid decarboxylase 65 [GADA] and insulinoma-associated protein-2 [IA-2A], and HLA-DRB1) were assessed in 99 individuals <18 years, recently (<18 months) clinically diagnosed with T1D. HLA-DRB1 genotypes for 56 of these Arab individuals with T1D were compared to a mixed control group of 198 healthy Arab (75%) and African (25%) individuals without T1D.

Results: Mean ± SD age at diagnosis was 10.1 ± 4.3 years (range 0.7-17.6 years) with mode at 9-12 years. A female preponderance was observed. Fifty-two individuals (55.3%) presented in diabetic ketoacidosis (DKA). Mean ± SD serum fasting C-peptide values were 0.22 ± 0.25 nmol/L (0.66±0.74 ng/ml). 31.3% were autoantibody negative, 53.4% were GADA positive, 27.2% were IA-2A positive, with 12.1% positive for both autoantibodies. Association analysis compared to 198 controls of similar ethnic origin revealed strong locus association with HLA-DRB1 (p < 2.4 × 10-14 ). Five HLA-DRB1 alleles exhibited significant T1D association: three alleles (DRB1*03:01, DRB1*04:02, and DRB1*04:05) were positively associated, while three (DRB1*10:01, DRB1*15:02, and DRB1*15:03) were protective. DRB1*03:01 had the strongest association (odds ratio = 5.04, p = 1.7 × 10-10 ).

Conclusions: Young Sudanese individuals with T1D generally have similar characteristics to reported European-origin T1D populations. However, they have higher rates of DKA and slightly lower autoantibody rates than reported European-origin populations, and a particularly strong association with HLA-DRB1*03:01.

Keywords: C-peptide; HLA; Sudan; autoantibodies; childhood diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age of Onset
  • Autoantibodies / blood
  • Biomarkers / analysis*
  • Biomarkers / blood
  • C-Peptide / blood
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Diabetes Mellitus, Type 1* / blood
  • Diabetes Mellitus, Type 1* / epidemiology
  • Diabetes Mellitus, Type 1* / genetics
  • Diabetes Mellitus, Type 1* / pathology
  • Diabetic Ketoacidosis / epidemiology
  • Diabetic Ketoacidosis / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Glutamate Decarboxylase / immunology
  • HLA-DRB1 Chains / genetics*
  • Humans
  • Infant
  • Male
  • Sudan / epidemiology

Substances

  • Autoantibodies
  • Biomarkers
  • C-Peptide
  • HLA-DRB1 Chains
  • Glutamate Decarboxylase