- Ibrahim, Tomader Ali Mohammed;
- Govender, Denira;
- Abdullah, Mohamed Ahmed;
- Noble, Janelle Annette;
- Hussien, Mohammed Osman;
- Lane, Julie Ann;
- Mack, Steven John;
- Martin, Gregory George Noble;
- Atkinson, Mark Alvin;
- Wasserfall, Clive Henry;
- Ogle, Graham David
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.