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

Abstract

Published information on diabetes in Pakistani youth is limited. We aimed to investigate the demographic, clinical, and biochemical features, and HLA-DRB1 alleles in new cases of diabetes affecting children and adolescents <22 years of age. The study was conducted at Baqai Institute of Diabetology and Endocrinology in Karachi from June 2013-December 2015. One hundred subjects aged <22 years at diagnosis were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase 65 (GAD65) and islet antigen 2 (IA-2) autoantibodies) were measured. DNA from 100 subjects and 200 controls was extracted and genotyped for HLA-DRB1 using high-resolution genotyping technology. Ninety-nine subjects were clinically diagnosed as type 1 diabetes (T1D) and one as type 2 diabetes (T2D). Of the 99 with T1D, 57 (57.6%) were males and 42 (42.4%) females, with mean age at diagnosis 11.0 ± 5.2 years (range 1.6-21.7 years) and peaks at six and fifteen years. Fifty-seven subjects were assessed within one month of diagnosis and all within eleven months. For the subjects diagnosed as T1D, mean C-peptide was 0.63 ± 0.51 nmol/L (1.91 ± 1.53 ng/mL), with 16 (16.2%) IA2 positive, 53 (53.5%) GAD-65 positive, and 10 (10.1%) positive for both autoantibodies. In T1D patients, the allele DRB1*03:01 demonstrated highly significant T1D association (p < 10^-16), with no apparent risk conferred by DRB1*04:xx alleles. CONCLUSIONS: Heterogeneous forms of T1D appear more common in children and youth in Pakistan than in European populations. Individual understanding of such cases could enable improved management strategies and healthier outcomes.

Keywords: Autoantibody; C-peptide; Childhood diabetes; HLA; Pakistan.

Figure 1.

The age of onset of T1D in young people <22 years of age in Pakistan.