C-Peptide Concentrations and Hla Drb1 Expression in Children and Adolescents with Type 1 Diabetes Mellitus Attending Nsambya Hospital

Abstract

ABSTRACT

Globally, it is estimated that 497,100 children under 15 years have type 1diabetes (T1D) with 79,100 newly diagnosed cases annually and an annual increase in incidence of 3%. Uganda has an estimate of 900 children less than 15 years with T1D. In most clinical settings, the clinical characteristics form the cornerstone of the classification of diabetes. This may lead to inaccurate classification. C-peptide may be used as an adjunct to characteristics to improve classification. In T1D, both environment and genetic susceptibility, in particular human leucocyte antigens (HLA), are involved in the pathogenesis of the disease. HLA DRB1 alleles predispose to T1D of which DRB1*03 or DRB1*04 have the highest susceptibility. Ninety percent (90%) of patients with T1D have at least one of the high risk alleles DRB1*03 or DRB1*04. In Uganda, there is no published data on the C-peptide concentrations and HLA DRB1 alleles in the children being managed as T1D

To determine C-peptide concentrations and the prevalence of HLA DRB1 alleles in children and adolescents being managed as T1D in Nsambya Hospital Paediatric Diabetes clinic

A cross sectional study was conducted at the Nsambya Hospital Paediatric Diabetes Clinic from January 2014 to May 2014.Participants for the study were identified using database of the electronic health records of the clinic. Patients managed as type 1 diabetes aged 1 – 19 years were enrolled into the study after signing the informed consent (and assent as appropriate). Data was collected using a structured questionnaire. Blood samples were taken for C-peptide and HLA DRB1 assays. Data was entered into a computer using Epidata v3.1 and analysed using Stata v11.0/IC software package

Seventy nine (79) participants were enrolled into the study. The mean ±Standard Error of Mean (SEM) of C-peptide concentration was 0.186±0.034ng/ml (range 0-1.9ng/ml). Six percent (6%) of the participants had undetectable C-peptide, 86% had a low C-peptide and 8% had normal concentrations of C-peptide. Twelve (12) HLA DRB1 alleles were identified from these participants. The prevalence of DRB1*03 was 55.7% (44/79) and DRB1*04 at 32.9% (26/79). The prevalence of DRB1*13 was 22.8% (18/79), DRB1*11 was 17.7% (14/79), DRB1*09 was 16.5% (13/79), DRB1*07 was 12.7% (10/79) and DRB1*15 at 10.1%(8/79). The least found alleles were DRB1*08, DRB1*10, DRB1*12 and DRB1*16 at 1.3%, 1.3%, 3.8% and 3.8% respectively. The prevalence of having the high risk alleles DRB1*03 or DRB1*04 was 88.6% (70/79)

92% of the patients who were being managed as T1D in the clinic had low or undetectable C-peptide suggesting a good correlation between classification based on clinical criteria and classic low C-peptide type 1 diabetes. DRB1*03, DRB1*04 and DRB1*13 were the most frequent HLA DRB1 alleles at 55.7%, 32.9% and 22.8% respectively and DRB1*08, DRB1*10,DRB1*12 and DRB1*16 were the least found. The prevalence of the high risk alleles DRB1*03 and DBR1*04 was high at 88.6%

In low resource settings where C-peptide test cannot be done routinely, use of clinical criteria is sufficient to classify diabetes and can continue to be used as a preferred method for classification. A case control study should be carried out to study the susceptibility of the HLA DRB1 alleles in the Ugandan population.

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