Clinical Features and HLA Genetics Differ in Children at Type 1 Diabetes Onset by Hispanic Ethnicity

Abstract

Context: Type 1 diabetes incidence continues to increase in children, especially among Hispanic White (HW) children.

Objective: We investigated the clinical, immunologic, and genetic characteristics of HW and non-Hispanic White (NHW) children who presented at type 1 diabetes diagnosis.

Methods: In this single-center, observational study, children who were diagnosed with type 1 diabetes (≤20 years old) and tested for islet autoantibodies within 1 year of diagnosis were included in the study and divided into 2 groups by Hispanic ethnicity.

Results: Of 1297 children, 398 HW children presented with a younger age at diabetes onset (10.2 ± 3.9 vs 11.1 ± 4.1 years, P < .001) and more diabetic ketoacidosis (62.4% vs 51.9%, P < .001) than NHW children (n = 899). There was no difference in sex, A1c levels, or the number and prevalence of islet autoantibodies between the 2 cohorts. A subset of our cohort was human leukocyte antigen (HLA) typed as specific alleles confer strong genetic risk for type 1 diabetes (eg, HLA-DR4 and DQ8). Among 637 HLA-typed children, HW children had a significantly higher prevalence of the DR4-DQ8 haplotype than NHW children (79.1% vs 60.1%, P < .001), and this frequency was much higher than a reference Hispanic population (OR 6.5, 95% CI 4.6-9.3).

Conclusion: Hispanic White children developing type 1 diabetes have a high prevalence of HLA DR4-DQ8, which can be utilized to select individuals for immune monitoring with islet autoantibodies to lessen diabetic ketoacidosis and potentially prevent diabetes onset.

Keywords: HLA genetics; Hispanic; diabetic ketoacidosis; ethnicity; islet autoantibodies; type 1 diabetes.