Heterogeneity of young patients with new-onset diabetes mellitus

The clinical phenotype of diabetes differs among newly-diagnosed children and adolescents. In this study, we asked whether heterogeneity in immunopathology, reflected by different autoantibody profiles, is associated with clinical phenotypes.

971 patients with new-onset diabetes, aged < 20 years were clustered according to type 1 diabetes-associated autoantibody profiles (IAA, GADA, IA-2A, ZnT8A) and analyzed with respect to clinical phenotype.

Patients presented with all possible autoantibody combinations with varying frequencies ranging from 2% (single IA-2A positive) to 30% (four autoantibodies). 62% had three/four, 22% two, and 11% one autoantibody. 49 patients (5%) were autoantibody-negative. Multiple and single autoantibody-positive patients had a similar age at onset (median, 10.1 vs. 10.5 years) and similar BMI (median, 15.2 vs. 15.9 kg/m²). Autoantibody-negative patients were older (13.5 years, p < 0.0001) and had a higher BMI (20.3 kg/m², p < 0.0001). Median HbA1c was 11.0 vs. 10.9% in multiple vs. single autoantibody-positive patients and 10.8% in autoantibody-negative patients. Median fasting C-peptide was 0.4 mg/dl for both multiple and single autoantibody-positive patients and 0.9 mg/dl (p < 0.0001) for autoantibody-negative patients. IAA-positive patients were younger (9.4 vs. 11.6 years, p < 0.0001), had lower BMI (15.7 vs. 16.3 kg/m², p = 0.008), lower Hba1C (10.8 vs. 11.7% p < 0.001) and similar fasting C-peptide (0.3 vs. 0.4 mg/dl) compared to IAA-negative patients who had other autoantibodies. No significant difference was observed for gender and HLA DR-DQ genotypes between IAA-positive and IAA-negative patients, and neither between any of the autoantibody clusters.

The clinical phenotype of newly-diagnosed diabetes in young patients is associated with positive/negative autoantibody status and with autoantibody profile.