Aim
To study whether DPD epitope‐specific glutamate decarboxylase autoantibodies are found more frequently in children with milder forms of Type 1 diabetes.
Methods
We prospectively evaluated 75 children with new‐onset autoimmune Type 1 diabetes, in whom we collected demographic, anthropometric and clinical data and measured islet autoantibodies. Glutamate decarboxylase 65 autoantibody‐positive samples were analysed for epitope specificities using recombinant Fab against the DPD‐defined epitope of glutamate decarboxylase 65.
Results
After adjustment for age, positive DPD epitope recognition was significantly associated with higher C‐peptide levels at onset (P = 0.02, r2=0.21, n = 35), and high DPD recognition in the highest quartile tended to be associated with HbA1c ≤ 53 mmol/mol (7%) at the last follow‐up [mean (sd) follow‐up 1.3 (0.4) years; P = 0.07; for the model, P = 0.044, n = 30)]. Age‐ and sex‐adjusted BMI percentile was significantly correlated with recognition of the DPD‐defined epitope (P < 0.03, r2=0.14, n = 34), but this correlation was driven by the older age group (age ≥ 10 years; P = 0.016, r2=0.27, n = 21) and was not significant in younger children (P = 0.93, n = 13). There were no independent associations with sex, race/ethnicity, diabetic ketoacidosis, HbA1c, HLA DR3‐DQ2/DR4‐DQ8 or autoantibody number.
Conclusions
Our findings suggest that recognition of the DPD‐defined glutamate decarboxylase 65 autoantibody epitope at Type 1 diabetes onset is directly associated with β‐cell function, BMI and age, which supports the hypothesis that immunological factors contribute to the clinical heterogeneity of Type 1 diabetes. Larger studies relating epitope‐specific glutamate decarboxylase 65 autoantibody to clinical phenotype in children with Type 1 diabetes are warranted.