Pattern and Persistence of Islet Autoantibodies and their Immunogenetic Association among Type 1 Diabetes Patients...

To determine the prevalence and persistence of islet autoantibodies and explore their HLA associations among patients with type 1 diabetes (T1DM).

Islet autoantibodies (GAD-65A, IA-2A, and ZnT8A) and fasting C-peptide (FCP) levels were assessed at baseline (prevalence) and 2-5 y, 5-10 y, and > 10 y from the baseline (persistence). HLA associations were evaluated for individual islet autoantibodies and their persistence.

The authors evaluated 366 participants with a median diabetes duration of 6 y at baseline. The overall positivity for any of the three autoantibodies was 67.5%, which increased to 76% in a subset of patients (n = 125) with diabetes duration ≤ 2 y. In the persistence analysis, positivity for IA-2A and ZnT8A declined earlier compared to GAD-65A (median survival times of 11, 12, and 31 y). The median survival time for FCP (time to undetectable levels) was 5 y, with significantly shorter survival in individuals with younger (< 10 y) age at diagnosis and in the autoantibody-positive group. The HLA-DRB1*03 allele was significantly associated with the GAD-65A, and the HLA-DRB1*04 allele with the ZnT8A. There was no association of HLA-DRB1 status with islet autoantibody persistence.

Nearly two in every three patients evaluated at a median disease duration of 6 y tested positive for one or more islet autoantibodies. GAD-65A was more prevalent and relatively stable over time, serving as a robust diagnostic marker for T1DM. A more rapid decline in beta cell reserve was noted in individuals with younger age at diagnosis and islet autoantibody positivity.