The following is a summary of “Islet Autoantibody Level Distribution in Type 1 Diabetes and Their Association With Genetic and Clinical Characteristics,” published in the December 2022 issue of Endocrinology & Metabolism by Grace, et al.


It was unclear how significant the autoantibody level was at the time of type 1 diabetes (T1D) diagnosis. For a study, researchers sought to determine the correlation between levels of the autoantibodies against glutamate decarboxylase (GADA), islet antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A) and clinical and genetic features at T1D diagnosis.

A prospective, cross-sectional investigation was carried out. Radiobinding assays were used to evaluate GADA, IA-2A, and ZnT8A in 1,644 T1D patients at the time of diagnosis. In those who tested positive for these autoantibodies, relationships between autoantibody levels and clinical and genetic features for individuals were examined for those who tested positive for these autoantibodies. In addition, they carried out replication in a separate group of 449 T1D patients.

At diagnosis, the levels of GADA and IA-2A showed a bimodal distribution. Age at diagnosis (median 27 years vs 19 years, P = 9 × 10-17), female sex (52% vs 37%, P = 1 × 10-8), other autoimmune illnesses (13% vs 6%, P = 3 × 10-6), and HLA-DR3-DQ2 (58% vs 51%, P =.006) were all related with high GADA levels. Younger diagnostic age (median 17 years vs 23 years, P = 3 × 10-7), HLA-DR4-DQ8 positive (66% vs 50%, P = 1 × 10-6), and ZnT8A positivity (77% vs 52%, P = 1 × 10-15) were all linked with high IA-2A levels. Using enzyme-linked immunosorbent assays to assess autoantibodies in a population of 449 T1D patients, they confirmed our findings.

Islet autoantibody levels offered extra information beyond T1D diagnostic positive. The unique component of the heterogeneity of T1D is highlighted by the bimodality of GADA and IA-2A autoantibody levels. It could have effects on the etiology, diagnosis, and therapy of T1D.

Reference: academic.oup.com/jcem/article/107/12/e4341/6693901