Zinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma-associated antigen-2 autoantibodies in the identification and characterization of Japanese type 1 diabetes

Abstract

Aims/Introduction: This study aimed to investigate the significance of zinc transporter 8 autoantibody (ZnT8A) in identifying and characterizing autoimmune-mediated type 1 diabetes in Japanese individuals. Methods: ZnT8A were determined in 324 patients with type 1 diabetes, 191 phenotypic type 2 diabetes and 288 healthy control individuals using bridging-type enzyme-linked immunosorbent assay in addition to autoantibodies to glutamic acid decarboxylase and insulinoma-associated antigen-2. Results: We set a cut-off value of 10.0 U/mL, and 25% of the type 1 diabetic patients had ZnT8A levels exceeding this level. The prevalence of ZnT8A was significantly higher in patients with acute-onset type 1 diabetes than in those with slowly progressive and fulminant type 1 diabetes (P < 0.05). ZnT8A were more frequent in patients aged ≤10 years, but less frequent in patients with duration ≥5 years (P < 0.05). ZnT8A were detected in 5.2% of phenotypic type 2 diabetic patients, with 90% of these being ZnT8A-single-positive. Furthermore, the ZnT8A levels in the phenotypic type 2 diabetes cohort (143.8 ± 194.9 U/mL) were significantly higher than those in the type 1 diabetes cohort (22.9 ± 8.3 U/mL, P < 0.05). In the acute-onset and slowly progressive type 1 diabetic patients with duration ≤5 years, additional measurement of glutamic acid decarboxylase autoantibodies significantly increased the disease sensitivity in patients aged ≤10 years, but not in patients aged ≥11 years (11.7 vs 3.6%, P < 0.05). Multivariate analysis showed that ZnT8A positivity was independently associated with age at sampling and insulinoma-associated antigen-2 autoantibody positivity. Conclusions: These results suggest that the bridging-type ZnT8A enzyme-linked immunosorbent assay might provide a valuable additional marker for Japanese patients with type 1 diabetes, which could, in turn, allow for an increase in the number of identifiable cases and differentiate clinical phenotypes.