Open AccessZinc transporter 8 autoantibodies complement glutamic acid decarboxylase and insulinoma‐associated antigen‐2 autoantibodies in the identification and characterization of Japanese type 1 diabetes
Author(s) -
Kawasaki Eiji,
Oikawa Yoichi,
Okada Akira,
Kanatsuorio,
Kawamura Tomoyuki,
Kikuchi Tadashi,
Terasaki Jungo,
Miura Junnosuke,
Ito Yoshihisa,
Hanafusa Toshiaki
Publication year - 2020
Publication title -
journal of diabetes investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.089
H-Index - 50
eISSN - 2040-1124
pISSN - 2040-1116
DOI - 10.1111/jdi.13251
Subject(s) - medicine , autoantibody , type 1 diabetes , type 2 diabetes , diabetes mellitus , glutamate decarboxylase , cohort , gastroenterology , insulinoma , endocrinology , insulin , immunology , antibody , biology , enzyme , biochemistry
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.