Diabetes Center, Shin-Koga Hospital, Kurume, Japan.
Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan.
J Diabetes Investig. 2020 Sep;11(5):1181-1187. doi: 10.1111/jdi.13251. Epub 2020 Apr 22.
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.
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.
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.
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.
目的/引言：本研究旨在探讨锌转运体 8 自身抗体（ZnT8A）在鉴定和描述日本人群自身免疫性 1 型糖尿病中的意义。
采用桥联酶联免疫吸附试验测定 324 例 1 型糖尿病患者、191 例表型 2 型糖尿病患者和 288 例健康对照者的 ZnT8A，以及谷氨酸脱羧酶自身抗体和胰岛细胞抗原 2 自身抗体。
我们设定了 10.0 U/mL 的截断值，25%的 1 型糖尿病患者 ZnT8A 水平超过此水平。急性起病的 1 型糖尿病患者的 ZnT8A 患病率显著高于缓慢进展和暴发性 1 型糖尿病患者（P < 0.05）。ZnT8A 在≤10 岁的患者中更为常见，但在≥5 年病程的患者中较少见（P < 0.05）。表型 2 型糖尿病患者中有 5.2%检测到 ZnT8A，其中 90%为 ZnT8A 单阳性。此外，表型 2 型糖尿病患者的 ZnT8A 水平（143.8 ± 194.9 U/mL）显著高于 1 型糖尿病患者（22.9 ± 8.3 U/mL，P < 0.05）。在≤5 年病程的急性起病和缓慢进展的 1 型糖尿病患者中，谷氨酸脱羧酶自身抗体的额外检测显著提高了≤10 岁患者的疾病敏感性，但对≥11 岁患者则不然（11.7%对 3.6%，P < 0.05）。多变量分析显示，ZnT8A 阳性与采样时的年龄和胰岛细胞抗原 2 自身抗体阳性独立相关。
这些结果表明，桥联型 ZnT8A 酶联免疫吸附试验可能为日本 1 型糖尿病患者提供有价值的附加标志物，从而增加可识别病例的数量，并区分临床表型。
