Diabetes Center, Shin-Koga Hospital, Kurume, Japan.
Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo, Japan.
J Diabetes Investig. 2021 Apr;12(4):510-515. doi: 10.1111/jdi.13370. Epub 2020 Aug 26.
AIMS/INTRODUCTION: This study aimed to investigate the dynamics associated with autoantibodies to insulinoma-associated antigen-2 (IA-2A) and zinc transporter 8 (ZnT8A) relating to the onset age and disease duration in patients with type 1 diabetes.
Using bridging-type enzyme-linked immunosorbent assay, IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies were evaluated in 269 patients with type 1 diabetes (median onset age 18.2 years, range 0.8-86 years; median diabetes duration 7 years, range 0-58 years). We then compared the prevalence of these autoantibodies among the different age groups, along with the duration of diabetes using the Cochran-Armitage trend test and multivariate logistic regression analysis.
The prevalence of IA-2A, ZnT8A and glutamic acid decarboxylase autoantibodies in patients with duration of ≤3 years was 41.1, 36.7 and 72.2%, respectively, with 80.0% expressing one or more of these autoantibodies. This prevalence declined according to the disease duration (P < 0.005). Both IA-2A and ZnT8A were more frequently observed in younger patients, whereas glutamic acid decarboxylase autoantibodies was more common in older patients. Multivariate logistic regression analysis showed that there was a significant interaction between the onset age and duration of diabetes in patients diagnosed when aged ≤10 years regarding all anti-islet autoantibodies (P < 0.05). However, for patients diagnosed in the middle tertile (aged 11-30 years), the interaction was significant only for ZnT8A, and for those with late-onset diabetes (aged ≥31 years) only for IA-2A.
The current study showed that the rate of disappearance of anti-islet autoantibodies is faster in patients aged ≤10 years, and that even though both proteins are localized in the insulin granule membrane, humoral autoimmunity to IA-2 and ZnT8 differs according to the age of onset.
目的/引言:本研究旨在探讨与 1 型糖尿病患者发病年龄和病程相关的胰岛素瘤相关抗原 2(IA-2A)和锌转运蛋白 8(ZnT8A)自身抗体的动态变化。
使用桥接型酶联免疫吸附试验,评估了 269 例 1 型糖尿病患者(中位发病年龄 18.2 岁,范围 0.8-86 岁;中位糖尿病病程 7 年,范围 0-58 年)的 IA-2A、ZnT8A 和谷氨酸脱羧酶自身抗体。然后,我们使用 Cochran-Armitage 趋势检验和多变量逻辑回归分析比较了不同年龄组之间这些自身抗体的患病率以及糖尿病病程。
病程≤3 年的患者 IA-2A、ZnT8A 和谷氨酸脱羧酶自身抗体的患病率分别为 41.1%、36.7%和 72.2%,80.0%的患者表达一种或多种这些自身抗体。随着病程的延长,这种患病率呈下降趋势(P<0.005)。IA-2A 和 ZnT8A 在年轻患者中更为常见,而谷氨酸脱羧酶自身抗体在老年患者中更为常见。多变量逻辑回归分析显示,在≤10 岁诊断的患者中,发病年龄与糖尿病病程之间存在显著的相互作用,所有胰岛自身抗体的 P 值均<0.05。然而,对于 11-30 岁中 tertile 诊断的患者,这种相互作用仅在 ZnT8A 中显著,而对于≥31 岁发病的患者,仅在 IA-2A 中显著。
本研究表明,≤10 岁的患者胰岛自身抗体消失的速度更快,尽管这两种蛋白都定位于胰岛素颗粒膜上,但针对 IA-2 和 ZnT8 的体液自身免疫反应因发病年龄而异。