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谷氨酸脱羧酶自身抗体酶联免疫吸附试验阳性、缓慢进展的 1 型糖尿病患者未来发生胰岛素缺乏的预测。

Prediction of future insulin-deficiency in glutamic acid decarboxylase autoantibody enzyme-linked immunosorbent assay-positive patients with slowly-progressive type 1 diabetes.

机构信息

Diabetes Center, Shin-Koga Hospital, Kurume, Japan.

Pancreatic Islet Cell Transplantation Center, National Center for Global Health and Medicine, Tokyo, Japan.

出版信息

J Diabetes Investig. 2024 Jul;15(7):835-842. doi: 10.1111/jdi.14178. Epub 2024 Mar 7.

Abstract

AIMS/INTRODUCTION: This study aimed to identify risk factors that contribute to the progression of slowly-progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin-dependent state.

MATERIALS AND METHODS

We selected 60 slowly-progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) techniques.

RESULTS

Compared with the non-progressor group (fasting C-peptide [F-CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F-CPR levels and a higher prevalence of insulinoma-associated antigen-2 autoantibodies (IA-2A). The PPV of RIA-GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis <47 years, BMI <22.6 kg/m, F-CPR <1.41 ng/mL and IA-2A positivity, respectively. In contrast, the PPV of ELISA-GADA (71.8%) remained the same at 73.1% in the high titer group (≥180 U/mL), but increased to 81.8, 82.4 and 79.0% when evaluated in conjunction with age at diagnosis, BMI and F-CPR level, respectively.

CONCLUSIONS

Our findings show that, unlike RIA-GADA, ELISA-GADA shows no association between GADA titers and the risk of progression to an insulin-dependent state. The PPV improves when age at diagnosis, BMI and F-CPR levels are considered in combination.

摘要

目的/引言:本研究旨在通过评估与进展为胰岛素依赖状态相关的因素的阳性预测值(PPV),来确定导致缓慢进展 1 型糖尿病进展的危险因素。

材料和方法

我们从日本 1 型糖尿病数据库研究中选择了 60 名在诊断时谷氨酸脱羧酶自身抗体(GADA)检测呈阳性的缓慢进展 1 型糖尿病患者。使用放射免疫分析(RIA)和酶联免疫吸附测定(ELISA)技术同时测量这些患者的 GADA 水平。

结果

与非进展组(空腹 C 肽[F-CPR]水平保持≥0.6ng/mL)相比,进展组患者的诊断年龄较小,体重指数(BMI)较低,F-CPR 水平较低,胰岛素瘤相关抗原-2 自身抗体(IA-2A)的患病率较高。RIA-GADA 的 PPV 从高滴度组(≥10U/mL)的 56.3%增加到 70.0%,当与特定的诊断年龄<47 岁、BMI<22.6kg/m、F-CPR<1.41ng/mL 和 IA-2A 阳性的阈值相结合时,进一步增加到 76.9%、84.2%、81.0%和 75.0%。相比之下,高滴度组(≥180U/mL)的 ELISA-GADA 的 PPV(71.8%)保持在 73.1%不变,但当与诊断年龄、BMI 和 F-CPR 水平相结合评估时,PPV 增加到 81.8%、82.4%和 79.0%。

结论

我们的研究结果表明,与 RIA-GADA 不同,ELISA-GADA 显示 GADA 滴度与进展为胰岛素依赖状态的风险之间没有关联。当综合考虑诊断年龄、BMI 和 F-CPR 水平时,PPV 会提高。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7df1/11215668/a1127cd33e56/JDI-15-835-g003.jpg

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