谷氨酸脱羧酶抗体（GADA）的持续存在与成人隐匿性自身免疫性糖尿病的临床特征相关：一项具有 3 年随访的前瞻性研究。
Persistence of glutamic acid decarboxylase antibody (GADA) is associated with clinical characteristics of latent autoimmune diabetes in adults: a prospective study with 3-year follow-up.
机构信息
Institute of Metabolism and Endocrinology, The Second Xiangya Hospital, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, National Clinical Research Centre for Metabolic Diseases, Changsha, Hunan, 410011, China.
出版信息
Diabetes Metab Res Rev. 2016 Sep;32(6):615-22. doi: 10.1002/dmrr.2779. Epub 2016 Mar 3.
BACKGROUND
Latent autoimmune diabetes in adults (LADA) is a form of autoimmune diabetes with heterogeneous features. This study aimed to investigate the persistent status of glutamic acid decarboxylase antibody (GADA) in patients with LADA and its association with clinical characteristics.
METHODS
This 3-year follow-up study enrolled 107 LADA and 40 type 2 diabetes mellitus (T2DM) patients from October 2005 to December 2013. GADA titer, epitopes, and clinical characteristics (including fasting C-peptide and HbA1c ) in LADA patients were assayed annually. The human leukocyte antigen DQ (HLA-DQ) genotypes were also analysed. The relationship between the persistence of GADA and the clinical characteristics was investigated in LADA patients.
RESULTS
After 3-year follow-up, 36.5% (39/107) LADA patients remained GADA positive (persistently positive group), 19.6% (21/107) patients fluctuated positively and negatively (fluctuating group), and 43.9% (47/107) patients became GADA negative, among which 61.7% (29/47) seroconversions occurred within 6 months of follow-up (transiently positive group). The GADA persistently positive group possessed higher titer of GADA than transiently positive group and fluctuant group (all p = 0.000), higher reactivities to middle and C-terminal regions of GAD65 than those in transiently positive group (p = 0.001 and p = 0.000, respectively), and lower baseline fasting C-peptide level than T2DM patients and transiently positive group [415(31-1862) vs 620(220-1658) pmol/L, p = 0.014; and 415(31-1862) vs 705(64-1541) pmol/L, p = 0.017, respectively]. The GADA transiently positive group retained a higher HbA1c level when compared with T2DM patients (p = 0.023). In addition, the three LADA groups shared similar frequencies of HLA-DQ susceptible haplotypes that were higher as compared with T2DM. The GADA persistently positive group had a higher annual declining rate in fasting C-peptide than T2DM patients [-14%(-174-33%) vs -1%(-27-28%), p = 0.007].
CONCLUSION
The LADA patients with GADA transient positivity account for a large proportion, whose clinical characteristics and HLA-DQ haplotypes are different from those of T2DM. The patients with high titer GADA and reactivities to GADA65 middle and C-terminal regions showed a persistent GADA positivity, in which a worse baseline and accelerated decline of β-cell function need early intervention in the practice. Copyright © 2016 John Wiley & Sons, Ltd.
背景
成人隐匿性自身免疫性糖尿病（LADA）是一种具有异质性特征的自身免疫性糖尿病。本研究旨在探讨 LADA 患者谷氨酸脱羧酶抗体（GADA）的持续状态及其与临床特征的关系。
方法
这项为期 3 年的随访研究纳入了 2005 年 10 月至 2013 年 12 月期间的 107 例 LADA 和 40 例 2 型糖尿病（T2DM）患者。每年检测 LADA 患者的 GADA 滴度、表位和临床特征（包括空腹 C 肽和 HbA1c）。还分析了人类白细胞抗原 DQ（HLA-DQ）基因型。在 LADA 患者中，研究了 GADA 持续存在与临床特征之间的关系。
结果
经过 3 年的随访，36.5%（39/107）的 LADA 患者 GADA 持续阳性（持续阳性组），19.6%（21/107）患者 GADA 阳性和阴性波动（波动组），43.9%（47/107）患者 GADA 阴性，其中 61.7%（29/47）在随访 6 个月内发生血清转换（一过性阳性组）。持续阳性组的 GADA 滴度高于一过性阳性组和波动组（均 p=0.000），对 GAD65 中、C 端的反应性高于一过性阳性组（p=0.001 和 p=0.000），空腹 C 肽水平低于 T2DM 患者和一过性阳性组[415（31-1862）比 620（220-1658）pmol/L，p=0.014；和 415（31-1862）比 705（64-1541）pmol/L，p=0.017]。GADA 一过性阳性组的 HbA1c 水平仍高于 T2DM 患者（p=0.023）。此外，三组 LADA 患者共享的 HLA-DQ 易感单倍型频率均高于 T2DM 患者。持续阳性组的空腹 C 肽年下降率高于 T2DM 患者[-14%（-174-33%）比-1%（-27-28%），p=0.007]。
结论
GADA 一过性阳性的 LADA 患者占很大比例，其临床特征和 HLA-DQ 单倍型与 T2DM 不同。高滴度 GADA 和 GAD65 中、C 端反应性的患者表现为 GADA 持续阳性，其基线较差，β细胞功能下降加速，在实践中需要早期干预。版权所有© 2016 约翰威立父子公司。
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