2型糖尿病合并外源性胰岛素抗体综合征的临床、遗传和蛋白质组学特征：一项病例对照研究

IF 6.1 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes research and clinical practice Pub Date : 2025-05-20 DOI:10.1016/j.diabres.2025.112262

Jinjing Wan , Leiluo Geng , Yiwen Fu , Qianting Zhang , Gaopeng Guan , Xue Jiang , Aimin Xu , Ping Jin

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引用次数: 0

摘要

胰岛素抗体（IAs）在胰岛素治疗的糖尿病患者中普遍存在，并可能导致免疫性血糖异常，即外源性胰岛素抗体综合征（EIAS）。本研究旨在阐明并发2型糖尿病（T2D）和EIAS患者的临床、遗传和蛋白质组学特征。方法对177例ia阳性和177例ia阴性t2dm患者进行胰岛素治疗的病例对照研究。在ia阳性组中，46例患者出现低血糖及胰岛素与c肽摩尔比(ICPR >；1)经确诊为EIAS病例，采用Olink平台进行人白细胞抗原（HLA）基因分型和血浆蛋白质组学分析。结果EIAS患者的血糖变异性高于其他组（ia阳性ICPR≤1或ia阴性）。在ia阳性组中，较高的ICPR与血糖变异性增加相关。DRB1*0405-DQA1*03-DQB1*0401、DRB1*0803-DQA1*0103-DQB1*0601、DRB1*1501-DQA1*0102-DQB1*0502为易感HLA单倍型。此外，在EIAS患者中鉴定出9种差异表达蛋白，其中GALNT3、IL10和CCL28显示出有希望的诊断性能。结论sia阳性且ICPR显著升高的患者易发生血糖变异性，应作为诊断EIAS的依据。在这项样本量有限的初步研究中，EIAS与独特的HLA-DR-DQ风险单倍型和增强的免疫炎症反应相关。

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Clinical, genetic, and proteomic characteristics of type 2 diabetes complicated with exogenous insulin antibody syndrome: a case-control study

Aims

Insulin antibodies (IAs) are prevalent in insulin-treated patients with diabetes and may cause immunological dysglycemia, known as exogenous insulin antibody syndrome (EIAS). This study aims to elucidate the clinical, genetic, and proteomic characteristics of patients with concurrent type 2 diabetes (T2D) and EIAS.

Methods

This was a case-control study with 177 IA-positive and 177 IA-negative T2D patients receiving insulin therapy. Among the IA-positive group, 46 patients with hypoglycemia and aberrantly elevated molar ratio of insulin to C-peptide (ICPR > 1) were identified as EIAS cases, followed with human leukocyte antigen (HLA) genotyping and plasma proteomic analysis by Olink platform.

Results

Patients with EIAS exhibited greater glycemic variability than patients in other groups (IA-positive ICPR ≤ 1 or IA-negative). Higher ICPR was associated with increased glycemic variability in the IA-positive group. DRB1*0405-DQA1*03-DQB1*0401, DRB1*0803-DQA1*0103-DQB1*0601, and DRB1*1501-DQA1*0102-DQB1*0502 are the susceptible HLA haplotypes for EIAS. Additionally, nine differentially expressed proteins were identified in EIAS patients, with GALNT3, IL10, and CCL28 showing promising diagnostic performance.

Conclusions

IA-positive patients with remarkably elevated ICPR are prone to glycemic variability and should be evaluated for the diagnosis of EIAS. In this pilot study with limited sample size, EIAS is associated with unique HLA-DR-DQ risk haplotypes and enhanced immunoinflammatory response.

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来源期刊

Diabetes research and clinical practice 医学-内分泌学与代谢

CiteScore

10.30

自引率

3.90%

发文量

862

审稿时长

32 days

期刊介绍： Diabetes Research and Clinical Practice is an international journal for health-care providers and clinically oriented researchers that publishes high-quality original research articles and expert reviews in diabetes and related areas. The role of the journal is to provide a venue for dissemination of knowledge and discussion of topics related to diabetes clinical research and patient care. Topics of focus include translational science, genetics, immunology, nutrition, psychosocial research, epidemiology, prevention, socio-economic research, complications, new treatments, technologies and therapy.