Exogenous insulin-associated autoimmunity and the emergence of double diabetes in type 2 diabetes.

IF 4.6 3区医学 Q1 ENDOCRINOLOGY & METABOLISM

World Journal of Diabetes Pub Date : 2025-09-15 DOI:10.4239/wjd.v16.i9.109130

Xin-Gang Li, Meng-Ya Qi, Xiang Li, Fan Ping

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Abstract

Background: Exogenous insulin may trigger immune-mediated complications, particularly among East Asian populations. Double diabetes, characterized by overlapping features of type 1 diabetes (T1D) and type 2 diabetes (T2D), may arise from insulin-induced autoimmunity. This study aimed to explore the association between high-risk human leukocyte antigen (HLA) class II genotypes and susceptibility to double diabetes in patients initially diagnosed with T2D.

Aim: To investigate clinical and immunogenic features of patients who develop double diabetes following exogenous insulin therapy.

Methods: We retrospectively analyzed five cases from Peking Union Medical College Hospital and 18 cases identified from published literature. Patients were categorized into two groups: The T2D→T1D group, characterized by autoimmune progression, and the stable T2D (T2D→T2D). Clinical characteristics and HLA class II genotypes were compared descriptively between the two groups.

Results: A total of 23 patients were included in the analysis. Of these, 10 progressed from theT2D→T1D with autoimmune features, while 13 remained in the stable T2D→T2D group. There was no statistically significant difference in age at diagnosis between the two groups (57.10 ± 16.11 years vs 60.31 ± 17.41 years). In the T2D→T1D group, 70% of patients carried the HLA-DRB1 04: 05 allele and 40% carried DRB1 09: 01, both of which are commonly associated with a high risk of T1D. In contrast, the T2D→T2D group showed greater genetic heterogeneity, with a broader distribution of HLA-DRB1 alleles, including DRB1 03: 02 (n = 4), DRB1 09: 01 (n = 4), and several lower frequency alleles such as DRB1*04: 05, *08: 03, *03: 01, *04: 06, *14: 01, *04: 01, *12: 02,*15: 02 and *02: 01.

Conclusion: These findings suggest that patients in the T2D→T1D group exhibit a stronger autoimmune genetic predisposition, characterized by an enrichment of high-risk HLA class II alleles. In contrast, individuals with stable T2D demonstrate greater HLA diversity and lack definitive autoimmune-associated markers.

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外源性胰岛素相关自身免疫与2型糖尿病中双重糖尿病的出现

背景：外源性胰岛素可能引发免疫介导的并发症，特别是在东亚人群中。双重糖尿病，以1型糖尿病（T1D）和2型糖尿病（T2D）的重叠特征为特征，可能是由胰岛素诱导的自身免疫引起的。本研究旨在探讨高危人类白细胞抗原（HLA） II类基因型与t2dm患者双重糖尿病易感性之间的关系。目的：探讨外源性胰岛素治疗后并发双重糖尿病患者的临床和免疫原性特点。方法：回顾性分析北京协和医院收治的5例病例和已发表文献中的18例病例。患者分为两组：T2D→T1D组，其特点是自身免疫进展，以及稳定的T2D （T2D→T2D）。比较两组患者的临床特征和HLAⅱ型基因型。结果：共有23例患者纳入分析。其中，10例从T2D→T1D发展为自身免疫特征，13例保持稳定的T2D→T2D组。两组患者的诊断年龄（57.10±16.11岁vs 60.31±17.41岁）差异无统计学意义。在T2D→T1D组中，70%的患者携带HLA-DRB1 04:05等位基因，40%的患者携带DRB1 09:01等位基因，这两种等位基因通常与T1D的高风险相关。而T2D→T2D组HLA-DRB1等位基因的遗传异质性更大，分布范围更广，包括DRB1 03: 02 （n = 4）、DRB1 09: 01 (n = 4)，以及DRB1*04: 05、*08:03、*03:01、*04:06、*14:01、*04:01、*12:02、*15:02和*02:01等几个频率较低的等位基因。结论：T2D→T1D组患者表现出更强的自身免疫遗传易感性，其特征是HLAⅱ类高危等位基因富集。相比之下，稳定的T2D患者表现出更大的HLA多样性，缺乏明确的自身免疫相关标志物。

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来源期刊

World Journal of Diabetes ENDOCRINOLOGY & METABOLISM-

自引率

2.40%

发文量

909

期刊介绍： The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.