{"title":"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","authors":"Xin-Gang Li, Meng-Ya Qi, Xiang Li, Fan Ping","doi":"10.4239/wjd.v16.i9.109130","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>To investigate clinical and immunogenic features of patients who develop double diabetes following exogenous insulin therapy.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>vs</i> 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 (<i>n</i> = 4), DRB1 09: 01 (<i>n</i> = 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 9","pages":"109130"},"PeriodicalIF":4.6000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444274/pdf/","citationCount":"0","resultStr":"{\"title\":\"Exogenous insulin-associated autoimmunity and the emergence of double diabetes in type 2 diabetes.\",\"authors\":\"Xin-Gang Li, Meng-Ya Qi, Xiang Li, Fan Ping\",\"doi\":\"10.4239/wjd.v16.i9.109130\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Aim: </strong>To investigate clinical and immunogenic features of patients who develop double diabetes following exogenous insulin therapy.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>vs</i> 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 (<i>n</i> = 4), DRB1 09: 01 (<i>n</i> = 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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":48607,\"journal\":{\"name\":\"World Journal of Diabetes\",\"volume\":\"16 9\",\"pages\":\"109130\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2025-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12444274/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"World Journal of Diabetes\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4239/wjd.v16.i9.109130\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"World Journal of Diabetes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4239/wjd.v16.i9.109130","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Exogenous insulin-associated autoimmunity and the emergence of double diabetes in type 2 diabetes.
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
