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.