Background <p>Type 2 diabetes (T2D) and autoimmune diseases are complex disorders shaped by genetic, immunological, and environmental factors. However, differences in genetic susceptibility to autoimmune disorders between diabetic and non-diabetic individuals remain poorly understood, particularly within the Indian population. This study aimed to compare polygenic susceptibility to multiple autoimmune diseases between individuals with and without T2D from Gujarat, India.</p> Results <p>Polygenic risk scores were evaluated for eleven autoimmune diseases in 474 individuals, including 99 diabetics and 375 non-diabetics. Significant differences were observed for systemic lupus erythematosus and rheumatoid arthritis. Individuals with diabetes showed a higher genetic risk for systemic lupus erythematosus, whereas non-diabetic individuals exhibited a higher genetic risk for rheumatoid arthritis. Pathway enrichment analysis of disease-associated genetic variants revealed significant involvement of immune-related pathways, including antigen processing and presentation, T-helper cell differentiation, and immune responses to viral infections.</p> Conclusions <p>The findings reveal disease-specific differences in genetic susceptibility to autoimmune disorders between diabetic and non-diabetic individuals. These results highlight the complex immunogenetic relationship between type 2 diabetes and autoimmune diseases and provide insight into shared and distinct immune pathways within an Indian population. Such information may support future efforts in risk stratification and precision medicine approaches for immune-related comorbidities in diabetes.</p>