Abstract
OBJECTIVES: To explore the possible role of inflammatory factors as mediators in the causal relationship between immune cells and type 1 diabetes mellitus (T1DM).Methods: An analysis using Mendelian randomization (MR) was carried out with publicly accessible genetic information to examine the correlation between 731 immune cell features and the susceptibility to T1DM. GWAS summary statistics for inflammatory factors from Ahola-Olli were utilized to assess genetically predicted T1DM. Additionally, we employed a two-step MR approach to investigate whether inflammatory factors mediate the impact of immune cell characteristics on T1DM.Results: Statistically significant effects of six immune cell traits on T1DM were observed after FDR correction. Notably, HLA DR on CD14 + monocyte, HLA DR on CD14 + CD16- monocyte, CD4 on activated Treg, CD8 on CM CD8br, CD25 on IgD- CD38dim, and CD38 on IgD+ showed significant associations with T1DM. Furthermore, the influence of five inflammatory factors on T1DM was also significant. Our findings suggest that certain inflammatory factors mediate the relationship between immune cell characteristics and T1DM.Conclusion: Our study provides genetic evidence of a close association between immune cell characteristics, inflammatory factors, and T1DM, potentially guiding future clinical research. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-01926-3.