Multi-omics profiling reveals microbiota, metabolite, lipid, and immunological heterogeneity underlying distinct pathophysiological mechanisms of age-related endotypes in type 1 diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by marked heterogeneity in age at diagnosis, clinical progression, and immune pathology. Increasing evidence suggests that age-related T1D endotypes may reflect distinct underlying molecular mechanisms; however, these mechanisms remain incompletely characterized at the cellular and transcriptional levels. To investigate age-associated immune heterogeneity in T1D, peripheral blood mononuclear cells (PBMCs) were collected from a selected cohort of newly diagnosed pediatric individuals with T1D and healthy controls. Single-cell RNA sequencing was performed on PBMCs from 27 individuals with T1D and 27 age- and sex-matched healthy controls to profile peripheral immune cell populations and characterize transcriptional differences associated with age-related T1D endotypes.