Longitudinal monitoring of type 1 diabetes progression to disease onset.

Abstract

Preventing autoimmune type 1 diabetes (T1D) necessitates improved monitoring for disease progression before symptom onset. Current diagnostic methods assess circulating autoantibodies, C-peptide levels, or dysglycemia, yet these approaches fail to identify β cell destruction preceding glucose dysregulation. Here, a subcutaneous microporous scaffold is used as an immunological niche (IN), which provides a nonvital accessible tissue reflecting many immune changes occurring in the pancreas. Sequencing analysis of the IN successfully delineates at-risk from nonrisk groups, as well as disease progressors from nonprogressors at 6 weeks of age in the nonobese diabetic mouse model. Within progressors, we identify disease 5 to 7 weeks before disease onset. Collectively, disease occurring in a poorly accessible site can be identified early by sampling a distant nonvital tissue, indicating the systemic nature of the disease and informing the timing of disease modifying therapies to halt or delay the progression of T1D.