Longitudinal monitoring of Type 1 Diabetes progression to disease onset

Preventing autoimmune type 1 diabetes (T1D) necessitates improved monitoring for disease progression prior to 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. Herein, a subcutaneous microporous scaffold is employed as an immunological niche (IN), which provides a non-vital accessible tissue reflecting many immune changes occurring in the pancreas. RNA sequencing analysis of the IN successfully delineates at-risk from non-risk groups, as well as disease progressors from non-progressors at six weeks of age in the NOD mouse model. Within progressors, we identify disease five to seven weeks prior to disease onset. Collectively, disease occurring in a poorly accessible site can be identified early by sampling a distant non-vital tissue, indicating the systemic nature of the disease and informing the timing of disease modifying therapies to halt or delay the progression of T1D.