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 ß 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. Overall design: RNA-seq profiling of microporous scaffolds implanted into NOD and NOR mice. Samples were taken from all mice at 6 weeks of age. Additional samples were taken at 7, 5, 3, and 1 week before symptom onset in NOD mice that progressed to hyperglycemia, as well as at the time of symptom onset. Samples were taken at 10, 14, 18, and 22 weeks of age for NOD mice that did not develop hyperglycemia and NOR controls.