Pancreas Pathology During the Natural History of Type 1 Diabetes

We provide an overview of pancreas pathology in type 1 diabetes (T1D) in the context of its clinical stages.

Recent studies of pancreata from organ donors with T1D and non-diabetic donors expressing T1D-associated autoantibodies reveal pathological changes/disease mechanisms beyond the well-known loss of β cells and lymphocytic infiltrates of the islets (insulitis), including β-cell stress, dysfunction, and viral infections. Pancreas pathology evolves through disease stages, is asynchronous, and demonstrates a chronic disease that remains active years after diagnosis. Critically, β-cell loss is not complete at onset, although young age is associated with increased severity. The recognition of multiple pathogenic alterations and the chronic nature of disease mechanisms during and after the development of T1D inform improved clinical trial design and reveal additional targets for therapeutic manipulation, in the context of an expanded time window for intervention.