100 YEARS OF INSULIN: Pancreas pathology in type 1 diabetes: an evolving story.

We review the current knowledge of pancreas pathology in type 1 diabetes. During the last two decades, dedicated efforts toward the recovery of pancreas from deceased patients with type 1 diabetes have promoted significant advances in the characterization of the pathological changes associated with this condition. The implementation of autoantibody screening among organ donors has also allowed examining pancreas pathology in the absence of clinical disease, but in the presence of serological markers of autoimmunity. The assessment of key features of pancreas pathology across various disease stages allows driving parallels with clinical disease stages. The main pathological abnormalities observed in the pancreas with type 1 diabetes are beta-cell loss and insulitis; more recently, hyperexpression of HLA class I and class II molecules have been reproduced and validated. Additionally, there are changes affecting extracellular matrix components, evidence of viral infections, inflammation, and ER stress, which could contribute to beta-cell dysfunction and the stimulation of apoptosis and autoimmunity. The increasing appreciation that beta-cell loss can be less severe at diagnosis than previously estimated, the coexistence of beta-cell dysfunction, and the persistence of key features of pancreas pathology for years after diagnosis impact the perception of the dynamics of this chronic process. The emerging information is helping the identification of novel therapeutic targets and has implications for the design of clinical trials.