Teresa Rodriguez-Calvo1, Sarah J Richardson2, Alberto Pugliese3,4. 1. Institute for Diabetes Research, Helmholtz Diabetes Center at Helmholtz Zentrum München, Munich, Germany. 2. Islet Biology Exeter (IBEx), Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, Exeter, UK. 3. Diabetes Research Institute, Department of Medicine, Division of Endocrinology, Department of Microbiology and Immunology, Leonard Miller School of Medicine, University of Miami, Miami, FL, USA. apuglies@med.miami.edu. 4. Diabetes Research Institute, 1450 NW 10th Avenue, Miami, FL, 33136, USA. apuglies@med.miami.edu.
Abstract
PURPOSE OF REVIEW: We provide an overview of pancreas pathology in type 1 diabetes (T1D) in the context of its clinical stages. RECENT FINDINGS: 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.
PURPOSE OF REVIEW: We provide an overview of pancreas pathology in type 1 diabetes (T1D) in the context of its clinical stages. RECENT FINDINGS: 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.
Entities:
Keywords:
Insulitis; Islet autoimmunity; Pancreas; Type 1 diabetes; β cell
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