3D imaging of human pancreas suggests islet size and endocrine composition influence their loss in type 1 diabetes

Summary A high-definition description of pancreatic islets would prove beneficial for understanding the pathophysiology of type 1 diabetes (T1D), yet significant knowledge voids exist in terms of their size, endocrine cell composition, and number in both health and disease. Here, 3-dimensional (3D) analyses of pancreata from control persons without diabetes (ND) revealed heretofore underappreciated frequencies (approximately 50%) of insulin-positive (INS+) glucagon-negative (GCG-) islets. Non-diabetic individuals positive for a single Glutamic acid decarboxylase autoantibody (GADA+) yet at increased risk for disease consistently demonstrated endocrine features, including islet volume and cell composition, closely resembling the age-matched ND controls. In contrast, pancreata from individuals with short-duration T1D demonstrated significantly reduced islet density and a dramatic loss of INS+GCG- islets with preservation of large INS+GCG+ islets. The size and cellular composition of pancreatic islets may, therefore, represent influential factors that impact β-cell loss during T1D disease progression. Highlights 3D imaging of non-diabetic (ND) pancreas suggests up to 50% of INS+ islets lack GCG INS+GCG- islets are typically small-sized in ND and preferentially lost in T1D In T1D pancreas, INS+ beta cells are preserved in large INS+GCG+ islets Islets from GADA+ individuals appear similar to ND for size and β-to-α cell ratios Competing Interest Statement The authors have declared no competing interest.