biostudies-literatureRippa ANIDDK NIH HHSNIAID NIH HHSFoundation for the National Institutes of HealthFoundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)11379https://www.ebi.ac.uk/biostudies/studies/S-EPMC12727770biostudies-literatureUnknown16(1)A high-definition description of pancreatic islets would prove beneficial for understanding the pathophysiology of type 1 diabetes (T1D), yet significant knowledge gaps 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) demonstrate approximately 50% of islets are insulin-positive (INS + ) glucagon-negative (GCG-). Non-diabetic individuals positive for a single Glutamic acid decarboxylase autoantibody (GADA + ) yet at increased risk for disease consistently demonstrate endocrine features, including islet volume and cell composition, closely resembling the age-matched ND controls. In contrast, pancreata from individuals with short-duration T1D demonstrate 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.Nature communications3D imaging of human pancreas suggests islet size and endocrine composition influence their loss in type 1 diabetes.PMC12727770R01 DK131059R01 DK123292U24 DK104162R01DK131059P01 AI042288P01AI042288R01DK123292U01 DK135001Rippa ACurrlin SKaddis JSWilliams MDWasserfall CHAtkinson MAKusmartseva IPosgai ALBrusko MCampbell-Thompson Mfalse3D imaging of human pancreas suggests islet size and endocrine composition influence their loss in type 1 diabetes.A high-definition description of pancreatic islets would prove beneficial for understanding the pathophysiology of type 1 diabetes (T1D), yet significant knowledge gaps 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) demonstrate approximately 50% of islets are insulin-positive (INS + ) glucagon-negative (GCG-). Non-diabetic individuals positive for a single Glutamic acid decarboxylase autoantibody (GADA + ) yet at increased risk for disease consistently demonstrate endocrine features, including islet volume and cell composition, closely resembling the age-matched ND controls. In contrast, pancreata from individuals with short-duration T1D demonstrate 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.2025-01-01T00:00:00Z2025 Dec2026-06-06T05:15:59.129Z2026-05-26T03:12:07.956ZS-EPMC127277704138147310.1038/s41467-025-66198-6