Year: 2021
Type: article
Abstract: Access to human pancreas samples from organ donors has greatly advanced our understanding of type 1 diabetes pathogenesis; however, previous studies have shown that donors have a high rate of substance use, and its impact on pancreatic histopathology in this disease is not well described. One-hundred-thirty-one type 1 diabetes and 111 control organ donor pancreata from persons 12-89 years of age (mean 29.8 ± 15.5 years) within the Network for Pancreatic Organ donors with Diabetes (nPOD) were examined for insulin positivity, insulitis, amyloid staining, acute and chronic pancreatitis, and chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis); findings were compared by history of substance use. A secondary analysis compared exocrine pancreatic histopathologic findings in type 1 diabetes versus control organ donors regardless of substance use history. We observed a high but congruent rate of substance use in type 1 diabetes and control organ donors (66.4% and 64% respectively). Among donors with type 1 diabetes (but not controls), islet amyloid (OR 9.96 [1.22, 81.29]) and acute pancreatitis (OR 3.2 [1.06, 9.63]) were more common in alcohol users while chronic exocrine changes (OR 8.86 [1.13, 69.31]) were more common in cocaine users. Substance use impacted the pancreata of donors with type 1 diabetes more than controls. Overall, despite similar rates of substance use, acute pancreatitis (15.3% versus 4.5%, p=0.0061), chronic pancreatitis (29.8% versus 9.9%, p=0.0001), and chronic exocrine changes (73.3% versus 36.9%, p<0.0001) were more common in type 1 diabetes donors than controls. Alcohol and/or cocaine use in type 1 diabetes organ donors increases exocrine pancreas pathology and islet amyloid deposition but does not affect insulitis or insulin positivity. Exocrine pathology in type 1 diabetes donors is common, and further study of the pathophysiology of these changes is needed.
Source: Frontiers in Endocrinology
Institutions: University of Florida Health, University of Florida
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,950
Funders: American Diabetes Association, Leona M. and Harry B. Helmsley Charitable Trust, Juvenile Diabetes Research Foundation United States of America, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Advancing Translational Sciences, College of Medicine, University of Florida
Awards: G1154828164, G1455447062, G2215772352, G2241387942, G258128023, G3540058113, UF Clinical and Translational Science Award, G4339928955, Regional and lobular heterogeneity of human pancreas morphology and function in type 1 diabetes pathogenesis, G445890114, G4606767805, G466735092, G5500374692, G6003976623, G6458857254, G6886305284, G7929470077, G9000025070, G9000037945, G9000111155, G9000277719, Continuation of Type 1 Diabetes in Acute Pancreatitis Consortium – UF Health and AdventHealth Combined Clinical Center
OpenAlex ID: W3216349627