Recent efforts addressing the pathogenesis of T1D have benefited greatly from access to transplant-quality human pancreas samples obtained from organ donors. While alcohol use is linked to pancreatitis clinically, the effect of alcohol and other illicit substances on pancreatic histopathology in T1D is not known. Hence, we determined the influence of alcohol, marijuana, tobacco, cocaine, and other controlled substances in T1D pancreata. In total, 140 T1D organ donor pancreata [median age at T1D onset=11 (range 0-36) years, duration=12 (0-84) years, 47% female] were recovered through the Network for Pancreatic Organ donors with Diabetes (nPOD) program. Paraffin sections were stained and reviewed for insulin positivity, insulitis (≥6 CD3+ cells adjacent/within the islet in ≥3 islets/section), amyloid staining, acute (acinar cell loss, mononuclear cell infiltrate, fat necrosis, and hemorrhage) and chronic pancreatitis (acinar cell loss, mononuclear cell infiltrate, and fibrosis) as well as chronic exocrine changes (acinar atrophy, fibrosis, fatty infiltration, or periductal fibrosis). Terminal hospital records were reviewed for a history of alcohol, tobacco, marijuana, and any illicit substance use. Of 140 T1D donors, 51% had a history of alcohol use, 40% tobacco use, 29% marijuana, and 20% other illicit substances. Urine drug screening on admission was available for 74 donors with 36 positive (49%). Alcohol use was associated with histopathological features of acute pancreatitis (p<0.05) and islet amyloid deposition (p<0.05). History of cocaine use (p<0.05) as well as a positive urine drug screen (p<0.05) were associated with chronic exocrine changes. To conclude, in T1D donor pancreata, alcohol use was associated with acute pancreatitis and islet amyloid deposition while a history of cocaine use and a positive urine drug screen were associated with chronic exocrine changes. These findings should be given consideration in studies aimed at interpreting histopathologic changes in T1D pancreata.
B.S. Bruggeman: None. M. Campbell-Thompson: None. A.L. Posgai: None. M.A. Atkinson: None. D. Schatz: None. L.M. Jacobsen: None.