Exocrine Pancreas in Type 1 and Type 2 Diabetes: Different Patterns of Fibrosis, Metaplasia, Angiopathy, and Adiposity

Abstract

The endocrine and exocrine compartments of the pancreas are spatially related but functionally distinct. Multiple diseases affect both compartments, including type 1 diabetes (T1D), pancreatitis, cystic fibrosis, and pancreatic cancer. To better understand how the exocrine pancreas changes with age, obesity, and diabetes, we performed a systematic analysis of well-preserved tissue sections from the pancreatic head, body, and tail of organ donors with T1D (n = 20) or type 2 diabetes (T2D) (n = 25) and donors with no diabetes (ND; n = 74). Among ND donors, we found that the incidence of acinar-to-ductal metaplasia (ADM), angiopathy, and pancreatic adiposity increased with age, and ADM and adiposity incidence also increased with BMI. Compared with age- and sex-matched ND organs, T1D pancreata had greater rates of acinar atrophy and angiopathy, with fewer intralobular adipocytes. T2D pancreata had greater rates of ADM and angiopathy and a higher total number of T lymphocytes, but no difference in adipocyte number, compared with ND organs. Although total pancreatic fibrosis was increased in both T1D and T2D, the patterns were different, with periductal and perivascular fibrosis occurring more frequently in T1D pancreata and lobular and parenchymal fibrosis occurring more frequently in T2D. Thus, the exocrine pancreas undergoes distinct changes as individuals age or develop T1D or T2D.