Histological changes in endocrine and exocrine pancreatic tissue from patients exposed to incretin-based therapies

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2016-12, Vol.18 (12), p.1253-1262
• Main Authors: Ueberberg, Sandra, Jütte, Hendrik, Uhl, Waldemar, Schmidt, Wolfgang, Nauck, Michael, Montanya, Eduard, Tannapfel, Andrea, Meier, Juris
• Format: Article
• Language: English
• Subjects: Acinar Cells - pathology; Adamantane - analogs & derivatives; Adamantane - therapeutic use; Adenocarcinoma - surgery; Adult; Aged; Beta cells; Carcinoma in Situ - epidemiology; Carcinoma in Situ - pathology; Carcinoma in Situ - surgery; Case-Control Studies; Cystadenoma - surgery; Diabetes; Diabetes Mellitus, Type 2 - drug therapy; Digestive System Surgical Procedures; Dipeptides - therapeutic use; DPP-4 inhibitors; Female; GLP-1; GLP-1 analogues; Glucagon - metabolism; Glucagon-Secreting Cells - metabolism; Glucagon-Secreting Cells - pathology; Humans; Incretins - therapeutic use; Insulin - metabolism; Insulin-Secreting Cells - metabolism; Insulin-Secreting Cells - pathology; Islets of Langerhans - metabolism; Islets of Langerhans - pathology; Male; Middle Aged; Neuroendocrine Tumors - surgery; Nitriles - therapeutic use; Organ donors; Organ Size; Pancreas - surgery; Pancreas, Exocrine - pathology; pancreatic cancer; Pancreatic Neoplasms - epidemiology; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - surgery; pancreatitis; Pancreatitis, Chronic - surgery; Peptides - therapeutic use; Pyrrolidines - therapeutic use; Sitagliptin Phosphate - therapeutic use; Tissue Donors; Venoms - therapeutic use
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12766

Aims Incretin‐based therapies have been associated with an increased risk of pancreatitis. Recently, various histological abnormalities have been reported in human pancreatic tissue from brain‐dead organ donors who had been exposed to incretin‐based drugs. In the present study we examined pancreatic tissue collected at surgery. Methods Human pancreatic tissue from 7 type 2‐diabetic patients treated with incretin‐based drugs (type 2‐I), 6 diabetic patients without incretin treatment (type 2‐NI), 11 patients without diabetes (no diabetes group) and 9 brain‐dead organ donors (BDOD group) was examined. Results Fractional beta‐cell area was reduced in the type 2‐NI group compared to the group without diabetes (P < .05), but there was no difference compared to the type 2‐I patients. Alpha‐cell area (P = .30), beta‐cell replication (P = .17) and alpha‐cell replication (P = .91) were not different. There were also no differences in acinar cell (P = .13) and duct cell replication (P = .099). Insulin‐positive duct cells were more frequent in the type 2‐I and the BDOD groups (P = .034). No co‐expression of insulin and glucagon was detected. Pancreatic intraepithelial neoplasia (PanIN) lesions were very rare, all low‐grade (PanIN 1a and 1b) and tended to occur more frequently in the type 2‐I group (P = .084). Conclusions The present results did not reveal marked histological abnormalities in the pancreas of incretin‐treated patients with type 2 diabetes. Low numbers of specimens available and a large inter‐individual variability of the findings warrant caution regarding the interpretation of histological data concerning drug effects on the human pancreas.