title: Histological changes in endocrine and exocrine pancreatic tissue from patients exposed to incretin-based therapies.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ueberberg
authors.affiliation: Department of Pathology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Jütte
authors.affiliation: Department of Surgery, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Uhl
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schmidt
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Nauck
authors.affiliation: Bellvitge Hospital, Department of Endocrinology, Feixa Llarga s/n, Hospitalet de Llobregat, 08907, Barcelona, Spain.
authors.forename: Eduard
authors.initials: E
authors.lastname: Montanya
authors.affiliation: Department of Pathology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Tannapfel
authors.affiliation: Diabetes Division, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Juris
authors.initials: J
authors.lastname: Meier
mesh_terms: D061354:Acinar Cells / Q000473:pathology*; D000218:Adamantane / Q000031:analogs & derivatives / Q000627:therapeutic use; D000230:Adenocarcinoma / Q000601:surgery; D000328:Adult; D000368:Aged; D002278:Carcinoma in Situ / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D016022:Case-Control Studies; D003537:Cystadenoma / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D013505:Digestive System Surgical Procedures; D004151:Dipeptides / Q000627:therapeutic use; D000077270:Exenatide; D005260:Female; D005934:Glucagon / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000601:surgery; D009570:Nitriles / Q000627:therapeutic use; D009929:Organ Size; D010179:Pancreas / Q000601:surgery*; D046790:Pancreas, Exocrine / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery; D050500:Pancreatitis, Chronic / Q000601:surgery; D010455:Peptides / Q000627:therapeutic use; D011759:Pyrrolidines / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate / Q000627:therapeutic use; D014019:Tissue Donors; D014688:Venoms / Q000627:therapeutic use; D000077597:Vildagliptin
chemical_list: D004151:Dipeptides; D054795:Incretins; D007328:Insulin; D009570:Nitriles; D010455:Peptides; D011759:Pyrrolidines; D014688:Venoms; D005934:Glucagon; C502994:saxagliptin; D000077270:Exenatide; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate
keywords: DPP-4 inhibitors; GLP-1; GLP-1 analogues; pancreatic cancer; pancreatitis