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

作者：Ueberberg Sandra; Juette Hendrik; Uhl Waldemar; Schmidt Wolfgang; Nauck Michael; Montanya Eduard; Tannapfel Andrea; Meier Juris^*

来源：Diabetes, Obesity and Metabolism, 2016, 18(12): 1253-1262.

DOI：10.1111/dom.12766

• DPP-4 inhibitors
• GLP-1
• GLP-1 analogues
• pancreatic cancer
• pancreatitis

AimsIncretin-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.
MethodsHuman 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.
ResultsFractional 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).
ConclusionsThe 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.

• 出版日期2016-12