incretins and Adenocarcinoma

The provision of parenteral nutrition (PN) to 'stressed' patients often results in hyperglycaemia, which may be detrimental. In animal models limited amounts of enteral nutrition (EN) improve intestinal integrity and stimulate intestinal incretin production, which may lead to improved glucose control. We set out to assess if combining EN with PN results in improved glucose homeostasis rather than PN given alone. We conducted a randomised trial in a university teaching hospital of patients undergoing a 'curative' oesophagectomy for adenocarcinoma. Differences between the two intervention groups were assessed for continuous glucose measurement, insulin sensitivity using insulin tolerance tests (ITT) and homeostasis model analysis (HOMA), the incretin glucose-dependent insulinotropic polypeptide (GIP) and intestinal permeability. The combination of PN with EN resulted in lower interstitial glucose concentrations (P = 0.002), reduced insulin resistance, improved insulin sensitivity (HOMA-insulin resistance (IR) P = 0.045; HOMA beta P = 0.037; ITT P = 0.006), improved intestinal permeability (P < 0.001) and increased GIP (P = 0.01) when compared with PN alone. The combination of EN with PN, when compared with PN alone, results in reduced glucose concentrations, reduced insulin resistance, increased incretins and improvements in intestinal permeability.

Topics: Adenocarcinoma; Aged; Blood Glucose; Enteral Nutrition; Esophageal Neoplasms; Esophagectomy; Female; Homeostasis; Humans; Incretins; Insulin; Insulin Resistance; Intestinal Absorption; Male; Middle Aged; Parenteral Nutrition; Postoperative Care

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.

Topics: Acinar Cells; Adamantane; Adenocarcinoma; Adult; Aged; Carcinoma in Situ; Case-Control Studies; Cystadenoma; Diabetes Mellitus, Type 2; Digestive System Surgical Procedures; Dipeptides; Exenatide; Female; Glucagon; Glucagon-Secreting Cells; Humans; Incretins; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Male; Middle Aged; Neuroendocrine Tumors; Nitriles; Organ Size; Pancreas; Pancreas, Exocrine; Pancreatic Neoplasms; Pancreatitis, Chronic; Peptides; Pyrrolidines; Sitagliptin Phosphate; Tissue Donors; Venoms; Vildagliptin