glucagon-like-peptide-1 and Esophageal-Neoplasms

Reduced appetite and weight loss are common after esophagectomy (ES), and this cohort demonstrates an exaggerated postprandial satiety gut hormone response. Satiety gut hormones modulate food reward, resulting in reduced energy intake.. This study aimed to determine the effect of satiety gut hormone modulation by measuring the effect of the somatostatin analog octreotide on appetitive behavior among patients after ES.. In this randomized, double-blind, placebo-controlled crossover study, patients ≥1 y after ES and matched controls received either 1 mL 0.9% saline or 1 mL (100 μg) octreotide subcutaneously before completing a progressive ratio task. A measure of appetitive behavior, this task requires subjects to undertake progressively increasing amounts of work to obtain a sweet-fat reinforcer; the final completed increment (breakpoint) represents reinforcer reward value. Separate cohorts were studied in the fasted or 1-h postprandial states.. Thirty-six subjects (ES, n = 18; matched controls, n = 18) were studied. The ES subjects were 2.5 ± 0.3 y postoperation and had a weight loss of 14.6% ± 2.6% and elevated postprandial glucagon-like peptide 1 compared with controls (49.2 ± 13.4 compared with 20.2 ± 2.3 pM; P = 0.04). Octreotide did not alter the breakpoint among ES or control subjects when tested in a fasting condition (ES: 980 ± 371 compared with 1700 ± 584 clicks; P = 0.16; controls: 1056 ± 274 compared with 1124 ± 273 clicks; P = 0.81). When tested 1 h postprandially, octreotide was associated with an increased breakpoint compared with placebo among ES subjects (322 ± 143 compared with 246 ± 149 clicks; P = 0.04) but not controls (248 ± 119 compared with 247 ± 120 clicks; P = 0.97).. Attenuation of the exaggerated postprandial satiety gut hormone response is associated with increased appetitive behavior toward a sweet-fat stimulus among patients post-ES. Suppression of satiety gut hormones may be a novel target to increase appetite, food intake, and body weight among patients after ES. This study was registered at clinicaltrials.gov as NCT02381249.

Topics: Adult; Appetite; Cross-Over Studies; Double-Blind Method; Esophageal Neoplasms; Esophagectomy; Esophagus; Female; Gastrointestinal Hormones; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Postoperative Complications; Postprandial Period; Satiation; Satiety Response; Somatostatin

Delayed gastric emptying (DGE) is common after an Ivor Lewis gastro-esophagectomy (ILGO). The risk of a dilated conduit is the much-feared anastomotic leak. Therefore, prompt management of DGE is required. However, the pathophysiology of DGE is unclear. We proposed that post-ILGO patients with/without DGE have different gut hormone profiles (GHP). Consecutive patients undergoing an ILGO from 1 December 2017 to 31 November 2019 were recruited. Blood sampling was conducted on either day 4, 5, or 6 with baseline sample taken prior to a 193-kcal meal and after every 30 minutes for 2 hours. If patients received pyloric dilatation, a repeat profile was performed post-dilatation and were designated as had DGE. Analyses were conducted on the following groups: patient without dilatation (non-dilated) versus dilatation (dilated); and pre-dilatation versus post-dilatation. Gut hormone profiles analyzed were glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) using radioimmunoassay. Of 65 patients, 24 (36.9%) had dilatation and 41 (63.1%) did not. For the non-dilated and dilated groups, there were no differences in day 4, 5, or 6 GLP-1 (P = 0.499) (95% confidence interval for non-dilated [2822.64, 4416.40] and dilated [2519.91, 3162.32]). However, PYY levels were raised in the non-dilated group (P = 0.021) (95% confidence interval for non-dilated [1620.38, 3005.75] and dilated [821.53, 1606.18]). Additionally, after pyloric dilatation, paired analysis showed no differences in GLP-1, but PYY levels were different at all time points and had an exaggerated post-prandial response. We conclude that DGE is associated with an obtunded PYY response. However, the exact nature of the association is not yet established.

Topics: Esophageal Neoplasms; Esophagectomy; Gastric Emptying; Gastroparesis; Glucagon-Like Peptide 1; Humans; Peptides; Postoperative Complications; Retrospective Studies; Tyrosine

To prospectively characterize changes in body weight, satiety, and postprandial gut hormone profiles following esophagectomy.. With improved oncologic outcomes in esophageal cancer, there is an increasing focus on functional status and health-related quality of life in survivorship. Early satiety and weight loss are common after esophagectomy, but the pathophysiology of these phenomena remains poorly understood.. In this prospective study, consecutive patients undergoing esophagectomy with gastric conduit reconstruction were studied preoperatively and at 10 days, 6 weeks, and 3 months postoperatively. Glucagon-like peptide 1 (GLP-1) immunoreactivity of plasma collected immediately before and at 15, 30, 60, 90, 120, 150, and 180 minutes after a standardized 400-kcal mixed meal was determined. Gastrointestinal symptom scores were computed using European Organization for Research and Treatment of Cancer questionnaires.. Body weight loss at 6 weeks and 3 months postoperatively among 13 patients undergoing esophagectomy was 11.1 ± 2.3% (P < 0.001) and 16.3 ± 2.2% (P < 0.0001), respectively. Early satiety (P = 0.043), gastrointestinal pain and discomfort (P = 0.01), altered taste (P= 0.006), and diarrhea (P= 0.038) scores increased at 3 months postoperatively. Area under the curve for the satiety gut hormone GLP-1 was significantly increased from 10 days postoperatively (2.4 ± 0.2-fold increase, P < 0.01), and GLP-1 peak increased 3.8 ± 0.6-, 4.7 ± 0.8-, and 4.4 ± 0.5-fold at 10 days, 6 weeks, and 3 months postoperatively (all P < 0.0001). Three months postoperatively, GLP-1 area under the curve was associated with early satiety (P = 0.0002, R = 0.74), eating symptoms (P = 0.007, R = 0.54), and trouble enjoying meals (P = 0.0004, R = 0.73).. After esophagectomy, patients demonstrate an exaggerated postprandial satiety gut hormone response, which may mediate postoperative changes in satiety, body weight, and gastrointestinal quality of life.

Topics: Aged; Blood Glucose; Esophageal Neoplasms; Esophagectomy; Female; Gastrointestinal Diseases; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Pain; Postoperative Complications; Postprandial Period; Prospective Studies; Quality of Life; Satiety Response; Taste Disorders; Treatment Outcome; Weight Loss

Postprandial concentrations of glucose and the immunoreactivity of insulin, glucagon-like peptide-1 (GLP-1), and pancreatic glucagon were measured in 10 patients who had undergone esophageal resection (ER) and replacement by the stomach. Emptying of the esophageal substitute was assessed by scintigraphy using a 99Tc-labeled solid test meal. The data were compared with measurements performed in 14 controls, in 7 of whom gastric emptying was measured. The gastric emptying half time was 6.8 +/- 6.2 min (median 144 s) in ER cases, significantly shorter than in controls: 70 +/- 29 min (median 51 min). The early integrated (first 30 min) and total integrated insulin and GLP-1 concentrations were significantly higher than in controls. In 3 of 10 esophagectomy patients the blood glucose concentration fell below 3.8 mmol/l postprandially. High GLP-1 concentrations in the first 30 min were associated with low serum glucose during the 2nd h postprandially when all the hypoglycemic episodes occurred. It is concluded that rapid emptying of the esophageal substitute induces the exaggerated GLP-1 response, which is a main factor for reactive hypoglycemia.

Topics: Blood Glucose; Eating; Esophageal Neoplasms; Esophagoplasty; Esophagus; Female; Gastric Emptying; Glucagon; Glucagon-Like Peptide 1; Humans; Insulin; Male; Middle Aged; Pancreas; Peptide Fragments; Protein Precursors; Stomach