Prospective clinical cohort study: low incidence of Barrett esophagus but high rate of reflux disease at 5-year follow-up after sleeve gastrectomy versus Roux-en-Y gastric bypass.

BACKGROUND: Gastroesophageal reflux disease seems more frequent after laparoscopic sleeve gastrectomy (LSG) than Roux-en-Y gastric bypass (LRYGB). Retrospective case series have raised concerns about a high incidence of Barrett esophagus (BE) after LSG. OBJECTIVE: This prospective clinical cohort study compared the incidence of BE ≥5 years after LSG and LRYGB. SETTING: St. Clara Hospital, Basel, and University Hospital, Zürich, Switzerland. METHODS: Patients were recruited from 2 bariatric centers where preoperative gastroscopy is standard practice and LRYGB is preferred for patients with preexisting gastroesophageal reflux disease. At follow-up ≥5 years after surgery, patients underwent gastroscopy with quadrantic biopsies from the squamocolumnar junction and metaplastic segment. Symptoms were assessed using validated questionnaires. Wireless pH measurement assessed esophageal acid exposure. RESULTS: A total of 169 patients were included, with a median 7.0 ± 1.5 years after surgery. In the LSG group (n = 83), 3 patients had endoscopically and histologically confirmed de novo BE; in the LRYGB group (n = 86), there were 2 patients with BE, 1 de novo and 1 preexisting (de novo BE, 3.6% versus 1.2%; P = .362). At follow-up, reflux symptoms were reported more frequently by the LSG group than by the LRYGB group (51.9% versus 10.5%). Similarly, moderate-to-severe reflux esophagitis (Los Angeles grade B-D) was more common (27.7% versus 5.8%) despite greater use of proton pump inhibitors (49.4% versus 19.7%), and pathologic acid exposure was more frequent in patients who underwent LSG than in patients who underwent LRYGB. CONCLUSIONS: After at least 5 years of follow-up, a higher incidence of reflux symptoms, reflux esophagitis, and pathologic esophageal acid exposure was found in patients who underwent LSG compared with patients who underwent LRYGB. However, the incidence of BE after LSG was low and not significantly different between the 2 groups.

Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.

AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS: Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS: We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS: Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.

Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men.

BACKGROUND: Exogenous glucagon-like peptide-1 (GLP-1) inhibits eating in healthy, overweight, and diabetic subjects. OBJECTIVE: The GLP-1 receptor antagonist exendin(9-39)NH2 (ex9-39) was used to further explore the role of GLP-1 as an endogenous satiation signal. DESIGN: Two double-blind, 4-way crossover studies were performed, each of which included 10 healthy men. In study A, subjects received an intravenous infusion of ex9-39 or saline plus an oral glucose preload and an intraduodenal infusion of saline or glucose for 60 min. In study B, intravenous infusions were identical, but an oral mixed-liquid meal preload and a 60-min intraduodenal infusion of saline or oleic acid were administered. Thirty minutes after oral preloads, subjects ate and drank ad libitum, and amounts ingested and the time to meal completion were quantified. In addition, appetite and plasma GLP-1, peptide YY (PYY), insulin, glucagon, and blood glucose concentrations were measured. RESULTS: In both studies, GLP-1, PYY, and glucagon were substantially higher with intravenous ex9-39 than with intravenous saline (P ≤ 0.001). Insulin was lower with intravenous ex9-39 during intraduodenal glucose (P ≤ 0.05). The decrease in prospective food consumption and desire to eat during ad libitum eating after glucose ingestion was slightly attenuated (P ≤ 0.05 and P ≤ 0.01, respectively) with ex9-39. However, with intravenous ex9-39, food and fluid intakes and eating duration were not changed in either study. CONCLUSIONS: GLP-1 receptor antagonism slightly modulates appetite during ad libitum eating, but food and fluid intakes and meal duration remain unchanged, suggesting that endogenous GLP-1 is a weak satiation signal. However, concomitant substantial increases in plasma PYY and glucagon may counteract a desatiating effect of ex9-39. The effect of ex9-39 on PYY secretion supports an autoinhibitory feedback mechanism that controls L cell secretion; the effect on insulin and glucagon confirms the role of GLP-1 in glycemic control through its action on pancreatic α and ß cells.

Gastric and intestinal satiation in obese and normal weight healthy people.

OBJECTIVE: The gastrointestinal tract plays a key role in feelings of satiation. It is known that there is a reciprocal interaction between the stomach and intestine, but it is not known which factors are of gastric origin and which are intestinal. This three-step study therefore sought to provide illumination on satiation parameters with respect to body mass. METHOD: In the first part, the time needed to reach maximal satiation and total caloric intake was calculated after participants (20 normal weight, 20 obese) imbibed a standardized nutrient drink. In the second part gastric emptying of solids and liquids was evaluated using the (13)C-breath test (participants: 16 normal weight, 9 obese for gastric emptying of solids; 15 normal weight, 14 obese for gastric emptying of liquids). And in the third part, fasting and post-prandial plasma glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY) and ghrelin levels were measured after a standardized nutrient drink (participants: 20 normal weight, 20 obese). RESULTS: Our results show that, when compared to those of normal weight, obese participants reached maximal satiation sooner (P=0.006), their total intake of calories was higher (P=0.013), and their gastric emptying rates were delayed (P<0.001). Furthermore, their post-prandial increase in plasma GLP-1 and PYY was reduced, (P<0.001 for both), as was their ghrelin suppression (P=0.001). DISCUSSION: We conclude that, in obese subjects gastric emptying can be impaired with delayed interaction of nutrients with the intestine resulting in decreased GLP-1 and PYY secretion. This could imply that obese participants would require more calories before their maximal satiation is reached and they stop eating.

Glucose-induced glucagon-like Peptide 1 secretion is deficient in patients with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are gastrointestinal peptide hormones regulating postprandial insulin release from pancreatic ß-cells. GLP-1 agonism is a treatment strategy in Type 2 diabetes and is evaluated in Non-alcoholic fatty liver disease (NAFLD). However, the role of incretins in its pathophysiology is insufficiently understood. Studies in mice suggest improvement of hepatic steatosis by GLP-1 agonism. We determined the secretion of incretins after oral glucose administration in non-diabetic NAFLD patients. METHODS: N=52 patients (n=16 NAFLD and n=36 Non-alcoholic steatohepatitis (NASH) patients) and n=50 matched healthy controls were included. Standardized oral glucose tolerance test was performed. Glucose, insulin, glucagon, GLP-1 and GIP plasma levels were measured sequentially for 120 minutes after glucose administration. RESULTS: Glucose induced GLP-1 secretion was significantly decreased in patients compared to controls (p<0.001). In contrast, GIP secretion was unchanged. There was no difference in GLP-1 and GIP secretion between NAFLD and NASH subgroups. All patients were insulin resistant, however HOMA2-IR was highest in the NASH subgroup. Fasting and glucose-induced insulin secretion was higher in NAFLD and NASH compared to controls, while the glucose lowering effect was diminished. Concomitantly, fasting glucagon secretion was significantly elevated in NAFLD and NASH. CONCLUSIONS: Glucose-induced GLP-1 secretion is deficient in patients with NAFLD and NASH. GIP secretion is contrarily preserved. Insulin resistance, with hyperinsulinemia and hyperglucagonemia, is present in all patients, and is more severe in NASH compared to NAFLD. These pathophysiologic findings endorse the current evaluation of GLP-1 agonism for the treatment of NAFLD.

Bile acids and gut peptide secretion after bariatric surgery: a 1-year prospective randomized pilot trial.

OBJECTIVE: Increased delivery of bile acid salts (BA) to distal L-cells and altered TGR5 receptor activation may contribute to the early and substantial increases in gut peptide secretion seen after bariatric surgery. To further elucidate a potential role of BA in the secretion of GLP-1 and PYY, we analyzed plasma BA concentrations in 14 morbidly obese patients undergoing gastric bypass or sleeve gastrectomy in a prospective, randomized 1-year trial. DESIGN AND METHODS: Patients received a standard test meal and blood was collected before and after eating, prior to, and 1 week, 3 months, and 12 months after surgery. RESULTS: Pre-surgery, basal BA concentrations were significantly lower in bariatric patients than in healthy controls. One year post-surgery, bariatric patients expressed variably increased BA concentrations (gastric bypass patients ∼2 fold increase, P ≤ 0.05). However, whereas in both patient groups, marked increases in GLP-1 and PYY and improved glycemic control was seen already 1 week and 3 months post-surgery, changes in plasma BA followed a different pattern: basal and postprandial plasma BA concentrations increased much slower, more progressively with significant increases only 1-year post-surgery. CONCLUSIONS: Based on these findings, BA do not appear to be key mediators of the early increase in GLP-1 and PYY response in post-bariatric patients.

The role of the stomach in the control of appetite and the secretion of satiation peptides.

It is widely accepted that gastric parameters such as gastric distention provide a direct negative feedback signal to inhibit eating; moreover, gastric and intestinal signals have been reported to synergize to promote satiation. However, there are few human data exploring the potential interaction effects of gastric and intestinal signals in the short-term control of appetite and the secretion of satiation peptides. We performed experiments in healthy subjects receiving either a rapid intragastric load or a continuous intraduodenal infusion of glucose or a mixed liquid meal. Intraduodenal infusions (3 kcal/min) were at rates comparable with the duodenal delivery of these nutrients under physiological conditions. Intraduodenal infusions of glucose elicited only weak effects on appetite and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). In contrast, identical amounts of glucose delivered intragastrically markedly suppressed appetite (P < 0.05) paralleled by greatly increased plasma levels of GLP-1 and PYY (≤3-fold, P < 0.05). Administration of the mixed liquid meal showed a comparable phenomenon. In contrast to GLP-1 and PYY, plasma ghrelin was suppressed to a similar degree with both intragastric and intraduodenal nutrients. Our data confirm that the stomach is an important element in the short-term control of appetite and suggest that gastric and intestinal signals interact to mediate early fullness and satiation potentially by increased GLP-1 and PYY secretions.