Jan Lysgård Madsen

Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass

Objective:To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB).Design:Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender.Materials and methods:Sixteen patients with good weight loss response, 17 patients with poor weight loss response, and eight control subjects were included in the study. Participants underwent dual energy X-ray absorptiometry scan, indirect calorimetry and a 9 h multiple-meal test with measurements of glucose, insulin, total bile acids (TBA), glucagon-like peptide (GLP)-1, peptide YY3–36 (PYY), cholecystokinin (CCK), ghrelin, neurotensin and pancreatic polypeptide (PP) as well as assessment of early dumping and appetite.Results:Suppression of hunger was more pronounced in the good than the poor responders in response to the multiple-meal test (P=0.006). In addition, the good responders had a larger release of GLP-1 (P=0.009) and a greater suppression of ghrelin (P=0.037) during the test, whereas the postprandial secretion of CCK was highest in the poor responders (P=0.005). PYY, neurotensin, PP and TBA release did not differ between the RYGB-operated groups. Compared with control subjects, patients had exaggerated release of GLP-1 (P<0.001), PYY (P=0.008), CCK (P=0.010) and neurotensin (P<0.001). Early dumping was comparable in the good and poor responders, but more pronounced than in controlled subjects. Differences in resting energy expenditure between the three groups were entirely explained by differences in body composition.Conclusion:Favorable meal-induced changes in hunger and gut hormone release in patients with good compared with poor weight loss response support the role of gut hormones in the weight loss after RYGB.

Effect of obesity and major weight reduction on gastric emptying.

BACKGROUND: An enhanced gastric emptying rate might reduce the satiating effect of food and thereby promote obesity. Gastric emptying rate has previously been compared between obese and lean subjects with conflicting outcome.OBJECTIVE: Comparison of gastric emptying rate in lean and obese subjects before and after a major weight reduction.DESIGN: The study was designed as a case–control study comparing obese and lean subjects and a subsequent comparison of obese subjects before and after a dietary induced major weight reduction.METHOD: Gastric emptying rate following a solid test meal was estimated scintigraphically for 3 h using the left anterior oblique projection.SUBJECTS: Nineteen non-diabetic obese (mean BMI=38.7 kg/m2) and 12 lean (mean BMI=23.1 kg/m2) males matched for age and height. All obese subjects were re-examined after a mean weight loss of 18.8 kg (95% CI, 14.4–23.2) achieved by 16 weeks of dietary intervention followed by 8 weeks of weight stability.RESULTS: When comparing obese and lean subjects no differences were seen in overall 3 h emptying rate (30.3% per hour vs 30.5% per hour). However, a trend towards a higher percentage gastric emptying during the initial 30 min was seen in the obese when compared to lean subjects (24.0% vs 17.8% of the test meal; P=0.08). Weight loss was associated with a reduction in percentage gastric emptying during the initial 30 min (from 24.0% to 18.3% of the test-meal; P<0.02), whereas the overall 3 h emptying rate was unaffected (30.3% vs 30.9% per hour). Neither initial or overall emptying rate differed between reduced-obese and lean subjects.CONCLUSION: Overall 3 h gastric emptying rate was similar in obese and normal weight males, and unaffected by a major weight loss. However, percentage gastric emptying during the initial 30 min for a solid meal appeared to be increased in obese males and was normalized after a major weight reduction.

Short-term Administration of Glucagon-like Peptide-2. Effects on Bone Mineral Density and Markers of Bone Turnover in Short-Bowel Patients with No Colon

Background: Glucagon-like peptide 2 (GLP-2) is a newly discovered intestinotrophic hormone. We have recently reported that a 5-week GLP-2 treatment improved the intestinal absorptive capacity of shortbowel patients with no colon. Additionally, GLP-2 treatment was associated with changes in body composition that included a significant increase in total body bone mass. This article describes the effect of GLP-2 on spinal and hip bone mineral density (BMD) and biochemical markers of bone turnover in these patients. Methods: In an open-labelled pilot study, eight short-bowel patients (3M, 5F; mean age 49 years) with small-bowel resection and no colon received 400 μg s.c. of GLP-2 twice daily for 5 weeks. Four received home parenteral nutrition (mean length of residual jejunum 83 cm) and 4 did not (mean length of ileum resected 106 cm). The outcome measures were the mean percent change from baseline in spinal and hip BMD measured by dual-energy X-ray absorptiometry, changes in four biochemical markers of bone-turnover, PTH, 25-hydroxy vitamin-D, and the intestinal absorption of calcium. Results: Mean ± s x (SEM) percent changes in spinal and hip BMD were 1.1 ± 0.4% ( P < 0.05) and 1.9 ± 0.8% ( P = 0.06), respectively. The intestinal calcium absorption increased by 2.7% ( P = 0.87). Serum ionized calcium increased in 5/8 patients with a concomitant decrease in serum PTH values. Three of the four markers of bone turnover decreased. Conclusion: A 5-week GLP-2 administration significantly increased spinal BMD in short-bowel patients with no colon. The mechanism by which GLP-2 affects bone metabolism remains unclear, but may be related to an increased mineralization of bone resulting from an improved intestinal calcium absorption.

Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux-en-Y gastric bypass.

Roux‐en‐Y gastric bypass (RYGB) causes extensive changes in gastrointestinal anatomy and leads to reduced appetite and large weight loss, which partly is due to an exaggerated release of anorexigenic gut hormones.

Pulmonary dysfunction and hepatopulmonary syndrome in cirrhosis and portal hypertension

Background: Pulmonary dysfunction including the hepatopulmonary syndrome (HPS) is an important complication to cirrhosis and portal hypertension. However, the precise relation to liver dysfunction and the prevalence of HPS are unclear.

A randomized, placebo-controlled, crossover, double-blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans.

Background  Little is known about the role of tachykinins on human gastrointestinal motility and no data exist on the possible effect of an NK1 receptor antagonist.

Bile Acid Malabsorption or Disturbed Intestinal Permeability in Patients Treated with Enzyme Substitution for Exocrine Pancreatic Insufficiency Is Not Caused by Bacterial Overgrowth

Introduction In some patients with severe exocrine pancreatic insufficiency, enzyme replacement therapy will not lead to clinical improvement or reduction of steatorrhea. Therefore, other mechanisms separately or in interplay with reduced enzyme secretion might be responsible for malabsorption in these patients. Aims To evaluate the prevalence of bacterial overgrowth, bile acid absorption capacity, and intestinal permeability in a group of patients with well-characterized exocrine pancreatic insufficiency. Methodology Eleven men with severe exocrine pancreatic insufficiency, of whom 10 were receiving enzyme replacement therapy, were studied. The prevalence of bacterial overgrowth was evaluated by means of a hydrogen and methane breath test with glucose. Gamma camera scintigraphy after intake of 75Se-homocholic acid taurine (75Se-HCAT) was used to evaluate bile acid absorption capacity. Intestinal permeability was assessed from urine excretion of ingested 14C-mannitol and 99mTc–diethylenetriaminepentaacetic acid (99mTc-DTPA), and these data were compared with results for 10 age-matched healthy men. Results No patients had abnormal breath hydrogen or methane concentrations after glucose intake. Abdominal retention of 75Se-HCAT was reduced in three of the patients. The patients had lower urine excretion of 14C-mannitol than the control subjects, whereas no difference was revealed in urine excretion of 99mTc-DTPA. Conclusion Bile acid absorption and small intestinal permeability might be affected in patients with exocrine pancreatic insufficiency who receive treatment with enzyme supplementation. The prevalence of bacterial overgrowth seems to be low among these patients and does not explain the findings.

Effect of sildenafil on gastric emptying and postprandial frequency of antral contractions in healthy humans

Background: Sildenafil is known to block phosphodiesterase type 5, which degrades nitric oxide‐stimulated cyclic guanosine monophosphate, thereby relaxing smooth muscle cells in various organs. The effect of sildenafil on gastric motor function after a meal was investigated in healthy humans. Methods: Ten healthy male volunteers (21–28 years) participated in a placebo‐controlled, double‐blind, cross‐over study. In random order and on two separate days each volunteer ingested either 50 mg sildenafil (Viagra, Pfizer, New York, N.Y., USA) or placebo. A gamma camera technique was used to measure gastric emptying and postprandial frequency of antral contractions. Results: The area under the curve of gastric retention versus time of liquid or solid radiolabelled marker was not changed by sildenafil intake, nor was the postprandial frequency of antral contractions affected by sildenafil. Conclusion: A single dose of 50 mg sildenafil does not change gastric emptying or postprandial frequency of antral contractions in healthy volunteers.

Cardiac sympathetic imaging with mIBG in cirrhosis and portal hypertension: relation to autonomic and cardiac function

Autonomic and cardiac dysfunction is frequent in cirrhosis and includes increased sympathetic nervous activity, impaired heart rate variability (HRV), and baroreflex sensitivity (BRS). Quantified (123)I-metaiodobenzylguanidine (mIBG) scintigraphy reflects cardiac noradrenaline uptake, and in patients with cardiac failure it predicts outcome. In this study, we aimed to investigate cardiac sympathetic neuronal function in cirrhosis by mIBG scintigraphy in relation to cardiovascular function. Ten patients with alcoholic cirrhosis and 10 age- and sex-matched healthy controls participated in the study. Heart/mediastinum (H/M) ratios of mIBG uptake were calculated 15 and 230 min after intravenous injection of mIBG. Furthermore, washout rate (WOR) of mIBG was calculated. The patients underwent a liver vein catheterization with determination of splanchnic and systemic hemodynamics and measurement of HRV and BRS. mIBG-scintigraphy revealed significantly increased WOR in patients with cirrhosis compared with controls (P < 0.005), whereas H/M uptakes were equal in the groups. Forty percent of the patients had reduced uptake of mIBG in the infero-lateral segment of the left ventricle. WOR correlated significantly with central circulation time, an estimate of central hypovolemia (r = -0.64, P < 0.05) and frequency-corrected QT(F) interval (r = 0.71, P = 0.01). Patients with cirrhosis had significantly decreased HRV and BRS correlating with indicators of abnormal cathecholamine uptake by mIBG although the catecholamine level was normal in the patients. In conclusion, in alcoholic cirrhosis, mIBG scintigraphy reveals autonomic dysfunction and impaired myocardial distribution of sympathetic nervous activity. It is associated to indicators of central hypovolemia, QT interval, and decreased HRV and BRS. Measurement of myocardial catecholamine uptake by mIBG may add important information on autonomic and cardiac dysfunction in cirrhosis.

The influence of sacral nerve stimulation on gastrointestinal motor function in patients with fecal incontinence

Background  Sacral nerve stimulation (SNS) is a well‐established treatment for fecal incontinence of various etiologies. However, the mechanism of action remains unclear. The aim of the present study was to determine whether SNS affects gastric emptying, small intestinal transit or colonic transit times.