Significant Differences In Gastric Emptying Research Articles

Effect of oral semaglutide on energy intake, appetite, control of eating and gastric emptying in adults living with obesity: A randomized controlled trial.

To investigate the effects of once-daily oral semaglutide 50 mg on energy intake, appetite, control of eating and gastric emptying. A clinical pharmacology, double-blind study was conducted in 61 adults with obesity randomized to once-daily oral semaglutide (dose-escalated to 50 mg) or placebo for 20 weeks. Energy intake was measured during an ad libitum lunch, and participant-reported appetite ratings and Control of Eating Questionnaire responses were assessed. Gastric emptying was measured using paracetamol absorption following a standardized breakfast. The relative change from baseline in ad libitum energy intake at week 20 (primary endpoint) was -39.2% points (95% confidence interval -59.0%, -19.4%) with semaglutide compared with placebo. Body weight was reduced by 9.8% with semaglutide and by 1.5% with placebo. Semaglutide reduced hunger, increased fullness and satiety, and was associated with fewer food cravings and better control of eating versus placebo. No statistically significant difference in gastric emptying was observed at week 20. In participants with obesity, once-daily oral semaglutide 50 mg reduced energy intake, body weight and appetite, and improved control of eating. There was no evidence of delayed gastric emptying at week 20, as measured through paracetamol absorption.

Leptin-Melanocortin pathway variants and gastric emptying in patients with obesity.

Accelerated gastric emptying (GE) is a trait seen in obesity. Mutations in the hypothalamic leptin-melanocortin 4 receptor (Leptin-MC4R) pathway have been associated with obesity. We sought to investigate the association of leptin-MC4R pathway variants and GE in patients with obesity. This is a cross-sectional study of patients with a history of severe obesity that were genotyped and completed a GE test by scintigraphy. We evaluated the percentage of GE (GE %) at 2 and 4 h between both groups using ANCOVA with weight and sex as covariates. We subdivide patients into carriers based on the location of the identified variants (i.e., upstream or downstream of the Leptin-MC4R pathway) and compared them with noncarriers using ANOVA. Results are presented as mean and standard deviation (± SD). A total of 95 patients; nine carriers (67% females; 39.78 ± 12.33 years; BMI: 49.14 ± 12.96 kg/m2) and 86 noncarriers (87% female; 49.98 ± 13.74 years; BMI: 40.75 ± 6.29 kg/m2) were included. At 2 and 4 h, carriers had a delayed GE when compared noncarriers (p = 0.03 and p = 0.005, respectively). In carriers, when compared upstream carriers vs. downstream carriers vs. noncarriers by location there was a significant difference in GE among groups at 2 h and at 4 h (p = 0.02 and p = 0.01, respectively). Carriers of heterozygous variants in the Leptin-MC4R pathway had a delayed GE compared to noncarriers. These findings point the important relationship between the Leptin-MC4R pathway and gastric motility.

β-Endorphins are not responsible for delayed gastric emptying of digestible solids after exercise in professional cyclists. A preliminary study

ObjectiveIt has been reported that professional cyclists had an accelerated solid gastric emptying which decreased by increasing the exercise intensity. That could be explained by a predominance of stress-dependent motility inhibitors such gastrointestinal hormones, neurotransmitters and or the predominance of the gastric inhibitory vagal motor circuit. The aim of this preliminary study was to evaluate the role of β-endorphins, inhibitors of gastric motility, in these findings. MethodsGastric emptying of solids marked with Tc99 while resting and plasmatic levels of β-endorphins were evaluated in 27 healthy controls and 19 professional cyclists (day 1). Besides, gastric emptying of solids was also assessed in cyclists when they reached 50% (day 1) and 75% (day 2) of the maximum oxygen consumption (low and high, respectively), during exercise on the cycle-ergometer. The third day, naloxone was administered in cyclists in order to block the β-endorphins receptors and gastric emptying was measured when they reached 75% of the maximum oxygen consumption. ResultsBasal β-endorphin levels were lower in cyclists vs controls (p<0.05) and they increased with the exercise intensity (p<0.001). There were no significant differences in gastric emptying of solids with or without naloxone when 75% of the maximum oxygen consumption was reached. ConclusionsThe inhibitory effect of the exercise in the gastric emptying of solids does not seem to be secondary to the action of β-endorphins, that leaves the gastric inhibitory vagal motor circuit a more likely predominant role.

Gastric emptying of milk in infants and children up to 5years of age: normative data and influencing factors.

Gastric emptying scintigraphy is widely used in infants and children, but there is a lack of age-specific normative data. The objectives of this retrospective study were: 1) to establish a range of gastric emptying of milk or formula as a surrogate for normal gastric emptying in infants and young children ≤5years of age, and 2) to investigate the effects of patient age, feeding volume, feeding route and gastroesophageal reflux on gastric emptying. The reports of 5,136 gastric emptying studies of children ≤5years of age performed at Children's National Medical Center from January 1990 to August 2012 were reviewed. Demographic data, 1-h and 3-h gastric emptying values and gastroesophageal reflux status of all patients were stored in a database. Using stringent inclusion and exclusion criteria, the studies of patients as similar to healthy children as possible were selected for this study. The study group included 2,273 children (57% male) ages 0-59months (median: 4.6months). The median 1-h gastric emptying was 43% (interquartile range [IQR] 34-54%). The median 3-h gastric emptying was 91% (IQR 79-98%). Sixty-one percent of patients with 1-h gastric emptying value of <50% had 3-h gastric emptying ≥80%. Gastric emptying was significantly faster in children ≤6months as compared with all older age groups. In each age group, the median gastric emptying decreased with increasing feeding volume. Gastric emptying was significantly faster in patients fed via combined nasogastric tube and oral routes as compared with those fed exclusively orally. There was no significant difference in gastric emptying of children with and without gastroesophageal reflux. Although there are statistically significant differences in gastric emptying based on age, volume and route of feeding, the data suggest that overall normal liquid gastric emptying in infants and children ≤5years of age is ≥80% at 3h. One-hour emptying measurements are not reliable for detecting delayed gastric emptying.

Changes in Time of Gastric Emptying After Surgical and Endoscopic Bariatrics and Weight Loss: A Systematic Review and Meta-Analysis

Gastric emptying (GE) is involved in the regulation of appetite. We compared times of GE after different bariatric endoscopic and surgical interventions and associations with weight loss. We performed a comprehensive search of publication databases, through September 14, 2018, for randomized and nonrandomized studies reporting outcomes of weight-loss surgeries. Two independent reviewers selected and appraised studies. The outcome of interest was GE T1/2 (min), measured before and after the procedure. A random-effects model was used to pool the mean change in T1/2 (min) after the intervention. We performed a meta-regression analysis to find associations between GE and weight loss. Heterogeneity was calculated using the I2 statistic. Methodologic quality was assessed. From 762 citations, the following studies were included in our analysis: 9 sleeve gastrectomies, 5 intragastric balloons, and 5 antral botulinum toxins. After sleeve gastrectomy, the pooled mean reduction in GE T1/2 at 3 months was 29.2 minutes (95% CI, 40.9-17.5 min; I2= 91%). Fluid-filled balloons increased GE T1/2 by 116 minutes (95% CI, 29.4-203.4 min; I2= 58.6%). Air-filled balloons did not produce a statistically significant difference in GE T1/2. Antral botulinum injections increased GE T1/2 by 9.6 minutes (95% CI, 2.8-16.4 min; I2= 13.3%). Placebo interventions reduced GE T1/2 by 6.3 minutes (95% CI, 10-2.6 min). Changes in GE were associated with weight loss after sleeve gastrectomy and intragastric balloons, but not botulinum toxin injections. In a systematic review and meta-analysis, we found that sleeve gastrectomy reduced GE T1/2 whereas fluid-filled balloons significantly increased GE T1/2. Air-filled balloons do not significantly change the time of GE, which could account for their low efficacy. Antral botulinum toxin injections produced small temporary increases in GE time, which were not associated with weight loss. Changes in GE time after surgical and endoscopic bariatric interventions correlated with weight loss and might be used to select interventions, based on patients' physiology.

Moderate‐Intensity Treadmill‐Training and Functional Changes in Solid Meal Gastric Emptying in a Rodent Model

PURPOSEExercise has long been known for the beneficial effects on numerous systems within the body; it improves cardiovascular function, improves brain functioning and memory, reduces adipose tissue lowering the risk of obesity and associated disorders. But the overall effect of exercise on the gastrointestinal (GI) tract remains unresolved. Patients suffering from GI dysfunction are frequently prescribed physical activity to improve their symptoms. Yet, physical activity has also been shown to provoke GI disturbances including diarrhea, abdominal pain, and gastroesophageal reflux. These GI disturbances commonly occur after bouts of prolonged or high‐intensity exercise, and the GI disturbance frequency is twice as high during running compared to other endurance sports. The effects of upper GI function following exercise are diverse; studies have reported increases, decreases, or no changes in gastric emptying (GE) rate following treadmill‐training. We hypothesize that exercise contributes to beneficial effects on the upper GI tract, like other systems, by altering peripheral and central signaling mechanisms regulating gastric motility. By gaining a greater understanding of the relationship between exercise and gastric functioning, exercise may serve a putative role as medicine in treating a number of upper GI‐related health disorders and dysfunctions (e.g. gastroparesis).METHODSIn this study, we evaluated the effects of moderate‐intensity treadmill‐training (66.6% VO2 max) on GE rate in rats. Male Wistar rats were exercised (n = 8) or placed (n = 8; control) on a treadmill five days week−1 for 8 weeks. Baseline, mid‐point, and final GE measurements were conducted throughout the study. On the days of the GE experiment, rats were fasted overnight with unlimited access to water, and then placed into individual chambers where GE was indirectly measured. Baseline air measurements were collected before the fasted rats received 1g of pancake containing 5μL of the stable isotope [13C]‐octanoic acid. The exhaled breath was collected and analyzed to determine the [13C]‐ to [12C]‐ carbon dioxide ratio.RESULTSBody mass increased over the duration of the study by 41%; however, there were no significant differences between exercise and control rats (325.40±3.11 vs. 325.99±3.06g; p&gt;0.05). Food intake remained similar between exercise and control rats (23.23±0.20 vs. 23.19±0.20; p&gt;0.05). Not surprisingly, mean energy intake (MEI; kcal/100g/day) also revealed no significant differences between exercise and control rats (28.99±0.50 vs. 28.90±0.55; p&gt;0.05). There was no significant difference in GE between the exercise and control group gastric emptying coefficient (5.10±1.37 vs 5.04±0.40; p&gt;0.05).CONCLUSIONModerate‐intensity treadmill‐training for 8‐weeks has no significant effect on anthropometric factors. Interestingly, however, as body mass and food intake increased, MEI decreased. We have validated that moderate‐intensity treadmill running has no significant effect on gastric emptying function but structural adaptations may be occurring prior to functional detection.Support or Funding InformationResearch &amp; Professional Development Grant (Gettysburg College Provost), Cross‐Disciplinary Science Institute at Gettysburg College (X‐SIG), X‐SIG Student Supply GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Intraoperative Fluid Restriction in Pancreatic Surgery: A Double Blinded Randomised Controlled Trial.

BackgroundPerioperative fluid restriction in a variety of operations has shown improvement of: complications, recovery of gastrointestinal function and length of stay (LOS). We investigated effects of crystalloid fluid restriction in pancreatic surgery. Our hypothesis: enhanced recovery of gastrointestinal function.MethodsIn this double-blinded randomized trial, patients scheduled to undergo pancreatoduodenectomy (PD) were randomized: standard (S:10ml/kg/hr) or restricted (R:5ml/kg/hr) fluid protocols. Primary endpoint: gastric emptying scintigraphically assessed on postoperative day 7.ResultsIn 66 randomized patients, complications and 6-year survival were analyzed. 54 patients were analyzed in intention to treat: 24 S-group and 30 R-group. 32 patients actually underwent a PD and 16 patients had a palliative gastrojejunostomy bypass operation in the full protocol analysis. The median gastric emptying time (T½) was 104 minutes (S-group, 95% confidence interval: 74–369) versus 159 minutes (R-group, 95% confidence interval: 61–204) (P = 0.893, NS). Delayed gastric emptying occurred in 10 patients in the S-group and in 13 patients in the R-group (45% and 50%, P = 0.779, NS). The primary outcome parameter, gastric emptying time, did not show a statistically significant difference between groups.ConclusionA fluid regimen of 10ml/kg/hr or 5ml/kg/hr during pancreatic surgery did not lead to statistically significant differences in gastric emptying. A larger study would be needed to draw definite conclusions about fluid restriction in pancreatic surgery.Trial registration ISRCTN62621488

A randomized, double-blind, placebo-controlled, multiple-dose, parallel-group clinical trial to assess the effects of teduglutide on gastric emptying of liquids in healthy subjects

BackgroundTeduglutide, a recombinant analog of human glucagon-like peptide (GLP)-2, is a novel therapy recently approved for the treatment of adult patients with short bowel syndrome who are dependent on parenteral support. Previous studies assessing the effect of GLP-2 on gastric emptying in humans have yielded inconsistent results, with some studies showing no effect and others documenting a GLP-2–dependent delay in gastric emptying. The primary objective of this study was to assess the effect of teduglutide on gastric emptying of liquids in healthy subjects, as measured by the pharmacokinetics of acetaminophen.MethodsThis double-blind, parallel-group, single-center study enrolled and randomized 36 healthy subjects (22 men, 14 women) to receive subcutaneous doses of teduglutide 4 mg or placebo (2:1 ratio; 23:13) once daily on Days 1 through 10 in the morning. Gastric emptying of a mixed nutrient liquid meal was assessed by measuring acetaminophen levels predose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12, and 14 hours after administration of 1000 mg acetaminophen on Days 0 and 10. The primary study endpoint was a pharmacokinetic analysis of acetaminophen absorption in subjects receiving teduglutide or placebo.ResultsNo significant differences in gastric emptying of liquids (acetaminophen area under the concentration [AUC] vs time curve from time 0 to the last measurable concentration, AUC extrapolated to infinity, maximum concentration [Cmax], and time to Cmax) were observed on Day 10 in subjects receiving teduglutide 4 mg versus subjects receiving placebo. There were no serious adverse events (AEs), deaths, or discontinuations due to an AE reported during the study.ConclusionsTeduglutide 4 mg/day for 10 days does not affect gastric emptying of liquids in healthy subjects as measured by acetaminophen pharmacokinetics. No unexpected safety signals were observed.Trial registrationThis study was registered at ClinicalTrials.gov, identifier NCT01209351.

Reproducibility of gastric emptying in overweight and obese males

To understand whether any change in gastric emptying (GE) is physiologically relevant, it is important to identify its variability. Information regarding the variability of GE in overweight and obese individuals is lacking. The aim of this study was to determine the reproducibility of GE in overweight and obese males. Fifteen overweight and obese males [body mass index 30.3 (4.9) kg/m(2)] completed two identical GE tests 7 days apart. GE of a standard pancake breakfast was assessed by (13)C-octanoic acid breath test. Data are presented as mean (±SD). There were no significant differences in GE between test days (half time (t1/2): 179 (15) and 176 (19 min), p = 0.56; lag time (tlag): 108 (14) and 104 (8) min, p = 0.26). Mean intra-individual coefficient of variation for t1/2 was 7.9% and tlag 7.5%. Based on these findings, to detect a treatment effect in a paired design with a power of 80% and α = 0.05, minimum mean effect sizes for t1/2 would need to be ≥14.4 min and tlag ≥ 8.1 min. These data show that GE is reproducible in overweight and obese males and provide minimum mean effect sizes required to detect a hypothetical treatment effect in this population.

Insuficiência renal crónica em hemodiálise: um fator de risco independente para angiodisplasias na enteroscopia por videocápsula na hemorragia digestiva obscura

IntroductionThe spectrum of small bowel pathology in terminal renal failure (TRF) - dialysis patients is not well characterized in the literature. The aim of this study was to evaluate the role of the wireless capsule enteroscopy (WCE) in the management of obscure digestive bleeding (ODB) in patients with chronic renal failure (CRF) undergoing haemodialysis, in comparison to a group of patients with creatinine clearance (CrCl) >60 mL/min. Material and methodsThis prospective cohort study included 90 patients with ODB: 12 patients with CrCl <30mL/min undergoing haemodialysis and 78 patients with CrCl >60 mL/min, all referred for WCE in a single institution in a 12 month-period. Estimated CrCL using Cockcroft-Gault formula was determined in the day of WCE for all patients. Patient's demographic data and clinical characteristics, WCE findings and outcome (including specific therapy, transfusion requirements and hospital admissions due to recurrent bleeding or severe anemia) were assessed. ResultsPatients’ age and the clinical presentation of ODB (occult/overt) were similar in the 2 groups. There were no significant differences in gastric emptying and small bowel transit times, or in the ratio of incomplete/inconclusive exams. In patients undergoing haemodialysis, there were fewer normal WCE procedures (17% versus 46%, respectively, p=0,031) and a higher prevalence of small bowel angiodysplasias (58% versus 23%, respectively, p=0,011). By logistic regression analysis, CRF in haemodyalisis was found to be the only predictive factor for angiodysplasias in WCE (p=0,017, 95% CI 0,061-0,758). The group of patients undergoing haemodyalisis also had greater transfusion requirements and hospital admissions due to bleeding recurrence/severe anaemia during the follow-up period (average time, 7,5 months). ConclusionsThis prospective study demonstrated that haemodyalisis is an independent predictive factor for angiodysplasias in WCE for ODB.

Size discrimination in rat and mouse gastric emptying

To investigate the relationship between particle size and gastric emptying in rodents using radiolabeled insoluble polymethyl methacrylate (PMMA) microcapsules/beads. PMMA microcapsules (50-500 µm) and beads (0.5-3 mm) loaded with technetium-99 m diethylenetriamine pentaacetic acid ((99m) Tc-DTPA) were administered to ICR mice or Sprague Dawley (SD) rats by oral gavage. Gamma scintiscans were acquired initially following administration and then at hourly intervals to 4 hours. Scintiscans revealed that the smallest PMMA microcapsules (50-100 µm) or beads (0.5-1 mm) were impeded in the stomach and emptied slower than large particles in both rodent species. In mice, no significant difference in gastric emptying was found with microcapsules between 100 and 300 µm in diameter (p = 0.25) and particles more than 300 µm could not be administered. In rats, capsules containing 0.5-3 mm beads were stuck to the esophagus (up to 1 hour), this was a limitation of dosing beads of this size because they cannot be suspended in a liquid media for oral gavage purposes. Beads with diameters of 2-3 mm stayed in the stomach for up to 4 hours. The cut-off emptying size in ICR mice could not be determined, due to the limitation of current available dosing methods. The cut-off emptying size in SD rats was between 1.5 and 2 mm. Therefore, particles with a diameter greater than 2 mm should not be used for gastric emptying studies of intact particles in SD rats, as their emptying is retarded in the stomach.

Effect ofGongronema latifoliumon gastric emptying in healthy dogs

To investigate sonographically the effect of Gonogronema latifolium (G. latifolium) on gastric emptying of semi-solid meals in healthy dogs. In a randomized, placebo-controlled experiment, twenty-five clinically healthy dogs were randomly allotted into five groups of five dogs in each group. The placebo group served as the control, and the low, moderate and high dose groups ingested the methanolic leaf extract of G. latifolium in capsules at 100 mg/kg, 250 mg/kg and 500 mg/kg, respectively, while the prokinetic group ingested 0.5 mg/kg capsules of metoclopramide. After a 12-h fast, each group ingested its treatment capsules 30 min before the administration of a test meal. Measurements of gastric emptying and blood glucose levels were obtained 30 min before and immediately after the ingestion of the test meal and thereafter every 15 min for 4 h. This was followed by further measurements every 30 min for another 2 h. The gastric emptying times of the placebo, low dose, moderate dose, high dose and prokinetic dose groups were 127.0 ± 8.2 min, 135.5 ± 3.7 min, 155.5 ± 3.9 min, 198.0 ± 5.3 min and 59.0 ± 2.5 min, respectively. Gastric emptying times of the moderate and high dose groups were significantly slower than in the placebo control group (155.5 ± 3.9 min, 198.0 ± 5.3 min vs 127.0 ± 8.2 min, P = 0.000). No significant difference in gastric emptying between the low dose and placebo control groups was noted (135.5 ± 3.7 min vs 127.0 ± 8.2 min, P = 0.072). Gastric emptying of the prokinetic group was significantly faster than that of the control group (59.0 ± 2.5 min vs 127.0 ± 8.2 min, P = 0.000). The hypoglycaemic effect of G. latifolium and gastric emptying were inversely related (r = -0.95, P = 0.000). G. latifolium delays gastric emptying and lowers postprandial blood glucose in healthy dogs. It reduces the postprandial blood glucose by delaying gastric emptying.

Gastric emptying, mouth-to-cecum transit, and glycemic, insulin, incretin, and energy intake responses to a mixed-nutrient liquid in lean, overweight, and obese males

Observations relating to the impact of obesity on gastric emptying (GE) and the secretion of gut hormones are inconsistent, probably because of a lack of studies in which GE, gastrointestinal hormone release, and energy intake (EI) have been evaluated concurrently with previous patterns of nutrient intake. GE is known to be a major determinant of postprandial glycemia and incretin secretion in health and type 2 diabetes. The aims of this study were to determine the effects of a mixed-nutrient drink on GE, oro-cecal transit, blood glucose, insulin and incretin concentrations and EI, and the relationship between the glycemic response to the drink with GE in lean, overweight, and obese subjects. Twenty lean, 20 overweight, and 20 obese males had measurements of GE, oro-cecal transit, and blood glucose, insulin, GLP-1, and GIP concentrations for 5 h after ingestion of a mixed-nutrient drink (500 ml, 532 kcal); EI at a subsequent buffet lunch was determined. Habitual EI was also quantified. Glycemic and insulinemic responses to the drink were greater in the obese (both P < 0.05) when compared with both lean and overweight, with no significant differences in GE, intragastric distribution, oro-cecal transit, incretins, or EI (buffet lunch or habitual) between groups. The magnitude of the rise in blood glucose after the drink was greater when GE was relatively more rapid (r = -0.55, P < 0.05). In conclusion, in the absence of differences in habitual EI, both GE and incretin hormones are unaffected in the obese despite greater glucose and insulin responses, and GE is a determinant of postprandial glycemia.

Sa1961 Teduglutide, a Human Recombinant Analog of Glucagon-Like Peptide-2 (GLP-2), Increases Plasma Citrulline Levels in Patients With Short Bowel Syndrome

Objective: Teduglutide, a human recombinant analog of glucagon-like peptide (GLP)-2, is a novel therapy in development for short bowel syndrome. GLPs are derived fromproglucagon and, therefore, may affect gastric emptying. Change in gastric emptying may alter drug bioavailability. Our primary objective was to assess the effect of teduglutide on gastric emptying in healthy subjects, as measured by acetaminophen pharmacokinetics, an accepted measure of gastric emptying kinetics. Secondary objectives included assessment of the effects of teduglutide on preprandial and postprandial insulin, glucagon, and glucose. Methods: This double-blind, single-center study randomized 36 healthy subjects (22 male, 14 female) to receive subcutaneous doses of teduglutide 4 mg or placebo (2:1 ratio; 23:13) once daily on days 1-10 in the morning. The dose was chosen based on 0.05mg/kg/day in healthy subjects up to 80 kg in body weight. Gastric emptying was assessed by measuring acetaminophen levels pre-dose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12, and 14 hours after administration of 1000 mg acetaminophen on days 0 and 10. Blood levels of glucagon, insulin, and glucose were obtained at screening, day 0, and day 10. Results: No significant differences in gastric emptying (acetaminophen area under the concentration vs time curve from time 0 to the last measureable concentration [AUC0-last], AUC0-∞, maximum concentration [Cmax]) were observed on day 10 in subjects receiving teduglutide 4 mg vs subjects receiving placebo. There was no significant difference in time to acetaminophen Cmax between the 2 groups. Similarly, there were no significant differences in preprandial or postprandial insulin level parameters (AUC0-last, AUC0-inf, Cmax, AUC0-3h, Cmax03h) between the teduglutide and placebo groups. Teduglutide increased both fasting and postprandial glucagon levels (Figure), although the differences were small and not considered clinically meaningful. Teduglutide also increased postprandial glucose up to 10 hours compared with placebo (Figure). These changes were not considered clinically meaningful (<10% increase). Conclusions: Teduglutide does not affect gastric emptying in healthy subjects as measured by acetaminophen pharmacokinetics. In healthy subjects, teduglutide did not exert any clinically meaningful effects on serum insulin, glucagon, or glucose in either the fasted or fed state.

Sa1959 A Randomized, Double-Blind, Placebo-Controlled, Multiple-Dose, Parallel-Group Study to Assess the Effects of Teduglutide on Gastric Emptying in Healthy Subjects

Objective: Teduglutide, a human recombinant analog of glucagon-like peptide (GLP)-2, is a novel therapy in development for short bowel syndrome. GLPs are derived fromproglucagon and, therefore, may affect gastric emptying. Change in gastric emptying may alter drug bioavailability. Our primary objective was to assess the effect of teduglutide on gastric emptying in healthy subjects, as measured by acetaminophen pharmacokinetics, an accepted measure of gastric emptying kinetics. Secondary objectives included assessment of the effects of teduglutide on preprandial and postprandial insulin, glucagon, and glucose. Methods: This double-blind, single-center study randomized 36 healthy subjects (22 male, 14 female) to receive subcutaneous doses of teduglutide 4 mg or placebo (2:1 ratio; 23:13) once daily on days 1-10 in the morning. The dose was chosen based on 0.05mg/kg/day in healthy subjects up to 80 kg in body weight. Gastric emptying was assessed by measuring acetaminophen levels pre-dose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12, and 14 hours after administration of 1000 mg acetaminophen on days 0 and 10. Blood levels of glucagon, insulin, and glucose were obtained at screening, day 0, and day 10. Results: No significant differences in gastric emptying (acetaminophen area under the concentration vs time curve from time 0 to the last measureable concentration [AUC0-last], AUC0-∞, maximum concentration [Cmax]) were observed on day 10 in subjects receiving teduglutide 4 mg vs subjects receiving placebo. There was no significant difference in time to acetaminophen Cmax between the 2 groups. Similarly, there were no significant differences in preprandial or postprandial insulin level parameters (AUC0-last, AUC0-inf, Cmax, AUC0-3h, Cmax03h) between the teduglutide and placebo groups. Teduglutide increased both fasting and postprandial glucagon levels (Figure), although the differences were small and not considered clinically meaningful. Teduglutide also increased postprandial glucose up to 10 hours compared with placebo (Figure). These changes were not considered clinically meaningful (<10% increase). Conclusions: Teduglutide does not affect gastric emptying in healthy subjects as measured by acetaminophen pharmacokinetics. In healthy subjects, teduglutide did not exert any clinically meaningful effects on serum insulin, glucagon, or glucose in either the fasted or fed state.

Sa1962 Short Bowel Syndrome Patients With Intestinal Failure (SBS-IF) Successfully Achieved Complete Independence From Parenteral Nutrition and/or Intravenous Fluid (PN/IV) With Teduglutide

Objective: Teduglutide, a human recombinant analog of glucagon-like peptide (GLP)-2, is a novel therapy in development for short bowel syndrome. GLPs are derived fromproglucagon and, therefore, may affect gastric emptying. Change in gastric emptying may alter drug bioavailability. Our primary objective was to assess the effect of teduglutide on gastric emptying in healthy subjects, as measured by acetaminophen pharmacokinetics, an accepted measure of gastric emptying kinetics. Secondary objectives included assessment of the effects of teduglutide on preprandial and postprandial insulin, glucagon, and glucose. Methods: This double-blind, single-center study randomized 36 healthy subjects (22 male, 14 female) to receive subcutaneous doses of teduglutide 4 mg or placebo (2:1 ratio; 23:13) once daily on days 1-10 in the morning. The dose was chosen based on 0.05mg/kg/day in healthy subjects up to 80 kg in body weight. Gastric emptying was assessed by measuring acetaminophen levels pre-dose and at 0.25, 0.5, 0.75, 1, 1.25, 1.5, 2, 3, 3.5, 4, 5, 6, 8, 10, 12, and 14 hours after administration of 1000 mg acetaminophen on days 0 and 10. Blood levels of glucagon, insulin, and glucose were obtained at screening, day 0, and day 10. Results: No significant differences in gastric emptying (acetaminophen area under the concentration vs time curve from time 0 to the last measureable concentration [AUC0-last], AUC0-∞, maximum concentration [Cmax]) were observed on day 10 in subjects receiving teduglutide 4 mg vs subjects receiving placebo. There was no significant difference in time to acetaminophen Cmax between the 2 groups. Similarly, there were no significant differences in preprandial or postprandial insulin level parameters (AUC0-last, AUC0-inf, Cmax, AUC0-3h, Cmax03h) between the teduglutide and placebo groups. Teduglutide increased both fasting and postprandial glucagon levels (Figure), although the differences were small and not considered clinically meaningful. Teduglutide also increased postprandial glucose up to 10 hours compared with placebo (Figure). These changes were not considered clinically meaningful (<10% increase). Conclusions: Teduglutide does not affect gastric emptying in healthy subjects as measured by acetaminophen pharmacokinetics. In healthy subjects, teduglutide did not exert any clinically meaningful effects on serum insulin, glucagon, or glucose in either the fasted or fed state.

Measurement of gastric emptying of a high-nutrient liquid by 3D ultrasonography in diabetic gastroparesis

Gastric emptying (GE) is delayed in 30-50% of patients with longstanding diabetes. Scintigraphy represents the 'gold standard' for measurement of GE, but is associated with a radiation burden. Three-dimensional (3D) ultrasonography has recently been demonstrated to provide a valid measure of liquid GE in healthy subjects; however, the technique has not been validated in patients with gastroparesis. The primary aim of this study was to compare measurements of GE of a high-nutrient glucose drink by 3D ultrasonography and scintigraphy in diabetic gastroparesis. Ten patients (eight type 1, two type 2, 6M, 4F, aged 46.1 ± 4.5 years, BMI 29.1 ± 1.6 kg m(-2), duration 19.6 ± 3.3 years) with diabetic gastroparesis [defined as retention at 100 min of solid (100 g minced beef) ≥ 61% and/or 50% emptying time (T50) of liquid (150 mL 10% dextrose) ≥ 31 min], were studied. Concurrent measurements of GE by scintigraphy and 3D ultrasonography were performed following ingestion of 75 g glucose in 300 mL water labeled with 20 MBq (99m) Tc-sulfur colloid. There was no significant difference in GE between the two techniques (T50s: scintigraphy - 103.3 ± 10.0 min VS 3D ultrasonography - 98.8 ± 10.4 min; P = 0.60). There was a significant correlation between scintigraphic and ultrasonographic T50s (r = 0.67, P = 0.03). The limits of agreement for the T50s were -57.22 min and +48.22 min (mean difference -4.5 min). Blood glucose after the drink was greater when GE was relatively more rapid (e.g. at t = 60 min; scintigraphy: r = -0.65, P = 0.04; 3D ultrasonography: r = -0.78, P = 0.008). Three-dimensional ultrasonography appears to provide a valid, and non-invasive, measure of GE of high-nutrient liquids in diabetic gastroparesis.

Utility of whole gut transit scintigraphy in patients with chronic gastrointestinal symptoms

To review our experience of doing whole gut transit scintigraphy in patients presenting with functional gastrointestinal problems and to determine its clinical usefulness. All whole gut transit studies using a liquid meal over a 5-year-period were reviewed and clinical outcome assessed. Fifty-five patients (44 women; mean age 43 years) underwent whole gut transit scintigraphy using indium-111 diethylene triamine penta-acetic acid in water. The main symptoms were constipation (49%), dyspepsia (25%) and diarrhoea (25%). Colonic transit was delayed in 63% of patients with constipation, which was significantly (P=0.005) higher than that in patients with dyspepsia. Delayed colonic transit was also seen in 43% of patients with diarrhoea. Only 26% of patients with constipation had a delay in liquid gastric emptying and small bowel transit. Gastric emptying, small bowel transit and colonic transit were normal in 43, 79 and 29% of patients with dyspepsia, respectively. There was no statically significant difference in gastric emptying and small bowel transit between patients with constipation, diarrhoea and dyspepsia. Liquid-phase whole gut transit scintigraphy seems to be a useful investigation in patients with chronic gastrointestinal symptoms. Rational use of this modality may help the clinician change the management or better characterize the underlying problem/diagnosis in the majority of patients with functional symptoms.

Hedonics of taste influence the gastric emptying in rats

It is known that taste sensation plays important roles in various functions including appetite, nutriental choices, food intake and digestion. To study the modulation of digestive functions by taste stimulation, we measured the gastric emptying of experimental foods with appetitive or aversive tastes in Wistar male rats. Rats were randomly divided into 3 groups: each group was trained to eat a mash mixture (8 g) made up with powdered food (4 g) and a solution (4 g) for 30 min per day. The solution was either distilled water, saccharin solution as a palatable taste, or quinine solution as an aversive taste. On the test day, the contents of the stomach of each rat were measured before and 30, 150, or 300 min after the start of eating the mash. The results showed that the food output from the stomach was increased by the palatable mash and was decreased by the aversive mash in comparison with non-adulterated mash 150 min after eating. There were no significant differences in gastric emptying among the 3 groups after deafferentation of the two peripheral taste nerve branches, the chorda tympani and glossopharyngeal nerves, or after intragastric infusions of each mash. After the establishment of conditioned taste aversions to saccharin, saccharin mash became ineffective in increasing gastric emptying. These results show that hedonically positive tastes increase, but hedonically negative tastes decrease gastric function in terms of gastric emptying.

UDP-glucose modulates gastric function through P2Y14 receptor-dependent and -independent mechanisms

P2Y receptors have been reported to modulate gastrointestinal functions. The newest family member is the nucleotide-sugar receptor P2Y14. P2ry14 mRNA was detected throughout the rat gut, with the highest level being in the forestomach. We investigated the role of the receptor in stomach motility using cognate agonists and knockout (KO) mice. In rat isolated forestomach, 100 microM UDP-glucose and 100 muM UDP-galactose both increased the baseline muscle tension (BMT) by 6.2+/-0.6 and 1.6+/-0.6 mN (P<0.05, n=3-4), respectively, and the amplitude of contractions during electrical field stimulation (EFS) by 3.7+/-1.7 and 4.3+/-2.5 mN (P<0.05, n=3-4), respectively. In forestomach from wild-type (WT) mice, 100 microM UDP-glucose increased the BMT by 1.0+/-0.1 mN (P<0.05, n=6) but this effect was lost in the KO mice (change of -0.1+/-0.1 mN, n=6). The 100 microM UDP-glucose also increased the contraction amplitude during EFS in this tissue from the WT animals (0.9+/-0.4 mN, P < 0.05, n=6) but not from the KO mice (0.0+/-0.2 mN, n=6). In vivo, UDP-glucose at 2,000 mg/kg ip reduced gastric emptying in rats by 49.7% (P<0.05, n=4-6) and in WT and KO mice by 56.1 and 66.2%, respectively (P<0.05, n=7-10) vs. saline-treated control animals. There was no significant difference in gastric emptying between WT and KO animals receiving either saline or d-glucose. These results demonstrate a novel function of the P2Y14 receptor associated with contractility in the rodent stomach that does not lead to altered gastric emptying after receptor deletion and an ability of UDP-glucose to delay gastric emptying without involving the P2Y14 receptor.