Gastric Emptying Of Liquids Research Articles

Simultaneous non-invasive measurement of liquid gastric emptying and small bowel transit by combined 13C-acetate and H2-lactulose breath test

The 13C-acetate breath test (13C-ABT) allows noninasive measurement of liquid gastric emptying time (LGET), the H2-lactulose breath (H2-LBT) measures orocecal transit time (OCTT). Because of different test principles, both tests can generally be combined. This would not only spare time and resources but may also deliver additional information on the integrated regulation of gastrointestinal motor functions. Our aim was to define an adequate test protocol and to generate normal values for the combined 13C-ABT/H2-LBT. Twenty two healthy volunteers participated (HV, 12 females, age: 26.5 ± 4.7 years, BMI: 22 ± 2.1 kg m−2). Fasting subjects received 200 ml of an aequous solution containing 150 mg 13C-acetate and 10 g lactulose. Breath samples for H2 measurements were collected before ingestion of the test solution and afterwards at 5 min intervals for 180 min, for 13C measurements sampling intervals were prolonged to 15 min after the first hour. LGET was defined as time of maximal 13C-exhalation, OCTT as increase in H2 of ⩾ 20 ppm above basal. Small bowel transit time (SBTT) was calculated as the difference between OCTT and LGET. Mean [95% CI] values for LGET, OCTT and SBTT were 26 [23–30] min, 85 [68–102] min and 60 [44–76] min, respectively. Normal values for LGET and OCTT corresponded with published data. SBTT was not correlated with LGET (R2 = 0.019; p = 0.546). By contrast, there was a very tight and highly significant correlation between SBTT and OCTT (R2 = 0.933; p < 0.001). Multivariate linear regression analyses confirmed that age, sex and BMI had no significant effects on OCTT or SBTT while LGET was weakly correlated with BMI (R2 = 0.240; p = 0.021). In conclusion, the combined 13C-ABT/H2-LBT allows simultaneous measurement of LGET and OCTT as well as calculation of SBTT.

18-3 Early effect of carbonated water administration on liquid gastric emptying: crossover study using the 13C breath test

18-3 Early effect of carbonated water administration on liquid gastric emptying: crossover study using the 13C breath test

Sa1358 Comparison of Gastric Motor Functions and Satiation in Overweight and Obese Adults With Allelic Variants At the TCF7l2 Locus to Adults With Common Alleles

Background: Candidate genes have been associated with development of obesity and diabetes. In three Caucasian population studies, the transcription factor 7-like 2 (TCF7L2) gene polymorphism rs7903146 (TT genotype) was predictive of the development of type 2 diabetes mellitus (T2DM). It is unclear whether TCF7L2 gene polymorphisms are associated with alterations of gastric motor functions or satiation. Aim: To determine whether genetic variations of TCF7L2 gene rs7903146 are associated with gastric emptying (GE), gastric accommodation (GA), satiation, satiety or postprandial plasma glucagon-like peptide 1 (GLP1) levels in overweight and obese people. Methods: 271 overweight or obese participants, predominantly Caucasian, underwent, on separate days, validated measurements of intermediate phenotypes: GE of solids and liquids by scintigraphy, gastric volume (GV) by SPECT during fasting and after 200mL Ensure® (accommodation GV), satiation (maximal tolerated volume, MTV) by Ensure® (1 kcal/mL) ingested at 30mL/min, satiety by kcal intake during a buffet meal ingested 4h after intake of the Ensure® meal for the GV test, and fasting and postprandial plasma GLP-1measured by radioimmunoassay. Genotyping of TCF7L2 gene rs7903146 was by TaqMan® SNP Assay. From the 271 participants, we identified 22 individuals with TCF7L2 rs7903146 TT homozygotes and 44 ageand gender-matched CC homozygotes. We tested associations of TCF7L2 genotype with each intermediate phenotype using ANCOVA based on the general genetic model. Results: Data are shown in table. Early phase of GE solids was faster with TCF7L2 TT compared to CC: T1/2 (p=0.031), GE lag time (or time for 10% emptied, p=0.031), percentage GE at 60min (p=0.029). However, percentage emptied at 2-4h was not different in the TT and CC groups. Mean postprandial GLP-1 levels (a measure of AUC) were higher in TT homozygotes compared to CC homozygotes (p=0.026). There were no associations of the TCF7L2 gene with age, BMI, GE of liquids, accommodation GV, satiation (MTV and aggregate symptoms score 30min postMTV), and satiety (kcal ingested 4h later). Although not statistically significant, the mean MTV was 140kcal greater with TT than CC genotype. Conclusion: TCF7L2 homozygous T genotype (rs7903146) is associated with faster gastric emptying of solids in overweight and obese adults; these findings may explain the propensity to develop postprandial hyperglycemia or T2DM, and the non-significant increase in kcal intake may contribute to obesity. The higher postprandial GLP-1 levels in TT homozygotes reflect the faster emptying of the first 50% of the meal; the data are consistent with elevated GLP-1 slowing the emptying of the second half of the meal. Overall, these data suggest important contribution of gastric function to the metabolic effects of TCF7L2 mechanisms. Funding: NIH DK67071

A pilot study of the effects of the somatostatin analog pasireotide in postoperative dumping syndrome.

Dumping syndrome is characterized by distinct pathophysiological features such as postprandial increase in hematocrit (HT) and pulse rate (PR) and delayed hypoglycemia (HG). Treatment is based on dietary measures and somatostatin analogs (SA), but current SAs have incomplete efficacy, possibly through limited affinity for various somatostatin receptor subtypes. We evaluated the effect of pasireotide, a novel SA with high affinity for 4/5 human somatostatin receptors, on pathophysiological events and symptoms in dumping. Randomized double-blind placebo-controlled cross-over study of nine patients (six women, 47±4years) with postoperative dumping. Baseline measurements included oral glucose tolerance testing (OGTT), abdominal ultrasound, and dumping symptom severity score (DSSS). Patients were treated for 2weeks with placebo or pasireotide 300μg s.c. t.i.d. with a 1-week wash-out in a randomized fashion. On day 13 and 14 of each treatment OGTT, DSSS, and solid and liquid gastric emptying (GE) were obtained. Baseline OGTT was pathological in all patients based on PR (n=5), HT (n=1) or HG (n=7). Compared to placebo, pasireotide suppressed the increase in PR (17.1±2.8 vs 8.2±3.5bpm; p<0.05) and late HG (nadir glycemia 55.6±4.3 vs 83.3±9.5mg/dL; p=0.007), increased peak glycemia (294.1±33.3 vs 221.0±23.1mg/dL; p=0.001) and delayed GE of solids (t1/2 83±23 vs 43±9min; p=0.05) and liquids (t1/2 70±10 vs 40±4min, p=0.05). The differences in DSSS did not reach statistical significance. Two patients dropped out because of adverse gastrointestinal events under pasireotide. Pasireotide affects pathophysiological features of both early and late dumping syndrome.

Gastric and intestinal satiation in obese and normal weight healthy people

ObjectiveThe 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. MethodIn 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 13C-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). ResultsOur 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). DiscussionWe 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.

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.

Neural mechanisms and delayed gastric emptying of liquid induced through acute myocardial infarction in rats.

BackgroundIn pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats.ObjectiveInvestigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats.MethodsWistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal.ResultsNo significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE.ConclusionGastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN.

Therapeutic potential of spinal cord stimulation for gastrointestinal motility disorders: a preliminary rodent study

Spinal cord electrical stimulation (SCS) has been applied for the management of chronic pain. Most of studies have revealed a decrease in sympathetic activity with SCS. The aim of this study was to investigate the effects and mechanisms of SCS on gastrointestinal (GI) motility in healthy and diabetic rats. Male rats chronically implanted with a unipolar electrode at T9/T10 were studied. The study included four experiments to assess the effects of SCS on (1) gastric tone; (2) gastric emptying of liquids and intestinal transit; (3) gastric emptying of solids; and (4) sympathovagal balance in healthy rats and/or in Streptozotocin (STZ)-induced diabetic rat. (1) Spinal cord stimulation intensity dependently increased gastric tone in healthy rats. The gastric volume was 0.97 ± 0.15 mL at baseline, and decreased to 0.92 ± 0.16 mL with SCS of the 30% motor threshold (MT; p = 0.13 vs baseline), 0.86 ± 0.14 mL with 60% MT (p = 0.045 vs baseline), and 0.46 ± 0.19 mL with 90% MT (p = 0.0050 vs baseline). (2) Spinal cord stimulation increased gastric emptying of liquids by about 17% and accelerated small intestinal transit by about 20% in healthy rats (p < 0.001). (3) Spinal cord stimulation accelerated gastric emptying of solids by about 24% in healthy rats and by about 78% in diabetic rats. (4) Spinal cord stimulation decreased sympathetic activity (1.13 ± 0.18 vs 0.68 ± 0.09, p < 0.04) and sympathovagal balance (0.51 ± 0.036 vs 0.40 ± 0.029, p = 0.028). Spinal cord stimulation accelerates gastric emptying of liquids and solids, and intestinal transit, probably by inhibiting the sympathetic activity. Spinal cord stimulation may have a therapeutic potential for treating GI motility disorders.

Effect of Intragastric Balloon on Gastric Emptying Time in Humans for Weight Control

This study evaluated the effect of fluid-filled intragastric balloon treatment on the scintigraphic gastric emptying times in humans for weight control. Ten obese patients were prospectively recruited in our study. Three participants followed a solid food diet, and 7 participants followed a liquid meal diet to evaluate their scintigraphic gastric emptying times before and 3 months after fluid-filled intragastric balloon treatment. The participants included 3 males and 7 females. The mean age, body mass index, and body weight before intragastric balloon treatment were 36.8 ± 9.16 years, 35.91 ± 8.86 kg/m(2), and 93.9 ± 24.09 kg, respectively. The mean body weight, body mass index, and body weight loss 3 months after the treatment were 80.2 ± 21.32 kg, 31.50 ± 8.90 kg/m(2), and 13.7 ± 6.60 kg, respectively. The solid gastric emptying times before and 3 months after intragastric balloon treatment were 114 ± 18.52 minutes and 375.33 ± 207.04 minutes, respectively. The liquid gastric emptying times before and after intragastric balloon treatment were 38.71 ± 15.91 minutes and 318.71 ± 168.07 minutes, respectively. Statistically significant differences were observed in the solid and liquid gastric emptying times before and 3 months after intragastric balloon treatment using the Wilcoxon t test (P = 0.027, P = 0.001). Significantly positive correlations were observed between body weight loss and solid and liquid gastric emptying times after intragastric balloon placement using the Spearman correlation (β = 1.0, P < 0.001; β = 0.95, P = 0.001). The solid and liquid scintigraphic gastric emptying half time is significantly longer after intragastric balloon treatment in humans. A significantly positive correlation between body weight loss and scintigraphic gastric emptying time was observed after intragastric balloon treatment. We can predict the effect of intragastric balloons on weight control through scintigraphic gastric emptying times after the treatment. The effect of intragastric balloons on weight loss may be reinforced by combining intragastric balloon treatment with medication that can reduce gastric motility.

Evidence for the involvement of peripheral β-adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg−1·day−1, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.

Gastric emptying and antral motility parameters in children with functional dyspepsia: Association with symptom severity

Functional dyspepsia (FD) is an important gastrointestinal problem with obscure etiology. Abnormal gastric motility is suggested as a possible pathophysiological mechanism for symptoms. The main objective of this study was to assess gastric motility in Sri Lankan children with FD. Forty-one children (19 [46.3%] males, age 4-14 years, mean 7.5 years, SD 2.6 years) referred to the Gastroenterology Research Laboratory, Faculty of Medicine, University of Kelaniya, from January 2007 to December 2011, were screened. Those fulfilling Rome III criteria for FD were recruited. None had clinical or laboratory evidence of organic disorders. Twenty healthy children were recruited as controls (eight [40%] males, age 4-14 years, mean 8.4 years, SD 3.0 years). Liquid gastric emptying rate (GE) and antral motility parameters were assessed using an ultrasound-based method. Average GE (45.6% vs 66.2% in controls), amplitude of antral contractions (58.2% vs 89.0%) and antral motility index (5.1 vs 8.3) were lower and fasting antral area (1.5 cm(2) vs 0.6 cm(2)) was higher in patients with FD (P < 0.01). Frequency of antral contractions (8.8 vs 9.3) did not show a significant difference (P = 0.07). Scores obtained for severity of abdominal pain negatively correlated with GE (r = -0.35, P = 0.025). Children with FD, exposed to stressful events had higher fasting antral area (1.9 cm(2)) than those not exposed to stress (1.0 cm(2)) (P = 0.02). GE and antral motility parameters were significantly impaired in children with FD compared with controls. GE negatively correlated with severity of symptoms. This study points to disturbances in gastric motility as an etiological factor for FD.

Novel and Validated Approaches for Gastric Emptying Scintigraphy in Patients with Suspected Gastroparesis

Controversy exists regarding the relation of upper gastrointestinal symptoms to gastroparesis, which centers on the reportedly weak correlation between symptoms and gastric emptying (GE) measurements. Appropriate management of patients with suspected gastroparesis thus requires the use of validated assessments of GE. GE scintigraphy (GES) using a low-fat EggBeaters (chicken egg white) meal (ConAgra Foods Inc., Omaha, NE, USA) [1] is regarded as the gold standard due to standardized procedures, methods, and well-established normal values. Although this meal has the advantage of good tolerability by the majority of symptomatic patients, there are potential drawbacks: a few patients may not tolerate any solid meal, or the low fat and caloric content may not be able to adequately stress the system, failing to identify impaired gastric motor function in a subset of individuals. Therefore, identification of an alternative, appropriate test meal may be important for clinical and research applications. In this issue, Sachdeva et al. [2] compared GE of the low-fat EggBeaters solid meal (255 kcal containing 2 % fat, 24 % protein, 72 % carbohydrate, and 2 % fiber) to an Ensure Plus (Abbott Laboratories, North Chicago, IL, USA) liquid meal (350 kcal containing 28 % fat, 15 % protein, 57 % carbohydrate, and no fiber) to identify a valid alternative for patients unable to consume the standard low-fat egg-white meal. On separate days, 20 healthy volunteers participated in a well-designed prospective study comparing GES with these two meals; simultaneously, the authors evaluated gastric contractility using a wireless motility capsule (WMC) during both assessments. The objectives were to demonstrate feasibility and to provide hypothesis-generating data (e.g., definition of coefficient of variation [COV; standard deviation/mean] to facilitate the design of future studies). The conclusion that GE of a liquid nutrient meal is similar to that of low-fat egg-white meal (of similar calorie content) is valid, at least in healthy subjects. Nevertheless, as acknowledged by the authors, their results will require replication in a larger cohort, and in subjects with suspected gastroparesis who might differ from a healthy population in terms of having differential GE of solid versus liquid meals. Jones et al. [3] previously reported a significant but weak (r = 0.42, p 0.01) correlation between GE of solids and nutrient-containing liquids among 86 patients with diabetes mellitus. In the study by Sachdeva et al. [2], the correlation between the GE T1/2 of the two meals was similarly weak (r = 0.53) among healthy subjects, suggesting that there are significant intraindividual differences in the emptying of the two meals, and that less than 30 % of the variance is attributable to the same mechanisms for emptying of the two types of meals. It is also necessary to clarify the inter-individual COV with the EggBeaters and the liquid nutrient meal. Diagnostic interpretation of GE T1/2 by GES in an individual patient requires robust definition of the intra-individual COV with the specific meal used. Thus, the estimated COVinter for GE T1/2 was 25 % with the EggBeaters meal and 24 % using a meal of higher fat and calorie content [4] in which the solid phase is radiolabeled. With the latter radiolabeled solid meal, the COVinter for GE at 4 h was 9.6 %, confirming the recommendation by Tougas et al. [1] that the percent retention at 4 h is an endpoint useful for gastroparesis screening. Similarly, others have shown greater sensitivity of detection of abnormal GE with use of M. Camilleri (&) A. Shin Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN 55905, USA e-mail: camilleri.michael@mayo.edu

The Ghrelin Agonist RM-131 Accelerates Gastric Emptying of Solids and Reduces Symptoms in Patients With Type 1 Diabetes Mellitus

RM-131, a synthetic ghrelin agonist, greatly accelerates gastric emptying of solids in patients with type 2 diabetes and delayed gastric emptying (DGE). We investigated the safety and effects of a single dose of RM-131 on gastric emptying and upper gastrointestinal (GI) symptoms in patients with type 1 diabetes and previously documented DGE. In a double-blind cross-over study, 10 patients with type 1 diabetes (age, 45.7 ± 4.4 y; body mass index, 24.1 ± 1.1 kg/m(2)) and previously documented DGE were assigned in random order to receive a single dose of RM-131 (100 μg, subcutaneously) or placebo. Thirty minutes later, they ate a radiolabeled solid-liquid meal containing EggBeaters (ConAgra Foods, Omaha, NE), and then underwent 4 hours of gastric emptying and 6 hours of colonic filling analyses by scintigraphy. Upper GI symptoms were assessed using a daily diary, gastroparesis cardinal symptom index (total GCSI-DD) and a combination of nausea, vomiting, fullness, and pain (NVFP) scores (each rated on a 0-5 scale). At screening, participants' mean level of hemoglobin A1c was 9.1% ± 0.5%; their total GCSI-DD score was 1.66 ± 0.38 (median, 1.71), and their total NVFP score was 1.73 ± 0.39 (median, 1.9). The t1/2 of solid gastric emptying was 84.9 ± 31.6 minutes when subjects were given RM-131 and 118.7 ± 26.7 when they were given a placebo. The median difference (Δ)was 33.9 minutes (interquartile range [IQR] -12, -49), or -54.7% (IQR, -21%,-110%). RM-131 decreased gastric retention of solids at 1 hour (P = .005) and 2 hours (P = .019). Numeric differences in t1/2 for gastric emptying of liquids, solid gastric emptying lag time, and colonic filling at 6 hours were not significant. Total GCSI-DD scores were 0.79 on placebo (IQR, 0.75, 2.08) and 0.17 on RM-131 (IQR, 0.00, 0.67; P = .026); NVFP scores were lower on RM-131 (P = .041). There were no significant adverse effects. RM-131 significantly accelerates gastric emptying of solids and reduces upper GI symptoms in patients with type 1 diabetes and documented DGE.

Early Effect of Single-dose Sitagliptin Administration on Gastric Emptying: Crossover Study Using the C Breath Test

Background/AimsThe gastrointestinal motility effects of endogenous incretin hormones enhanced by dipeptidyl peptidase-IV (DPP-IV) inhibitors have not yet been sufficiently investigated. The aim of this study was to determine whether single pre-prandial sitagliptin, the DPP-IV inhibitor, administration might have an effect on the rate of liquid gastric emptying using the 13C-acetic acid breath test.MethodsTen healthy male volunteers participated in this randomized, two-way crossover study. The subjects fasted for overnight and were randomly assigned to receive 50 mg sitagliptin 2 hours before ingestion of the liquid test meal (200 kcal per 200 mL, containing 100 mg 13C-acetate) or the test meal alone. Under both conditions, breath samples were collected for 150 minutes following the meal. Liquid gastric emptying was estimated by the values of the following parameters: the time required for 50% emptying of the labeled meal (T1/2), the analog to the scintigraphy lag time for 10% emptying of the labeled meal (Tlag), the gastric emptying coefficient and the regression-estimated constants (β and κ), calculated by using the 13CO2 breath excretion curve using the conventional formulae. The parameters between the 2 test conditions were compared statistically.ResultsNo significant differences in the calculated parameters, including T1/2, Tlag, gastric emptying coefficient or β and κ, were observed between the 2 test conditions.ConclusionsThe present study revealed that single-dose sitagliptin intake had no significant influence on the rate of liquid gastric emptying in asymptomatic volunteers.

Ultrasonographic Assessment of Liquid Gastric Emptying and Antral Motility According to the Subtypes of Irritable Bowel Syndrome in Children

Gastric motor abnormalities have been reported in adults with irritable bowel syndrome (IBS), commonly in constipation-predominant IBS (IBS-C); however, such studies are uncommon in children. Furthermore, differences of gastric motility have not been studied in children with different IBS subtypes. Seventy-six children (33 [43%] boys, age 4-14 years, mean 7.9 years, SD 3.0 years) fulfilling Rome III criteria for IBS and 20 healthy controls (8 [40%] boys, age 4-14 years, mean 8.4 years, SD 3.0 years) were recruited (diarrhea-predominant IBS=21, IBS-C=31, mixed IBS=19, and unsubtyped IBS=5). Liquid gastric emptying rate (GER) and antral motility were assessed using an ultrasound method. Average GER (43.8% vs 66.2% in controls), amplitude of antral contractions (56.4% vs 89%), and antral motility index (5.1 vs 8.3) were lower and fasting antral area (1.6 vs 0.6) was higher in patients with IBS (P<0.0001). Frequency of antral contractions F (8.9 vs 9.3) did not show a significant difference. Patients exposed to stressful events had a significantly lower GER, compared to those not exposed to such events (P=0.03). Gastric motility parameters had no correlation with severity of symptoms. GER (42.6%, 46.3%, 39.6%), fasting antral area (1.4 cm², 1.8 cm², 1.8 cm²), amplitude of antral contractions (53%, 58.9%, 51.8%), frequency of antral contractions (8.7, 8.9, 9.2), and antral motility index (4.7, 5.3, 4.8) were not different among diarrhea-predominant IBS, IBS-C, and mixed IBS (P>0.05). GER and antral motility parameters were significantly impaired in children with IBS compared with controls. GER and antral motility parameters were not different between IBS subtypes.

Aortocaval fistula delays gastric emptying of liquid test meal in awake rats

Arteriovenous anastomoses disrupt cardiovascular and renal homeostasis, eliciting hemodynamic adjustments, resetting the humoral pattern, and inducing cardiac hypertrophy. Because acute circulatory imbalance alters gut motor behavior, we studied the effects of arteriovenous fistula placement on the gastric emptying (GE) of a liquid meal in awake rats. After laparotomy, we created an aortocaval fistula (ACF) by aorta and cava wall puncture with a 21-, 23-, or 26-gauge needle. The ACF was not created in the control group, which underwent sham operation. After 12, 24, or 48 h, mean arterial pressure, heart rate, and central venous pressure were continuously recorded, and cardiac output was estimated by thermal dilution. The rats were then gavage fed a test meal (i.e., phenol red in glucose solution), and fractional dye retention was determined 10, 20, or 30 min later. The effect of prior bleeding on ACF-induced GE delay, the role of neuroautonomic pathways, and changes in plasma hormone levels (i.e., angiotensin II, arginine vasopressin, atrial natriuretic peptide, corticosterone, and oxytocin) were evaluated. When compared with the sham-operated group, ACF rats exhibited arterial hypotension, higher (P < 0.05) heart rate, central venous pressure, and cardiac output values and increased (P < 0.05) gastric dye retention, a phenomenon prevented by bilateral subdiaphragmatic vagotomy and hexamethonium treatment. Pirenzepine also impaired the occurrence of gastric delay in subjects with ACF. In addition to causing hyperkinetic circulation, ACF placement delayed the GE of liquid in awake rats, an effect that likely involves a parasympathetic pathway.

Prognosis of diabetic gastroparesis—a 25‐year evaluation

To evaluate the prognosis of diabetic gastroparesis. Eighty-six patients with diabetes had measurements of gastric emptying of a mixed meal using a dual isotope test of solid and liquid meal components, mean blood glucose levels, HbA1c , upper gastrointestinal symptoms and autonomic nerve function performed in 1984-1989. These patients were followed up in 2011, after a mean period of ~25 years. Of the 86 patients, gastric emptying of solid (the percentage remaining in the stomach at 100 min) was delayed in 35 (41%), and of liquid (the time taken for 50% of the liquid to empty) was delayed in 38 (44%). In 2011, 53 patients were known to be alive, 29 had died and four were lost to follow-up. In those who had died, both age at baseline (P < 0.001) and the score for autonomic nerve dysfunction (P < 0.001) were greater than those who were alive, while there was no difference in emptying of either the solid or liquid between the two groups. When patients with delayed gastric emptying were divided according to the median value ('delayed' and 'markedly delayed'), mortality tended to be greater in the 'markedly delayed' group for both solids (P = 0.12) and liquids (P = 0.09). Of the 82 patients who could be followed up, 23 of the 35 (66%) with delayed gastric emptying of solid and 25 of 38 (66%) with delayed gastric emptying of liquid were alive. After adjustment for age and autonomic dysfunction, there was no association between gastric emptying of either solid or liquid and death. Over a period of ~25 years, diabetic gastroparesis is apparently not usually associated with a poor prognosis, or increased mortality. T100 min, the percentage remaining in the stomach at 100 mins; T50%, the time taken for 50% of the liquid to empty.

Atrial stretch delays gastric emptying of liquids in awake rats

AimsWe previously reported that mechanical atrial stretch (AS) by balloon distention increased gastric tonus in anesthetized rats. The present study evaluated the effect of AS on the gastric emptying of a liquid test meal in awake rats and its underlying neural mechanisms. Main methodsAnesthetized male rats received a balloon catheter into the right atrium and a gastrostomy cannula. The next day, mean arterial pressure (MAP), heart rate (HR), central venous pressure (CVP), and cardiac output (CO) were continuously monitored. After the first 20min of monitoring (basal interval), the balloon was either distended or not (control) with 30, 50, or 70μl saline for 5min. Fifteen minutes later, the rats received the test meal (glucose solution with phenol red), and fractional gastric dye retention was determined 10, 20, or 30min later. Key findingsHeart rate and CVP values were transiently increased by 50 or 70μl AS but not 30μl AS, whereas gastric emptying was slower after 30, 50, or 70μl AS than after sham distention. Subdiaphragmatic vagotomy or splanchnicotomy+celiac ganglionectomy and capsaicin, ondansetron, hexamethonium, L-NAME, and glibenclamide treatment prevented the AS-induced delay in gastric emptying, whereas atropine and guanethidine treatment failed to prevent it. SignificanceAtrial stretch inhibited the gastric emptying of liquid via non-adrenergic and non-cholinergic pathways that activate nitric oxide-K+ATP channels.

Effect of amitriptyline on gastrointestinal function and brain-gut peptides: A double-blind trial

To study the effects of low-dose amitriptyline (AMT) on gastrointestinal function and brain-gut peptides in healthy Chinese volunteers. This was a double-blind, randomised, placebo-controlled, two-period cross-over trial. Twenty-eight healthy volunteers were randomised and administered 1-wk treatments of AMT (12.5 mg tid) or placebo. Before and during the final two days of treatment, gastric emptying, proximal gastric accommodation and visceral sensitivity were measured by drinking-ultrasonography test; the orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, and fasting blood was collected. Plasma levels of ghrelin, motilin and neuropeptide Y (NPY) were measured by enzyme-linked immunosorbent assay kits. AMT slowed the OCTT (109.2 ± 29.68 min vs 96.61 ± 23.9 min, P = 0.004) but did not affect liquid gastric emptying and had no effect on proximal gastric accommodation. AMT resulted in decreases in the visual analogue scale (VAS) for difficulty in drinking 600 and 800 mL of water (3.57 ± 0.94 vs 2.98 ± 0.85, 5.57 ± 0.82 vs 4.57 ± 0.98, P < 0.01 for both), although it had no significant effect on the VAS for difficulty in drinking 200 mL and 400 mL of water. AMT significantly increased the plasma ghrelin level (442.87 ± 176.79 pg/mL vs 526.87 ± 158.44 pg/mL, P = 0.04) and the neuropeptide-Y level (890.15 ± 131.46 pg/mL vs 965.64 ± 165.63 pg/mL, P = 0.03), whereas it had no effect on the MTL level. Low-dose AMT could slow OCTT, make the stomach less sensitive and increase the plasma levels of ghrelin and NPY. Thus, we recommend the use of low-dose AMT for functional gastrointestinal disorders.

Domperidone

Domperidone