13C-octanoic Acid Research Articles

Gastric emptying is slower in women than men with type 2 diabetes and impacts on postprandial glycaemia.

To evaluate sex differences in gastric emptying and the glycaemic response to a glucose drink and a high carbohydrate meal in type 2 diabetes (T2D). In cohort 1, 70 newly diagnosed, treatment-naïve Chinese patients with T2D (44 men) recruited from a diabetes outpatient clinic ingested a 75-g glucose drink containing 150 mg 13C-acetate. In cohort 2, 101 Australian patients with T2D (67 male) recruited from the community, managed by diet and/or metformin monotherapy, ingested a semi-solid mashed potato meal, labelled with 100 μl 13C-octanoic acid. Breath samples were collected over 3 and 4 h, respectively, for assessment of gastric emptying, and venous blood was sampled for evaluation of glycaemia (with and without adjustment for each participant's estimated total blood volume). Gastric emptying was slower in female than male subjects in both cohorts (both p < .01). Multiple linear regression analyses revealed that gastric emptying was independently associated with sex (both p < .05). Without adjustment for blood volume, the glycaemic responses to oral glucose and the mixed meal were greater in female subjects (both p < .001). However, after adjustment for blood volume, the glycaemic responses were greater in men (both p < .05). Gastric emptying is slower in women than men with T2D, associated with a reduced blood volume-adjusted glycaemic response to oral glucose and a mixed meal in women. These observations highlight the sex difference in postprandial glucose handling, which is relevant to the personalized management of postprandial glycaemia in T2D.

Phenylalanine requirements using the direct amino acid oxidation technique, and the effects of dietary phenylalanine on food intake, gastric emptying, and macronutrient metabolism in adult cats.

Despite Phe being an indispensable amino acid for cats, the minimum Phe requirement for adult cats has not been empirically defined. The objective of study 1 was to determine the minimum Phe requirement, where Tyr is in excess, in adult cats using the direct amino acid oxidation (DAAO) technique. Four adult male cats were used in an 8 × 4 Latin rectangle design. Cats were adapted to a basal diet for 7 d, top dressed with Phe to meet 140% of the adequate intake (NRC, 2006. Nutrient requirements of dogs and cats. Washington, DC: Natl. Acad. Press). Cats were randomly assigned to one of eight experimental Phe diets (0.29%, 0.34%, 0.39%, 0.44%, 0.54%, 0.64%, 0.74%, and 0.84% Phe in the diet on a dry matter [DM] basis). Following 1 d of diet adaptation, individual DAAO studies were performed. During each DAAO study, cats were placed into individual indirect calorimetry chambers, and 75% of the cat's daily meal was divided into 13 equal meals supplied with a dose of L-[1-13C]-Phe. Oxidation of L-[1-13C]-Phe (F13CO2) during isotopic steady state was determined from the enrichment of 13CO2 in breath. Competing models were applied using the NLMIXED procedure in SAS to determine the effects of dietary Phe on 13CO2. The mean population minimum requirement for Phe was estimated at 0.32% DM and the upper 95% population confidence limit at 0.59% DM on an energy density of 4,200 kcal of metabolizable energy/kg DM calculated using the modified Atwater factors. In study 2, the effects of a bolus dose of Phe (44mg kg-1 BW) on food intake, gastric emptying (GE), and macronutrient metabolism were assessed in a crossover design with 12 male cats. For food intake, cats were given Phe 15min before 120% of their daily food was offered and food intake was measured. Treatment, day, and their interaction were evaluated using PROC GLIMMIX in SAS. Treatment did not affect any food intake parameters (P > 0.05). For GE and macronutrient metabolism, cats were placed into individual indirect calorimetry chambers, received the same bolus dose of Phe, and 15min later received 13C-octanoic acid (5mg kg-1 BW) on 50% of their daily food intake. Breath samples were collected to measure 13CO2. The effect of treatment was evaluated using PROC GLIMMIX in SAS. Treatment did not affect total GE (P > 0.05), but cats receiving Phe tended to delay time to peak enrichment (0.05 < P ≤ 0.10). Overall, Phe at a bolus dose of 44mg kg-1 BW had no effect on food intake, GE, or macronutrient metabolism. Together, these results suggest that the bolus dose of Phe used may not be sufficient to elicit a GE response, but a study with a greater number of cats and greater food intake is warranted.

Macronutrients effects on satiety and food intake in older and younger adults: A randomised controlled trial

Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (∼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the 13C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed.

Nausea is the only symptom associated with delayed gastric emptying in pediatric functional dyspepsia patients.

Functional dyspepsia (FD) is a heterogeneous functional gastrointestinal disorder (FGID) with a highly prevalent symptom complex. The aim of our study is to investigate the relation between symptoms of FD and results of gastric emptying (GE) breath test in children. This study included patients (6-17 years old) presented at the general gastroenterology outpatient clinic with dyspeptic symptoms (Rome IV criteria) and underwent careful history taking with clinical examination. A GE breath test with a 13 C-octanoic acid labeled (250 kcal) solid meal was performed and dyspepsia symptom scores, clarified using pictograms for postprandial fullness, bloating, belching, nausea, vomiting, epigastric pain and burning, were obtained every 15 min ranging from 0 to 4 for a total of 240 min. The severity of the complaints (overall and individual symptoms) as displayed by the symptom questionnaire was compared between normal and delayed GE groups. The relationship between GE time and the severity of FD symptoms was assessed using Mann-Whitney test. Thirty nine FD patients (55% girls; mean age: 11.9 ± 3.3 years) participated in the study. Of these, 43% had delayed GE. The overall symptom severity in patients with delayed GE was similar to the symptoms of patients with a normal GE rate (149.5 ± 12.7 points vs. 123.9 ± 9.0; p = 0.19). Individual symptoms scores showed only nausea to be significantly increased in the group with delayed GE (21.5 ± 1.9 points vs. 33.2 ± 4.6; p = 0.048, p < 0.1). Especially in children with nausea as presenting symptom of FD, a low threshold should be withheld to perform a GE breath test.

The ‘early’ postprandial glucagon response is related to the rate of gastric emptying in type 2 diabetes

Gastric emptying (GE) is a major determinant of the postprandial glycemic and insulinemic responses in health and type 2 diabetes (T2D). However, the effect of GE on the postprandial glucagon response, which is characteristically augmented in T2D, is unknown. This study examined the relationship between plasma glucagon and GE of a standardized mixed meal in individuals with well-controlled T2D. 89 individuals with T2D (HbA1c 6.6 ± 0.1%) consumed a mashed potato meal labeled with 100 µL 13C-octanoic acid between 0 and 5 min. Venous blood was sampled frequently over 4 h for measurements of blood glucose and plasma glucagon. The gastric half-emptying time (T50) was calculated by quantification of 13C in the breath. Blood glucose peaked at t = 90 min after the meal. Plasma glucagon increased to a peak at t = 30 min and then decreased to a nadir at t = 180 min. The T50 was 68.3 ± 1.6 min. The incremental area under the plasma glucagon curve between t = 0–30 min (glucagon iAUC0–30 min) was related inversely to the T50 (r = −0.23, P = 0.029), while the increase in blood glucose at t = 30 min was related directly to the plasma glucagon iAUC0–30 min (r = 0.25, P = 0.018). Accordingly, individuals with relatively faster GE exhibited higher postprandial glucagon and glucose levels (ANOVA: P<0.01 for each). In well-controlled T2D, the early postprandial glucagon response to a mixed meal is related to the rate of GE, and predictive of the initial glycemic response. These observations suggest that a reduction in plasma glucagon may contribute to the effect of dietary and pharmacological strategies which reduce postprandial glycemia in T2D by slowing GE.

IN VIVO MONITORING STRATEGIES FOR EVALUATION OF FLOATING DRUG DELIVERY SYSTEMS

In recent years, various advancements have been introduced in the development of controlled drug release devices for resolving different physiological problems for example, gastric retention inconsistency along with erratic gastric emptying time. Gastroretentive delivery formulations receive considerable attention to overcome these drawbacks and in optimizing the absorption of different medicaments. Gastroretentive technologies considerably extend the stomach retention time of dosage forms with increased bioavailability as well as therapeutic efficacy. Gastroretention can be successfully achieved utilizing gastric floating system. The rationale of the present manuscript focuses on current advancements of gastric floating systems so as to accomplish appropriate drug bioavailability and, subsequently drug targeting to the stomach. In vivo evaluation parameters, especially pivotal imaging techniques including roentgenography, gamma scintigraphy, gastroscopy, magnetic marker monitoring, magnetic resonance imaging, ultrasonography, 13C octanoic acid breath test etc. have been emphasized in this manuscript for monitoring drug formulation behavior which extensively revolutionized thorough understanding in the avenue of improved bioavailability of gastroretentive systems.

Measurement of Gastric Emptying Using a 13C-octanoic Acid Breath Test with Wagner-Nelson Analysis and Scintigraphy in Type 2 Diabetes.

Breath tests utilising 13C-labelled substrates for the assessment of gastric emptying have been applied widely. Wagner-Nelson analysis is a pharmacokinetic model that can be utilised to generate a gastric emptying curve from the % 13CO2 measured in breath samples. We compared Wagner-Nelson analysis with (i) scintigraphy and (ii) conventional breath test modelling to quantify gastric emptying in type 2 diabetes. Thirteen patients (age 68.1±1.5 years, body mass index 31.0±0.9 kg/m2, HbA1c 6.3±0.2%) consumed a mashed potato meal comprising 65 g powdered potato, 20 g glucose, 250 ml water, an egg yolk labelled with 100 μL 13C-octanoic acid and 20MBq 99mTc-calcium phytate. Scintigraphic data were acquired and breath samples collected for 4 hours after the meal. Gastric emptying curves were derived based on each technique; the 50% emptying time and intragastric retention at 60 min were also calculated. With Wagner-Nelson analysis, a Kel=0.60 (the elimination constant) best approximated the scintigraphic gastric emptying curve. There was a relationship between the T50 calculated with scintigraphy and by both Wagner-Nelson Kel=0.60 (r2=0.45, P<0.05) and conventional analysis (r2=0.44, P<0.05). There was no significant difference in the 50% gastric emptying time for scintigraphy (68.5±4.8 min) and Wagner-Nelson Kel=0.60 (71.3±4.5 min), however, the 50% gastric emptying time calculated by conventional analysis was much greater at 164.7±6.0 min (P<0.001). In type 2 diabetes, gastric emptying of a mashed potato meal measured using a 13C-octanoic acid breath test analysed with Wagner-Nelson Kel=0.60 closely reflects measurements obtained with scintigraphy, whereas, in absolute terms, the conventional breath test analysis does not.

Matched whole grain wheat and refined wheat milled products do not differ in glycemic response or gastric emptying in a randomized, crossover trial

Epidemiologic and some clinical studies support the view that whole grain foods have lower glycemic response than refined grain foods. However, from the perspective of food material properties, it is not clear why whole grain cereals containing mostly insoluble and nonviscous dietary fibers (e.g., wheat) would reduce postprandial glycemia. We hypothesized that glycemic response for whole grain wheat milled products would not differ from that of refined wheat when potentially confounding variables (wheat source, food form, particle size, viscosity) were matched. Our objective was to study the effect of whole grain wheat compared with refined wheat milled products on postprandial glycemia, gastric emptying, and subjective appetite. Using a randomized crossover design, healthy participants (n=16) consumed 6 different medium-viscosity porridges made from whole grain wheat or refined wheat milled products, all from the same grain source and mill: whole wheat flour, refined wheat flour, cracked wheat, semolina, reconstituted wheat flour with fine bran, and reconstituted wheat flour with coarse bran. Postprandial glycemia, gastric emptying, and appetitive response were measured using continuous glucose monitors, the 13C-octanoic acid (8:0) breath test, and visual analog scale (VAS) ratings. Bayes factors were implemented to draw inferences about null effects. Little-to-no differences were observed in glycemic responses, with lower incremental AUC between 0 and 120min glycemic responses only for semolina [mean difference (MD): -966mg min/dL; 95% CI: -1775, -156mg min/dL; P = 0.02) and cracked wheat (MD: -721mg min/dL; 95% CI: -1426, -16mg min/dL; P = 0.04) than for whole wheat flour porridge. Bayes factors suggested weak to strong evidence for a null effect (i.e., no effect of treatment type) in glycemic response, gastric emptying, and VAS ratings. Although whole grain wheat foods provide other health benefits, they did not in their natural composition confer lower postprandial glycemia or gastric emptying than their refined wheat counterparts.This trial was registered at clinicaltrials.gov as NCT03467659.

Iron tablets delay gastric emptying, which is ameliorated by 5-HT&lt;sub&gt;3&lt;/sub&gt; receptor antagonist.

Gastrointestinal symptoms, including nausea and vomiting, are common adverse effects of oral iron tablets, but the mechanism of iron-induced nausea and vomiting is not yet known. Studies have shown that there are close relationships between gastrointestinal motility and gastrointestinal symptoms such as nausea, vomiting, and diarrhea, with more than 90% of patients with delayed gastric emptying experiencing nausea and vomiting. However, the effect of iron on gastrointestinal motility has not yet been investigated. In the present study, we aimed to elucidate the effects of iron on gastrointestinal motility using sodium ferrous citrate (SFC), the most commonly used iron tablets. Gastric emptying in mice was assessed by 13C-octanoic acid breath test to examine the effect of SFC (3-30 mg Fe/kg, p.o.) with or without the 5-HT3 receptor antagonist, palonosetron hydrochloride (5 mg/kg. s.c.). Colon transit was also measured by the beads method. The results showed that SFC delayed the gastric emptying, which was ameliorated by administration of palonosetron hydrochloride. It was also confirmed that ingredients of the tablets had no effect on gastric emptying. SFC also had no effect on the colon transit in vivo. These results lead the possibility that the iron-induced delayed gastric emptying may be mediated through nausea and vomiting.

Assessment of physiological barriers to nutrition following critical illness

Nutrition may be important for recovery from critical illness. Gastrointestinal dysfunction is a key barrier to nutrition delivery in the Intensive Care Unit (ICU) and metabolic rate is elevated exacerbating nutritional deficits. Whether these factors persist following ICU discharge is unknown. We assessed whether delayed gastric emptying (GE) and impaired glucose absorption persist post-ICU discharge. A prospective observational study was conducted in mechanically ventilated adults at 3 time-points: in ICU (V1); on the post-ICU ward (V2); and 3-months after ICU discharge (V3); and compared to age-matched healthy volunteers. On each visit, all participants received a test-meal containing 100ml of 1kcal/ml liquid nutrient, labelled with 0.1g 13C-octanoic acid and 3g 3-O-Methyl-glucose (3-OMG), and breath and blood samples were collected over 240min to quantify GE (gastric emptying coefficient (GEC)), and glucose absorption (3-OMG concentration; area under the curve (AUC)). Data are mean±standard error of the mean (SEM) and differences shown with 95% confidence intervals (95%CI). Twenty-six critically ill patients completed V1 (M:F 20:6; 62.0±2.9y; BMI 29.8±1.2kg/m2; APACHE II 19.7±1.9), 15 completed V2 and eight completed V3; and were compared to 10 healthy volunteers (M:F 6:4; 60.5±7.5y; BMI 26.0±1.0kg/m2). GE was significantly slower on V1 compared to health (GEC difference:-0.96 (95%CI -1.61,-0.31); and compared to V2 (-0.73 (-1.16,-0.31) and V3 (-1.03 (-1.47,-0.59). GE at V2 and V3 were not different to that in health (V2:-0.23 (-0.61, 0.14); V3: 0.10 (-0.27, 0.46)). GEC: V1: 2.64±0.19; V2: 3.37±0.12; V3: 3.67±0.10; health: 3.60±0.13. Glucose absorption (3-OMG AUC0-240) was impaired on V1 compared to V2 (-37.9 (-64.2,-11.6)), and faster on V3 than in health (21.8 (0.14, 43.4) but absorption at V2 and V3 did not differ from health. Intestinal glucose absorption: V1: 63.8±10.4; V2: 101.7±7.0; V3: 111.9±9.7; health: 90.7±3.8. This study suggests that delayed GE and impaired intestinal glucose absorption recovers rapidly post-ICU. This requires further confirmation in a larger population. The REINSTATE trial was prospectively registered at www.anzctr.org.au. ACTRN12618000370202.

Effect of Combined Interval and Continuous Exercise Training on Gastric Emptying, Appetite, and Adaptive Responses in Men With Overweight and Obesity.

Background/Objectives: Characterizing compensatory and adaptive responses to exercise assists in understanding changes in energy balance and health outcomes with exercise interventions. This study investigated the effects of a short-term exercise intervention (combining high intensity interval (HII) and continuous exercise) on (1) gastric emptying, appetite and energy intake; and (2) other adaptive responses including cardiorespiratory fitness, in inactive men with overweight/obesity.Methods: Fifteen men (BMI: 29.7 ± 3.3 kg/m−2) completed a 4-wk supervised exercise intervention, consisting of 5 exercise sessions per week alternating between HII (30 s at 100% VO2max followed by 30 s recovery) and continuous (at 50% VO2max) training on a cycle ergometer, progressing from 30 to 45 min session duration. Gastric emptying (13C-octanoic acid breath test), appetite (visual analog scale), energy intake (ad libitum lunch meal), body composition (air displacement plethysmography), non-exercise activity (accelerometery) VO2max, blood pressure, and fasting concentrations of glucose, insulin, and ghrelin were measured before and after (≥48 h) the intervention.Results: Gastric emptying, glucose, insulin and ghrelin were unchanged, but energy intake at the ad libitum lunch test meal significantly increased at post-intervention (+171 ± 116 kcal, p < 0.01). Body weight (−0.9 ± 1.1 kg), waist circumference (−2.3 ± 3.5 cm) and percent body fat (−0.9 ± 1.1%) were modestly reduced (P < 0.05). VO2max increased (+4.4 ± 2.1 ml.kg.min−1) by 13% and systolic (−6.2 ± 8.4 mmHg) and diastolic (−5.8 ± 2.2 mmHg) blood pressure were significantly reduced (P ≤ 0.01 for all).Conclusions: Four weeks of exercise training did not alter gastric emptying, indicating gastric emptying may only adapt to a higher volume/longer duration of exercise or changes in other characteristics associated with regular exercise. The combination of HII and continuous exercise training had beneficial effects on body composition, cardiorespiratory fitness, and blood pressure and warrants further investigation in larger randomized controlled trials.

Astroglial Regulation of Caloric Intake Following Acute High‐Fat Diet Exposure

Chronic high fat diet (HFD) exposure results in hyperphagia and the development of obesity. Caloric intake during acute (3-5 days) HFD exposure, however, is regulated. We have previously shown that increased activation of NMDA receptors on the motoneurons of the dorsal motor nucleus of the vagus (DMV) contributes to the regulation of caloric intake during acute HFD exposure (Clyburn, et. al. 2018). The mechanism that is responsible for altered excitatory drive to DMV neurons is unknown. HFD exposure is associated with inflammation. Neuroinflammation and astroglial activation have been shown to modulate neural activity and glutamatergic signaling. The purpose of this study is to test the hypothesis that during acute HFD exposure, astrocyte activation increases the glutamatergic drive to DMV neurons and regulates caloric intake. Male and female Sprague-Dawley rats were transfected with the astrocyte inhibitory DREADD, pAAV-GFAP-hM4D(Gi)-mCherry, (“hM4Di”; Addgene #50479-AAV5; titer 1x1013 diluted 1:10) or AAV-GFAP104-mCherry, (“empty vector”; UNC vector core, titer 2.7x1012 diluted 1:10). Microinjections were made into the dorsal vagal complex. After recovery, rats were fed a control or HFD (14% and 60% kcal from fat, respectively) for 3-5 days. Whole-cell patch clamp recordings were made of gastric-projecting DMV neurons in thin brainstem slices of transfected rats. The effects of the NMDA receptor antagonist, AP5 (25μM), in the presence of clozapine (10μM) or the DREADD agonist, clozapine-N-oxide (CNO; 10μM) on miniature excitatory postsynaptic current (mEPSC) kinetics and action potential (AP) firing rate were examined. The effects of CNO and clozapine on caloric intake and gastric emptying rates using the 13C octanoic acid breath test were also assessed. As shown previously, following acute HFD, AP5 decreases mEPSC frequency and AP firing rate. This AP5-mediated decrease was unaffected by clozapine or CNO application to empty vector control groups. CNO in the hM4Di group attenuated the AP5-mediated decrease in mEPSC frequency and AP firing rate (mEPSC frequency: 54±5.0% vs. 53±9.5% vs. 100±1.5% of baseline, respectively; AP firing rate: 8±5.3% vs. 41±14.9% vs. 111±3.5%; P<0.05 with two-way ANOVA and post-hoc Bonferroni; N=7-9 cells from 3-5 rats). In addition, the delay in gastric emptying rates observed 4 days following HFD exposure was attenuated by CNO administration to hM4Di rats, while empty vector or clozapine controls were uneffected (119±7.9% vs. 166±7.4% vs. 144±6.7% of baseline, respectively; P<0.05 with two-way ANOVA and post-hoc Bonferroni; N=6-7 rats). CNO administration to hM4Di rats also prevented the regulation of caloric intake normally observed 3-5 days of HFD exposure, compared to clozapine and empty vector controls (AUC: 964±34.4a.u. vs. 843±14.3a.u. vs. 815±17.9a.u., respectively; P<0.05 from Student's unpaired t-test; N=6). These data suggest that astrocyte activation is involved in the alteration of glutamatergic currents and the homeostatic regulation of food intake following acute HFD. Understanding the mechanism responsible for the regulation of caloric intake is critical in identifying potential therapeutic targets for the treatment of obesity when such neuroplasticity may be absent.

Pyloric dilation with the esophageal functional lumen imaging probe in gastroparesis improves gastric emptying, pyloric distensibility, and symptoms

The role of decreased pyloric distensibility in gastroparesis as measured by the endolumenal functional luminal imaging probe (EndoFLIP) has been receiving increasing attention. In this study, we present clinical outcomes to pyloric dilation with the esophageal FLIP (EsoFLIP) in regard to gastric emptying, symptom evolution, and FLIP metrics. Patients evaluated for gastroparesis (gastric emptying studies of t1/2≥180 minutes during 13C-octanoic acid breath test and/or gastric remnants during gastroscopy after a sufficient fasting period) were scheduled for EsoFLIP controlled pyloric dilation. Pre- and postprocedural gastric emptying studies, questionnaires (Patient Assessment of Upper GI Symptoms Severity Index [PAGI-SYM; including the Gastroparesis Cardinal Symptom Index] and Patient Assessment of Quality of Life Index [PAGI-QOL]), and FLIP metrics were documented. Dilation was conducted according to a self-developed algorithm. Forty-six patients were analyzed (72% women; median age, 39 years [range, 18-88]). Etiologies of gastroparesis were diabetic in 10 patients (22%), idiopathic in 33 (72%), and postoperative in 3 (6%). Postprocedural gastric emptying time decreased from a median of 211 minutes to 179 minutes (P= .001). In accordance, pyloric distensibility, PAGI-SYM, PAGI-QOL, and Gastroparesis Cardinal Symptom Index values improved significantly. After a median follow-up of 3.9 months, 57% of all treated patients with returned questionnaires reported improved symptoms. Pyloric EsoFLIP controlled dilation shows value in the treatment of gastroparesis, both subjectively and objectively. Long-term follow-up to assess efficacy and comparative trials are warranted.

Relationship Between Gastric Emptying Rate and Simultaneously Assessed Symptoms in Functional Dyspepsia

During a GE test (breath test with 13C-octanoic acid labelled 250 kcal solid meal), the severity of 6 symptoms (postprandial fullness, epigastric pain and burning, bloating, nausea and belching) was assessed, every 15 min, before meal-intake and 4h postprandially. The sum of individual symptom scores generated the meal-related symptoms score; the sum of all symptoms generated overall meal-related symptom severity (OSS). Data were compared in patients with normal and delayed GE (cut-off T1/2≥ 109 min). Data are shown as mean±SEM. 504 patients were included, of which 382 patients (67% female, age 43.8±0.8 years, BMI 23.3±0.2 kg/m2) had normal and 122 patients (77% female, age 42.7±1.5 years, BMI 23.2±0.6 kg/m2) had delayed GE. OSS tended to be higher in patients with delayed GE (81.8±3.4 vs. 99.5±7.1, p=.05). Only nausea was significantly higher in patients with delayed GE (11±0.8 vs. 16±1.6, p=.01). No correlations were observed between GE rate and any of the symptoms (OSS: r=0.06, p=.2; nausea: r=0.06, p=.1). The symptom severity time course showed a significant difference only for nausea, with increased severity ratings 90 min after the meal (p<.01) in delayed GE compared to normal GE patients. The severity of symptoms in functional dyspepsia and idiopathic gastroparesis, even when assessed during the GE test meal, is not correlated to gastric emptying rate. (Ethics committee University Hospital of Leuven study number S55426).

Resistance of postprandial gastric functions and autonomic balance to taste stimulation.

Exposure to unpleasant tastes leads to disturbances of interdigestive gastric myoelectrical activity (GMA) and may affect sympathetic/parasympathetic balance (SPB). We made a careful study to determine whether taste stimulation modulates the postprandial GMA, SPB, and gastric emptying (GE) of a solid meal. Eighteen healthy volunteers (9F/9M) entered the study. On six separate days, we recorded a four-channel electrogastrogram from each volunteer during a 35-min fasting period, then for 90 min after ingestion of a solid test meal of 300 kcal. GE was measured using a 13C-octanoic acid breath test. Heart rate variability (HRV) analysis was simultaneously performed. At the start of the 21st min after the test meal, subjects received an agar cube delivering either a sweet, salty, sour, or bitter taste, which they kept in the mouth for 35 min. Control procedures involved sessions performed with a tasteless agar cube, and without any stimulation. There was no effect of the experimental intervention upon the relative power share of particular GMA rhythms. Stimulation with the salty and the bitter taste evoked a statistically significant increase in the dominant frequency, whereas the sweet and sour taste did not affect it. Taste stimulation did not interfere with the meal-induced rise in the dominant power, nor affect slow wave coupling. The kinetics of the solid GE remained unchanged by the intervention. None of the taste stimulations affected the postprandial SPB. Taste stimulation elicited after ingestion of a meal, in contrast to that during a fast, did not adversely modify the postprandial pattern of either the GMA or SPB, nor affect the GE of solids.

Some pearl millet-based foods promote satiety or reduce glycaemic response in a crossover trial.

In a previous trial in Mali, we showed that traditional pearl millet couscous and thick porridge delayed gastric emptying (about 5 h half-emptying times) in a normal-weight population compared with non-traditional carbohydrate-based foods (pasta, potatoes, white rice; about 3 h half-emptying times), and in a gastric simulator we showed millet couscous had slower digestion than wheat couscous. In light of these findings, we tested the hypothesis in a normal-weight US population (n 14) that millet foods would reduce glycaemic response (continuous glucose monitor), improve appetitive sensations (visual analogue scale ratings), as well as reduce gastric emptying rate (13C-octanoic acid breath test). Five carbohydrate-based foods (millet couscous - commercial and self-made, millet thick porridge, wheat couscous, white rice) were fed in a crossover trial matched on available carbohydrate basis. Significantly lower overall glycaemic response was observed for all millet-based foods and wheat couscous compared with white rice (P≤0·05). Millet couscous (self-made) had significantly higher glycaemic response than millet couscous (commercial) and wheat couscous (P<0·0001), but as there were no differences in peak glucose values an extended glycaemic response was indicated for self-made couscous. Millet couscous (self-made) had significantly lower hunger ratings and higher fullness ratings (P<0·05) than white rice, millet thick porridge and millet couscous (commercial). A normal gastric emptying rate (<3 h half-emptying times) was observed for all foods, with no significant differences among them. In conclusion, some traditionally prepared pearl millet foods show the potential to reduce glycaemic response and promote satiety.

A Close Relationship Between Networks of Interstitial Cells of Cajal and Gastrointestinal Transit In Vivo.

The interstitial cells of Cajal associated with the myenteric plexus (ICC-MP) are located in the same area as the myenteric plexus. ICC-MP networks are linked to the generation of electrical pacemaker activity that causes spontaneous gastrointestinal (GI) contractions; however, its role in GI transit is not clear. The aim of this study was to comprehensively investigate the effect of ICC-MP disruption on GI transit in vivo using W/W v mice, partially ICC-deficient model mice. In this study, we measured GI transit using a 13C-octanoic acid breath test, an orally administered dye and a bead expulsion assay. ICC were detected by immunohistochemical staining for c-Kit, a specific marker for ICC. Interestingly, we found that gastric emptying in W/W v mice was normal. We also found that the ability of small intestinal and colonic transit was significantly reduced in W/W v mice. Immunohistochemical staining using whole-mount muscularis samples revealed that c-Kit-positive ICC-MP networks were formed in wild-type mice. In contrast, ICC-MP networks in W/W v mice were maintained only in the gastric antrum and were significantly reduced in the ileum and colon. No significant changes were observed in the nerve structures of the myenteric plexus in W/W v mice. These findings suggest that ICC-MP contribute to GI transit as a powerful driving function in vivo.

Joint Hypermobility Syndrome in Patients With Functional Dyspepsia.

INTRODUCTION:The pathophysiology underlying functional dyspepsia (FD) is multifactorial and focuses on gastric sensorimotor dysfunction. Recent studies demonstrated that joint hypermobility syndrome (JHS) is strongly associated with unexplained dyspeptic symptoms in patients attending gastrointestinal clinics. We aimed to study the relationship between symptoms, gastric sensorimotor function, and JHS in FD patients.METHODS:Tertiary care FD patients who underwent a gastric barostat study and a gastric emptying breath test with 13C-octanoic acid were recruited for assessment of JHS. The presence of JHS was evaluated by a 2-phase interview and clinical examination that included major and minor criteria of the Brighton classification.RESULTS:A total of 62 FD patients (68% women, age 44 ± 1.8 years, and body mass index: 21.7 ± 0.7 kg/m2) accepted to participate in the study. JHS was diagnosed in 55% of FD patients. Assessed symptom profiles during the visit did not differ between the groups. Delayed gastric emptying was not significantly more common in JHS group compared with non-JHS group (JHS group 32% vs non-JHS group 16%, P = 0.31). Prevalence of hypersensitivity to distention (JHS group 24% vs non-JHS group 29%, P = 0.76) and impaired gastric accommodation (JHS group 38% vs non-JHS group 42%, P = 0.79) was similar in patients with or without JHS. No correlations were found between the Beighton hypermobility score and gastric compliance (r = 0.09).DISCUSSION:A large subset of this study cohort of tertiary care FD patients has coexisting JHS. We did not identify any specific differences in gastric sensorimotor function between patients with and without JHS. Further prospective research will be required to elucidate the relationship between JHS, a multisystemic disorder with widespread manifestations, and FD symptoms.

Plasma dosage of ghrelin, IGF-1, GLP-1 and leptin related to gastric emptying and esophageal pH-impedance in children with obesity.

The main aim of the study was to assess the relationship between leptin, ghrelin, insulin-like growth factor 1 (IGF-1), and glucagon-like peptide 1 (GLP-1) blood levels and gastric motility in children with obesity compared to healthy children. Secondary aims were to assess the possible association between these hormones and obesity, reflux impedance parameters, reflux symptoms, other GI disorders, and quality-of-life scores within the same groups. Children with obesity plus GERD symptoms and 2 control groups of children with obesity without GERD and healthy lean children aged 4-17years underwent an auxological evaluation, an assessment of gastro-intestinal symptoms and quality of life, hormonal dosages, and an evaluation of gastric emptying time (GET) through 13C-octanoic acid breath test. No significant association was found between hormones and gastric motility. Leptin and ghrelin levels were significantly associated with obesity parameters. No significant differences were found between GET and hormones of the patients with obesity, either with or without GERD. Although we found an association between auxological parameters and both leptin and ghrelin levels, this association did not imply an effect on the upper GI motility. Therefore, our hypothesis that alterations of these hormones in children with obesity could affect gastric emptying, triggering GERD, was not supported by our data.

Contribution of Serotonin 3A Receptor to Motor Function and Its Expression in the Gastrointestinal Tract

Introduction: The serotonin 3A receptor (5-HT_3AR) is involved in vomiting and gastrointestinal motility. However, it is not well understood the expression pattern of 5-HT_3AR in the gut immunohistochemically and how much contribution of 5-HT_3AR to upper or lower intestinal motility. Objectives: We investigated the contribution of 5-HT_3AR to gastrointestinal motor function by using 5-HT_3AR KO mice and sought to identify 5-HT_3AR-expressing cells via immunohistochemical staining using 5-HT_3AR-GFP reporter mice. Methods: The expression of 5-HT_3AR was measured in each section of the gut through real-time PCR. The motor function of the stomach and colon was assessed via the ¹³C-octanoic acid breath test and colonic bead expulsion test, respectively, using 5-HT_3AR KO mice. 5-HT_3AR-expressing cells in the muscle layer of the gut were identified by immunohistochemical staining using 5-HT_3AR-GFP reporter mice. Results: 5-HT_3AR was expressed throughout the digestive tract, and 5-HT_3AR expression in the stomach and lower digestive tract was higher than that in the other sections. Motor function in the stomach and colon was lower in 5-HT_3AR KO mice than in WT mice. As a result of immunohistochemical staining using GFP reporter mice, cholinergic neurons and PDGFRα⁺ cells were shown to express 5-HT_3AR. In contrast, 5-HT_3AR indicated by GFP fluorescence was rarely detected in ICC and smooth muscle cells. Conclusions: These results show that 5-HT_3AR is highly expressed in the stomach and large intestine and that the activation of 5-HT_3AR accelerates gastric emptying and large intestine transit. Additionally, 5-HT_3AR is highly expressed in cholinergic neurons and some interstitial cells, such as PDGFRα⁺ cells.