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1.
Semaglutide improves postprandial glucose and lipid metabolism, and delays first-hour gastric emptying in subjects with obesity.
Hjerpsted, JB, Flint, A, Brooks, A, Axelsen, MB, Kvist, T, Blundell, J
Diabetes, obesity & metabolism. 2018;(3):610-619
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Abstract
AIM: To investigate the effects of semaglutide on fasting and postprandial glucose and lipid responses, and on gastric emptying. MATERIALS AND METHODS This was a randomized, double-blind, placebo-controlled, 2-period, crossover trial. Subjects with obesity (N = 30) received once-weekly subcutaneous semaglutide, dose-escalated to 1.0 mg, or placebo. After each 12-week treatment period, glucose and lipid metabolism were assessed before and after standardized meals. Gastric emptying (paracetamol absorption test) and peptide YY (PYY) response were also assessed. RESULTS Semaglutide treatment significantly lowered fasting concentrations of glucose and glucagon, and increased insulin vs placebo (estimated treatment ratio: 0.95 [95% confidence interval: 0.91, 0.98]; 0.86 [0.75, 0.98]; 1.45 [1.20, 1.75], respectively). Postprandial glucose metabolism significantly improved with semaglutide vs placebo (incremental area under the curve 0 to 5 hours [iAUC0-5h ]; estimated treatment difference: glucose -1.34 mmol h/L [-2.42, -0.27]; insulin -921 pmol h/L [-1461, -381]; C-peptide -1.42 nmol h/L [-2.33, -0.51]). Fasting and postprandial lipid metabolism improved with semaglutide vs placebo. First-hour gastric emptying after the meal was delayed with semaglutide vs placebo (AUC0-1h ; estimated treatment ratio: 0.73 [0.61, 0.87]); this may have contributed to the lower postprandial glucose increase in semaglutide-treated subjects. Overall gastric emptying (AUC0-5h ) was not statistically different between treatments. Fasting and postprandial PYY responses were significantly lower with semaglutide vs placebo (P = .0397 and P = .0097, respectively). CONCLUSION Semaglutide improved fasting and postprandial glucose and lipid metabolism. Overall gastric emptying was similar to that with placebo; however, the observed first-hour delay with semaglutide may contribute to a slower entry of glucose into the circulation.
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Bidirectional Relationship between Gastric Emptying and Plasma Glucose Control in Normoglycemic Individuals and Diabetic Patients.
Mihai, BM, Mihai, C, Cijevschi-Prelipcean, C, Grigorescu, ED, Dranga, M, Drug, V, Sporea, I, Lăcătușu, CM
Journal of diabetes research. 2018;:1736959
Abstract
Gastric emptying and glycemic control pathways are closely interrelated processes. Gastric chyme is transferred into the duodenum with velocities depending on its solid or liquid state, as well as on its caloric and nutritional composition. Once nutrients enter the intestine, the secretion of incretins (hormonal products of intestinal cells) is stimulated. Among incretins, glucagon-like peptide-1 (GLP-1) has multiple glycemic-regulatory effects that include delayed gastric emptying, thus triggering a feedback loop lowering postprandial serum glucose levels. Glycemic values also influence gastric emptying; hyperglycemia slows it down, and hypoglycemia accelerates it, both limiting glycemic fluctuations. Disordered gastric emptying in diabetes mellitus is understood today as a complex pathophysiological condition, with both irreversible and reversible components and high intra- and interindividual variability of time span and clinical features. While limited delays may be useful for reducing postprandial hyperglycemias, severely hindered gastric emptying may be associated with higher glycemic variability and worsened long-term glycemic control. Therapeutic approaches for both gastric emptying and glycemic control include dietary modifications of meal structure or content and drugs acting as GLP-1 receptor agonists. In the foreseeable future, we will probably witness a wider range of dietary interventions and more incretin-based medications used for restoring both gastric emptying and glycemic levels to nearly physiological levels.
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A pilot study on disturbed gastric myoelectric activity in obstructed defecation syndrome.
Farid, M, Emile, SH, Haleem, M, El-Hak, NG
The Journal of surgical research. 2018;:95-100
Abstract
BACKGROUND Electrogastrography (EGG) is a noninvasive technique for recording gastric myoelectric activity. The aim of this study was to measure and record gastric myoelectric activity in patients with obstructed defecation syndrome (ODS) and to compare their results with those of normal individuals. METHODS Forty-two patients (22 male) with ODS and a mean age of 41.02 y were enrolled in this prospective study after thorough clinical and physiologic assessment. Eleven normal subjects (six female) with a mean age of 39.2 ± 8.4 y were assigned to the control group. Both patients and controls were subjected to surface EGG in fasting and postprandial states. Data were recorded and analyzed via a computer system to reveal the EGG pattern in both groups. RESULTS Abnormalities in the EGG were found in 24 (57.1%) of the 42 patients with ODS. EGG in ODS patients showed alterations in the fasting state in the form of a significant decrease of the normal gastric slow wave (P = 0.03) and a nonsignificant increase in gastric dysrhythmias. The EGG alterations of ODS patients were significantly improved in the postprandial state as the normal gastric slow waves significantly (P = 0.006) increased and the gastric bradycardia declined significantly (P = 0.02). No significant differences were observed in the power distribution between the ODS patients and the healthy controls. CONCLUSIONS Patients with ODS showed an altered EGG pattern compared with that of healthy control subjects. The alterations in ODS patients were more clearly observed during the fasting state and improved significantly after eating.
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Gastric emptying and intestinal appearance of nonabsorbable drugs phenol red and paromomycin in human subjects: A multi-compartment stomach approach.
Paixão, P, Bermejo, M, Hens, B, Tsume, Y, Dickens, J, Shedden, K, Salehi, N, Koenigsknecht, MJ, Baker, JR, Hasler, WL, et al
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2018;:162-174
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Abstract
The goal of this study was to create a mass transport model (MTM) model for gastric emptying and upper gastrointestinal (GI) appearance that can capture the in vivo concentration-time profiles of the nonabsorbable drug phenol red in solution in the stomach and upper small intestine by direct luminal measurement while simultaneously recording the contractile activity (motility) via manometry. We advanced from a one-compartmental design of the stomach to a much more appropriate, multi-compartmental 'mixing tank' gastric model that reflects drug distribution along the different regions of the stomach as a consequence of randomly dosing relative to the different contractile phases of the migrating motor complex (MMC). To capture the intraluminal phenol red concentrations in the different segments of the GI tract both in fasted and fed state conditions, it was essential to include a bypass flow compartment ('magenstrasse') to facilitate the transport of the phenol red solution directly to the duodenum (fasted state) or antrum (fed state). The fasted and fed state models were validated with external reference data from an independent aspiration study using another nonabsorbable marker (paromomycin). These results will be essential for the development and optimization of computational programs for GI simulation and absorption prediction, providing a realistic gastric physiologically-based pharmacokinetic (PBPK) model based on direct measurement of gastric concentrations of the drug in the stomach.
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Indirect vs direct assessment of gastric emptying: A randomized crossover trial comparing C-isotope breath analysis and MRI.
Camps, G, Mars, M, Witteman, BJM, de Graaf, C, Smeets, PAM
Neurogastroenterology and motility. 2018;(7):e13317
Abstract
BACKGROUND Indirect methods to assess gastric emptying (GE), such as 13 C breath tests (BT), are commonly used. However, BT usually use a sampling time of 4+ hours. The current study aims to assess the validity of BT for four liquid meals differing in physicochemical properties. To this aim, we compared them to MRI GE-measurements. METHODS Fifteen healthy males (age 22.6 ± 2.4 years, BMI 22.6 ± 1.8 kg/m2 ) participated in a randomized 2 × 2 crossover experiment. Test foods were liquid meals, which were either thin/thick and 100/500 kcal, labeled with 100 mg of 13 C-octanoate. GE was measured with MRI and assessed by 13 C recovery from breath. Participants were scanned every 10 minutes and at six time points breath samples were collected up to t = 90 minutes. Two curves were fitted to the data to estimate emptying halftime (t50 Ghoos and t50 Bluck ). T50 times were ranked per participant and compared between methods. KEY RESULTS On average, MRI and BT showed similar t50 rankings for the four liquid meals. In comparison to MRI, t50 Ghoos overestimated, while t50 Bluck underestimated GE time. Moreover, more viscous foods were overestimated. In most participants individual t50 time rankings differed significantly between methods. CONCLUSIONS & INFERENCES BT can assess relative emptying differences on group level and collecting breath data for 90 minutes constitutes a lower burden for participants and the research facility. However, BT has severe shortcomings compared to MRI for individual GE assessment. Notably, food matrix effects should be considered when interpreting the results of BT.
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Effects of Glutamine on Gastric Emptying of Low- and High-Nutrient Drinks in Healthy Young Subjects-Impact on Glycaemia.
Du, YT, Piscitelli, D, Ahmad, S, Trahair, LG, Greenfield, JR, Samocha-Bonet, D, Rayner, CK, Horowitz, M, Jones, KL
Nutrients. 2018;(6)
Abstract
Glutamine is a potent stimulus for the release of glucagon-like peptide-1, which increases postprandial insulin and slows gastric emptying (GE). We determined the effects of glutamine on GE of, and glycaemic responses to, low- and high-nutrient drinks in eight healthy males (mean age 21.6 ± 0.7 years and BMI 22.9 ± 0.7 kg/m²). Participants were studied on four occasions on which they consumed either a low-nutrient (beef soup; 18 kcal) or high-nutrient (75 g dextrose; 255 kcal) drink, each with or without 30 g of glutamine (120 kcal), in a randomised, crossover design. GE (2D ultrasound), blood glucose and plasma insulin concentrations were measured concurrently. Glutamine slowed GE (half emptying time (T50)) of both low- (45 ± 3 min vs. 26 ± 2 min, p < 0.001), and high-nutrient, (100 ± 5 min vs. 77 ± 5 min, p = 0.03) drinks, however, there was no effect on GE of the high nutrient drinks when expressed as kcal/min (3.39 ± 0.21 kcal/min vs. 3.81 ± 0.20 kcal/min, p = 0.25). There was no change in blood glucose after the low-nutrient drinks with or without glutamine, despite a slight increase in plasma insulin with glutamine (p = 0.007). The rise in blood glucose following the high-nutrient drink (p = 0.0001) was attenuated during the first 60 min by glutamine (p = 0.007). We conclude that in healthy subjects, glutamine slows GE of both low- and high-nutrient drinks comparably and attenuates the rise in blood glucose after the high-nutrient glucose drink.
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Gavage Feed Volume Determines the Gastric Emptying Rate in Preterm Infants.
Ferreira, CHF, Martinez, FE, Crott, GC, Belik, J
Journal of pediatric gastroenterology and nutrition. 2018;(3):e43-e46
Abstract
OBJECTIVE Feeding intolerance, manifesting as increased gastric residual, is a common finding in preterm neonates. Little is known about the regulation of gastric emptying early in life and the extent to which this plays a role in the preterm infants' feeding tolerance. The goal of this study was to evaluate clinically stable 28- to 32-week gestation neonates during the first 4 weeks of life and noninvasively determine their gastric emptying rate. STUDY DESIGN Ultrasound measurements of gastric milk content volume were obtained from 25 neonates immediately after, 30 and/or 60 minutes following routine gavage feeds. The content emptying rate was calculated from the gastric volume data. RESULTS Gastric emptying rate was not postnatal age-dependent, was significantly higher at 30 minutes, whenever compared with 60-minute postfeed and directly proportional to the feed volume. At any postnatal age, the gastric emptying rate was at least 6-fold greater, when comparing the lowest and highest average stomach content volumes. CONCLUSIONS The gastric emptying rate of preterm infants is content volume-dependent and unrelated to the postnatal age. Given the present findings, further investigation on the gastric residual of preterm infants receiving larger than currently administered feed volumes at the initiation of enteral nutrition, is warranted.
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[Ultrasound dynamics of gastric content volumes after the ingestion of coconut water or a meat sandwich. A randomized controlled crossover study in healthy volunteers].
Carmona, BM, Almeida, CCA, Vieira, WB, Fascio, MNC, Carvalho, LR, Vane, LA, Barbosa, FT, do Nascimento Junior, P, Módolo, NSP
Brazilian journal of anesthesiology (Elsevier). 2018;(6):584-590
Abstract
BACKGROUND Adequate preoperative fasting is critical in preventing pulmonary aspiration of gastric content. We proposed to study the sonographic gastric content dynamics after the ingestion of liquid or solid food in healthy volunteers and confront it with current guidelines for preoperative fasting times. METHODS We performed a prospective, crossover, evaluator-blinded study involving 17 healthy volunteers of both sexes. Each participant fasted for 10 h and was subjected to a baseline gastric ultrasound, intake of 400 mL of coconut water or a 145 g, 355 kcal meat sandwich, and sonographic gastric evaluations after 10 min and every hour until the stomach was completely empty. RESULTS At baseline, all subjects had an empty stomach. At 10 min, gastric content [mean + standard deviation (SD)] was 240.4 + 69.3 and 248.2 + 119.2 mL for liquid and solid foods, respectively (p > 0.05). Mean + SD gastric emptying times were 2.5 + 0.7 and 4.5 + 0.9 h for liquid and solid foods, respectively (p < 0.001). For the drink, the stomach was completely empty in 59% and 100% of the subjects after two and four hours, and for the sandwich, 65% and 100% of the subjects after four and seven hours, respectively. CONCLUSIONS Sonographic gastric dynamics for coconut water and a meat sandwich resulted in complete gastric emptying times higher and lower, respectively, than those suggested by current guidelines for preoperative fasting.
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Brown rice compared to white rice slows gastric emptying in humans.
Pletsch, EA, Hamaker, BR
European journal of clinical nutrition. 2018;(3):367-373
Abstract
BACKGROUND/OBJECTIVES Consumption of whole vs. refined grain foods is recommended by nutrition or dietary guideline authorities of many countries, yet specific aspects of whole grains leading to health benefits are not well understood. Gastric emptying rate is an important consideration, as it is tied to nutrient delivery rate and influences glycemic response. Our objective was to explore two aspects of cooked rice related to gastric emptying, (1) whole grain brown vs. white rice and (2) potential effect of elevated levels of slowly digestible starch (SDS) and resistant starch (RS) from high-amylose rice. SUBJECTS/METHODS Ten healthy adult participants were recruited for a crossover design study involving acute feeding and testing of 6 rice samples (50 g available carbohydrate). Gastric emptying rate was measured using a 13C-labeled octanoic acid breath test. A rice variety (Cocodrie) with high-amylose content was temperature-cycled to increase SDS and RS fractions. RESULTS In vitro starch digestibility results showed incremental increase in RS in Cocodrie after two temperature cycles. For low-amylose varieties, SDS was higher in the brown rice form. In human subjects, low-amylose and high-amylose brown rice delayed gastric emptying compared to white rices regardless of amylose content or temperature-cycling (p < 0.05). CONCLUSIONS Whole grain brown rice had slower gastric emptying rate, which appears to be related to the physical presence of the bran layer. Extended gastric emptying of brown rice explains in part comparably low glycemic response observed for brown rice.
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The Effect of Exercise Intensity on Gastric Emptying Rate, Appetite and Gut Derived Hormone Responses after Consuming a Standardised Semi-Solid Meal in Healthy Males.
Mattin, LR, Yau, AMW, McIver, V, James, LJ, Evans, GH
Nutrients. 2018;(6)
Abstract
This study investigated the acute circulating gut hormone, appetite and gastric emptying rate responses to a semi-solid meal following exercise at different intensities. Twelve men completed three trials in a randomised-crossover design, consisting of continuous cycling at 70% V˙O2Peak (HIGH), 40% V˙O2Peak (LOW) or rest (CONTROL). Baseline samples were collected after an overnight fast before undertaking the 60 min exercise or rest period, followed by 30 min rest before consumption of a standardised semi-solid meal (~242 kcal). During the 2 h postprandial period, gastric emptying rate of the meal was examined using the 13C-breath test method, appetite was measured using visual analogue scales, and serum concentrations of acylated ghrelin, pancreatic polypeptide, peptide YY, glucagon-like peptide-1, insulin, glucose, triglycerides, total cholesterol and non-esterified fatty acids were assessed. Subjective appetite response was not different between trials (p > 0.05). Half emptying time of the meal was 89 ± 13, 82 ± 8 and 94 ± 31 min on CONTROL, LOW and HIGH, respectively (p = 0.247). In healthy un-trained adult males, responses to exercise at intensities of 70% and 40% V˙O2Peak did not differ to a non-exercise control for measurements of subsequent gastric emptying, circulating gut hormone response or appetite. These results suggest that exercise intensity has little effect on post-exercise appetite response to a semi-solid meal.