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Oral lactate slows gastric emptying and suppresses appetite in young males.
Pedersen, MGB, Søndergaard, E, Nielsen, CB, Johannsen, M, Gormsen, LC, Møller, N, Jessen, N, Rittig, N
Clinical nutrition (Edinburgh, Scotland). 2022;(2):517-525
Abstract
BACKGROUND Lactate serves as an alternative energy fuel but is also an important signaling metabolite. We aimed to investigate whether oral lactate administration affects appetite-regulating hormones, slows gastric emptying rate, and dampens appetite. METHODS Ten healthy male volunteers were investigated on two separate occasions: 1) following oral ingestion of D/L-Na-lactate and 2) following oral ingestion of isotonic iso-voluminous NaCl and intravenous iso-lactemic D/L-Na-lactate infusions. Appetite was evaluated by questionnaires and ad libitum meal tests were performed at the end of each study day. Gastric emptying rate was evaluated using the acetaminophen test. RESULTS Plasma concentrations of growth differential factor 15 (GDF15, primary outcome) increased following oral and iv administration of lactate (p < 0.001) with no detectable difference between interventions (p = 0.15). Oral lactate administration lowered plasma concentrations of acylated ghrelin (p = 0.02) and elevated glucagon like peptide-1 (GLP-1, p = 0.045), insulin (p < 0.001), and glucagon (p < 0.001) compared with iv administration. Oral lactate administration slowed gastric emptying (p < 0.001), increased the feeling of being "full" (p = 0.008) and lowered the "anticipated future food intake" (p = 0.007) compared with iv administration. Food intake during the ad libitum meal test did not differ between the two study days. CONCLUSION Oral lactate administration has a direct effect on the upper gastrointestinal tract, affecting gut hormone secretion, motility and appetite sensations which cannot be mediated through lactate in the systemic circulation alone. These data suggest that compounds rich in lactate may be useful in the treatment of metabolic disease. CLINICAL TRIAL REGISTRY NUMBER NCT0429981, https://clinicaltrials.gov/ct2/show/NCT04299815.
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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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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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Oatmeal particle size alters glycemic index but not as a function of gastric emptying rate.
Mackie, AR, Bajka, BH, Rigby, NM, Wilde, PJ, Alves-Pereira, F, Mosleth, EF, Rieder, A, Kirkhus, B, Salt, LJ
American journal of physiology. Gastrointestinal and liver physiology. 2017;(3):G239-G246
Abstract
The aim of this study was to determine the extent to which oat particle size in a porridge could alter glucose absorption, gastric emptying, gastrointestinal hormone response, and subjective feelings of appetite and satiety. Porridge was prepared from either oat flakes or oat flour with the same protein, fat, carbohydrate, and mass. These were fed to eight volunteers on separate days in a crossover study, and subjective appetite ratings, gastric contents, and plasma glucose, insulin, and gastrointestinal hormones were determined over a period of 3 h. The flake porridge gave a lower glucose response than the flour porridge, and there were apparent differences in gastric emptying in both the early and late postprandial phases. The appetite ratings showed similar differences between early- and late-phase behavior. The structure of the oat flakes remained sufficiently intact to delay their gastric emptying, leading to a lower glycemic response, even though initial gastric emptying rates were similar for the flake and flour porridge. This highlights the need to take food structure into account when considering relatively simple physiological measures and offering nutritional guidance.NEW & NOTEWORTHY The impact of food structure on glycemic response even in simple foods such as porridge is dependent on both timing of gastric emptying and the composition of what is emptied as well as duodenal starch digestion. Thus structure should be accounted for when considering relatively simple physiological measures and offering nutritional guidance.
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Normal gastric emptying time of a carbohydrate-rich drink in elderly patients with acute hip fracture: a pilot study.
Hellström, PM, Samuelsson, B, Al-Ani, AN, Hedström, M
BMC anesthesiology. 2017;(1):23
Abstract
BACKGROUND Guidelines for fasting in elderly patients with acute hip fracture are the same as for other trauma patients, and longer than for elective patients. The reason is assumed stress-induced delayed gastric emptying with possible risk of pulmonary aspiration. Prolonged fasting in elderly patients may have serious negative metabolic consequences. The aim of our study was to investigate whether the preoperative gastric emptying was delayed in elderly women scheduled for surgery due to acute hip fracture. METHODS In a prospective study gastric emptying of 400 ml 12.6% carbohydrate rich drink was investigated in nine elderly women, age 77-97, with acute hip fracture. The emptying time was assessed by the paracetamol absorption technique, and lag phase and gastric half-emptying time was compared with two gender-matched reference groups: ten elective hip replacement patients, age 45-71 and ten healthy volunteers, age 28-55. RESULTS The mean gastric half-emptying time in the elderly study group was 53 ± 5 (39-82) minutes with an expected gastric emptying profile. The reference groups had a mean half-emptying time of 58 ± 4 (41-106) and 59 ± 5 (33-72) minutes, indicating normal gastric emptying time in elderly with hip fracture. CONCLUSION This pilot study in women with an acute hip fracture shows no evidence of delayed gastric emptying after an orally taken carbohydrate-rich beverage during the pre-operative fasting period. This implies no increased risk of pulmonary aspiration in these patients. Therefore, we advocate oral pre-operative management with carbohydrate-rich beverage in order to mitigate fasting-induced additive stress in the elderly with hip fracture. TRIAL REGISTRATION ClinicalTrials.gov NCT02753010 . Registered 17 April 2016, retrospectively.
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Lixisenatide reduces postprandial hyperglycaemia via gastrostatic and insulinotropic effects.
Becker, RH, Stechl, J, Steinstraesser, A, Golor, G, Pellissier, F
Diabetes/metabolism research and reviews. 2015;(6):610-8
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BACKGROUND Lixisenatide is a once-daily, prandial, short-acting glucagon-like peptide-1 receptor agonist. Its main antidiabetic effect is to delay gastric emptying to control postprandial plasma glucose excursions. The dose-response relationship of the integrated insulinotropic and gastrostatic response to lixisenatide in healthy volunteers after a standardized liquid meal was investigated. METHODS Twenty healthy subjects received acetaminophen 1000 mg with a standardized liquid meal 60 min after a single subcutaneous injection of placebo or lixisenatide 2.5, 5, 10 or 20 µg in randomized order separated by a 2- to 7-day washout. Acetaminophen pharmacokinetics served as a surrogate to assess rate of gastric emptying. Postprandial plasma glucose, insulin, C-peptide and glucagon were assessed for 5 h after the meal test, and lixisenatide pharmacokinetics were determined for 6 h. RESULTS After lixisenatide administration and prior to the standardized meal, insulin and C-peptide transiently increased, while fasting plasma glucose decreased in a dose-dependent manner. After the meal, postprandial plasma glucose, insulin and C-peptide were dose proportionally reduced with lixisenatide versus placebo for up to 6 h. Compared with placebo, glucagon levels were transiently lower after any lixisenatide dose, with more sustained reductions after the meal and no apparent dose-related trends. Acetaminophen absorption was significantly reduced and delayed compared with placebo for lixisenatide doses ≥5 µg and demonstrated dose-dependent slowing of gastric emptying. Lixisenatide displayed near dose-proportional exposure, with gastrointestinal events increasing with dose. CONCLUSIONS Lixisenatide reduced fasting plasma glucose via stimulation of glucose-dependent insulin release and controlled postprandial plasma glucose by delaying gastric emptying, demonstrating it to be a valuable option for overall glycaemic control.
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Unchanged gastric emptying and visceral perception in early Parkinson's disease after a high caloric test meal.
Epprecht, L, Schreglmann, SR, Goetze, O, Woitalla, D, Baumann, CR, Waldvogel, D
Journal of neurology. 2015;(8):1946-53
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Delayed gastric emptying (GE) is a frequent non-motor feature in Parkinson´s disease (PD). This prospective study (clinicaltrials.gov Identifier NCT01518751) investigated GE and visceral perception in early motor phase PD patients in comparison to age-matched and younger controls. In addition, the effect of Levodopa on GE was assessed in healthy aged controls. 16 PD patients (Hoehn & Yahr 2), 11 sex-/age-matched Ctrl1 and 10 young, male Ctrl2 subjects were subjected to a high caloric (428 kcal) (13)C-Sodium Octanoate breath test strictly OFF dopaminergic medication. Visceral appetite sensation was monitored using visual analogue scales (VAS). GE was similarly studied in 7 controls ON/OFF oral Levodopa. GE was not altered in PD patients compared to age-/sex-matched and younger controls (p = 0.76). Subjective appetite perception was not altered in the PD group in comparison to Ctrl1, but was significantly higher in Ctrl2 subjects (p = 0.02). 100 mg oral Levodopa/25 mg Benserazide significantly slowed GE by 18% among healthy controls (p = 0.04). In early motor stage PD OFF dopaminergic medication, there was no GE slowing after a high caloric test meal. Levodopa, however, caused a robust GE slowing in healthy aged individuals. Our data indicate that clinically relevant GE slowing in early PD is related to the iatrogenic effect of dopamine treatment. Subjective appetite perception is not affected in this disease stage. This data add to the understanding of gastrointestinal symptoms in early motor stage PD and highlight the influence of dopaminergic medication.
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Incomplete stomach emptying as a complication of intragastric balloon treatment and a solution suggestion: Pineapple juice drinking.
Simşek, Z, Altınbaş, A, Delibaşı, T, Yüksel, O
The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology. 2013;(4):330-3
Abstract
BACKGROUND/AIMS: During removal of intragastric balloon, there is a great deal of gastric undigested food even after an eight-hour starvation. Bromelain, a proteolytic enzyme existing in the pineapple juice seems to be a good choice for the undigested food remnants in the stomach. We aimed to investigate the effect of drinking pineapple juice on dissolving food remnants in patients undergoing endoscopic procedure for removal of intragastric balloon. MATERIALS AND METHOD In this study, we included patients who had undergone endoscopic placement of intragastric balloon (BIB®, BioEnterics Intragastric Balloon, Inamed Health, CA, USA) between February 2009 and March 2012. First 8 patients were asked to fast the whole night before the procedure (at least 8 hours) and to apply clear liquid diet for 3 days before the endoscopic removal. A great amount of food remnants was seen in the stomach during the endoscopic balloon removal procedure. A second endoscopic procedure was planned 3 days later and, in order to decrease the food remnants, the patients were asked to drink 1 L pineapple juice per day. The next 11 patients were also advised to drink 1 liter per day of 100% pineapple juice for 3 days before the endoscopic removal. RESULTS Totally, 19 obese patients (17 female, 2 male) were included in the study. Mean age was 38,68±7,95 years, mean weigh was 124,23±19,30 kg, and mean body mass index was 49,73±9,22 kg/m 2 . There was undigested food in the stomach during endoscopic removal in the first 8 patients. However, no undigested food in the stomach was found at the second endoscopic examination. In the other 11 patients, no food remnants were observed after taking pineapple juice prior to the endoscopic removal procedure. CONCLUSION Drinking pineapple juice for 3 days before endoscopic balloon removal seems to be effective in dissolving food remnants in the stomach. Drinking pineapple juice may be recommended in all patients undergoing endoscopic procedure for removal of intragastric balloon.
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Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans.
Wu, T, Zhao, BR, Bound, MJ, Checklin, HL, Bellon, M, Little, TJ, Young, RL, Jones, KL, Horowitz, M, Rayner, CK
The American journal of clinical nutrition. 2012;(1):78-83
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BACKGROUND Macronutrient "preloads" can stimulate glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), slow gastric emptying, and reduce postprandial glycemic excursions. After sweet preloads, these effects may be signaled by sodium-glucose cotransporter-1 (SGLT1), sweet taste receptors, or both. OBJECTIVE We determined the effects of 4 sweet preloads on GIP and GLP-1 release, gastric emptying, and postprandial glycemia. DESIGN Ten healthy subjects were studied on 4 separate occasions each. A preload drink containing 40 g glucose, 40 g tagatose/isomalt mixture (TIM), 40 g 3-O-methylglucose (3OMG; a nonmetabolized substrate of SGLT1), or 60 mg sucralose was consumed 15 min before a (13)C-octanoic acid-labeled mashed potato meal. Blood glucose, plasma total GLP-1 and GIP, serum insulin, and gastric emptying were determined. RESULTS Both glucose and 3OMG stimulated GLP-1 and GIP release in advance of the meal (each P < 0.05), whereas TIM and sucralose did not. The overall postprandial GLP-1 response was greater after glucose, 3OMG, and TIM than after sucralose (P < 0.05), albeit later after TIM than the other preloads. The blood glucose and insulin responses in the first 30 min after the meal were greatest after glucose (each P < 0.05). Gastric emptying was slower after both 3OMG and TIM than after sucralose (each P < 0.05). CONCLUSIONS In healthy humans, SGLT1 substrates stimulate GLP-1 and GIP and slow gastric emptying, regardless of whether they are metabolized, whereas the artificial sweetener sucralose does not. Poorly absorbed sweet tastants (TIM), which probably expose a greater length of gut to nutrients, result in delayed GLP-1 secretion but not in delayed GIP release. These observations have the potential to optimize the use of preloads for glycemic control. This trial was registered at www.actr.org.au as ACTRN12611000775910.
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Orlistat accentuates the fat-induced fall in blood pressure in older adults.
Tai, K, Gentilcore, D, Jones, KL, Banh, L, Gilja, OH, Hammond, AJ, Feinle-Bisset, C, Horowitz, M, Chapman, IM
The British journal of nutrition. 2011;(3):417-24
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Postprandial hypotension may be influenced by the digestion of fat. The aim of the present study was to evaluate the hypothesis that products of fat digestion mediate the hypotensive response to fat. In part A of the study, nine healthy older subjects were studied on three separate occasions in randomised order. Blood pressure, heart rate (HR), plasma TAG and gastric emptying were measured following the ingestion of equivolaemic drinks: (1) 300 ml of high-fat drink (88 % fat); (2) fat drink mixed with 120 mg orlistat (lipase inhibitor); (3) water (control). In part B of the study, ten healthy older subjects were studied on two separate occasions. Blood pressure, HR, plasma TAG and superior mesenteric artery flow were measured during 90 min intraduodenal infusions of 10 % intralipid (2·7 ml/min), with and without 120 mg orlistat. Oral fat ingestion was associated with decreases in systolic and diastolic blood pressures (both P = 0·0001) that were greater when orlistat was co-administered (both P < 0·05), and an increase in HR (P = 0·0001) that was inhibited by orlistat co-administration (P < 0·03). Gastric emptying was slowed by oral fat digestion, and orlistat administration inhibited this slowing (P < 0·04). Intraduodenal fat infusion was not associated with changes in blood pressure but increased HR (P < 0·0001), an effect attenuated by orlistat (P < 0·05). In conclusion, orlistat potentiates the hypotensive response to oral fat in older adults, possibly as a result of faster gastric emptying of fat. The results do not support a role for fat digestion in lowering blood pressure.
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Gastric emptying after pickle-juice ingestion in rested, euhydrated humans.
Miller, KC, Mack, GW, Knight, KL
Journal of athletic training. 2010;(6):601-8
Abstract
CONTEXT Small volumes of pickle juice (PJ) relieve muscle cramps within 85 seconds of ingestion without significantly affecting plasma variables. This effect may be neurologic rather than metabolic. Understanding PJ's gastric emptying would help to strengthen this theory. OBJECTIVE To compare gastric emptying and plasma variables after PJ and deionized water (DIW) ingestion. DESIGN Crossover study. SETTING Laboratory. PATIENTS OR OTHER PARTICIPANTS Ten men (age = 25.4 ± 0.7 years, height = 177.1 ± 1.6 cm, mass = 78.1 ± 3.6 kg). INTERVENTION(S): Rested, euhydrated, and eunatremic participants ingested 7 mL·kg⁻¹ body mass of PJ or DIW on separate days. MAIN OUTCOME MEASURE(S): Gastric volume was measured at 0, 5, 10, 20, and 30 minutes postingestion (using the phenol red dilution technique). Percentage changes in plasma volume and plasma sodium concentration were measured preingestion (-45 minutes) and at 5, 10, 20, and 30 minutes postingestion. RESULTS Initial gastric volume was 624.5 ± 27.4 mL for PJ and 659.5 ± 43.8 mL for DIW (P > .05). Both fluids began to empty within the first 5 minutes (volume emptied: PJ = 219.2 ± 39.1 mL, DIW = 305.0 ± 40.5 mL, P < .05). Participants who ingested PJ did not empty further after the first 5 minutes (P > .05), whereas in those who ingested DIW, gastric volume decreased to 111.6 ± 39.9 mL by 30 minutes (P < .05). The DIW group emptied faster than the PJ group between 20 and 30 minutes postingestion (P < .05). Within 5 minutes of PJ ingestion, plasma volume decreased 4.8% ± 1.6%, whereas plasma sodium concentration increased 1.6 ± 0.5 mmol·L⁻¹ (P < .05). Similar changes occurred after DIW ingestion. Calculated plasma sodium content was unchanged for both fluids (P > .05). CONCLUSIONS The initial decrease in gastric volume with both fluids is likely attributable to gastric distension. Failure of the PJ group to empty afterward is likely due to PJ's osmolality and acidity. Cardiovascular reflexes resulting from gastric distension are likely responsible for the plasma volume shift and rise in plasma sodium concentration despite nonsignificant changes in plasma sodium content. These data support our theory that PJ does not relieve cramps via a metabolic mechanism.