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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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Assessment of physiological barriers to nutrition following critical illness.
Whitehead, J, Summers, MJ, Louis, R, Weinel, LM, Lange, K, Dunn, B, Chapman, MJ, Chapple, LS
Clinical nutrition (Edinburgh, Scotland). 2022;(1):11-20
Abstract
BACKGROUND & AIMS 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. METHODS 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 100 ml of 1 kcal/ml liquid nutrient, labelled with 0.1 g 13C-octanoic acid and 3 g 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). RESULTS Twenty-six critically ill patients completed V1 (M:F 20:6; 62.0 ± 2.9 y; BMI 29.8 ± 1.2 kg/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 ± 7.5 y; BMI 26.0 ± 1.0 kg/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. CONCLUSION 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. TRIAL ID ACTRN12618000370202.
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Emulsion acid colloidal stability and droplet crystallinity modulate postprandial gastric emptying and short-term satiety: a randomized, double-blinded, crossover, controlled trial in healthy adult males.
Hamad, S, Tari, NR, Mathiyalagan, G, Wright, AJ
The American journal of clinical nutrition. 2021;(3):997-1011
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Abstract
BACKGROUND Emulsion droplet triacylglycerol (TAG) crystallinity and colloidal stability can alter the postprandial metabolism, although evidence of their interactive effects is limited. OBJECTIVES This acute meal crossover study investigated the influences of droplet TAG crystallinity at 37°C and colloidal gastric stability on gastric emptying (GE), acute lipemia, and satiety. METHODS We gave 15 healthy adult males (mean ± SD age, 24.9 y ± 4.5 y; BMI, 26.0 kg/m2 ± 2.0 kg/m2; fasting TAG, 0.9 mmol/L ± 0.3 mmol/L) 250 mL of four 20% palm stearin or palm olein emulsions with similar particle size distributions and containing partially crystalline droplets that remained stable (SS) or destabilized (SU) or containing liquid droplets that remained stable (LS) or destabilized (LU) when exposed to simulated gastric conditions. Baseline and 6-h postprandial ultrasound gastric antrum measurements, satiety visual analogue scales (VAS), and blood samples for analyses of plasma TAG, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), ghrelin, leptin, glucose-dependent insulinotropic polypeptide, insulin, and glucose were collected. Changes from baseline and incremental area under the curve (iAUC) values were analyzed by repeated-measures ANOVA. RESULTS TAG responses did not differ significantly. The gastric antrum area decreased faster (P ≤ 0.01) after treatment with the acid-unstable emulsions (SU and LU), and satiety VAS ratings and plasma endpoints differed between treatments. After LS treatment, participants had 65% and 59% lower 3-h iAUC values for hunger (P = 0.021) and desire to eat (P = 0.031), respectively, compared to after SU treatment. LS treatment resulted in higher 6-h iAUC values for ghrelin (141%; P = 0.023) and PYY (150%; P = 0.043) compared to SU treatment, and LS treatment also resulted in higher GLP-1 values compared to SU (38%; P = 0.016) and LU (76%; P = 0.001) treatment. CONCLUSION Emulsion acid colloidal stability, independent of TAG physical state, delayed GE, and satiety was enhanced after consuming acid stable emulsions containing TAG in the liquid state. The study was registered at clinicaltrials.gov as NCT03990246.
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Diagnostic Evaluation of Gastric Motor and Sensory Disorders.
Lacy, BE, Crowell, MD, Cangemi, DJ, Lunsford, TN, Simren, M, Tack, J
The American journal of gastroenterology. 2021;(12):2345-2356
Abstract
Disorders of gastric motor and sensory function affect 10%-20% of the world's population and adversely impact nutrition, quality of life, work productivity, and health care costs. Classifying these disorders can be challenging given the heterogeneity of symptom presentation, the presence of symptoms unexplained by endoscopic, radiographic and/or laboratory evaluation, and overlap with other luminal gastrointestinal disorders. Accurately diagnosing these highly prevalent disorders relies upon an understanding of epidemiology and risk factors, the ability to take a careful clinical history focused on symptoms, and the presence of predisposing medical, surgical, and psychological conditions. A variety of diagnostic studies are now available to assess gastric motor function and identify maladaptive relaxation, accommodation, and abnormal sensation. FDA-approved treatment options are limited and thus many patients undergo a series of empirical treatment trials that target individual symptoms, often without much benefit. This article provides updated recommendations for identifying and classifying the most common gastric motor and sensory disorders using currently accepted diagnostic tests, and provides a brief supplemental overview on treatment options. "Things sweet to taste prove in digestion sour." -Shakespeare, Richard II, 1595.
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Comparative Effects of the Branched-Chain Amino Acids, Leucine, Isoleucine and Valine, on Gastric Emptying, Plasma Glucose, C-Peptide and Glucagon in Healthy Men.
Elovaris, RA, Bitarafan, V, Agah, S, Ullrich, SS, Lange, K, Horowitz, M, Feinle-Bisset, C
Nutrients. 2021;(5)
Abstract
(1) Background: Whey protein lowers postprandial blood glucose in health and type 2 diabetes, by stimulating insulin and incretin hormone secretion and slowing gastric emptying. The branched-chain amino acids, leucine, isoleucine and valine, abundant in whey, may mediate the glucoregulatory effects of whey. We investigated the comparative effects of intragastric administration of leucine, isoleucine and valine on the plasma glucose, C-peptide and glucagon responses to and gastric emptying of a mixed-nutrient drink in healthy men. (2) Methods: 15 healthy men (27 ± 3 y) received, on four separate occasions, in double-blind, randomised fashion, either 10 g of leucine, 10 g of isoleucine, 10 g of valine or control, intragastrically, 30 min before a mixed-nutrient drink. Plasma glucose, C-peptide and glucagon concentrations were measured before, and for 2 h following, the drink. Gastric emptying of the drink was quantified using 13C-acetate breath-testing. (3) Results: Amino acids alone did not affect plasma glucose or C-peptide, while isoleucine and valine, but not leucine, stimulated glucagon (p < 0.05), compared with control. After the drink, isoleucine and leucine reduced peak plasma glucose compared with both control and valine (all p < 0.05). Neither amino acid affected early (t = 0-30 min) postprandial C-peptide or glucagon. While there was no effect on overall gastric emptying, plasma glucose at t = 30 min correlated with early gastric emptying (p < 0.05). (4) Conclusion: In healthy individuals, leucine and isoleucine lower postprandial blood glucose, at least in part by slowing gastric emptying, while valine does not appear to have an effect, possibly due to glucagon stimulation.
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Intragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes.
Elovaris, RA, Hajishafiee, M, Ullrich, SS, Fitzgerald, PCE, Lange, K, Horowitz, M, Feinle-Bisset, C
Diabetes research and clinical practice. 2021;:108618
Abstract
AIMS: In healthy individuals, intragastric administration of the branched-chain amino acids, leucine and isoleucine, diminishes the glycaemic response to a mixed-nutrient drink, apparently by stimulating insulin and slowing gastric emptying, respectively. This study aimed to evaluate the effects of leucine and isoleucine on postprandial glycaemia and gastric emptying in type-2 diabetes mellitus (T2D). METHODS 14 males with T2D received, on 3 separate occasions, in double-blind, randomised fashion, either 10 g leucine, 10 g isoleucine or control, intragastrically 30 min before a mixed-nutrient drink (500 kcal; 74 g carbohydrates, 18 g protein, 15 g fat). Plasma glucose, insulin and glucagon were measured from 30 min pre- until 120 min post-drink. Gastric emptying of the drink was also measured. RESULTS Leucine and isoleucine stimulated insulin, both before and after the drink (all P < 0.05; peak (mU/L): control: 70 ± 15; leucine: 88 ± 17; isoleucine: 74 ± 15). Isoleucine stimulated (P < 0.05), and leucine tended to stimulate (P = 0.078), glucagon before the drink, and isoleucine stimulated glucagon post-drink (P = 0.031; peak (pg/mL): control: 62 ± 5; leucine: 70 ± 9; isoleucine: 69 ± 6). Neither amino acid affected gastric emptying or plasma glucose (peak (mmol/L): control: 12.0 ± 0.5; leucine: 12.5 ± 0.7; isoleucine: 12.0 ± 0.6). CONCLUSIONS In contrast to health, in T2D, leucine and isoleucine, administered intragastrically in a dose of 10 g, do not lower the glycaemic response to a mixed-nutrient drink. This finding argues against a role for 'preloads' of either leucine or isoleucine in the management of T2D.
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Gastric content and perioperative pulmonary aspiration in patients with diabetes mellitus: a scoping review.
Xiao, MZX, Englesakis, M, Perlas, A
British journal of anaesthesia. 2021;(2):224-235
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Abstract
BACKGROUND Gastric emptying may be delayed in patients with diabetes mellitus (DM). However, the incidence of full stomach in fasting patients with DM and their risk of pulmonary aspiration under anaesthesia is not well understood. METHODS A scoping review was undertaken to map the literature on aspiration risk in DM. A search was conducted in seven bibliographic databases, including MEDLINE and Embase, for original articles that studied aspiration risk, gastric emptying, or gastric content and volume. Selection and characterisation were performed by two independent reviewers using a predefined protocol registered externally. RESULTS The search identified 5063 unique records, and 16 studies (totalling 775 patients with DM) were selected: nine studied gastric emptying and seven studied gastric content or volume. There were no studies reporting the incidence of aspiration in subjects with DM. All nine studies reported delayed emptying in patients with DM compared with healthy controls. Amongst the seven studies that compared gastric residual content/volume (GRV) in the perioperative period, five reported clinically negligible GRV in both patients with DM and controls, whereas two observed a higher incidence of 'full' stomach in patients with DM. CONCLUSIONS The evidence concerning the aspiration risk for surgical patients with DM is based on a limited number of studies, mostly unblinded, reporting physiological data on gastric emptying and gastric volume as surrogate markers of aspiration risk. Data on fasting gastric content and volume in patients with DM are limited and contradictory; hence, the true risk of aspiration in fasting patients with DM is unknown.
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The Effect of Continuous Intake of Lactobacillus gasseri OLL2716 on Mild to Moderate Delayed Gastric Emptying: A Randomized Controlled Study.
Ohtsu, T, Haruma, K, Ide, Y, Takagi, A
Nutrients. 2021;(6)
Abstract
Probiotics have been suggested to be effective for functional dyspepsia, but their effect on gastric motility is not clear. We evaluated the effect of Lactobacillus gasseri OLL2716 (LG21 strain) on mild to moderate delayed gastric emptying by a double-blind, parallel-group, placebo-controlled, randomized trial. Participants (n = 28) were randomly assigned to ingest LG21 strain-containing yogurt (LG21 strain group) or LG21 strain-free yogurt (placebo group) for 12 weeks. The 13C gastric emptying breath test was performed to measure the gastric emptying rate over time following ingestion of a liquid meal, and the time to reach the peak (Tmax) was used as an indicator of gastric emptying. We also measured the salivary amylase concentration, an indicator of autonomic dysfunction under stress. The per-protocol population (n = 27, male n = 4, female n = 23) was evaluated for efficacy. When a ≥30% reduction in the difference between participant's Tmax and the Japanese mean Tmax was defined as an improvement, the odds ratio of improvement in delayed gastric emptying compared to placebo after 12 weeks was 4.1 (95% confidence interval, 0.8 to 20.2). Moreover, salivary amylase concentrations were significantly lower than in the placebo group, indicating an improvement in autonomic function. The present data were not enough to support the beneficial effects of the LG21 strain on delayed gastric emptying. However, if we define the odds ratio in further study investigated with a larger number of participants, LG21 strain might be expected to have some impact on delayed gastric emptying.
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Effect of obesity on gastrointestinal transit, pressure and pH using a wireless motility capsule.
Steenackers, N, Wauters, L, Van der Schueren, B, Augustijns, P, Falony, G, Koziolek, M, Lannoo, M, Mertens, A, Meulemans, A, Raes, J, et al
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2021;:1-8
Abstract
BACKGROUND Despite the increasing prevalence and medical burden of obesity, the understanding of gastrointestinal physiology in obesity is scarce, which hampers drug development. AIM: To investigate the effect of obesity and food intake on gastrointestinal transit, pressure and pH. MATERIAL AND METHODS An exploratory cross-sectional study using a wireless motility capsule (SmartPill©) was performed in 11 participants with obesity and 11 age- and gender-matched participants with normal weight (group) in fasted and fed state (visit). During the first visit, the capsule was ingested after an overnight fast. During a second visit, the capsule was ingested after a nutritional drink to simulate fed state. Linear mixed models were constructed to compare segmental gastrointestinal transit, pressure and pH between groups (obesity or control) and within every group (fasted or fed). RESULTS Food intake slowed gastric emptying in both groups (both P < 0.0001), though food-induced gastric contractility was higher in participants with obesity compared to controls (P = 0.02). In the small intestine, a higher contractility (P = 0.001), shorter transit (P = 0.04) and lower median pH (P = 0.002) was observed in participants with obesity compared to controls. No differences were observed for colonic measurements. CONCLUSION Obesity has a profound impact on gastrointestinal physiology, which should be taken into account for drug development.
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Effects of intragastric administration of L-tryptophan on the glycaemic response to a nutrient drink in men with type 2 diabetes - impacts on gastric emptying, glucoregulatory hormones and glucose absorption.
Hajishafiee, M, Elovaris, RA, Jones, KL, Heilbronn, LK, Horowitz, M, Poppitt, SD, Feinle-Bisset, C
Nutrition & diabetes. 2021;(1):3
Abstract
BACKGROUND The rate of gastric emptying and glucoregulatory hormones are key determinants of postprandial glycaemia. Intragastric administration of L-tryptophan slows gastric emptying and reduces the glycaemic response to a nutrient drink in lean individuals and those with obesity. We investigated whether tryptophan decreases postprandial glycaemia and slows gastric emptying in type 2 diabetes (T2D). METHODS Twelve men with T2D (age: 63 ± 2 years, HbA1c: 49.7 ± 2.5 mmol/mol, BMI: 30 ± 1 kg/m2) received, on three separate occasions, 3 g ('Trp-3') or 1.5 g ('Trp-1.5') tryptophan, or control (0.9% saline), intragastrically, in randomised, double-blind fashion, 30 min before a mixed-nutrient drink (500 kcal, 74 g carbohydrates), containing 3 g 3-O-methyl-D-glucose (3-OMG) to assess glucose absorption. Venous blood samples were obtained at baseline, after tryptophan, and for 2 h post-drink for measurements of plasma glucose, C-peptide, glucagon and 3-OMG. Gastric emptying of the drink was quantified using two-dimensional ultrasound. RESULTS Tryptophan alone stimulated C-peptide (P = 0.002) and glucagon (P = 0.04), but did not affect fasting glucose. In response to the drink, Trp-3 lowered plasma glucose from t = 15-30 min and from t = 30-45 min compared with control and Trp-1.5, respectively (both P < 0.05), with no differences in peak glucose between treatments. Gastric emptying tended to be slower after Trp-3, but not Trp-1.5, than control (P = 0.06). Plasma C-peptide, glucagon and 3-OMG increased on all days, with no major differences between treatments. CONCLUSIONS In people with T2D, intragastric administration of 3 g tryptophan modestly slows gastric emptying, associated with a delayed rise, but not an overall lowering of, postprandial glucose.