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Gastrointestinal hormones and regulation of gastric emptying.
Camilleri, M
Current opinion in endocrinology, diabetes, and obesity. 2019;(1):3-10
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Abstract
PURPOSE OF REVIEW This review examines the hormonal regulation of gastric emptying, a topic of increasing relevance, given the fact that medications that are analogs of some of these hormones or act as agonists at the hormonal receptors, are used in clinical practice for optimizing metabolic control in the treatment of type 2 diabetes and in obesity. RECENT FINDINGS The major effects on gastric emptying result from actions of incretins, particularly gastric inhibitory polypeptide, glucagon-like peptide-1, and peptide tyrosine-tyrosine, the duodenal and pancreatic hormones, motilin, glucagon, and amylin, and the gastric orexigenic hormones, ghrelin and motilin. All of these hormones delay gastric emptying, except for ghrelin and motilin which accelerate gastric emptying. These effects on gastric emptying parallel the effects of the hormones on satiation (by those retarding emptying) and increase appetite by those that accelerate emptying. Indeed, in addition to the effects of these hormones on hypothalamic appetite centers and glycemic control, there is evidence that some of their biological effects are mediated through actions on the stomach, particularly with the glucagon-like peptide-1 analogs or agonists used in treating obesity. SUMMARY Effects of gastrointestinal hormones on gastric emptying are increasingly recognized as important mediators of satiation and postprandial glycemic control.
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Rapid gastric emptying in diabetes mellitus: Pathophysiology and clinical importance.
Goyal, RK, Cristofaro, V, Sullivan, MP
Journal of diabetes and its complications. 2019;(11):107414
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Abstract
Although slow gastric emptying (gastroparesis) is a well-known complication of chronic hyperglycemia in diabetes mellitus (DM), it recently has become clear that rapid gastric emptying also is a frequent and important diabetic complication. In contrast, acute hyperglycemia causes slow gastric emptying, and acute hypoglycemia causes rapid gastric emptying. Rapid gastric emptying is frequent in T2DM; however, it may also occur in T1DM, particularly in the early stages of the disease, but may persist even into late stages. Recent studies suggest that usually, the stomach restricts the emptying of nutrients to 1-4 kcals/min. This restriction is due to the action of the gastric 'braking' hormones such as GLP-1, leptin, and amylin acting via the gastric inhibitory vagal motor circuit (GIVMC). Disruption of this braking system leads to rapid gastric emptying. Acute hyperglycemia also slows gastric emptying by stimulating the GIVMC, while acute hypoglycemia causes rapid gastric emptying by stimulating the gastric excitatory vagal motor circuit (GEVMC). In contrast, chronic hyperglycemia causes rapid gastric emptying by inducing oxidative stress in the stomach wall that disrupts inhibitory neuromuscular transmission and increases the contractility of the smooth muscle, while chronic hyperglycemia may also cause slow gastric emptying via severe inflammatory stress caused by proinflammatory macrophages and reduce contractility of the smooth muscle. There is a bidirectional relationship between blood glucose and gastric emptying. Thus, rapid gastric emptying may lead to a sizeable postprandial spike, and slow gastric emptying may blunt it. Postprandial hyperglycemia is involved in the development, progression, and complications of DM. Correction of fast gastric emptying involves agents that activate GIVMC and the use of gastric 'braking' hormones or their analogs. Recognition and treatment of rapid gastric emptying may contribute to better management of postprandial hyperglycemia and prevention of some diabetic complications.
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Any news from the prokinetic front?
Deane, AM, Chapman, MJ, Abdelhamid, YA
Current opinion in critical care. 2019;(4):349-355
Abstract
PURPOSE OF REVIEW This review provides an update of recently conducted studies and randomized controlled trials evaluating prokinetic drugs. RECENT FINDINGS Prokinetic drugs accelerate gastric emptying and, particularly in patients with gastric dysmotility and enteral feed intolerance, their use increases the delivery of enteral nutrition. However, prokinetic drugs have not been shown to improve patient-centered outcomes in trials but benefit is assumed on the basis of observational studies, which report close associations between gastric dysmotility, enteral feed intolerance and poor outcomes, and improvement in surrogate physiological outcomes when prokinetic drugs are administered. SUMMARY It may not be feasible to establish superiority of a prokinetic drug within a randomized controlled trial with a patient-centered event as the primary outcome. The use of metoclopramide and erythromycin as prokinetic drugs is based on observations from trials measuring surrogate physiological outcomes. Randomized controlled trials of alternative drug regimens and novel prokinetic drugs have recently been completed and results outlined.
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Postprandial Glucose Control in Type 1 Diabetes: Importance of the Gastric Emptying Rate.
Lupoli, R, Pisano, F, Capaldo, B
Nutrients. 2019;(7)
Abstract
The achievement of optimal post-prandial (PP) glucose control in patients with type 1 diabetes (T1DM) remains a great challenge. This review summarizes the main factors contributing to PP glucose response and discusses the likely reasons why PP glucose control is rarely achieved in T1DM patients. The macronutrient composition of the meal, the rate of gastric emptying and premeal insulin administration are key factors affecting the PP glucose response in T1DM. Although the use of continuous insulin infusion systems has improved PP glucose control compared to conventional insulin therapy, there is still need for further ameliorations. T1DM patients frequently present a delayed gastric emptying (GE) that produces a lower but more prolonged PP hyperglycemia. In addition, delayed GE is associated with a longer time to reach the glycemic peak, with a consequent mismatch between PP glucose elevation and the timing of premeal insulin action. On this basis, including GE time and meal composition in the algorithms for insulin bolus calculation of the insulin delivery systems could be an important step forward for optimization of PP glucose control in T1DM.
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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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Drug-resin drug interactions in patients with delayed gastric emptying: What is optimal time window for drug administration?
Camilleri, M
Neurogastroenterology and motility. 2016;(8):1268-71
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Abstract
Most drug-drug interactions involve overlap or competition in drug metabolic pathways. However, there are medications, typically resins, whose function is to bind injurious substances such as bile acids or potassium within the digestive tract. The objective of this article is to review the functions of the stomach and the kinetics of emptying of different food forms or formulations to make recommendations on timing of medication administration in order to avoid intragastric drug interactions. Based on the profiles and kinetics of emptying of liquid nutrients and homogenized solids, a window of 3 h between administration of a resin drug and another 'target' medication would be expected to allow a median of 80% of medications with particle size <1 mm to empty from the stomach and, hence, avoid potential interaction such as binding of the 'target' medication within the stomach.
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Acute exercise and gastric emptying: a meta-analysis and implications for appetite control.
Horner, KM, Schubert, MM, Desbrow, B, Byrne, NM, King, NA
Sports medicine (Auckland, N.Z.). 2015;(5):659-78
Abstract
BACKGROUND Gastric emptying (GE) could influence exercise-induced changes in appetite and energy intake. GE also could contribute to changes in gastric symptoms and the availability of nutrients during exercise, which will subsequently affect performance. OBJECTIVE The objective of this review was to determine the effects of acute exercise on GE using a systematic review and meta-analysis. The most common parameters to determine GE were selected, consisting of half-emptying time and volume emptied. Oral-caecal transit time (OCTT) was also examined. DATA SOURCES Research databases (PubMed, Scopus, Google Scholar, EBSCOhost, SPORTDiscus) were searched through November 2013 for original studies, abstracts, theses and dissertations that examined the influence of acute exercise on GE. STUDY SELECTION Studies were included if they evaluated GE or OCTT during and/or after exercise and involved a resting control trial. STUDY APPRAISAL AND SYNTHESIS Initially, 195 studies were identified. After evaluation of study characteristics and quality and validity, data from 20 studies (35 trials) involving 221 participants (157 men; 52 women; 12 unknown) were extracted for meta-analysis. Random-effects meta-analyses were utilised for the three main outcome variables, and effect sizes (ES) are reported as Hedge's g due to numerous small sample sizes. RESULTS Random-effects modelling revealed non-significant and small/null main effect sizes for volume emptied (ES = 0.195; 95% CI -0.25 to 0.64), half-time (ES = -0.109, 95% CI -0.66 to 0.44) and OCTT (ES = 0.089; 95% CI -0.64 to 0.82). All analyses exhibited significant heterogeneity and numerous variables moderated the results. There was a dose response of exercise intensity; at lower intensities GE was faster, and at high exercise intensities GE was slower. Walking was associated with faster GE and cycling with slower GE. Greater volume of meal/fluid ingested, higher osmolality of beverage and longer exercise duration were also associated with slower GE with exercise. LIMITATIONS The major limitation is that the majority of studies utilised a liquid bolus administered pre-exercise to determine GE; the relationship to post-exercise appetite and energy intake remains unknown. Study populations were also generally active or trained individuals. Furthermore, our review was limited to English language studies and studies that utilised resting control conditions. CONCLUSIONS These results suggest that exercise intensity, mode, duration and the nature of meal/fluid ingested all influence GE during and after acute exercise. The relationship of GE parameters with appetite regulation after exercise remains largely unexplored. Further integrative studies combining GE and alterations in gut hormones, as well as in populations such as overweight and obese individuals are needed.
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Gastrointestinal dysfunction relating to the provision of nutrition in the critically ill.
Chapman, MJ, Deane, AM
Current opinion in clinical nutrition and metabolic care. 2015;(2):207-12
Abstract
PURPOSE OF REVIEW During critical illness, enteral nutrition remains central to clinical care and an understanding of gut dysfunction is therefore important. Contemporary data have contributed to our knowledge in this area and this review will concentrate on recently published studies. RECENT FINDINGS It is difficult to precisely measure gastric emptying and nutrient absorption as part of routine clinical care. However, techniques for the measurement of these parameters for research purposes have been refined, studied and validated. These methodologies allow the evaluation of novel treatments that modulate gastric emptying. Quantification and an understanding of the mechanisms of nutrient malabsorption may facilitate the development of therapeutic agents to improve absorption and/or formulae, which are more readily absorbed, thereby improving nutritional and clinical outcomes. SUMMARY Improved understanding of gut pathophysiology in critical illness provides opportunities for the development and testing of novel and targeted treatment strategies, with the objective to improve clinical outcomes in this group.
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The role of alginates in regulation of food intake and glycemia: a gastroenterological perspective.
El Khoury, D, Goff, HD, Anderson, GH
Critical reviews in food science and nutrition. 2015;(10):1406-24
Abstract
Regulation of food intake through modulation of gastrointestinal responses to ingested foods is an ever-growing component of the therapeutic approaches targeting the obesity epidemic. Alginates, viscous and gel-forming soluble fibers isolated from the cell wall of brown seaweeds and some bacteria, are recently receiving considerable attention because of their potential role in satiation, satiety, and food intake regulation in the short term. Enhancement of gastric distension, delay of gastric emptying, and attenuation of postprandial glucose responses may constitute the basis of their physiological benefits. Offering physical, chemical, sensorial, and physiological advantages over other viscous and gel-forming fibers, alginates constitute promising functional food ingredients for the food industry. Therefore, the current review explores the role of alginates in food intake and glycemic regulation, their underlying modes of action and their potential in food applications.
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Systematic review of the impact of feed protein type and degree of hydrolysis on gastric emptying in children.
Meyer, R, Foong, RX, Thapar, N, Kritas, S, Shah, N
BMC gastroenterology. 2015;:137
Abstract
BACKGROUND The choice of infant formula is thought to play an important role on gastric emptying (GE) in a variety of gastrointestinal disorders. It is known that many ingredients impact on GE, including the type of protein and level of hydrolysis. In clinical practice, feeds are often recommended due to putative improved GE related to the type of protein and level of hydrolysis, however whether this is scientifically justified still needs to be established. A systematic review comparing the impact of protein type and hydrolysis on GE in children was therefore performed. METHODS The Patient, Intervention, Comparison and Outcome system was used. A structured literature search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines, searching PubMed, Cochrane databases and Google Scholar from 1990 to 2014. We only included articles published in full text English language using specific search terms, including both scintigraphy and C13-octanoic acid breath test. RESULTS We identified 126 publications of which 20 were eligible for inclusion but only 8 were included. Studies reviewed GE in both healthy children as well as those with neurodevelopmental delay and reflux. Two studies investigating GE of breast milk versus formula indicated a faster GE for breast milk. Four studies found that feeds containing whole whey in varying amounts emptied faster than predominant whole casein feeds and one study found no difference in GE. Five studies investigated a mix of whole versus hydrolysed protein and found conflicting results related to study population and hydrolysis. CONCLUSIONS Breast milk has a faster GE than formula milk. Although there seems to be a trend towards whey feeds emptying faster, different methodologies, feed compositions and patient groups makes it difficult to draw firm conclusions. Future studies should be performed with comparable feeds in populations where increased GE may be of clinical benefit.