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Gastroenterology Jan 2022Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review... (Review)
Review
Gastroparesis is characterized by symptoms suggestive of, and objective evidence of, delayed gastric emptying in the absence of mechanical obstruction. This review addresses the normal emptying of solids and liquids from the stomach and details the myogenic and neuromuscular control mechanisms, including the specialized function of the pyloric sphincter, that result in normal emptying, based predominantly on animal research. A clear understanding of fundamental mechanisms is necessary to comprehend derangements leading to gastroparesis, and additional research on human gastric muscles is needed. The section on pathophysiology of gastroparesis considers neuromuscular diseases that affect nonsphincteric gastric muscle, disorders of the extrinsic neural control, and pyloric dysfunction that lead to gastroparesis. The potential cellular basis for gastroparesis is attributed to the effects of oxidative stress and inflammation, with increased pro-inflammatory and decreased resident macrophages, as observed in full-thickness biopsies from patients with gastroparesis. Predominant diagnostic tests involving measurements of gastric emptying, the use of a functional luminal imaging probe, and high-resolution antral duodenal manometry in characterizing the abnormal motor functions at the gastroduodenal junction are discussed. Management is based on supporting nutrition; dietary interventions, including the physical reduction in particle size of solid foods; pharmacological agents, including prokinetics and anti-emetics; and interventions such as gastric electrical stimulation and pyloromyotomy. These are discussed briefly, and comment is added on the potential for individualized treatments in the future, based on optimal gastric emptying measurement and objective documentation of the underlying pathophysiology causing the gastroparesis.
Topics: Animals; Enteric Nervous System; Gastric Emptying; Gastroparesis; Humans; Predictive Value of Tests; Pylorus; Treatment Outcome
PubMed: 34717924
DOI: 10.1053/j.gastro.2021.10.028 -
The American Journal of Gastroenterology Aug 2022Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical...
Gastroparesis is characterized by symptoms suggesting retention of food in the stomach with objective evidence of delayed gastric emptying in the absence of mechanical obstruction in the gastric outflow. This condition is increasingly encountered in clinical practice. These guidelines summarize perspectives on the risk factors, diagnosis, and management of gastroparesis in adults (including dietary, pharmacological, device, and interventions directed at the pylorus), and they represent the official practice recommendations of the American College of Gastroenterology. The scientific evidence for these guidelines was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation process. When the evidence was not appropriate for Grading of Recommendations, Assessment, Development, and Evaluation, we used expert consensus to develop key concept statements. These guidelines should be considered as preferred but are not the only approaches to these conditions.
Topics: Adult; Gastric Emptying; Gastroenterology; Gastroparesis; Humans; Pylorus; Risk Factors
PubMed: 35926490
DOI: 10.14309/ajg.0000000000001874 -
Gut Dec 2019Gastroparesis is defined by delayed gastric emptying (GE) and symptoms of nausea, vomiting, bloating, postprandial fullness, early satiety and abdominal pain. Most... (Review)
Review
Gastroparesis is defined by delayed gastric emptying (GE) and symptoms of nausea, vomiting, bloating, postprandial fullness, early satiety and abdominal pain. Most common aetiologies include diabetes, postsurgical and postinfectious, but in many cases it is idiopathic. Clinical presentation and natural history vary by the aetiology. There is significant morbidity and healthcare utilisation associated with gastroparesis. Mechanistic studies from diabetic animal models of delayed GE as well as human full-thickness biopsies have significantly advanced our understanding of this disorder. An innate immune dysregulation and injury to the interstitial cells of Cajal and other components of the enteric nervous system through paracrine and oxidative stress mediators is likely central to the pathogenesis of gastroparesis. Scintigraphy and C breath testing provide the most validated assessment of GE. The stagnant gastroparesis therapeutic landscape is likely to soon see significant changes. Relatively newer treatment strategies include antiemetics (aprepitant), prokinetics (prucalopride, relamorelin) and fundic relaxants (acotiamide, buspirone). Endoscopic pyloromyotomy appears promising over the short term, especially for symptoms of nausea and vomiting. Further controlled trials and identification of the appropriate subgroup with pyloric dysfunction and assessment of long-term outcomes are essential. This review highlights the clinical presentation, diagnosis, mechanisms and treatment advancements for gastroparesis.
Topics: Endoscopy, Gastrointestinal; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans
PubMed: 31563877
DOI: 10.1136/gutjnl-2019-318712 -
Sports Medicine (Auckland, N.Z.) Mar 2017The gastrointestinal (GI) tract plays a critical role in delivering carbohydrate and fluid during prolonged exercise and can therefore be a major determinant of... (Review)
Review
The gastrointestinal (GI) tract plays a critical role in delivering carbohydrate and fluid during prolonged exercise and can therefore be a major determinant of performance. The incidence of GI problems in athletes participating in endurance events is high, indicating that GI function is not always optimal in those conditions. A substantial body of evidence suggests that the GI system is highly adaptable. Gastric emptying as well as stomach comfort can be "trained" and perceptions of fullness decreased; some studies have suggested that nutrient-specific increases in gastric emptying may occur. Evidence also shows that diet has an impact on the capacity of the intestine to absorb nutrients. Again, the adaptations that occur appear to be nutrient specific. For example, a high-carbohydrate diet will increase the density of sodium-dependent glucose-1 (SGLT1) transporters in the intestine as well as the activity of the transporter, allowing greater carbohydrate absorption and oxidation during exercise. It is also likely that, when such adaptations occur, the chances of developing GI distress are smaller. Future studies should include more human studies and focus on a number of areas, including the most effective methods to induce gut adaptations and the timeline of adaptations. To develop effective strategies, a better understanding of the exact mechanisms underlying these adaptations is important. It is clear that "nutritional training" can improve gastric emptying and absorption and likely reduce the chances and/or severity of GI problems, thereby improving endurance performance as well as providing a better experience for the athlete. The gut is an important organ for endurance athletes and should be trained for the conditions in which it will be required to function.
Topics: Athletes; Diet; Dietary Carbohydrates; Exercise; Gastric Emptying; Humans; Physical Endurance; Physical Exertion
PubMed: 28332114
DOI: 10.1007/s40279-017-0690-6 -
Diabetes, Obesity & Metabolism Mar 2021To investigate the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity. (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To investigate the effects of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg on gastric emptying, appetite, and energy intake in adults with obesity.
MATERIALS AND METHODS
A double-blind, parallel-group trial was conducted in 72 adults with obesity, randomized to once-weekly s.c. semaglutide (dose-escalated to 2.4 mg) or placebo for 20 weeks. Gastric emptying was assessed using paracetamol absorption following a standardized breakfast. Participant-reported appetite ratings and Control of Eating Questionnaire (CoEQ) responses were assessed, and energy intake was measured during ad libitum lunch.
RESULTS
The area under the concentration-time curve (AUC) for paracetamol 0 to 5 hours after a standardized meal (AUC ; primary endpoint) was increased by 8% (P = 0.005) with semaglutide 2.4 mg versus placebo at week 20 (non-significant when corrected for week 20 body weight; P = 0.12). No effect was seen on AUC , maximum observed paracetamol concentration, or time to maximum observed paracetamol concentration. Ad libitum energy intake was 35% lower with semaglutide versus placebo (1736 versus 2676 kJ; estimated treatment difference -940 kJ; P <0.0001). Semaglutide reduced hunger and prospective food consumption, and increased fullness and satiety when compared with placebo (all P <0.02). The CoEQ indicated better control of eating and fewer/weaker food cravings with semaglutide versus placebo (P <0.05). Body weight was reduced by 9.9% with semaglutide and 0.4% with placebo. Safety was consistent with the known profile of semaglutide.
CONCLUSIONS
In adults with obesity, once-weekly s.c. semaglutide 2.4 mg suppressed appetite, improved control of eating, and reduced food cravings, ad libitum energy intake and body weight versus placebo. There was no evidence of delayed gastric emptying at week 20, assessed indirectly via paracetamol absorption.
Topics: Adult; Appetite; Double-Blind Method; Energy Intake; Gastric Emptying; Glucagon-Like Peptides; Humans; Obesity; Prospective Studies
PubMed: 33269530
DOI: 10.1111/dom.14280 -
Diabetes, Obesity & Metabolism Jul 2021To assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D). (Randomized Controlled Trial)
Randomized Controlled Trial
AIM
To assess the effects of oral semaglutide on postprandial glucose and lipid metabolism, and gastric emptying, in subjects with type 2 diabetes (T2D).
MATERIALS AND METHODS
In this randomized, double-blind, single-centre, crossover trial, subjects with T2D received once-daily oral semaglutide (escalated to 14 mg) followed by placebo, or vice versa, over two consecutive 12-week periods. Glucose and lipid metabolism, and gastric emptying (paracetamol absorption) were assessed before and after two types of standardized meals (standard and/or fat-rich) at the end of each treatment period. The primary endpoint was area under the glucose 0-5-h curve (AUC ) after the standard breakfast.
RESULTS
Fifteen subjects were enrolled (mean age 58.2 years, HbA1c 6.9%, body weight 93.9 kg, diabetes duration 3.1 years; 13 [86.7%] males). Fasting concentrations of glucose were significantly lower, and C-peptide significantly greater, with oral semaglutide versus placebo. Postprandial glucose (AUC ) was significantly lower with oral semaglutide versus placebo (estimated treatment ratio, 0.71; 95% CI, 0.63, 0.81; p < .0001); glucose incremental AUC (iAUC ) and glucagon AUC were also significantly reduced, with similar results after the fat-rich breakfast. Fasting concentrations of triglycerides, very low-density lipoprotein (VLDL) and apolipoprotein B48 (ApoB48) were significantly lower with oral semaglutide versus placebo. AUC for triglycerides, VLDL and ApoB48, and triglycerides iAUC , were significantly reduced after oral semaglutide versus placebo. During the first postprandial hour, gastric emptying was delayed (a 31% decrease in paracetamol AUC ) with oral semaglutide versus placebo. One serious adverse event (acute myocardial infarction) occurred during oral semaglutide treatment.
CONCLUSION
Oral semaglutide significantly improved fasting and postprandial glucose and lipid metabolism, and delayed gastric emptying.
Topics: Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Gastric Emptying; Glucagon-Like Peptides; Glucose; Humans; Hypoglycemic Agents; Lipid Metabolism; Male; Middle Aged; Postprandial Period
PubMed: 33710717
DOI: 10.1111/dom.14373 -
American Journal of Physiology.... May 2021This study was designed to investigate whether transcutaneous auricular vagal nerve stimulation (taVNS) would be able to improve major pathophysiologies of functional...
This study was designed to investigate whether transcutaneous auricular vagal nerve stimulation (taVNS) would be able to improve major pathophysiologies of functional dyspepsia (FD) in patients with FD. Thirty-six patients with FD (21 F) were studied in two sessions (taVNS and sham-ES). Physiological measurements, including gastric slow waves, gastric accommodation, and autonomic functions, were assessed by the electrogastrogram (EGG), a nutrient drink test and the spectral analysis of heart rate variability derived from the electrocardiogram (ECG), respectively. Thirty-six patients with FD (25 F) were randomized to receive 2-wk taVNS or sham-ES. The dyspeptic symptom scales, anxiety and depression scores, and the same physiological measurements were assessed at the beginning and the end of the 2-wk treatment. In comparison with sham-ES, acute taVNS improved gastric accommodation ( = 0.008), increased the percentage of normal gastric slow waves (%NSW, fasting: = 0.010; fed: = 0.007) and vagal activity (fasting: = 0.056; fed: = 0.026). In comparison with baseline, 2-wk taVNS but not sham-ES reduced symptoms of dyspepsia ( = 0.010), decreased the scores of anxiety ( = 0.002) and depression ( < 0.001), and improved gastric accommodation ( < 0.001) and the %NSW (fasting: < 0.05; fed: < 0.05) by enhancing vagal efferent activity (fasting: = 0.015; fed: = 0.048). Compared with the HC, the patients showed increased anxiety ( < 0.001) and depression ( < 0.001), and decreased gastric accommodation ( < 0.001) and %NSW ( < 0.001) as well as decreased vagal activity (fasting: = 0.047). The noninvasive taVNS has a therapeutic potential for treating nonsevere FD by improving gastric accommodation and gastric pace-making activity via enhancing vagal activity. Treatment of functional dyspepsia is difficult due to various pathophysiological factors. The proposed method of transcutaneous auricular vagal nerve stimulation improves symptoms of both dyspepsia and depression/anxiety, and gastric functions (accommodation and slow waves), possibly mediated via the enhancement of vagal efferent activity. This noninvasive and easy-to-implement neuromodulation method will be well received by patients and healthcare providers.
Topics: Adolescent; Adult; Aged; Autonomic Nervous System; Dyspepsia; Female; Gastric Emptying; Gastrointestinal Motility; Humans; Male; Middle Aged; Stomach; Treatment Outcome; Vagus Nerve; Vagus Nerve Stimulation; Young Adult
PubMed: 33624527
DOI: 10.1152/ajpgi.00426.2020 -
United European Gastroenterology Journal Apr 2021Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is...
BACKGROUND
Gastroparesis is a condition characterized by epigastric symptoms and delayed gastric emptying (GE) rate in the absence of any mechanical obstruction. The condition is challenging in clinical practice by the lack of guidance concerning diagnosis and management of gastroparesis.
METHODS
A Delphi consensus was undertaken by 40 experts from 19 European countries who conducted a literature summary and voting process on 89 statements. Quality of evidence was evaluated using grading of recommendations assessment, development, and evaluation criteria. Consensus (defined as ≥80% agreement) was reached for 25 statements.
RESULTS
The European consensus defined gastroparesis as the presence of symptoms associated with delayed GE in the absence of mechanical obstruction. Nausea and vomiting were identified as cardinal symptoms, with often coexisting postprandial distress syndrome symptoms of dyspepsia. The true epidemiology of gastroparesis is not known in detail, but diabetes, gastric surgery, certain neurological and connective tissue diseases, and the use of certain drugs recognized as risk factors. While the panel agreed that severely impaired gastric motor function is present in these patients, there was no consensus on underlying pathophysiology. The panel agreed that an upper endoscopy and a GE test are required for diagnosis. Only dietary therapy, dopamine-2 antagonists and 5-HT receptor agonists were considered appropriate therapies, in addition to nutritional support in case of severe weight loss. No consensus was reached on the use of proton pump inhibitors, other classes of antiemetics or prokinetics, neuromodulators, complimentary, psychological, or more invasive therapies. Finally, there was consensus that gastroparesis adversely impacts on quality of life and healthcare costs and that the long-term prognosis of gastroparesis depends on the cause.
CONCLUSIONS AND INFERENCES
A multinational group of European experts summarized the current state of consensus on definition, symptom characteristics, pathophysiology, diagnosis, and management of gastroparesis.
Topics: Consensus; Delphi Technique; Diet Therapy; Dopamine D2 Receptor Antagonists; Dyspepsia; Endoscopy, Gastrointestinal; Europe; Gastric Emptying; Gastroenterology; Gastroparesis; Humans; Nausea; Neurology; Nutritional Support; Postprandial Period; Risk Factors; Serotonin Receptor Agonists; Societies, Medical; Symptom Assessment; Vomiting
PubMed: 33939892
DOI: 10.1002/ueg2.12060 -
Appetite May 2022This paper is based on a presentation given at the Annual Meeting of the Society for the Study of Ingestive Behavior in July 2021 and provides a personal view on some of... (Review)
Review
This paper is based on a presentation given at the Annual Meeting of the Society for the Study of Ingestive Behavior in July 2021 and provides a personal view on some of the milestones in the discovery of amylin as a constituent of pancreatic islet amyloid deposits, as a pancreatic beta-cell hormone, and on its role in physiology and pathophysiology. Only selected effects of amylin are discussed here because we recently published extensive reviews on the physiology and pathophysiology of amylin. Amylin was discovered as the main constituent of islet amyloid that is predominantly found in pancreatic islets in type 2 diabetics. These deposits, and in particular small oligomer aggregates of amylin seem to contribute to the progressive beta-cell damage seen in type 2 diabetics. Amylin is also a physiologically relevant circulating hormone with diverse metabolic functions, e.g. inhibition of eating, of pancreatic glucagon secretion and of gastric emptying. Knowledge of these types of functions and amylin's mechanisms of action lead to the development of amylin analogues that are now among the most promising anti-obesity targets in clinical testing. With this review, I want to give a short overview of 35 exciting years of amylin research.
Topics: Amyloid; Feeding Behavior; Gastric Emptying; Humans; Islet Amyloid Polypeptide; Obesity
PubMed: 35183619
DOI: 10.1016/j.appet.2022.105965 -
Gastroenterology Clinics of North... Mar 2015Gastroparesis is a chronic symptomatic disorder of the stomach characterized by delayed emptying without evidence of mechanical obstruction. Idiopathic gastroparesis... (Review)
Review
Gastroparesis is a chronic symptomatic disorder of the stomach characterized by delayed emptying without evidence of mechanical obstruction. Idiopathic gastroparesis refers to gastroparesis of unknown cause not from diabetes; not from prior gastric surgery; not related to other endocrine, neurologic, rheumatologic causes of gastroparesis; and not related to medications that can delay gastric emptying. There is overlap in the symptoms of idiopathic gastroparesis and functional dyspepsia. Patients with idiopathic gastroparesis often have a constellation of symptoms including nausea, vomiting, early satiety, postprandial fullness, and upper abdominal pain. Current treatment options of dietary management, prokinetics agents, antiemetic agents, and symptom modulators do not adequately address clinical need for idiopathic gastroparesis.
Topics: Combined Modality Therapy; Diet Therapy; Electric Stimulation Therapy; Gastric Emptying; Gastrointestinal Agents; Gastroparesis; Humans
PubMed: 25667023
DOI: 10.1016/j.gtc.2014.11.015