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Context: Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction., Data Acquisition: We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events., Data Synthesis: Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration., Conclusion: Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Aims: The aim of this study was to evaluate the comparative effects of low-carbohydrate (LC), full-strength (FS), and low-alcohol (LA) beer on gastric emptying (GE), ethanol absorption, glycaemia and insulinaemia in health., Methods: Eight subjects (four male, four female; age: 20.4 ± 0.4 years; BMI 22.7 ± 0.4 kg/m 2 ) had concurrent measurements of GE, plasma ethanol, blood glucose and plasma insulin for 180 min on three separate occasions after ingesting 600 mL of (i) FS beer (5.0% w/v, 246 kcal, 19.2 g carbohydrate), (ii) LC beer (4.6% w/v, 180 kcal, 5.4 g carbohydrate) and (iii) LA beer (2.6% w/v, 162 kcal, 17.4 g carbohydrate) labelled with 20 MBq 99mTc-calcium phytate, in random order., Results: There was no difference in the gastric 50% emptying time (T50) (FS: 89.0 ± 13.5 min vs LC: 79.5 ± 12.9 min vs LA: 74.6 ± 12.4 min; P = .39). Plasma ethanol was less after LA than LC (P < .001) and FS (P < .001), with no difference between LC and FS (P = 1.0). There was an inverse relationship between plasma ethanol at 15 min and GE after LA (r = -0.87, P < .01) and a trend for inverse relationships after LC (r = -0.67, P = .07) and FS (r = -0.69, P = .06). The AUC 0-180 min for blood glucose was greater for LA than LC (P < .001), with no difference between LA and FS (P = .40) or LC and FS (P = 1.0)., Conclusion: In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Postprandial glycemic control is an important target for optimal type 2 diabetes management, but is often difficult to achieve. The gastrointestinal tract plays a major role in modulating postprandial glycaemia in both health and diabetes. The various strategies that have been proposed to modulate gastrointestinal function, particularly by slowing gastric emptying and/or stimulating incretin hormone GLP-1, are summarized in this review., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kamruzzaman, Horowitz, Jones and Marathe.)

Context: Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe" hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked" hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild" hypoglycemia (3.0-3.9 mmol/L) is unknown., Objective: To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health., Design, Setting, and Subjects: Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days., Results: Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia., Conclusion: In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Gastric emptying is a major determinant of the glycaemic response to carbohydrate and is frequently abnormal in type 2 diabetes (T2DM). There is little information about how chronic glycaemic control affects gastric emptying in T2DM. We evaluated gastric emptying of a 75 g glucose drink in community-based patients with T2DM of short duration with good or poor glycaemic control, and compared this to young and older controls., Methods: T2DM patients managed by diet and/or metformin, either well-controlled or poorly-controlled, together with young and age-matched older controls without diabetes, consumed a 75 g oral glucose drink containing 150 mg 13 C-acetate for evaluation of gastric emptying (breath test) and blood glucose over 180 min., Results: The gastric half-emptying time (T50) was longer in the older than the young non-diabetic subjects (P = 0.041), but shorter in well-controlled T2DM patients than age-matched older controls (P = 0.043). The T50 in poorly-controlled T2DM patients was shorter than in older controls (P = 0.006), but similar to young non-diabetic subjects., Conclusions: Gastric emptying of a glucose drink is delayed with ageing, but more rapid in patients with T2DM of relatively short duration, regardless of their glycaemic status. These observations support interventions that slow gastric emptying to improve postprandial glycaemia in these patients with T2DM., Competing Interests: Declaration of Competing Interest KLJ has received research funding from Sanofi and drug supplies from Merck Sharp & Dohme. MH has participated in the advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. CKR has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly, Novartis, and Sanofi. RLY has received research funding from AstraZeneca and Pfizer and drug supplies from Boehringer Ingelheim and Takeda Pharmaceuticals. TW has received travel support from Novartis and Sanofi and research funding from Novartis and AstraZeneca. None of the other authors has any personal or financial conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Glucagon-like peptide-1 receptor agonists induce weight loss, which has been suggested to relate to the slowing of gastric emptying (GE). In health, energy intake (EI) is more strongly related to the content of the distal, than the total, stomach. We evaluated the effects of lixisenatide on GE, intragastric distribution, and subsequent EI in 15 healthy participants and 15 patients with type 2 diabetes (T2D). Participants ingested a 75-g glucose drink on two separate occasions, 30 min after lixisenatide (10 mcg) or placebo subcutaneously, in a randomised, double-blind, crossover design. GE and intragastric distribution were measured for 180 min followed by a buffet-style meal, where EI was quantified. Relationships of EI with total, proximal, and distal stomach content were assessed. In both groups, lixisenatide slowed GE markedly, with increased retention in both the proximal ( p < 0.001) and distal ( p < 0.001) stomach and decreased EI ( p < 0.001). EI was not related to the content of the total or proximal stomach but inversely related to the distal stomach at 180 min in health on placebo ( r = -0.58, p = 0.03) but not in T2D nor after lixisenatide in either group. In healthy and T2D participants, the reduction in EI by lixisenatide is unrelated to changes in GE/intragastric distribution, consistent with a centrally mediated effect.

Aims: To evaluate the effects of 8 weeks' administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the "gold standard" technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people., Material and Methods: A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m 2 ) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m 2 ) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99m Tc-sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67 Ga-EDTA), and containing 5 g 3-O-methyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment., Results: The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC] 0-120min : P < 0.05) and liquids (AUC 0-120min : P = 0.01) substantially, and attenuated glucose absorption (3-OMG incremental AUC [iAUC] 0-30min : P = 0.001) and the postprandial rise in plasma glucose (iAUC 0-30min : P = 0.008). Plasma glucagon at 2 h was reduced by EXE once weekly (P = 0.001). The magnitude of the reduction in plasma glucose at t = 30 min from baseline to 8 weeks with EXE once weekly was related inversely to the 50% emptying time of the glucose drink (r = -0.55, P = 0.03)., Conclusions: In healthy participants, 8 weeks' administration of the "long-acting" glucagon-like peptide-1 receptor agonist EXE, slowed gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia., (© 2020 John Wiley & Sons Ltd.)

Aims: Gastric emptying is a major determinant of postprandial glycaemia in both health and type 2 diabetes (T2DM); the potential impact of ethnicity on gastric emptying is unclear. We compared the rate of gastric emptying of a standardised meal and the associated glycaemic response in Han Chinese and Caucasian patients with T2DM., Methods: 14 Han Chinese and 14 Caucasian T2DM patients, managed by diet and/or metformin monotherapy, underwent concurrent measurements of gastric emptying and blood glucose for 240 min after a 99mTc-calcium phytate-labelled mashed potato meal., Results: Han Chinese patients were slightly younger (P < 0.05), and had a lower BMI (P < 0.05), than Caucasians. There were no differences in either HbA1c or fasting blood glucose between them. Gastric half-emptying time (T50) was shorter (P < 0.05) and the postprandial blood glucose increment greater (P < 0.05) in Han Chinese than Caucasian patients. Both the increment in blood glucose from baseline at 60 min and peak blood glucose were related inversely to T50 (P < 0.05 each)., Conclusions: Han Chinese with relatively well-controlled T2DM have more rapid gastric emptying compared to Caucasians, which is associated with a greater postprandial glycaemic excursion. These differences may inform the choice of management, e.g. Han Chinese may particularly benefit from therapies that slow gastric emptying., Competing Interests: Declaration of Competing Interest MH has participated in advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, and AstraZeneca and has received honoraria for this activity. KLJ has received research funding from Sanofi, AstraZeneca, Omniblend Innovations and trial medication from Merck Sharp & Dohme. CKR has received research funding from AstraZeneca, Merck Sharp & Dohme, Eli Lilly, Novartis, and Sanofi. ZS has received research funding from AstraZeneca. TW has received research funding from Novartis and AstraZeneca. None of the other authors has any personal or financial conflict of interest to declare., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose of Review: Gastroparesis is an important complication of diabetes that may have a major impact on the quality of life as a result of upper gastrointestinal symptoms and impaired glycaemic control. Current management strategies include optimising blood glucose control, dietary modifications and supportive nutrition. Pharmacologic approaches with drugs that have prokinetic and/or antiemetic effects are also used widely; however, current available treatments have major limitations. There is increasing recognition that the rate of gastric emptying (GE) is a key determinant of the glycaemic response to a meal., Recent Findings: There is ongoing uncertainty regarding the impact of longstanding hyperglycaemia on GE, which requires clarification. New diagnostic techniques have been developed to better characterise the mechanisms underlying gastroparesis in individual patients, and these have the potential to lead to more personalised therapy. Management of gastroparesis is complex and suboptimal; novel approaches are desirable. This review summarises recent advances in the understanding of diabetic gastroparesis, with an emphasis on the current therapies that influence GE, and the bidirectional relationship between glycaemic control and GE.

Aim: To evaluate the effects of the prandial glucagon-like peptide-1 receptor agonist lixisenatide on gastric emptying and blood pressure (BP) and superior mesenteric artery (SMA) blood flow, and the glycaemic responses to a 75-g oral glucose load in healthy people and those with type 2 diabetes (T2DM)., Materials and Methods: Fifteen healthy participants (nine men, six women; mean ± SEM age 67.2 ± 2.3 years) and 15 participants with T2DM (nine men, six women; mean ± SEM age 61.9 ± 2.3 years) underwent measurement of gastric emptying, BP, SMA flow and plasma glucose 180 minutes after a radiolabelled 75-g glucose drink on two separate days. All participants received lixisenatide (10 μg subcutaneously) or placebo in a randomized, double-blind, crossover fashion 30 minutes before the glucose drink., Results: Lixisenatide slowed gastric emptying (retention at 120 minutes, P < 0.01), attenuated the rise in SMA flow (P < 0.01) and markedly attenuated the decrease in systolic BP (area under the curve [AUC] 0-120 minutes, P < 0.001) compared to placebo in healthy participants and those with T2DM. Plasma glucose (incremental AUC 0-120 minutes) was greater in participants with T2DM (P < 0.005) than in healthy participants, and lower after lixisenatide in both groups (P < 0.001)., Conclusions: In healthy participants and those with T2DM, the marked slowing of gastric emptying of glucose induced by lixisenatide was associated with attenuation of the increments in glycaemia and SMA flow and decrease in systolic BP. Accordingly, lixisenatide may be useful in the management of postprandial hypotension., (© 2019 John Wiley & Sons Ltd.)

Hypoglycaemia is arguably the most important complication of insulin therapy in type 1 and type 2 diabetes. Counter-regulation of hypoglycaemia is dependent on autonomic function and frequent hypoglycaemia may lead to reductions in both autonomic warning signals and the catecholamine response, the so-called "impaired awareness of hypoglycaemia". It is now appreciated that gastric emptying is a major determinant of the glycaemic response to carbohydrate-containing meals in both health and diabetes, that disordered (especially delayed) gastric emptying occurs frequently in diabetes, and that acute hypoglycaemia accelerates gastric emptying substantially. However, the potential relevance of gastric emptying to the predisposition to, and counter-regulation of, hypoglycaemia has received little attention. In insulin-treated patients, the rate of gastric emptying influences the timing of the postprandial insulin requirement, and gastroparesis is likely to predispose to postprandial hypoglycaemia. Conversely, the marked acceleration of gastric emptying induced by hypoglycaemia probably represents an important counter-regulatory response to increase the rate of carbohydrate absorption. This review summarizes the current knowledge of the inter-relationships between hypoglycaemia and gastric emptying, with a focus on clinical implications., (© 2018 John Wiley & Sons Ltd.)

The oral disposition index, the product of the early insulin secretory response during an oral glucose tolerance test and insulin sensitivity, is used widely for both the prediction of, and evaluation of the response to interventions, in type 2 diabetes. Gastric emptying, which determines small intestinal exposure of nutrients, modulates postprandial glycemia. The aim of this study was to determine whether the insulin secretory response and the disposition index (DI) related to gastric emptying in subjects with normal glucose tolerance. Thirty-nine subjects consumed a 350 mL drink containing 75 g glucose labeled with 99m Tc-sulfur colloid. Gastric emptying (by scintigraphy), blood glucose (G) and plasma insulin (I) were measured between t  = 0-120 min. The rate of gastric emptying was derived from the time taken for 50% emptying ( T 50 ) and expressed as kcal/min. The early insulin secretory response was estimated by the ratio of the change in insulin (∆I 0-30 ) to that of glucose at 30 min (∆G 0-30 ) represented as ∆I 0-30 /∆G 0-30 Insulin sensitivity was estimated as 1/fasting insulin and the DI was then calculated as ∆I 0-30 /∆G 0-30 and gastric emptying ( 0-30 and gastric emptying ( r  = 0.47, P  = 0.003). While there was no association of either ∆I 0-30 ( r  = -0.16, P  = 0.34) or fasting insulin ( r  = 0.21, P  = 0.20), there were inverse relationships between the early insulin secretory response ( r  = -0.45, P  = 0.004) and the DI ( r  = 0.041), with gastric emptying. We conclude that gastric emptying is associated with both insulin secretion and the disposition index in subjects with normal glucose tolerance, such that when gastric emptying is relatively more rapid, both the early insulin secretory response and the disposition index are less. These findings should be interpreted as "hypothesis generating" and provide the rationale for longitudinal studies to examine the impact of baseline rate of gastric emptying on the prospective risk of type 2 diabetes.P  = 0.041), with gastric emptying. We conclude that gastric emptying is associated with both insulin secretion and the disposition index in subjects with normal glucose tolerance, such that when gastric emptying is relatively more rapid, both the early insulin secretory response and the disposition index are less. These findings should be interpreted as "hypothesis generating" and provide the rationale for longitudinal studies to examine the impact of baseline rate of gastric emptying on the prospective risk of type 2 diabetes., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Postprandial hypotension occurs frequently in diabetes. We show in 9 type 2 patients, that the fall in systolic blood pressure is greater in response to intraduodenal glucose infused at 4 kcal/min than 2 kcal/min, implying that strategies to slow gastric emptying may be effective in the management of postprandial hypotension., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The short-acting glucagon-like peptide 1 receptor agonist exenatide reduces postprandial glycemia, partly by slowing gastric emptying, although its impact on small intestinal function is unknown. In this study, 10 healthy subjects and 10 patients with type 2 diabetes received intravenous exenatide (7.5 μg) or saline (-30 to 240 min) in a double-blind randomized crossover design. Glucose (45 g), together with 5 g 3-O-methylglucose (3-OMG) and 20 MBq (99m)Tc-sulfur colloid (total volume 200 mL), was given intraduodenally (t = 0-60 min; 3 kcal/min). Duodenal motility and flow were measured using a combined manometry-impedance catheter and small intestinal transit using scintigraphy. In both groups, duodenal pressure waves and antegrade flow events were fewer, and transit was slower with exenatide, as were the areas under the curves for serum 3-OMG and blood glucose concentrations. Insulin concentrations were initially lower with exenatide than with saline and subsequently higher. Nausea was greater in both groups with exenatide, but suppression of small intestinal motility and flow was observed even in subjects with little or no nausea. The inhibition of small intestinal motor function represents a novel mechanism by which exenatide can attenuate postprandial glycemia., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Recent data from the Diabetes Control and Complications Trial/Epidemiology of Diabetic Interventions and Complications cohort indicate that the disease burden of gastroparesis in diabetes remains high, consistent with the outcome of cross-sectional studies in type 1 and 2 diabetes. An improved understanding of the pathogenesis of diabetic gastroparesis at the cellular level has emerged in the last decade, particularly as a result of initiatives such as the National Institute of Health funded Gastroparesis Clinical Research Consortium in the US. Management of diabetic gastroparesis involves dietary and psychological support, attention to glycaemic control, and the use of prokinetic agents. Given that the relationship between upper gastrointestinal symptoms and the rate of gastric emptying is weak, therapies targeted specifically at symptoms, such as nausea or pain, are important. The relationship between gastric emptying and postprandial glycaemia is complex and inter-dependent. Short-acting glucagon-like peptide-1 agonists, that slow gastric emptying, can be used to reduce postprandial glycaemic excursions and, in combination with basal insulin, result in substantial reductions in glycated haemoglobin in type 2 patients.

Context: The early glycemic response during a 75-g oral glucose tolerance test (OGTT) is directly related to the rate of gastric emptying (GE). There is little information about the effect of GE on the blood glucose at either 60 min (a predictor of diabetes) or 120 min (used diagnostically)., Objective: This study aimed to evaluate the relationships between glycemic responses at 30, 60, and 120 min and GE following a 75-g OGTT in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (T2D)., Design, Setting, and Subjects: Eighty-two subjects in the general community without diabetes (57 NGT, 25 IGT) and 16 with T2D consumed a 75-g glucose drink labeled with (99m)Tc-sulfur colloid. GE (by scintigraphy) and glycemia were measured from t = 0-120 min and relationships between blood glucose (absolute, change from baseline, and area under the curve) and GE at 30, 60, and 120 min determined., Results: There were no differences in GE. There were relationships between the blood glucose at 30 min and GE (NGT: r = 0.40; P < .01; IGT: r = 0.49; P = .02; T2D: r = 0.62; P = .01). There was also a relationship between the blood glucose at 60 min and GE in IGT (r = 0.52; P = .02) and T2D (r = 0.77; P < .01), but not NGT (r = 0.16; P = .24). In NGT, there was an inverse relationship between blood glucose at 120 min and GE (r = -0.30; P = .02), but not in IGT (r = 0.05; P = .82) or T2D (r = 0.37; P = .16)., Conclusions: GE is a determinant of the glycemic response to an OGTT in NGT, IGT, and T2D but these relationships differ and are time dependent.

Glucagon-like peptide-1 (GLP-1) receptor agonists and the dual GLP-1- and glucose-dependent insulinotropic polypeptide receptor co-agonist tirzepatide (referred to here collectively as "GLP-1-based therapy") are incretin-based therapies being used increasingly in the management of both type 2 diabetes and obesity. They are now recognized to have beneficial effects beyond improved glycemic control and weight loss, including cardiovascular and renal protection. GLP-1-based therapy also slows gastric emptying, which has benefits (lowering postprandial glucose), but also potential risks (eg, hypoglycemia in individuals on insulin or sulphonylurea therapy). Their effects on the gallbladder may also be beneficial, contributing to reducing postprandial triglycerides, but they also potentially increase the risk of biliary disease. In this review, we summarize the effects of GLP-1 and incretin-based therapeutics on gastric, biliary and small intestinal function. An improved understanding of these effects will optimize the use of these drugs. [ABSTRACT FROM AUTHOR]

Context Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps to limit postprandial glycemic excursions and reduce chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, eg, retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration or bowel obstruction. Data Acquisition We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. Data Synthesis Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs but rarely are associated with pulmonary aspiration. Well-justified recommendations for the periprocedural management of GLP-1RAs (eg, whether to withhold these medications and for how long) are compromised by limited evidence. Important aspects to be considered are (1) their long half-lives, (2) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (ie, in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. Conclusion Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful and represent an important area needing further study to increase patient safety for those treated with GLP-1 RAs. [ABSTRACT FROM AUTHOR]

The article discusses the effects of glucagon-like peptide-1 (GLP-1) receptor agonists on blood pressure. GLP-1 receptor agonists have been shown to have cardiovascular and renal protective effects, independent of their glucose-lowering properties. While these drugs have been found to reduce systolic blood pressure in hypertensive individuals, they have little effect on diastolic blood pressure or normotensive individuals. The article also highlights the importance of accurately measuring blood pressure, including postprandial blood pressure, and suggests that further research is needed to optimize the assessment of the effects of GLP-1 receptor agonists on blood pressure. [Extracted from the article]

Background: The pattern of the plasma glucose response curve during an oral glucose tolerance test (OGTT) is of prognostic significance with "biphasic" when compared with "monophasic" patterns being associated with greater insulin sensitivity/secretion and a reduced risk of progression to diabetes. The relationships of the glucose response curves with gastric emptying and incretin hormone secretion are not known. Methods: Thirty-six adults (age > 65 years) without known diabetes consumed a 300 mL drink containing 75 g glucose and 150 mg C13-acetate at baseline and follow-up after 5.8 ± 0.1 years. Plasma glucose, glucagon-like peptide-1 (GLP-1), glucose independent insulinotropic polypeptide (GIP) and insulin were measured, and participants classified according to the pattern of their glucose response. Gastric emptying was measured on breath samples (stable isotope breath test). Results: At baseline, 22 participants had a "monophasic" and 14 a "biphasic" glucose response. The 1 h plasma glucose response curve was greater and the GLP-1 AUC0–120 min and insulin secretion lower in the monophasic group. There were no differences in gastric emptying, GIP or insulin sensitivity. At the follow-up, the 1 h glucose response curve was greater again, while GLP-1 AUC0–120 min was lower in the monophasic group. Conclusions: A biphasic curve is associated with a higher 60 min glucose response curve and increases in GLP-1, but no difference in either GIP or gastric emptying. [ABSTRACT FROM AUTHOR]

Context The relationships of gastric emptying (GE) with the glycemic response at 120 minutes, glucagon-like peptide-1 (GLP-1), and insulin secretion following a glucose load in type 2 diabetes (T2D) are uncertain. Objective: We evaluated the relationship of plasma glucose, GLP-1, and insulin secretion with GE of a 75-g oral glucose load in T2D. Design: Single-center, cross-sectional, post hoc analysis. Setting: Institutional research center. Participants: 43 individuals with T2D age 65.6 ± 1.1 years, hemoglobin A1c 7.2 ± 1.0%, median duration of diabetes 5 years managed by diet and/or metformin. Intervention: Participants consumed the glucose drink radiolabeled with 99mTc-phytate colloid following an overnight fast. GE (scintigraphy), plasma glucose, GLP-1, insulin, and C-peptide were measured between 0 and 180 minutes. Main Outcome Measures: The relationships of the plasma glucose at 120 minutes, plasma GLP-1, and insulin secretion (calculated by Δinsulin0-30/Δglucose0-30 and ΔC-peptide0-30/Δglucose0-30) with the rate of GE (scintigraphy) were evaluated. Results: There were positive relationships of plasma glucose at 30 minutes (r = 0.56, P < 0.001), 60 minutes (r = 0.57, P < 0.001), and 120 minutes (r = 0.51, P < 0.001) but not at 180 minutes (r = 0.13, P = 0.38), with GE. The 120-minute plasma glucose and GE correlated weakly in multiple regression models adjusting for age, GLP-1, and insulin secretion (P = 0.04 and P = 0.06, respectively). There was no relationship of plasma GLP-1 with GE. Multiple linear regression analysis indicated that there was no significant effect of GE on insulin secretion. Conclusion: In T2D, while insulin secretion is the dominant determinant of the 120-minute plasma glucose, GE also correlates. Given the relevance to interpreting the results of an oral glucose tolerance test, this relationship should be evaluated further. There appears to be no direct effect of GE on either GLP-1 or insulin secretion. [ABSTRACT FROM AUTHOR]

Background Slow gastric emptying occurs frequently during critical illness and is roughly quantified at bedside by large gastric residual volumes (GRVs). A previously published trial (The Augmented versus Routine approach to Giving Energy Trial; TARGET) reported larger GRVs with energy-dense (1.5 kcal/mL) compared with standard (1.0 kcal/mL) enteral nutrition (EN), warranting further exploration. Objective To assess the incidence, risk factors, duration, and timing of large GRVs (≥250 mL) and its relation to clinical outcomes in mechanically ventilated adults. Methods A post-hoc analysis of TARGET data in patients with ≥1 GRV recorded. Data are n (%) or median [IQR]. Results Of 3876 included patients, 1777 (46%) had ≥1 GRV ≥250 mL, which was more common in males (50 compared with 39%; P < 0.001) and in patients receiving energy-dense compared with standard EN (52 compared with 40%; RR = 1.27 (95% CI: 1.19, 1.36); P < 0.001) in whom it also lasted longer (1 [0–2] compared with 0 [0–1] d; P < 0.001), with no difference in time of onset after EN initiation (day 1 [0–2] compared with 1 [0–2]; P = 0.970). Patients with GRV ≥250 mL were more likely to have the following: vasopressor administration (88 compared with 76%; RR = 1.15 [1.12, 1.19]; P < 0.001), positive blood cultures (16 compared with 8%; RR = 1.92 [1.60, 2.31]; P < 0.001), intravenous antimicrobials (88 compared with 81%; RR = 1.09 [1.06, 1.12]; P < 0.001), and prolonged intensive care unit (ICU) stay (ICU-free days to day 28; 12.9 [0.0–21.0] compared with 20.0 [3.9–24.0]; P < 0.001), hospital stay (hospital-free days to day 28: 0.0 [0.0–12.0] compared with 7.0 [0.0–17.6] d; P < 0.001), ventilatory support (ventilator-free days to day 28: 16.0 [0.0–23.0] compared with 22.0 [8.0–25.0]; P < 0.001), and a higher 90-d mortality (29 compared with 23%; adjusted: RR = 1.17 [1.05, 1.30]; P = 0.003). Conclusion Large GRVs were more common in males and those receiving energy-dense formulae, occurred early and were short-lived, and were associated with a number of negative clinical sequelae, including increased mortality, even when adjusted for illness severity. This trial was registered at clinicaltrials.gov as NCT02306746. [ABSTRACT FROM AUTHOR]

Meal consumption leads to an increase in sympathetic output to compensate for hemodynamic changes and maintain blood pressure (BP). Obesity is associated with a blunting of the sympathetic response to meal ingestion, but interpretation of studies investigating these responses is compromised by their failure to account for the rate of gastric emptying, which is an important determinant of postprandial cardiovascular and sympathetic responses and, in both health and obesity, exhibits a wide interindividual variation. We sought to determine the effects of intraduodenal glucose infusion, bypassing gastric emptying, on BP, heart rate (HR), and noradrenaline responses in obese and healthy control subjects. 12 obese subjects (age 36.6 ± 3.9 years, body mass index (BMI) 36.1 ± 1.3 kg/m2) and 23 controls (age 27.8 ± 2.4 years, BMI 22.4 ± 0.5 kg/m2) received intraduodenal infusions of glucose at 1 or 3 kcal/ min, or saline, for 60 min (t = 0–60 min), followed by intraduodenal saline (t = 60–120 min). BP and HR were measured with an automatic cuff, and blood samples collected for measurement of plasma noradrenaline. Intraduodenal glucose at 1 kcal/min was associated with a fall in diastolic BP in the control subjects only (P < 0.01), with no change in systolic BP, HR or noradrenaline in either group. In both groups, intraduodenal glucose at 3 kcal/min was associated with a fall in diastolic (P < 0.01), but not systolic, BP, and rises in HR (P < 0.001) and plasma noradrenaline (P < 0.01), with no difference in responses between the groups. We conclude that cardiovascular and sympathetic responses to intraduodenal glucose infusion are comparable between obese and control subjects, and dependent on the rate of glucose delivery. [ABSTRACT FROM AUTHOR]

The article presents a case study of reactive hypoglycaemia having breakthrough followed by intraduodenal glucose infusion in case of a type 2 diabetes patient. The article also includes the established result of reactive hypoglycaemia may lead to type 2 diabetes whereas postprandial reactive hypoglycaemia is rare in type 2 diabetes.

The majority of studies relating to the oral glucose tolerance test (OGTT) have not taken gastric emptying (GE), which exhibits a substantial inter-individual variation, into account. We sought to evaluate the impact of GE, on the glycemic and insulinemic responses to a 75-g oral glucose load in older subjects with normal and impaired glucose tolerance. Eighty-seven healthy 'older' subjects (47F, 40M; age 71.0 ± 0.5 year) were given a drink comprising of 75-g glucose and 150 mg C13-acetate made up to 300 mL with water on a single occasion. Exhaled breath was obtained for analysis of 13CO2 and calculation of the 50% GE time (T50). Blood glucose, serum insulin and plasma glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured, and the insulin sensitivity index (ISI), and the disposition index (DI), were calculated. Thirty-one subjects had normal glucose tolerance (NGT) and 46 had impaired glucose tolerance (IGT). Blood glucose at t = 60 min and t = 120 min were related inversely to ISI (P < 0.001) and DI P < 0.001). The rise in blood glucose at t = 60 min was related inversely to the T50 in all subjects (P < 0.01), and those with IGT (P < 0.001), but not NGT. There were no significant relationships between the blood glucose at t = 120 min with the T50, but in both groups the change in blood glucose from baseline at t = 180 min was related (NGT: P < 0.001; IGT: P < 0.001) to the T50. We conclude that in NGT and IGT, the effect of GE on both the 'early' and 'late' glycemic responses to a 75-g oral glucose load is complementary to that of insulin sensitivity. [ABSTRACT FROM AUTHOR]

Abstract: The gut derived peptides, glucagon-like peptides 1 and 2 (GLP-1 and GLP-2), are secreted following nutrient ingestion. GLP-1 and another gut peptide, glucose-dependent insulinotropic polypeptide (GIP) are collectively referred to as ‘incretin’ hormones, and play an important role in glucose homeostasis. Incretin secretion shares a complex interdependent relationship with both postprandial glycemia and the rate of gastric emptying. GLP-1 based therapies are now well established in the management of type 2 diabetes, while recent literature has suggested potential applications to treat obesity and protect against cardiovascular and neurological disease. The mechanism of action of GLP-2 is not well understood, but it shows promise as an intestinotropic agent. [Copyright &y& Elsevier]

Gastrointestinal autonomic neuropathy represents an important and diverse, but poorly appreciated, manifestation of diabetic autonomic neuropathy that impacts negatively on quality of life. There is no test to assess gastrointestinal autonomic nerve damage directly in humans; cardiovascular autonomic reflex tests are often used as a surrogate, but are suboptimal. Gastrointestinal symptoms are common in diabetes, but usually correlate only weakly with disordered motility. Diabetic gastroparesis, or abnormally delayed gastric emptying, occurs frequently and is the best characterized manifestation of gastrointestinal autonomic neuropathy. There is a bi-directional relationship between postprandial glycaemia and the rate of gastric emptying. However, autonomic neuropathy can affect the function of any gut segment from the esophagus to the anus. Current management options for gastrointestinal autonomic neuropathy are, for the main part, empirical and sub-optimal. • Gastrointestinal autonomic neuropathy represents an important and diverse, but poorly appreciated, manifestation of diabetic autonomic neuropathy that impacts negatively on quality of life. • There is no test to assess gastrointestinal autonomic nerve damage directly in humans; cardiovascular autonomic reflex tests are often used as a surrogate, but are suboptimal. • Gastrointestinal symptoms are common in diabetes, but usually correlate only weakly with disordered motility. • Diabetic gastroparesis, or abnormally delayed gastric emptying, occurs frequently and is the best characterized manifestation of gastrointestinal autonomic neuropathy. • There is a bi-directional relationship between postprandial glycaemia and the rate of gastric emptying. • However, autonomic neuropathy can affect the function of any gut segment from the esophagus to the anus. • Current management options for gastrointestinal autonomic neuropathy are, for the main part, empirical and sub-optimal. [ABSTRACT FROM AUTHOR]