ORCID Profile
0000-0002-1155-5816
Current Organisation
University of Adelaide
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Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.BEEM.2009.03.009
Abstract: Postprandial glycaemia is now recognised as the major determinant of average glycaemic control in type 2 diabetes, as assessed by glycated haemoglobin. Therefore, an understanding of the factors influencing both the rise in blood glucose and insulin secretion after a meal is fundamental to the development of dietary and pharmacological approaches to optimise glycaemic control. The gastrointestinal tract regulates the rate at which carbohydrate and other nutrients are absorbed and is the source of regulatory peptides that stimulate pancreatic insulin secretion in the setting of elevated blood glucose levels. This article highlights the importance of the gastrointestinal tract in insulin secretion and glucose homeostasis and discusses potential strategies directed at modification of gastrointestinal function in order to improve glycaemic control in the management of diabetes.
Publisher: The Endocrine Society
Date: 02-2016
DOI: 10.1210/JC.2015-4138
Publisher: Springer Science and Business Media LLC
Date: 13-07-2023
DOI: 10.1007/S11154-023-09823-3
Abstract: Background and aims : Bariatric surgery is the most effective treatment in in iduals with obesity to achieve remission of type 2 diabetes. Post-bariatric surgery hypoglycaemia occurs frequently, and management remains suboptimal, because of a poor understanding of the underlying pathophysiology. The glucoregulatory hormone responses to nutrients in in iduals with and without post-bariatric surgery hypoglycaemia have not been systematically examined. Materials and methods : The study protocol was prospectively registered with PROSPERO. PubMed, EMBASE, Web of Science and the Cochrane databases were searched for publications between January 1990 and November 2021 using MeSH terms related to post-bariatric surgery hypoglycaemia. Studies were included if they evaluated in iduals with post-bariatric surgery hypoglycaemia and included measurements of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide and/or glucagon concentrations following an ingested nutrient load. Glycated haemoglobin (HbA 1c ) was also evaluated. A random-effects meta-analysis was performed, and Hedges’ g (standardised mean difference) and 95% confidence intervals were reported for all outcomes where sufficient studies were available. The τ 2 estimate and I 2 statistic were used as tests for heterogeneity and a funnel plot with the Egger regression-based test was used to evaluate for publication bias. Results : From 377 identified publications, 12 were included in the analysis. In all 12 studies, the type of bariatric surgery was Roux-en-Y gastric bypass (RYGB). Comparing in iduals with and without post-bariatric surgery hypoglycaemia following an ingested nutrient load, the standardised mean difference in peak GLP-1 was 0.57 (95% CI, 0.32, 0.82), peak GIP 0.05 (-0.26, 0.36), peak insulin 0.84 (0.44, 1.23), peak C-peptide 0.69 (0.28, 1.1) and peak glucagon 0.05 (-0.26, 0.36). HbA 1c was less in in iduals with hypoglycaemia − 0.40 (-0.67, -0.12). There was no evidence of substantial heterogeneity in any outcome except for peak insulin: τ 2 = 0.2, I 2 = 54.3. No publication bias was evident. Conclusion : Following RYGB, postprandial peak plasma GLP-1, insulin and C-peptide concentrations are greater in in iduals with post-bariatric surgery hypoglycaemia, while HbA 1c is less. These observations support the concept that antagonism of GLP-1 would prove beneficial in the management of in iduals with hypoglycaemia following RYGB. PROSPERO Registration Number: CRD42021287515.
Publisher: Elsevier BV
Date: 05-2015
DOI: 10.1016/J.DIABRES.2015.02.019
Abstract: We have shown that the capacity of 25g whey preloads to slow gastric emptying and reduce postprandial glycaemia persists after 4 weeks regular exposure in patients with diet-controlled type 2 diabetes. This dietary strategy therefore appears feasible for larger clinical trials to evaluate beneficial effects on long-term glycaemic control. Registered with the Australian New Zealand Clinical Trials Registry: ACTRN12614000831684.
Publisher: Wiley
Date: 03-12-2018
DOI: 10.1111/DOM.13570
Abstract: 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.
Publisher: Wiley
Date: 11-11-2014
DOI: 10.1111/DME.12622
Abstract: To evaluate the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin on blood pressure and heart rate, measured during a previously reported study, in which the effects of sitagliptin during intraduodenal glucose infusion at the rate of 2 kcal/min on glucose homeostasis were examined in patients with Type 2 diabetes. A total of 10 people with Type 2 diabetes were studied on two different days, 30 min after oral ingestion of sitagliptin (100 mg) or placebo. Intraduodenal glucose was infused at 2 kcal/min (60 g over 120 min), and blood pressure, heart rate, plasma glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (total and intact), glucose, insulin and glucagon responses were evaluated. In response to intraduodenal glucose infusion, heart rate (treatment effect: P = 0.001) and serum insulin concentration (treatment × time interaction: P = 0.041) were higher after sitagliptin treatment than placebo, without a significant difference in blood pressure, plasma glucagon or glucose. During intraduodenal glucose infusion, there was a substantial increase in plasma total glucose-dependent insulinotropic polypeptide on both days (time effect: P < 0.001), but not in total glucagon-like peptide-1. After sitagliptin, plasma intact glucagon-like peptide-1 concentration increased slightly (treatment × time interaction: P = 0.044) and glucose-dependent insulinotropic polypeptide concentration increased substantially (treatment × time interaction: P = 0.003).The heart rate response to intraduodenal glucose was related directly to plasma intact glucose-dependent insulinotropic polypeptide concentrations (r = 0.75, P = 0.008). Sitagliptin increased the heart rate response to intraduodenal glucose infusion at 2 kcal/min in people with Type 2 diabetes, which was associated with augmentation of plasma intact glucose-dependent insulinotropic polypeptide concentrations. These observations warrant further clarification of a potential role for glucose-dependent insulinotropic polypeptide in the control of the 'gut-heart' axis.
Publisher: Springer Science and Business Media LLC
Date: 04-2005
DOI: 10.1007/S10620-005-2555-3
Abstract: The aims of this study were to evaluate (i) the relationship between transpyloric flow (TF) assessed by Doppler ultrasonography and scintigraphy, (ii) the effects of healthy aging on TF and gastric emptying (GE), and (iii) the relationship between the glycemic response to oral glucose and TF. Ten healthy "young" (7 M, 3 F) and 8 "older" (4 M, 4 F), subjects had simultaneous measurements of TF, GE, and blood glucose after a 600-ml drink (75 g glucose labeled with 20 MBq 99mTc-sulfur colloid) while seated. TF measured by ultrasound was measured during drink ingestion and for 30 min thereafter. GE was measured scintigraphically for 180 min after drink ingestion. Blood glucose was measured before the drink and at regular intervals until 180 min. During drink ingestion, TF was greater (P < 0.05) and GE faster (retention at 60 min: 70.8+/-3.3 vs. 83.8+/-4.6% P < 0.05) in young compared to older subjects. There was no difference in fasting blood glucose between the two groups but the magnitude of the rise in blood glucose was greater in the young compared to the older subjects (at 15 min 2.4+/-0.3 vs. 1.5+/-0.5 mmol/L P < 0.05). In contrast, after 90 min blood glucose concentrations were higher in the older subjects. There were significant relationships between the early blood glucose concentration and both TF (e.g., at 15 min: r = 0.56, P < 0.05) and GE (e.g., at 15 min: r = -0.51, P < 0.05). In conclusion, the results of this study indicate that (i) TF is initially less, and GE slower, in older compared to young subjects (ii) the initial glycemic response to oral glucose is related to TF and (iii) measurements of TF by ultrasound and scintigraphy correlate significantly.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2016
Publisher: The Endocrine Society
Date: 12-2014
DOI: 10.1210/JC.2014-2475
Abstract: Studies relating to the cardiovascular effects of glucagon-like peptide-1 (GLP-1) and its agonists, which slow gastric emptying, have not discriminated between fasting and postprandial, blood pressure (BP) and heart rate (HR). To determine whether exogenous GLP-1 modulates the effects of an intraduodenal (ID) glucose infusion on BP, HR, and splanchnic blood flow in healthy older subjects. A double-blind randomized trial was conducted. Community-dwelling residents attended a clinical research laboratory. Ten healthy "older" subjects (9 male, 1 female age 73.2 ± 1.5 y) were studied. Intravenous infusion of GLP-1 (0.9 pmol/kg/min), or saline (0.9%) for 90 min (t = -30-60 min). Between t = 0-60 min, ID glucose was infused at 3 kcal/min. BP, HR, superior mesenteric artery (SMA) flow, blood glucose, and serum insulin were measured. During the fasting period (t = -30-0 min), GLP-1 had no effect on BP or HR. In response to ID glucose (t = 0-60 min), systolic BP decreased (P < .001), and both HR (P < .001) and SMA flow (P < .05) increased, on both days. GLP-1 attenuated the maximum decrease in systolic BP (P < .05), tended to increase HR (P = .09), and increased SMA flow (P < .01). GLP-1 diminished the glycemic response (P < .05). In healthy older subjects, acute administration of GLP-1 attenuates the hypotensive response to ID glucose, and potentiates the increase in SMA flow.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Springer Science and Business Media LLC
Date: 25-10-2013
DOI: 10.1007/S00134-012-2719-5
Abstract: To compare nutrient-stimulated changes in superior mesenteric artery (SMA) blood flow, glucose absorption and glycaemia in in iduals older than 65 years with, and without, critical illness. Following a 1-h 'observation' period (t (0)-t (60)), 0.9 % saline and glucose (1 kcal/ml) were infused directly into the small intestine at 2 ml/min between t (60)-t (120), and t (120)-t (180), respectively. SMA blood flow was measured using Doppler ultrasonography at t (60) (fasting), t (90) and t (150) and is presented as raw values and nutrient-stimulated increment from baseline (Δ). Glucose absorption was evaluated using serum 3-O-methylglucose (3-OMG) concentrations during, and for 1 h after, the glucose infusion (i.e. t (120)-t (180) and t (120)-t (240)). Mean arterial pressure was recorded between t (60)-t (240). Data are presented as median (25th, 75th percentile). Eleven mechanically ventilated critically ill patients [age 75 (69, 79) years] and nine healthy volunteers [70 (68, 77) years] were studied. The magnitude of the nutrient-stimulated increase in SMA flow was markedly less in the critically ill when compared with healthy subjects [Δt (150): patients 115 (-138, 367) versus health 836 (618, 1,054) ml/min P = 0.001]. In patients, glucose absorption was reduced during, and for 1 h after, the glucose infusion when compared with health [AUC(120-180): 4.571 (2.591, 6.551) versus 11.307 (8.447, 14.167) mmol/l min P < 0.001 and AUC(120-240): 26.5 (17.7, 35.3) versus 40.6 (31.7, 49.4) mmol/l min P = 0.031]. A close relationship between the nutrient-stimulated increment in SMA flow and glucose absorption was evident (3-OMG AUC(120-180) and ∆SMA flow at t (150): r (2) = 0.29 P 65 years, stimulation of SMA flow by small intestinal glucose infusion may be attenuated, which could account for the reduction in glucose absorption.
Publisher: American Diabetes Association
Date: 18-06-2009
DOI: 10.2337/DC09-0723
Abstract: We evaluated whether a whey preload could slow gastric emptying, stimulate incretin hormones, and attenuate postprandial glycemia in type 2 diabetes. Eight type 2 diabetic patients ingested 350 ml beef soup 30 min before a potato meal 55 g whey was added to either the soup (whey preload) or potato (whey in meal) or no whey was given. Gastric emptying was slowest after the whey preload (P & 0.0005). The incremental area under the blood glucose curve was less after the whey preload and whey in meal than after no whey (P & 0.005). Plasma glucose-dependent insulinotropic polypeptide, insulin, and cholecystokinin concentrations were higher on both whey days than after no whey, whereas glucagon-like peptide 1 was greatest after the whey preload (P & 0.05). Whey protein consumed before a carbohydrate meal can stimulate insulin and incretin hormone secretion and slow gastric emptying, leading to marked reduction in postprandial glycemia in type 2 diabetes.
Publisher: Wiley
Date: 05-10-2010
DOI: 10.1111/J.1365-2982.2010.01609.X
Abstract: Numerous hormones secreted by the gut, during both the fasted state and in response to a meal, influence gastrointestinal motor and/or sensory function, and appear to contribute to the pathogenesis of delayed gastric emptying associated with gastroparesis, functional dyspepsia (FD) and feed intolerance in critical illness. Gut hormones are, accordingly, potential targets for the management of these patients. This article will discuss the hypersensitivity to enteral fat and endogenous (nutrient-stimulated) and exogenous cholecystokinin (CCK) in patients with FD, and the elevation in both fasting and postprandial CCK levels evident in this group. It will review the use of pharmacological agonists of motilin and ghrelin, which accelerate gastric emptying, in the management of gastroparesis and FD. The frequent finding of markedly delayed gastric emptying in the critically ill will be examined this is associated with elevated plasma CCK and peptide YY in both the fasted and postprandial states, which may account for the increase in small intestinal nutrient inhibitory feedback on gastric motility in this group. The concepts that the rate of gastric emptying is a major determinant of postprandial glycemic excursions in diabetes, and that modulation of gastric emptying may improve glycemic control, will be addressed in type 1 and insulin-treated type 2 diabetic patients, co-ordination of insulin administration with nutrient delivery and absorption should be optimized, while type 2 patients who are not on insulin are likely to respond to dietary and/or pharmacological interventions which slow gastric emptying.
Publisher: American Diabetes Association
Date: 14-02-2019
DOI: 10.2337/DC18-2156
Abstract: Cells releasing glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are distributed predominately in the proximal and distal gut, respectively. Hence, the region of gut exposed to nutrients may influence GIP and GLP-1 secretion and impact on the incretin effect and gastrointestinal-mediated glucose disposal (GIGD). We evaluated glycemic and incretin responses to glucose administered into the proximal or distal small intestine and quantified the corresponding incretin effect and GIGD in health and type 2 diabetes mellitus (T2DM). Ten healthy subjects and 10 patients with T2DM were each studied on four occasions. On two days, a transnasal catheter was positioned with infusion ports opening 13 cm and 190 cm beyond the pylorus, and 30 g glucose with 3 g 3-O-methylglucose (a marker of glucose absorption) was infused into either site and 0.9% saline into the alternate site over 60 min. Matching intravenous isoglycemic cl studies were performed on the other two days. Blood glucose, serum 3-O-methylglucose, and plasma hormones were evaluated over 180 min. In both groups, blood glucose and serum 3-O-methylglucose concentrations were higher after proximal than distal glucose infusion (all P & 0.001). Plasma GLP-1 increased minimally after proximal, but substantially after distal, glucose infusion, whereas GIP increased promptly after both infusions, with concentrations initially greater, but less sustained, with proximal versus distal infusion (all P & 0.001). Both the incretin effect and GIGD were less with proximal than distal glucose infusion (both P ≤ 0.009). The distal, as opposed to proximal, small intestine is superior in modulating postprandial glucose metabolism in both health and T2DM.
Publisher: Wiley
Date: 21-11-2016
DOI: 10.1111/DOM.12812
Abstract: In rodents, metformin slows intestinal glucose absorption, potentially increasing exposure of the distal gut to glucose to enhance postprandial glucagon-like peptide-1 (GLP-1) secretion. We evaluated the effects of metformin on serum 3-O-methylglucose (3-OMG a marker of glucose absorption) and plasma total GLP-1 concentrations during a standardized intraduodenal infusion of glucose and 3-OMG in patients with type 2 diabetes. A total of 12 patients, treated with metformin 850 mg twice daily or placebo for 7 days each in a double-blind, randomized, crossover design (14 days' washout between treatments), were evaluated on days 5 or 8 of each treatment (6 subjects each). On each study day, 30 minutes after ingesting 850 mg metformin or placebo, patients received an infusion of glucose (60 g + 5 g 3-OMG, dissolved in water to 240 mL) via an intraduodenal catheter over the course of 120 minutes. Compared with placebo, metformin was associated with lower serum 3-OMG ( P < .001) and higher plasma total GLP-1 ( P = .003) concentrations. The increment in plasma GLP-1 after metformin vs placebo was related to the reduction in serum 3-OMG concentrations ( P = .019). Accordingly, metformin inhibits small intestinal glucose absorption, which may contribute to augmented GLP-1 secretion in type 2 diabetes.
Publisher: Wiley
Date: 08-03-2022
DOI: 10.1111/DOM.14673
Publisher: Springer Science and Business Media LLC
Date: 16-11-2014
Publisher: Springer Science and Business Media LLC
Date: 10-08-2016
Publisher: The Endocrine Society
Date: 06-09-2016
DOI: 10.1210/JC.2016-2813
Abstract: The rate of gastric emptying is an important determinant of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion and may influence the magnitude of glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors. To evaluate the effects of the DPP-4 inhibitor, vildagliptin (VILD), during intraduodenal (ID) glucose infusion at 2 different rates within the physiological range of gastric emptying, in type 2 diabetes. A total of 16 diet-controlled type 2 diabetic patients were studied on 4 separate days in double-blind, randomized, fashion. On each day, either 5-mg VILD or placebo (PLBO) was given 60 minutes before a 120-minute ID glucose infusion at 2 or 4 kcal/min (ID2 or ID4). Plasma glucose and hormones were measured frequently. Plasma glucose, insulin, C-peptide, glucagon, total GIP, and total and intact GLP-1 concentrations were higher during ID4 than ID2 (P & .01 for each). Compared with PLBO, VILD was associated with higher intact GLP-1, insulin, and C-peptide and lower glucose and total GIP and GLP-1 (P & .01 for each), without affecting glucagon. There were significant interactions between the rate of ID glucose and VILD treatment on plasma glucose, intact and total GLP-1, and GIP (P & .05 for each) but not insulin, C-peptide, or glucagon. The reduction in glucose and the increment in intact GLP-1 after VILD vs PLBO were 3.3- and 3.8-fold greater, respectively, during ID4 compared with ID2. These observations warrant further study to clarify whether type 2 diabetic patients with relatively more rapid gastric emptying have greater glucose lowering during treatment with DPP-4 inhibitors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2002
DOI: 10.1111/J.1572-0241.2002.05422.X
Abstract: Corticotropin-releasing factor (CRF) has been shown to affect GI motor function and appetite in animals. We have evaluated the effects of exogenous CRF on antropyloroduodenal motility and appetite in humans. On 2 separate days, six healthy volunteers received, in randomized, double-blind fashion, i.v. CRF as a 1.0-microg/kg bolus (0-5 min) followed by a constant infusion (1.0 microg/kg/h) (5-150 min), or an identical volume of saline. At t = 28 min each subject drank 200 ml of a nutrient liquid containing 20 mg/kg of paracetamol. Antropyloroduodenal pressures were measured with sleeve/sidehole manometry and perceptions of appetite by visual analog scales. Venous blood was obtained for measurements of serum cortisol and paracetamol. At t = 150 min the manometric catheter was removed and subjects offered a buffet meal (150-180 min). The amount and macronutrient content of food consumed were quantified. CRF increased serum cortisol (p < 0.001), the number of isolated pyloric pressure waves (p < 0.05), duodenal pressure waves (p < 0.05), and the percentage of antegrade duodenal pressure waves (p < 0.05). CRF had no significant effect on the number of antral pressure waves, basal pyloric pressure, serum paracetamol concentrations, perceptions of appetite, or food intake. Intravenous CRF stimulates phasic pyloric and duodenal pressure waves in humans.
Publisher: Springer Science and Business Media LLC
Date: 22-04-2022
Publisher: Wiley
Date: 03-2002
DOI: 10.1046/J.1464-5491.2002.00658.X
Abstract: The outcome of recent studies has led to redefinition of concepts relating to the prevalence, pathogenesis and clinical significance of disordered gastric emptying in patients with diabetes mellitus. The use of scintigraphic techniques has established that gastric emptying is abnormally slow in approx. 30-50% of outpatients with long-standing Type 1 or Type 2 diabetes, although the magnitude of this delay is modest in many cases. Upper gastrointestinal symptoms occur frequently and affect quality of life adversely in patients with diabetes, although the relationship between symptoms and the rate of gastric emptying is weak. Acute changes in blood glucose concentration affect both gastric motor function and upper gastrointestinal symptoms. Gastric emptying is slower during hyperglycaemia when compared with euglycaemia and accelerated during hypoglycaemia. The blood glucose concentration may influence the response to prokinetic drugs. Conversely, the rate of gastric emptying is a major determinant of post-prandial glycaemic excursions in healthy subjects, as well as in Type 1 and Type 2 patients. A number of therapies currently in development are designed to improve post-prandial glycaemic control by modulating the rate of delivery of nutrients to the small intestine.
Publisher: Wiley
Date: 07-2017
DOI: 10.14814/PHY2.13341
Publisher: Humana Press
Date: 24-08-2012
Publisher: Wiley
Date: 05-12-2019
DOI: 10.1111/DOM.13906
Abstract: To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin on glycaemic and energy expenditure responses during intraduodenal fat infusion, as well as the contribution of endogenous glucagon-like peptide-1 (GLP-1) signalling, in people with type 2 diabetes (T2DM). A total of 15 people with T2DM managed by diet and/or metformin (glycated haemoglobin 49.3 ± 2.1 mmol/mol) were studied on three occasions (two with vildagliptin and one with placebo) in a double-blind, randomized, crossover fashion. On each day, vildagliptin 50 mg or placebo was given orally, followed by intravenous exendin (9-39) 600 pmol/kg/min, on one of the two vildagliptin treatment days, or 0.9% saline over 180 minutes. At between 0 and 120 minutes, a fat emulsion was infused intraduodenally at 2 kcal/min. Energy expenditure, plasma glucose and glucose-regulatory hormones were evaluated. Intraduodenal fat increased plasma GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and energy expenditure, and decreased plasma glucose (all P < 0.05). On the two intravenous saline days, plasma glucose and glucagon were lower, plasma intact GLP-1 was higher (all P < 0.05), and energy expenditure tended to be lower after vildagliptin (P = 0.08) than placebo. On the two vildagliptin days, plasma glucose, glucagon and GLP-1 (both total and intact), and energy expenditure were higher during intravenous exendin (9-39) than saline (all P < 0.05). In well-controlled T2DM during intraduodenal fat infusion, vildagliptin lowered plasma glucose and glucagon, and tended to decrease energy expenditure, effects that were mediated by endogenous GLP-1.
Publisher: MDPI AG
Date: 17-08-2021
DOI: 10.3390/NU13082826
Abstract: Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.
Publisher: Humana Press
Date: 24-08-2012
Publisher: Informa UK Limited
Date: 04-2009
DOI: 10.1586/EGH.09.10
Abstract: Gastroparesis is characterized by upper gastrointestinal symptoms associated with delayed gastric emptying, without mechanical obstruction. However, symptoms do not correlate well with the magnitude of delay in gastric emptying. Diabetes mellitus and surgery are the most common causes, although more than 30% of cases are idiopathic. Coordination of insulin action with nutrient delivery is important in diabetics, as postprandial blood glucose levels and gastric emptying are interdependent, and gastroparesis probably represents a major cause of poor glycemic control. Scintigraphy is the gold standard for measuring gastric emptying. Current treatment mainly involves the use of prokinetic drugs. Pyloric botulinum toxin injection and gastric electrical stimulation require more evidence from controlled studies before their use can be recommended. Surgical options remain inadequately studied.
Publisher: BMJ
Date: 29-03-2011
Abstract: It is assumed that delayed gastric emptying (GE) occurs frequently in critical illness however, the prevalence of slow GE has not previously been assessed using scintigraphy. Furthermore, breath tests could potentially provide a convenient method of quantifying GE, but have not been validated in this setting. The aims of this study were to (i) determine the prevalence of delayed GE in unselected, critically ill patients and (ii) evaluate the relationships between GE as measured by scintigraphy and carbon breath test. Prospective observational study. Mixed medical/surgical intensive care unit. 25 unselected, mechanically ventilated patients (age 66 years (49-72) and 14 healthy subjects (age 62 years (19-84)). GE was measured using scintigraphy and (14)C-breath test. A test meal of 100 ml Ensure (standard liquid feed) labelled with (14)C octanoic acid and (99m)Technetium sulphur colloid was placed in the stomach via a nasogastric tube. Gastric 'meal' retention (scintigraphy) at 60, 120, 180 and 240 min, breath test t(50) (BTt(50)), and GE coefficient were determined. Of the 24 patients with scintigraphic data, GE was delayed at 120 min in 12 (50%). Breath tests correlated well with scintigraphy in both patients and healthy subjects (% retention at 120 min vs BTt(50) r(2)=0.57 healthy r(2)=0.56 patients p≤0.002 for both). GE of liquid nutrient is delayed in approximately 50% of critically ill patients. Breath tests correlate well with scintigraphy and are a valid method of GE measurement in this group.
Publisher: The Endocrine Society
Date: 24-05-2022
Abstract: 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. We evaluated the relationship of plasma glucose, GLP-1, and insulin secretion with GE of a 75-g oral glucose load in T2D. Single-center, cross-sectional, post hoc analysis. Institutional research center. 43 in iduals 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. 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. 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. 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. 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.
Publisher: American Diabetes Association
Date: 14-11-2012
DOI: 10.2337/DC12-0028
Abstract: To evaluate the natural history of gastric emptying in diabetes. Thirteen patients with diabetes (12, type 1 1, type 2) had measurements of gastric emptying, blood glucose levels, glycated hemoglobin, upper gastrointestinal symptoms, and autonomic nerve function at baseline and after 24.7 ± 1.5 years. There was no change in gastric emptying of either solids (% retention at 100 min) (baseline 58.5 ± 5% vs. follow-up 51.9 ± 8% P = 0.35) or liquids (50% emptying time) (baseline 29.8 ± 3 min vs. follow-up 34.3 ± 6 min P = 0.37). Gastric emptying of solid at follow-up was related to emptying at baseline (r = 0.56, P & 0.05). At follow-up, blood glucose concentrations were lower (P = 0.006), autonomic function deteriorated (P = 0.03), and gastrointestinal symptoms remained unchanged (P = 0.17). In unselected patients with diabetes, gastric emptying appears remarkably stable over 25 years.
Publisher: SAGE Publications
Date: 20-10-2016
Abstract: To evaluate the effects of the glucagon-like peptide-1 receptor agonist, exenatide, on blood pressure and heart rate during an intraduodenal glucose infusion in type 2 diabetes. Nine subjects with type 2 diabetes were randomised to receive intravenous exenatide or saline control in a crossover design. Glucose (3 kcal min −1 ) was infused via an intraduodenal manometry catheter for 60 min. Blood pressure, heart rate, and the frequency and litude of duodenal pressure waves were measured at regular intervals. Gastrointestinal symptoms were monitored using 100 mm visual analogue scales. During intraduodenal glucose infusion (0–60 min), diastolic ( p (0–60) = 0.03) and mean arterial ( p (0–60) = 0.03) blood pressures and heart rate ( p (0–60) = 0.06 p (0–120) = 0.03)) were higher with exenatide compared to placebo. The increase in the area under the curve for diastolic blood pressure and mean arterial blood pressure was related directly to the suppression of the duodenal motility index with exenatide compared to control ( p = 0.007 and 0.04, respectively). In type 2 diabetes, intravenous exenatide increases mean arterial blood pressure and heart rate during an intraduodenal glucose infusion, supporting the need for further research with exenatide for its potential use in postprandial hypotension.
Publisher: The Endocrine Society
Date: 04-2019
Abstract: Gastric emptying is a major determinant of postprandial glycemia and is often delayed in long-standing, complicated type 2 diabetes mellitus (T2DM). However, there is little information about gastric emptying in well-controlled T2DM. To evaluate the rate of gastric emptying in community-based patients with relatively well-controlled T2DM compared with young and older control subjects without diabetes. A total of 111 patients with T2DM managed by diet (n = 52) or metformin monotherapy (n = 59) (HbA1c 6.6 ± 0.1%/49.0 ± 0.9 mmol/mol), 18 age- and body mass index (BMI)-matched older subjects without diabetes, and 15 young healthy subjects consumed a standardized mashed potato meal (368.5 kcal) containing 100 μL 13C-octanoic acid. Gastric emptying (by breath test) and blood glucose were evaluated over 240 minutes. Gastric emptying was slower in the older than in the young subjects without diabetes (2.3 ± 0.1 vs 3.0 ± 0.1 kcal/min, P = 0.0008). However, relative to the age- and BMI-matched subjects without diabetes, gastric emptying (2.8 ± 0.1 kcal/min) was faster in patients with T2DM (P = 0.0005). Furthermore, gastric emptying was faster in the metformin-treated (3.0 ± 0.1 kcal/min) than in the diet-controlled (2.7 ± 0.1 kcal/min) patients with T2DM (P = 0.011), although there were no differences in age, BMI, HbA1c, or the duration of known diabetes. The increments in blood glucose (at t = 30 and 60 minutes and the incremental area under the curve during t = 0 to 120 minutes) after the meal were related directly to the rate of gastric emptying in the subjects with T2DM regardless of treatment with or without metformin (P < 0.05 each). Gastric emptying is slowed with aging but otherwise is relatively more rapid in patients with well-controlled T2DM. This provides a strong rationale for slowing gastric emptying to improve postprandial glycemic control in these patients.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2015
DOI: 10.1038/NUTD.2015.5
Abstract: To determine the independent and commingling effect of android and gynoid percent fat (measured using Dual Energy X-Ray Absorptiometry) on cardiometabolic dysregulation in normal weight American adults. The 2005–2006 data ( n =1802) from the United States National Health and Nutritional Examination Surveys (NHANES) were used in this study. Associations of android percent fat, gynoid percent fat and their joint occurrence with risks of cardiometabolic risk factors were estimated using prevalence odds ratios from logistic regression analyses. Android-gynoid percent fat ratio was more highly correlated with cardiometabolic dysregulation than android percent fat, gynoid percent fat or body mass index. Commingling of android and gynoid adiposities was associated with much greater odds of cardiometabolic risk factors than either android or gynoid adiposities. Commingling of android and gynoid adiposities was associated with 1.75 (95% confidence interval (CI)=1.42–2.93), 1.48 (95% CI=1.32–1.91), 1.61 (95% CI=1.50–1.89), 3.56 (95% CI=2.91–4.11) and 1.86 (95% CI=1.49–1.96) increased odds of elevated glucose, elevated blood pressure, elevated low-density lipoprotein-cholesterol, elevated triglyceride and low high-density lipoprotein-cholesterol, respectively. Normal weight subjects who present with both android and gynoid adiposities should be advised of the associated health risks. Both android and gynoid fat accumulations should be considered in developing public health strategies for reducing cardiometabolic disease risk in normal weight subjects.
Publisher: Elsevier BV
Date: 2016
Abstract: Resveratrol has been reported to lower glycemia in rodent models of type 2 diabetes associated with the stimulation of glucagon-like peptide 1 (GLP-1), which is known to slow gastric emptying, stimulate insulin secretion, and suppress glucagon secretion and energy intake. We evaluated the effects of 5 wk of resveratrol treatment on GLP-1 secretion, gastric emptying, and glycemic control in type 2 diabetes. Fourteen patients with diet-controlled type-2 diabetes [mean ± SEM glycated hemoglobin (HbA1c): 6.4 ± 0.2% (46.4 ± 2.2 mmol/mol)] received resveratrol (500 mg twice daily) or a placebo over two 5-wk intervention periods with a 5-wk washout period in between in a double-blind, randomized, crossover design. Before and after each intervention period (4 visits), body weight and HbA1c were measured, and patients were evaluated after an overnight fast with a standardized mashed-potato meal labeled with 100 μg (13)C-octanoic acid to measure blood glucose and plasma GLP-1 concentrations and gastric emptying (breath test) over 240 min. Daily energy intake was estimated from 3-d food diaries during the week before each visit. Fasting and postprandial blood glucose and plasma total GLP-1 as well as gastric emptying were similar at each assessment, and the change in each variable from weeks 0 to 5 did not differ between resveratrol and placebo groups. Similarly, changes in HbA1c, daily energy intake, and body weight after 5 wk did not differ between the 2 treatments. In patients with diet-controlled type 2 diabetes, 5 wk of twice-daily 500 mg-resveratrol supplementation had no effect on GLP-1 secretion, glycemic control, gastric emptying, body weight, or energy intake. Our observations do not support the use of resveratrol for improving glycemic control. This trial was registered at www.anzctr.org.au as ACTRN12613000717752.
Publisher: Wiley
Date: 21-11-2018
DOI: 10.1111/DOM.13567
Abstract: The gastrointestinal tract, particularly the lower gut, may be key to the anti-diabetic action of metformin. We evaluated whether administration of metformin into the distal, vs the proximal, small intestine would be more effective in lowering plasma glucose by stimulating glucagon-like pepetide-1 (GLP-1) and/or slowing gastric emptying (GE) in type 2 diabetes (T2DM). Ten diet-controlled T2DM patients were studied on three occasions. A transnasal catheter was positioned with proximal and distal infusion ports located 13 and 190 cm beyond the pylorus, respectively. Participants received infusions of (a) proximal + distal saline (control), (b) proximal metformin (1000 mg) + distal saline or (c) proximal saline + distal metformin (1000 mg) over 5 minutes, followed 60 minutes later by a glucose drink containing 50 g glucose and 150 mg Compared with control, both proximal and distal metformin reduced plasma glucose and augmented GLP-1 responses to oral glucose comparably (P < 0.05 each), without affecting plasma insulin or glucagon. GE was slower after proximal metformin than after control (P < 0.05) and tended to be slower after distal metformin, without any difference between proximal and distal metformin. In diet-controlled T2DM patients, glucose-lowering via a single dose of metformin administered to the upper and lower gut was comparable and was associated with stimulation of GLP-1 and slowing of GE. These observations suggest that the site of gastrointestinal administration is not critical to the glucose-lowering capacity of metformin.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2015
DOI: 10.1038/NUTD.2015.6
Abstract: The region of enteral nutrient exposure may be an important determinant of postprandial incretin hormone secretion and blood glucose homoeostasis. We compared responses of plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon, and blood glucose to a standardised glucose infusion into the proximal jejunum and duodenum in healthy humans. Ten healthy males were evaluated during a standardised glucose infusion (2 kcal min −1 over 120 min) into the proximal jejunum (50 cm post pylorus) and were compared with another 10 healthy males matched for ethnicity, age and body mass index who received an identical glucose infusion into the duodenum (12 cm post pylorus). Blood was s led frequently for measurements of blood glucose and plasma hormones. Plasma GLP-1, GIP and insulin responses, as well as the insulin:glucose ratio and the insulinogenic index 1 (IGI 1 ) were greater ( P .05 for each) after intrajejunal (i.j.) than intraduodenal glucose infusion, without a significant difference in blood glucose or plasma glucagon. Pooled analyses revealed direct relationships between IGI 1 and the responses of GLP-1 and GIP ( r =0.48 and 0.56, respectively, P .05 each), and between glucagon and GLP-1 ( r =0.70, P .001). In conclusion, i.j. glucose elicits greater incretin hormone and insulin secretion than intraduodenal glucose in healthy humans, suggesting regional specificity of the gut–incretin axis.
Publisher: Wiley
Date: 02-2001
DOI: 10.1046/J.1532-5415.2001.49037.X
Abstract: To determine whether slowing of gastric emptying and glucose absorption with guar gum would reduce the fall in blood pressure after an oral glucose load in older subjects. A randomized, experimental, cross-over study. Department of Nuclear Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia. Ten healthy subjects, age 67 to 78. Simultaneous measurements of gastric emptying, blood pressure, blood glucose, serum insulin, and oral glucose absorption (3-O-methyl-D-glucose [3-OMG]) on two occasions after ingestion of 300 mL water containing 50 g glucose and 30 mL lemon juice, 3 g 3-OMG labeled with 99mTc-sulphur colloid with or without 9 g guar gum. Blood pressure and gastric emptying were monitored for 180 minutes. The magnitude of the falls in systolic (P = .02), diastolic (P < .05), and mean arterial (P = .05) blood pressure were less, and gastric emptying slower (P < .05), after guar. Blood glucose, insulin, and 3-OMG concentrations were reduced (P < .001 for all) by guar. 3-OMG concentrations were inversely related to the intragastric retention of glucose (r = -0.72, P = .02) and blood pressure was inversely related to 3-OMG (r = -0.64, P 0.64, P < .05). Guar gum reduces the magnitude of the fall in blood pressure after oral glucose. Slowing of gastric emptying and glucose absorption may represent a novel approach to the treatment of postprandial hypotension.
Publisher: American Diabetes Association
Date: 19-01-2016
DOI: 10.2337/DC15-2298
Abstract: Nutrient “preloads” given before meals can attenuate postprandial glycemic excursions, at least partly by slowing gastric emptying and stimulating secretion of the incretins (i.e., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). This study was designed to evaluate whether a protein preload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying, and lower postprandial glycemia in type 2 diabetes. Twenty-two patients with type 2 diabetes treated with metformin were studied on four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) on both the evening before and the morning of each study day. The latter dose was followed after 60 min by a preload drink containing either 25 g whey protein (WHEY) or control flavoring (CTRL), and after another 30 min by a 13C-octanoate–labeled mashed potato meal. Plasma glucose and hormones, and gastric emptying, were evaluated. Compared with PLBO/CTRL, PLBO/WHEY reduced postprandial peak glycemia, increased plasma insulin, glucagon, and incretin hormones (total and intact), and slowed gastric emptying, whereas VILD/CTRL reduced both the peak and area under the curve for glucose, increased plasma intact incretins, and slowed gastric emptying but suppressed plasma glucagon and total incretins (P & 0.05 each). Compared with both PLBO/WHEY and VILD/CTRL, VILD/WHEY was associated with higher plasma intact GLP-1 and GIP, slower gastric emptying, and lower postprandial glycemia (P & 0.05 each). In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.DIABRES.2016.01.024
Abstract: 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.
Publisher: MDPI AG
Date: 29-10-2020
DOI: 10.3390/NU12113318
Abstract: Ageing is associated with changes in feeding behavior. We have reported that there is suppression of energy intake three hours after whey protein drink ingestion in young, but not older, men. This study aimed to determine these effects over a time period of 9 h. Fifteen younger (27 ± 1 years, 25.8 ± 0.7 kg/m2) and 15 older (75 ± 2 years, 26.6 ± 0.8 kg/m2) healthy men were studied on three occasions on which they received, in a randomized order, a 30 g/120 kcal, 70 g/280 kcal whey-protein, or control (~2 kcal) drink. Ad-libitum energy intake (sum of breakfast, lunch, and dinner) was suppressed in a protein load responsive fashion (P = 0.001). Suppression was minimal at breakfast, substantial at lunch (~−16%, P = 0.001), no longer present by dinner, and was less in older than younger men (−3 ± 4% vs. −8 ± 4%, P = 0.027). Cumulative protein intake was increased in the younger and older men (+20% and +42%, P 0.001). Visual analogue scale ratings of fullness were higher and desire to eat and prospective food consumption were lower after protein vs. control, and these effects were smaller in older vs. younger men (interaction effect P 0.05). These findings support the use of whey-protein drink supplements in older people who aim to increase their protein intake without decreasing their overall energy intake.
Publisher: Wiley
Date: 07-2000
DOI: 10.1046/J.1365-2036.2000.00790.X
Abstract: Delayed gastric emptying and upper gastrointestinal symptoms occur frequently in patients with diabetes mellitus. To evaluate the effects of fedotozine on gastric emptying and gastrointestinal symptoms in diabetic gastroparesis. Thirty-one diabetic patients (20 type 1, 11 type 2) with gastroparesis were randomized to receive fedotozine (30 mg as the tartrate) or placebo t.d.s. Measurements of gastric emptying (100 g ground beef labelled with 20 MBq 99mTc-sulphur colloid chicken liver and 150 mL 10% dextrose labelled with 10 MBq 113mIn-DTPA) and gastrointestinal symptoms were performed before and after 12-16 days of treatment. Data are the mean +/- s.d. Of the 31 patients enrolled, two were excluded from analysis. Data from the remaining 29 patients (18 type 1, 11 type 2 22 female, seven male), aged 42.7 +/- 11.1 years (of whom 14 were randomized to fedotozine and 15 to placebo), were analysed. Fedotozine had no effect on either gastric emptying (solid retention at 100 min fedotozine: baseline, 84 +/- 15% treatment, 73 +/- 23% vs. placebo: baseline, 83 +/- 10% treatment, 70 +/- 20%) or liquid 50% emptying time (fedotozine: baseline, 59 +/- 32 min treatment, 58 +/- 38 min vs. placebo: baseline, 44 +/- 9 min treatment, 43 +/- 21 min) or gastrointestinal symptoms (fedotozine: baseline, 4.4 +/- 2.9 treatment, 4.1 +/- 3.9 vs. placebo: baseline, 4.9 +/- 4.2 treatment, 4.8 +/- 3.9). Fedotozine has no effect on gastric emptying in patients with diabetic gastroparesis.
Publisher: American Diabetes Association
Date: 15-10-2015
DOI: 10.2337/DB15-0893
Abstract: 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 99mTc-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.
Publisher: Informa UK Limited
Date: 09-2001
DOI: 10.1080/003655201750305468
Abstract: Studies in animals indicate that endogenous nitric oxide (NO) is an important inhibitory neurotransmitter in the gastrointestinal tract and that it modulates food intake. We evaluate the role of NO mechanisms in mediating the effects of small intestinal nutrients on antropyloroduodenal motility and appetite in humans. On 2 separate days, 8 healthy adult men received intravenous L-NAME 180 microg/kg/h or 0.9% saline (0-150 min) between 30 min and 120 min, an intraduodenal lipid infusion (2 kcal/min) was administered, and at 120 min subjects were offered a buffet meal (120-150 min). Antropyloroduodenal pressures were measured with a sleeve/sidehole manometric assembly. During the infusions, perceptions of hunger and fullness were assessed with visual analog questionnaires and amount and macronutrient content of food consumed at the buffet meal were quantified. Blood pressure and heart rate were monitored at regular intervals. Intraduodenal lipid infusion was associated with increases in fullness (P < 0.05) and in frequency of isolated pyloric pressure waves (P < 0.05) and basal pyloric pressure (P < 0.05) and decreases in hunger (P < 0.05) and in frequency of antral (P < 0.05) and duodenal (P < 0.05) pressure waves. L-NAME increased diastolic blood pressure (P = 0.08) and decreased heart rate (P < 0.05), but had no effect on antropyloroduodenal pressures or food intake. Intravenous administration of the systemic NO synthase inhibitor, L-NAME, in a dose that affects cardiovascular function in healthy humans does not modify the antropyloroduodenal motor and appetite responses to intraduodenal lipid infusion.
Publisher: Cambridge University Press (CUP)
Date: 11-2006
DOI: 10.1017/BJN20061922
Abstract: The rate of alcohol absorption is dependent on gastric emptying (GE). As the slowing of GE by fat is dependent on lipolysis, orlistat may increase the rise in blood alcohol when alcohol is consumed with, or after, fat. The aim of the study was to evaluate the effects of orlistat on GE and blood alcohol after an alcohol-containing drink following a fat ‘preload’, in healthy subjects. Ten healthy males consumed 120 ml cream with or without 120 mg orlistat, 30 min before an alcohol-containing drink labelled with 20 MBq [ 99 m Tc]sulfur colloid on 2 d. GE, plasma alcohol and blood glucose were measured. GE was slightly faster with orlistat ( P ·05) compared with control. Plasma alcohol at 15 min was slightly higher with orlistat (0·034 (sem 0·006) g/100 ml) v. control (0·029 (sem 0·005) g/100 ml) ( P ·05), but there was no effect on the area under the curve 0–240 min. The increase in blood glucose was greater with orlistat, for ex le, at 15 min (1·07 (sem 0·2) mmol/l) v. control (0·75 (sem 0·2) mmol/l) ( P =0·05). The rise in blood glucose and plasma alcohol were related (for ex le, at 15 min r 0·49 P =0·03). In conclusion, lipase inhibition accelerates GE of an alcohol-containing drink following a fat ‘preload’ with a minor increase in the initial rise in plasma alcohol.
Publisher: American Diabetes Association
Date: 03-03-2017
DOI: 10.2337/DC16-2391
Abstract: To evaluate effects of vildagliptin and metformin on blood pressure (BP) and heart rate (HR) responses to intraduodenal (ID) glucose in diet-controlled type 2 diabetes. Study A compared vildagliptin (50 mg) and placebo, given 60 min before a 120-min ID glucose infusion at 2 or 4 kcal/min (ID2 or ID4) in 16 patients. Study B compared metformin (850 mg) and placebo, given 30 min before ID2 over 120 min in 9 patients. Systolic (P = 0.002) and diastolic (P & 0.001) BP were lower and HR greater (P = 0.005) after vildagliptin compared with placebo, without interaction between vildagliptin and the glucose infusion rate. In contrast, HR was greater after metformin than placebo (P & 0.001), without any difference in systolic or diastolic BP. Vildagliptin reduces BP and increases HR, whereas metformin increases HR without affecting BP during ID glucose infusion in type 2 diabetes. These distinct cardiovascular profiles during enteral nutrient exposure may have implications for postprandial hypotension.
Publisher: Informa UK Limited
Date: 28-01-2016
DOI: 10.1586/17474124.2016.1129898
Abstract: 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.
Publisher: MDPI AG
Date: 06-09-2023
DOI: 10.3390/NU15183889
Publisher: Elsevier BV
Date: 02-2008
DOI: 10.1016/J.REGPEP.2007.09.032
Abstract: The "incretin" hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), account for some 60% of the stimulation of insulin by oral glucose, but the determinants of their secretion from the small intestine are poorly understood. Cells which release GIP (K cells) are localized to the proximal small intestine, while GLP-1 releasing cells (L cells) predominate in the distal gut. It has been suggested that a threshold rate of duodenal glucose delivery (approximately 1.8 kcal/min) needs to be exceeded for stimulation of GLP-1. To determine whether a low intraduodenal glucose load (1 kcal/min) has the capacity to stimulate GLP-1, and if so, the characteristics of the response. Retrospective analysis of all studies in our laboratory involving healthy humans administered intraduodenal glucose at 1 kcal/min for 120 min. Clinical research laboratory. 27 healthy subjects (24 male age 36+/-3 years BMI 25.2+/-0.7 kg/m(2)). Plasma GLP-1, GIP, insulin, and blood glucose concentrations, reported as mean+/-SEM. During intraduodenal glucose, plasma GLP-1 increased at 15 and 30 min (P<0.001 for both) and returned to baseline thereafter. In contrast, there were sustained increases in plasma GIP (P<0.001), insulin (P<0.001), and blood glucose (P<0.001). In healthy subjects, there is early, transient stimulation of GLP-1 by glucose loads hitherto believed to be "sub-threshold". The mechanisms underlying this effect, which could be attributed to initially rapid transit to jejunal L cells, or a duodeno-jejunoileal neural or hormonal loop, remain to be determined.
Publisher: American Diabetes Association
Date: 16-07-2011
DOI: 10.2337/DC11-ER08C
Publisher: Wiley
Date: 17-12-2012
DOI: 10.1111/DOM.12043
Abstract: Glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), secreted by enteroendocrine L-cells located most densely in the colon and rectum, are of fundamental importance in blood glucose and appetite regulation. In animal models, colonic administration of bile acids can stimulate GLP-1 and PYY by TGR5 receptor activation. We evaluated the effects of taurocholic acid (TCA), administered as an enema, on plasma GLP-1 and PYY, as well as gastrointestinal sensations in 10 healthy male subjects, and observed that rectal administration of TCA promptly stimulated secretion of both GLP-1 and PYY, and increased fullness, in a dose-dependent manner. These observations confirm that topical application of bile acids to the distal gut may have potential for the management of type 2 diabetes and obesity.
Publisher: Elsevier
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 14-10-2014
Publisher: MDPI AG
Date: 26-08-2022
DOI: 10.3390/NU14173506
Abstract: Background: Gastrointestinal symptoms have been reported to occur frequently in diabetes, but their prevalence in Chinese community-dwelling in iduals with diabetes is unknown. The present study aimed to address this issue and explore the risk factors for gastrointestinal symptoms. Methods: A total of 1304 community-dwelling participants (214 with diabetes, 360 with prediabetes and 730 with normoglycemia) were surveyed for gastrointestinal symptoms using the Diabetes Bowel Symptom Questionnaire. Logistic regression analyses were applied to identify risk factors for gastrointestinal symptoms. Results: Of the overall study population, 18.6% reported at least one gastrointestinal symptom, without a significant difference between subjects with normoglycemia (17.7%), prediabetes (19.7%) and diabetes (20.1%). In all three groups, lower gastrointestinal symptoms, particularly diarrhea and constipation, were the most frequent. There was an interaction between age (≥65 years) and diabetes on the prevalence of at least one gastrointestinal symptom (p = 0.01) and of constipation (p = 0.004), with these being most frequent in subjects with diabetes aged ≥ 65 years. After multivariable adjustment, female gender and older age were associated with increased odds of at least one gastrointestinal symptom, specifically lower gastrointestinal symptoms. Older age was also associated with an increase in upper gastrointestinal symptoms. Conclusions: Gastrointestinal symptoms are common in Chinese community-dwelling adults with and without diabetes. Females, and the elderly with diabetes, are at an increased risk of symptoms.
Publisher: American Physiological Society
Date: 04-2009
Abstract: The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in glucose homeostasis in both health and diabetes. In mice, sucralose, an artificial sweetener, stimulates GLP-1 release via sweet taste receptors on enteroendocrine cells. We studied blood glucose, plasma levels of insulin, GLP-1, and GIP, and gastric emptying (by a breath test) in 7 healthy humans after intragastric infusions of 1) 50 g sucrose in water to a total volume of 500 ml (∼290 mosmol/l), 2) 80 mg sucralose in 500 ml normal saline (∼300 mosmol/l, 0.4 mM sucralose), 3) 800 mg sucralose in 500 ml normal saline (∼300 mosmol/l, 4 mM sucralose), and 4) 500 ml normal saline (∼300 mosmol/l), all labeled with 150 mg 13 C-acetate. Blood glucose increased only in response to sucrose ( P 0.05). GLP-1, GIP, and insulin also increased after sucrose ( P = 0.0001) but not after either load of sucralose or saline. Gastric emptying of sucrose was slower than that of saline ( t 50 : 87.4 ± 4.1 min vs. 74.7 ± 3.2 min, P 0.005), whereas there were no differences in t 50 between sucralose 0.4 mM (73.7 ± 3.1 min) or 4 mM (76.7 ± 3.1 min) and saline. We conclude that sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1097/CCM.0000000000001715
Abstract: To quantify gallbladder dysfunction during critical illness. Prospective observational comparison study of nutrient-stimulated gallbladder emptying in health and critical illness. Single-centre mixed medical/surgical ICU. Twenty-four mechanically ventilated critically ill patients suitable to receive enteral nutrition were compared with 12 healthy subjects. Participants were studied after an 8-hour fast. Between 0 and 120 minutes, high-fat nutrient (20% intralipid) was infused via a postpyloric catheter into the duodenum at 2 kcal/min. Three-dimensional images of the gallbladder were acquired at 30-minute intervals from –30 to 180 minutes. Ejection fraction (%) was calculated as changes between 0 and 120 minutes. Blood s les were obtained at 30-minute intervals for plasma cholecystokinin. Data are mean ( sd ) or median [interquartile range]. In the critically ill, fasting gallbladder volumes (critically ill, 61 mL [36–100 mL] vs healthy, 22 mL [15–25] mL p 0.001] and wall thickness (0.45 mm [0.15 mm] vs 0.26 mm [0.08 mm] p 0.001] were substantially greater, and sludge was evident in the majority of patients (71% vs 0%). Nutrient-stimulated emptying was incomplete in the critically ill after 120 minutes but was essentially complete in the healthy in iduals (22 mL [9–66 mL] vs 4 mL [3–5 mL] p 0.01]. In five critically ill patients (21%), there was no change in gallbladder volume in response to nutrient, and overall ejection fraction was reduced in the critically ill (50% [8–83%] vs 77 [72–84%] p = 0.01]. There were no differences in fasting or incremental cholecystokinin concentrations. Fasted critically ill patients have larger, thicker-walled gallbladders than healthy subjects and nutrient-stimulated gallbladder emptying is impaired with “gallbladder paresis” occurring in approximately 20%.
Publisher: Wiley
Date: 21-03-2022
DOI: 10.1111/BCP.15297
Abstract: 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. 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. 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). In healthy young subjects, GE of FS, LC and LA beer is comparable and a determinant of the plasma ethanol response.
Publisher: Wiley
Date: 16-07-2021
DOI: 10.1111/DOM.14473
Publisher: Wiley
Date: 16-04-2012
DOI: 10.1111/J.1464-5491.2011.03496.X
Abstract: Postprandial glucagon-like peptide-1 (GLP-1) secretion and the 'incretin effect' have been reported to be deficient in Type 2 diabetes, but most studies have not controlled for variations in the rate of gastric emptying. We evaluated blood glucose, and plasma insulin, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) responses to intraduodenal glucose in Type 2 diabetes, and compared these with data from healthy controls. Eight males with well-controlled Type 2 diabetes, managed by diet alone, were studied on four occasions in single-blind, randomized order. Blood glucose, and plasma insulin, GLP-1, and GIP were measured during 120-min intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2) and 4 kcal/min (G4) or saline control. Type 2 patients had higher basal (P < 0.0005) and incremental (P < 0.0005) blood glucose responses to G2 and G4, when compared with healthy controls. In both groups, the stimulation of insulin and GLP-1 by increasing glucose loads was not linear responses to G1 and G2 were minimal, whereas responses to G4 were much greater (P < 0.005 for each) (incremental area under the GLP-1 curve 224 ± 65, 756 ± 331 and 2807 ± 473 pmol/l.min, respectively, in Type 2 patients and 373 ± 231, 505 ± 161 and 1742 ± 456 pmol/l.min, respectively, in healthy controls). The GLP-1 responses appeared comparable in the two groups. In both groups there was a load-dependent increase in plasma GIP with no difference between them. In patients with well-controlled Type 2 diabetes, blood glucose, insulin and GLP-1 responses are critically dependent on the small intestinal glucose load, and GLP-1 responses are not deficient.
Publisher: American Physiological Society
Date: 09-2007
DOI: 10.1152/AJPENDO.00159.2007
Abstract: Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 (“G1”), 2) 2 (“G2”), and 3) 4 (“G4”) kcal/min or of 4) saline (“control”) were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions ( P 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 ( P 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load ( r 0.82, P 0.05). All glucose infusions suppressed antral ( P 0.05), but only G4 decreased duodenal, pressure waves ( P 0.01), resulted in a sustained stimulation of basal pyloric pressure ( P 0.01), and decreased energy intake ( P 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2007
DOI: 10.1111/J.1572-0241.2007.01142.X
Abstract: The herbal preparation Iberogast has been reported to improve upper abdominal symptoms in functional dyspepsia (FD) and to decrease fundic tone, increase antral contractility, and decrease afferent nerve sensitivity in experimental animals. The effects of Iberogast on the human gastrointestinal tract have not been evaluated. We investigated the effects of oral control and Iberogast, each administered as a single dose (1.1 mL), in a double-blind randomized fashion, on proximal gastric volume (part A), antropyloroduodenal motility (part B), and gastric emptying and intragastric distribution of a solid/liquid meal (part C) for 120 minutes, in nine (part A), 12 (part B), and eight (part C) healthy men. Iberogast increased proximal gastric volume (max volume control 104+/-12 mL, Iberogast 174+/-23 mL, P<0.05) (part A), increased the motility index of antral pressure waves in the first 60 minutes (P<0.05) without affecting pyloric or duodenal pressures (part B), and slightly increased the retention of liquid in the total stomach between 10 and 50 minutes (P<0.01), but had no effect on gastric emptying of solids or intragastric distribution (part C). Iberogast affects gastric motility in humans, probably in a region-dependent manner. The stimulation of gastric relaxation and antral motility may contribute to the reported therapeutic efficacy of Iberogast in FD.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2000
DOI: 10.1111/J.1572-0241.2000.02250.X
Abstract: Diabetic gastroparesis is usually treated with prokinetic drugs, of which the most potent, when given intravenously during euglycemia, is erythromycin. Recent studies have demonstrated that the gastrokinetic effects of erythromycin are attenuated by hyperglycemia. The aim of this study was to determine whether the effects of erythromycin on antropyloroduodenal motility, including the organization of antral pressure waves, are modified by hyperglycemia. A total of eight healthy male volunteers (median age 24 yr) were studied on 2 days each in randomized order. A manometric assembly, incorporating six antral, two pyloric, and seven duodenal sideholes and a pyloric sleeve sensor, was positioned with the sleeve spanning the pylorus. The blood glucose concentration was stabilized at about 5 mmol/L (euglycemia) or 15 mmol/L (hyperglycemia). After 30 min (T = 0), an intraduodenal lipid infusion (1.5 kcal/min) was commenced and continued until the end of the study. At T = 20 minutes, erythromycin (200 mg) as the lactobionate was infused intravenously over 20 min, followed by 100 mg over the next 40 min. Intravenous erythromycin increased the litude of antral waves during intraduodenal lipid infusion at both blood glucose concentrations (p < 0.01 for euglycemia and p < 0.05 for hyperglycemia). After erythromycin (T = 20 to T = 80), the frequency (p < 0.05) and litude (p < 0.01) of antral waves were less during hyperglycemia than euglycemia. Both propagated (p < 0.0005) and nonpropagated (p < 0.01) antral waves were decreased by hyperglycemia, but the suppression of propagated waves was greater (p < 0.05). Erythromycin reduced the frequency (p = 0.09) but increased the litude (p < 0.05) of phasic pyloric pressures, and decreased basal pyloric pressure (p < 0.0005). The frequency (p = 0.06) and litude (p < 0.05) of phasic pyloric waves during erythromycin infusion were slightly less during hyperglycemia than euglycemia, whereas there was no effect of the blood glucose concentration on basal pyloric pressure. Erythromycin increased the litude (p < 0.001) but not the frequency of duodenal waves the frequency and litude of duodenal waves did not differ between the two blood glucose concentrations. Hyperglycemia attenuates the stimulation of antral pressures and propagated antral sequences by erythromycin, but not the effects of erythromycin on pyloric or duodenal motility.
Publisher: The Endocrine Society
Date: 29-03-2023
Abstract: Premenopausal women are at a lower risk of type 2 diabetes (T2D) compared to men, but the underlying mechanism(s) remain elusive. The secretion of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), from the small intestine is a major determinant of glucose homeostasis and may be influenced by sex. This study compared blood glucose and plasma insulin and incretin responses to intraduodenal glucose infusions in healthy young males and females. In Study 1, 9 women and 20 men received an intraduodenal glucose infusion at 2 kcal/min for 60 minutes. In Study 2, 10 women and 26 men received an intraduodenal glucose at 3 kcal/min for 60 minutes. Venous blood was s led every 15 minutes for measurements of blood glucose and plasma insulin, GLP-1 and GIP. In response to intraduodenal glucose at 2 kcal/min, the incremental area under the curve between t = 0-60 minutes (iAUC0-60min) for blood glucose and plasma GIP did not differ between the 2 groups. However, iAUC0-60min for plasma GLP-1 (P = 0.016) and insulin (P = 0.011) were ∼2-fold higher in women than men. In response to intraduodenal glucose at 3 kcal/min, iAUC0-60min for blood glucose, plasma GIP, and insulin did not differ between women and men, but GLP-1 iAUC0-60min was 2.5-fold higher in women (P = 0.012). Healthy young women exhibit comparable GIP but a markedly greater GLP-1 response to intraduodenal glucose than men. This disparity warrants further investigations to delineate the underlying mechanisms and may be of relevance to the reduced risk of diabetes in premenopausal women when compared to men.
Publisher: American Diabetes Association
Date: 17-01-2013
DOI: 10.2337/DC12-1903
Publisher: Springer Science and Business Media LLC
Date: 17-12-2019
DOI: 10.1007/S00592-019-01461-Z
Abstract: Glucose-dependent insulinotropic polypeptide (GIP) is released primarily from the proximal small intestine and glucagon-like peptide-1 (GLP-1) from the more distal small intestine and colon. Their relative importance to the incretin effect in health has been contentious in the past, although it now appears that GIP has the dominant role. It is uncertain whether there is a relationship between GIP and GLP-1 secretion. We aimed to evaluate the relationship between plasma GIP and GLP-1 responses to a 75-g oral glucose load in in iduals with normal (NGT) and impaired glucose tolerance (IGT). One hundred healthy subjects had measurements of blood glucose, serum insulin, plasma GIP and GLP-1 concentrations for 240 min after a 300 mL drink containing 75 g glucose. Fifty had NGT and 41 IGT 9 had type 2 diabetes and were excluded from analysis. In both groups, there were increases in plasma GIP and GLP-1 following the glucose drink, with no difference in the magnitude of the responses between t = 0-240 min. There was a weak relationship between the iAUC There is a weak relationship between oral glucose-induced GIP and GLP-1 secretions in non-diabetic subjects.
Publisher: The Endocrine Society
Date: 16-05-2018
Publisher: Elsevier BV
Date: 03-2017
Publisher: Baishideng Publishing Group Inc.
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 12-2015
DOI: 10.1186/S13054-014-0718-3
Abstract: Insulin is used to treat hyperglycaemia in critically ill patients but can cause hypoglycaemia, which is associated with poorer outcomes. In health glucose-dependent insulinotropic polypeptide (GIP) is a potent glucose-lowering peptide that does not cause hypoglycaemia. The objectives of this study were to determine the effects of exogenous GIP infusion on blood glucose concentrations, glucose absorption, insulinaemia and gastric emptying in critically ill patients without known diabetes. A total of 20 ventilated patients (Median age 61 (range: 22 to 79) years, APACHE II 21.5 (17 to 26), BMI 28 (21 to 40) kg/m 2 ) without known diabetes were studied on two consecutive days in a randomised, double blind, placebo controlled, cross-over fashion. Intravenous GIP (4 pmol/kg/min) or placebo (0.9% saline) was infused between T = −60 to 300 minutes. At T0, 100 ml of liquid nutrient (2 kcal/ml) containing 3-O-Methylglucose (3-OMG), 100 mcg of Octanoic acid and 20 MBq Tc-99 m Calcium Phytate, was administered via a nasogastric tube. Blood glucose and serum 3-OMG (an index of glucose absorption) concentrations were measured. Gastric emptying, insulin and glucagon levels and plasma GIP concentrations were also measured. While administration of GIP increased plasma GIP concentrations three- to four-fold (T = −60 23.9 (16.5 to 36.7) versus T = 0 84.2 (65.3 to 111.1) P .001) and plasma glucagon (iAUC 300 4217 (1891 to 7715) versus 1232 (293 to 4545) pg/ml.300 minutes P = 0.04), there were no effects on postprandial blood glucose (AUC 300 2843 (2568 to 3338) versus 2819 (2550 to 3497) mmol/L.300 minutes P = 0.86), gastric emptying (AUC 300 15611 (10993 to 18062) versus 15660 (9694 to 22618) %.300 minutes P = 0.61), glucose absorption (AUC 300 50.6 (22.3 to 74.2) versus 64.3 (9.9 to 96.3) mmol/L.300 minutes P = 0.62) or plasma insulin (AUC 300 3945 (2280 to 6731) versus 3479 (2316 to 6081) mU/L.300 minutes P = 0.76). In contrast to its profound insulinotropic effect in health, the administration of GIP at pharmacological doses does not appear to affect glycaemia, gastric emptying, glucose absorption or insulinaemia in the critically ill patient. Australian New Zealand Clinical Trials Registry ACTRN12612000488808 . Registered 3 May 2012.
Publisher: American Physiological Society
Date: 09-2005
DOI: 10.1152/AJPENDO.00099.2005
Abstract: The rate of gastric emptying of glucose-containing liquids is a major determinant of postprandial glycemia. The latter is also dependent on stimulation of insulin secretion by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). Although overall emptying of glucose approximates 1–3 kcal/min, the “early phase” of gastric emptying is usually more rapid. We have evaluated the hypothesis that increased stimulation of incretin hormones and insulin by a more rapid initial rate of small intestinal glucose delivery would reduce the overall glycemic response to a standardized enteral glucose load. Twelve healthy subjects were studied on two separate days in which they received an intraduodenal (id) glucose infusion for 120 min. On one day, the infusion rate was variable, being more rapid (6 kcal/min) between t = 0 and 10 min and slower (0.55 kcal/min) between t = 10 and 120 min, whereas on the other day the rate was constant (1 kcal/min) from t = 0–120 min, i.e., on both days 120 kcal were given. Between t = 0 and 75 min, plasma insulin, GIP, and GLP-1 were higher with the variable infusion. Despite the increase in insulin and incretin hormones, blood glucose levels were also higher. Between t = 75 and 180 min, blood glucose and plasma insulin were lower with the variable infusion. There was no difference in the area under the curve 0–180 min for blood glucose. We conclude that stimulation of incretin hormone and insulin release by a more rapid initial rate of id glucose delivery does not lead to an overall reduction in glycemia in healthy subjects.
Publisher: The Endocrine Society
Date: 07-2004
DOI: 10.1210/JC.2004-0334
Publisher: American Physiological Society
Date: 04-2007
Abstract: Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel technique that allows flow events to be quantified. Eight healthy volunteers were studied twice, in random order. A catheter incorporating six pairs of electrodes at 3-cm intervals, and six corresponding manometry sideholes, was positioned in the duodenum. Hyoscine butylbromide (20 mg) or saline was given as an intravenous bolus, followed by a continuous intravenous infusion of either hyoscine (20 mg/h) or saline over 60 min. Concurrently, glucose and 3- O-methylglucose (3-OMG) were infused into the proximal duodenum (3 kcal/min), with frequent blood s ling to measure glucose, 3-OMG, insulin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). The frequency of duodenal pressure waves and propagated pressure wave sequences was reduced by hyoscine in the first 10 min ( P 0.01 for both), but not after that time. In contrast, there were markedly fewer duodenal flow events throughout 60 min with hyoscine ( P 0.005). Overall, blood glucose ( P 0.01) and plasma 3-OMG concentrations ( P 0.05) were lower during hyoscine than saline, whereas plasma insulin, GLP-1, and GIP concentrations were initially ( t = 20 min) lower during hyoscine ( P 0.05). In conclusion, intraluminal impedance measurement may be more sensitive than manometry in demonstrating alterations in duodenal motor function. A reduction in the frequency of duodenal flow events is associated with a decreased rate of glucose absorption and incretin release in healthy subjects.
Publisher: Hindawi Limited
Date: 2011
DOI: 10.1155/2011/279530
Abstract: Glucagon-like peptide 1 (GLP-1) is a hormone secreted predominantly by the distal small intestine and colon and released in response to enteral nutrient exposure. GLP-1-based therapies are now used widely in the management of type 2 diabetes and have the potential to be effective antiobesity agents. Although widely known as an incretin hormone, there is a growing body of evidence that GLP-1 also acts as an enterogastrone, with profound effects on the gastrointestinal motor system. Moreover, the effects of GLP-1 on gastrointestinal motility appear to be pivotal to its effect of reducing postprandial glycaemic excursions and may, potentially, represent the dominant mechanism. This review summarizes current knowledge of the enterogastrone properties of GLP-1, focusing on its effects on gut motility at physiological and pharmacological concentrations, and the motor actions of incretin-based therapies. While of potential importance, the inhibitory action of GLP-1 on gastric acid secretion is beyond the scope of this paper.
Publisher: Georg Thieme Verlag KG
Date: 03-2022
DOI: 10.1055/A-1784-6185
Abstract: Introduction Breath tests utilising 13C-labelled substrates for the assessment of gastric emptying have been applied widely. Wagner-Nelson analysis is a pharmacokinetic model that can be utilised to generate a gastric emptying curve from the % 13CO2 measured in breath s les. We compared Wagner-Nelson analysis with (i) scintigraphy and (ii) conventional breath test modelling to quantify gastric emptying in type 2 diabetes. Methods Thirteen patients (age 68.1±1.5 years, body mass index 31.0±0.9 kg/m2, HbA1c 6.3±0.2%) consumed a mashed potato meal comprising 65 g powdered potato, 20 g glucose, 250 ml water, an egg yolk labelled with 100 μL 13C-octanoic acid and 20MBq 99mTc-calcium phytate. Scintigraphic data were acquired and breath s les collected for 4 hours after the meal. Gastric emptying curves were derived based on each technique the 50% emptying time and intragastric retention at 60 min were also calculated. Results With Wagner-Nelson analysis, a Kel=0.60 (the elimination constant) best approximated the scintigraphic gastric emptying curve. There was a relationship between the T50 calculated with scintigraphy and by both Wagner-Nelson Kel=0.60 (r2=0.45, P .05) and conventional analysis (r2=0.44, P .05). There was no significant difference in the 50% gastric emptying time for scintigraphy (68.5±4.8 min) and Wagner-Nelson Kel=0.60 (71.3±4.5 min), however, the 50% gastric emptying time calculated by conventional analysis was much greater at 164.7±6.0 min (P .001). Conclusion In type 2 diabetes, gastric emptying of a mashed potato meal measured using a 13C-octanoic acid breath test analysed with Wagner-Nelson Kel=0.60 closely reflects measurements obtained with scintigraphy, whereas, in absolute terms, the conventional breath test analysis does not.
Publisher: Oxford University Press (OUP)
Date: 24-03-2021
DOI: 10.1093/BJS/ZNAB101
Abstract: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18–49, 50–69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351 best case 196, worst case 816) or non-cancer surgery (733 best case 407, worst case 1664). Both exceeded the NNV in the general population (1840 best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.
Publisher: Wiley
Date: 22-03-2022
DOI: 10.1111/DOM.14683
Abstract: To determine the serum bile acid (BA) response to 75‐g oral glucose in in iduals without diabetes, and whether this is attenuated in patients with ‘early’ type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group. Forty newly diagnosed, treatment‐naïve Han Chinese T2D subjects and 40 age‐, gender‐, and body mass index‐matched controls without T2D ingested a 75‐g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and in idual BAs, fibroblast growth factor‐19 (FGF‐19), total glucagon‐like peptide‐1 (GLP‐1), and insulin, were measured before and 2 hours after oral glucose. Fasting total BA levels were higher in T2D than control subjects ( P .05). At 2 hours, the BA profile exhibited a shift from baseline in both groups, with increases in conjugated BAs and/or decreases in unconjugated BAs. There were increases in total BA and FGF‐19 levels in control (both P .05), but not T2D, subjects. Plasma glucose concentrations at 2 hours related inversely to serum total BA levels in control subjects ( r = −0.42, P = .006). Total GLP‐1 and the insulin/glucose ratio were increased at 2 hours in both groups, and the magnitude of the increase was greater in control subjects. The serum BA response to a 75‐g oral glucose load is attenuated in patients with ‘early’ T2D, as is the secretion of FGF‐19 and GLP‐1, while in in iduals without T2D it correlates with 2‐hour plasma glucose levels. These observations support a role for BAs in the regulation of postprandial glucose metabolism.
Publisher: Elsevier BV
Date: 06-2013
DOI: 10.1016/J.PEPTIDES.2013.01.014
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.
Publisher: Wiley
Date: 08-12-2016
DOI: 10.1111/DOM.12822
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CGER.2015.04.003
Abstract: Aging is characterized by a diminished homeostatic regulation of physiologic functions, including slowing of gastric emptying. Gastric and small intestinal motor and humoral mechanisms in humans are complex and highly variable: ingested food is stored, mixed with digestive enzymes, ground into small particles, and delivered as a liquefied form into the duodenum at a rate allowing efficient digestion and absorption. In healthy aging, motor function is well preserved whereas deficits in sensory function are more apparent. The effects of aging on gastric emptying are relevant to the absorption of oral medications and the regulation of appetite, postprandial glycemia, and blood pressure.
Publisher: MDPI AG
Date: 05-11-2019
DOI: 10.3390/NU11112666
Abstract: A whey protein/guar gum preload reduces postprandial glycaemia in type 2 diabetes through slowing gastric emptying. However, gastric emptying has previously been assessed using a stable isotope breath test technique, which cannot discriminate between slowing of gastric emptying and small intestinal absorption. This preload also may be useful in the management of postprandial hypotension. We evaluated the effects of a whey protein/guar preload on gastric emptying, glucose absorption, glycaemic/insulinaemic and blood pressure (BP) responses to an oral glucose load. Eighteen healthy older participants underwent measurements of gastric emptying (scintigraphy), plasma glucose and insulin, glucose absorption, superior mesenteric artery (SMA) flow, BP and heart rate (HR) after ingesting a 50 g glucose drink, with or without the preload. The preload reduced plasma glucose (p = 0.02) and serum 3-O-methylglucose (3-OMG) (p = 0.003), and increased plasma insulin (p = 0.03). There was no difference in gastric emptying or BP between the two days. The reduction in plasma glucose on the preload day was related to the reduction in glucose absorption (r = 0.71, p = 0.002). In conclusion, the glucose-lowering effect of the preload may relate to delayed small intestinal glucose absorption and insulin stimulation, rather than slowing of gastric emptying.
Publisher: The Endocrine Society
Date: 08-2010
DOI: 10.1210/JC.2009-2514
Abstract: Acute hyperglycemia slows gastric emptying, but its effects on small intestinal motor activity and glucose absorption are unknown. In type 2 diabetes, the postprandial secretion of glucose-dependent insulinotropic polypeptide (GIP) is preserved, but that of glucagon-like peptide-1 (GLP-1) is possibly reduced whether the latter is secondary to hyperglycemia or diabetes per se is unknown. The aim was to investigate the effects of acute hyperglycemia on duodenal motility and flow events, glucose absorption, and incretin hormone secretion. Nine healthy volunteers were studied on two occasions. A combined manometry/impedance catheter was positioned in the duodenum. Blood glucose was cl ed at either 9 mmol/liter (hyperglycemia) or 5 mmol/liter (euglycemia) throughout the study. Manometry and impedance recordings continued between T=-10 min and T=180 min. Between T=0 and 60 min, an intraduodenal glucose infusion was given (approximately 3 kcal/min), together with 14C-labeled 3-O-methylglucose (3-OMG) to evaluate glucose absorption. Hyperglycemia had no effect on duodenal pressure waves or flow events during the 60 min of intraduodenal glucose infusion, when compared to euglycemia. During hyperglycemia, there was an increase in plasma GIP (P<0.05) and 14C-3-OMG (P<0.05) but no effect on GLP-1 concentrations in response to the intraduodenal infusion, compared to euglycemia. Acute hyperglycemia in the physiological range has no effect on duodenal pressure waves and flow events but is associated with increased GIP secretion and rate of glucose absorption in response to intraduodenal glucose.
Publisher: MDPI AG
Date: 07-2020
DOI: 10.3390/NU12071962
Abstract: 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.
Publisher: The Endocrine Society
Date: 05-2011
DOI: 10.1210/JC.2010-2460
Abstract: Postprandial hyperglycemia is an important clinical problem in cystic fibrosis (CF), but the contribution of fat malabsorption, rapid gastric emptying, and the incretin axis has not been widely considered. The aim of this study was to evaluate these aspects of gut function in nondiabetic CF patients. We conducted a randomized, double-blind, placebo-controlled crossover study at a clinical research laboratory. Five nondiabetic CF patients (three males age, 25.8 ± 1.0 yr body mass index, 20.2 ± 1.1 kg/m(2)) with exocrine pancreatic insufficiency and six healthy subjects of similar age and body mass index participated in the study. CF patients consumed a radiolabeled mashed potato meal on 2 separate days, together with four capsules of Creon Forte (100,000 IU lipase) or placebo. Healthy subjects consumed the meal once, without pancreatic enzymes. Gastric emptying was measured using scintigraphy, and blood was s led frequently for blood glucose and plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon concentrations. CF patients had more rapid gastric emptying (P < 0.001), impaired secretion of GLP-1 (P < 0.01) and GIP (P < 0.001), and greater postprandial glycemic excursions (P < 0.001) than healthy subjects. Pancreatic enzyme supplementation normalized gastric emptying and GLP-1 secretion and tended to increase glucagon (P = 0.08), but did not completely restore GIP secretion or normalize postprandial blood glucose. There was an excellent correlation between gastric emptying and blood glucose concentration at 60 min (R = 0.75 P = 0.01). Pancreatic enzyme supplementation plays an important role in incretin secretion, gastric emptying, and postprandial hyperglycemia in CF.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2016
DOI: 10.1097/CCM.0000000000001815
Abstract: The optimal blood glucose target in critically ill patients with preexisting diabetes and chronic hyperglycemia is unknown. In such patients, we aimed to determine whether a “ liberal” approach to glycemic control would reduce hypoglycemia and glycemic variability and appear safe. Prospective, open-label, sequential-period exploratory study. Medical-surgical ICU. During sequential 6-month periods, we studied 83 patients with preexisting type 2 diabetes and chronic hyperglycemia (glycated hemoglobin, ≥ 7.0% at ICU admission). During the “standard care” period, 52 patients received insulin to treat blood glucose concentrations greater than 10 mmol/L whereas during the “liberal” period, 31 patients received insulin to treat blood glucose concentrations greater than 14 mmol/L. Time-weighted mean glucose concentrations and the number and duration of moderate ( 4.0 mmol/L) and severe (≤ 2.2 mmol/L) hypoglycemic episodes were recorded, with moderate and severe hypoglycemic episodes grouped together. Glycemic variability was assessed by calculating the coefficient of variability for each patient. Safety was evaluated using clinical outcomes and plasma concentrations of markers of inflammation, glucose-turnover, and oxidative stress. Mean glucose (TWglucose day 0–7 , standard care: 9.3 [1.8] vs liberal: 10.3 [2.1] mmol/L p = 0.02) and nadir blood glucose (4.4 [1.5] vs 5.5 [1.6] mmol/L p 0.01) were increased during the liberal period. There was a signal toward reduced risk of moderate-severe hypoglycemia (relative risk: liberal compared with standard care: 0.47 [95% CI, 0.19–1.13] p = 0.09). Ten patients (19%) during the standard period and one patient (3%) during the liberal period had recurrent episodes of moderate-severe hypoglycemia. Liberal therapy reduced glycemic variability (coefficient of variability, 33.2% [12.9%] vs 23.8% [7.7%] p 0.01). Biomarker data and clinical outcomes were similar. In critically ill patients with type 2 diabetes and chronic hyperglycaemia, liberal glycemic control appears to attenuate glycemic variability and may reduce the prevalence of moderate-severe hypoglycemia.
Publisher: American Physiological Society
Date: 12-2009
Abstract: Gastric emptying (GE) of glucose is regulated closely, not only as a result of inhibitory feedback arising from the small intestine, but also because of the resulting hyperglycemia. Fructose is used widely in the diabetic diet and is known to empty from the stomach slightly faster than glucose but substantially slower than water. The aims of this study were to determine whether intravenous (iv) fructose affects GE and antropyloroduodenal motility and how any effects compare to those induced by iv glucose. Six healthy males (age: 26.7 ± 3.8 yr) underwent concurrent measurements of GE of a solid meal (100 g ground beef labeled with 20 MBq 99m Tc-sulfur colloid) and antropyloroduodenal motility on three separate days in randomized order during iv infusion of either fructose (0.5 g/kg), glucose (0.5 g/kg), or isotonic saline for 20 min. GE (scintigraphy), antropyloroduodenal motility (manometry), and blood glucose (glucometer) were measured for 120 min. There was a rise in blood glucose ( P 0.001) after iv glucose (peak 16.4 ± 0.6 mmol/l) but not after fructose or saline. Intravenous glucose and fructose both slowed GE substantially ( P 0.005 for both), without any significant difference between them. Between t = 0 and 30 min, the number of antral pressure waves was less after both glucose and fructose ( P 0.002 for both) than saline, and there were more isolated pyloric pressure waves during iv glucose ( P = 0.003) compared with fructose and saline ( P = NS for both) infusions. In conclusion, iv fructose slows GE and modulates gastric motility in healthy subjects, and the magnitude of slowing of GE is comparable to that induced by iv glucose.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-2009
Publisher: Springer Science and Business Media LLC
Date: 2003
Abstract: Postprandial hypotension occurs frequently in diabetes the fall in blood pressure is greatest after ingestion of carbohydrate, particularly glucose and, in type 2 diabetes, is related to the rate of gastric emptying. The aim of this study was to determine whether slowing of gastric emptying by guar gum reduces the fall in blood pressure after oral glucose in patients with type 2 diabetes. Eleven type 2 patients managed by diet alone, age 61.9 +/- 1.3 years, had measurements of gastric emptying, blood pressure, blood glucose, and serum insulin on two occasions after ingestion of 300 ml water containing 50 g glucose, with or without 9 g guar gum. The magnitude of the fall in blood pressure was less (P < 0.05) and gastric emptying slower (P < 0.05) after guar. Blood glucose (P < 0.05) and serum insulin (P < 0.01) concentrations were lower after guar. The magnitude of the fall in systolic blood pressure was related to gastric emptying of glucose at 30 min on the control day (r = 0.67, P < 0.05). We conclude that guar gum attenuates the fall in blood pressure after oral glucose in patients with type 2 diabetes mellitus, presumably by slowing glucose absorption.
Publisher: Wiley
Date: 09-1997
DOI: 10.1111/J.1469-7793.1997.455BH.X
Abstract: 1. Gastric mechanics were investigated by categorizing the temporal and spatial patterning of pressure waves associated with in idual gastric contractions. 2. In twelve healthy volunteers, intraluminal pressures were monitored from nine side hole recording points spaced at 1.5 cm intervals along the antrum, pylorus and duodenum. 3. Pressure wave sequences that occurred during phase II fasting contractions (n = 221) and after food (n = 778) were evaluated. 4. The most common pattern of pressure wave onset along the antrum was a variable combination of antegrade, synchronous and retrograde propagation between side hole pairs. This variable pattern accounted for 42% of sequences after food, and 34% during fasting (P < 0.05). Other common pressure wave sequence patterns were: purely antegrade-29% after food and 42% during fasting (P < 0.05) purely synchronous-23% fed and 17% fasting and purely retrograde-6% fed and 8% fasting. The length of sequences was shorter after food (P < 0.05). Some sequences 'skipped' in idual recording points. 5. The spatial patterning of gastric pressure wave sequences is erse, and may explain the differing mechanical outcomes among in idual gastric contractions. 6. Better understanding of gastric mechanics may be gained from temporally precise correlations of luminal flows and pressures and gastric wall motion during in idual gastric contraction sequences.
Publisher: Wiley
Date: 02-2010
Publisher: Wiley
Date: 02-1995
DOI: 10.1111/J.1365-2362.1995.TB01536.X
Abstract: The relationship between calcium absorption and gastric emptying and the precision of measurement of fractional calcium absorption using a single isotope technique were evaluated in 14 normal postmenopausal women (age range 61-72 years). On two occasions separated by between 5 and 15 days, each subject was given 250 mL water containing 0.2 MBq of 45Ca in 20 mg of calcium carrier as the chloride, 20 mg kg-1 paracetamol and 9 MBq of 99mTc sulphur colloid. Venous blood s les were taken at -2, 15, 30, 45, 60, 90, 120, 150 and 180 min after consumption of the drink, and gastric emptying (GE) was monitored with a gamma camera. Fractional calcium absorption in the first hour (alpha 6) was calculated from the blood s les obtained at 15, 30, 45, 60, 90 and 120 min. An absorption rate was also derived from the 60 min s le using only a calibration curve (alpha 1). There were close correlations between radiocalcium absorption on the two study days (r = 0.89, P < 0.001 for both alpha 1 and alpha 6) and between alpha 1 and alpha 6 (r = 0.93, P < 0.001). Plasma paracetamol concentrations at 15 min were directly related to the early phase of GE (r = 0.42, P < 0.05). In contrast, calcium absorption was inversely related to GE (r = 0.45, P < 0.05). We conclude that radiocalcium absorption is not greatly influenced by gastric emptying rate and that the single blood s le procedure has similar precision to the six-blood s le test.
Publisher: Wiley
Date: 02-06-2015
Abstract: Enteral feed intolerance occurs frequently in critically ill patients and can be associated with adverse outcomes. "Energy-dense formulae" (ie, >1 kcal/mL) are often prescribed to critically ill patients to reduce administered volume and are presumed to maintain or increase calorie delivery. The aim of this study was to compare gastric emptying of standard and energy-dense formulae in critically ill patients. In a retrospective comparison of 2 studies, data were analyzed from 2 groups of patients that received a radiolabeled 100-mL "meal" containing either standard calories (1 kcal/mL) or concentrated calories (energy-dense formulae 2 kcal/mL). Gastric emptying was measured using a scintigraphic technique. Radioisotope data were collected for 4 hours and gastric emptying quantified. Data are presented as mean ± SE or median [interquartile range] as appropriate. Forty patients were studied (n = 18, energy-dense formulae n = 22, standard). Groups were well matched in terms of demographics. However, patients in the energy-dense formula group were studied earlier in their intensive care unit admission (P = .02) and had a greater proportion requiring inotropes (P = .002). A similar amount of calories emptied out of the stomach per unit time (P = .57), but in patients receiving energy-dense formulae, a greater volume of meal was retained in the stomach (P = .045), consistent with slower gastric emptying. In critically ill patients, the administration of the same volume of a concentrated enteral nutrition formula may not result in the delivery of more calories to the small intestine over time because gastric emptying is slowed.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CLNU.2014.11.003
Abstract: Enteral nutrition is important in critically ill patients and is usually administered via a nasogastric tube. As gastric emptying is frequently delayed, and this compromises the delivery of nutrient, it is important that the emptying rate can be quantified. A comprehensive search of MEDLINE/PubMed, of English articles, from inception to 1 July 2014. References of included manuscripts were also examined for additional studies. A number of methods are available to measure gastric emptying and these broadly can be categorised as direct- or indirect-test and surrogate assessments. Direct tests necessitate visualisation of the stomach contents during emptying and are unaffected by liver or kidney metabolism. The most frequently used direct modality is scintigraphy, which remains the 'gold standard'. Indirect tests use a marker that is absorbed in the proximal small intestine, so that measurements of the marker, or its metabolite measured in plasma or breath, correlates with gastric emptying. These tests include drug and carbohydrate absorption and isotope breath tests. Gastric residual volumes (GRVs) are used frequently to quantify gastric emptying during nasogastric feeding, but these measurements may be inaccurate and should be regarded as a surrogate measurement. While the inherent limitations of GRVs make them less suitable for research purposes they are often the only technique that is available for clinicians at the bedside. Each of the available techniques has its strength and limitations. Accordingly, the choice of gastric emptying test is dictated by the particular requirement(s) and expertise of the investigator or clinician.
Publisher: American Diabetes Association
Date: 12-02-2018
DOI: 10.2337/DC17-1916
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.DIABRES.2019.107822
Abstract: To determine the prevalence of low faecal elastase-1 (FE-1) (≤200 μg/g) in type 2 diabetes (T2DM), and to test the hypothesis that pancreatic enzyme replacement therapy (PERT) would reduce postprandial glycaemia after a high-fat, high-carbohydrate meal in T2DM subjects with low FE-1. Of 109 community-based patients who submitted stool s les, 10 had low FE-1 and 8 were recruited (6 male, 2 female, 67.8 ± 3.0 years). Participants were given a high-fat, high-carbohydrate meal (718 kcal) with either pancrelipase (50,000 units) or placebo in a randomised, double-blind, crossover fashion. The primary outcome was the difference in postprandial glycaemia following PERT vs placebo, as evaluated by the incremental area under the postprandial plasma glucose curve (iAUC). Secondary outcomes included differences in gastric half-emptying time (T50) measured using scintigraphy, and C-peptide iAUC. The prevalence of low FE-1 in T2DM was 9.2% (95% CI 3.8-14.6%). There was no difference in postprandial glycaemia iAUC (P = 0.38), gastric emptying T50 (P = 0.69) or C-peptide iAUC (P = 0.25) after PERT compared to placebo. Decreased FE-1 has a relatively low prevalence in community-based patients with T2DM, and PERT does not reduce postprandial glycaemia in these patients. ACTRN12617000349347.
Publisher: Wiley
Date: 2011
DOI: 10.1111/J.1440-1746.2010.06573.X
Abstract: Diabetic gastroparesis was once thought to be rare, associated with a poor prognosis, and to affect only patients with type 1 diabetes and irreversible autonomic neuropathy. A landmark study conducted by Horowitz et al. and published in JGH in 1986 paved the way for further studies to examine the pathophysiology, natural history and prognosis of diabetic gastroparesis, as well as its optimal management. This review summarizes the developments in knowledge gained over the last ∼25 years that have led to understanding about normal and disordered gastric emptying in diabetes, with a particular emphasis on the inter-relationship between the rate of gastric emptying and the regulation of blood glucose.
Publisher: Springer Science and Business Media LLC
Date: 2009
DOI: 10.1186/CC8021
Publisher: Wiley
Date: 02-2017
DOI: 10.14814/PHY2.13122
Publisher: The Endocrine Society
Date: 08-08-2019
Abstract: It is not known whether glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) levels correlate within in iduals, nor whether levels change with age. Previous studies have all been cross-sectional in design. To evaluate longitudinal changes in fasting and glucose-stimulated incretin hormone concentrations in healthy older subjects. Forty-one healthy older subjects had measurements of plasma GLP-1 and GIP while fasting and after a 75-g oral glucose load on two occasions separated by 5.9 ± 0.1 years [mean age at the initial study: 71.2 ± 3.8 (SD) years]. Breath s les were collected to calculate the gastric 50% emptying time (T50). For GLP-1, both fasting concentrations (P 0.001) and area under the curve 0 to 120 minutes (P = 0.001) were decreased at followup. Fasting GIP was also lower (P = 0.03) at follow up, but there was no change in the area under the curve 0 to 120 minutes (P = 0.26). The gastric emptying T50 was slower at followup (P = 0.008). Neither the change in T50 nor the body mass index at the initial study was a determinant of the change in incretin responses. Between the two study days, fasting GIP (r = 0.72, P 0.001) correlated well, but not fasting GLP-1 (r = 0.23, P = 0.18). However, both glucose-stimulated GLP-1 (r = 0.50, P = 0.002) and GIP (r = 0.60, P 0.001) showed correlations between the initial and follow-up studies. Fasting GIP and glucose-stimulated GLP-1 and GIP concentrations correlate within in iduals over a follow-up period of ∼5.9 years. Aging is associated with reductions in fasting GLP-1 and GIP, and glucose-stimulated GLP-1, which may predispose to the development of glucose intolerance and type 2 diabetes.
Publisher: American Physiological Society
Date: 08-2008
DOI: 10.1152/AJPREGU.00169.2008
Abstract: Postprandial ghrelin suppression arises from the interaction of meal contents with the small intestine and may relate to elevations in blood glucose and/or plasma insulin. We sought to determine whether the suppression of ghrelin by small intestinal glucose is dependent on the glucose load and can be accounted for by changes in blood glucose and/or plasma insulin. Blood glucose, plasma insulin, and plasma ghrelin levels were measured in 10 healthy males (aged 32 ± 4 yr body mass index: 25.1 ± 0.4 kg/m 2 ) during intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2), and 4 kcal/min (G4), as well as intraduodenal hypertonic saline (control) for 120 min. There was a progressive decrease in ghrelin with all treatments, control at 45 min and between 90 and 120 min ( P 0.05) and G1 ( P 0.05), G2 ( P 0.0001), and G4 ( P 0.0001) between 30 and 120 min to reach a plateau at ∼90 min. There was no difference in plasma ghrelin between G1, G2, or G4. Control suppressed ghrelin to a lesser extent than intraduodenal glucose ( P 0.05). The suppression of ghrelin was not related to rises in blood glucose or plasma insulin. Suppression of ghrelin by intraduodenal glucose in healthy males is apparently independent of the glucose load and unrelated to blood glucose or insulin levels.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.DIABRES.2012.02.016
Abstract: Liraglutide reduces bodyweight in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the mechanisms underlying this effect. The comparative effects of liraglutide, glimepiride and placebo on energy intake, appetite, nausea, gastric emptying, antral distension, bodyweight, gastrointestinal hormones, fasting plasma glucose and resting energy expenditure (REE), were assessed in subjects with T2DM randomised to treatment A (liraglutide-placebo), B (placebo-glimepiride) or C (glimepiride-liraglutide). Assessments were performed at the end of each 4-week treatment period. Energy intake was less (NS) with liraglutide vs placebo and glimepiride, and 24-h REE was higher (NS) with liraglutide vs placebo and glimepiride. Fasting hunger was less (p=0.01) with liraglutide vs placebo and glimepiride, and meal duration was shorter with liraglutide (p=0.002) vs placebo. Paracetamol AUC(0-60 min) and C(max) were less (p<0.01) and fasting peptide YY was lower (p ≤ 0.001) after liraglutide vs placebo and glimepiride. Bodyweight reductions of 1.3 and 2.0 kg were observed with liraglutide vs placebo and glimepiride (p<0.001). There were no differences on antral distension, nausea, or other gastro-intestinal hormones. Liraglutide caused decreased gastric emptying and increased reduction in bodyweight. The mechanisms of the liraglutide-induced weight-loss may involve a combined effect on energy intake and energy expenditure.
Publisher: Oxford University Press (OUP)
Date: 23-01-2019
Abstract: The rate of gastric emptying is a major determinant of the hypotensive response to a meal. Cross-sectional studies suggest that healthy aging is associated with a modest slowing of gastric emptying. We aimed to determine longitudinal changes in the blood pressure (BP) response to, and gastric emptying of, glucose in healthy older people. Thirty-three participants (77.0 ± 0.7 years) had baseline and follow-up measurements after 5.8 ± 0.1 years. Participants consumed a 300-mL drink containing 75 g glucose and 150 mg C13-acetate. BP and heart rate (HR) were measured at 5-minute intervals for 120 minutes after the drink. Exhaled breath was collected to calculate the gastric 50% emptying time. The prevalence of postprandial hypotension (PPH) doubled from 9.1% to 18.2%. Gastric emptying was slower at follow-up (p = .04). The fall in systolic BP (SBP) was related directly to the rate of gastric emptying at both the initial study (r = .54, p = .005) and at follow-up (r = .41, p = .04). The change in the maximum fall in SBP was related to the increase in baseline SBP (r = -.63, p < .001). In conclusion, in healthy older people over a period of ~5.8 years, there was an increased prevalence of PPH and a modest slowing of gastric emptying. The latter was related directly to a greater hypotensive response.
Publisher: Elsevier BV
Date: 10-2008
DOI: 10.1016/J.REGPEP.2008.02.006
Abstract: Cells containing GIP and CCK predominate in the upper small intestine, while those containing GLP-1 are located more distally. Our aim was to compare the hormonal, glycemic and appetite responses to different sites of glucose delivery. Ten healthy males were each studied twice, in randomized order. A catheter was positioned with openings 15 cm beyond the pylorus ("duodenal"), and 100 cm beyond ("mid-jejunal"). On one day, glucose was infused into the duodenum (1 kcal/min) and saline into the mid-jejunum, for 90 min. On the other day, the infusion sites were reversed. Blood was s led frequently, and hunger was scored by questionnaires. The tube was removed and energy intake measured from a buffet meal. Stimulation of CCK and suppression of hunger were greater (each P<0.05), and energy intake less (P=0.05), with duodenal compared to mid-jejunal glucose infusion. Blood glucose, GIP, and insulin did not differ, and there was minimal GLP-1 increment on either day. There is regional variation in CCK, but not incretin hormone release, in the upper small intestine, and modest differences in the site of glucose exposure affect appetite and energy intake.
Publisher: American Diabetes Association
Date: 10-05-2014
DOI: 10.2337/DC13-1813
Abstract: Exogenous GLP-1 slows gastric emptying in health and diabetes leading to diminished glycemic excursions. Gastric emptying is markedly accelerated by hypoglycemia. The primary objective was to determine whether GLP-1 attenuates the acceleration of gastric emptying induced by hypoglycemia. Ten healthy volunteers were studied on four separate days in a randomized double-blind fashion. Blood glucose was stabilized using a glucose/insulin cl at hypoglycemia (2.6 mmol/L on two occasions [hypo]) or euglycemia (6.0 mmol/L on two occasions [eu]) between T = −15 and 45 min before cl ing at 6.0 mmol/L until 180 min. During hypoglycemia and euglycemia, subjects received intravenous GLP-1 (1.2 pmol/kg/min) or placebo. At T = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq 99mTc-sulfur-colloid and 3 g of 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from T = 0 to 180 min and serum 3-OMG taken at 15-min intervals. The areas under the curve for gastric emptying and 3-OMG concentration were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. Gastric emptying was accelerated during hypoglycemia (hypo lacebo vs. eu lacebo P & 0.001), as was glucose absorption (P & 0.03). GLP-1 slowed emptying during euglycemia (eu lacebo vs. eu/GLP-1 P & 0.001). However, hypoglycemia-induced acceleration of gastric emptying on placebo was markedly diminished by GLP-1 (hypo lacebo vs. hypo/GLP-1 P & 0.008), as was glucose absorption (P & 0.01). Acute administration of exogenous GLP-1 attenuates, but does not abolish, the acceleration of gastric emptying by insulin-induced hypoglycemia in healthy subjects.
Publisher: Springer Science and Business Media LLC
Date: 08-03-2013
DOI: 10.1007/S00125-013-2876-2
Abstract: Glucagon-like peptide-1 (GLP-1), an important mediator of postprandial glycaemia, could potentially be stimulated by delivering small quantities of nutrient to a long length of distal gut. We aimed to determine whether enteric-coated pellets, releasing small amounts of lauric acid throughout the ileum and colon, could reduce glycaemic responses to meals in type 2 diabetes, associated with stimulation of GLP-1. Eligible patients, who had type 2 diabetes controlled by diet or metformin, were each studied on two occasions in a hospital setting. After an overnight fast, patients consumed 5 g active pellets (47% lauric acid by weight) or placebo with breakfast (T = 0 min) and lunch (T = 240 min), in a crossover design with order randomised by the hospital pharmacy and allocation concealed by numbered containers. Patients and investigators making measurements were blinded to the intervention. Blood was s led frequently for blood glucose (the primary outcome) and hormone assays. Eight patients were randomised (four to receive either intervention first), and all completed the study without adverse effects. Blood glucose was lower after breakfast (T = 0-240 min, area under the curve (AUC) 2,075 ± 368 vs 2,216 ± 163 mmol/l × min) and lunch (T = 240-480 min, AUC 1,916 ± 115 vs 2,088 ± 151 mmol/l × min) (p = 0.02 for each) after active pellets than after placebo. Plasma GLP-1 concentrations were higher after breakfast (p = 0.08) and lunch (p = 0.04) for active pellets. While there were no differences in insulin or glucose-dependent insulinotropic polypeptide concentrations, glucagon concentrations were higher after breakfast and lunch (p = 0.002 for each) for active pellets. Delivering small amounts of nutrient to the ileum and colon can stimulate substantial endogenous GLP-1 release and attenuate postprandial glycaemia. This novel approach has therapeutic potential in type 2 diabetes. Australian New Zealand Clinical Trials Registry ACTRN12612000600842. The study was funded by Meyer Nutriceuticals.
Publisher: Wiley
Date: 21-04-2008
DOI: 10.1111/J.1365-2958.2008.06224.X
Abstract: Post-translational modifications account for much of the biological ersity generated at the proteome level. Of these, glycosylation is the most prevalent. Long thought to be unique to Eukarya, it is now clear that both Bacteria and Archaea are also capable of N-glycosylation, namely the covalent linkage of oligosaccharides to select target asparagine residues. However, while the eukaryal and bacterial N-glycosylation pathways are relatively well defined, little is known of the parallel process in Archaea. Of late, however, major advances have been made in describing the process of archaeal N-glycosylation. Such efforts have shown, as is often the case in archaeal biology, that protein N-glycosylation in Archaea combines particular aspects of the eukaryal and bacterial pathways along with traits unique to this life form. For instance, while the oligosaccharides of archaeal glycoproteins include nucleotide-activated sugars formed by bacterial pathways, the lipid carrier on which such oligosaccharides are assembled is the same as used in eukaryal N-glycosylation. By contrast, transfer of assembled oligosaccharides to their protein targets shows Archaea-specific properties. Finally, addressing N-glycosylation from an archaeal perspective is providing new general insight into this event, as exemplified by the solution of the first crystal structure of an oligosaccharide transferase from an archaeal source.
Publisher: The Endocrine Society
Date: 08-2003
Abstract: This study examined the effects of the lipase inhibitor, orlistat, on gastric emptying of, and the glycemic and incretin hormone responses to, a drink containing oil and glucose components in patients with type 2 diabetes. Seven patients (aged 58 +/- 5 yr), managed by diet alone, consumed 60 ml olive oil (labeled with 20 MBq (99m)Tc-V-thiocyanate) and 300 ml water containing 75 g glucose (labeled with 6 MBq (67)Ga-EDTA), on two occasions, with and without 120 mg orlistat, positioned in the left lateral decubitus position with their back against a gamma camera. Venous blood s les, for measurement of blood glucose and plasma insulin, glucagon-like peptide-1 and glucose-dependent insulintropic polypeptide were obtained immediately before, and after, the drink. Gastric emptying of both oil (P < 0.001) and glucose (P < 0.0005) was faster after orlistat compared with control. Postprandial blood glucose (P < 0.001) and plasma insulin (P < 0.05) were substantially greater after orlistat compared with control. In contrast, plasma glucagon-like peptide-1 (P < 0.005) and glucose-dependent insulintropic polypeptide (P < 0.05) were less after orlistat. In conclusion, inhibition of fat digestion, by orlistat, may exacerbate postprandial glycemia, as a result of more rapid gastric emptying and a diminished incretin response.
Publisher: Springer Science and Business Media LLC
Date: 06-06-2015
DOI: 10.1007/S00125-015-3638-0
Abstract: A postprandial fall in BP occurs frequently in older in iduals and in patients with type 2 diabetes. The magnitude of this decrease in BP is related to the rate of gastric emptying (GE). Intravenous administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal glucose in healthy older in iduals. We sought to determine the effects of exogenous GLP-1 on BP, GE, superior mesenteric artery (SMA) flow and glycaemic response to oral ingestion of glucose in healthy older in iduals and patients with type 2 diabetes. Fourteen older volunteers (six men, eight women age 72.1 ± 1.1 years) and ten patients with type 2 diabetes (six men, four women age 68.7 ± 3.4 years HbA1c 6.6 ± 0.2% [48.5 ± 2.0 mmol/mol] nine with blood glucose managed with metformin, two with a sulfonylurea and one with a dipeptidyl-peptidase 4 inhibitor) received an i.v. infusion of GLP-1 (0.9 pmol kg(-1) min(-1)) or saline (154 mmol/l NaCl) for 150 min (t = -30 min to t = 120 min) in randomised order. At t = 0 min, volunteers consumed a radiolabelled 75 g glucose drink. BP was assessed with an automated device, GE by scintigraphy and SMA flow by ultrasonography. Blood glucose and serum insulin were measured. GLP-1 attenuated the fall in diastolic BP after the glucose drink in older in iduals (p < 0.05) and attenuated the fall in systolic and diastolic BP in patients with type 2 diabetes (p < 0.05). GE was faster in patients with type 2 diabetes than in healthy in iduals (p < 0.05). In both groups, in iduals had slower GE (p < 0.001), decreased SMA flow (p < 0.05) and a lower degree of glycaemia (p < 0.001) when receiving GLP-1. Intravenous GLP-1 attenuates the hypotensive response to orally administered glucose and decreases SMA flow, probably by slowing GE. GLP-1 and 'short-acting' GLP-1 agonists may be useful in the management of postprandial hypotension.
Publisher: The Endocrine Society
Date: 26-07-2017
Publisher: Springer Science and Business Media LLC
Date: 13-07-2006
DOI: 10.1007/S10620-005-9010-3
Abstract: Previous studies suggest that posture has relatively little effect on gastric emptying of high-nutrient liquids these studies have, however, only assessed overall rates of gastric emptying, whereas gastric emptying is known to be predominantly a pulsatile phenomenon. In healthy subjects perceptions of appetite, such as hunger, are inversely related to antral area and content hence, changes in intragastric meal distribution induced by posture may affect appetite. Gastric emptying is a major determinant of postprandial glycemia. The aims of this study were to evaluate the effects of posture on patterns of transpyloric flow (TF), gastric emptying (GE), antral area (AA), hunger, and the glycemic response to oral glucose. Eight healthy young subjects (five males, three females mean age, 24.0 +/- 2.4 years BMI, 21.2 +/- 0.6 kg/m2) were studied twice in random order, once in the sitting position and once in the lying (supine) position. After consuming 600 ml water with 75 g glucose, labeled with 20 MBq 99mTc-sulfur colloid, subjects had simultaneous measurements of (i) TF during consumption of the drink by Doppler ultrasonography, (ii) GE with scintigraphy, (iii) AA at t = -5 and t = 30 min by ultrasonography, and (iv) perceptions of appetite with a visual analogue scale. During drink ingestion TF was greater in the sitting, compared with the lying, position (586 +/- 170 vs. 177 +/- 65 [cm/sec] x sec P < 0.05). Posture affected intragastric distribution more of the drink was retained in the distal stomach in the sitting position (e.g., at 30 min: sitting, 29 +/- 3%, vs. lying, 12 +/- 3% P < 0.0001) but had no effect on the overall rate of GE or the blood glucose response. AA at t = 30 min (P < 0.005) was greater in the sitting position there was an inverse relationship between hunger and AA at 30 min (r = -0.53, P < 0.05). We conclude that posture influences initial TF and intragastric distribution, but not the overall rate of GE of, or the glycemic response to, a large-volume nutrient liquid. The increases in AA and content in the sitting position are associated with a reduction in hunger.
Publisher: American Physiological Society
Date: 15-10-2015
DOI: 10.1152/AJPREGU.00213.2015
Abstract: Protein-rich supplements are used widely for the management of malnutrition in young and older people. Protein is the most satiating of the macronutrients in young. It is not known how the effects of oral protein ingestion on energy intake, appetite, and gastric emptying are modified by age. The aim of the study was to determine the suppression of energy intake by protein compared with control and underlying gastric-emptying and appetite responses of oral whey protein drinks in eight healthy older men (69–80 yr) compared with eight young male controls (18–34 yr). Subjects were studied on three occasions to determine the effects of protein loads of 30 g/120 kcal and 70 g/280 kcal compared with a flavored water control-drink (0 g whey protein) on energy intake (ad libitum buffet-style meal), and gastric emptying (three-dimensional-ultrasonography) and appetite (0–180 min) in a randomized, double-blind, cross-over design. Energy intake was suppressed by the protein compared with control ( P = 0.034). Suppression of energy intake by protein was less in older men (1 ± 5%) than in young controls (15 ± 2% P = 0.008). Cumulative energy intake (meal+drink) on the protein drink days compared with the control day increased more in older (18 ± 6%) men than young (1 ± 3%) controls ( P = 0.008). Gastric emptying of all three drinks was slower in older men (50% gastric-emptying time: 68 ± 5 min) than young controls (36 ± 5 min P = 0.007). Appetite decreased in young, while it increased in older ( P 0.05). In summary, despite having slower gastric emptying, elderly men exhibited blunted protein-induced suppression of energy intake by whey protein compared with young controls, so that in the elderly men, protein ingestion increased overall energy intake more than in the young men.
Publisher: American Diabetes Association
Date: 16-10-2020
DOI: 10.2337/DB20-0361
Abstract: The glucose portal sensor informs the brain of changes in glucose inflow through vagal afferents that require an activated glucagon-like peptide 1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions, and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1–dependent portal glucose signaling was identified, in vivo, using a novel 68Ga-labeled GLP-1r positron-emitting probe that supplied a quantitative in situ tridimensional representation of the portal sensor with specific reference to the receptor density expressed in binding potential units. It also served as a map for single-neuron electrophysiology driven by an image-based abdominal navigation. We determined that in insulin-resistant animals, portal vagal afferents failed to inhibit their spiking activity during glucose infusion, a GLP-1r–dependent function. This reflected a reduction in portal GLP-1r binding potential, particularly between the splenic vein and the entrance of the liver. We propose that insulin resistance, through a reduction in GLP-1r density, leads to functional portal desensitization with a consequent suppression of vagal sensitivity to portal glucose.
Publisher: Springer Science and Business Media LLC
Date: 2002
Abstract: This study evaluated the relationship between gastric emptying and upper gastrointestinal symptoms with H. pylori status in patients with diabetes mellitus. Sixty-three outpatients (44 type 1, 19 type 2, age 45 +/- 1.5 years) underwent measurements of gastric emptying of a mixed solid and liquid meal, gastrointestinal symptoms (gastric and esophageal), glycemic control (HbA1c), and autonomic nerve function. Anti-H. pylori IgG antibodies were quantified using a validated kit. Gastric emptying of solid and/or liquid was delayed in 47 (75%) patients, and 31 (49%) had autonomic neuropathy. Fifteen (24%) of the patients were H. pylori positive. There were no differences in gastric emptying (solid retention at 100 min: 67.5 +/- 5.7% vs 63.2 +/- 3.6% P = 0.63, liquid T50: 35.5 +/- 2.9 min vs 42.5 +/- 3.4 min P = 0.42), upper gastrointestinal symptoms (gastric 3.9 +/- 0.7 vs 4.0 +/- 0.4 P = 0.94 or esophageal 1.7 +/- 0.5 vs 1.3 +/- 0.2 P = 0.42) or HbA1c (8.8 +/- 0.4% vs 8.6 +/- 0.2% P = 0.89) between H. pylori-positive and -negative patients. We conclude that H. pylori infection is not associated with delayed gastric emptying or upper gastrointestinal symptoms in diabetes.
Publisher: MDPI AG
Date: 28-03-2021
DOI: 10.3390/NU13041104
Abstract: Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.
Publisher: MDPI AG
Date: 07-10-2018
DOI: 10.3390/NU10101451
Abstract: Whey protein, when ingested on its own, load-dependently slows gastric emptying and stimulates gut hormone concentrations in healthy young men. The aim of this study was to determine the effects of substitution, and addition, of carbohydrate (dextrose) and fat (olive oil) to whey protein. In randomized, double-blind order, 13 healthy young men (age: 23 ± 1 years, body mass index: 24 ± 1 kg/m2) ingested a control drink (450 mL ~2 kcal/‘control’) or iso-volumetric drinks containing protein/carbohydrate/fat: (i) 14 g/28 g/12.4 g (280 kcal/‘M280′), (ii) 70 g/28 g/12.4 g (504kcal/‘M504′), and (iii) 70 g/0 g/0 g (280 kcal/‘P280′), on 4 separate study days. Gastric emptying (n = 11, 3D-ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK) and glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), appetite (visual analogue scales), and ad-libitum buffet-meal energy intake (180–210 min) were determined. Substitution of protein with carbohydrate and fat was associated with faster gastric emptying (lower 50% emptying time (T50)), reduced suppression of ghrelin, and stimulation of GLP-1 (all P 0.001) while the addition of carbohydrate and fat to protein did not affect gastric emptying or gut hormone responses significantly. Total energy intake (i.e., drink plus meal) was greater after all caloric drinks than control (P 0.001). In conclusion, substitution of whey protein with dextrose and olive oil accelerated gastric emptying. Higher protein content of a mixed macronutrient drink increased gut hormone and insulin responses.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.NUT.2015.11.004
Abstract: Hydroxycitric acid (HCA), derived from the fruit Garcinia cambogia, reduces the rate of glucose absorption and lowers postprandial glycemia in rodents, but its effect in humans is unknown. The aim of this study was to investigate the effects of small intestinal perfusion with HCA on glucose absorption, as well as the incretin and glycemic responses to a subsequent intraduodenal glucose infusion, in both healthy in iduals and patients with type 2 diabetes. Twelve healthy participants and 8 patients with type 2 diabetes received an intraduodenal infusion of HCA (2800 mg in water) or control (water) over 60 min, followed by an intraduodenal infusion of 60 g glucose over 120 min, in a double-blind, randomized crossover design. In healthy in iduals, 5 g 3-O-methylglucose (3-OMG) was co-infused with glucose as a marker of glucose absorption. Blood was s led frequently. In healthy in iduals, blood glucose was lower with HCA than control, both before and during the intraduodenal glucose infusion (P < 0.05 for each). Plasma glucose-dependent insulinotropic polypeptide (GIP P = 0.01) and glucagon (P = 0.06) were higher with HCA, but there were no differences in plasma glucagon-like peptide (GLP)-1, insulin, or serum 3-OMG concentrations. In patients with type 2 diabetes, blood glucose, and plasma GIP, GLP-1, and insulin did not differ between HCA and control either before or after intraduodenal glucose, but during glucose infusion, plasma glucagon was higher with HCA (P = 0.04). In healthy in iduals, small intestinal exposure to HCA resulted in a modest reduction in glycemia and stimulation of plasma GIP and glucagon, but no effect on plasma GLP-1 or insulin, or on glucose absorption. HCA had no effect on glycemia in patients with type 2 diabetes.
Publisher: Wiley
Date: 30-09-2019
DOI: 10.1111/DOM.13864
Abstract: To determine the effects of the dipeptidyl peptidase-4 inhibitor, sitagliptin, on gastric emptying (GE) of a high-carbohydrate meal and associated glycaemic and blood pressure (BP) responses in type 2 diabetes mellitus (T2DM). Fourteen patients with T2DM (nine men, five women age 67.8 ± 1.5 years body mass index 31.2 ± 0.9 kg/m Sitagliptin reduced postprandial plasma glucose (P < .005) without affecting GE (P = .88). The magnitude of the glucose-lowering effect (change in incremental area under the curve In T2DM, while sitagliptin has no effect on either GE or postprandial BP, its ability to lower postprandial glucose are dependent on the basal rate of GE.
Publisher: American Diabetes Association
Date: 13-11-2013
DOI: 10.2337/DC13-0958
Publisher: MDPI AG
Date: 23-01-2018
DOI: 10.3390/NU10020113
Publisher: The Endocrine Society
Date: 09-2015
DOI: 10.1210/JC.2015-2482
Publisher: Springer Science and Business Media LLC
Date: 2012
DOI: 10.1186/CC11522
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PEPTIDES.2016.10.010
Abstract: The importance of the region, as opposed to the length, of small intestine exposed to glucose in determining the secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) remains unclear. We sought to compare the glycemic, insulinemic and incretin responses to glucose administered to the proximal (12-60cm beyond the pylorus), or more distal (>70cm beyond the pylorus) small intestine, or both. 10 healthy subjects (9M,1F aged 70.3±1.4years) underwent infusion of glucose via a catheter into the proximal (glucose proximally GP), or distal (glucose distally GD) small intestine, or both (GPD), on three separate days in a randomised fashion. Blood glucose, serum insulin and plasma GLP-1, GIP and CCK responses were assessed. The iAUC for blood glucose was greater in response to GPD than GP (P<0.05), with no difference between GD and GP. GP was associated with minimal GLP-1 response (P=0.05), but substantial increases in GIP, CCK and insulin (P<0.001 for all). GPD and GD both stimulated GLP-1, GIP, CCK and insulin (P<0.001 for all). Compared to GP, GPD induced greater GLP-1, GIP and CCK responses (P<0.05 for all). Compared with GPD, GD was associated with greater GLP-1 (P<0.05), but reduced GIP and CCK (P<0.05 for both), responses. We conclude that exposure of glucose to the distal small intestine appears necessary for substantial GLP-1 secretion, while exposure of both the proximal and distal small intestine result in substantial secretion of GIP.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.JAMDA.2015.01.097
Abstract: Postprandial hypotension (PPH) occurs frequently in older in iduals with disease and/or living in residential care, but its prevalence in "healthy" older in iduals has not been evaluated in large cohorts. PPH is associated with substantial morbidity and increased mortality current management is suboptimal. Recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is related to the rate of gastric emptying (GE), so that relatively more rapid GE may potentially be a risk factor for PPH. We aimed to determine the prevalence of, and evaluate the association of GE with PPH. A total of 88 healthy "older", community-dwelling residents (47 women, 41 men age 71.0 ± 0.5 years) attended a clinical research laboratory on a single occasion. In iduals consumed a 300 mL drink containing 75 g glucose and 150 mg C(13)-acetate. Exhaled breath was obtained for analysis of (13)CO2 and calculation of the 50% GE time (T50). BP and heart rate were assessed with an automated device. Eleven (12.8%) of 86 subjects had PPH (2 had diabetes and were excluded). GE was faster in subjects with PPH than the remainder of the group (T50 118.0 ± 9.4 vs 142.3 ± 4.6 minutes, P < .05). We conclude the prevalence of PPH in a cohort of otherwise healthy "older" in iduals is 12.8% and PPH is associated with relatively more rapid GE. Therapies that slow GE may be useful in the management of PPH.
Publisher: MDPI AG
Date: 03-05-2022
DOI: 10.3390/NU14091913
Abstract: Postprandial hypotension (PPH) occurs frequently in older people years old. Protein-rich supplements, particularly whey protein (WP), are increasingly used by older people for various health benefits. We have reported that 70 g WP drinks cause significant, and in some cases marked, falls in blood pressure (BP) in older men. The effects of lower, more widely used, doses (~30 g) on systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR) are not known. In a randomized order, eight older men (age: 72 ± 1 years body mass index (BMI): 25 ± 1 kg/m2) after overnight fast ingested a drink containing (i) a non-caloric control (~2 kcal), (ii) 30 g of whey protein (120 kcal ‘WP30’), or (iii) 70 g of whey protein (280 kcal ‘WP70’). The BP and HR were measured in this pilot study with an automated device before and at 3-min intervals for 180 min following drink ingestion. Drink condition effects were determined by repeated-measures ANOVA. The SBP decreased after both WP drinks compared to the control (p = 0.016), particularly between 120 and 180 min, with no difference in the effects of WP30 and WP70. The SBP decreased by ≥20 mmHg in more than 50% of people after both WP drinks (WP30: 63% WP70: 75%) compared to 38% after the control. The maximum fall in the SBP occurred during the third hour, with the nadir occurring latest after WP70. The DBP decreased non-significantly by several mmHg more after the WP drinks than after the control. The maximum HR increases occurred during the third hour, with the greatest increase after WP70. The SBP decreased after both WP drinks compared to the control, with the effects most evident between 120 and 180 min. Accordingly, ingestion of even relatively modest protein loads in older men has the potential to cause PPH.
Publisher: MDPI AG
Date: 25-07-2019
DOI: 10.3390/NU11081717
Abstract: Postprandial hypotension (PPH) is under-recognised, but common, particularly in the elderly, and is of clear clinical importance due to both the independent association between PPH and an increase in mortality and lack of effective management for this condition. Following health concerns surrounding excessive consumption of sugar, there has been a trend in the use of low- or non-nutritive sweeteners as an alternative. Due to the lack of literature in this area, we conducted a systematic search to identify studies relevant to the effects of different types of sweeteners on postprandial blood pressure (BP). The BP response to ingestion of sweeteners is generally unaffected in healthy young subjects, however in elderly subjects, glucose induces the greatest decrease in postprandial BP, while the response to sucrose is less pronounced. The limited studies investigating other nutritive and non-nutritive sweeteners have demonstrated minimal or no effect on postprandial BP. Dietary modification by replacing high nutritive sweeteners (glucose, fructose, and sucrose) with low nutritive (d-xylose, xylitol, erythritol, maltose, maltodextrin, and tagatose) and non-nutritive sweeteners may be a simple and effective management strategy for PPH.
Publisher: MDPI AG
Date: 06-04-2020
DOI: 10.3390/NU12041008
Abstract: Protein-rich supplements are used commonly to increase energy intake in undernourished older people. This study aimed to establish age effects on energy intake, appetite, gastric emptying, blood glucose, and gut hormones in response to protein-rich drinks. In a randomized double-blind, order, 13 older men (age: 75 ± 2 yrs, body mass index (BMI): 26 ± 1 kg/m2) and 13 younger (23 ± 1 yrs, 24 ± 1 kg/m2) men consumed (i) a control drink (~2 kcal) or drinks (450 mL) containing protein/fat/carbohydrate: (ii) 70 g/0 g/0 g (280 kcal/‘P280′), (iii) 14 g/12.4 g/28 g (280 kcal/‘M280′), (iv) 70 g/12.4 g/28 g (504 kcal/‘M504′), on four separate days. Appetite (visual analog scales), gastric emptying (3D ultrasonography), blood glucose, plasma insulin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), and ad-libitum energy intake (180–210 min) were determined. Older men, compared to younger men, had higher fasting glucose and CCK concentrations and lower fasting GLP-1 concentrations (all p 0.05). Energy intake by P280 compared to control was less suppressed in older men (increase: 49 ± 42 kcal) than it was in younger men (suppression: 100 ± 54 kcal, p = 0.038). After the caloric drinks, the suppression of hunger and the desire to eat, and the stimulation of fullness was less (p 0.05), and the stimulation of plasma GLP-1 was higher (p 0.05) in older men compared to younger men. Gastric emptying, glucose, insulin, ghrelin, and CCK responses were similar between age groups. In conclusion, ageing reduces the responses of caloric drinks on hunger, the desire to eat, fullness, and energy intake, and protein-rich nutrition supplements may be an effective strategy to increase energy intake in undernourished older people.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2017
Publisher: The Endocrine Society
Date: 04-2013
DOI: 10.1210/JC.2012-3961
Abstract: In vitro and animal studies suggest that bile acids have the capacity to reduce blood glucose by stimulating glucagon-like peptide-1 (GLP-1) and, thereby, insulin. This study evaluated the effects of intrajejunal taurocholic acid (TCA) on blood glucose, GLP-1, and insulin responses to jejunal glucose infusion in healthy men. Ten healthy men were each studied on 2 days in a double-blind, randomized order. After the subjects fasted overnight, a jejunal catheter was positioned and a balloon inflated 30 cm beyond the pylorus with aspiration of endogenous bile. Two grams TCA in saline, or saline control, was infused beyond the balloon over 30 minutes, followed by 2 g TCA or control, together with 60 g glucose, over the next 120 minutes. Blood was s led frequently for the measurements of blood glucose, total GLP-1, insulin, C-peptide, and glucagon. Intrajejunal infusion of TCA alone (t = -30 to 0 minutes) had no effect on blood glucose, GLP-1, insulin, C-peptide, or glucagon concentrations. During intrajejunal glucose infusion (t = 0 to 120 minutes), blood glucose concentrations were lower (P < .001), and plasma GLP-1 (P < .001) and the C-peptide/glucose ratio (P = .008) were both greater, whereas plasma insulin, C-peptide, and glucagon levels were not significantly different after TCA than after control. In healthy humans, small intestinal infusion of TCA potently reduces the glycemic response to small intestinal glucose, associated with an increase in GLP-1 and C-peptide/glucose ratio. These observations indicate the potential for bile acid-based therapy in type 2 diabetes.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.PEPTIDES.2017.08.001
Abstract: The interaction of nutrients with the small intestine stimulates the secretion of numerous enteroendocrine hormones that regulate postprandial metabolism. However, differences in gastrointestinal hormonal responses between the macronutrients are incompletely understood. In the present study, we compared blood glucose and plasma hormone concentrations in response to standardised intraduodenal (ID) fat and glucose infusions in healthy humans. In a parallel study design, 16 healthy males who received an intraduodenal fat infusion were compared with 12 healthy males who received intraduodenal glucose, both at a rate of 2kcal/min over 120min. Venous blood was s led at frequent intervals for measurements of blood glucose, and plasma total and active glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Plasma concentrations of the incretin hormones (both total and active GLP-1 and GIP) and glucagon were higher, and plasma insulin and blood glucose concentrations lower, during intraduodenal fat, when compared with intraduodenal glucose, infusion (treatment by time interaction: P<0.001 for each). Compared with glucose, intraduodenal fat elicits substantially greater GLP-1, GIP and glucagon secretion, with minimal effects on blood glucose or plasma insulin in healthy humans. These observations are consistent with the concept that fat is a more potent stimulus of the 'gut-incretin' axis than carbohydrate.
Publisher: Wiley
Date: 28-01-2020
DOI: 10.1111/DOM.13956
Abstract: 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. 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 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] 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.
Publisher: Informa UK Limited
Date: 02-2009
Abstract: C ylobacter species are a major cause of disease in mammalian systems. The most common human etiological agent within this genus is C ylobacter jejuni - the leading cause of bacterial gastroenteritis in the developed world. While this organism has been extensively studied at the cellular level, and the genome sequences of several strains have now been elucidated, little is known regarding the role of in idual proteins in virulence processes, such as adhesion, colonization and toxicity towards host cells. Proteomics encompasses the global analysis of proteins at the organism level. The technologies included under this term have now started to be utilized for understanding how C ylobacter species respond to changes in the environment, with an emphasis on the human host, as well as to map subcellular locations of proteins, in particular those that are surface-associated. C. jejuni is also of great significance as, unlike most other bacteria, it is able to post-translationally modify its proteins. The analysis of such proteins represents a major challenge in understanding this organism at the proteomic and cellular levels. This review will examine the state-of-the-art in C ylobacter proteomics, as well as provide insights into strategies that need to be undertaken to provide a comprehensive understanding of this organism at the molecular and functional level.
Publisher: American Physiological Society
Date: 08-2005
Abstract: Postprandial hypotension (PPH) occurs frequently in the elderly the magnitude of the fall in blood pressure (BP) is related to the rate of glucose entry into the duodenum during intraduodenal glucose infusion and spontaneous gastric emptying (GE). It is unclear if glucose concentration affects the hypotensive response. Gastric distension may attenuate PPH therefore, meal volume could influence the BP response. We aimed to determine the effects of 1) drink volume, 2) glucose concentration, and 3) glucose content on the BP and heart rate (HR) responses to oral glucose. Ten subjects (73.9 ± 1.2 yr) had measurements of BP, GE, and blood glucose on 4 days after 1) 25 g glucose in 200 ml (12.5%), 2) 75 g glucose in 200 ml (37.5%), 3) 25 g glucose in 600 ml (4%), and 4) 75 g glucose in 600 ml (12.5%). GE, BP, HR, and blood glucose were measured for 180 min. After all drinks, duodenal glucose loads were similar in the first 60 min. Regardless of concentration, 600-ml (but not 200-ml) drinks initially increased BP, and in the first 30 min, systolic BP correlated ( P 0.01) with volume in both the proximal and total stomach. At the same concentration (12.5%), systolic BP fell more ( P = 0.02) at the smaller volume at the same volumes, there were no effects of concentration on BP. There was no difference in the glycemic response to drinks of identical glucose content. We conclude that 1) ingestion of glucose at a higher volume attenuates and 2) under constant duodenal load, glucose concentration (4–37%) does not affect the fall in BP.
Publisher: Wiley
Date: 24-04-2023
DOI: 10.1111/APT.17499
Abstract: This article is linked to Sanger and Andrews paper. To view this article, visit 0.1111/apt.17466 .
Publisher: MDPI AG
Date: 22-11-2020
DOI: 10.3390/PH13110410
Abstract: Metformin, the most widely prescribed drug therapy for type 2 diabetes, has pleiotropic benefits, in addition to its capacity to lower elevated blood glucose levels, including mitigation of cardiovascular risk. The mechanisms underlying the latter remain unclear. Mechanistic studies have, hitherto, focused on the direct effects of metformin on the heart and vasculature. It is now appreciated that effects in the gastrointestinal tract are important to glucose-lowering by metformin. Gastrointestinal actions of metformin also have major implications for cardiovascular function. This review summarizes the gastrointestinal mechanisms underlying the action of metformin and their potential relevance to cardiovascular benefits.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2008
DOI: 10.1111/J.1572-0241.2008.02041.X
Abstract: In patients with functional dyspepsia (FD), symptoms are frequently triggered, or exacerbated, by fatty foods. We hypothesized that in FD patients, a high-fat (high-FAT) meal would induce more symptoms than a high-carbohydrate (high-CHO) meal, associated with an altered secretion of cholecystokinin (CCK), peptide-YY (PYY), and ghrelin and an increased antral size, when compared to healthy subjects (HS). FD symptoms, appetite perceptions, plasma hormones, and antral area were measured in 8 FD patients and 8 HS on three separate days after the ingestion of high-CHO or high-FAT (500 kcal/400 g) meals, or a low-nutrient control (180 kcal/400 g) the energy intake was quantified 60 min later. Nausea (P < 0.01) and pain (P= 0.05) were greater in FD after the high-FAT, when compared to high-CHO and control meals and in HS. Discomfort was greater after all meals in FD when compared to HS (P < 0.05). Fasting CCK and stimulation of CCK by the high-FAT (P < 0.01) meal were greater in FD, while fasting and postprandial PYY were lower (P < 0.001) in FD than in HS, with no differences in fasting, or postprandial, plasma ghrelin between FD and HS. Fasting antral area was greater in FD (P < 0.05), with no differences postprandially between FD and HS. There were no differences in the energy intake between the two groups. In FD patients: (a) a high-FAT meal induces more symptoms than an isocaloric high-CHO meal, and (b) fasting and postprandial plasma CCK concentrations are greater and PYY concentrations are less. Our findings have important implications for the development of diet-based therapies for the treatment of FD.
Publisher: Wiley
Date: 04-2002
DOI: 10.1113/JPHYSIOL.2001.013442
Abstract: Postprandial hypotension occurs frequently in older people and may lead to syncope and falls. Some recent studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate of gastric emptying. The aim of this study was, therefore, to determine whether the fall in blood pressure induced by intraduodenal glucose is influenced by the rate of nutrient delivery into the small intestine, bypassing the effects of gastric emptying. Eight healthy elderly subjects (four male and four female, age 70.3 +/- 3.4 years) were studied on two separate days, in double-blind, randomised order. Glucose was infused intraduodenally at a rate of either 1 or 3 kcal min(-1), for 60 min, (0-60 min) followed by 0.9 % saline for a further 60 min (60-120 min). Blood pressure and heart rate were recorded at baseline and every 3 min during the study. Blood glucose and plasma insulin were also determined. Only the 3 kcal min(-1) infusion caused a significant fall in systolic (P < 0.001) and diastolic (P < 0.0001) blood pressure and an increase in the heart rate (P < 0.0001). The rises in blood glucose (P < 0.01) and plasma insulin (P < 0.05) concentrations were greater during the 3 kcal min(-1) infusion. We conclude that in healthy older subjects, the magnitude of the fall in blood pressure and increase in heart rate induced by intraduodenal glucose infusion is dependent on the rate of nutrient delivery into the small intestine. These results may have relevance to the treatment of postprandial hypotension.
Publisher: Springer Science and Business Media LLC
Date: 02-2013
DOI: 10.1007/S12325-013-0009-4
Abstract: "Incretin-based" therapies, such as the glucagon-like peptide-1 (GLP-1) receptor agonists, represent a major advance in type 2 diabetes mellitus (T2DM) treatment. GLP-1 receptor agonists differ substantially in their duration of action, frequency of administration and clinical profile. This article reviews the mechanisms of action and clinical evidence for GLP-1 receptor targeting and discusses differences between GLP-1 therapies, focusing particularly on clinical data for the GLP-1 receptor agonist, lixisenatide. GLP-1 therapies target islet cell "defects" of insufficient insulin and excessive glucagon secretion in T2DM, in a glucose-dependent manner, with minimal risk of hypoglycemia. Different GLP-1 therapies exert differential effects on fasting and postprandial glycemia (both being major determinants of glycemic control). They also slow gastric emptying to different extents, probably accounting for different effects to reduce postprandial glycemia. The GetGoal phase 3 studies in T2DM have confirmed the efficacy of once-daily lixisenatide in reducing plasma glucose and glycated hemoglobin (HbA1c), with a pronounced lowering of postprandial plasma glucose (PPG), as monotherapy and as add-on to oral antidiabetic drugs and to basal insulin. Lixisenatide's ability to diminish PPG is probably partly mediated by its marked ability to delay gastric emptying. Lixisenatide is generally well tolerated, with possibly better gastrointestinal tolerability and lower risk of hypoglycemia than exenatide immediate release. Lixisenatide is associated with a beneficial effect on weight, with either no change or a decrease in body weight when administered as add-on therapy to basal insulin in overweight patients with T2DM. Lixisenatide improves glycemic control, by primarily affecting PPG, while preventing weight gain or reducing body weight with a low risk of hypoglycemia in T2DM. Lixisenatide is likely to represent a significant advance in the management of T2DM, perhaps particularly in those patients with relatively faster gastric emptying and lower levels of HbA1c, including those receiving basal insulin.
Publisher: The Endocrine Society
Date: 2010
DOI: 10.1210/JC.2009-1503
Abstract: The role of glucagon-like peptide-1 (GLP-1) in the regulation of gastric emptying is uncertain. The aim of this study was to determine the effects of endogenous GLP-1 on gastric emptying, glucose absorption, and glycemia in health. Ten healthy fasted subjects (eight males, two females 48 +/- 7 yr) received the specific GLP-1 antagonist, exendin(9-39) amide [ex(9-39)NH(2)] (300 pmol/kg x min iv), or placebo, between -30 and 180 min in a randomized, double-blind, crossover fashion. At 0 min, a mashed potato meal ( approximately 2600 kJ) containing 3 g 3-ortho-methyl-D-glucose (3-OMG) and labeled with 20 MBq (99m)Technetium-sulphur colloid was eaten. Gastric emptying, including the time taken for 50% of the meal to empty from the stomach (T50), blood glucose, plasma 3-OMG, and plasma insulin were measured. Ex(9-39)NH(2) accelerated gastric emptying [T50 ex(9-39)NH(2), 68 +/- 8 min, vs. placebo, 83 +/- 7 min P < 0.001] and increased the overall glycemic response to the meal [area under the curve (0-180 min) ex(9-39)NH(2), 1540 +/- 106 mmol/liter x min, vs. placebo, 1388 +/- 90 mmol/liter x min P < 0.02]. At 60 min, ex(9-39)NH(2) increased the rise in glycemia [ex(9-39)NH(2), 9.9 +/- 0.5 mmol/liter, vs. placebo, 8.4 +/- 0.5 mmol/liter P < 0.01], plasma 3-OMG [ex(9-39)NH(2), 0.25 +/- 0.01 mmol/liter, vs. placebo, 0.21 +/- 0.01 mmol/liter P < 0.05], and plasma insulin [ex(9-39)NH(2), 82 +/- 13 mU/liter, vs. placebo, 59 +/- 9 mU/liter P < 0.05] concentrations. There was a close within-subject correlation between glycemia and gastric emptying [e.g. at 60 min, the increment in blood glucose and gastric emptying (T50) r = -0.89 P < 0.001]. GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.
Publisher: Wiley
Date: 02-2018
DOI: 10.14814/PHY2.13610
Publisher: American Diabetes Association
Date: 12-06-2013
DOI: 10.2337/DC12-2294
Abstract: Macronutrient “preloads” can reduce postprandial glycemia by slowing gastric emptying and stimulating glucagon-like peptide-1 (GLP-1) secretion. An ideal preload would entail minimal additional energy intake and might be optimized by concurrent inhibition of dipeptidyl peptidase-4 (DPP-4). We evaluated the effects of a low-energy d-xylose preload, with or without sitagliptin, on gastric emptying, plasma intact GLP-1 concentrations, and postprandial glycemia in type 2 diabetes. Twelve type 2 diabetic patients were studied on four occasions each. After 100 mg sitagliptin (S) or placebo (P) and an overnight fast, patients consumed a preload drink containing either 50 g d-xylose (X) or 80 mg sucralose (control [C]), followed after 40 min by a mashed potato meal labeled with 13C-octanoate. Blood was s led at intervals. Gastric emptying was determined. Both peak blood glucose and the litude of glycemic excursion were lower after PX and SC than PC (P & 0.01 for each) and were lowest after SX (P & 0.05 for each), while overall blood glucose was lower after SX than PC (P & 0.05). The postprandial insulin-to-glucose ratio was attenuated (P & 0.05) and gastric emptying was slower (P & 0.01) after d-xylose, without any effect of sitagliptin. Plasma GLP-1 concentrations were higher after d-xylose than control only before the meal (P & 0.05) but were sustained postprandially when combined with sitagliptin (P & 0.05). In type 2 diabetes, acute administration of a d-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.
Publisher: Wiley
Date: 04-01-2019
DOI: 10.1111/DOM.13604
Abstract: To evaluate the effects of 12 weeks of treatment with a whey/guar preload on gastric emptying, postprandial glycaemia and glycated haemoglobin (HbA1c) levels in people with type 2 diabetes (T2DM). A total of 79 people with T2DM, managed on diet or metformin (HbA1c 49 ± 0.7 mmol/mol [6.6 ± 0.1%]), were randomized, in single-blind fashion, to receive 150 mL flavoured preloads, containing either 17 g whey protein plus 5 g guar (n = 37) or flavoured placebo (n = 42), 15 minutes before two meals, each day for 12 weeks. Blood glucose and gastric emptying (breath test) were measured before and after a mashed potato meal at baseline (without preload), and after the preload at the beginning (week 1) and end (week 12) of treatment. HbA1c levels, energy intake, weight and body composition were also evaluated. Gastric emptying was slower (P < 0.01) and postprandial blood glucose levels lower (P < 0.05) with the whey/guar preload compared to placebo preload, and the magnitude of reduction in glycaemia was related to the rate of gastric emptying at both week 1 (r = -0.54, P < 0.001) and week 12 (r = -0.54, P < 0.0001). At the end of treatment, there was a 1 mmol/mol [0.1%] reduction in HbA1c in the whey/guar group compared to the placebo group (49 ± 1.0 mmol/mol [6.6 ± 0.05%] vs. 50 ± 0.8 mmol/mol [6.7 ± 0.05%] P < 0.05). There were no differences in energy intake, body weight, or lean or fat mass between the groups. In patients with well-controlled T2DM, 12 weeks' treatment with a low-dose whey/guar preload, taken twice daily before meals, had sustained effects of slowing gastric emptying and reducing postprandial blood glucose, which were associated with a modest reduction in HbA1c, without causing weight gain.
Publisher: MDPI AG
Date: 28-07-2022
DOI: 10.3390/NU14153111
Abstract: The ingestion of dietary protein with, or before, carbohydrate may be a useful strategy to reduce postprandial hyperglycemia, but its effect in older people, who have an increased predisposition for type 2 diabetes, has not been clarified. Blood glucose, plasma insulin and glucagon concentrations were measured for 180 min following a drink containing either glucose (120 kcal), whey-protein (120 kcal), whey-protein plus glucose (240 kcal) or control (~2 kcal) in healthy younger (n = 10, 29 ± 2 years 26.1 ± 0.4 kg/m2) and older men (n = 10, 78 ± 2 years 27.3 ± 1.4 kg/m2). Mixed model analysis was used. In both age groups the co-ingestion of protein with glucose (i) markedly reduced the increase in blood glucose concentrations following glucose ingestion alone (p 0.001) and (ii) had a synergistic effect on the increase in insulin concentrations (p = 0.002). Peak insulin concentrations after protein were unaffected by ageing, whereas insulin levels after glucose were lower in older than younger men (p 0.05) and peak insulin concentrations were higher after glucose than protein in younger (p 0.001) but not older men. Glucagon concentrations were unaffected by age. We conclude that the ability of whey-protein to reduce carbohydrate-induced postprandial hyperglycemia is retained in older men and that protein supplementation may be a useful strategy in the prevention and management of type 2 diabetes in older people.
Publisher: American Diabetes Association
Date: 29-05-2020
DOI: 10.2337/DC20-0190
Abstract: Tachyphylaxis for slowing of gastric emptying is seen with continuous exposure to glucagon-like peptide 1 (GLP-1). We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist, lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. A total of 30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75-g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20 μg subcutaneously daily) or placebo, in a double-blind randomized parallel design. Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under the curve [AUC] over 240 min of 2.19 [95% CI 1.82, 2.64], P & 0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P & 0.001) and incremental AUC for blood glucose (P & 0.001). Lixisenatide suppressed both glucagon (P = 0.003) and insulin (P = 0.032), but not endogenous glucose production, over 120 min after oral glucose intake. Postprandial glucose lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = −0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048) but unrelated to β-cell function (assessed by β-cell glucose sensitivity). Eight weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1 receptor agonists therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.
Publisher: American Diabetes Association
Date: 12-07-2016
DOI: 10.2337/DBI16-0023
Publisher: Elsevier BV
Date: 06-2014
DOI: 10.1016/J.JAMDA.2014.01.011
Abstract: Postprandial hypotension (PPH) is an important clinical problem, which has received inappropriately little attention. A systematic search of the databases PubMed, Embase, Cochrane Library, and Web of Knowledge, from their inception to the present time, was conducted to identify studies relevant to the epidemiology, pathophysiology, and/or management of PPH. A total of 417 full-text papers were retrieved from database searching and, following screening, 248 were retained. Of these, 167 papers were considered eligible for inclusion. PPH occurs commonly in older people and represents a major cause of morbidity. Although the pathophysiology of PPH remains poorly defined, erse factors, including impairments in sympathetic and baroreflex function, release of vasodilatory peptides, the rate of small intestinal nutrient delivery, gastric distension, and splanchnic blood pooling, appear important. Current pharmacologic and nonpharmacologic management is suboptimal. Research into the pathophysiology of PPH represents a priority so that management can be targeted more effectively.
Publisher: MDPI AG
Date: 21-08-2020
DOI: 10.3390/PHARMACEUTICS12090790
Abstract: It is now widely appreciated that gastrointestinal function is central to the regulation of metabolic homeostasis. Following meal ingestion, the delivery of nutrients from the stomach into the small intestine (i.e., gastric emptying) is tightly controlled to optimise their subsequent digestion and absorption. The complex interaction of intraluminal nutrients (and other bioactive compounds, such as bile acids) with the small and large intestine induces the release of an array of gastrointestinal hormones from specialised enteroendocrine cells (EECs) distributed in various regions of the gut, which in turn to regulate gastric emptying, appetite and postprandial glucose metabolism. Stimulation of gastrointestinal hormone secretion, therefore, represents a promising strategy for the management of metabolic disorders, particularly obesity and type 2 diabetes mellitus (T2DM). That EECs are distributed distinctively between the proximal and distal gut suggests that the region of the gut exposed to intraluminal stimuli is of major relevance to the secretion profile of gastrointestinal hormones and associated metabolic responses. This review discusses the process of intestinal digestion and absorption and their impacts on the release of gastrointestinal hormones and the regulation of postprandial metabolism, with an emphasis on the differences between the proximal and distal gut, and implications for the management of obesity and T2DM.
Publisher: American Diabetes Association
Date: 13-01-2021
DOI: 10.2337/DCI20-0067
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.AMJMED.2006.02.005
Abstract: Mixed alcoholic drinks are increasingly being consumed in "diet" varieties, which could potentially empty more rapidly from the stomach and thereby increase the rate of alcohol absorption when compared with "regular" versions containing sugar. We studied 8 healthy males twice in randomized order. On each day, they consumed an orange-flavored vodka beverage (30 g ethanol in 600 mL), made with either "regular" mixer containing sucrose (total 478 kcal), or "diet" mixer (225 kcal). Gastric half-emptying time measured by ultrasound (mean+/-standard deviation) was less for the "diet" than the "regular" drink (21.1+/-9.5 vs 36.3+/-15.3 minutes, P <.01). Both the peak blood ethanol concentration (0.053+/-0.006 vs 0.034+/-0.008 g%, P <.001) and the area under the blood ethanol concentration curve between 0 and 180 minutes (5.2+/-0.7 vs 3.2+/-0.7 units, P <.001) were greater with the "diet" drink. Substitution of artificial sweeteners for sucrose in mixed alcoholic beverages may have a marked effect on the rate of gastric emptying and the blood alcohol response.
Publisher: S. Karger AG
Date: 2002
DOI: 10.1159/000051930
Abstract: i Background/Aims: /i The effect of erythromycin on gastric emptying is attenuated during hyperglycaemia. The aim of this study was to determine in patients with diabetic gastroparesis whether the effect of cisapride on gastric emptying of solids and liquids is influenced by the plasma glucose concentration. i Methods: /i Nineteen patients with type 1 diabetes mellitus, who had delayed gastric emptying of solids and/or liquids, were studied. On 2 separate days, each patient received cisapride (20 mg) or placebo orally 60 min before scintigraphic measurement of gastric emptying of a mixed solid (ground beef) and liquid (dextrose) meal. The plasma glucose concentrations were measured at –5, 30, 60, 90, and 120 min during each gastric emptying measurement. i Results: /i Cisapride accelerated both solid (retention at 100 min 43 ± 4 vs. 69 ± 4%, p 0.001) and liquid (T sub /sub 27 ± 2 vs. 39 ± 2 min, p 0.001) gastric emptying. The mean plasma glucose level was not significantly different after placebo when compared with cisapride (19.5 ± 1.1 vs. 18.2 ± 1.0 mmol/l). The change in the 50% emptying time (T sub /sub ) for liquid, but not solid, emptying was related (r = 0.55, p = 0.01) to the change in the plasma glucose AUC from 0 to 30 min between the placebo and cisapride tests, i.e., the acceleration was greater if the plasma glucose concentration was relatively less during the gastric emptying test performed on cisapride. i Conclusion: /i The effect of cisapride on gastric emptying, at least that of liquids, in patients with diabetic gastroparesis appears to be dependent on the plasma glucose concentration.
Publisher: American Diabetes Association
Date: 20-04-2011
DOI: 10.2337/DC11-0195
Publisher: Informa UK Limited
Date: 02-2013
DOI: 10.1586/EGH.12.82
Abstract: Delayed gastric emptying affects a substantial proportion of patients with long-standing diabetes, and when associated with symptoms and/or disordered glycemic control, affects quality of life adversely. Important clinicopathological insights have recently been gained by the systematic analysis of gastric biopsies from patients with severe diabetic gastroparesis, which may stimulate the development of new therapies in the coming decade. Experience with prokinetic therapies and treatments, such as pyloric botulinum toxin injection and gastric electrical stimulation, has established that relief of symptoms does not correlate closely with acceleration of delayed gastric emptying, and that well-designed controlled trials are essential to determine the efficacy of emerging therapies.
Publisher: The Endocrine Society
Date: 24-11-2020
Abstract: 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 (& .9 mmol/L) and 2 (& 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. 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. 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 cl . Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. 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. In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.
Publisher: American Diabetes Association
Date: 13-04-2013
DOI: 10.2337/DC12-1609
Publisher: Wiley
Date: 12-1994
DOI: 10.1111/J.1440-1746.1994.TB01560.X
Abstract: The amino acid tryptophan (tryp) is a potent inhibitor of gastric emptying in both animals and humans. Animal studies suggest that this effect may be specific for the L-enantiomer. The effects of D- and L-tryptophan on gastric emptying, intragastric distribution and appetite in humans were evaluated. Ten volunteers ingested 300 mL of either L-tryp (50 mmol/L), D-tryp (50 mmol/L) or normal saline labelled with 99mTc sulfur colloid on three occasions, separated by between 3 and 7 days. Hunger and fullness were measured with a visual analogue scale at -2, 15, 30 and 60 min after ingestion of each drink. Saline emptied faster from the stomach than both L-tryp and D-tryp (P < 0.05) and D-tryp emptied faster than L-tryp (P < 0.005). Emptying from the proximal stomach was fastest for saline (P < 0.05) and faster for D-tryp than L-tryp (P < 0.005). Emptying from the distal stomach was faster for saline than both D- and L-tryp (P < 0.05). A reduction in hunger (P < 0.05) and a non-significant trend for an increase in fullness were observed after all three drinks. At 60 min, fullness was greater after L-tryp than after ingestion of D-tryp (P < 0.01). These observations indicate that the effect of tryptophan on gastric emptying in humans is stereospecific, consistent with the concept that stereospecific receptors for tryptophan exist in the human small intestine.
Publisher: Wiley
Date: 22-02-2023
DOI: 10.1111/DOM.14983
Abstract: To investigate whether co‐ingestion of dietary protein with, or before, carbohydrate may be a useful strategy to reduce postprandial hyperglycaemia in older men with type 2 diabetes (T2D). Blood glucose, plasma insulin and glucagon concentrations were measured for 180 minutes following ingestion of a drink containing 30 g of glucose (G 120 kcal), 30 g of whey protein (120 kcal), 30 g of glucose plus 30 g of whey protein (GP 240 kcal), or control (~2 kcal) in older men with T2D (n = 10, 77 ± 1 years 31 ± 1.7 kg/m 2 ) and without T2D (n = 10, 78 ± 2 years 27 ± 1.4 kg/m 2 ). Mixed model analysis was used. GP versus G markedly reduced the increase in blood glucose concentrations ( P .001) and had a synergistic effect on the increase in insulin concentrations ( P .001), in men both with and without T2D. Glucose concentrations were higher in men with T2D compared with those without T2D, whereas insulin and glucagon concentrations were largely unaffected by the presence of T2D. Gastric emptying was faster in men with T2D than in those without T2D. The ability of whey protein to reduce carbohydrate‐induced, postprandial hyperglycaemia is retained in older men with T2D compared with those without T2D, and whey protein supplementation may be a useful strategy in the prevention and management of T2D in older people.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2017
Publisher: Wiley
Date: 07-03-2013
DOI: 10.1111/DME.12147
Abstract: To evaluate the prognosis of diabetic gastroparesis. Eighty-six patients with diabetes had measurements of gastric emptying of a mixed meal using a dual isotope test of solid and liquid meal components, mean blood glucose levels, HbA1c , upper gastrointestinal symptoms and autonomic nerve function performed in 1984-1989. These patients were followed up in 2011, after a mean period of ~25 years. Of the 86 patients, gastric emptying of solid (the percentage remaining in the stomach at 100 min) was delayed in 35 (41%), and of liquid (the time taken for 50% of the liquid to empty) was delayed in 38 (44%). In 2011, 53 patients were known to be alive, 29 had died and four were lost to follow-up. In those who had died, both age at baseline (P < 0.001) and the score for autonomic nerve dysfunction (P < 0.001) were greater than those who were alive, while there was no difference in emptying of either the solid or liquid between the two groups. When patients with delayed gastric emptying were ided according to the median value ('delayed' and 'markedly delayed'), mortality tended to be greater in the 'markedly delayed' group for both solids (P = 0.12) and liquids (P = 0.09). Of the 82 patients who could be followed up, 23 of the 35 (66%) with delayed gastric emptying of solid and 25 of 38 (66%) with delayed gastric emptying of liquid were alive. After adjustment for age and autonomic dysfunction, there was no association between gastric emptying of either solid or liquid and death. Over a period of ~25 years, diabetic gastroparesis is apparently not usually associated with a poor prognosis, or increased mortality. T100 min, the percentage remaining in the stomach at 100 mins T50%, the time taken for 50% of the liquid to empty.
Publisher: Springer Science and Business Media LLC
Date: 11-2018
DOI: 10.1038/S41572-018-0038-Z
Abstract: Gastroparesis is a disorder characterized by delayed gastric emptying of solid food in the absence of a mechanical obstruction of the stomach, resulting in the cardinal symptoms of early satiety, postprandial fullness, nausea, vomiting, belching and bloating. Gastroparesis is now recognized as part of a broader spectrum of gastric neuromuscular dysfunction that includes impaired gastric accommodation. The overlap between upper gastrointestinal symptoms makes the distinction between gastroparesis and other disorders, such as functional dyspepsia, challenging. Thus, a confirmed diagnosis of gastroparesis requires measurement of delayed gastric emptying via an appropriate test, such as gastric scintigraphy or breath testing. Gastroparesis can have idiopathic, diabetic, iatrogenic, post-surgical or post-viral aetiologies. The management of gastroparesis involves: correcting fluid, electrolyte and nutritional deficiencies identifying and treating the cause of delayed gastric emptying (for ex le, diabetes mellitus) and suppressing or eliminating symptoms with pharmacological agents as first-line therapies. Several novel pharmacologic agents and interventions are currently in the pipeline and show promise to help tailor in idualized therapy for patients with gastroparesis.
Publisher: Wiley
Date: 17-03-2023
DOI: 10.1111/DOM.15042
Abstract: To evaluate the effect of gastric distension, induced using a gastric ‘barostat’, on the secretion of glucose‐dependent insulinotropic polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) in the presence and absence of small intestinal nutrients in healthy in iduals. Eight healthy participants (two females, six males, mean age 69.3 ± 1.2 years, body mass index 23.5 ± 0.8 kg/m 2 ) were each studied on four occasions when they received an intraduodenal infusion of either (i) 0.9% saline or (ii) glucose delivered at a rate of 3 kcal/min both with, and without, an intragastric balloon with the pressure set to 8 mmHg above the intragastric minimum distending pressure. Following intraduodenal saline or glucose infusion, there was no difference in plasma GLP‐1 with or without gastric distension ( P = 1.00 for both saline and glucose infusions). There was also no difference in plasma GIP with or without gastric distension ( P = 1.00 for saline infusion and P = .99 for glucose infusion). Gastric distension, either alone or during small intestinal glucose exposure, does not stimulate incretin hormone secretion significantly in healthy humans.
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0196-9781(98)00052-7
Abstract: Glucagon-like peptide-1 (GLP-1) may play a role in regulating gastric emptying. The aim of this study was to determine the relationship between gastric emptying of glucose and plasma concentrations of GLP-1. Gastric emptying of 75 g of glucose dissolved in 350 ml of water was measured by the use of scintigraphy in 12 normal volunteers. Venous blood s les for measurement of GLP-1 were obtained immediately before and for 180 min after ingestion of glucose. Plasma GLP-1 rose rapidly from a baseline of 8.5 +/- 1.2 pmol/l to 14.3 +/- 1.3 pmol/l at 10 min (p = 0.024), with a peak of 19.2 +/- 3.0 pmol/l at 30 min (p = 0.0006) after the glucose drink. The rate of gastric emptying was inversely related to the early rise in GLP-1, e.g., the 50% emptying time was related to the change in GLP-1 from baseline at 10 min (r = 0.57 p < 0.05). We conclude that there is an inverse relationship between gastric emptying of glucose and plasma GLP-1. This observation is consistent with the concept that GLP-1 is a determinant of, rather than determined by, the rate of gastric emptying.
Publisher: Informa UK Limited
Date: 17-01-2018
Publisher: American Diabetes Association
Date: 18-10-2021
DOI: 10.2337/DC20-2987
Publisher: Wiley
Date: 14-07-2004
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.REGPEP.2009.11.009
Abstract: In rodents, cephalosporin antibiotics can mimic peptones and stimulate release of cholecystokinin (CCK), a hormone that slows gastric emptying. The rate of gastric emptying is a major determinant of postprandial blood glucose and insulin concentrations. We therefore evaluated the effect of orally administered cefaclor on plasma CCK and gastric emptying, as well as postprandial glycemic and insulinemic responses, in healthy humans. We studied 8 healthy subjects on two days in double-blind, randomized order. On each day, subjects consumed 1000 mg cefaclor or placebo 30 min before a mashed potato meal labeled with (13)C octanoic acid. Blood and breath s les were collected for 4h after the meal. Blood glucose, serum insulin and plasma CCK increased in response to the carbohydrate meal on both study days, and cefaclor had no effect on these responses. Similarly, the gastric half-emptying time (measured by breath test) did not differ (placebo: 137.5+/-6.0 min vs. cefaclor: 143.1+/-8.0 min). Cefaclor, when given before a meal in the form of a capsule, does not stimulate CCK release or slow gastric emptying in healthy humans.
Publisher: American Diabetes Association
Date: 17-07-2014
DOI: 10.2337/DB13-1627
Abstract: The impact of variations in gastric emptying, which influence the magnitude of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) secretion, on glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors is unclear. We evaluated responses to intraduodenal glucose infusion (60 g over 120 min [i.e., 2 kcal/min], a rate that predominantly stimulates GIP but not GLP-1) after sitagliptin versus control in 12 healthy lean, 12 obese, and 12 type 2 diabetic subjects taking metformin 850 mg b.i.d. versus placebo. As expected, sitagliptin augmented plasma-intact GIP substantially and intact GLP-1 modestly. Sitagliptin attenuated glycemic excursions in healthy lean and obese but not type 2 diabetic subjects, without affecting glucagon or energy intake. In contrast, metformin reduced fasting and glucose-stimulated glycemia, suppressed energy intake, and augmented total and intact GLP-1, total GIP, and glucagon in type 2 diabetic subjects, with no additional glucose lowering when combined with sitagliptin. These observations indicate that in type 2 diabetes, 1) the capacity of endogenous GIP to lower blood glucose is impaired 2) the effect of DPP-4 inhibition on glycemia is likely to depend on adequate endogenous GLP-1 release, requiring gastric emptying & kcal/min and 3) the action of metformin to lower blood glucose is not predominantly by way of the incretin axis.
Publisher: American Diabetes Association
Date: 12-02-2018
DOI: 10.2337/DC17-1536
Abstract: If you haven’t measured something, you really don’t know much about it. —Karl Pearson (attributed) Gastrointestinal (GI) symptoms represent an important and often unappreciated cause of morbidity in diabetes, although the significance of this burden across the spectrum of patients and the underlying pathophysiology, including the relationship of symptoms with glycemic control, remain poorly defined. The relevance of GI symptoms and the necessity for their accurate assessment have increased with the greater focus on the gut as a therapeutic target for glucose lowering. This review addresses the prevalence, assessment, pathogenesis, and management of GI symptoms in diabetes, beginning with broad principles and then focusing on specific segments of the GI tract. We initially performed a literature search of PubMed by using synonyms and combinations of the following search terms: “gastrointestinal symptoms”, “diabetes”, “prevalence”, “pathogenesis”, “diagnosis”, and “management”. We restricted the search results to English only. Review papers and meta-analyses are presented as the highest level of evidence where possible followed by randomized controlled trials, uncontrolled trials, retrospective and observational data, and expert opinion.
Publisher: American Diabetes Association
Date: 16-01-2014
DOI: 10.2337/DB13-0893
Abstract: Acute administration of glucagon-like peptide 1 (GLP-1) and its agonists slows gastric emptying, which represents the major mechanism underlying their attenuation of postprandial glycemic excursions. However, this effect may diminish during prolonged use. We compared the effects of prolonged and intermittent stimulation of the GLP-1 receptor on gastric emptying and glycemia. Ten healthy men received intravenous saline (placebo) or GLP-1 (0.8 pmol/kg ⋅ min), as a continuous 24-h infusion (“prolonged”), two 4.5-h infusions separated by 20 h (“intermittent”), and a 4.5-h infusion (“acute”) in a randomized, double-blind, crossover fashion. Gastric emptying of a radiolabeled mashed potato meal was measured using scintigraphy. Acute GLP-1 markedly slowed gastric emptying. The magnitude of the slowing was attenuated with prolonged but maintained with intermittent infusions. GLP-1 potently diminished postprandial glycemia during acute and intermittent regimens. These observations suggest that short-acting GLP-1 agonists may be superior to long-acting agonists when aiming specifically to reduce postprandial glycemic excursions in the treatment of type 2 diabetes.
Publisher: American Physiological Society
Date: 12-2010
Abstract: The contribution of small intestinal motor activity to nutrient absorption is poorly defined. A reduction in duodenal flow events after hyoscine butylbromide, despite no change in pressure waves, was associated with reduced secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and a delay in glucose absorption. The aim of this study was to investigate the effect of metoclopramide on duodenal motility and flow events, incretin hormone secretion, and glucose absorption. Eight healthy volunteers (7 males and 1 female age 29.8 ± 4.6 yr body mass index 24.5 ± 0.9 kg/m 2 ) were studied two times in randomized order. A combined manometry and impedance catheter was used to measure pressure waves and flow events in the same region of the duodenum simultaneously. Metoclopramide (10 mg) or control was administered intravenously as a bolus, followed by an intraduodenal glucose infusion for 60 min (3 kcal/min) incorporating the 14 C-labeled glucose analog 3- O-methylglucose (3-OMG). We found that metoclopramide was associated with more duodenal pressure waves and propagated pressure sequences than control ( P 0.05 for both) during intraduodenal glucose infusion. However, the number of duodenal flow events, blood glucose concentration, and plasma 3-[ 14 C]OMG activity did not differ between the two study days. Metoclopramide was associated with increased plasma concentrations of GLP-1 ( P 0.05) and GIP ( P = 0.07) but lower plasma insulin concentrations ( P 0.05). We concluded that metoclopramide was associated with increased frequency of duodenal pressure waves but no change in duodenal flow events and glucose absorption. Furthermore, GLP-1 and GIP release increased with metoclopramide, but insulin release paradoxically decreased.
Publisher: Springer Science and Business Media LLC
Date: 06-2009
DOI: 10.2165/00003495-200969080-00003
Abstract: Gastric emptying is frequently abnormal in patients with long-standing type 1 and type 2 diabetes mellitus. Symptoms commonly associated with disordered gastric emptying include nausea, vomiting, bloating and epigastric pain, while patients are also at risk of malnutrition, weight loss, impaired drug absorption, disordered glycaemic control and poor quality of life. Although often attributed to the presence of irreversible autonomic neuropathy, acute hyperglycaemia represents a potentially reversible cause of gastric dysfunction in diabetes. Scintigraphy represents the gold standard for measuring gastric emptying. The management of diabetic gastroparesis is less than optimal, partly because the pathogenesis has not been clearly defined. Treatment approaches include dietary modification and optimization of glycaemia, and the use of prokinetic drugs, while novel therapies such as gastric electrical stimulation are the subject of ongoing investigation.
Publisher: Elsevier BV
Date: 10-2014
DOI: 10.1016/J.DIABRES.2014.08.004
Abstract: Metformin was reported to increase plasma intact glucagon-like peptide-1 (GLP-1) concentrations in type 2 diabetes. This is, at least partly, attributable to stimulation of GLP-1 secretion. A reduction in soluble dipeptidyl peptidase-4 activity may also make a modest contribution.
Publisher: Elsevier BV
Date: 12-2010
DOI: 10.1016/J.ECL.2010.08.007
Abstract: Diabetes is the most common cause of gastroparesis and it is now recognized that the relationship between gastric emptying and glycemia is complex and intertwined. Postprandial blood glucose levels influence, and are influenced by, the rate of gastric emptying, highlighting the difficulty in determining which is the cause and which is the effect. Novel diagnostic techniques and therapeutic strategies have been developed for the management of diabetic gastroparesis. This article highlights recent advances in knowledge about diabetic gastroparesis, with an emphasis on the inter-relationships between disordered gastric motor function on glycemia and vice versa, as well as therapeutic strategies for optimizing glycemic control using modulation of gastric emptying.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-2007
Publisher: Wiley
Date: 14-02-2019
DOI: 10.1111/DOM.13633
Abstract: 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). 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. 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). 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.
Publisher: American Physiological Society
Date: 15-12-2014
Abstract: Endothelial function, measured by flow-mediated dilatation (FMD), predicts cardiovascular events and is impaired postprandially. The objective of this study was to evaluate the effects of changes in composition or duration of ingestion of a meal, which slows gastric emptying and/or small intestinal nutrient exposure, on postprandial endothelial function. Twelve healthy subjects (6 male, 6 female 33 ± 6 yr) were each studied on three occasions, in a randomized crossover design. After an overnight fast, subjects consumed a [ 13 C]octanoic acid-labeled mashed potato meal (“ meal 1”), or meal 1 mixed with 9 g guar (“ meal 2”) within 10 min, or meal 1 ided into 12 equal portions over 60 min (“ meal 3”). Brachial artery FMD was measured every 30 min for 120 min. Blood glucose, serum insulin, and gastric emptying (breath test) were evaluated for 240 min. Data are means ± SE. Compared with meal 1, meal 2 was associated with slower gastric emptying (half-emptying time 285 ± 27 vs. 208 ± 15 min, P 0.05), lower postprandial blood glucose and insulin ( P 0.001 for both), and a delayed, but more sustained, suppression of FMD ( P 0.001). After meal 3, both glycemic increment and reduction in FMD were less than after meal 2 ( P 0.05 for both). The decrement in FMD was directly related to the increment in blood glucose ( r = 0.46, P = 0.02). We conclude that, in health, postprandial FMD is influenced by perturbation of gastric emptying and the duration of meal consumption, which also impact on glycemia.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2019
Publisher: American Diabetes Association
Date: 17-07-2014
DOI: 10.2337/DB13-1757
Abstract: The potential influence of gastric emptying on the “incretin effect,” mediated by glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), is unknown. The objectives of this study were to determine the effects of intraduodenal (ID) glucose infusions at 2 (ID2) and 4 (ID4) kcal/min (equating to two rates of gastric emptying within the physiological range) on the size of the incretin effect, gastrointestinal glucose disposal (GIGD), plasma GIP, GLP-1, and glucagon secretion in health and type 2 diabetes. We studied 10 male BMI-matched controls and 11 male type 2 patients managed by diet or metformin only. In both groups, GIP, GLP-1, and the magnitude of incretin effect were greater with ID4 than ID2, as was GIGD plasma glucagon was suppressed by ID2, but not ID4. There was no difference in the incretin effect between the two groups. Based on these data, we conclude that the rate of small intestinal glucose exposure (i.e., glucose load) is a major determinant of the comparative secretion of GIP and GLP-1, as well as the magnitude of the incretin effect and GIGD in health and type 2 diabetes.
Publisher: Wiley
Date: 03-09-2020
DOI: 10.1111/DOM.14166
Publisher: Springer Science and Business Media LLC
Date: 2007
DOI: 10.2165/00003495-200767120-00003
Abstract: Delayed gastric emptying is frequently observed in patients with long-standing type 1 and type 2 diabetes mellitus, and potentially impacts on upper gastrointestinal symptoms, glycaemic control, nutrition and oral drug absorption. The pathogenesis remains unclear and management strategies are currently suboptimal. Therapeutic strategies focus on accelerating gastric emptying, controlling symptoms and improving glycaemic control. The potential adverse effects of hyperglycaemia on gastric emptying and upper gut symptoms indicate the importance of normalising blood glucose if possible. Nutritional and psychological supports are also important, but often neglected. A number of recent pharmacological and non-pharmacological therapies show promise, including gastric electrical stimulation. As with all chronic illnesses, a multidisciplinary approach to management is recommended, but there are few data regarding long-term outcomes.
Publisher: Wiley
Date: 03-05-2006
Publisher: Cambridge University Press (CUP)
Date: 27-04-2010
DOI: 10.1017/S0007114510001327
Abstract: It has been reported that the artificial sweetener, sucralose, stimulates glucose absorption in rodents by enhancing apical availability of the transporter GLUT2. We evaluated whether exposure of the proximal small intestine to sucralose affects glucose absorption and/or the glycaemic response to an intraduodenal (ID) glucose infusion in healthy human subjects. Ten healthy subjects were studied on two separate occasions in a single-blind, randomised order. Each subject received an ID infusion of sucralose (4 m m in 0·9 % saline) or control (0·9 % saline) at 4 ml/min for 150 min ( T = − 30 to 120 min). After 30 min ( T = 0), glucose (25 %) and its non-metabolised analogue, 3- O -methylglucose (3-OMG 2·5 %), were co-infused intraduodenally ( T = 0–120 min 4·2 kJ/min (1 kcal/min)). Blood was s led at frequent intervals. Blood glucose, plasma glucagon-like peptide-1 (GLP-1) and serum 3-OMG concentrations increased during ID glucose/3-OMG infusion ( P 0·005 for each). However, there were no differences in blood glucose, plasma GLP-1 or serum 3-OMG concentrations between sucralose and control infusions. In conclusion, sucralose does not appear to modify the rate of glucose absorption or the glycaemic or incretin response to ID glucose infusion when given acutely in healthy human subjects.
Publisher: Wiley
Date: 30-01-2019
DOI: 10.1111/DOM.13632
Abstract: Metformin has been shown to modulate the cardiovascular response to intraduodenal glucose in patients with type 2 diabetes (T2DM), and may have the capacity to regulate postprandial blood pressure (BP), which is often inadequately compensated in T2DM, resulting in postprandial hypotension. In the present study, we evaluated the acute effects of metformin on the BP and heart rate (HR) responses to oral glucose in patients with T2DM. Ten diet-controlled T2DM patients were evaluated on two occasions in a double-blind, randomized, crossover design. Participants received either metformin 1 g or saline (control) intraduodenally 60 minutes before ingesting a 50 g glucose drink labelled with 150 mg
Publisher: American Physiological Society
Date: 02-2013
DOI: 10.1152/AJPENDO.00533.2012
Abstract: Observations relating to the impact of obesity on gastric emptying (GE) and the secretion of gut hormones are inconsistent, probably because of a lack of studies in which GE, gastrointestinal hormone release, and energy intake (EI) have been evaluated concurrently with previous patterns of nutrient intake. GE is known to be a major determinant of postprandial glycemia and incretin secretion in health and type 2 diabetes. The aims of this study were to determine the effects of a mixed-nutrient drink on GE, oro-cecal transit, blood glucose, insulin and incretin concentrations and EI, and the relationship between the glycemic response to the drink with GE in lean, overweight, and obese subjects. Twenty lean, 20 overweight, and 20 obese males had measurements of GE, oro-cecal transit, and blood glucose, insulin, GLP-1, and GIP concentrations for 5 h after ingestion of a mixed-nutrient drink (500 ml, 532 kcal) EI at a subsequent buffet lunch was determined. Habitual EI was also quantified. Glycemic and insulinemic responses to the drink were greater in the obese (both P 0.05) when compared with both lean and overweight, with no significant differences in GE, intragastric distribution, oro-cecal transit, incretins, or EI (buffet lunch or habitual) between groups. The magnitude of the rise in blood glucose after the drink was greater when GE was relatively more rapid ( r = −0.55, P 0.05). In conclusion, in the absence of differences in habitual EI, both GE and incretin hormones are unaffected in the obese despite greater glucose and insulin responses, and GE is a determinant of postprandial glycemia.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 08-1999
DOI: 10.1111/J.1572-0241.1999.01280.X
Abstract: The aim of this study was to determine whether variations in the blood glucose concentration within the normal postprandial range affect the gastrokinetic action of erythromycin. Six healthy male volunteers, aged 20-33 yr underwent measurements of gastric emptying on 2 separate days blood glucose concentrations were maintained at approximately 4 mmol/L (72 mg/dl) on 1 day and at 8 mmol/L (144 mg/dl) on the other. The order of the two studies was randomized and they were separated by 4-7 days. On both days, erythromycin (3 mg/kg) was administered intravenously over 15 min immediately before consumption of 300 g minced beef labeled with 20 MBq 99mTc-sulphur colloid chicken liver and 150 ml water labeled with 67Ga-EDTA. Gastric emptying of solid (p < 0.05) and liquid (p < 0.0001) were slower at a blood glucose concentration of 8 mmol/L (144 mg/dl) when compared to 4 mmol/L (72 mg/dl). The slowing of gastric emptying was associated with greater retention of both solid and liquid in the proximal (p < 0.06) and distal (p < 0.01) stomach. After administration of erythromycin, gastric emptying and intragastric distribution of solids and liquids is influenced by physiological changes in the blood glucose concentration.
Publisher: Wiley
Date: 04-06-2015
DOI: 10.1111/DME.12802
Abstract: In healthy subjects, the oral disposition index (ratio of insulin response to insulin sensitivity) is predictive of the development of Type 2 diabetes. Gastric emptying, which exhibits a substantial interin idual variation, is a major determinant of postprandial glycaemia in health and diabetes. We sought to determine whether the rate of intraduodenal glucose delivery affects the disposition index in people without diabetes. Nineteen Caucasian males received glucose infusions via an intraduodenal catheter at either 2 kcal/min (ID2) or 4 kcal/min (ID4) for 120 min, on two separate days with measurements of blood glucose (G) and plasma insulin (I) at frequent intervals. The insulin response was estimated by the ratio of the change in insulin to that of change in glucose at 30 min (∆I(0-30)/∆G(0-30)) and 60 min (∆I(0-60)/∆G(0-60)). Insulin sensitivity was estimated as 1/fasting insulin. The oral disposition index (DI) was calculated as ∆I(0-30)/∆G(0-30) × 1/fasting insulin and ∆I(0-60)/∆G(0-60) × 1/fasting insulin. The overall glycaemic response was comparable on both days, but the insulin response was much greater at ID4 when calculated at either 30 or 60 min (P < 0.05). DI was also greater (P < 0.05) in response to ID4 than ID2. The rate of duodenal glucose delivery has a major impact on insulin release and, thereby, DI. This suggests that the rate of gastric emptying, which determines duodenal glucose delivery, is a determinant of DI.
Publisher: Wiley
Date: 28-06-2012
DOI: 10.1111/J.1365-2036.2012.05198.X
Abstract: The rate of gastric emptying (GE) and subsequent release of the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are critical determinants of postprandial glycaemia in health and type 2 diabetes. Slowing of GE may be the dominant mechanism by which exogenous GLP-1, and some GLP-1 analogues, improve postprandial glycaemia. To determine the effect of sitagliptin on GE in healthy subjects, and the relationships between GE with glycaemia and incretin hormone secretion. Fifteen volunteers (22.8 ± 0.7 years) were studied on two occasions following 2 days dosing with sitagliptin (100 mg/day) or placebo. GE (scintigraphy), glycaemia and plasma GLP-1 and GIP (total and intact), insulin and glucagon were measured for 240 min following a mashed potato meal (1808 kJ). There was no difference in GE between sitgaliptin and placebo [50% emptying time (T50): P = 0.4]. Mean blood glucose was slightly less (P = 0.02) on sitagliptin. Sitagliptin reduced plasma glucagon between 75 and 120 min (P < 0.05), and increased intact GLP-1 (P = 0.0002) and intact GIP (P = 0.0001) by approximately twofold, but reduced total GIP (P = 0.0003) and had no effect on total GLP-1 (P = 0.16) or insulin (P = 0.75). On sitagliptin the initial rise in blood glucose (r = -0.66, P = 0.008) and the intact GIP response (r = -0.66, P = 0.007) were inversely related, whereas the intact GLP-1 response was related directly (r = 0.52, P = 0.05) to the T50. While the effects of sitagliptin on glycaemic control are unlikely to relate to slowing of GE in healthy humans, the rate of GE is a significant determinant of postprandial glycaemia on sitagliptin.
Publisher: Wiley
Date: 11-2014
DOI: 10.14814/PHY2.12204
Publisher: Springer Science and Business Media LLC
Date: 29-07-1999
Abstract: Many radiopharmaceuticals and test meals that are used to measure gastric emptying are less than optimal. A vegetable-based solid meal, such as rice, labelled with a radiopharmaceutical that also has the capacity to measure gastric emptying of liquids, is likely to be ideal. The role of Technegas as a radioisotopic marker to measure gastric emptying of rice and liquids was evaluated. Technegas-labelled rice was incubated in 0.9% saline, 1 M HCl and simulated gastric fluid (3.2 g/l pepsinogen, pH 2-3) to assess stability of the label. In eight healthy volunteers gastric emptying of two meals - 200 g rice (370 kcal) and 75 g dextrose dissolved in 300 ml water (300 kcal), both labelled with 20 MBq of Technegas - was measured scintigraphically. Over 4 h, the average label stability was 93.7%+/-0.5% in 0.9% saline, 91.0%+/-0.4% in 1 M HCl and 93.6%+/-0.7% in simulated gastric juice. The lag phase was longer for rice than dextrose (25+/-7 min vs 4+/-2 min P<0.05), but there was no difference in the post-lag emptying rate (2.1+/-0.3 kcal/min vs 1.7+/-0.2 kcal/min P=0.2) between the two meals. We conclude that Technegas is a suitable radiopharmaceutical for measurement of gastric emptying of rice and nutrient-containing liquids.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2010
Publisher: Informa Healthcare
Date: 11-05-2013
DOI: 10.1517/14656566.2013.795948
Abstract: Gastroparesis is an important clinical disorder characterised by delayed gastric emptying in the absence of mechanical outlet obstruction. Idiopathic, diabetes and postsurgical causes represent the most common aetiologies. The condition commonly manifests as upper gastrointestinal symptoms, including nausea, vomiting, postprandial fullness, early satiety, abdominal pain and bloating. This paper provides a review of the prevalence, pathophysiology and clinical features associated with gastroparesis, with a particular focus on current pharmacological management options and novel and emerging therapies. A literature search was undertaken using the search terms: gastroparesis, diabetic gastroparesis, idiopathic gastroparesis, gastric emptying, prokinetic, metoclopramide, domperidone, erythromycin, motilin, alemcinal, KC11458, mitemcinal, ghrelin, TZP-101, TZP-102, RM-131, tegaserod, prucalopride, naronapride, velusetrag, levosulpiride, itopride, botulinum toxin, gastric electrical stimulation, Enterra. Strategies for the management of gastroparesis include correction of malnutrition, dehydration and electrolyte imbalance, relief of symptoms by appropriate use of prokinetic and antiemetic agents and, in patients with gastroparesis associated with diabetes or critical illness-induced hyperglycaemia, optimisation of glycaemic control. Conventional prokinetic agents form the mainstay of treatment. While novel pharmacotherapies are in development, compelling evidence for their efficacy, particularly in symptom relief, remains to be established.
Publisher: Wiley
Date: 25-05-2022
DOI: 10.1111/DOM.14730
Abstract: Cholecystectomy has been reported to be associated with increased risk of diabetes in cross‐sectional studies. In the current study, we performed both cross‐sectional and prospective analyses to examine the association between cholecystectomy and dysglycaemia in Chinese community‐dwelling adults. A total of 1612 participants (n = 1564 without cholecystectomy and n = 48 with cholecystectomy) were evaluated for glycaemic status (according to the World Health Organization (WHO) 1999 criteria) and then followed up over ~3.2 years. Percent changes (Δ) in fasting blood glucose and HbA1c from baseline at the follow‐up visit were calculated to define glycaemic control as stable (−10% ≤ Δ 10%), improved (Δ −10%), or worsened (Δ ≥ 10%). The baseline cross‐sectional analyses indicated that cholecystectomy was associated with an increased risk of both prediabetes and diabetes, while the prospective analysis indicated that cholecystectomy was also associated with a greater risk of deterioration in glycaemic control (ΔFPG ≥10% and ΔHbA1c ≥10%) ( P 0.05 for each, both before and after adjusting for potential confounding covariates). These observations suggest that in iduals in the Chinese community‐dwelling population who have undergone cholecystectomy are at increased risk of dysglycaemia. Further studies are warranted to both delineate the underlying mechanisms and to clarify whether more intense surveillance for future development of diabetes is needed in this group.
Publisher: Springer Science and Business Media LLC
Date: 06-12-2016
DOI: 10.1038/IJO.2016.202
Abstract: Studies concerning the glycaemic response to oral glucose, or meals in obesity have usually failed to account for gastric emptying. It has been suggested that the incretin effect may be diminished in obesity as a result of a reduction in glucagon-like peptide-1 (GLP-1) secretion. We sought to determine the effect of two different rates of intraduodenal glucose infusions on glycaemic, insulinaemic and incretin hormone responses in lean and obese subjects and compare the effects of oral and intraduodenal glucose in obese subjects. Eleven obese subjects (age 37.5±4.1 years, body mass index (BMI) 35.7±1.4 kg m In both the groups (P<0.001), the incremental areas under the curve (iAUC) The rate of duodenal glucose delivery is a major determinant of glycaemia, insulinaemia and incretin hormone release in obese subjects. Obesity is not apparently associated with impaired GLP-1 secretion.
Publisher: American Diabetes Association
Date: 02-1999
Abstract: OBJECTIVE: The major aims of this study were to determine in normal subjects whether the effects of erythromycin on gastric emptying, postprandial hunger, and fullness are modified by the blood glucose concentration. RESEARCH DESIGN AND METHODS: A total of 10 normal subjects (aged 20-39 years) underwent concurrent measurements of gastric emptying, blood glucose, hunger, and fullness on four separate occasions: twice during euglycemia (approximately 4 mmol/l) and twice during hyperglycemia (approximately 15 mmol/l). Either erythromycin (3 mg/kg) or saline (0.9%) was administered intravenously immediately before ingestion of a radioisotopically labeled solid meal. RESULTS: Gastric emptying was slower (P & 0.0001) during hyperglycemia when compared with euglycemia after both erythromycin and saline administration. During hyperglycemia, erythromycin reduced the lag phase (77.8 +/- 12.6 vs. 20.3 +/- 7.3 min P & 0.05) but had no effect on the postlag emptying rate (0.32 +/- 0.077% per min vs. 0.24% per min). Hunger decreased (P & 0.001) and fullness increased (P & 0.001) after the meal. Postprandial hunger was less during hyperglycemia after saline infusion (P & 0.05) but not after erythromycin. Hunger was greater after erythromycin during both hyperglycemia and euglycemia (P & 0.05). CONCLUSIONS: At a blood glucose concentration of approximately 15 mmol/l, 1) gastric emptying of a solid meal is slower, when compared with euglycemia, even after administration of erythromycin 2) the effect of erythromycin on gastric emptying of a solid meal is attenuated and 3) the perception of postprandial hunger is reduced.
Publisher: American Diabetes Association
Date: 17-03-2015
DOI: 10.2337/DC14-3091
Abstract: Acute hyperglycemia markedly slows gastric emptying. Exogenous GLP-1 also slows gastric emptying, leading to diminished glycemic excursions. The primary objective was to determine whether hyperglycemia potentiates the slowing of gastric emptying induced by GLP-1 administration. Ten healthy participants were studied on 4 separate days. Blood glucose was cl ed at hyperglycemia using an intravenous infusion of 25% dextrose (∼12 mmol/L hyper) on 2 days, or maintained at euglycemia (∼6 mmol/L eu) on 2 days, between t = −15 and 240 min. During hyperglycemic and euglycemic days, participants received intravenous GLP-1 (1.2 pmol/kg/min) and placebo in a randomized double-blind fashion. At t = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq technetium-99m–sulfur colloid and 3 g 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from t = 0 to 240 min and serum 3-OMG taken at regular intervals from t = 15 to 240 min. The areas under the curve for gastric emptying and 3-OMG were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. Hyperglycemia slowed gastric emptying (eu lacebo vs. hyper lacebo P & 0.001) as did GLP-1 (eu lacebo vs. eu/GLP-1 P & 0.001). There was an additive effect of GLP-1 and hyperglycemia, such that gastric emptying was markedly slower compared with GLP-1 administration during euglycemia (eu/GLP-1 vs. hyper/GLP-1 P & 0.01). Acute administration of exogenous GLP-1 profoundly slows gastric emptying during hyperglycemia in excess of the slowing induced by GLP-1 during euglycemia. Studies are required to determine the effects of hyperglycemia on gastric emptying with the subcutaneously administered commercially available GLP-1 agonists in patients with type 2 diabetes.
Publisher: Elsevier BV
Date: 10-2002
DOI: 10.1016/S0002-9343(02)01228-7
Abstract: To evaluate the natural history of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. We enrolled 20 patients (6 men, 14 women) with diabetes mellitus (16 with type 1 diabetes, 4 with type 2 diabetes). Each had measurements of gastric emptying of a solid (100 g of ground beef) and liquid (150 mL of 10% dextrose) meal using scintigraphy, glycemic control (glycosylated hemoglobin [HbA(1c)] and mean blood glucose levels), upper gastrointestinal symptoms, and autonomic nerve function at baseline and after a mean (+/- SD) of 12.3 +/- 3.1 years of follow-up. There were no differences in mean gastric emptying of the solid component (retention at 100 minutes at baseline: 56% +/- 19% vs. follow-up: 51% +/- 21%, P = 0.23) or the liquid component (time for 50% to empty at baseline: 33 +/- 11 minutes vs. follow-up: 31 +/- 12 minutes, P = 0.71) during follow-up. Mean blood glucose (17.0 +/- 5.6 mmol/L vs. 13.8 +/- 4.9 mmol/L, P = 0.007) and HbA(1c) (8.4% +/- 2.3% vs. 7.6% +/- 1.3%, P = 0.03) levels were lower at follow-up. There was no difference in symptom score (baseline: 3.9 +/- 2.7 vs. follow-up: 4.2 +/- 4.0, P = 0.78). There was evidence of autonomic neuropathy in 7 patients (35%) at baseline and 16 (80%) at follow-up. In patients with diabetes mellitus, we did not observe any marked changes in either gastric emptying or upper gastrointestinal symptoms during a 12-year period.
Publisher: Springer Science and Business Media LLC
Date: 02-2006
DOI: 10.1007/S10286-006-0308-9
Abstract: Gastric emptying (GE) of a solid (100 g beef) and liquid (150 ml 10 % dextrose) meal was measured in eight patients with type 1 diabetes during intravenous infusion of C-peptide (6 pmol/kg/ min) or isotonic saline. C-peptide had no effect on either solid or liquid GE.
Publisher: American Diabetes Association
Date: 11-2004
Publisher: Springer Science and Business Media LLC
Date: 13-07-2018
DOI: 10.1038/S41387-018-0048-7
Abstract: Protein supplements, usually drinks rich in whey protein, are used widely for weight loss purposes in overweight adults. Information comparing the effects of whey protein on appetite and energy intake in men and women is limited. The objective was to compare the acute effects of whey-protein intake on energy intake, appetite, gastric emptying and gut hormones in healthy young men and women. Gastric emptying (3D-ultrasonography), blood glucose and plasma insulin, glucagon, ghrelin, cholecystokinin (CCK), gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) concentrations (0–180 min), appetite (visual analogue scales), and ad libitum energy intake from a buffet meal (180–210 min) were determined after ingestion of 30 g (120 kcal) or 70 g (280 kcal) whey protein, or a flavoured-water control drink (~2 kcal) in 8 healthy young men (25 ± 2 y, 72 ± 3 kg, 23 ± 1 kg/m 2 ) and 8 women (23 ± 1 y, 64 ± 2 kg, 24 ± 0.4 kg/m 2 ). There was a protein-load effect on gastric emptying, blood glucose, plasma insulin, glucagon, ghrelin, CCK, GIP and GLP-1 concentrations, and perceptions of hunger, desire to eat and prospective food consumption ( P 0.05). Ad libitum energy intake (average decrease of 206 ± 39 kcal (15 ± 2%) for men and of 46 ± 54 kcal (0 ± 26%) for women for the mean of the intakes after the 30 and 70 g whey-protein loads) and hunger were suppressed more by whey-protein ingestion in men than women ( P = 0.046). There was no difference in suppression of energy intake between the 30 and 70 g protein loads ( P = 0.75, interaction effect P = 0.19). Consequently, total energy intake (protein drink plus buffet meal) increased more compared to control in women than men ( P = 0.010). The drinks emptied more slowly, and plasma glucagon, CCK and GLP-1 increased less after the protein drinks, in women than men ( P 0.05). The acute effects of whey protein ingestion on appetite, energy intake, gastric emptying and gut hormone responses are influenced by gender in healthy young adults.
Start Date: 2009
End Date: 2012
Funder: National Health and Medical Research Council
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