Significant Delay In Gastric Emptying Research Articles

Quantified Metrics of Gastric Emptying Delay by Glucagon-Like Peptide-1 Agonists: A Systematic Review and Meta-Analysis With Insights for Periprocedural Management.

Divergent recommendations for periprocedural management of glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA) medications rely on limited evidence. We performed a systematic review and meta-analysis to provide quantitative measures of gastric emptying relevant to mechanisms of weight loss and to periprocedural management of GLP-1 RA. We hypothesized that the magnitude of gastric emptying delay would be low and of limited clinical significance to procedural sedation risks. A protocolized search identified studies on GLP-1 RA that quantified gastric emptying measures. Pooled estimates using random effects were presented as a weighted mean difference with 95% confidence intervals (CIs). Univariate meta-regression was performed to assess the influence of GLP-1 RA type, short-acting vs long-acting mechanism of action, and duration of treatment on gastric emptying. Fifteen studies met the inclusion criteria. Five studies (n = 247) utilized gastric emptying scintigraphy. Mean T 1/2 was 138.4 minutes (95% CI 74.5-202.3) for GLP-1 RA vs 95.0 minutes (95% CI 54.9-135.0) for placebo, with a pooled mean difference of 36.0 minutes (95% CI 17.0-55.0, P < 0.01, I2 = 79.4%). Ten studies (n = 411) utilized the acetaminophen absorption test, with no significant delay in gastric emptying measured by T max , area under the curve (AUC) 4hr , and AUC 5hr with GLP-1 RA ( P > 0.05). On meta-regression, the type of GLP-1 RA, mechanism of action, and treatment duration did not impact gastric emptying ( P > 0.05). While a gastric emptying delay of ∼36 minutes is quantifiable on GLP-1 RA medications, it is of limited magnitude relative to standard periprocedural fasting periods. There were no substantial differences in gastric emptying on modalities reflective of liquid emptying (acetaminophen absorption test), particularly at time points relevant to periprocedural care.

Bariatric endoscopic antral myotomy: first-in-human proof of concept of a novel therapeutic method to delay gastric emptying and induce weight loss

Bariatric endoscopic antral myotomy: first-in-human proof of concept of a novel therapeutic method to delay gastric emptying and induce weight loss

Metformin acts as a dual glucose regulator in mouse brain.

Aims: Metformin improves glucose regulation through various mechanisms in the periphery. Our previous study revealed that oral intake of metformin activates several brain regions, including the hypothalamus, and directly activates hypothalamic S6 kinase in mice. In this study, we aimed to identify the direct effects of metformin on glucose regulation in the brain. Materials and methods: We investigated the role of metformin in peripheral glucose regulation by directly administering metformin intracerebroventricularly in mice. The effect of centrally administered metformin (central metformin) on peripheral glucose regulation was evaluated by oral or intraperitoneal glucose, insulin, and pyruvate tolerance tests. Hepatic gluconeogenesis and gastric emptying were assessed to elucidate the underlying mechanisms. Liver-specific and systemic sympathetic denervation were performed. Results: Central metformin improved the glycemic response to oral glucose load in mice compared to that in the control group, and worsened the response to intraperitoneal glucose load, indicating its dual role in peripheral glucose regulation. It lowered the ability of insulin to decrease serum glucose levels and worsened the glycemic response to pyruvate load relative to the control group. Furthermore, it increased the expression of hepatic G6pc and decreased the phosphorylation of STAT3, suggesting that central metformin increased hepatic glucose production. The effect was mediated by sympathetic nervous system activation. In contrast, it induced a significant delay in gastric emptying in mice, suggesting its potent role in suppressing intestinal glucose absorption. Conclusion: Central metformin improves glucose tolerance by delaying gastric emptying through the brain-gut axis, but at the same time worsens it by increasing hepatic glucose production via the brain-liver axis. However, with its ordinary intake, central metformin may effectively enhance its glucose-lowering effect through the brain-gut axis, which could surpass its effect on glucose regulation via the brain-liver axis.

1203 Low Viscosity Soluble Dietary Fibre for Gastroparesis Sufferers

INTRODUCTION: Gastroparesis is a chronic idiopathic disorder which affects 125,000 people in Australia. The symptoms of gastroparesis can range from mild to very severe. Current management of gastroparesis involves enteral strategies such as prescription drugs, feeding tubes using jejunostomy and gastric electric simulation (GES). Medical practitioners currently recommend that gastroparesis sufferers take little to no fibre in their diet regardless of the severity of their symptoms but low-viscosity soluble fibres have been proposed as a solution for dietary fibre intake in mild to moderate gastroparesis sufferers. METHODS: The rheological properties of ten soluble dietary fibres were studied under normal and simulated gastric conditions. A clinical trial involving two soluble fibres (test fibres), one partially-soluble fibre (positive control) and no fibre (negative control) was approved under the UID H12254 at Western Sydney University, AUS. The clinical trial is used to study blood glucose absorption, symptoms and mouth-to-caecum emptying times of eligible patients after consumption of soluble dietary fibres under controlled conditions. The polysaccharide chain length and monosaccharide unit composition in these dietary fibres will be analysed using Q-ToF-MS. RESULTS: The rheological stress σ (Pa) at the visco-elastic relaxation modulus Gc under normal and simulated gastric conditions was characterised for 10 different fibres. There was a significant reduction in the rheological stress from normal to gastric conditions for three low-stress soluble fibres. Two of those three low-stress fibres and one medium-stress fibre were selected for the clinical trial. Preliminary results of the clinical trial (6 patients) indicate that most patients find the low-stress fibres more palatable than the medium-stress fibre based on the Gastroparesis Cardinal symptom Index (GCSI). No significant differences in postprandial blood glucose absorption over 3 hours were observed for both the low-stress and medium-stress fibres. The low-stress fibres also show no significant delay in gastric emptying up to 3 hours compared to the negative control using hydrogen breath test analysis. CONCLUSION: The preliminary results of the rheology and the clinical trial indicate that soluble fibres could be incorporated into the diet of a gastroparesis patient. We hope to summarize the rheological, chemical and clinical data about these fibres and provide the relevant information to dieticians and gastroenterologists.

A novel calcimimetic agent, evocalcet (MT-4580/KHK7580), suppresses the parathyroid cell function with little effect on the gastrointestinal tract or CYP isozymes in vivo and in vitro.

Cinacalcet hydrochloride (cinacalcet), an oral calcimimetic agent has been widely used for the management of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD). In sharp contrast to vitamin D receptor activators, cinacalcet suppresses SHPT without inducing hypercalcemia or hyperphosphatemia. Nevertheless, some patients remain refractory to SHPT with this agent, as the dose cannot be sufficiently increased due to gastrointestinal symptoms. In order to resolve this issue, we have developed a newly synthesized calcimimetic agent, evocalcet (MT-4580/KHK7580). In a rat model of CKD induced by 5/6 nephrectomy, oral administration of evocalcet efficiently suppressed the secretion of parathyroid hormone (PTH). With regard to the gastro-intestinal effects, cinacalcet induced a significant delay in gastric emptying in rats, while evocalcet did no marked effects on it. Evocalcet also demonstrated the less induction of emesis compared to cinacalcet in common marmosets. The pharmacological effects of evocalcet were observed at lower doses because of its higher bioavailability than cinacalcet, which may have contributed to the reduced GI tract symptoms. In addition, evocalcet showed no substantial direct inhibition of any CYP isozymes in in vitro liver microsome assay, suggesting a better profile in drug interactions than cinacalcet that inhibits cytochrome P450 (CYP) 2D6. These findings suggest that evocalcet can be a better alternative to cinacalcet, an oral calcimimetic agent, with a wider safety margin.

The Effect of Gastrostomy Placement on Gastric Function in Children: a Prospective Cohort Study

BackgroundA gastrostomy placement is frequently performed in pediatric patients who require long-term enteral tube feeding. Unfortunately, postoperative complications such as leakage, feeding intolerance, and gastroesophageal reflux frequently occur. These complications may be due to postoperative gastric dysmotility. Our aim was to evaluate the effect of gastrostomy placement on gastric emptying in children. MethodsA prospective study was performed including 50 children undergoing laparoscopic gastrostomy. Before and 3 months after gastrostomy, assessment was performed using the 13C-octanoic acid breath test, 24-h pH monitoring, and reflux symptom questionnaires. ResultsGastric half-emptying time significantly increased from the 57th to the 79th percentile (p < 0.001) after gastrostomy (p < 0.001). Fifty percent of patients with normal preoperative gastric emptying develop delayed gastric emptying (DGE, P > 95) after gastrostomy (p = 0.01). Most patients (≥75%) with leakage and/or feeding intolerance after gastrostomy had DGE after operation. A decrease in gastric emptying was associated with an increase in esophageal acid exposure time (r = 0.375, p < 0.001). ConclusionGastrostomy placement in children causes a significant delay in gastric emptying. Postoperative DGE was associated with gastroesophageal reflux and was found in most patients with postoperative leakage and feeding intolerance. These negative physiologic effects should be taken into account when considering gastrostomy placement in children.

Effect of temperature and diet on growth and gastric emptying time of the hybrid, Epinephelus fuscoguttatus ♀ × E. lanceolatus ♂

The effects of temperatures (22, 26, 30 and 34°C) and diets (commercial pellet and shrimp) on the growth properties and gastric emptying time (GET) of the tiger grouper×giant grouper (TGGG) hybrid were analyzed over a 30day experimental period under controlled laboratory conditions. Food consumption (FC), food conversion rate (FCR), specific growth rate (SGR) and GET were significantly influenced by temperature and diet type. The highest mean SGR (1.00% BM day−1, p<0.05) was observed in the 30°C+shrimp group of fish, while the lowest SGR was observed in the 22°C+pellet group (0.59% BM day−1). No significant differences in growth (P>0.05) were observed between any of the groups at 22 and 34°C fed on either the shrimp or the pellet diet. The lowest statistically significant (p<0.05) FC was observed at 22°C on both diets. The highest FCR (1.208, p<0.05) was observed in the 22°C+shrimp and 22°C+pellet groups. The fastest GETs were observed at 30°C, 12h for fish on the shrimp diet and 13h for fish on the pellet diet. A significant delay in gastric emptying (16h) was observed at 22°C in the group fed the commercial pellet diet (16h). The best growth performances and digestion rates were observed at 30°C followed by 26, 34 and 22°C regardless of diet. The results suggest that 26 and 30°C are optimum water temperatures for the aquaculture of this newly developed fish species fed on either a shrimp or pellet diet.

Does Adding Milk to Tea Delay Gastric Emptying?

Hillyard, S.*†; Cowman, S.†; Ramasundaram, R.†; Seed, P. T.‡; G., O’Sullivan† Author Information

Does adding milk to tea delay gastric emptying?

BackgroundMany preoperative fasting guidelines suggest that hot tea or coffee with milk added should be considered similar to solid food, allowing an interval of 6 h before commencing anaesthesia. There is little evidence to support these instructions, with recent guidelines undecided on the issue. This study aimed to establish whether there was a clinically significant delay in gastric emptying associated with adding a modest amount of milk to tea. MethodsThis randomized controlled crossover study was conducted in 10 healthy volunteers. The paracetamol absorption technique and real-time ultrasound measurement of the cross-sectional area of the gastric antrum were used to assess gastric emptying after ingestion of 300 ml of black tea or 300 ml of tea with milk (250 ml black tea plus 50 ml of full fat milk). ResultsThe mean difference in the time to reach the peak paracetamol concentration (tmax) was −8 min [95% confidence interval (CI) −23.1 to 7] in favour of tea with milk. Ultrasound assessment indicated that the geometric mean of the half-time to gastric emptying (T1/2) after tea without milk was 22.7 (95% CI 12.7–40.9) min and after tea with milk 23.6 (95% CI 13.5–41.0) min (ratio 1.04) (95% CI 0.47–2.29). ConclusionsThis study demonstrated no difference in gastric emptying times when a modest amount of milk was added to tea. These findings suggest that it may be acceptable to allow patients to add a small quantity of milk to their tea or coffee and follow the same fasting restrictions applied to clear fluids.

Gastroparesis in a Dermatomyositis Patient Successfully Treated with Intravenous Immunoglobulin

Purpose: A 27-year-old African-American male with a past medical history of discoid lupus, hypertension, and DM presented with a 2-month history of a 20-lb weight loss and vomiting. Symptoms were associated with abdominal distension and early satiety. Physical exam showed cachexia, severe muscle atrophy, erythematous violaceous rash involving cheeks and forehead in malar region, gottron's papules, and multiple healing ulcers. Abdominal exam was unremarkable. Labs remarkable for CK 274 U/L, aldolase 8.1 U/L, ESR 47 mm/hr, CRP 1.7 mg/dl, ANA 1:160, and SSA 32.3 AU/ml. SSB, anti-Smith, Anti-RNP, dsDNA, Anti-B2 glycoprotein and anticardiolipin antibodies were all negative. EGD showed multiple erosions in the antrum and duodenitis in the bulb. Gastric biopsies were negative for H. pylori and vasculitis. Gastric emptying studying revealed significant delay in gastric emptying with 85% of the nuclear material retained at 4 hours. His DM was difficult to control with different immune modulators/suppressants including methotrexate (MTX), prednisone, hydroxychlorquine, mycophenolate and cyclosporine- either due to treatment failure or side effects intolerance. Azathioprine was not initiated due to low thiopurine methyltransferase RBC assay. He refused any surgical interventions and was started on monthly intravenous immunoglobulin (IVIG) and given metoclopramide for symptom relief (macrolides could not be used as his QTc was prolonged). He was also continued on prednisone and hydroxychlorquine. Six months later, he noted improvement in his rash and early satiety symptoms, along with a 22-lb weight gain. His hemoglobin, CK, CRP and aldolase have also normalized. Gastrointestinal involvement is well recognized in dermatomyositis (DM) with the esophagus being affected in up to one third of the cases. Dysphagia is the most common presenting symptom due to striated muscle involvement in the upper third of the esophagus. Gastrointestinal vasculitis with ulceration and intestinal perforation is also described. Gastric dysmotility is a rare but serious manifestation of DM. Horowitz et al have reported varying degrees of gastric emptying in eight out of thirteen patients with DM. Whether they were symptomatic or asymptomatic, the degree of delayed emptying correlated with the severity of peripheral muscle weakness. This may suggest smooth muscle involvement even in the absence of gastrointestinal vasculitis. Treatment of gastrointestinal manifestations should target controlling the primary disease by using immune suppressive medications typically by using azathioprine, methotrexate or hydroxychlorquine. Our patient achieved partial control of DM and gastroparesis with IVIG and had significant weight gain on follow-up.

Amylin Level and Gastric Emptying in Obese Children : Before and after Weight Loss

Amylin is a neuroendocrine hormone that inhibits food intake and gastric emptying in animal studies. Its role in obese human beings is still controversial. We aimed to estimate the fasting and postprandial amylin levels in obese children before and after weight loss [through weight loss intervention program (WLIP)] and to relate these levels to the lipid profile, homeostasis model assessment of insulin resistance (HOMA-IR) and ultrasonography gastric half emptying time (t1/2). This study was conducted initially on 20 obese children, 10 of them only continued 6 months follow up strategy on WLIP. Ten lean children served as controls. All children were subjected initially and on follow up to dietetic history taking, anthropometric measurements and laboratory assessment oflipid profile, HOMA-IR, fasting and postprandial amylin levels and ultrasonography gastric half emptying time (t1/2). The results showed that IR, significantly increased in fasting and postprandial amylin levels and significant delay in gastric emptying among obese children. After WLIP completion, IR was reversible, fasting and postprandial amylin levels decreased and gastric emptying significantly improved yet still significantly delayed than controls. There was significant positive correlation between fasting amylin levels and body mass index %, fasting insulin and HOMA-IR.

Tu1977 IL-17 Induces Hypercontractility in Intestinal Smooth Muscle Strips and Cells via Nf?B Signaling

Introduction: Gastric emptying (GE) in rats is mostly determined after gavaging a radioactive or colored meal, with determination of the percentage of food remaining in the stomach after sacrificing the animal as a measure for gastric emptying. We hereby present a novel method to directly and continuously assess gastric emptying of a liquid meal in conscious rats without the need to sacrifice animals. Methods: After an overnight fast, 6 Wistar HAN rats were placed in a custom-made Bolmann cage to minimize movement artefacts. Rats were treated with atropine (1 mg kg-1; subcutaneous), pancreatic polypeptide (PP; 100 pmol kg-1 min-1; intravenous infusion) or vehicle (administered on 2 occasions). 15 minutes after the start of the treatment, rats were gavaged with 3 ml of a liquid test meal containing 1% hydroxypropyl methylcellulose solution and 0.5 g ml-1 BaSO4 (0 cal). The abdomen was visualized as a dorsal projection using X-ray imaging (29 kV, 40mAs; Embracemammography device; Selenia software (Hologic)). X-ray imaging was possible throughout the whole experiment. In order to estimate the test meal fraction in the stomach, X-rays were taken every 5-10 minutes and analyzed using Image J software. After manually outlining the stomach, the software was used to calculate the area of the image of the stomach. The area directly after gavage of the meal was set at 100% and GE was expressed as the fraction of the original stomach area over time. The average percentage emptied over 60 minutes was compared. Data were represented as mean±S.E.M. and compared using a paired ttest (p 0.1). Atropine caused a significant delay in GE compared to vehicle (55.6±3.1 vs. 40.3±2.7% emptied over 60 minutes, p<0.01). Similarly, PP-treatment significantly inhibited GE (60.5±3.2 vs. 48.5±1.9% emptied over 60 minutes, p<0.05; Fig.1). Conclusion: Using X-rays to visualize a radio-opaque meal allows to determine gastric emptying in a continuous non-invasive manner. Both atropine and PP significantly delayed gastric emptying rate.

Tu1976 A Method to Directly and Continuously Assess Gastric Emptying in Conscious Rats: Effect of Pancreatic Polypeptide and Atropine

Introduction: Gastric emptying (GE) in rats is mostly determined after gavaging a radioactive or colored meal, with determination of the percentage of food remaining in the stomach after sacrificing the animal as a measure for gastric emptying. We hereby present a novel method to directly and continuously assess gastric emptying of a liquid meal in conscious rats without the need to sacrifice animals. Methods: After an overnight fast, 6 Wistar HAN rats were placed in a custom-made Bolmann cage to minimize movement artefacts. Rats were treated with atropine (1 mg kg-1; subcutaneous), pancreatic polypeptide (PP; 100 pmol kg-1 min-1; intravenous infusion) or vehicle (administered on 2 occasions). 15 minutes after the start of the treatment, rats were gavaged with 3 ml of a liquid test meal containing 1% hydroxypropyl methylcellulose solution and 0.5 g ml-1 BaSO4 (0 cal). The abdomen was visualized as a dorsal projection using X-ray imaging (29 kV, 40mAs; Embracemammography device; Selenia software (Hologic)). X-ray imaging was possible throughout the whole experiment. In order to estimate the test meal fraction in the stomach, X-rays were taken every 5-10 minutes and analyzed using Image J software. After manually outlining the stomach, the software was used to calculate the area of the image of the stomach. The area directly after gavage of the meal was set at 100% and GE was expressed as the fraction of the original stomach area over time. The average percentage emptied over 60 minutes was compared. Data were represented as mean±S.E.M. and compared using a paired ttest (p 0.1). Atropine caused a significant delay in GE compared to vehicle (55.6±3.1 vs. 40.3±2.7% emptied over 60 minutes, p<0.01). Similarly, PP-treatment significantly inhibited GE (60.5±3.2 vs. 48.5±1.9% emptied over 60 minutes, p<0.05; Fig.1). Conclusion: Using X-rays to visualize a radio-opaque meal allows to determine gastric emptying in a continuous non-invasive manner. Both atropine and PP significantly delayed gastric emptying rate.

Myosin Light Chain Kinase Is Involved in the Mechanism of Gastrointestinal Dysfunction in Diabetic Rats

It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca(2+) via myosin light chain phosphorylation, which is activated by myosin light chain kinase (MLCK). Recently, MLCK has been demonstrated to play an important role in smooth muscle contraction and normal gastrointestinal motility. The aim of our study is to investigate whether MLCK is involved in the mechanism of gastrointestinal dysfunction and the ameliorating effects of insulin on gastrointestinal dysfunction in diabetic rats. A diabetic rat model was established by an intravenous injection with streptozotocin. Rats were randomized into three groups: control group, diabetic group, and insulin-treated group. The gastrointestinal functions were assessed in terms of gastric emptying and intestinal transit. The expression of MLCK in the pylorus and ileum of the three groups was determined by real-time polymerase chain reaction (PCR) and Western blot methods. The diabetic group exhibited a significant delay in gastric emptying and intestinal transit than the control group. Insulin treatment significantly ameliorated the gastric emptying and intestinal transit in diabetic rats. The expression levels of MLCK in the pylorus and ileum of the diabetic group were both significantly decreased compared with the control group, and the changes of MLCK expression in these tissues of diabetic rats were partially reversed after treatment with insulin. Decreased expression of MLCK in gastrointestinal tissues could be a possible cause for gastrointestinal dysfunction. Insulin may partly ameliorate gastrointestinal dysfunction by restoring the expression of MLCK.

The once-daily human glucagon-like peptide-1 (GLP-1) analog liraglutide improves postprandial glucose levels in type 2 diabetes patients

Fasting and postprandial plasma glucose (FPG, PPG) control are both necessary to achieve glycosylated hemoglobin (HbA(1c)) regulation goals. Liraglutide, based on its glucagon-like peptide 1 (GLP-1)-mediated pharmacology and pharmacokinetics may reduce HbA(1c) through both FPG and PPG levels. The objective of the present study was to investigate the effect of once-daily liraglutide (0.6, 1.2, and 1.8 mg) at steady state on FPG, PPG, postprandial insulin, and gastric emptying. Eighteen subjects with type 2 diabetes, aged 18-70 years, with a body mass index of 18.5-40 kg/m(2) and HbA(1c) of 7.0%-9.5% were included in this single-centre, randomized, placebo-controlled, double-blind, two-period, cross over trial. Patients were randomized into two groups (A or B). Group A received oncedaily liraglutide for 3 weeks, followed by a 3-4-week washout period and 3 weeks of oncedaily placebo. Group B was treated as for Group A, but treatment periods were reversed (ie, placebo followed by liraglutide). A meal test was performed at steady-state liraglutide/placebo doses of 0.6, 1.2, and 1.8 mg/day. Plasma glucose, insulin, and paracetamol (acetaminophen) concentrations (to assess gastric emptying) were measured pre- and postmeal. PPG levels significantly decreased (P<0.001) after all three liraglutide doses when compared with placebo. This decrease was also apparent when corrected for baseline (incremental excursions), with the exception of average incremental increase calculated as area under the concentration curve (AUC) over the fasting value from time zero to 5 hours (iAUC (0-5 h)/5 hours) after liraglutide 0.6 mg, where there was a trend to decrease (P=0.082). In addition, FPG levels significantly decreased at all three liraglutide dose levels when compared to placebo (P<0.001). Fasting and postprandial insulin levels significantly increased with liraglutide versus placebo at all doses studied (P<0.001). A significant delay in gastric emptying during the first hour postmeal was observed at the two highest liraglutide doses versus placebo. In addition to lowering FPG levels, liraglutide improves PPG levels (absolute and incremental) possibly by both stimulating postprandial insulin secretion and delaying gastric emptying.

Effects of a diet with inulin-enriched pasta on gut peptides and gastric emptying rates in healthy young volunteers

Our group has previously shown that the administration of pasta enriched along with the prebiotic inulin induces a significant reduction in triglyceride and glucose levels with a significant delay in gastric emptying (GE) rates. This protective effect may occur by affecting the release of a number of gut peptides involved in the control of gastrointestinal motility. The aim of the present study was to evaluate the effects of inulin-enriched pasta on the circulating levels of neurotensin (NT), somatostatin (SS), and corticotropin-releasing factor (CRF) in relation to the GE time in young healthy subjects. Twenty healthy young male volunteers completed a randomized double-blind crossover study consisting of a 2-week run-in period and two 5-week study periods (11% inulin-enriched/control pasta), with an 8-week wash-out period in between. Gut peptide concentrations were evaluated by radioimmunoassay. GE time was evaluated by ultrasonography. The prebiotic treatment significantly increased the area under the curve (AUC) values of both NT and SS (p<0.05 Dunn's post-test). With regard to gastric motility, along with a significant delay in both the final time and T (1/2) gastric emptying time, a positive correlation was found between T (1/2) and SS AUC values (r=0.57, p=0.009) in the inulin-enriched pasta group. These results support the hypothesis that inulin plays an active role in mechanisms affecting the release of these gut peptides, which may modulate the gastric emptying of digesta.

Hyperglycemia Acutely Lowers the Postprandial Excursions of Glucagon-Like Peptide-1 and Gastric Inhibitory Polypeptide in Humans

Impaired secretion of glucagon-like peptide 1 (GLP-1) has been suggested to contribute to the deficient incretin effect in patients with type 2 diabetes. It is unclear whether this is a primary defect or a consequence of the hyperglycemia in type 2 diabetes. We examined whether acute hyperglycemia reduces the postprandial excursions of gastric inhibitory polypeptide (GIP) and GLP-1, and if so, whether this can be attributed to changes in gastric emptying. Fifteen nondiabetic individuals participated in a euglycemic clamp and a hyperglycemic clamp experiment, carried out over 285 min. A mixed meal was ingested after 45 min. Plasma concentrations of glucose, insulin, C-peptide, glucagon, triglycerides, GIP, and GLP-1 were determined, and gastric emptying was assessed using a (13)C-octanoate breath test. Glucose levels were 160 +/- 1 mg/dl during the hyperglycemic clamp experiments and 83 +/- 3 mg/dl during the euglycemia (P < 0.0001). Glucose infusion rates were higher during hyperglycemia, but meal ingestion led to a decline in glucose requirements in both experiments (P < 0.0001). Insulin and C-peptide levels were higher during the hyperglycemic clamp experiments (P < 0.0001), whereas glucagon levels were higher during euglycemia (P < 0.0001). The postprandial increases in GIP and GLP-1 concentrations were 46 and 52% lower during the experiments with hyperglycemia (P = 0.0017 and P = 0.021). Hyperglycemia also elicited a significant delay in gastric emptying (P < 0.0001). Hyperglycemia acutely reduces the postprandial levels of GIP and GLP-1, possibly through a deceleration of gastric emptying. This supports the concept that reduced incretin levels in some patients with type 2 diabetes are a consequence rather than a cause of type 2 diabetes.

Gastrointestinal dysfunction in diabetic rats relates with a decline in tissue l-arginine content and consequent low levels of nitric oxide

Diabetic subjects exhibit low levels of nitric oxide (NO), its precursor l-arginine, and nitric oxide synthase (NOS) in tissues like endothelium and kidney. In view of this, we speculated that gastrointestinal (GI) dysfunction in diabetes could be related to similar changes in NO turnover in GI tissues. Hence, the studies were carried out in rats after eight weeks of streptozotocin-induced hyperglycemia, wherein the GI functions were assessed in terms of gastric emptying and intestinal transit using barium sulfate semisolid test meal, and the levels of l-arginine and NO in pylorus and ileum were estimated, respectively, by HPLC and amperometry. The results revealed that diabetic group exhibited significant delay in gastric emptying and intestinal transit, and the pylorus and ileum tissues had significantly low levels of NO and l-arginine. Daily treatment of non-diabetic rats with NOS inhibitor [ Nω-nitro- l-arginine methyl ester (10 mg/kg/day, p.o.)] for eight weeks produced similar delay in gastric emptying and intestinal transit with associated low levels of NO in GI tissues. Daily supplementation of l-arginine (100 mg/kg, p.o.) for eight weeks to diabetic and NOS inhibitor treated non-diabetic group was found to restore the gastric emptying and intestinal transit and improved the levels of NO in GI tissues. The findings indicate that diabetes-induced l-arginine deficiency and consequent low levels of NO in GI tissues could be possible cause for the GI dysfunction, and l-arginine supplementation can prevent the same. However, extensive clinical investigations are necessary to recommend the use of l-arginine for the treatment of GI dysfunctions in diabetes.

Does the Use of Nizatidine, as a Pro-kinetic Agent, Improve Gastric Emptying in Patients Post-oesophagectomy?

PurposeDelayed gastric emptying following oesophagectomy is common and can often lead to weight loss, malnutrition and a poor quality of life. Animal models have shown that nizatidine, a histamine H2-receptor antagonist, has pro-kinetic properties and can accelerate gastric emptying. Patients post-oesophagectomy require long-term acid suppression medication; if nizatidine can improve gastric emptying, it can be adopted for its dual pharmacological actions. MethodologyTwenty consecutive patients were prospectively enrolled in this trial following oesophagectomy. All patients were more than 6 months post-surgery and had no evidence of recurrent cancer. A baseline nuclear medicine scan following a radiolabelled meal was conducted and then repeated after 1 week of nizatidine (150 mg bd) treatment. Quality of life and eating comfort data were collected. ResultsOesophagectomy causes a significant delay in gastric emptying. Early satiety (80%) and reflux (65%) were the most common post-operative complaints. The percentage of food remaining in the stomach at 60 min post-meal was significantly more than normal values in both the pre- and post-nizatidine studies. There is no advantage in using nizatidine as a pro-kinetic agent. ConclusionsImpaired gastric emptying post-surgery causes a change in eating habits. Patients in this study did not lose a significant amount of weight despite all indicating worse eating comfort. Patients required more regular meals or snacks throughout the day and avoid foods that are difficult to swallow. It is likely that gastric motility only plays a small role in the emptying process and gravity combined with appropriate drainage procedures (pyloroplasty/pyloromyotomy) at the time of surgery are more important.

Effect of Roux-en-Y reconstruction on the gastric emptying of a solid meal

The gastric emptying of a solid meal was measured in 39 patients after Roux-en-Y reconstruction and compared with that in 27 patients after truncal vagotomy and pyloroplasty and that in 22 patients after Polya gastrectomy. There were no significant differences among the groups. It is concluded that despite the disruption of the normal motor pathway produced by the Roux-en-Y reconstruction it does not lead to clinically significant delay in gastric emptying.