glucagon-like-peptide-1 and Gastroparesis

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.

Topics: Adipose Tissue; Blood Glucose; Cholecystokinin; Critical Illness; Diabetes Mellitus; Dyspepsia; Gastric Emptying; Gastroparesis; Ghrelin; Glucagon-Like Peptide 1; Humans; Insulin; Peptide YY; Postprandial Period

Gastroparesis is a well-known consequence of long-standing diabetes that presents with gastric dysmotility in the absence of gastric outlet obstruction. This study aimed to evaluate the therapeutic effects of mosapride and levosulpiride on improving gastric emptying in type 2 diabetes mellitus (T2DM) while regulating glycemic levels.. Rats were divided into the normal control, untreated diabetic, metformin-treated (100 mg/kg/day), mosapride-treated (3 mg/kg/day), levosulpiride-treated (5 mg/kg/day), metformin (100 mg/kg/day) + mosapride (3 mg/kg/day)-treated, and metformin (100 mg/kg/day) + levosulpiride (5 mg/kg/day)-treated diabetic groups. T2DM was induced by a streptozotocin-nicotinamide model. Fourweeks from diabetes onset, the treatment was started orally daily for 2 weeks. Serum glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels were measured. Gastric motility study was performed using isolated rat fundus and pylorus strip preparations. Moreover, the intestinal transit rate was measured.. Mosapride and levosulpiride administration showed a significant decrease in serum glucose levels with improvement of gastric motility and intestinal transit rate. Mosapride showed a significant increase in serum insulin and GLP-1 levels. Metformin with mosapride and levosulpiride co-administration showed better glycemic control and gastric emptying than either drug administered alone.. Mosapride and levosulpiride showed comparable prokinetic effects. Metformin administration with mosapride and levosulpiride showed better glycemic control and prokinetic effects. Mosapride provided better glycemic control than levosulpiride. Metformin + mosapride combination provided superior glycemic control and prokinetic effects.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Gastroparesis; Glucagon-Like Peptide 1; Glycemic Control; Insulins; Metformin; Rats

Topics: Blood Glucose; Gastroparesis; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Insulin; Peptide Fragments

Three patients presented for orthopaedic surgery on glucagon-like peptide receptor agonist (GLP-1 RA) medications with a minimum fasting time of 10 hours. Gastric ultrasound confirmed the presence of retained solids in the stomach; all 3 cases were postponed.. There is growing concern for increased perioperative aspiration risk related to delayed gastric emptying associated with GLP-1 RA and a paucity of literature to guide perioperative management. This may cause case cancellation over safety concerns for elective procedures. The presented cases illustrate the association of GLP-1 RA drugs and delayed gastric emptying causing case postponement.

Topics: Fasting; Gastroparesis; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans

Delayed gastric emptying (DGE) is common after an Ivor Lewis gastro-esophagectomy (ILGO). The risk of a dilated conduit is the much-feared anastomotic leak. Therefore, prompt management of DGE is required. However, the pathophysiology of DGE is unclear. We proposed that post-ILGO patients with/without DGE have different gut hormone profiles (GHP). Consecutive patients undergoing an ILGO from 1 December 2017 to 31 November 2019 were recruited. Blood sampling was conducted on either day 4, 5, or 6 with baseline sample taken prior to a 193-kcal meal and after every 30 minutes for 2 hours. If patients received pyloric dilatation, a repeat profile was performed post-dilatation and were designated as had DGE. Analyses were conducted on the following groups: patient without dilatation (non-dilated) versus dilatation (dilated); and pre-dilatation versus post-dilatation. Gut hormone profiles analyzed were glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) using radioimmunoassay. Of 65 patients, 24 (36.9%) had dilatation and 41 (63.1%) did not. For the non-dilated and dilated groups, there were no differences in day 4, 5, or 6 GLP-1 (P = 0.499) (95% confidence interval for non-dilated [2822.64, 4416.40] and dilated [2519.91, 3162.32]). However, PYY levels were raised in the non-dilated group (P = 0.021) (95% confidence interval for non-dilated [1620.38, 3005.75] and dilated [821.53, 1606.18]). Additionally, after pyloric dilatation, paired analysis showed no differences in GLP-1, but PYY levels were different at all time points and had an exaggerated post-prandial response. We conclude that DGE is associated with an obtunded PYY response. However, the exact nature of the association is not yet established.

Topics: Esophageal Neoplasms; Esophagectomy; Gastric Emptying; Gastroparesis; Glucagon-Like Peptide 1; Humans; Peptides; Postoperative Complications; Retrospective Studies; Tyrosine

Gastrointestinal complications in diabetes may affect glucose and endocrine homeostasis. Glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and leptin regulate glucose homeostasis, food intake, and gastric emptying.. The aim was to investigate associations between diabetes complications and glucose homeostasis and plasma levels of GIP, GLP-1, and leptin.. Sixteen diabetes patients (seven men) were examined with gastric emptying scintigraphy and 72-h continuous subcutaneous glucose monitoring, 14 with the deep-breathing test, and 12 with esophageal manometry. A fiber-rich breakfast was given during the second day of glucose registration. Blood samples were taken 10 min and right before a fat-rich breakfast, as well as 10, 20, 30, 45, 60, 90, 120, 150, and 180 min afterwards. 20 healthy volunteers acted as controls. Plasma was analyzed regarding GIP, GLP-1, and leptin by Luminex.. Gastroparesis lowered maximal concentration (c-max) (p = 0.003) and total area under the curve (tAUC) (p = 0.019) of glucose levels as well as d-min (p = 0.043) of leptin levels. It tended to lower baseline (p = 0.073), c-max (p = 0.066), change from baseline (d-max) (p = 0.073), and tAUC (p = 0.093) of GLP-1 concentrations. Esophageal dysmotility tended to lower tAUC of glucose levels (p = 0.063), and c-min (p = 0.065) and tAUC (p = 0.063) of leptin levels. Diabetes patients had a higher baseline concentration of glucose (p = 0.013), GIP (p = 0.023), and leptin (p = 0.019) compared with healthy subjects.. Gastric and esophageal dysmotility are associated with both lesser increases in postprandial glucose elevations and decreased postprandial changes in GLP-1 and leptin.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Esophageal Motility Disorders; Female; Gastric Inhibitory Polypeptide; Gastroparesis; Glucagon-Like Peptide 1; Humans; Insulin; Leptin; Male; Middle Aged; Postprandial Period

Incretin hormones [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP)] released by the gut modulate gastrointestinal motility and influence gastric emptying (GE). Abnormal secretion or sensitivity to these hormones could contribute to the pathogenesis of gastroparesis. The aim of this study was to investigate incretin hormone secretion during a prolonged oral glucose load in non-diabetic patients with documented idiopathic gastroparesis.. Fifteen patients referred for digestive postprandial discomfort with delayed GE demonstrated by a (13) C-labeled octanoate breath test were included and compared with 10 healthy controls. A 75 g oral glucose load was performed, with blood samplings every 30 min for 5 h, to determine glucose, insulin, GIP, and GLP-1 blood levels.. Fasting GIP concentration was significantly higher in the patient group (56.1 ± 5.8 pg mL(-1) vs 29.9 ± 7.7 pg mL(-1), P =0.012). Postglucose load GIP concentrations were also significantly elevated in patients with gastroparesis, whereas GLP-1 concentrations during fasting and postglucose load conditions were not different to those of healthy controls. Moreover, glucose tolerance during glucose load was abnormal in patients, combining hyperglycemic insulin resistance and hyperinsulinism patterns, while fasting values for glycemia, insulin sensitivity, and insulin concentrations were normal.. Patients with idiopathic gastroparesis exhibit abnormal GIP levels associated with impaired insulin sensitivity during oral glucose load. Further studies are needed to establish the involvement of these defects in the pathophysiology of gastroparesis.

Topics: Administration, Oral; Adult; Blood Glucose; Female; Gastric Emptying; Gastric Inhibitory Polypeptide; Gastroparesis; Glucagon-Like Peptide 1; Glucose; Humans; Incretins; Insulin Resistance; Male; Middle Aged; Pilot Projects; Postprandial Period

Topics: Adult; Bezoars; Diabetes Mellitus, Type 1; Endoscopy, Gastrointestinal; Exenatide; Female; Gastroparesis; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Islets of Langerhans Transplantation; Kidney Transplantation; Peptides; Venoms