Julie E. Stevens

Effects of a Protein Preload on Gastric Emptying, Glycemia, and Gut Hormones After a Carbohydrate Meal in Diet-Controlled Type 2 Diabetes

OBJECTIVE We evaluated whether a whey preload could slow gastric emptying, stimulate incretin hormones, and attenuate postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS 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. RESULTS 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). CONCLUSIONS 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.

Endogenous Glucagon-Like Peptide-1 Slows Gastric Emptying in Healthy Subjects, Attenuating Postprandial Glycemia

INTRODUCTION 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. METHODS 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. RESULTS 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]. CONCLUSION GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.

A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus

PURPOSE To evaluate the natural history of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. SUBJECTS AND METHODS 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. RESULTS 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. CONCLUSION 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.

Guar attenuates fall in postprandial blood pressure and slows gastric emptying of oral glucose in type 2 diabetes.

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.

Pathophysiology and pharmacotherapy of gastroparesis: current and future perspectives.

Introduction: 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. Areas covered: 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. Expert opinion: 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.

Gastric emptying, incretin hormone secretion, and postprandial glycemia in cystic fibrosis - Effects of pancreatic enzyme supplementation

CONTEXT 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. OBJECTIVE The aim of this study was to evaluate these aspects of gut function in nondiabetic CF patients. DESIGN AND SETTING We conducted a randomized, double-blind, placebo-controlled crossover study at a clinical research laboratory. PATIENTS 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. INTERVENTIONS 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. MAIN OUTCOME MEASURES Gastric emptying was measured using scintigraphy, and blood was sampled frequently for blood glucose and plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and glucagon concentrations. RESULTS 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). CONCLUSIONS Pancreatic enzyme supplementation plays an important role in incretin secretion, gastric emptying, and postprandial hyperglycemia in CF.

Effect of the motilin agonist KC 11458 on gastric emptying in diabetic gastroparesis.

Background : KC 11458, a motilin agonist without antibiotic properties, accelerates gastric emptying in animals and healthy humans.

The effects of sitagliptin on gastric emptying in healthy humans – a randomised, controlled study

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.

Measurement of gastric emptying of a high‐nutrient liquid by 3D ultrasonography in diabetic gastroparesis

Background  Gastric emptying (GE) is delayed in 30–50% of patients with longstanding diabetes. Scintigraphy represents the ‘gold standard’ for measurement of GE, but is associated with a radiation burden. Three‐dimensional (3D) ultrasonography has recently been demonstrated to provide a valid measure of liquid GE in healthy subjects; however, the technique has not been validated in patients with gastroparesis. The primary aim of this study was to compare measurements of GE of a high‐nutrient glucose drink by 3D ultrasonography and scintigraphy in diabetic gastroparesis.

Sustained effects of a protein ‘preload’ on glycaemia and gastric emptying over 4 weeks in patients with type 2 diabetes: A randomized clinical trial

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.