Waking up the gut in critically ill patients

Multiorgan failure frequently develops in critically ill patients. While therapeutic efforts in such patients are often focused on the lungs, on the cardiovascular system as well as on the kidneys, it is important to also consider the functional alterations in gut motility and hormone secretion. Given the central regulatory functions of many gut hormones, such as glucagon-like peptide 1, glucagon-like peptide 2, ghrelin and others, exogenous supplementation of some of these factors may be beneficial under conditions of critical illness. From a pragmatic point of view, the most feasible way towards a restoration of gut hormone secretion in critically ill patients is to provide enteral nutritional supply as soon as possible

Impaired Hyperglycemia-Induced Delay in Gastric Emptying in Patients With Type 1 Diabetes Deficient for Islet Amyloid Polypeptide

OBJECTIVE—Slowing of gastric emptying by hyperglycemia, a physiological response to minimize postprandial hyperglycemia, may be impaired in patients with type 1 diabetes. The causes and consequences on glucose homeostasis are unknown

Upper gastrointestinal function and glycemic control in diabetes mellitus

Recent evidence has highlighted the impact of glycemic control on the incidence and progression of diabetic micro- and macrovascular complications, and on cardiovascular risk in the non-diabetic population. Postprandial blood glucose concentrations make a major contribution to overall glycemic control, and are determined in part by upper gastrointestinal function. Conversely, poor glycemic control has an acute, reversible effect on gastrointestinal motility. Insights into the mechanisms by which the gut contributes to glycemia have given rise to a number of novel dietary and pharmacological strategies designed to lower postprandial blood glucose concentrations.Reawika Chaikomin, Christopher K Rayner, Karen L Jones, Michael Horowit

Effects of intraluminal local anesthetic on upper gastrointestinal motor, sensory, and peptide hormone responses to intraduodenal glucose

ObjectiveEnterally administered glucose modifies gut sensation, diminishes hunger, and slows gastric emptying by suppressing antral motility and stimulating pyloric pressures. We aimed to clarify the mechanism of small intestinal glucose sensing.MethodsWe studied eight healthy males twice, in random order. An antroduodenal manometry catheter was positioned with a sleeve sensor across the pylorus. Benzocaine, or vehicle alone, was given into the proximal duodenum as a bolus, followed by continuous infusion for 105 min (T=-15 to 90 min). Glucose was also infused into the proximal duodenum at 3 kcal/min for 90 min (T=0-90 min). Sensations of hunger, bloating, and nausea were assessed with visual analog questionnaires, blood was sampled at intervals, and energy intake at a buffet meal (T=90-120 min) was measured.ResultsPerceptions of bloating and nausea were markedly less with benzocaine when compared with vehicle (PConclusionMucosal anesthesia ameliorates unpleasant sensations induced by enteral glucose, but does not inhibit the release of gut peptides that feed back on appetite and gastroduodenal motility.Chaikomin, Reawika; Jones, Karen L.; Feinle-Bisset, Christine; Meyer, James H.; Horowitz, Michael; Rayner, Christopher K

Artificially sweetened versus regular mixers increase gastric emptying and alcohol absorption

BackgroundMixed 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.MethodsWe 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).ResultsGastric 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 ConclusionsSubstitution 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.Keng-Liang Wu, Reawika Chaikomin, Selena Doran, Karen L. Jones, Michael Horowitz and Christopher K. Rayne

Role of nitric oxide mechanisms in gastric emptying of, and the blood pressure and glycemic responses to, oral glucose in healthy older subjects

Published abstract used with permission of the copyright owner.The primary aims of this study were to evaluate the effects of the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on gastric emptying (GE) of, and the blood pressure (BP), glycemic, insulin, and incretin responses to, oral glucose in older subjects. Eight healthy subjects (4 males and 4 females, aged 70.9 ± 1.3 yr) were studied on two separate days, in double-blind, randomized order. Subjects received an intravenous infusion of either L-NAME (180 µg·kg–1·h–1) or saline (0.9%) at a rate of 3 ml/min for 150 min. Thirty minutes after the commencement of the infusion (0 min), subjects consumed a 300-ml drink containing 50 g glucose labeled with 20 MBq 99mTc-sulfur colloid, while sitting in front of a gamma camera. GE, BP (systolic and diastolic), heart rate (HR), blood glucose, plasma insulin, and incretin hormones, glucose-dependant insulinotropic-polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), were measured. L-NAME had no effect on GE, GIP, and GLP-1. Between –30 and 0 min L-NAME had no effect on BP or HR. After the drink (0–60 min), systolic and diastolic BP fell (P < 0.05) and HR increased (P < 0.01) during saline; these effects were attenuated (P < 0.001) by L-NAME. Blood glucose levels between 90 and 150 min were higher (P < 0.001) and plasma insulin were between 15 and 150 min less (P < 0.001) after L-NAME. The fall in BP, increase in HR, and stimulation of insulin secretion by oral glucose in older subjects were mediated by NO mechanisms by an effect unrelated to GE or changes in incretin hormones.Diana Gentilcore, Renuka Visvanathan, Antonietta Russo, Reawika Chaikomin, Julie E. Stevens, Judith M. Wishart, Anne Tonkin, Michael Horowitz, and Karen L. Jone

Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP and GLP-1 but does not improve overall glycemia in healthy subjects

Published abstract used with permission of the copyright owner.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.Reawika Chaikomin, Selena Doran, Karen L. Jones, Christine Feinle-Bisset, Deirdre O’Donovan, Christopher K. Rayner, and Michael Horowit

Effect of small intestinal glucose load on plasma ghrelin in healthy men

Copyright © 2008 by the American Physiological Society.Background: 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. Objective: 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. Subjects and methods: Blood glucose, plasma insulin and plasma ghrelin levels were measured in ten healthy males (age: 32 ± 4 yr; body mass index: 25.1 ± 0.4 kg/m2) during intraduodenal glucose infusions at 1 kcal/min ("G1"), 2 kcal/min ("G2") and 4 kcal/min ("G4") and intraduodenal hypertonic saline ("control") for 120 min. Results: There was a progressive decrease in ghrelin with all treatments, control at 45 min and between 90 - 120 min (P < 0.05) and G1 (P < 0.05), G2 (P < 0.0001) and G4 (P < 0.0001) between 30 - 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. Conclusion: Suppression of ghrelin by intraduodenal glucose in healthy males is apparently independent of the glucose load and unrelated to blood glucose or insulin levels.Kimberly Cukier, Amelia N Pilichiewicz, Reawika Chaikomin, Ixchel M Brennan, Judith M. Wishart, Christopher K Rayner, Karen L. Jones, Michael Horowitz, and Christine Feinle-Bisse

Effects of mid-jejunal compared to duodenal glucose infusion on peptide hormone release and appetite in healthy men

IntroductionCells 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.MethodsTen 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 sampled frequently, and hunger was scored by questionnaires. The tube was removed and energy intake measured from a buffet meal.ResultsStimulation of CCK and suppression of hunger were greater (each PConclusionsThere 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.Reawika Chaikomin, Keng-Liang Wu, Selena Doran, James H. Meyer, Karen L. Jones, Christine Feinle-Bisset, Michael Horowitz and Christopher K. Rayne