title: Effects of glucose-dependent insulinotropic polypeptide on gastric emptying, glycaemia and insulinaemia during critical illness: a prospective, double blind, randomised, crossover study.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 <0.001) and plasma glucagon (iAUC300 4217 (1891 to 7715) versus 1232 (293 to 4545) pg/ml.300 minutes; P = 0.04), there were no effects on postprandial blood glucose (AUC300 2843 (2568 to 3338) versus 2819 (2550 to 3497) mmol/L.300 minutes; P = 0.86), gastric emptying (AUC300 15611 (10993 to 18062) versus 15660 (9694 to 22618) %.300 minutes; P = 0.61), glucose absorption (AUC300 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 (AUC300 3945 (2280 to 6731) versus 3479 (2316 to 6081) mU/L.300 minutes; P = 0.76).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Australian New Zealand Clinical Trials Registry ACTRN12612000488808. Registered 3 May 2012.
authors.affiliation: Intensive Care Unit, Level 4, Emergency Services Building, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000, Australia. p_kar@hotmail.com.
authors.forename: Palash
authors.initials: P
authors.lastname: Kar
authors.affiliation: Intensive Care Unit, Level 4, Emergency Services Building, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000, Australia. Caroline.Cousins@health.sa.gov.au.
authors.forename: Caroline E
authors.initials: CE
authors.lastname: Cousins
authors.affiliation: Intensive Care Unit, Level 4, Emergency Services Building, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000, Australia. Chris.Annink@health.sa.gov.au.
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Annink
authors.affiliation: Discipline of Medicine, The University of Adelaide, Royal Adelaide Hospital, Level 6 Eleanor Harrald Building, North Terrace, Adelaide, South Australia, 5000, Australia. karen.jones@adelaide.edu.au.|Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 6, Eleanor Harrald Building, North Terrace, Adelaide, South Australia, 5000, Australia. karen.jones@adelaide.edu.au.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Jones
authors.affiliation: Intensive Care Unit, Level 4, Emergency Services Building, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000, Australia. Marianne.Chapman@health.sa.gov.au.|Discipline of Acute Care Medicine, The University of Adelaide, North Terrace, Adelaide, South Australia, 5000, Australia. Marianne.Chapman@health.sa.gov.au.
authors.forename: Marianne J
authors.initials: MJ
authors.lastname: Chapman
authors.affiliation: Diabetes Division, Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Gudrunstraße 56, Bochum, 44791, Germany. juris.meier@rub.de.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.affiliation: Diabetes Centre, Bad Lauterberg, Kirchberg 21, Bad Lauterberg, Harz, 37431, Germany. nauck@diabeteszentrum.de.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.affiliation: Discipline of Medicine, The University of Adelaide, Royal Adelaide Hospital, Level 6 Eleanor Harrald Building, North Terrace, Adelaide, South Australia, 5000, Australia. michael.horowitz@adelaide.edu.au.|Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Level 6, Eleanor Harrald Building, North Terrace, Adelaide, South Australia, 5000, Australia. michael.horowitz@adelaide.edu.au.
authors.forename: Michael
authors.initials: M
authors.lastname: Horowitz
authors.affiliation: Intensive Care Unit, Level 4, Emergency Services Building, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000, Australia. adam.deane@adelaide.edu.au.|Discipline of Acute Care Medicine, The University of Adelaide, North Terrace, Adelaide, South Australia, 5000, Australia. adam.deane@adelaide.edu.au.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Deane
mesh_terms: D000328:Adult; D000368:Aged; D016638:Critical Illness; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology* / Q000627:therapeutic use; D005934:Glucagon / Q000097:blood; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000503:physiopathology; D007003:Hypoglycemia / Q000209:etiology; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies
chemical_list: D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D004763:Glucagon-Like Peptides; D005934:Glucagon; D005947:Glucose