Effects of exogenous glucagon-like peptide-1 on gastric emptying and glucose absorption in the critically ill: relationship to glycemia.
OBJECTIVE
To determine the acute effects of exogenous glucagon-like peptide-1 on gastric emptying, glucose absorption, glycemia, plasma insulin, and glucagon in critically ill patients.


METHODS
Randomized, double-blind, crossover study.


METHODS
Intensive care unit.


METHODS
Twenty-five mechanically ventilated patients, without known diabetes, studied on consecutive days.


METHODS
Intravenous glucagon-like peptide-1 (1.2 pmol/kg/min) or placebo was infused between -30 and 330 mins. At 0 min, 100 mL liquid nutrient (1 kcal/mL) including 100 microg of 13C-octanoic acid and 3 grams of 3-O-methyl-glucose was administered.


RESULTS
Blood glucose, serum 3-O-methyl-glucose (as an index of glucose absorption), insulin and glucagon concentrations, as well as exhaled 13CO2 were measured. The gastric emptying coefficient was calculated to quantify gastric emptying. Data are presented as mean (sd). There was a nonsignificant trend for glucagon-like peptide-1 to slow gastric emptying (gastric emptying coefficient) (glucagon-like peptide-1, 2.45 [0.93] vs. placebo, 2.75 [0.83]; p = .09). In 11 of the 25 patients, gastric emptying was delayed during placebo infusion and glucagon-like peptide-1 had no detectable effect on gastric emptying in this group (1.92 [0.82] vs. 1.90 [0.68]; p = .96). In contrast, in patients who had normal gastric emptying during placebo, glucagon-like peptide-1 slowed gastric emptying substantially (2.86 [0.58] vs. 3.41 [0.37]; p = .006). Glucagon-like peptide-1 markedly reduced the rate of glucose absorption (3-O-methyl-glucose area under the curve(0-330), 37 [35] vs. 76 [51] mmol/L/min; p < .001), decreased preprandial glucagon (at 0 min change in glucagon, -15 [15] vs. -3 [14] pmol/L; p < .001), increased the insulin/glucose ratio throughout the infusion (area under the curve(-30-330), 1374 [814] vs. 1172 [649] mU/mmol/min; p = .041), and attenuated the glycemic response to the meal (glucose area under the curve(0-330), 2071 [353] vs. 2419 [594] mmol/L/min; p = .001).


CONCLUSIONS
Exogenous glucagon-like peptide-1 lowers postprandial glycemia in the critically ill. This may occur, at least in part, by slowing gastric emptying when the latter is normal but not when it is delayed.
Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia. Adam.Deane@adelaide.edu.au
Adam M
AM
Deane
Marianne J
MJ
Chapman
Robert J L
RJ
Fraser
Matthew J
MJ
Summers
Antony V
AV
Zaknic
James P
JP
Storey
Karen L
KL
Jones
Christopher K
CK
Rayner
Michael
M
Horowitz
D019325:3-O-Methylglucose / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D001944:Breath Tests; D016638:Critical Illness; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D007362:Intensive Care Units; D012121:Respiration, Artificial
D001786:Blood Glucose; D007328:Insulin; D019325:3-O-Methylglucose; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose