Exogenous glucagon-like peptide-1 attenuates the glycaemic response to postpyloric nutrient infusion in critically ill patients with type-2 diabetes.
BACKGROUND
Glucagon-like peptide-1 (GLP-1) attenuates the glycaemic response to small intestinal nutrient infusion in stress-induced hyperglycaemia and reduces fasting glucose concentrations in critically ill patients with type-2 diabetes. The objective of this study was to evaluate the effects of acute administration of GLP-1 on the glycaemic response to small intestinal nutrient infusion in critically ill patients with pre-existing type-2 diabetes.


METHODS
Eleven critically ill mechanically-ventilated patients with known type-2 diabetes received intravenous infusions of GLP-1 (1.2 pmol/kg/minute) and placebo from t = 0 to 270 minutes on separate days in randomised double-blind fashion. Between t = 30 to 270 minutes a liquid nutrient was infused intraduodenally at a rate of 1 kcal/min via a naso-enteric catheter. Blood glucose, serum insulin and C-peptide, and plasma glucagon were measured. Data are mean ± SEM.


RESULTS
GLP-1 attenuated the overall glycaemic response to nutrient (blood glucose AUC30-270 min: GLP-1 2,244 ± 184 vs. placebo 2,679 ± 233 mmol/l/minute; P = 0.02). Blood glucose was maintained at < 10 mmol/l in 6/11 patients when receiving GLP-1 and 4/11 with placebo. GLP-1 increased serum insulin at 270 minutes (GLP-1: 23.4 ± 6.7 vs. placebo: 16.4 ± 5.5 mU/l; P < 0.05), but had no effect on the change in plasma glucagon.


CONCLUSIONS
Exogenous GLP-1 in a dose of 1.2 pmol/kg/minute attenuates the glycaemic response to small intestinal nutrient in critically ill patients with type-2 diabetes. Given the modest magnitude of the reduction in glycaemia the effects of GLP-1 at higher doses and/or when administered in combination with insulin, warrant evaluation in this group.


BACKGROUND
ANZCTR:ACTRN12610000185066.
Discipline of Acute Care Medicine, University of Adelaide, North Terrace, Adelaide, South Australia 5000, Australia. adam.deane@adelaide.edu.au
Adam M
AM
Deane
Matthew J
MJ
Summers
Antony V
AV
Zaknic
Marianne J
MJ
Chapman
Robert J L
RJ
Fraser
Anna E
AE
Di Bartolomeo
Judith M
JM
Wishart
Michael
M
Horowitz
D001786:Blood Glucose / Q000187:drug effects*; D003422:Critical Care / Q000379:methods*; D016638:Critical Illness; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004750:Enteral Nutrition / Q000379:methods*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011708:Pylorus; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D052216:Glucagon-Like Peptide 1
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