Abstract
IntroductionGlucagon-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.MethodsEleven 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.ResultsGLP-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.ConclusionsExogenous 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.Trial registrationANZCTR:ACTRN12610000185066
Highlights
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
In ambulant type-2 diabetics the GLP-1 analogue, exenatide, has been reported to achieve comparable reductions in glycated haemoglobin, but with less hypoglycaemia and a reduction in glycaemic variability when compared to insulin glargine [7]
For the above reasons GLP-1 is a potentially attractive therapeutic option for the management of hyperglycaemia in the substantial number of critically ill patients with pre-existing type-2 diabetes. This concept has been strengthened by our recent reports that acute administration of GLP-1 markedly attenuates the glycaemic response to enteral nutrients in critically ill patients with stress-hyperglycaemia [8,9]
Summary
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. For the above reasons GLP-1 is a potentially attractive therapeutic option for the management of hyperglycaemia in the substantial number of critically ill patients with pre-existing type-2 diabetes. This concept has been strengthened by our recent reports that acute administration of GLP-1 markedly attenuates the glycaemic response to enteral nutrients in critically ill patients with stress-hyperglycaemia [8,9]
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