Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1

Aims: It was the aim of the study to examine whether the insulinotropic gut hormone GLP-1 is able to control or even normalise glycaemia in healthy subjects receiving intravenous glucose infusions and in severely ill patients hyperglycaemic during total parenteral nutrition. Patients and methods: Eight healthy subjects and nine patients were examined. The volunteers received, in six separate experiments in randomised order, intravenous glucose at doses of 0, 2 and 5mg kg(-1) min(-1), each with intravenous GLP-l or placebo for 6 h. Patients were selected on the basis of hyperglycaemia (>150 mg/dl) during complete parenteral nutrition with glucose (3.2 +/- 1.4 mg kg(-1) min(-1)), amino acids (n = 8; 0.9 +/- 0.2 mg kg(-1) min(-1)), with or without lipid emulsions. Four hours (8 a.m. to 12 a.m. on parenteral nutrition plus NaCl as placebo) were compared to 4 h (12 a.m. to 4 p.m.) with additional GLP-1 administered intravenously. The dose of GLP-1 was 1.2 pmol kg(-1) min(-1). Blood was drawn for the determination of glucose, insulin, C-peptide, GLP-1, glucagon, and free fatty acids. Results: Glycaemia was raised dose-dependently by glucose infusions in healthy volunteers (p<0.0001). GLP-1 (similar to100-150 pmol/l) stimulated insulin and reduced glucagon secretion and reduced glucose concentrations into the normoglycaemic fasting range (all p < 0.05). In hyperglycaemic patients, glucose concentrations during the placebo period averaged 211 24 mg/dl. This level was reduced to 159 25 mg/dl with GLP-1 (p < 0.0001), accompanied by a rise in insulin (p = 0.0002) and C-peptide (p < 0.0001), and by trend towards a reduction in glucagon (p = 0.08) and free fatty acids (p = 0.02). GLP-1 was well tolerated. Conclusions: Hyperglycaemia during parenteral nutrition can be controlled by exogenous GLP-1, e.g. the natural peptide (available today), whereas the chronic therapy of Type 2 diabetes requires GLP-1 derivatives with longer duration of action. (C) 2004 Published by Elsevier B.V.