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


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-1 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 ( approximately 100-150 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.
Nauck
Michael A
MA
Medizinische Klinik 1, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Gudrunstr. 56, D-44791 Bochum, Germany. M.Nauck@diabeteszentrum.de
Walberg
Jörg
J
Vethacke
Arndt
A
El-Ouaghlidi
Andrea
A
Senkal
Metin
M
Holst
Jens J
JJ
Gallwitz
Baptist
B
Gallwitz
J Baptist
JB
Schmidt
Wolfgang E
WE
Schmiegel
W
W
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1; D004763:Glucagon-Like Peptides; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D010919:Placebos
D001786:Blood Glucose; D005227:Fatty Acids; D007328:Insulin; D010446:Peptide Fragments; D010919:Placebos; C055453:glucagon-like peptide 1 (7-36)amide; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose