title: Blood glucose control in healthy subject and patients receiving intravenous glucose infusion or total parenteral nutrition using glucagon-like peptide 1.
abstract: 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.
authors.affiliation: Medizinische Klinik 1, St. Josef-Hospital, Klinikum der Ruhr-Universität Bochum, Gudrunstr. 56, D-44791 Bochum, Germany. M.Nauck@diabeteszentrum.de
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Jörg
authors.initials: J
authors.lastname: Walberg
authors.forename: Arndt
authors.initials: A
authors.lastname: Vethacke
authors.forename: Andrea
authors.initials: A
authors.lastname: El-Ouaghlidi
authors.forename: Metin
authors.initials: M
authors.lastname: Senkal
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Baptist
authors.initials: B
authors.lastname: Gallwitz
authors.forename: J Baptist
authors.initials: JB
authors.lastname: Gallwitz
authors.forename: Wolfgang E
authors.initials: WE
authors.lastname: Schmidt
authors.forename: W
authors.initials: W
authors.lastname: Schmiegel
mesh_terms: 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
chemical_list: 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