title: Antidiabetogenic action of glucagon-like peptide-1 related to administration relative to meal intake in subjects with type 2 diabetes.
abstract: OBJECTIVE
  To establish the antidiabetogenic effect of glucagon-like peptide-1 (GLP-1) when differently administered relative to meal intake in subjects with type 2 diabetes.
  
  
  METHODS
  The study was a placebo-controlled comparison with random assignment to treatment sequence. A 3-h stepwise infusion of GLP-1 (17 nmol) was started either at the onset of a standard meal (550 kCal) (A) or at 30 min (B) or 60 min (C) after the start of the meal.
  
  
  METHODS
  The study was conducted at a university hospital.
  
  
  METHODS
  Eight patients with type 2 diabetes (four women and four men), age 62 +/- 3.9 years (range 47-74 years), weight 79.8 +/- 5.4 kg (range 62-104 kg), BMI 26.2 +/- 1.3 kg m(-2) (range 21-31 kg m(-2)), diabetes duration 10.5 +/- 2.0 years (range 3-19 years) and HbA1c levels 6.1 +/- 0.3% (range 4.7-7.7%) participated in the study. All patients were treated with oral sulphonylureas.
  
  
  RESULTS
  Glucagon-like peptide-1 significantly lowered postprandial glycaemia by a similar degree in all three situations versus the control meal (P < 0.05). Postprandial insulin levels were not different in the four experimental series, whereas the postprandial glucagon levels were significantly lowered by GLP-1 in (A) and (B) (P < 0.03) but not in (C). Gastric emptying, as determined by the paracetamol test, was retarded by GLP-1 only in (A) (P < 0.01), but not affected in (B) or (C).
  
  
  CONCLUSIONS
  GLP-1 reduced postprandial hyperglycaemia in subjects with type 2 diabetes regardless of administration at the onset of meal intake or at 30 or 60 min after start of meal intake, although the mechanism of the antidiabetogenic action of GLP-1 depended on administration versus meal intake. Thus, when administered at the start of a meal, GLP-1 was antidiabetogenic mainly through retarding gastric emptying, whereas when given at 30 or 60 min after meal ingestion, changes in islet hormone secretion seem to be predominant.
authors.affiliation: Department of Medicine, Södersjukhuset, Stockholm, Sweden.
authors.forename: M K
authors.initials: MK
authors.lastname: Gutniak
authors.forename: J
authors.initials: J
authors.lastname: Svartberg
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: N
authors.initials: N
authors.lastname: Adner
authors.forename: B
authors.initials: B
authors.lastname: Ahrén
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D004435:Eating; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000494:pharmacology*; D011498:Protein Precursors / Q000008:administration & dosage* / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D052216:Glucagon-Like Peptide 1; D005934:Glucagon