title: Glucagon responses to increasing oral loads of glucose and corresponding isoglycaemic intravenous glucose infusions in patients with type 2 diabetes and healthy individuals.
abstract: OBJECTIVE
  Type 2 diabetes is associated with hypersecretion of glucagon during an OGTT, whereas i.v. glucose suppresses glucagon levels. This suggests that type 2 diabetic hyperglucagonaemia may result from glucose stimulation of the gastrointestinal tract. We evaluated glucagon responses to increasing amounts of glucose given orally and corresponding isoglycaemic i.v. glucose infusions (IIGIs) in patients with type 2 diabetes and in healthy controls.
  
  
  METHODS
  Plasma glucagon responses were measured during three 4 h OGTTs with increasing loads of glucose (25 g, 75 g and 125 g) and three corresponding IIGIs in eight patients with type 2 diabetes (age [mean ± SEM] 57 ± 4 years; BMI 29.5 ± 1.0 kg/m(2); HbA1c 7.0 ± 0.3% [53 ± 2 mmol/mol]) and eight healthy individuals (age 57 ± 4 years; BMI 28.9 ± 0.7 kg/m(2); HbA1c 5.4 ± 0.1% [36 ± 1 mmol/mol]).
  
  
  RESULTS
  In healthy controls no difference in glucagon suppression during the first 45 min of the 25 g OGTT and the corresponding IIGI (-153 ± 35 vs -133 ± 24 min × pmol/l; p = NS) was observed, whereas patients with type 2 diabetes only exhibited significant glucagon suppression following IIGI (29 ± 27 vs -144 ± 20 min × pmol/l; p = 0.005). At higher oral glucose loads this difference increased and also became evident in healthy controls.
  
  
  CONCLUSIONS
  In patients with type 2 diabetes increasing amounts of oral glucose elicit hypersecretion of glucagon, whereas corresponding IIGIs result in significant glucagon suppression; a phenomenon that is also observed in healthy individuals when larger glucose loads are ingested orally. This suggests that the hyperglucagonaemic response to oral glucose in type 2 diabetes may represent a pathological version of a gut-derived physiological phenomenon.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00529048.
authors.affiliation: Center for Diabetes Research, Department of Medicine, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, 2900, Hellerup, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.forename: Asger
authors.initials: A
authors.lastname: Lund
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000284:Administration, Oral; D001786:Blood Glucose; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005934:Glucagon / Q000097:blood*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007262:Infusions, Intravenous; D007328:Insulin / Q000097:blood; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D005947:Glucose