title: Mechanisms Regulating Insulin Response to Intragastric Glucose in Lean and Non-Diabetic Obese Subjects: A Randomized, Double-Blind, Parallel-Group Trial.
abstract: OBJECTIVE
  The changes in blood glucose concentrations that result from an oral glucose challenge are dependent on the rate of gastric emptying, the rate of glucose absorption and the rate of insulin-driven metabolism that include the incretins, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). The rate of insulin-driven metabolism is clearly altered in obese subjects, but it is controversial which of these factors is predominant. We aimed to quantify gastric emptying, plasma insulin, C-peptide, glucagon and glucose responses, as well as incretin hormone secretions in obese subjects and healthy controls during increasing glucose loads.
  
  
  METHODS
  The study was conducted as a randomized, double-blind, parallel-group trial in a hospital research unit. A total of 12 normal weight (6 men and 6 women) and 12 non-diabetic obese (BMI > 30, 6 men and 6 women) participants took part in the study. Subjects received intragastric loads of 10 g, 25 g and 75 g glucose dissolved in 300 ml tap water.
  
  
  RESULTS
  Main outcome measures were plasma GLP-1 and GIP, plasma glucagon, glucose, insulin, C-peptide and gastric emptying. The primary findings are: i) insulin resistance (P < 0.001) and hyperinsulinemia (P < 0.001); ii) decreased insulin disposal (P < 0.001); iii) trend for reduced GLP-1 responses at 75 g glucose; and iv) increased fasting glucagon levels (P < 0.001) in obese subjects.
  
  
  CONCLUSIONS
  It seems that, rather than changes in incretin secretion, fasting hyperglucagonemia and consequent hyperglycemia play a role in reduced disposal of insulin, contributing to hyperinsulinemia and insulin resistance.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01875575.
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Anne Christin
authors.initials: AC
authors.lastname: Meyer-Gerspach
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Lucian
authors.initials: L
authors.lastname: Cajacob
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Daniele
authors.initials: D
authors.lastname: Riva
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Raphael
authors.initials: R
authors.lastname: Herzog
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Juergen
authors.initials: J
authors.lastname: Drewe
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
authors.affiliation: Department of Biomedicine, Division of Gastroenterology, University Hospital Basel, Basel, Switzerland.
authors.forename: Bettina K
authors.initials: BK
authors.lastname: Wölnerhanssen
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D001835:Body Weight; D002096:C-Peptide / Q000097:blood; D016022:Case-Control Studies; D003920:Diabetes Mellitus; D004311:Double-Blind Method; D005260:Female; D005746:Gastric Emptying; D005749:Gastric Inhibitory Polypeptide / Q000097:blood; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D054795:Incretins / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D054795:Incretins; D007328:Insulin; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D005947:Glucose