title: A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads.
abstract: OBJECTIVE
  An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic glucose production during a hyperinsulinaemic-euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome.
  
  
  METHODS
  rs560887 was genotyped in the Inter99 cohort (n = 5,899), in 366 young, healthy Danes, in non-diabetic relatives of type 2 diabetic patients (n = 196), and in young and elderly twins (n = 159). Participants underwent an OGTT, an IVGTT or a 2 h hyperinsulinaemic-euglycaemic clamp.
  
  
  RESULTS
  The rs560887 G allele associated with elevated fasting plasma glucose (p = 2 x 10(-14)) but not with plasma glucose levels at 30 min (p = 0.9) or 120 min (p = 0.9) during an OGTT. G allele carriers had elevated levels of serum insulin at 30 min during an OGTT (p = 1 x 10(-4)) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p = 4 x 10(-4)) during an IVGTT. Among elderly twins, G allele carriers had higher basal hepatic glucose production (p = 0.04). Finally, the G allele associated with the risk of having IFG (OR 1.26, 95% CI 1.08-1.47, p = 0.002), but not with IGT (OR 0.94, 95% CI 0.82-1.08, p = 0.4) or type 2 diabetes (OR 0.93, 95% CI 0.84-1.04, p = 0.2).
  
  
  CONCLUSIONS
  The common rs560887 G allele in the G6PC2/ABCB11 locus is associated with increased fasting glycaemia and increased risk of IFG, associations that may be partly related to an increased basal hepatic glucose production rate.
authors: Hagedorn Research Institute, Gentofte, Denmark.
authors: C S
authors: CS
authors: Rose
authors: N
authors: N
authors: Grarup
authors: N T
authors: NT
authors: Krarup
authors: P
authors: P
authors: Poulsen
authors: L
authors: L
authors: Wegner
authors: T
authors: T
authors: Nielsen
authors: K
authors: K
authors: Banasik
authors: K
authors: K
authors: Faerch
authors: G
authors: G
authors: Andersen
authors: A
authors: A
authors: Albrechtsen
authors: K
authors: K
authors: Borch-Johnsen
authors: J O
authors: JO
authors: Clausen
authors: T
authors: T
authors: Jørgensen
authors: A
authors: A
authors: Vaag
authors: O
authors: O
authors: Pedersen
authors: T
authors: T
authors: Hansen
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D001786:Blood Glucose / Q000235:genetics*; D005215:Fasting / Q000097:blood*; D005260:Female; D005838:Genotype; D005947:Glucose / Q000096:biosynthesis*; D005951:Glucose Tolerance Test; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
chemical_list: C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D007328:Insulin; D005952:Glucose-6-Phosphatase; C492194:G6PC2 protein, human; D005947:Glucose