Article

Diabetologia

, Volume 52, Issue 10, pp 2122-2129

First online:

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

  • C. S. RoseAffiliated withHagedorn Research Institute
  • , N. GrarupAffiliated withHagedorn Research Institute
  • , N. T. KrarupAffiliated withHagedorn Research Institute
  • , P. PoulsenAffiliated withSteno Diabetes Center
  • , L. WegnerAffiliated withHagedorn Research Institute
  • , T. NielsenAffiliated withHagedorn Research Institute
  • , K. BanasikAffiliated withHagedorn Research Institute
  • , K. FærchAffiliated withSteno Diabetes Center
  • , G. AndersenAffiliated withHagedorn Research Institute
    • , A. AlbrechtsenAffiliated withDepartment of Biostatistics, University of Copenhagen
    • , K. Borch-JohnsenAffiliated withFaculty of Health Sciences, University of AarhusSteno Diabetes Center
    • , J. O. ClausenAffiliated withSteno Diabetes Center
    • , T. JørgensenAffiliated withResearch Centre for Prevention and Health, Glostrup University HospitalFaculty of Health Sciences, University of Copenhagen
    • , A. VaagAffiliated withSteno Diabetes Center
    • , O. PedersenAffiliated withHagedorn Research InstituteFaculty of Health Sciences, University of AarhusFaculty of Health Sciences, University of Copenhagen
    • , T. HansenAffiliated withHagedorn Research InstituteFaculty of Health Sciences, University of Southern Denmark Email author 

Abstract

Aims/hypothesis

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 × 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 × 10−4) and relatives of type 2 diabetes patients carrying the G allele had an increased acute insulin response (p = 4 × 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/interpretation

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.

Keywords

ABCB11 Association study G6PC2 Genetic variants Glucose production Hepatic Insulin release Type 2 diabetes