title: Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia.
abstract: BACKGROUND
  In healthy carriers of the T allele of the transcription factor 7-like 2 (TCF7L2), fasting plasma glucagon concentrations are lower compared with those with the C allele. We hypothesised that presence of the T allele is associated with a diminished glucagon response during hypoglycaemia and a higher frequency of severe hypoglycaemia (SH) in type 1 diabetes (T1DM).
  
  
  METHODS
  This is a post hoc study of an earlier prospective observational study of SH and four mechanistic studies of physiological responses to hypoglycaemia. 269 patients with T1DM were followed in a one-year observational study. A log-linear negative binomial model was applied with events of SH as dependent variable and TCF7L2 alleles as explanatory variable. In four experimental studies including 65 people, TCF7L2 genotyping was done and plasma glucagon concentration during experimental hypoglycaemia was determined.
  
  
  RESULTS
  Incidences of SH were TT 0.54, TC 0.98 and CC 1.01 episodes per patient-year with no significant difference between groups. During experimental hypoglycaemia, the TCF7L2 polymorphism did not influence glucagon secretion.
  
  
  CONCLUSIONS
  Patients with T1DM carrying the T allele of the TCF7L2 polymorphism do not exhibit diminished glucagon response during hypoglycaemia and are not at increased risk of severe hypoglycaemia compared with carriers of the C allele.
authors.affiliation: Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark peter.lommer.kristensen.01@regionh.dk.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Kristensen
authors.affiliation: Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark.|Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Pedersen-Bjergaard
authors.affiliation: Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark.|Lægerne på EllemarksvejKøge, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Due-Andersen
authors.affiliation: Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark.|Department of CardiologyHerlev-Gentofte University Hospital, Herlev, Denmark.
authors.forename: Thomas
authors.initials: T
authors.lastname: Høi-Hansen
authors.affiliation: Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark.|Novo Nordisk A/SSøborg, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Grimmeshave
authors.affiliation: Steno Diabetes CenterGentofte, Denmark.|Lund University Diabetes CentreSkåne University Hospital, Malmø, Sweden.
authors.forename: Valeriya
authors.initials: V
authors.lastname: Lyssenko
authors.affiliation: Lund University Diabetes CentreSkåne University Hospital, Malmø, Sweden.|Finnish Institute for Molecular Medicine (FIMM)Helsinki University, Helsinki, Finland.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.|Department of Biomedical SciencesNNF Center for Basic Metabolic Research, The Panum Institute, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.|Department of EndocrinologyCopenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Allan A
authors.initials: AA
authors.lastname: Vaag
authors.affiliation: Department of CardiologyNephrology and Endocrinology, Nordsjællands Hospital, Hillerød, Denmark.|Faculty of Health and Medical SciencesUniversity of Copenhagen, Copenhagen, Denmark.
authors.forename: Birger
authors.initials: B
authors.lastname: Thorsteinsson
keywords: TCF7L2; epidemiology; experimental hypoglycaemia; glucagon; severe hypoglycaemia; type 1 diabetes