Impact of the tcf7l2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia

Research output: Contribution to journalArticle


Introduction: 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). Material and 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. Discussion: 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.


External organisations
  • Nordsjællands Hospital
  • University of Copenhagen
  • Herlev Hospital
  • Novo Nordisk A/S
  • Steno Diabetes Center
  • Skåne University Hospital
  • Institute for Molecular Medicine Finland (FIMM)
  • University of Helsinki
  • Panum Institute
  • Copenhagen University Hospital
  • Lægerne på Ellemarksvej
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes


  • Epidemiology, Experimental hypoglycaemia, Glucagon, Severe hypoglycaemia, TCF7L2, Type 1 diabetes
Original languageEnglish
Pages (from-to)53-60
Number of pages8
JournalEndocrine Connections
Issue number6
StatePublished - 2016 Nov 1
Publication categoryResearch