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

Kristensen, Peter L.; Pedersen-Bjergaard, Ulrik; Due-Andersen, Rikke; Høi-Hansen, Thomas; Grimmeshave, Lise; Lyssenko, Valeriya LU ; Groop, Leif LU ; Holst, Jens J.; Vaag, Allan A. LU and Thorsteinsson, Birger (2016) In Endocrine Connections 5(6). p.53-60
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Epidemiology, Experimental hypoglycaemia, Glucagon, Severe hypoglycaemia, TCF7L2, Type 1 diabetes
in
Endocrine Connections
volume
5
issue
6
pages
8 pages
publisher
BioScientifica Ltd.
external identifiers
  • scopus:85046234366
ISSN
2049-3614
DOI
10.1530/EC-16-0050
language
English
LU publication?
yes
id
32dbb845-fe57-4763-bc5a-09084998b69a
date added to LUP
2018-05-16 15:45:23
date last changed
2018-10-03 12:09:03
@article{32dbb845-fe57-4763-bc5a-09084998b69a,
  abstract     = {<p>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.</p>},
  author       = {Kristensen, Peter L. and Pedersen-Bjergaard, Ulrik and Due-Andersen, Rikke and Høi-Hansen, Thomas and Grimmeshave, Lise and Lyssenko, Valeriya and Groop, Leif and Holst, Jens J. and Vaag, Allan A. and Thorsteinsson, Birger},
  issn         = {2049-3614},
  keyword      = {Epidemiology,Experimental hypoglycaemia,Glucagon,Severe hypoglycaemia,TCF7L2,Type 1 diabetes},
  language     = {eng},
  month        = {11},
  number       = {6},
  pages        = {53--60},
  publisher    = {BioScientifica Ltd.},
  series       = {Endocrine Connections},
  title        = {Impact of the tcf7l2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia},
  url          = {http://dx.doi.org/10.1530/EC-16-0050},
  volume       = {5},
  year         = {2016},
}