Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia

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Kristensen , P L , Pedersen-Bjergaard , U , Due-Andersen , R , Hoi-Hansen , T , Grimmeshave , L , Lyssenko , V , Groop , L , Holst , J J , Vaag , A A & Thorsteinsson , B 2016 , ' Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia ' , Endocrine Connections , vol. 5 , no. 6 , pp. 53-60 . https://doi.org/10.1530/EC-16-0050

Title: Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia
Author: Kristensen, Peter L.; Pedersen-Bjergaard, Ulrik; Due-Andersen, Rikke; Hoi-Hansen, Thomas; Grimmeshave, Lise; Lyssenko, Valeriya; Groop, Leif; Holst, Jens J.; Vaag, Allan A.; Thorsteinsson, Birger
Contributor: University of Helsinki, Institute for Molecular Medicine Finland
Date: 2016-11-01
Language: eng
Number of pages: 8
Belongs to series: Endocrine Connections
ISSN: 2049-3614
URI: http://hdl.handle.net/10138/173648
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 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.
Subject: type 1 diabetes
severe hypoglycaemia
TCF7L2
glucagon
epidemiology
experimental hypoglycaemia
ANGIOTENSIN-CONVERTING ENZYME
TYPE-1 DIABETES-MELLITUS
SYSTEM ACTIVITY
ADULT PATIENTS
FREQUENCY
GENE
AWARENESS
VARIANTS
GLUCOSE
ADOLESCENTS
3121 General medicine, internal medicine and other clinical medicine
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