Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia
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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; Groop, Leif; Holst, Jens J; Vaag, Allan; Thorsteinsson, Birger.
In: Endocrine Connections, Vol. 5, No. 6, 2016, p. 53-60.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Impact of the TCF7L2 genotype on risk of hypoglycaemia and glucagon secretion during hypoglycaemia
AU - Kristensen, Peter L
AU - Pedersen-Bjergaard, Ulrik
AU - Due-Andersen, Rikke
AU - Høi-Hansen, Thomas
AU - Grimmeshave, Lise
AU - Lyssenko, Valeriya
AU - Groop, Leif
AU - Holst, Jens J
AU - Vaag, Allan
AU - Thorsteinsson, Birger
N1 - © 2016 The authors.
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Journal Article
U2 - 10.1530/EC-16-0050
DO - 10.1530/EC-16-0050
M3 - Journal article
C2 - 27758844
VL - 5
SP - 53
EP - 60
JO - Endocrine Connections
JF - Endocrine Connections
SN - 2049-3614
IS - 6
ER -
ID: 176451142