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No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect

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@article{79a79c7517e84e3a987146979f067336,
title = "No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect",
abstract = "The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes (T2D), possibly by modulation of incretin action. In this study, we evaluated the effect of the TCF7L2 rs7903146 T allele on the incretin effect and other glucometabolic parameters in normal glucose tolerant individuals (NGT) and participants with T2D. The rs7903146 variant was genotyped in cohorts of 61 NGT individuals (23 were heterozygous (CT) or homozygous (TT) T allele carriers) and 43 participants with T2D (20 with CT/TT). Participants were previously examined by an oral glucose tolerance test (OGTT) and a subsequent isoglycemic intravenous glucose infusion (IIGI). The incretin effect was assessed by quantification of the difference in integrated beta cell secretory responses during the OGTT and IIGI. Glucose and hormonal levels were measured during experimental days, and from these, indices of beta cell function and insulin sensitivity were calculated. No genotype-specific differences in the incretin effect were observed in the NGT group (P = 0.70) or the T2D group (P = 0.68). NGT T allele carriers displayed diminished glucose-dependent insulinotropic polypeptide response during OGTT (P = 0.01) while T allele carriers with T2D were characterized by lower C-peptide AUC after OGTT (P = 0.04) and elevated glucose AUC after OGTT (P = 0.04). In conclusion, our findings do not exclude that this specific TCF7L2 variant increases the risk of developing T2D via diminished incretin effect, but genotype-related defects were not detectable in these cohorts.",
keywords = "SNP, TCF7L2, incretin effect, incretins, transcription factor 7-like 2, type 2 diabetes, Incretins, Type 2 diabetes, Transcription factor 7-like 2, Incretin effect",
author = "Mathiesen, {David S} and Bagger, {Jonatan I} and Hansen, {Katrine Bagge} and Junker, {Anders E} and Astrid Plamboeck and Signe Harring and Thomas Idorn and Mads Hornum and Holst, {Jens J} and Jonsson, {Anna E} and Torben Hansen and Tina Vilsb{\o}ll and Asger Lund and Knop, {Filip K}",
year = "2020",
month = dec,
doi = "10.1530/EC-20-0471",
language = "English",
volume = "9",
pages = "1221--1232",
journal = "Endocrine Connections",
issn = "2049-3614",
publisher = "BioScientifica Ltd",
number = "12",

}

RIS

TY - JOUR

T1 - No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect

AU - Mathiesen, David S

AU - Bagger, Jonatan I

AU - Hansen, Katrine Bagge

AU - Junker, Anders E

AU - Plamboeck, Astrid

AU - Harring, Signe

AU - Idorn, Thomas

AU - Hornum, Mads

AU - Holst, Jens J

AU - Jonsson, Anna E

AU - Hansen, Torben

AU - Vilsbøll, Tina

AU - Lund, Asger

AU - Knop, Filip K

PY - 2020/12

Y1 - 2020/12

N2 - The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes (T2D), possibly by modulation of incretin action. In this study, we evaluated the effect of the TCF7L2 rs7903146 T allele on the incretin effect and other glucometabolic parameters in normal glucose tolerant individuals (NGT) and participants with T2D. The rs7903146 variant was genotyped in cohorts of 61 NGT individuals (23 were heterozygous (CT) or homozygous (TT) T allele carriers) and 43 participants with T2D (20 with CT/TT). Participants were previously examined by an oral glucose tolerance test (OGTT) and a subsequent isoglycemic intravenous glucose infusion (IIGI). The incretin effect was assessed by quantification of the difference in integrated beta cell secretory responses during the OGTT and IIGI. Glucose and hormonal levels were measured during experimental days, and from these, indices of beta cell function and insulin sensitivity were calculated. No genotype-specific differences in the incretin effect were observed in the NGT group (P = 0.70) or the T2D group (P = 0.68). NGT T allele carriers displayed diminished glucose-dependent insulinotropic polypeptide response during OGTT (P = 0.01) while T allele carriers with T2D were characterized by lower C-peptide AUC after OGTT (P = 0.04) and elevated glucose AUC after OGTT (P = 0.04). In conclusion, our findings do not exclude that this specific TCF7L2 variant increases the risk of developing T2D via diminished incretin effect, but genotype-related defects were not detectable in these cohorts.

AB - The T allele of TCF7L2 rs7903146 is a common genetic variant associated with type 2 diabetes (T2D), possibly by modulation of incretin action. In this study, we evaluated the effect of the TCF7L2 rs7903146 T allele on the incretin effect and other glucometabolic parameters in normal glucose tolerant individuals (NGT) and participants with T2D. The rs7903146 variant was genotyped in cohorts of 61 NGT individuals (23 were heterozygous (CT) or homozygous (TT) T allele carriers) and 43 participants with T2D (20 with CT/TT). Participants were previously examined by an oral glucose tolerance test (OGTT) and a subsequent isoglycemic intravenous glucose infusion (IIGI). The incretin effect was assessed by quantification of the difference in integrated beta cell secretory responses during the OGTT and IIGI. Glucose and hormonal levels were measured during experimental days, and from these, indices of beta cell function and insulin sensitivity were calculated. No genotype-specific differences in the incretin effect were observed in the NGT group (P = 0.70) or the T2D group (P = 0.68). NGT T allele carriers displayed diminished glucose-dependent insulinotropic polypeptide response during OGTT (P = 0.01) while T allele carriers with T2D were characterized by lower C-peptide AUC after OGTT (P = 0.04) and elevated glucose AUC after OGTT (P = 0.04). In conclusion, our findings do not exclude that this specific TCF7L2 variant increases the risk of developing T2D via diminished incretin effect, but genotype-related defects were not detectable in these cohorts.

KW - SNP

KW - TCF7L2

KW - incretin effect

KW - incretins

KW - transcription factor 7-like 2

KW - type 2 diabetes

KW - Incretins

KW - Type 2 diabetes

KW - Transcription factor 7-like 2

KW - Incretin effect

UR - http://www.scopus.com/inward/record.url?scp=85098247597&partnerID=8YFLogxK

U2 - 10.1530/EC-20-0471

DO - 10.1530/EC-20-0471

M3 - Journal article

C2 - 33252353

VL - 9

SP - 1221

EP - 1232

JO - Endocrine Connections

JF - Endocrine Connections

SN - 2049-3614

IS - 12

ER -

ID: 61371249