No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect
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No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect. / Mathiesen, David S.; Bagger, Jonatan; Hansen, Katrine B.; Junker, Anders E.; Plamboeck, Astrid; Harring, Signe; Idorn, Thomas; Hornum, Mads; Holst, Jens J.; Jonsson, Anna E.; Hansen, Torben; Vilsbøll, Tina; Lund, Asger; Knop, Filip K.
I: Endocrine Connections, Bind 9, Nr. 12, 2020, s. 1221-1232.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - No detectable effect of a type 2 diabetes-associated TCF7L2 genotype on the incretin effect
AU - Mathiesen, David S.
AU - Bagger, Jonatan
AU - Hansen, Katrine B.
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
Y1 - 2020
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 - TCF7L2
KW - transcription factor 7-like 2
KW - SNP
KW - incretin effect
KW - incretins
KW - type 2 diabetes
KW - ORAL GLUCOSE-TOLERANCE
KW - BETA-CELL FUNCTION
KW - INSULIN-SECRETION
KW - GENETIC-VARIATION
KW - NONDIABETIC PATIENTS
KW - RISK
KW - RS7903146
KW - POLYMORPHISMS
KW - GLUCAGON
KW - GLP-1
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: 255051278