Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele

TY - JOUR

T1 - Incretin and pancreatic hormone secretion in Caucasian non-diabetic carriers of the TCF7L2 rs7903146 risk T allele

AU - Faerch, Kristine

AU - Pilgaard, Kasper

AU - Knop, Filip K

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Jørgensen, Torben

AU - Holst, Jens J

N1 - © 2012 Blackwell Publishing Ltd.

PY - 2013/1

Y1 - 2013/1

N2 - We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production. All participants had a 3-h oral glucose tolerance test (OGTT), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels (p=0.030), reduced first-phase insulin response (p=0.048), higher peripheral insulin sensitivity (p=0.050) and lower fasting GIP concentrations (p=0.003) than CC allele carriers. The latter was also reflected by lower total GIP secretion during the OGTT (p=0.018). We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1 between the groups. The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.

AB - We characterised 62 non-diabetic, middle-aged, Caucasians with and without the T risk allele of rs7903146 in transcription factor 7-like 2 (TCF7L2) with regard to secretion of insulin, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) as well as insulin sensitivity and endogenous glucose production. All participants had a 3-h oral glucose tolerance test (OGTT), an intravenous glucose tolerance test and a euglycaemic, hyperinsulinaemic clamp. After adjustment for age and sex, risk T allele carriers had higher haemoglobin A1c levels (p=0.030), reduced first-phase insulin response (p=0.048), higher peripheral insulin sensitivity (p=0.050) and lower fasting GIP concentrations (p=0.003) than CC allele carriers. The latter was also reflected by lower total GIP secretion during the OGTT (p=0.018). We found no significant differences in endogenous glucose production, hepatic insulin sensitivity or fasting concentrations of glucose, insulin, glucagon and GLP-1 between the groups. The findings suggest that the effect of TCF7L2 on diabetes risk may include reduced secretion of GIP.

U2 - 10.1111/j.1463-1326.2012.01675.x

DO - 10.1111/j.1463-1326.2012.01675.x

M3 - Journal article

C2 - 22862926

SN - 1462-8902

VL - 15

SP - 91

EP - 95

JO - Diabetes, Obesity and Metabolism

JF - Diabetes, Obesity and Metabolism

IS - 1

ER -