Carriers of the TCF7L2 rs7903146 TT genotype have elevated levels of plasma glucose, serum proinsulin and plasma gastric inhibitory polypeptide (GIP) during a meal test

TY - JOUR

T1 - Carriers of the TCF7L2 rs7903146 TT genotype have elevated levels of plasma glucose, serum proinsulin and plasma gastric inhibitory polypeptide (GIP) during a meal test

AU - Gjesing, A P

AU - Kjems, L L

AU - Vestmar, M A

AU - Grarup, N

AU - Linneberg, A

AU - Deacon, C F

AU - Holst, J J

AU - Pedersen, O

AU - Hansen, Torben

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Aims/hypothesis: The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele associates with type 2 diabetes in several populations, possibly mediated via decreased incretin secretion and/or action and altered beta and alpha cell function. We aimed to study circulating levels of glucose, proinsulin, insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and gastric inhibitory polypeptide (GIP) among individuals carrying the high-risk rs7903146 TT genotype and lowrisk CC genotype following a meal test. Methods: A meal challenge was performed in 31 glucose-tolerant men (age 54±7 years and BMI 26±3 kg/m2) with rs7903146 TT genotype and 31 glucose-tolerant age- and BMI-matched men with CC genotype (age 53±6 years and BMI 26±3 kg/m2). Serum proinsulin, insulin, C-peptide and plasma glucose, glucagon, GLP-1, GLP-2 and GIP were obtained 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 210, and 240 min after ingestion of a standardised breakfast meal. Results: An elevated incremental AUC for plasma glucose was observed among TT genotype carriers (CC carriers 21.8±101.9 mmol/lxmin vs TT carriers 97.9±89.2 mmol/ lxmin, p=0.001). TT carriers also had increased AUCs for proinsulin (CC carriers 6,030±3,001 pmol/lxmin vs TT carriers 6,917±4,820 pmol/lxmin, p=0.03), C-peptide (CC carriers 397.6±131.9 nmol/lxmin vs TT carriers 417.1± 109.3 nmol/lxmin, p=0.04) and GIP (CC carriers 12,310± 3,840 pmol/lxmin vs TT carriers 14,590±5,910 pmol/lx min, p=0.004). Conclusions/interpretation: Middle-aged normoglycaemic individuals carrying the rs7903146 TCF7L2 risk TT genotype show early signs of dysregulated glucose metabolism, decreased processing of proinsulin and elevated GIP secretion following a meal challenge.

AB - Aims/hypothesis: The transcription factor 7-like 2 (TCF7L2) rs7903146 T allele associates with type 2 diabetes in several populations, possibly mediated via decreased incretin secretion and/or action and altered beta and alpha cell function. We aimed to study circulating levels of glucose, proinsulin, insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-2 (GLP-2) and gastric inhibitory polypeptide (GIP) among individuals carrying the high-risk rs7903146 TT genotype and lowrisk CC genotype following a meal test. Methods: A meal challenge was performed in 31 glucose-tolerant men (age 54±7 years and BMI 26±3 kg/m2) with rs7903146 TT genotype and 31 glucose-tolerant age- and BMI-matched men with CC genotype (age 53±6 years and BMI 26±3 kg/m2). Serum proinsulin, insulin, C-peptide and plasma glucose, glucagon, GLP-1, GLP-2 and GIP were obtained 0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 210, and 240 min after ingestion of a standardised breakfast meal. Results: An elevated incremental AUC for plasma glucose was observed among TT genotype carriers (CC carriers 21.8±101.9 mmol/lxmin vs TT carriers 97.9±89.2 mmol/ lxmin, p=0.001). TT carriers also had increased AUCs for proinsulin (CC carriers 6,030±3,001 pmol/lxmin vs TT carriers 6,917±4,820 pmol/lxmin, p=0.03), C-peptide (CC carriers 397.6±131.9 nmol/lxmin vs TT carriers 417.1± 109.3 nmol/lxmin, p=0.04) and GIP (CC carriers 12,310± 3,840 pmol/lxmin vs TT carriers 14,590±5,910 pmol/lx min, p=0.004). Conclusions/interpretation: Middle-aged normoglycaemic individuals carrying the rs7903146 TCF7L2 risk TT genotype show early signs of dysregulated glucose metabolism, decreased processing of proinsulin and elevated GIP secretion following a meal challenge.

KW - Alleles

KW - Blood Glucose

KW - Gastric Inhibitory Polypeptide

KW - Genetic Predisposition to Disease

KW - Genotype

KW - Humans

KW - Male

KW - Middle Aged

KW - Proinsulin

KW - Transcription Factor 7-Like 2 Protein

U2 - 10.1007/s00125-010-1940-4

DO - 10.1007/s00125-010-1940-4

M3 - Journal article

C2 - 20957343

SN - 0012-186X

VL - 54

SP - 103

EP - 110

JO - Diabetologia

JF - Diabetologia

IS - 1

ER -