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
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
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. / Gjesing, A P; Kjems, L L; Vestmar, M A; Grarup, N; Linneberg, A; Deacon, C F; Holst, J J; Pedersen, O; Hansen, Torben.
In: Diabetologia, Vol. 54, No. 1, 01.01.2011, p. 103-10.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
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 low-risk 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/l¿×¿min vs TT carriers 97.9¿±¿89.2 mmol/l¿×¿min, p¿=¿0.001). TT carriers also had increased AUCs for proinsulin (CC carriers 6,030¿±¿3,001 pmol/l¿×¿min vs TT carriers 6,917¿±¿4,820 pmol/l¿×¿min, p¿=¿0.03), C-peptide (CC carriers 397.6¿±¿131.9 nmol/l¿×¿min vs TT carriers 417.1¿±¿109.3 nmol/l¿×¿min, p¿=¿0.04) and GIP (CC carriers 12,310¿±¿3,840 pmol/l¿×¿min vs TT carriers 14,590¿±¿5,910 pmol/l¿×¿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 low-risk 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/l¿×¿min vs TT carriers 97.9¿±¿89.2 mmol/l¿×¿min, p¿=¿0.001). TT carriers also had increased AUCs for proinsulin (CC carriers 6,030¿±¿3,001 pmol/l¿×¿min vs TT carriers 6,917¿±¿4,820 pmol/l¿×¿min, p¿=¿0.03), C-peptide (CC carriers 397.6¿±¿131.9 nmol/l¿×¿min vs TT carriers 417.1¿±¿109.3 nmol/l¿×¿min, p¿=¿0.04) and GIP (CC carriers 12,310¿±¿3,840 pmol/l¿×¿min vs TT carriers 14,590¿±¿5,910 pmol/l¿×¿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
VL - 54
SP - 103
EP - 110
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 1
ER -
ID: 35322786