Advanced

The rs7903146 variant in the tcf7l2 gene increases the risk of prediabetes/type 2 diabetes in obese adolescents by impairing b-cell function and hepatic insulin sensitivity

Cropano, Catrina; Santoro, Nicola; Groop, Leif LU ; Man, Chiara Dalla; Cobelli, Claudio; Galderisi, Alfonso; Kursawe, Romy; Pierpont, Bridget; Goffredo, Martina and Caprio, Sonia (2017) In Diabetes Care 40(8). p.1082-1089
Abstract

OBJECTIVE In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents. RESEARCH DESIGN AND METHODS The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 6 2.36 years. RESULTS The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P =... (More)

OBJECTIVE In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents. RESEARCH DESIGN AND METHODS The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 6 2.36 years. RESULTS The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P = 0.009), and a trendwas seen also in Hispanics (P = 0.072). Also, the T allele was associated with decreased b-cell responsivity and IGT (P < 0.05). Suppression of endogenous hepatic glucose productionwas lower in subjects with the risk variant (P = 0.006). Finally, the odds of showing IGT/T2D at follow-up were higher in subjects carrying the minor allele (odds ratio 2.224; 95% CI 1.370-3.612; P = 0.0012). CONCLUSIONS The rs7903146 variant in the TCF7L2 gene increases the risk of IGT/T2D in obese adolescents by impairing b-cell function, and hepatic insulin sensitivity predicts the development of IGT/T2D over time.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes Care
volume
40
issue
8
pages
8 pages
publisher
American Diabetes Association
external identifiers
  • scopus:85028062087
  • wos:000406014200025
ISSN
0149-5992
DOI
10.2337/dc17-0290
language
English
LU publication?
yes
id
d8224f66-b187-484c-87dd-2f8453b258da
date added to LUP
2017-09-04 09:42:37
date last changed
2018-04-29 04:41:57
@article{d8224f66-b187-484c-87dd-2f8453b258da,
  abstract     = {<p>OBJECTIVE In this study, we aimed to explore the mechanism by which TCF7L2 rs7903146 risk allele confers susceptibility to impaired glucose tolerance (IGT) or type 2 diabetes (T2D) in obese adolescents. RESEARCH DESIGN AND METHODS The rs7903146 variant in the TCF7L2 gene was genotyped in a multiethnic cohort of 955 youths. All subjects underwent an oral glucose tolerance test with the use of the Oral Minimal Model to assess insulin secretion, and 33 subjects underwent a hyperinsulinemic-euglycemic clamp. In 307 subjects, a follow-up oral glucose tolerance test was repeated after 3.11 6 2.36 years. RESULTS The TCF7L2 rs7903146 risk allele was associated with higher 2-h glucose levels in Caucasians (P = 0.006) and African Americans (P = 0.009), and a trendwas seen also in Hispanics (P = 0.072). Also, the T allele was associated with decreased b-cell responsivity and IGT (P &lt; 0.05). Suppression of endogenous hepatic glucose productionwas lower in subjects with the risk variant (P = 0.006). Finally, the odds of showing IGT/T2D at follow-up were higher in subjects carrying the minor allele (odds ratio 2.224; 95% CI 1.370-3.612; P = 0.0012). CONCLUSIONS The rs7903146 variant in the TCF7L2 gene increases the risk of IGT/T2D in obese adolescents by impairing b-cell function, and hepatic insulin sensitivity predicts the development of IGT/T2D over time.</p>},
  author       = {Cropano, Catrina and Santoro, Nicola and Groop, Leif and Man, Chiara Dalla and Cobelli, Claudio and Galderisi, Alfonso and Kursawe, Romy and Pierpont, Bridget and Goffredo, Martina and Caprio, Sonia},
  issn         = {0149-5992},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {1082--1089},
  publisher    = {American Diabetes Association},
  series       = {Diabetes Care},
  title        = {The rs7903146 variant in the tcf7l2 gene increases the risk of prediabetes/type 2 diabetes in obese adolescents by impairing b-cell function and hepatic insulin sensitivity},
  url          = {http://dx.doi.org/10.2337/dc17-0290},
  volume       = {40},
  year         = {2017},
}