Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

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
; ; ; ; ; ; ; ; and
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
  • pmid:28611053
  • 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
2025-02-05 01:06:27
@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}},
  doi          = {{10.2337/dc17-0290}},
  volume       = {{40}},
  year         = {{2017}},
}