Gene Variants of TCF7L2 Influence Weight Loss and Body Composition During Lifestyle Intervention in a Population at Risk for Type 2 Diabetes

Overview

Journal Diabetes

Specialty Endocrinology

Date 2009 Dec 24

PMID 20028944

Citations 36

Authors

Axel Haupt

Claus Thamer

Martin Heni

Caroline Ketterer

Jurgen Machann

Fritz Schick

Fausto Machicao

Norbert Stefan

Claus D Claussen

Hans-Ulrich Haring

Andreas Fritsche

Harald Staiger

Affiliations

Soon will be listed here.

Abstract

Objective: The impact of the diabetes risk gene transcription factor 7-like 2 (TCF7L2) on body weight is unclear. As TCF7L2 is expressed in adipose tissue and involved in Wnt-dependent regulation of adipogenesis, we studied the impact of TCF7L2 variants on body composition and weight loss during lifestyle intervention.

Research Design And Methods: We genotyped 309 German subjects at increased risk for type 2 diabetes for single nucleotide polymorphisms (SNPs) rs7903146, rs12255372, rs11196205, and rs7895340 in TCF7L2 and performed oral glucose tolerance tests before and after a 9-month lifestyle intervention. Fat distribution was quantified using whole-body magnetic resonance imaging/spectroscopy in a subgroup of 210 subjects.

Results: After adjustment for confounding variables, we observed a negative impact of the type 2 diabetes allele of SNP rs7903146 on change in BMI (P = 0.0034) and on changes in nonvisceral (P = 0.0032) and visceral fat (P = 0.0165) during lifestyle intervention. An association of rs7903146 with lifestyle intervention-induced changes in insulin secretion, glucose concentrations, liver fat, or insulin sensitivity were not detected (all P > 0.2). Essentially the same results were obtained with SNP rs1255372. In contrast, we found no effects of SNPs rs11196205 and rs7895340 on change in BMI (all P > or = 0.5).

Conclusions: Our data reveal that diabetes-associated alleles of TCF7L2 are associated with less weight loss in response to lifestyle intervention. Thus, diabetes-associated TCF7L2 gene variation predicts the success of lifestyle intervention in terms of weight loss and determines individual susceptibility toward environmental factors.

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