Gene variants of TCF7L2 influence weight loss and body composition during lifestyle intervention in a population at risk for type 2 diabetes

Diabetes. 2010 Mar;59(3):747-50. doi: 10.2337/db09-1050. Epub 2009 Dec 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Body Composition / genetics*
  • Diabetes Mellitus, Type 2 / epidemiology*
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Genetic Variation*
  • Glucose Tolerance Test
  • Humans
  • Life Style
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk Factors
  • TCF Transcription Factors / genetics*
  • Transcription Factor 7-Like 2 Protein
  • Weight Loss / genetics*
  • Young Adult


  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein