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Evidence for an influence of TCF7L2 polymorphism rs7903146 on insulin resistance and sensitivity indices in overweight children and adolescents during a lifestyle intervention

International Journal of Obesity volume 32, pages 1521–1524 (2008)Cite this article

Abstract

Objective:

The T allele of the single-nucleotide polymorphism rs7903146 in TCF7L2 (transcription factor 7 like 2 gene) is associated with type 2 diabetes mellitus. The aim of this study was to analyze whether there is an allele-dosage effect on changes of insulin resistance and sensitivity indices in overweight children participating in a lifestyle intervention.

Methods:

We genotyped rs7903146 in 236 overweight children (mean age 10.7 years, mean body mass index (BMI) 28.1 kg/m2) completing a 1-year lifestyle intervention. Degree of overweight as BMI-SDS, homeostasis model assessment for insulin resistance (HOMA-IR) and the insulin sensitivity index QUICKI were measured before and after intervention.

Results:

Lifestyle intervention resulted in an overweight reduction of −0.29±0.02 BMI-SDS. HOMA-IR (−0.63±0.22) and QUICKI (+0.008±0.003) indices improved significantly (P<0.05) in the course of the intervention in the 155 children with a decrease of BMI-SDS. There was an additive negative effect of T allele on changes of HOMA-IR (P=0.041) and QUICKI (P=0.001) in linear regression analyses adjusted to changes of weight status, age, gender and pubertal stage.

Conclusion:

Overweight children showed a negative dosage-allele effect per T allele at single-nucleotide polymorphism rs7903146 in TCF7L2 concerning an improvement of insulin resistance and sensitivity after overweight reduction in a lifestyle intervention. This finding further suggests that this polymorphism might be involved in glucose metabolism.

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Acknowledgements

We thank all probands and their families for their participation. This work was supported by grants from the German Ministry of Education and Research (Bundesministerium für Bildung und Forschung; National Genome Research Network, NGFN1 and 2 and NGFNplus, obesity network LARGE), the European Union (FP6 LSHMCT-2003-503041) and the Deutsche Forschungsgemeinschaft (DFG; HE 1446/4-1). The skilful technical assistance of S Düerkop and Essen was highly appreciated.

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Authors and Affiliations

  1. Department of Pediatric Nutrition Medicine, Vestische Hospital for Children and Adolescents, University of Witten/Herdecke, Witten, Germany

    T Reinehr

  2. Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany

    S Friedel, T D Mueller, J Hebebrand & A Hinney

  3. Division of Health and Social Care Research, King's College London, London, UK

    A M Toschke

Authors
  1. T Reinehr
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  2. S Friedel
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  3. T D Mueller
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  4. A M Toschke
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  5. J Hebebrand
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  6. A Hinney
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Corresponding author

Correspondence to T Reinehr.

Additional information

This study is registered at clinicaltrials.gov (NCT00435734).

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Reinehr, T., Friedel, S., Mueller, T. et al. Evidence for an influence of TCF7L2 polymorphism rs7903146 on insulin resistance and sensitivity indices in overweight children and adolescents during a lifestyle intervention. Int J Obes 32, 1521–1524 (2008). https://doi.org/10.1038/ijo.2008.146

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