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

Abstract

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. 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. 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. 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.