TCF7L2 genetic variants modulate the effect of dietary fat intake on changes in body composition during a weight-loss intervention

Abstract

Background: TCF7L2 gene variants have been associated with increased risk of type 2 diabetes and higher adiposity. Observational studies and short-term trials have suggested that macronutrients may modify these effects. However, to our knowledge, this has yet to be verified in long-term interventions.

Objective: In a long-term intervention setting, we investigated the effects of TCF7L2 polymorphisms rs7903146 and rs12255372 and dietary total fat on changes in body composition and subsequent glycemic control.

Design: Data were analyzed for 591 participants in the Preventing Overweight Using Novel Dietary Strategies (Pounds Lost) trial, which is a 2-y weight-loss randomized clinical trial of diets that differed in macronutrient proportions. Adjusted means for changes in body composition at 6 and 24 mo were obtained for gene main effects and interactions with a low-fat diet (20% from energy) compared with a high-fat diet (40% from energy). Interactions with protein and carbohydrate intakes were also tested. Predicted changes in glycemic control from changes in adiposity were determined by genotype and diet type.

Results: Significant interactions were observed for rs12255372 TT (risk genotype) and fat intake for changes in BMI, total fat mass, and trunk fat mass (all P/q < 0.05) at 6 mo, with nonsignificant larger decreases for TT carriers on a low-fat diet. No significant associations were observed at 24 mo or for other macronutrients. Changes in body composition for TT carriers predicted reductions in plasma glucose and insulin only on the low-fat diet.

Conclusions: Individuals with the TCF7L2 rs12255372 risk genotype may reduce body adiposity by consuming a diet lower in total fat. These reductions may induce better glycemic control for such individuals predisposed to type 2 diabetes. The Pounds Lost trial was registered at clinicaltrials.gov as NCT00072995.

Figures

FIGURE 1.

Adjusted mean (±SE) gene-nutrient interactions between TCF7L2 rs12255372 and total dietary fat intake as assigned at random to participants in the Preventing Overweight Using Novel Dietary Strategies trial for changes in body-composition measures at 6 mo. Values were from linear mixed models adjusted for age, sex, center, and baseline value. The mean difference (±SE) and adjusted P value by using Tukey's test for multiple comparisons are indicated at the bottom of each panel. The low-fat group (black bars) included individuals who were randomly assigned to consume diets with a target for total fat of 20% from energy; the high-fat group (gray bars) included individuals who were randomly assigned to consume diets with a target for total fat of 40% from energy. Significance for interactions is reported as the P value/adjusted q value from a positive false discovery rate correction.