Effect of Diet Quality and Genetic Predisposition on Hemoglobin A1c and Type 2 Diabetes Risk: Gene-Diet Interaction Analysis of 357,419 Individuals

<b>OBJECTIVE</b>: To assess the interactions between diet quality and genetic predisposition to incident type 2 diabetes (T2D). <p><b>RESEARCH DESIGN AND METHODS:</b><b> </b>357,419 participants with genetic and complete dietary data from the UK Biobank, were enrolled between 2006 and 2010 and were prospectively followed up to 2017.<b> </b><a>The genetic risk score (GRS) was calculated on the basis of 424 variants associated with T2D risk and a higher GRS indicates a higher genetic predisposition to T2D. </a>The adherence to a healthy diet was assessed by a diet quality score comprising of 10 important dietary components, with a higher score representing a higher overall diet quality.<b></b></p> <p><b>RESULTS<a>:</a></b> 5,663 incident T2D cases were documented during an average of 8.1 years of follow-up. A significant negative interaction was observed between GRS and diet quality score. After adjusting for major risk factors, per SD increment in GRS and diet quality score was associated with a 54% higher and a 9% lower risk of T2D, respectively. Besides, a simultaneous increment of 1 SD in both diet quality score and GRS was additionally associated with a 3% lower T2D risk due to the antagonistic interaction. In categorical analyses, a sharp reduction of 23% in T2D risk associated with 1 SD increment in diet quality score was detected among participants in the extremely high GRS group (GRS>95%). We also observed a strong negative interaction between GRS and diet quality score on blood HbA1c level at baseline (P<0.001).</p> <b>CONCLUSIONS: </b>The adherence to a healthy diet was associated with more reductions in blood HbA1c levels and subsequent T2D risk among individuals with higher genetic risk. Our findings support tailoring dietary recommendations to an individual’s genetic makeup for T2D prevention.