In this light, the aim of the present pilot study is to evaluate the effects of the interaction between variants in 5 candidate genes (namely rs9939609 in FTO, rs17782313 near MC4R, rs326 in LPL, rs16147 in NPY, rs2943641 near IRS-1) and nutritional intervention as well as the impact/changes of the PREDIMED score and physical activity levels on the mid-term changes in the anthropometric and clinical parameters of overweight or obese subjects affected by T2D or impaired glucose regulation (IGR) over one-year period/12 months. This evidence concerns the gene MC4R and type 2 diabetes mellitus.