We examined interactions between macronutrients and SNPs from 9 candidate genetic loci [TCF7L2, gastric inhibitory polypeptide receptor (GIPR), insulin receptor substrate 1 (IRS1), peroxisome proliferator–activated receptor γ (PPARγ), apolipoprotein A2 (APOA2), CAV2, fatty acid binding protein 1/2/3/4 (FABP1/2/3/4), PPARγ coactivator-1α (PGC-1α), and peptidase D (PEPD)] and a genetic risk score comprising variants in 15 T2D-associated loci (36). This evidence concerns the gene IRS1 and type 2 diabetes mellitus.