This work leverages detailed weight history data to provide further evidence for a complex mechanism underlying TCF7L2 action across the life course that may explain its associations with both T2D and BMI [3, 10–12], or the apparent statistical interaction between TCF7L2 genotype and adiposity on T2D related traits seen in previous cross-sectional studies of US Hispanic/Latinos [31]. This evidence concerns the gene TCF7L2 and type 2 diabetes mellitus.