Due to the mounting evidence on potential selection bias and the multi-faceted action of TCF7L2 variation on insulin and glucose biology [5, 6, 18], we aimed 1) to replicate the multivariable association between TCF7L2 T2D risk alleles and lower BMI in a population-based study of US Hispanic/Latinos accounting for key covariates, and 2) to model the structured pathways between rs7903146, at TCF7L2, BMI over time, and age of diabetes diagnosis. This evidence concerns the gene INS and diabetes mellitus.