Taken together, these mechanistic and epidemiologic data indicate that studies of arsenic and glucose–insulin dysregulation should be stratified by sex and include an assessment of arsenic methylation profiles (MMA/DMA and their reduced forms), hormonal status (e.g., pregnancy, estrogen/androgen levels) and relevant genotypes (e.g., AS3MT) to accurately evaluate sex-dependent risk of insulin resistance and T2D. This evidence concerns the gene INS and Insulin resistance.