Changes in insulin content have also been associated with T2D-associated risk genes, such as at the peptidylglycine α-amidating monooxygenase (PAM) locus where T2D risk alleles cause reduced expression and/or function and reduced PAM expression is associated with reduced insulin content or for TCF7L2, the locus mediating the strongest risk for T2D and a master regulator of insulin production with decreased insulin content in carriers of the risk allele23–25. This evidence concerns the gene INS and type 2 diabetes mellitus.