Taken together, these findings support that the oxidative stress system (bilirubin or metabolites of bilirubin), the brain natriuretic peptide (BNP) hormone system, D6D activity and dimethylglycine may contribute to the development of diabetes or insulin resistance through secondary effects (i.e., pleiotropy) or direct mechanisms (11, 37, 42). Here, NPPB is linked to Insulin resistance.