For instance, individual studies have shown that the renin–angiotensin–aldosterone system inhibitors might decrease the risk of new-onset type 2 diabetes,10, 11, 12, 13 whereas diuretics could increase that risk (appendix p 13).14, 15 Consequently, it remains uncertain whether the protective or adverse events associated with blood pressure lowering medications are due to blood pressure reduction or off-target effects of the drugs. The gene discussed is REN; the disease is type 2 diabetes mellitus.