NOS3 and diabetes mellitus: As a novel therapeutic target for diabetes and its complications, BH4 supplementation improves insulin sensitivity (Nystrom et al, 2004) and attenuates hyperglycemia (Abudukadier et al, 2013), with previous studies describing a BH4–eNOS–mediated enhancement of vascular relaxation and diastolic function in cardiovascular disease (Baumgardt et al, 2016).