NRG4 and complication: Slattery et al. and our laboratory demonstrated that levels of Nrg4 gene expression were negatively regulated by oxidative stress [12], and circulating Nrg4 were negatively correlated with markers of oxidative stress (8-iso-prostaglandin F2α and gamma-glutamyltransferase) [3], raising the possibility that circulating Nrg4 may be protective against diabetic micro- and macrovascular complications because of its antioxidant properties, and altered level of circulating Nrg4 may be associated with the development of DN and DR.