[Oxidative stress].

Increased oxidative stress has been paid attention to as an important causative factor for diabetic cardiovascular complications. Hyperglycemic state are supposed to induce the overproduction of reactive oxygen species (ROS) through various mechanisms including increased non-enzymatic glycation end products (AGEs) formation, increased polyol pathway flux, increased O2-production from mitochondrial and protein kinase C (PKC)-dependent NAD (P) H oxidase activation in cardiovasucular tissues. Oxidative modification of lipoprotein is critical for atheromatous lesion formation. O2- reacts with nitric oxide (NO), resulting in loss of NO's anti-atherogenic properties. Thus, the causative role of oxidative stress in diabetic cardiovascular complications has been implicated, but there has been little human evidence showing the beneficial effect of antioxidants. Here we introduce our human study showing that congenital hyperbilirubinemia in diabetic patients with Gilbert's syndrome protects against cardiovascular events as well as microangiopathy along with the amelioration of enhanced oxidative stress in diabetes, implicating the causative role of oxidative stress.