The Relationship Between Macrovascular Complications Of Type 2 Diabetes Mellitus And The Level Of Plasma Tetrahydrobiopterin

Background:Tetrahydrobiopterin(BH4) is a kind of essential cofactor of nitric oxide synthase,which can regulate nitric oxide synthase function and activity of nitric oxide. BH4 is the necessary cofactor for coupling L-arginine to the NAD(P)H oxidase enzyme in order for L-arginine to be oxidized to NO and L-citrulline. If this cofactor is not functioning properly the entire eNOS reaction uncouples and the endothelium becomes a net producer of superoxide (O2-) through the uncoupled NAD(P)H oxidase reaction. In addition to BH4 being the necessary cofactor it also serves as a naturally occurring antioxidant capable of scavenging reactive oxygen species (ROS) such as superoxide (O2-) and perioxynitrite (ONOO-). If BH4 is deficient in supply or function the eNOS reaction not only is capable of uncoupling with subsequent excess O2- and ONOO- but also is at a disadvantage in that there would be less BH4 to scavenge these local occurring reactive oxygen species being produced in excess amounts. More and more evidences show that maintenance of adequate BH4 levels in the endothelium is likely to be critical in regulating the balance of NO and superoxide synthesis by eNOS in vascular disease. It has been evident that decreased bioavailability of endothelial nitric oxide (NO) produced from endothelial NO synthase (eNOS), plays a crucial role in the development and progression of macrovascular complications. The purpose of this study is to evaluate the relationship between macrovascular complications of type 2 diabetes mellitus and the level of plasma BH4.Methods: This study was carried out on the patients with type 2 diabetes mellitus in TongJi Hospital between the years 2005 to 2006. 100 patients with type 2 diabetes mellitus were studied. According to whether complicated with macrovascular complications,these 100 patients were divided into two groups: 59 cases of type 2 diabetic patients with macrovascular complications and 41 cases of type 2 diabetic patients without macrovascular complications. All patients underwent a full physical examination and completed a general questionnaire. Body mass index(BMI), diabetes duration and age were recorded. Blood samples were collected for the determination of total cholesterol,HDL cholesterol,LDL cholesterol,triglyceride,serum insulin, serum glucose,tetrahydrobiopterin and C-reactive protein concentrations.Twenty-five healthy subjects were served as a control group.Results: The plasma BH4 levels were significantly decreased in T2DM group compared with control group(P<0.01). The plasma BH4 levels in the group of type 2 diabetes with macrovascular complications were decreased compared with that in the group of type 2 diabetes without macrovascular complications and that in the control group (P<0.01). Increasing as the HbA1c concentration,there is a decreasing tendency of the plasma BH4 level. Multiple regression analysis revealed that the plasma BH4 level was correlated negatively with total cholesterol and C-reactive protein.Conclusion The levels of plasma BH4 in type 2 diabetic patient is significantly decreased compared with that in control group. The levels of plasma BH4 is decreased in type 2 diabetic patient with macrovascular complications compared with that in type 2 diabetic patient without macrovascular complications. The results suggest that the decreasing BH4 may be associated with the incident and progress of macrovascular complications of type 2 diabetes mellitus.