Increased basal levels of plasma nitric oxide in Type 2 diabetic subjects - Relationship to microvascular complications

To assess the underlying mechanisms of decreased endothelial function and a dvanced vascular complications in patients with Type 2 diabetes, we determi ned basal levels of plasma nitric oxide (NOx: NO2 (-) and NO3 (-)) using a newly developed high-performance liquid chromatography (HPLC)-Griess method in hospitalized 129 diabetic and 76 nondiabetic subjects, and examined the ir clinical characteristics. Serum lipid peroxide and advanced glycation en d products (AGEs) as markers of oxidative stress were also measured, and in tima-media thickness (IMT) of the carotid artery was evaluated as a marker of atherosclerosis. In diabetic subjects, microvascular complications were newly evaluated during their admission. There were no differences in age or sex between the diabetic and nondiabetic subjects. Although there was no d ifference in basal plasma NO2 (-) levels between the two groups, the basal levels of plasma NO3 (-) in diabetic subjects were significantly higher tha n those in nondiabetic subjects. Plasma NOx levels in neither diabetic nor nondiabetic subjects correlated with serum lipids, HbAlc, or IMT. In diabet ic subjects, plasma NO3 (-) levels were related not only to the presence of hypertension but also to advanced microvascular complications. Moreover, p lasma NO3 (-) levels were positively correlated with both serum lipid perox ide and AGEs. Multiple regression analysis revealed that serum AGEs level w as strongly associated with plasma NO3 (-) level. Thus, the findings are co nsistent with the hypothesis that decreased endothelium-dependent vasodilat ion in diabetic subjects is associated with the impaired action of NO secon dary to its inactivation resulting from increased oxidative stress, rather than decreased NO production from vascular endothelium, and that abnormal N O metabolism is related to advanced diabetic microvascular complications. ( C) 2001 Elsevier Science Inc. All rights reserved.