Abstract
BackgroundEndothelial dysfunction in diabetes has been attributed to lack of nitric oxide (NO) bioavailability. Oxidized LDL (OxLDL) and NO play antagonist roles in endothelium dysfunction. OxLDL inhibits NO-mediated arterial vasodilatory function, but it is not clear whether other modified LDLs influence NO availability or not. We investigated the relationship between plasma NO and modified LDLs in African Americans with diabetes.Methods146 patients with diabetes were recruited from medical clinics over 6-month period. Plasma total NO and modified LDLs levels (Glycated, gLDL; Oxidized, oxLDL; Nitrated, nLDL; and Carbamylated, cLDL) were measured by ELISA. Microvascular function was assessed by vascular reactivity index (VRI), which assess changes in digital temperature before and after release of arterial cuff occlusion. Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV) using applanation tonometry. Patient population was categorized into two groupsgood glycemic control (HbA1c≤7.0; N=85) and poor glycemic control (HbA1c>7.0; N=61).ResultsAge 60±8 years, female 64%, hypertension 82%, dyslipidemia 83%, diabetes duration 10.2±7.6 years, HbA1c= 8.1±2.2%. In the total population, NO levels were negatively correlated with oxLDL (r=-0.425, p=0.0001) and gLDL (r=-0.303, p=0.0001), but not nLDL nor cLDL. OxLDL alone correlated with VRI (r=-0.252, p=0.002) and PWV (r=0.187, p=0.027). There was no correlation between NO and vascular outcome. In poorly-controlled group, NO correlated with oxLDL (r=-0.455, p=0.0001), gLDL (r=-0.265, p=0.0001) and nLDL (r=- 0.265, p=0.0140). Univariate analysis showed that oxLDL independently predicted NO availability (β=-0.551, p=0.0001) and VRI (β=-0.853, p=0.007) but not PWV. Multiple linear regression analysis showed that total NO was independently associated with plasma oxLDL levels (β=-0.422, p=0.034, r=0.462) even after adjusting for other variables.ConclusionoxLDL is the only predictor for NO bioavailability, suggesting that generation of oxLDL and reduced NO bioavailability could contribute to early microvascular dysfunction in diabetic patients. Larger prospective studies are needed to clarify these findings.