Nitric oxide metabolism is impaired by type 1 diabetes and diabetic nephropathy

Diabetes leads to reduced nitric oxide bioavailability, resulting in endothelial dysfunction. However, overproduction of nitric oxide due to hyperglycaemia is associated with oxidative stress and tissue damage. The objective of this study was to characterise nitric oxide production (NO) and added nitrite and nitrate (NO₂ ^-+NO₃ ^-) concentration in the blood and urine of patients with and without diabetic nephropathy. A total of 268 patients with type 1 diabetes and 69 healthy subjects were included. Diabetic nephropathy was defined as macroalbuminuria and/or estimated glomerular filtration rate below 60 ml/min/1.73 cm². NO₂ ^-+NO₃ ^- concentration was measured by Griess reaction. Production of NO was detected by electron paramagnetic resonance spectroscopy. Blood NO was demonstrated to be higher (P<0.001) and serum NO₂ ^-+NO₃ ^- was lower (P=0.003) in patients with type 1 diabetes and no nephropathy vs. healthy subjects. However, serum NO₂ ^-+NO₃ ^- concentration in patients with diabetes and nephropathy did not differ from the levels observed in healthy controls. Urine excretion of NO₂ ^-+NO₃ ^- was significantly decreased in patients with nephropathy, compared with patients without diabetic kidney disease (P=0.006) and healthy subjects (P=0.010). A significant positive correlation was observed between urine NO₂ ^-+NO₃ ^- and estimated glomerular filtration rate in patients with type 1 diabetes (P=0.002) and healthy subjects (P=0.008). Estimated glomerular filtration rate, albuminuria and diabetic nephropathy status were significant predictors of the whole blood NO and NO₂ ^-+NO₃ ^- in serum and urine in patients with type 1 diabetes, as identified by linear regression models. The present study concludes that NO metabolism is impaired by type 1 diabetes and diabetic nephropathy.