Endocrine Abstracts

Background: Hypoxia, oxidative stress and inflammation induced by hyperglycaemia are ‘key players’ in development of diabetic complications.

Aim: To analyze differences in levels of nitric oxide (NO) and its metabolites nitrate and nitrite (NO2/NO3) and well as angiopoietin 2 (Ang2) and neuropeptide Y (NPY) in patients with type 1 diabetes and different complications status; to analyze associations between these markers.

Methods: Samples of 315 of LatDiane study patients with type 1 diabetes duration more than 1 year were analyzed. Albuminuria was estimated via morning spot urine albumin/creatinine ratio. eGFR was calculated with CKD-EPI equation. Ang2 and NPY in serum were measured by for Luminex xMAP Technology and ELISA respectively. Added concentration of NO2/NO3 in serum and urine was measured by Griess reaction. Production of NO in the whole blood was detected by means of ESP spectroscopy of Fe-DETC-NO complex.

Results: NO2/NO3 in serum was higher and in urine - lower in patients with macroalbuminuria and ESRD compared to normo- and microalbuminuric patients (serum: 50.054±38.00 μM vs 32.35±22.41 μM, P=0.02; urine: 550.63±550.77 μM vs 917.84±813.19 μM, P=0.018). Similarly, patients with proliferative retinopathy had lower NO2/NO3 levels in urine compared to earlier stages of retinopathy (701.26±620.04 μM vs 961.35±848.79 μM; P=0.02). Significantly lower levels of NO2/NO3 in urine were found also in patients with diabetic polyneuropathy. Ang2 levels were higher in patients with macroalbuminuria/ESRD (1696.7±1379.88 pg/ml vs 785.0±450.7 pg/ml, P=0.001), proliferative retinopathy (1015±845.28 pg/ml vs 808.68±538.09 pg/ml, P=0.017), history if CVD (1381.38±1256.51 pg/ml vs 823.36±548 pg/ml, P=0.000) compared to patients without these determinants. Higher NPY levels were found in patients with macroalbuminuria and ESRD compared to normo- and microalbuminuric patients (19.91±7.14 ng/ml vs 14.52±7.57 ng/ml, P=0.001). NO, NO2/NO3 in urine and serum as well as Ang2 and NPY correlated with eGFR (P<0.05). Serum NPY correlated with blood NO and serum Ang2 levels (P<0.05).

Conclusions: Differences in levels of nitric oxide metabolites, Ang2 and NPY levels are observed in biological fluids of patients with different stages of diabetic complications. Data on association between these markers provide new knowledge about links between hypoxia, inflammation and oxidative stress in type 1 diabetes.