Levels of Nitric Oxide Metabolites and Myeloperoxidase in Subjects with Type 2 Diabetes Mellitus on Metformin Therapy

Abstract

Introduction: Endothelial dysfunction is involved in the pathogenesis of insulin resistance, diabetes mellitus type 2, diabetic complications and preceded clinical manifestation of cardiovascular complications. Increased myeloperoxidase activity has been linked to a number of pathologies with compelling evidence in initiation and progression of inflammatory events. The aim of this study was to compare concentrations of metabolite nitric oxide and myeloperoxidase in the plasma of diabetes mellitus type 2 patients on metformin therapy, without clinical signs of cardiovascular disease and healthy subjects, as well as evaluation of concentrations of analytes in association with glycemic control.

Materials and methods: Forty four study subjects with diabetes mellitus type 2 and thirty healthy subjects were included in this study. The concentration of myeloperoxidase was determined by enzyme-linked immunosorbent assay, the concentration of nitrate and nitrite with high performance liquid chromatography method. Student's t test, Mann-Whitney U test, Chi-square test and Fisher's exact test were used for statistical analysis.

Results: The mean concentration of myeloperoxidase was significantly higher in the diabetic group compared to the control group (16.2±4.9 vs. 3.7±1.8; P<0.001).The nitrite concentration was comparable in both groups while the concentration of nitrate was significantly higher in the diabetic group (41.2 [42.9] vs 31.9 [23]; P=0.017). In this study, plasma myeloperoxidase (Spearman's rho=0.421; P=0.004) and nitrate concentration was significantly positively associated with the HbA1c levels while nitrate concentration (Spearman's rho=- 0.308; P=0.047) were was significantly positively negatively associated with the HbA1c levels.

Conclusion: Concertation of MPO and nitric oxide were significantly increased in a T2DM subject even when on metformin therapy. However, increased concentration of NO strongly correlates with lower levels of HbA1c showing a postive effect of a gylcemic control on endothelial dysfuction. Increased concentrations of NO3- in T2DM subject compared to control, indicates the variety of NO pathways that should be taken into consideration win relation to endothelial function.