Abstract
(1) Background: Type-2-diabetes-mellitus (DM) is one the most important cardiovascular-risk-factors. Among many molecules regulating vascular tone, nitric oxide appears to be the most pivotal. Although micro- and macrovascular-abnormalities are extensively studied, the alterations in the nitric-oxide-metabolic-pathway require further investigations. Additionally, the role of erythrocytes in the vascular tone regulation has not been extensively explored. The aim of this study was to evaluate the endothelial-function and the nitric-oxide-metabolic-pathway in erythrocytes and plasma of diabetic individuals. (2) Methods: A total of 80 subjects were enrolled in this cross-sectional study, including 35 patients with DM and 45 healthy individuals. The endothelial-function was evaluated in response to different stimuli. (3) Results: In the DM group, decreased Arginine and citrulline concentrations in the plasma compartment with reduced Arginine/ADMA and ADMA/DMA-ratios were observed. Preserved nitric-oxide-metabolism in erythrocytes with reduced citrulline level and significantly higher NO-bioavailability were noted. Significant endothelial dysfunction in DM individuals was proved in response to the heat-stimulus. (4) Conclusions: DM patients at an early stage of disease show significant differences in the nitric-oxide-metabolic-pathway, which are more pronounced in the plasma compartment. Erythrocytes constitute a buffer with a higher nitric-oxide-bioavailability, less affected by the DM-related deviations. Patients at an early-stage of DM reveal endothelial-dysfunction, which could be diagnosed earlier using the laser-Doppler-flowmetry.
Highlights
Type 2 diabetes mellitus (DM) is one of the most important health emergencies in the 21st century
The results showed that the augmentation index (AI) in diabetics was statistically higher, strictly corresponding with the increased vascular stiffness and the reduced flexibility of the aorta among diabetic patients the AI-75 positively correlated with brain natriuretic peptide (BNP) concentration (r = 0.55) and negatively with the estimated glomerular filtration rate (eGFR) value (r = −0.43)
Patients at an early stage of DM revealed endothelial dysfunction, which could be diagnosed earlier using the laser Doppler flowmetry. This group of subjects showed significant differences in the nitric oxide metabolism, which was more pronounced in the plasma compartment
Summary
Type 2 diabetes mellitus (DM) is one of the most important health emergencies in the 21st century. Cardiovascular disease in DM patients occurs approximately 15 years earlier than in healthy subjects It is the main cause of mortality in this group which is different based on sex-dependence. CVD mortality in men with diabetes increases 1–3 times compared to diabetes-free individuals, while the same coefficient estimated in women varies from 2 to 5 times [3]. It is not clear what plays the major role in inducing the differences, but the most important factor seems to be the attenuation of estrogens protective influence against cardiovascular complications in DM women. Catalan et al proved that, despite the fact that men more often present carotid plaques in general, in a subgroup of newly diagnosed diabetic women, carotid atherosclerosis was more prevalent [7]
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