The Relationship Between Disease Diagnosis and Severity and Serum ADMA, SDMA and L-NMMA in Patients With Obsessive Sleep Apnoea Syndrome
Authors: BOLCA EMRAH , ERGÜN DİLEK , ERGÜN RECAİ , KANAT FİKRET , ÜNLÜ ALİ , ONMAZ DUYGU ERYAVUZ , KÖREZ MUSLU KAZIM 
Published: November 2024

Abstract

Background Recurrent hypoxaemia and reoxygenation in patients with Obstructive Sleep Apnoea Syndrome (OSAS) may trigger oxidative stress mechanisms. Oxidative stress alters the activities of enzymes involved in the production of asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and N-Monomethyl L-arginine (L-NMMA), leading to changes in their amounts. In previous studies, it was observed that intermittent hypoxia and hypoxia-reoxygenation events increased NO synthesis by increasing eNOS synthase activity 24 in OSAS patients. In our study, we analysed in which direction the balance between L-arginine-nitric oxide and L-arginine-methylated arginine metabolites (ADMA, SDMA, L-NMMA) pathways changed and which pathways were activated due to intermittent hypoxia in newly diagnosed OSAS patients who had not yet developed complications due to OSAS. At the end of our study, we aimed to examine the effect of increased metabolites in predicting complications that may develop in the future due to OSAS.
Materials and methods Male and female patients aged 18 years and older who voluntarily agreed to participate in the study were included in the study. Patients with an apnoea-hypopnoea index of 5 and above were included in the study. Patients with central apnoea and laboratory abnormalities (Hg, AST, ALT, HbA1c, bilurubin, electrolytes, cre, urea, homocysteine, folic acid, thyroid function tests) were excluded. Detailed anamnesis was obtained from the patients and patients with comorbidities that would affect the study; cardiovascular system diseases (essential hypertension, hypercholesterolemia, hyperhomocysteinaemia, acute coronary events, congestive heart failure), diabetes, hyperthyroidism, chronic renal failure, insulin resistance and metabolic syndrome, low serum folic acid and high homocysteine levels were excluded from the study. Blood samples were obtained from the other patients with their informed consent for ADMA, SDMA, L-NMMA, arginine, complete blood count, renal function tests, lipid panel, thyroid function tests, fasting blood glucose, HbA1c, folic acid and homocysteine controls. The study included 121 patients including 31 healthy and newly diagnosed mild ouas 30, moderate ouas 30 and severe ouas 31. The demographic characteristics, laboratory findings and clinical indices of the study participants according to the study groups were compared by One-Way Analysis of Variance, Welch F test or Kruskal Wallis tests. Tukey HSD, Games Howell and Bonferroni corrected Dunn's tests were used for multiple comparisons 25 for the parameters found to be significant as a result of these tests, respectively. The level of significance was taken as 5% in the evaluation of statistical hypotheses. Findings As a result of our study, we found that arginine metabolites (ADMA and L-NMMA) levels were lower in patients with OSAS compared to the healthy group. SDMA values of healthy controls and OSAS patient groups were similar. When the laboratory findings of the study groups were analysed, TMAL value was significantly lower in OSAS patients compared to healthy controls.
CONCLUSION The patients we included in the study were newly diagnosed with the polysomnography results and had not developed any complications related to the disease because of the early stage of the disease. Therefore, we did not observe an increase in arginine metabolites (ADMA, L-NMMA) due to the fact that the larginine pathway was registered to nitric oxide synthesis for compensation and therefore the methylated arginine pathway was not yet activated. There is a need for further controlled, prospective, prospective studies including NO measurement and nitric oxide synthase enzyme activities in terms of monitoring treatment efficacy, monitoring of complications and monitoring of disease progression in patients with OSAS.