Endothelin-1 and endothelial nitric oxide (eNOs) synthase as predictive biomarkers of clinical-subclinical atherosclerosis related to diabetes mellitus: a cross-sectional study

Introduction
Atherosclerosis is a chronic inflammatory disease characterized by arterial hardening and narrowing due to fibrous plaque formation.

Aim
This study aimed to evaluate the relationship between endothelin-1, endothelial nitric oxide synthase (eNOS), and clinical versus subclinical coronary atherosclerosis in male patients, as well as their association with type 2 diabetes mellitus.

Material and methods
This cross-sectional study included 90 male patients aged 20–60 years (mean age: 33.00 ±6.13), divided equally into clinical (n = 45, mean age: 34.50 ±4.95) and subclinical (n = 45, mean age: 32.25 ±7.23) coronary atherosclerosis groups. Serum endothelin-1 and endothelial nitric oxide (eNOS) were measured using ELISA kits. Insulin resistance was estimated by HOMA-IR: (fasting insulin × fasting glucose)/405. Lipid profiles, glucose parameters, and other biochemical markers were assessed.

Results
Clinical atherosclerosis patients had significantly higher endothelin-1 (19.646 ±5.045 pg/ml), insulin (4.175 ±1.667 µIU/ml), HOMA-IR (2.137 ±1.059), HbA1c (8.893 ±2.462 mmol/mol), C-peptide (123.614 ±32.939 pg/ml), and lipid parameters compared to the subclinical group (endothelin-1: 7.555 ±0.881 pg/ml; insulin: 2.582 ±0.238 µIU/ml; HOMA-IR: 0.760 ±0.091; HbA1c: 7.240 ±2.747 mmol/mol; C-peptide: 40.291 ±9.174 pg/ml). eNOS was higher in subclinical (825.528 ±321.027 pg/ml) versus clinical (299.499 ±57.810 pg/ml) patients. ROC analysis showed that endothelin-1 had the highest diagnostic accuracy (AUC 98.025%, sensitivity 95.533%, specificity 95.556%, cutoff 10.189 pg/ml). eNOS and HOMA-IR also showed strong predictive power (AUC 95.358% and 97.037%, respectively).

Conclusions
An imbalance of elevated endothelin-1 and reduced eNOS contributes to endothelial dysfunction and atherosclerosis progression. These biomarkers may serve as strong predictive indicators for clinical and subclinical disease.