Amal A MohamedAbbas M AbbasRasha ElgamalMaysa I. FarghlyHanan A. HegazyMahmoud M ShaheenShaimaa A. FathyMohamed El SherbinyGhada Maher ThabetKarima NasraldinNaglaa K. MadkourReem ElmahdyMoamen Abdelfadil IsmailNoheir Ashraf Ibrahem Fathy HassanAhmed AbdelrahmanMina Wassef GirgissWael HafezSamar S Khalaf2025-06-092025-06-092025-05-19Mohammed, A. A., Abbas, A. M., Elgamal, R., Farghly, M. I., Hegazy, H. A., Shaheen, M. M., Fathy, S. A., Sherbiny, M. E., Thabet, G. M., Nasraldin, K., Madkour, N. K., Elmahdy, R., Ismail, M. A., Hassan, N. a. I. F., Abdelrahman, A., Girgiss, M. W., Hafez, W., & Khalaf, S. S. (2025). Serum miRNA-146 and Cortisol levels in Type 2 Diabetes Mellitus: Novel Biomarkers for Diagnosis and Pathophysiological Insights. Egyptian Journal of Chemistry, 0(0), 0. https://doi.org/10.21608/ejchem.2025.345284.11003https://doi.org/10.21608/ejchem.2025.345284.11003https://repository.msa.edu.eg/handle/123456789/6433SJR 2024 0.269 Q3 H-Index 36Background: Type 2 Diabetes Mellitus (T2DM) is a chronic condition characterized by hyperglycemia due to defects in insulin action or secretion. Its rising prevalence poses a significant global health challenge. Evidence suggests that T2DM involves non-coding RNA molecules, such as miRNAs, which regulate gene expression. Cortisol, a stress hormone, is also implicated in T2DM by influencing glucose metabolism and contributing to complications. Aim: This study aimed to evaluate the diagnostic and pathophysiological relevance of miRNA-146 and cortisol in T2DM. This study explored their potential as biomarkers for identifying metabolic and inflammatory abnormalities and examined their interactions with glycemic markers (HbA1c and RBG). Methods: This cross-sectional study included 100 T2DM patients and 100 healthy controls from the Suez Canal University outpatient clinic. Biochemical assessments included RBG, fasting insulin, HbA1c, vitamin D, cholesterol, triglycerides (TG), LDL, HDL, cortisol, and miRNA-146. Cortisol and vitamin D levels were measured using ELISA, while miRNA-146 levels were quantified using RT-qPCR. Diagnostic performance was assessed using Receiver Operating Characteristic (ROC) curves, and statistical analyses were performed using IBM SPSS. Results: miRNA-146 levels were significantly lower in T2DM patients than in controls, with a cut-off value of ≤ 6.83, achieving 83.0% sensitivity and 79.0% specificity (AUC = 0.832). This makes miRNA-146 a highly effective diagnostic biomarker for early detection. Cortisol levels were elevated in T2DM patients and positively correlated with HbA1c and RBG, indicating its role in glucose metabolism dysregulation. A cortisol cut-off of ≥ 3.8 nmol/L showed 95.0% sensitivity and 71.0% specificity (AUC = 0.819), suggesting its utility as a secondary screening tool. However, its lower specificity may warrant further confirmatory testing . Conclusion: This study highlights the complementary roles of miRNA-146 and cortisol as T2DM biomarkers. While miRNA-146 demonstrates the highest diagnostic accuracy, cortisol offers additional insights into metabolic disturbances. These findings provide a foundation for improving T2DM diagnosis and monitoring. Further research is needed to validate these biomarkers and to explore their potential as targeted therapeutic strategies.en-USBiomarkerhyperglycemiaCortisolHBA1cMiRNA-146Type 2 diabetes mellitusArticlehttps://doi.org/10.21608/ejchem.2025.345284.11003