{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:20:45Z","timestamp":1772576445369,"version":"3.50.1"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T00:00:00Z","timestamp":1742860800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Abdullah International Medical Research Center (KAIMRC)","award":["RA-18\/021A"],"award-info":[{"award-number":["RA-18\/021A"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In individuals with type 2 diabetes mellitus (T2DM), elevated levels of both plasma and urinary cystatin C (Cys-C) contribute to increased oxidation, which in turn accelerates the oxidation of low-density lipoprotein (LDL). This process may worsen the development of atherosclerosis and cardiovascular disease by promoting endothelial dysfunction and inflammation. Despite its potential significance, the relationship between Cys-C and oxidized LDL (ox-LDL) in T2DM remains poorly understood. This study investigated the relationship between plasma and urinary Cys-C and ox-LDL levels in T2DM patients. The cohort included 57 patients with T2DM (mean age 61.14 \u00b1 9.99 years; HbA1c 8.66 \u00b1 1.60% and BMI 35.15 \u00b1 6.65 kg\/m2). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, 59% had an estimated glomerular filtration rate (eGFR) &lt; 60 mL\/min\/1.73 m2, 14% had coronary artery disease (CAD), and 5% had a history of stroke. Plasma and urinary Cys-C and ox-LDL levels were measured using ELISA. Adipokine and cytokine levels were measured using the multiplex\u00ae MAP Human Adipokine Magnetic Bead Panels. Spearman\u2019s correlation analysis revealed a significant positive correlation of plasma and urinary Cys-C with ox-LDL (r = 0.569, p = 0.0001 and r = 0.485, p = 0.0001, respectively). Multivariable regression analysis indicated that both plasma and urinary Cys-C were independently associated with ox-LDL, after adjusting for confounding factors (\u03b2 = 0.057, p = 0.0001 and \u03b2 = 0.486, p = 0.003, respectively). Stepwise linear regression identified TNF\u03b1 and adiponectin as the strongest predictors of the relationship between urinary Cys-C and ox-LDL (\u03b2 = 0.382, p = 0.0001; r2 = 0.64), while adiponectin alone was the best predictor of the plasma Cys-C and ox-LDL association (\u03b2 = 0.051, p = 0.005; r2 = 0.46). Furthermore, adiponectin partly mediated the relationship between plasma Cys-C and ox-LDL, explaining 18% of the variance in this association. In contrast, TNF\u03b1 partly mediated the relationship between urinary Cys-C and ox-LDL, accounting for 28% of the variance. This study emphasizes the complex interaction between Cys-C and ox-LDL in T2DM. It highlights the need for additional research involving larger patient cohorts to improve our understanding of the therapeutic potential of plasma and urinary Cys-C in conjunction with ox-LDL for managing complications associated with T2DM.<\/jats:p>","DOI":"10.3390\/ijms26073001","type":"journal-article","created":{"date-parts":[[2025,3,25]],"date-time":"2025-03-25T12:18:52Z","timestamp":1742905132000},"page":"3001","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Adiponectin and TNF-Alpha Differentially Mediate the Association Between Cystatin C and Oxidized LDL in Type 2 Diabetes Mellitus Patients"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5434-1976","authenticated-orcid":false,"given":"Ahmed","family":"Bakillah","sequence":"first","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Ahsa 36428, Saudi Arabia"},{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayman Farouk","family":"Soliman","sequence":"additional","affiliation":[{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maram","family":"Al Subaiee","sequence":"additional","affiliation":[{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khamis Khamees","family":"Obeid","sequence":"additional","affiliation":[{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arwa","family":"Al Hussaini","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Ahsa 36428, Saudi Arabia"},{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahinaz Faisal","family":"Bashir","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Ahsa 36428, Saudi Arabia"},{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad","family":"Al Arab","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Ahsa 36428, Saudi Arabia"},{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-6437-3074","authenticated-orcid":false,"given":"Abeer","family":"Al Otaibi","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Ahsa 36428, Saudi Arabia"},{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sindiyan Al Shaikh","family":"Mubarak","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Ahsa 36428, Saudi Arabia"},{"name":"Ministry of National Guard-Health Affairs (MNG-HA), King Abdulaziz Hospital, Al Ahsa 36428, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali Ahmed","family":"Al Qarni","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Ahsa 31982, Saudi Arabia"},{"name":"Division of Biomedical Research Core 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