{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:53:16Z","timestamp":1781513596878,"version":"3.54.1"},"reference-count":47,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2025,7,13]],"date-time":"2025-07-13T00:00:00Z","timestamp":1752364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-136\/2025-03\/200161"],"award-info":[{"award-number":["451-03-136\/2025-03\/200161"]}]},{"name":"Ministry of Science, Technological Development and Innovation, Republic of Serbia","award":["451-03-137\/2025-03\/200161"],"award-info":[{"award-number":["451-03-137\/2025-03\/200161"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Although emerging evidence suggests that epigenetic mechanisms contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM), data remain limited for patients with suboptimal metabolic control. The aim of this study was to assess global DNA methylation in patients with poorly controlled T2DM and to identify diabetes-related factors associated with DNA methylation levels. The study included 107 patients and 50 healthy controls. Global DNA methylation (5mC) was measured by UHPLC-DAD method. Pro-oxidant and antioxidant biomarkers, advanced glycation end-products, high-sensitivity C-reactive protein (hsCRP) and complete blood count were determined and leukocyte indices calculated. Patients had a significantly lower 5mC than controls (3.56 \u00b1 0.31% vs. 4.00 \u00b1 0.68%; p &lt; 0.001), with further reductions observed in those with longer disease duration and diabetic foot ulcers. Oxidative stress and inflammatory biomarkers were higher in the patient group. DNA hypomethylation was associated with a higher monocyte-to-lymphocyte ratio and hsCRP, pro-oxidant\u2013antioxidant balance, ischemia-modified albumin, and advanced oxidation protein products levels. Conversely, 5mC levels showed positive correlations with total antioxidant status and total sulfhydryl groups. Principal component analysis identified five key factors: proinflammatory, pro-oxidant, aging, hyperglycemic, and antioxidant. The pro-oxidant factor emerged as the sole independent predictor of global DNA hypomethylation in T2DM (OR = 2.294; p = 0.027). Our results indicate that global DNA hypomethylation could be a biomarker of T2DM progression, reflecting the complex interactions between oxidative stress, inflammation, and epigenetic modifications in T2DM.<\/jats:p>","DOI":"10.3390\/ijms26146716","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T09:45:52Z","timestamp":1752572752000},"page":"6716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Global DNA Methylation in Poorly Controlled Type 2 Diabetes Mellitus: Association with Redox and Inflammatory Biomarkers"],"prefix":"10.3390","volume":"26","author":[{"given":"Sanja","family":"Vujcic","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Kotur-Stevuljevic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoran","family":"Vujcic","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Belgrade-Faculty of Chemistry, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Stojanovic","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Belgrade-Institute of Chemistry, Technology and Metallurgy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0730-8185","authenticated-orcid":false,"given":"Teodora","family":"Beljic Zivkovic","sequence":"additional","affiliation":[{"name":"Department of 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Serbia"},{"name":"Division of Endocrinology, Diabetes and Metabolic Disorders, Department of Internal Medicine, Zvezdara University Medical Center, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8418-4238","authenticated-orcid":false,"given":"Iva","family":"Perovic Blagojevic","sequence":"additional","affiliation":[{"name":"Clinical Hospital Center \u201cDr. Dragisa Misovic-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Koprivica-Uzelac","sequence":"additional","affiliation":[{"name":"Clinical Hospital Center \u201cDr. Dragisa Misovic-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Ilic-Mijailovic","sequence":"additional","affiliation":[{"name":"Clinical Hospital Center \u201cDr. Dragisa Misovic-Dedinje\u201d, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90100 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-8404","authenticated-orcid":false,"given":"Aleksandra","family":"Zeljkovic","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatjana","family":"Stefanovic","sequence":"additional","affiliation":[{"name":"General Hospital Pozarevac, 12000 Pozarevac, 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