{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:55:35Z","timestamp":1792007735537,"version":"4.4.0"},"reference-count":158,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T00:00:00Z","timestamp":1727395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014677","name":"George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Research","doi-asserted-by":"publisher","award":["163\/8\/10.01.2023"],"award-info":[{"award-number":["163\/8\/10.01.2023"]}],"id":[{"id":"10.13039\/501100014677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is an increasing prevalence of diabetes mellitus (DM), particularly type 2 DM (T2DM), and its associated complications. T2DM is linked to insulin resistance, chronic inflammation, and oxidative stress, which can lead to both macrovascular and microvascular complications, including peripheral diabetic neuropathy (PDN). Inflammatory processes play a key role in the development and progression of T2DM and its complications, with specific markers like C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor (TNF)-\u03b1 being associated with increased risk. Other key inflammatory markers such as nuclear factor kappa B (NF-\u03baB) are activated under hyperglycemic and oxidative stress conditions and contribute to the aggravation of PDN by regulating inflammatory gene expression and enhancing endothelial dysfunction. Other important roles in the inflammatory processes are played by Toll-like receptors (TLRs), caveolin 1 (CAV1), and monocyte chemoattractant protein 1 (MCP1). There is a relationship between vitamin D deficiency and PDN, highlighting the critical role of vitamin D in regulating inflammation and immune responses. The involvement of macrophages in PDN is also suspected, emphasizing their role in chronic inflammation and nerve damage in diabetic patients. Vitamin D supplementation has been found to reduce neuropathy severity, decrease inflammatory markers, and improve glycemic control. These findings suggest that addressing vitamin D deficiency could offer therapeutic benefits for PDN. These molecular pathways are critical in understanding the pathogenesis of DM complications and may offer potential biomarkers or therapeutic targets including anti-inflammatory treatments, vitamin D supplementation, macrophage phenotype modulation, and lifestyle modifications, aimed at reducing inflammation and preventing PDN. Ongoing and more extensive clinical trials with the aim of investigating anti-inflammatory agents, TNF-\u03b1 inhibitors, and antioxidants are needed to advance deeper into the understanding and treatment of painful diabetic neuropathy.<\/jats:p>","DOI":"10.3390\/ijms251910395","type":"journal-article","created":{"date-parts":[[2024,9,27]],"date-time":"2024-09-27T03:44:13Z","timestamp":1727408653000},"page":"10395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Update on Biomarkers of Chronic Inflammatory Processes Underlying Diabetic Neuropathy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-4926","authenticated-orcid":false,"given":"Adina","family":"Stoian","sequence":"first","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8056-1339","authenticated-orcid":false,"given":"Carmen","family":"Muntean","sequence":"additional","affiliation":[{"name":"Department of Pediatrics 1, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4004-9648","authenticated-orcid":false,"given":"Drago\u0219-Florin","family":"Bab\u0103","sequence":"additional","affiliation":[{"name":"Emergency Institute for Cardiovascular Diseases and Transplantation, 540142 Targu Mures, Romania"},{"name":"Department of Cell and Molecular Biology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0922-8565","authenticated-orcid":false,"given":"Andrei","family":"Manea","sequence":"additional","affiliation":[{"name":"Department of Radiology, Mure\u0219 County Emergency Hospital, 540136 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8319-8134","authenticated-orcid":false,"given":"L\u00f3r\u00e1nd","family":"D\u00e9nes","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Embryology, Faculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-5987","authenticated-orcid":false,"given":"Zsuzs\u00e1nna","family":"Simon-Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-8262","authenticated-orcid":false,"given":"Irina Bianca","family":"Kosovski","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enik\u0151","family":"Nemes-Nagy","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Medical Biochemistry, Faculty of Medicine in English, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0356-822X","authenticated-orcid":false,"given":"Florina Ioana","family":"Gliga","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6297-0378","authenticated-orcid":false,"given":"Mircea","family":"Stoian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Intensive Care, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"IDF Diabetes Atlas: Global, Regional and Country-Level Diabetes Prevalence Estimates for 2021 and Projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. 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