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The release of mtDNA into the plasma results from mitochondrial dysfunction, cell death, and NETosis, all of which are elevated in diabetes and its complications. Due to its resemblance to pathogenic DNA, mitochondrial DNA can activate several immunological pathways, leading to inflammation\u2014a key factor in diabetes and its complications. Studies reveal a significant overlap between the immunological pathways involved in diabetes and those triggered by ccf\u2010mtDNA. Thus, ccf\u2010mtDNA may play a crucial role in the pathophysiology of diabetes and its complications, making it a potential diagnostic, prognostic, and therapeutic target. This review aims to summarize research findings on the role of ccf\u2010mtDNA in diabetes, including gestational diabetes and related complications. Most studies have focused on type 2 diabetes, whereas research on ccf\u2010mtDNA in other forms, including type 1 diabetes, remains limited. By synthesizing these insights, we seek to clarify the role of ccf\u2010mtDNA in diabetes and identify gaps for future research.<\/jats:p>","DOI":"10.1111\/jdi.70071","type":"journal-article","created":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T09:44:01Z","timestamp":1749721441000},"page":"1575-1582","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Circulating cell\u2010free mitochondrial <scp>DNA<\/scp> in diabetes mellitus: Current insights and unexplored frontiers"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-1513","authenticated-orcid":false,"given":"Mohammadreza","family":"Akbari","sequence":"first","affiliation":[{"name":"Nephro\u2010Urology Research Center Shiraz University of Medical Sciences  Shiraz 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