{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T12:19:22Z","timestamp":1787660362939,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Diabetes mellitus and periodontitis are bidirectionally associated chronic disorders linked through metabolic dysregulation, host inflammation, microbial dysbiosis, and impaired tissue remodeling. This review summarizes clinical, molecular, cellular, genomic, epigenomic, transcriptomic, and microbial evidence concerning the mechanisms underlying this relationship and their potential translational relevance. Chronic hyperglycemia is associated with advanced glycation end product signaling through the receptor for advanced glycation end products, mitogen-activated protein kinase\/nuclear factor-\u03baB activation, reactive oxygen species production, oxidative stress, and NLR family pyrin domain-containing 3 inflammasome activation, which may contribute to enhanced cytokine responses and periodontal tissue injury. Diabetes is also associated with altered neutrophil and macrophage function, increased T helper 17\/interleukin-17 signaling, and an elevated receptor activator of nuclear factor-\u03baB ligand\/osteoprotegerin ratio, thereby favoring osteoclastogenesis and alveolar bone loss. Conversely, periodontal inflammation and microbial products may contribute to systemic low-grade inflammation, insulin resistance, and metabolic dysregulation. Multi-omics studies have identified shared susceptibility loci, regulatory networks, and disease-associated cell states, although their causal and clinical significance remains incompletely defined. These findings suggest potential roles for integrated medical\u2013dental care, glycemic screening in dental settings, periodontal inflammation control, host-modulatory therapies, and regenerative biomaterials. Further longitudinal and experimental studies are needed to determine their clinical applicability.<\/jats:p>","DOI":"10.3390\/ijms27177609","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:27:19Z","timestamp":1787657239000},"page":"7609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Molecular and Genomic Mechanisms Linking Diabetes Mellitus and Periodontitis: From Pathogenesis to Translational Opportunities"],"prefix":"10.3390","volume":"27","author":[{"given":"Nozomi","family":"Harai","sequence":"first","affiliation":[{"name":"Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo 409-3898, Yamanashi, Japan"},{"name":"Department of Endocrinology and Metabolism, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoichiro","family":"Tsuchiya","sequence":"additional","affiliation":[{"name":"Department of Diabetes and Endocrinology, Graduate School of Interdisciplinary Research, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Chuo 409-3898, Yamanashi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S237","DOI":"10.1002\/JPER.17-0733","article-title":"Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of Workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"Jepsen","year":"2018","journal-title":"J. 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