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Diabetes, particularly when poorly controlled, significantly increases the risk, severity, and progression of periodontitis. The biological mechanisms involved are complex and numerous. Hyperglycemia in diabetes is linked to oral microbial dysbiosis, which is in turn associated with increased inflammation, epithelial barrier dysfunction, impaired neutrophil and macrophage function, altered T-cell profiles, and cytokine imbalance, collectively fostering chronic inflammation and immune dysregulation. Moreover, diabetes alters bone metabolism, promoting osteoclastogenesis and reducing reparative bone regeneration by limiting coupled bone formation through an effect on growth factor production, mesenchymal stems cells, and osteoblasts. Conversely, periodontitis is strongly linked to poor glycemic control. Clinical studies and longitudinal meta-analyses report consistent positive associations, while randomized controlled trials show that periodontal therapy reduces HbA1c by ~0.43%. Emerging evidence suggests that periodontitis and oral preclinical dysbiosis contribute to diabetogenesis, although causality remains uncertain. Periodontitis may drive metabolic dysfunction through several biological mechanisms. The dysbiotic oral microbiome and subsequent periodontitis may promote systemic inflammation and subsequent insulin resistance and glucose intolerance. Moreover, oral dysbiosis may deplete nitrate-reducing taxa and impair nitric oxide pathways, which has relevance to both periodontal and cardiometabolic health. Accordingly, periodontal treatment in diabetic populations has shown potential health care savings. Nevertheless, trials assessing the influence of periodontitis treatment on systemic outcomes consistently show significant treatment heterogeneity, which requires explication in future studies. This review underscores the systemic implications of periodontitis in diabetes and highlights the value of integrating periodontal care into diabetes management. A better understanding of the shared pathophysiology between these diseases supports interdisciplinary approaches and points toward novel preventive and therapeutic strategies targeting inflammation, microbial balance, and host response modulation to jointly benefit periodontal and cardiometabolic health.<\/jats:p>","DOI":"10.1177\/00220345251388340","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T05:12:23Z","timestamp":1764133943000},"page":"21-30","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":47,"title":["Understanding the Periodontitis\u2013Diabetes Linkage: Mechanisms and Evidence"],"prefix":"10.1177","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4664-8529","authenticated-orcid":false,"given":"D.T.","family":"Graves","sequence":"first","affiliation":[{"name":"Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0036-7809","authenticated-orcid":false,"given":"M.A.","family":"Levine","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Philadelphia, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Aldosary","sequence":"additional","affiliation":[{"name":"Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.T.","family":"Demmer","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Quantitative Health Sciences, College of Medicine and Science, Mayo Clinic, Rochester, MN, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,11,25]]},"reference":[{"key":"e_1_3_2_2_1","doi-asserted-by":"crossref","unstructured":"Adam HS et al. 2024. 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