{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:12:03Z","timestamp":1791396723666,"version":"4.3.3"},"reference-count":60,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T00:00:00Z","timestamp":1760745600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","award":["860-20250055"],"award-info":[{"award-number":["860-20250055"]}],"id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Dent Res"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>Diabetes-associated periodontitis has long been attributed to hyperglycemia, primarily through advanced glycation end products (AGEs) and RAGE-mediated oxidative stress. However, recent clinical and experimental findings show that periodontitis risk persists even under good glycemic control, suggesting additional pathological factors. This review highlights hyperinsulinemia\u2014a hallmark of insulin resistance and early-stage type 2 diabetes\u2014as a distinct and underappreciated contributor. In mouse models, excessive insulin signaling in insulin-responsive immune cells, such as T cells and macrophages, promotes proinflammatory polarization, while insulin receptor knockout suppresses immune activation, underscoring insulin\u2019s direct immunomodulatory role. Hyperinsulinemia also drives adipose tissue dysfunction and lipotoxicity, amplifying systemic inflammation and elevating circulating cytokines such as interleukin-6 and tumor necrosis factor\u2013\u03b1, which may affect periodontal tissues. Moreover, in vivo studies show that insulin excess induces endothelial activation and leukocyte recruitment via CX3CL1 and angiopoietin-2 signaling. Human clamp studies further demonstrate increased levels of inflammatory mediators under euglycemic hyperinsulinemia. Collectively, these findings support a model wherein hyperinsulinemia may contribute to periodontal inflammation and bone loss through mechanisms that are independent of blood glucose levels.<\/jats:p>","DOI":"10.1177\/00220345251366952","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:17:12Z","timestamp":1760782632000},"page":"294-301","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":5,"title":["The Link between Hyperinsulinemia and Periodontitis in Diabetics"],"prefix":"10.1177","volume":"105","author":[{"given":"Y.","family":"Sohn","sequence":"first","affiliation":[{"name":"Department of Oral Histology and Developmental Biology, School of Dentistry, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.J.","family":"Jeong","sequence":"additional","affiliation":[{"name":"Collage of Dental Medicine, Columbia University, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6146-6213","authenticated-orcid":false,"given":"J.","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Oral Histology and Developmental Biology, School of Dentistry, Seoul National University, Seoul, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,10,18]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2021.111315"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.17-0384"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1119038109"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.12.009"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2020.06.016"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2014.130554"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad287"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12031147"},{"key":"e_1_3_3_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000528503"},{"key":"e_1_3_3_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.06.003"},{"key":"e_1_3_3_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2002"},{"key":"e_1_3_3_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1601011"},{"key":"e_1_3_3_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12270"},{"key":"e_1_3_3_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(16)30010-9"},{"key":"e_1_3_3_16_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1302181"},{"key":"e_1_3_3_17_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.17-21929"},{"key":"e_1_3_3_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/00220345211059418"},{"key":"e_1_3_3_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/omi.12449"},{"key":"e_1_3_3_20_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1800065"},{"key":"e_1_3_3_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2018.05.013"},{"key":"e_1_3_3_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2012.09.039"},{"key":"e_1_3_3_23_1","first-page":"17","article-title":"Relationship between severity of periodontal disease and control of diabetes (glycated hemoglobin) in patients with type 1 diabetes mellitus","volume":"7","author":"Jindal A","year":"2015","unstructured":"Jindal A, Parihar AS, Sood M, Singh P, Singh N. 2015. 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