{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T16:20:20Z","timestamp":1781886020395,"version":"3.54.5"},"reference-count":42,"publisher":"Georg Thieme Verlag KG","issue":"02","license":[{"start":{"date-parts":[[2024,10,1]],"date-time":"2024-10-01T00:00:00Z","timestamp":1727740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Dent"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Objective\u2003The aim of this cross-sectional study was to investigate the relationship between periodontitis, potential periodontitis oral fluid biomarkers, and prediabetes.<\/jats:p><jats:p>\n          Materials and Methods\u2003This study included 150 Greek adults aged 25 to 78 years who were tested with an Hemoglobin A1C (HBA1c) diagnostic system, an active-matrix metalloproteinase-8 (aMMP-8) point-of-care (PoC) test, and several salivary biomarkers enzyme-linked immunosorbent assay tests and gelatin zymography. A full-mouth clinical examination was performed to assess their periodontal and oral health status.<\/jats:p><jats:p>\n          Statistical Analysis\u2003The Kruskal\u2013Wallis test was used to determine the statistically significant difference in the levels of periodontal oral fluid biomarkers between the different periodontitis stages, periodontitis grades, and the stages and grades of periodontitis combined. Spearman's rank correlation was performed to assess the strength and direction of the association between aMMP-8 and HbA1c levels (&lt;5.7 and \u22655.7%) and with the other oral fluid biomarkers among patients with severe periodontitis. A two-sided p-value below 0.05 was considered statistically significant in this study.<\/jats:p><jats:p>\n          Results\u2003aMMP-8, but not total MMP-8 or other biomarkers, associated significantly with the stage and grade of periodontitis combined (p\u2009&lt;\u20090.001, Kruskal\u2013Wallis test). Among stage III grade C periodontitis patients, aMMP-8 levels were significantly positively correlated with prediabetes (Spearman's rho\u2009=\u20090.646, p\u2009=\u20090.044), total MMP-8 (rho\u2009=\u20090.636, p\u2009=\u20090.048), PMN Elastase (rho\u2009=\u20090.729, p\u2009=\u20090.017), total MMP-9 (rho\u2009=\u20090.721, p\u2009=\u20090.019), and total MMP-8\/TIMP-1 molar ratio (rho\u2009=\u20090.879, p\u2009&lt;\u20090.001).<\/jats:p><jats:p>\n          Conclusion\u2003Prediabetic disease development can upregulate MMP-8 expression (total MMP-8) in rapidly progressing, severe periodontitis, where MMP-8 latent species are further activated into their active forms (aMMP-8). Simultaneously, several proinflammatory biomarker levels are elevated in this tissue-destructive biomarker cascade. This development is easily detectable online\/in real-time within 5\u2009minutes by aMMP-8 PoC testing at the dentist's office.<\/jats:p>","DOI":"10.1055\/s-0044-1788797","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:03:22Z","timestamp":1727827402000},"page":"305-314","source":"Crossref","is-referenced-by-count":12,"title":["Prediabetes Associates with Matrix Metalloproteinase-8 Activation and Contributes to the Rapid Destruction of Periodontal Tissues"],"prefix":"10.1055","volume":"19","author":[{"given":"Kehinde Adesola","family":"Umeizudike","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Department of Preventive Dentistry, Faculty of Dental Sciences, College of Medicine, University of Lagos, Lagos, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1779-8763","authenticated-orcid":false,"given":"Nur Rahman Ahmad Seno","family":"Aji","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Department of Periodontics, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katariina","family":"Niskanen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iina","family":"Rantala","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Sakellari","sequence":"additional","affiliation":[{"name":"Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5542-2230","authenticated-orcid":false,"given":"Andreas","family":"Grigoriadis","sequence":"additional","affiliation":[{"name":"Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece"},{"name":"Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommi","family":"P\u00e4til\u00e4","sequence":"additional","affiliation":[{"name":"Department of Pediatric Surgery, Children's Hospital University, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2097-2459","authenticated-orcid":false,"given":"Shipra","family":"Gupta","sequence":"additional","affiliation":[{"name":"Unit of Periodontology, Oral Health Sciences Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Sorsa","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"},{"name":"Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5821-5299","authenticated-orcid":false,"given":"Ismo T.","family":"R\u00e4is\u00e4nen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,10,1]]},"reference":[{"issue":"02","key":"ref1","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1111\/jcpe.12808","article-title":"Scientific evidence on the links between periodontal diseases and diabetes: Consensus report and guidelines of the joint workshop on periodontal diseases and diabetes by the International Diabetes Federation and the European Federation of Periodontology","volume":"45","author":"M Sanz","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"S 01","key":"ref2","first-page":"S173","article-title":"Periodontitis: Consensus report of workgroup 2 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions","volume":"89","author":"P N Papapanou","year":"2018","journal-title":"J Periodontol"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/prd.12270","article-title":"Diabetes as a potential risk for periodontitis: association studies","volume":"83","author":"R J Genco","year":"2020","journal-title":"Periodontol 2000"},{"issue":"02","key":"ref4","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1007\/s40200-021-00861-9","article-title":"Association of hyperglycaemia and periodontitis: an updated systematic review and meta-analysis","volume":"20","author":"A Mirzaei","year":"2021","journal-title":"J Diabetes Metab Disord"},{"issue":"01","key":"ref5","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1111\/jcpe.13202","article-title":"Accuracy of single molecular biomarkers in saliva for the diagnosis of periodontitis: A systematic review and meta-analysis","volume":"47","author":"N Arias-Bujanda","year":"2020","journal-title":"J Clin Periodontol"},{"issue":"03","key":"ref6","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.3390\/ijms23031806","article-title":"The role of matrix metalloproteinases (MMP-8, MMP-9, MMP-13) in periodontal and peri-implant pathological processes","volume":"23","author":"I Luchian","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"11","key":"ref7","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1111\/jcpe.13854","article-title":"Accuracy of periodontitis diagnosis obtained using multiple molecular biomarkers in oral fluids: a systematic review and meta-analysis","volume":"50","author":"T Blanco-Pintos","year":"2023","journal-title":"J Clin Periodontol"},{"issue":"06","key":"ref8","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1056\/NEJM198902093200606","article-title":"Tissue destruction by neutrophils","volume":"320","author":"S J Weiss","year":"1989","journal-title":"N Engl J Med"},{"issue":"02","key":"ref9","doi-asserted-by":"crossref","first-page":"61","DOI":"10.3390\/diagnostics10020061","article-title":"Active MMP-8 (aMMP-8) as a grading and staging biomarker in the periodontitis classification","volume":"10","author":"T Sorsa","year":"2020","journal-title":"Diagnostics (Basel)"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.3390\/biomedicines11112885","article-title":"Active matrix metalloproteinase-8 (aMMP-8) versus total MMP-8 in periodontal and peri-implant disease point-of-care diagnostics","volume":"11","author":"I T R\u00e4is\u00e4nen","year":"2023","journal-title":"Biomedicines"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1902\/jop.1999.70.11.1292","article-title":"Assessment of a novel screening test for neutrophil collagenase activity in the diagnosis of periodontal diseases","volume":"70","author":"S Mancini","year":"1999","journal-title":"J Periodontol"},{"issue":"03","key":"ref12","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1111\/jre.12423","article-title":"Matrix metalloproteinase-8 activity in gingival crevicular fluid: development of a novel assay","volume":"52","author":"M TC Mc Crudden","year":"2017","journal-title":"J Periodontal Res"},{"issue":"01","key":"ref13","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12903-018-0512-8","article-title":"Matrix metalloproteinase-8 levels in oral samples as a biomarker for periodontitis in the Chinese population: an observational study","volume":"18","author":"C Yuan","year":"2018","journal-title":"BMC Oral Health"},{"issue":"01","key":"ref14","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12903-019-0784-7","article-title":"A rapid, non-invasive tool for periodontitis screening in a medical care setting","volume":"19","author":"M JL Verhulst","year":"2019","journal-title":"BMC Oral Health"},{"issue":"01","key":"ref15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/s10266-019-00435-5","article-title":"Relationship between TNF-\u03b1, MMP-8, and MMP-9 levels in gingival crevicular fluid and the subgingival microbiota in periodontal disease","volume":"108","author":"N S Romero-Castro","year":"2020","journal-title":"Odontology"},{"issue":"04","key":"ref16","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1111\/jre.12999","article-title":"Diagnostic accuracy of active matrix metalloproteinase-8 point-of-care test for the discrimination of periodontal health status: comparison of saliva and oral rinse samples","volume":"57","author":"K Deng","year":"2022","journal-title":"J Periodontal Res"},{"issue":"06","key":"ref17","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s00430-015-0413-2","article-title":"Activated matrix metalloproteinase-8 in saliva as diagnostic test for periodontal disease? A case-control study","volume":"204","author":"S Izadi Borujeni","year":"2015","journal-title":"Med Microbiol Immunol (Berl)"},{"issue":"07","key":"ref18","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1111\/odi.12521","article-title":"Rapid assessment of salivary MMP-8 and periodontal disease using lateral flow immunoassay","volume":"22","author":"N Johnson","year":"2016","journal-title":"Oral Dis"},{"issue":"02","key":"ref19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1111\/jre.12392","article-title":"Evaluation of a novel point-of-care test for active matrix metalloproteinase-8: agreement between qualitative and quantitative measurements and relation to periodontal inflammation","volume":"52","author":"K Lorenz","year":"2017","journal-title":"J Periodontal Res"},{"issue":"02","key":"ref20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.diagmicrobio.2019.05.006","article-title":"Associations of chairside salivary aMMP-8 findings with periodontal parameters, potentially periodontal pathogenic bacteria and selected blood parameters in systemically healthy adults","volume":"95","author":"G Schmalz","year":"2019","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"08","key":"ref21","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1111\/jcpe.13485","article-title":"Diagnostic accuracy of a point-of-care aMMP-8 test in the discrimination of periodontal health and disease","volume":"48","author":"K Deng","year":"2021","journal-title":"J Clin Periodontol"},{"issue":"12","key":"ref22","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1111\/jcpe.13856","article-title":"Development of a machine learning multiclass screening tool for periodontal health status based on non-clinical parameters and salivary biomarkers","volume":"51","author":"K Deng","year":"2024","journal-title":"J Clin Periodontol"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1080\/14789450.2020.1858056","article-title":"Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study","volume":"17","author":"M Keskin","year":"2020","journal-title":"Expert Rev Proteomics"},{"issue":"S 20","key":"ref24","first-page":"S149","article-title":"Staging and grading of periodontitis: Framework and proposal of a new classification and case definition","volume":"45","author":"M S Tonetti","year":"2018","journal-title":"J Clin Periodontol"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1111\/odi.14008","article-title":"Linking oral microbial proteolysis to aMMP-8 PoC diagnostics along with the stage and grade of periodontitis: a cross-sectional study","volume":"29","author":"S Gupta","year":"2023","journal-title":"Oral Dis"},{"issue":"03","key":"ref26","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1111\/j.1600-051X.2011.01788.x","article-title":"Matrix metalloproteinase-8 expression in periodontal tissues surgically removed from diabetic and non-diabetic patients with periodontal disease","volume":"39","author":"D C Hardy","year":"2012","journal-title":"J Clin Periodontol"},{"issue":"07","key":"ref27","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1038\/s41415-019-0794-5","article-title":"Periodontitis and diabetes","volume":"227","author":"P M Preshaw","year":"2019","journal-title":"Br Dent J"},{"issue":"01","key":"ref28","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1002\/cre2.338","article-title":"Prediabetes\/diabetes screening strategy at the periodontal clinic","volume":"7","author":"A Grigoriadis","year":"2021","journal-title":"Clin Exp Dent Res"},{"issue":"11","key":"ref29","first-page":"821","article-title":"The application of IFCC reference methods in methodological evaluation of glycated hemoglobin measurement systems","volume":"41","author":"T Zhang","year":"2018","journal-title":"Chin J Lab Med"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1002\/cre2.537","article-title":"Active MMP-8 point-of-care (PoC)\/chairside enzyme-test as an adjunctive tool for early and real-time diagnosis of peri-implantitis","volume":"8","author":"H L\u00e4hteenm\u00e4ki","year":"2022","journal-title":"Clin Exp Dent Res"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/j.1600-0765.1995.tb01249.x","article-title":"Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: role of active enzyme in human periodontitis","volume":"30","author":"W Lee","year":"1995","journal-title":"J Periodontal Res"},{"issue":"01","key":"ref32","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1111\/prd.12235","article-title":"Periodontal complications of hyperglycemia\/diabetes mellitus: Epidemiologic complexity and clinical challenge","volume":"78","author":"T Kocher","year":"2018","journal-title":"Periodontol 2000"},{"issue":"03","key":"ref33","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/jre.13127","article-title":"Biomarker panel discriminates diabetics with and without periodontitis pre- and post-therapy","volume":"58","author":"C S Miller","year":"2023","journal-title":"J Periodontal Res"},{"issue":"03","key":"ref34","doi-asserted-by":"crossref","first-page":"319","DOI":"10.4103\/1305-7456.163222","article-title":"The influence of type 2 diabetes mellitus on salivary matrix metalloproteinase-8 levels and periodontal parameters: a study in an Indian population","volume":"9","author":"N Gupta","year":"2015","journal-title":"Eur J Dent"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1111\/odi.15014","article-title":"Association between metabolic syndrome and salivary MMP-8, myeloperoxidase in periodontitis","author":"J T Thomas","year":"2024","journal-title":"Oral Dis"},{"issue":"12","key":"ref36","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1111\/jcpe.12014","article-title":"Gingival crevicular fluid levels of matrix metalloproteinases cross-sectionally related to periodontitis and metabolic syndrome in community Koreans","volume":"39","author":"D H Han","year":"2012","journal-title":"J Clin Periodontol"},{"issue":"01","key":"ref37","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1055\/s-0033-1358762","article-title":"The impact of type 2 diabetes and atorvastatin treatment on serum levels of MMP-7 and MMP-8","volume":"122","author":"N P Kadoglou","year":"2014","journal-title":"Exp Clin Endocrinol Diabetes"},{"issue":"09","key":"ref38","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/eci.12649","article-title":"Association of MMP-8 with obesity, smoking and insulin resistance","volume":"46","author":"A Lauhio","year":"2016","journal-title":"Eur J Clin Invest"},{"issue":"01","key":"ref39","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/prd.12315","article-title":"Periodontal therapeutics: current host-modulation agents and future directions","volume":"82","author":"L M Golub","year":"2020","journal-title":"Periodontol 2000"},{"issue":"06","key":"ref40","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1111\/jcpe.13807","article-title":"Association between periodontal diseases and cardiovascular diseases, diabetes and respiratory diseases: Consensus report of the Joint Workshop by the European Federation of Periodontology (EFP) and the European arm of the World Organization of Family Doctors (WONCA Europe)","volume":"50","author":"D Herrera","year":"2023","journal-title":"J Clin Periodontol"},{"issue":"02","key":"ref41","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1111\/jcpe.12837","article-title":"A systematic review and meta-analysis of epidemiologic observational evidence on the effect of periodontitis on diabetes. An update of the EFP-AAP review","volume":"45","author":"F Graziani","year":"2018","journal-title":"J Clin Periodontol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/jphsr\/rmac008","article-title":"Health economic potential of oral aMMP-8 biomarker diagnostics for personalised prevention of periodontal and peri-implant diseases","volume":"13","author":"R Frankenberger","year":"2022","journal-title":"J Pharm Health Serv Res"}],"container-title":["European Journal of Dentistry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0044-1788797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T22:34:05Z","timestamp":1744756445000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0044-1788797"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,1]]},"references-count":42,"journal-issue":{"issue":"02","published-online":{"date-parts":[[2025,4,15]]},"published-print":{"date-parts":[[2025,5]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0044-1788797","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["1305-7456","1305-7464"],"issn-type":[{"value":"1305-7456","type":"print"},{"value":"1305-7464","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,1]]}}}