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CC BY 4.0 · Eur J Dent 2025; 19(02): 305-314
DOI: 10.1055/s-0044-1788797
Original Article

Prediabetes Associates with Matrix Metalloproteinase-8 Activation and Contributes to the Rapid Destruction of Periodontal Tissues

Kehinde Adesola Umeizudike
1   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
2   Department of Preventive Dentistry, Faculty of Dental Sciences, College of Medicine, University of Lagos, Lagos, Nigeria
,
Nur Rahman Ahmad Seno Aji 
1   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
3   Department of Periodontics, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia
,
Katariina Niskanen
1   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
,
Iina Rantala
1   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
,
Dimitra Sakellari
4   Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
,
Andreas Grigoriadis 
4   Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
5   Department of Preventive Dentistry, Periodontology and Implant Biology, Dental School, Aristotle University of Thessaloniki, Thessaloniki, Greece
,
Tommi Pätilä
6   Department of Pediatric Surgery, Children's Hospital University, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
,
Shipra Gupta 
7   Unit of Periodontology, Oral Health Sciences Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India
,
Timo Sorsa
1   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
8   Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden
,
Ismo T. Räisänen 
1   Department of Oral and Maxillofacial Diseases, Head and Neck Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
› Author Affiliations Funding T.S. has received financial support from the Finnish Dental Society Apollonia, Finland; the Karolinska Institutet, Stockholm, Sweden; the Helsinki and Uusimaa Hospital District (HUS), Grant/Award Numbers: Y1014SULE1, Y1014SL018, Y1014SL017, TYH2019319, TYH2018229, TYH2017251, TYH2016251, and TYH2022225. K.A.U. was supported by the Fogarty International Center of the National Institutes of Health under Award Number D43TW010934. The content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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Abstract

Objective The aim of this cross-sectional study was to investigate the relationship between periodontitis, potential periodontitis oral fluid biomarkers, and prediabetes.

Materials and Methods This 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.

Statistical Analysis The Kruskal–Wallis 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 (<5.7 and ≥5.7%) 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.

Results aMMP-8, but not total MMP-8 or other biomarkers, associated significantly with the stage and grade of periodontitis combined (p < 0.001, Kruskal–Wallis test). Among stage III grade C periodontitis patients, aMMP-8 levels were significantly positively correlated with prediabetes (Spearman's rho = 0.646, p = 0.044), total MMP-8 (rho = 0.636, p = 0.048), PMN Elastase (rho = 0.729, p = 0.017), total MMP-9 (rho = 0.721, p = 0.019), and total MMP-8/TIMP-1 molar ratio (rho = 0.879, p < 0.001).

Conclusion Prediabetic 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 minutes by aMMP-8 PoC testing at the dentist's office.

Keywords

periodontitis - diagnosis - matrix metalloproteinase 8 - biomarkers - point-of-care testing - prediabetes - diabetes

Data Availability Statement

The data that support the findings of this study are available on reasonable request from the corresponding author. The data are not publicly available due to privacy and ethical restrictions.


Ethical Approval Statement

This study was approved by the Ethics Committee of the School of Dentistry, Aristotle University of Thessaloniki, Thessaloniki, Greece (#64, 12/6/2018). All procedures performed in the present study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards and informed written consent was obtained from all individual participants included in the study.


Supplementary Material



Publication History

Article published online:
01 October 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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