From biological evidence to clinical application: a scoping review of oral fluid biomarkers in type 2 diabetic periodontitis

Abstract

Background Diabetes mellitus and periodontitis share a bidirectional inflammatory relationship. Oral fluids provide non-invasive access to host and microbial signals relevant to both diseases, but clinical translation of oral fluid biomarkers in diabetic periodontitis remains limited. Objectives To map the evidence on salivary, gingival crevicular fluid (GCF), and oral rinse biomarkers in adults with type 2 diabetes mellitus and periodontitis, emphasizing analytical platforms, diagnostic performance, and chair-side readiness. Materials and methods PubMed/MEDLINE, Scopus, Web of Science, Embase, and the Cochrane Library were searched from 2005 to April 2026. Forward and backward citation tracking supplemented the search. Peer-reviewed human studies involving adults with physician-diagnosed diabetes and clinically assessed periodontitis reporting quantitative oral fluid biomarkers were included. Eligible studies examined associations with glycemic status, periodontal parameters, or diagnostic accuracy. Intervention studies were excluded. Two reviewers independently screened records. A pre-specified charting form captured study design, oral fluid type, biomarker class, assay platform, and diagnostic performance. Findings were synthesized narratively. Results Diabetic periodontitis was associated with elevated active-matrix metalloproteinase-8 (aMMP-8), MMP-9, interleukin-1 beta (IL-1β), IL-6, advanced glycation end products, oxidative stress markers, selected microRNAs, and disrupted MMP/TIMP (tissue inhibitor of metalloproteinases) balance. Among single analytes, aMMP-8 and IL-1β were the most consistently reported. aMMP-8 discriminated periodontitis [area under the curve (AUC) 0.84 in oral rinse and 0.81 in saliva], whereas IL-1β showed high reported accuracy (AUC 0.87–0.93). Multi-marker panels generally achieved higher accuracy (AUC up to 0.92–1.00). Among point-of-care approaches, aMMP-8 had the most extensive chair-side validation. Due to substantial heterogeneity in study design, reference standards, and clinical objectives, findings are presented by intended application (diagnosis, differentiation of diabetic from non-diabetic periodontitis, severity assessment, glycemic assessment, monitoring, and screening) rather than direct biomarker comparison. Conclusions Oral fluid biomarkers, particularly aMMP-8, show reproducible associations with glycemic progression and periodontal tissue destruction in type 2 diabetic periodontitis and demonstrate promise for non-invasive screening and monitoring. Standardization of sampling protocols, assay thresholds, and biomarker panels is required before routine clinical implementation.