Salivary 1H NMR metabolic profiling of diabetic patients with and without periodontitis: an exploratory pilot study

BACKGROUND: Periodontitis is a widespread chronic inflammatory condition that frequently coexists with diabetes mellitus (DM). Identifying non-invasive biomarkers is essential for early detection, targeted therapy, and better understanding of the bidirectional relationship between these two diseases. This study aimed to investigate salivary metabolomic profiles in diabetic individuals with and without periodontitis to identify candidate metabolites associated with periodontitis in patients with diabetes. METHODS: H NMR metabolomic profiles of patients with diabetes with and without periodontitis (n = 13 per group). Unstimulated whole saliva was collected from both groups. Partial least squares discriminant analysis (PLS-DA) was applied to differentiate between the groups. Spectral variables with VIP > 1 were selected for metabolite annotation, followed by metabolite set enrichment analysis (MSEA) to identify dysregulated metabolic pathways. RESULTS: Using the PLS-DA model, a total of 78 discriminating variables were identified, leading to the annotation of ten key metabolites: glycolic acid, thymidine, tyramine, deoxyguanosine, cytidine, uridine, NADPH, ADP, serotonin, and nicotinate. MSEA revealed significant pathway disturbances, with pyrimidine metabolism emerging as a notably enriched pathway. CONCLUSION: H NMR showed distinct metabolic disturbances, particularly in pyrimidine metabolism, in diabetic periodontitis. Although these altered metabolites could serve as potential candidates for non-invasive biomarkers, independent validation from a large cohort is still required before they can be translated into clinical diagnostic use.