Identification of NFKB1, miR-342-5p, -5192, and − 15b as diagnostic biomarkers for periodontitis in type 2 diabetes mellitus: a cross-sectional and experimental study

Type 2 diabetes mellitus (T2DM) and chronic periodontitis share a bidirectional relationship, with T2DM exacerbating periodontal inflammation and periodontitis impairing glycemic control. We aim to identify the diagnostic potential of NFKB1, hsa-miR-(342–5192, and 15b) in serum as well as gingival crevicular fluid (GCF) in individuals with T2DM+chronic periodontitis. A total of 140 participants (Healthy controls, individuals with chronic periodontitis, and those with T2DM+chronic periodontitis) were involved in the study. The NFKB1 protein levels were analyzed by ELISA, and the differential miRNA expression was analyzed using In silico bioinformatics analysis, followed by Quantitative polymerase chain reaction(qPCR) in both serum and GCF. Periodontitis parameters, such as probing pocket depth (PPD), clinical attachment loss (CAL), and metabolic markers, were also assessed. Forty-eight male rats were used to validate the molecular findings in a controlled environment. Periodontitis was induced using sterile silk ligatures placed subgingivally, and after two weeks, rats were sacrificed for histological analysis of inflammatory cell infiltration in both periodontitis and control groups. Levels of NFKB1 and the selected miRNAs were significantly heightened in T2DM with periodontitis cases compared to controls. These biomarkers exhibited strong positive correlations with periodontal parameters such as CAL and PPD. Receiver Operating Characteristic (ROC) curve analysis revealed excellent diagnostic performance for NFKB1 and miRNAs in both serum and GCF, with hsa-miR-15b(G) showing the highest Area under the curve (AUC) of 0.995. The animal model confirmed these findings, showing significant inflammatory cell infiltration in the periodontitis group. NFKB1 and miRNAs hsa-miR-342-5p -5192, and − 15b exhibit strong potential biomarkers for diagnosing periodontitis and T2DM-associated periodontitis. Their non-invasive nature and robust clinical associations make them promising candidates for personalized management strategies.