Abstract
AIM: Diabetes mellitus (DM), a metabolic disorder, exhibits a bidirectional relationship with periodontitis (PD), and recently, microRNAs (miRNAs) were associated with their progression. This review aims to assess the role of miRNAs in the pathogenesis of DM-associated PD and their plausible application as a biomarker for PD in individuals with DM. MATERIALS AND METHODS: The search conducted until September 2023 on Medline (Pubmed), Scopus, Embase, and Web of Science using the keywords "microRNA," "miRNA," or "miR," combined with "Diabetes" and "PD" yielded 100 articles. Only research focusing on the role of miRNAs in the pathogenesis of DM-associated PD and their potential application as biomarkers for both conditions were included. Finally, 14 studies were assessed for any bias, and the collected data included study design, sample size, participant groups, age, sample obtained, PD severity, miRNAs examined, clinical and biochemical parameters related to DM and PD, and primary outcomes. RESULTS: In vivo studies indicated altered expression of miRNAs-146a, -146b, -155, -200b, -203, and -223, specifically in the comorbid subjects with both conditions. Animal, ex vivo, and in vitro studies demonstrated altered expression of miRNAs-126, -147, -31, -25-3p, -508-3p, -214, 124-3p, -221, -222, and the SIRT6-miR-216/217 axis. These miRNAs impact innate and adaptive immune mechanisms, oxidative stress, hyperglycemia, and insulin sensitivity, thereby promoting periodontal destruction in DM. miRNA-146a emerges as a reliable biomarker of PD in DM, whereas miRNA-155 is a consistent predictor of PD in subjects without DM. CONCLUSIONS: miRNAs exert influence on immuno-inflammation in DM-associated PD. Although they can be biomarkers of PD and DM, their clinical utility is hindered by the absence of standardized tests to evaluate their sensitivity and specificity. Moreover, there has been limited exploration of the role of miRNAs in DM-associated PD through human studies. Future clinical trials are warranted to address this gap, focusing on standardizing sample collection, miRNA sources, and detection methods. This approach will enable the identification of specific miRNAs for DM-associated PD.