Salivary advanced glycated end products, their receptors, and aMMP‐8 in periodontitis patients with varying glycemic levels: A cross‐sectional study
Authors: Thomas Julie Toby , Joseph Betsy , Varghese Sajit , Kamalasanan Vijayakumari Baiju , Sorsa Timo , Mauramo Matti , Anil Sukumaran , Waltimo Tuomas 
Published: December 2024

AbstractBackgroundAdvanced glycation end products (AGE) and their receptors (RAGE) have been implicated in developing periodontal complications in diabetic patients. This study aimed to identify salivary AGE, RAGE, soluble RAGE (sRAGE), and active‐matrix metalloproteinase‐8 (aMMP‐8) levels at varying glycemic levels in periodontitis patients.MethodsNinety‐eight participants were categorized into uncontrolled DM‐PD group (n = 27)—periodontitis patients with uncontrolled Type 2 diabetes mellitus (T2DM) (glycated hemoglobin [HbA1c] ≥7%); controlled DM‐PD group (n = 33)—periodontitis patients with controlled T2DM (HbA1c 5.7%–6.9%); SH‐PD group (n = 18)—systemically healthy periodontitis patients; and SH‐PH group (n = 20)—systemically and periodontally healthy individuals. HbA1c along with the periodontal parameters bleeding on probing (BoP), periodontal probing depth (PPD), clinical attachment loss (CAL), number of missing teeth, and periodontal inflamed surface area (PISA) were estimated. Enzyme‐linked immunosorbent assay (ELISA) was used for analyzing salivary AGE, RAGE, sRAGE, and aMMP‐8. Multiple linear regression analysis was conducted to develop predictive models for HbA1c based on relevant predictor variables.ResultsPeriodontitis participants with uncontrolled T2DM exhibited significantly higher BoP, PPD, CAL, number of missing teeth, and PISA, along with elevated AGE, RAGE, and aMMP‐8, compared to other groups (p < 0.01). A significant positive association was observed between RAGE and HbA1c levels (p < 0.01). Among the predictors, BoP (p = 0.046) and CAL (p < 0.001) demonstrated a significant positive effect on salivary AGE. PPD was positively associated with RAGE (p < 0.05), and BoP was negatively associated with salivary sRAGE levels (p = 0.038).ConclusionsSalivary biomarkers like RAGE and aMMP‐8 exert a potential role in monitoring periodontal health and glycemic control in T2DM patients.Plain language summaryAdvanced glycation end products (AGE) and their receptors (RAGE) have been implicated in developing periodontal complications in diabetic patients. This study aimed to identify salivary AGE, RAGE, soluble RAGE (sRAGE), and aMMP‐8 levels at varying glycemic levels in periodontitis patients. Ninety‐eight participants were categorized into Group 1 (n = 27)—periodontitis patients with uncontrolled Type 2 diabetes mellitus (T2DM); Group 2 (n = 33)—periodontitis patients with controlled T2DM; Group 3 (n = 18)—systemically healthy periodontitis patients; and Group 4 (n = 20)—systemically and periodontally healthy individuals. Enzyme‐linked immunosorbent assay (ELISA) was used for analyzing salivary AGE, RAGE, sRAGE, and aMMP‐8. The study revealed that participants with uncontrolled T2DM and severe periodontitis exhibited significantly higher levels of salivary AGE, RAGE, and aMMP‐8, along with increased periodontal parameters, compared to controlled T2DM and systemically healthy groups. Conversely, salivary sRAGE levels were significantly lower in the uncontrolled T2DM group. The study also found significant associations between salivary RAGE levels and glycated hemoglobin (HbA1c), as well as between aMMP‐8, AGE, and clinical periodontal parameters. The findings of this study highlight the potential clinical utility of salivary biomarkers, particularly RAGE and aMMP‐8, as noninvasive diagnostic and monitoring tools to evaluate glycemic control and periodontal health in individuals with diabetes.