Abstract
OBJECTIVE: To systematically review and meta-analyze proinflammatory cytokines and advanced glycation end products (AGEs) levels in gingival crevicular fluid (GCF) among individuals with type 2 diabetes mellitus (T2DM) undergoing fixed orthodontic treatment (FOT), compared with non-diabetic counterparts, incorporating recent evidence on hyperglycemia-driven inflammation and periodontal biomarkers. METHODS: This PRISMA-compliant systematic review and meta-analysis (PROSPERO: CRD420251237402) searched PubMed, Scopus, ScienceDirect, Web of Science, EBSCO, and Google Scholar, without date or language restrictions, using descriptors including "Cytokines," "Chemokines," "Advanced Glycation Endproducts," "Gingival Crevicular Fluid," "Type 2 Diabetes Mellitus," and "Fixed Orthodontic." Risk of bias was assessed using a modified Quality Assessment Instrument (QAI). Meta-analysis was performed with Review Manager 5.4.1, using fixed- or random-effects models based on heterogeneity. RESULTS: Of 224 records, three cross-sectional studies (all moderate risk of bias) were included. Meta-analysis showed elevated AGE levels AGEs (MD = 154.06 [95% CI = 72.25 to 235.87]; p = 0.03; I (2) = 36%) and TNF-α (MD = 17.45 [95% CI = 1.97 to 32.92]; p = 0.04; I (2) = 0%) in T2DM + FOT compared to non-T2DM + FOT groups. CONCLUSIONS: T2DM is associated with elevated inflammatory responses during FOT, as indicated by increased GCF levels of TNF-α and AGEs. However, further well-designed studies are needed to determine whether these biological differences lead to clinically relevant outcomes or justify tailored orthodontic approaches for this population.