Longitudinal Study of the Influence of Periodontal Treatment on the Levels of Insulin Receptor Substrate-2 and Superoxide Dismutase 1 in Individuals with Type 2 Diabetes Mellitus

Objective: To longitudinally investigate the effect of non-surgical periodontal therapy (NSPT) on the transcriptional and translational levels of Superoxide Dismutase (SOD) and Insulin Receptor Substrate type 2 (IRS2) in individuals with Type 2 Diabetes Mellitus (T2DM) and Periodontitis (P). Methods: This clinical study was registered at the Brazilian Clinical Trials Registry (ReBEC-RBR-5m3yxmb). Saliva, peripheral blood mononuclear cells (PBMCs), and gingival biopsies were collected from 156 individuals, distributed into five groups, each with at least 30 participants: T2DMₚoorlycontrolled+P, T2DMwellcontrolled+P, T2DMwithoutP, Periodontitis, and Control. Systemic levels of messenger RNA (mRNA) of Superoxide Dismutase 1 (SOD1) and IRS2 were measured using real-time polymerase chain reaction at baseline, 90, and 180 days after NSPT. SOD enzymatic activity in Saliva and IRS-2 immunohistochemistry in gingival biopsies were also assessed. Results: Higher SOD1 mRNA levels were observed in Control individuals at baseline. In contrast, higher IRS2 mRNA levels were detected in individuals with Periodontitis at baseline, followed by a significant reduction over time. A significant positive longitudinal correlation was identified between IRS2 and SOD1 gene expression in the groups without T2DM, indicating potential functional interaction between the molecules. Salivary SOD enzymatic activity was lower in individuals from the T2DMₚoorlyControlled+P and T2DMwellControlled+P groups. SOD concentration (U/g) normalized to the total protein content was higher in the saliva of individuals with Periodontitis. T2DM+P and Periodontitis groups showed extensive inflammatory infiltrate in the gingival biopsies, with predominant IRS-2 immunopositive cells in the T2DM+P groups, independently of the metabolic control. Conclusions: This study shows that non-surgical periodontal therapy (NSPT) is followed by longitudinal changes in IRS2 and SOD1 expression at the mRNA and protein levels in individuals with T2DM+P (poorly/well controlled) and periodontitis, reinforcing the clinical relevance of periodontal treatment in the systemic context of T2DM.