Biochemical analysis of the impact of glycemic control on inducible nitric oxide synthase and proinflammatory cytokine levels in the gingival tissues of patients with type 2 diabetes mellitus and periodontitis

This study aimed to evaluate inducible nitric oxide synthase (iNOS) and proinflammatory mediator levels in participants with type 2 diabetes mellitus (T2DM) and periodontitis and to investigate the relationship between glycemic control and inflammatory status. A total of 118 participants were categorized into six groups based on periodontal status and metabolic control. The levels of prostaglandin E 2 (PGE 2 ), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), iNOS, and interferon-gamma (IFN-γ) were measured in gingival biopsy supernatants using enzyme-linked immunosorbent assay (ELISA). Participants with uncontrolled T2DM and periodontitis presented higher concentrations of TNF-α ( p < 0.001), iNOS ( p < 0.05), and IFN-γ ( p < 0.001) than the control group. Compared with participants with controlled T2DM and periodontitis, IL-1β ( p < 0.001), TNF-α ( p < 0.001), iNOS ( p < 0.001), and IFN-γ ( p < 0.001) levels were elevated in participants with uncontrolled T2DM and periodontitis. The iNOS concentration was significantly greater in periodontally healthy participants with uncontrolled T2DM than in those with controlled T2DM ( p < 0.05). A strong correlation was found between IL-1β and iNOS in all participants with periodontitis ( p < 0.001), and between IFN-γ and iNOS in participants with controlled T2DM and in periodontally healthy participants with uncontrolled T2DM ( p < 0.001). Poor glycemic control was associated with an enhanced inflammatory response, whereas well-controlled T2DM participants presented inflammatory profiles similar to those of systemically healthy participants. This study was registered in the Protocol Registration and Results System at https://www.clinicaltrials.gov with the registration number NCT06803836 on 2025-01-31.