Diabetes mellitus (DM) is associated with periodontal disease. Clinically, periodontal treatment is less effective for patients with DM. Oxidative stress is one of the mechanisms that link DM to periodontitis. The production of reactive oxygen species (ROS) is increased in the periodontal tissues of patients with DM and is involved in the development of insulin resistance in periodontal tissues. Insulin resistance decreases Akt activation and inhibits cell proliferation and angiogenesis. This results in the deterioration of wound healing and tissue repair in periodontal tissues. Antioxidants and insulin resistance ameliorants may inhibit ROS production and improve wound healing, which is worsened by DM. This manuscript provides a comprehensive review of the most recent basic and clinical evidence regarding the generation of ROS in periodontal tissues resulting from microbial challenge and DM. This study also delves into the impact of oxidative stress on wound healing in the context of periodontal and dental implant therapies. Furthermore, it discusses the potential benefits of administering antioxidants and anti-insulin resistance medications, which have been shown to counteract ROS production and inflammation. This approach may potentially enhance wound healing, especially in cases exacerbated by hyperglycemic conditions.

This review investigated whether the adjunctive use of antioxidants with periodontal therapy improves periodontal parameters in patients with type 2 diabetes. A systematic and extensive literature search for randomized controlled trials (RCTs) conducted before April 2021 was performed on the PubMed, Cochrane Library, and Web of Science databases. The risk of bias was assessed using the Cochrane risk-of-bias tool. A meta-analysis was performed to quantitatively evaluate the clinical outcomes following periodontal therapy. After independent screening of 137 initial records, nine records from eight RCTs were included. The risk-of-bias assessment revealed that all RCTs had methodological weaknesses regarding selective bias, although other risk factors for bias were not evident. This meta-analysis of two RCTs showed that periodontal pocket depths were significantly reduced in the groups treated with combined non-surgical periodontal therapy and melatonin than in those treated with non-surgical periodontal therapy alone. The present systematic review and meta-analysis suggest that the adjunctive use of melatonin, resveratrol, omega-3 fatty acids with cranberry juice, propolis, and aloe vera gel with periodontal therapy significantly improves periodontal disease parameters in patients with type 2 diabetes, and melatonin application combined with non-surgical periodontal therapy might significantly reduce periodontal pocket depth. However, there are still limited studies of melatonin in combination with non-surgical periodontal therapy in Type 2 diabetic patients, and more well-designed RCTs are required to be further investigated.

Periodontitis has been documented to increase the risk of diabetic nephropathy. However, the specific mechanisms through which periodontitis affects renal function remain unclear. This study aimed to investigate the mechanism by which an inflammatory reaction stimulated by periodontal pathogens affects mesangial cell fibrosis under hyperglycemic conditions in vitro. Murine mesangial cells were stimulated with 1,000 ng/mL of Porphyromonas gingivalis-derived lipopolysaccharide (PgLPS) in a control or high glucose (HG) medium. Activation of the extracellular signal-regulated kinase (ERK1/2) and expression of alpha-smooth muscle actin (α-SMA) and collagen type 1a2 (Col1a2) were analyzed for fibrosis and transformation via the transforming growth factor (TGF)-β1/Smad signaling pathway. PgLPS stimulation significantly upregulated TGF-β1 expression and Smad3 phosphorylation in the HG group compared to the control group. Additionally, activation of ERK1/2 and expression of Col1a2 and α-SMA were significantly elevated in the HG group compared to the control following PgLPS stimulation. The TGF-β1 inhibitor significantly suppressed Smad3 phosphorylation and mRNA expression of Col1a2 in the HG group. Under HG conditions, PgLPS may aggravate fibrosis in mesangial cells via the TGF-β1/Smad signaling pathway, leading to nephrosclerotic modifications. The presented study may support the association between periodontitis and chronic kidney disease, mediated by hyperglycemia.