Diabetes mellitus and periodontitis are both common, chronic diseases and have a two-way relationship. In addition to persistent, low-grade inflammation, oxidative stress is a common link between them. Periodontitis patients present with more severe loss of tooth attachment when their oral polymorphonuclear neutrophils (oPMNs) produce high levels of Reactive Oxygen Species (ROS). The elevation of blood glucose levels, or hyperglycemia also triggers the excessive production of free radicals through various biochemical pathways leading to oxidative stress. 

At the forefront of resistance against oxidative stress stands Nuclear factor erythroid 2-related factor 2 (Nrf2), a central player in the control of cellular redox balance. In response to oxidative stress, cytoplasmic Nrf2 is released from Kelch-like ECH Associated Protein-1 (KEAP-1) and binds to Antioxidant Response Elements (AREs) in the promoter region of many antioxidant enzymes. In addition, Nrf2 plays critical roles in the control of inflammation. Down-regulation of the Nrf2 pathway in oPMNs is associated with increased recruitment in the oral cavity and severe periodontitis. Furthermore, dysregulation of the Nrf2 pathway has been implicated in the pathogenesis of T2DM. Nrf2 activation can ameliorate oxidative damage, block tissue destruction in periodontitis and protect against diabetic complications. 

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors latent in the cytoplasm that consist of seven different members: STAT-1, -2, -3, -4, -5A, -5B, and -6. STAT3 transmits signals from the cellular membrane to the nucleus from diverse cytokine families. Changes in subgingival microbial communities activate pathways that increase the secretion of cytokines. Some of these cytokines, such as the IL-6 family of cytokines, use a common intracellular signaling pathway mediated by STAT3. STAT3 signaling pathways are also involved in determining peripheral and hepatic insulin sensitivities and participate in the development of IL-6 induced insulin resistance in subjects with impaired glucose tolerance.

Nrf2 and STAT3 have been individually associated with PD and T2DM. However, a comprehensive understanding of the relationship between Nrf2 and STAT3 in both periodontal disease and diabetes has not been investigated in humans. Hence, the aim of this study is to comparatively evaluate salivary and serum levels of Nrf2 and STAT3 in patients with generalized periodontitis and T2DM.