The role of resistin as a mediator of cross-susceptibility between periodontal disease and type 2 diabetes mellitus

Abstract

Resistin is a cytokine involved in insulin resistance, inflammation, and immunity. Evidence suggests that resistin expression is elevated in diabetes and inflammatory diseases. Diabetes and periodontitis are associated with each other; however, the pathogenic links between these two diseases are not completely understood. Both diseases are deemed to be inflammatory conditions and, therefore, resistin may possibly play a pathogenic role in the two diseases. Therefore, the objective of this study was to investigate the possible relationship between resistin levels in saliva and serum, and periodontal disease in patients with or without type 2 diabetes mellitus (T2DM). The regulation of resistin expression and release from human monocytes and macrophages by LPS, as well as the impact of resistin on cytokine expression and secretion in vitro were also investigated. The present study demonstrated that salivary resistin was significantly elevated in periodontitis subjects as compared to gingivitis and periodontally healthy subjects in both T2DM and non-diabetic groups. However, there were no significant differences in salivary resistin between T2DM and non-diabetic groups irrespective of periodontal status. These data suggest that there is an association between salivary resistin and periodontitis rather than diabetic status. This hypothesis is supported by the finding that salivary resistin was significantly associated with bleeding on probing (BOP), mean probing depth (PD), mean loss of attachment (LOA) and periodontal inflamed surface area (PISA). Furthermore, saliva samples from both T2DM and non-diabetic subjects showed significant reductions in resistin levels at 3, 6 and 12 months after non-surgical periodontal management, which suggests that salivary resistin, may reflect improvements in periodontal inflammation following periodontal treatment. Serum levels of resistin were significantly higher in T2DM subjects compared to non-diabetic controls, confirming the association between serum resistin and diabetes. This hypothesis is supported by the finding that serum resistin positively correlated with HbA1c, BMI and hsCRP. There were no significant differences in serum resistin between subjects with healthy periodontal tissues, gingivitis and periodontitis within both the T2DM and non-diabetic groups. However, serum resistin was positively correlated with BOP, mean PD and PISA. The relationship of serum resistin to periodontal disease therefore remains unclear. In vitro, LPS from both P.gingivalis and E.coli significantly enhanced resistin expression and secretion in human monocytes and macrophages, suggesting that resistin is induced by inflammatory stimuli and probably involved in inflammatory responses. Resistin displays potent proinflammatory properties itself as it upregulated the expression and secretion of several proinflammatory mediators such as TNF-α, IL-1β, IL-6, MIP-1α and CXCL10 in THP-1 monocytes. In conclusion, salivary resistin could provide a novel local biomarker for periodontal disease. The upregulation of serum resistin in T2DM could influence periodontitis through the induction of inflammatory mediators that are responsible for exacerbating inflammation in periodontal tissues, and this process could contribute to the shared susceptibility between periodontal disease and T2DM.