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

PhD ThesisResistin 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.Iraqi Ministry of Higher Education and Scientific Research

Do patients with aggressive periodontitis have evidence of diabetes? A pilot study

BACKGROUND AND OBJECTIVE: Complex relationships exist between diabetes and periodontal disease. Diabetes is accepted as a risk factor for periodontal disease, and recent evidence supports the existence of a bidirectional relationship between these two diseases. It has been hypothesized that inflammation, lipids and adipokines may mediate these relationships. However, research regarding the above relationships with respect to aggressive periodontitis is very limited. This pilot study aimed to investigate whether patients with aggressive periodontitis (not previously diagnosed with diabetes) have evidence of diabetes and have altered serum levels of inflammatory mediators, lipids and adipokines. MATERIAL AND METHODS: Glycaemic control markers (random plasma glucose and glycated haemoglobin), inflammatory mediators (high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin-1β, interleukin-6, interferon-γ and interleukin-18), lipids (triglycerides, total cholesterol and high-density lipoprotein-cholesterol) and adipokines (leptin, adiponectin and resistin) were measured in serum samples from 30 patients with aggressive periodontitis and 30 age- and sex-matched periodontally healthy control subjects, none of whom had a previous diagnosis of diabetes. RESULTS: Levels of glycaemic control markers, inflammatory mediators, lipids and adipokines were not significantly different (p > 0.05) between the aggressive periodontitis patients and healthy subjects for unadjusted and adjusted analyses (adjusting for body mass index, smoking, ethnicity, age and sex). The p-value for the adjusted analysis of adiponectin in female aggressive periodontitis patients compared with the female control subjects reached 0.064, the mean adiponectin level being lower in the female aggressive periodontitis patients (4.94 vs. 5.97 μg/mL). CONCLUSION: This pilot study provided no evidence to suggest that patients with aggressive periodontitis (not previously diagnosed with diabetes) have evidence of diabetes or altered serum levels of inflammatory mediators, lipids and adipokines

Treatment of periodontitis reduces systemic inflammation in type 2 diabetes

Aims: To assess the impact of periodontal treatment on systemic inflammation in type 2 diabetes. Materials and methods: Adults with type 2 diabetes (n = 83) and without diabetes (controls, n = 75) were recruited, and participants with periodontitis received periodontal treatment and 12 months' follow-up. Biomarkers for periodontal inflammation (gingival crevicular fluid interleukin-6, tumour necrosis factor-α, interleukin-1β, interferon-γ, matrix metalloproteinase-8, matrix metalloproteinase-9, adiponectin) and serum markers of inflammation and diabetes control (glycated haemoglobin, high sensitivity C-reactive protein, interleukin-6, tumour necrosis factor-α, interleukin-1β, interferon-γ, leptin, adiponectin) were measured. Structural equation modelling was used to evaluate periodontal treatment effects on oral and systemic inflammation. Results: Periodontal treatment resulted in significant improvements in clinical status and reductions in gingival crevicular fluid biomarkers from baseline to month 12. Structural equation modelling identified that, at baseline, individuals with diabetes and periodontitis had significantly higher systemic inflammation than non-diabetic controls with periodontitis (Δ = 0.20, p = .002), with no significant differences between groups for oral inflammation. There was a greater reduction in systemic inflammation following periodontal treatment in individuals with diabetes and periodontitis compared to those with periodontitis but not diabetes (Δ = -0.25, p = .01). Conclusions: Diabetes and periodontitis together appear to increase systemic inflammation, with evidence of reductions following periodontal treatment