Common Inflammatory Burden

Evaluation of longitudinal data in large-scale cross-sectional studies, including the National Health and Nutrition Examination Survey (NHANES), demonstrates obesity is correlated with deep periodontal pockets, independent of glucose tolerance status55 and BMI is posititvely correlated with severity of periodontal attachment loss in a relationship modulated by insulin resistance.56 Adipose tissue secretes a host of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). TNF-α and IL-6 are the main inducers of acute-phase hepatic protein production, including C-reactive protein (CRP).57 Additionally, both TNF-α and IL-6 have been shown to impair intracellular insulin signaling, which may lead to insulin resistance.58,59 Human plasma levels of TNF-α, IL-6, and CRP are associated with obesity and insulin resistance60,61 as well as periodontal inflammation and destruction of periodontal tissues,62-64 and periodontal treatment has been demonstrated to reduced levels of circulating TNF-α.65 In persons with periodontal disease, bacterial pathogens, endotoxins, and inflammatory cytokines may systemically trigger an upregulated leukocytosis, synthesis of acute-phase proteins (e.g. CRP, Amyloid A), and enhanced lipid metabolism as well as increase serum cholesterol and triglyceride levels.66-71 This pathway may then lead to an increased risk of other systemic diseases. Additionally, the introduction of periodontal pathogens and their toxic by-products in a hyper-inflammatory environment, as is produced in obesity, may lead to a more robust immune-inflammatory response favoring progression of clinical disease and tissue destruction (Figure 4).

Figure 4. Adipocytes produce pro-inflammatory mediators.103

Diagram showing Adipocytes production of pro-inflammatory mediators

It is interesting to note previous investigations have suggested periodontal disease has a greater effect on overall systemic inflammation in patients with normal BMI and this influence decreases as BMI increases.72,73 This suggests that the inflammatory burden associated with periodontal disease may be overwhelmed by the larger influence of obesity-related inflammation in overweight and/or obese patients. When C-reactive protein (CRP) was used as a measure of systemic inflammation, the association between elevated CRP levels associated with extensive periodontal disease was dependent upon the subject’s BMI.73 Obesity has also been shown to negate the effects of nonsurgical periodontal treatment on systemic CRP levels in patients with at least mild chronic periodontitis.72 This may indicate the interaction between periodontal disease and obesity may have a BMI “ceiling” for the effect, and individual patient responses to therapy may differ based upon their obesity status.