Periodontitis and Systemic Diseases

Table 1-5 Clinical studies assessing the epidemiological association between periodontitis and T1DM

BoP = bleeding on probing; CAL = clinical attachment level; HbA1c = glycated haemoglobin; OR = odds ratio; PPD = pocket probing depth; T1DM = type 1 diabetes; T2DM = type-2 diabetes.

SUMMARY

● The prevalence of diabetes is 13.1% among subjects with periodontitis and 9.6% among ­subjects without periodontitis according to a 2018 meta-analysis.

● There is strong evidence for an association between periodontitis and glycaemic status, ­expressed as HbA1c, fasting blood glucose levels and/or glucose tolerance test, the latter in ­people without diabetes.

● HbA1c is significantly reduced at 3 to 4 months following periodontal therapy. However, there are insufficient data to demonstrate that this effect is maintained after 6 months.

● Some studies identified that periodontitis increases insulin resistance (HOMA-IR levels) in ­people with diabetes.

● People with diabetes and periodontitis are more likely to suffer from diabetes-related ­com­plications than people with diabetes only.

1.3 Cellular and molecular mechanisms

The principal mechanisms that link oral infection with systemic diseases are:

● metastatic spread of infection from the oral cavity as a consequence of transient bacteraemia

● metastatic spread of cellular injuries because of the circulation of oral bacterial toxins

● metastatic spread of inflammation triggered by oral bacteria 121.

In obesity, the mechanism behind its impact on periodontitis is still controversial. However, inflammation and the role of cytokines are surely of great importance in explaining a possible mechanism. Obesity is associated with a state of chronic low-grade systemic inflammation. Evidence from animal and human studies demonstrates a clear association between weight regulation and inflammation, with abnormalities of innate and adaptive immune function, including elevated serum levels of inflammatory cytokines, such as IL-5, -10, -12, -13, interferon (IFN)γ and TNF-α and peripheral blood lymphocyte subpopulation levels 122. For example, in obese mice under a high-fat diet, pro-inflammatory T-helper cells 1 (Th1) and pro-inflammatory M1 macrophages, are activated and produce IFNγ, TNF-α, and IL-12 123 , 124, whereas the differentiation of naïve T cells into anti-inflammatory Th2 and the activity of regulatory T cells (Treg), are reduced 125. Moreover, as explained earlier, peri­odontal pathogen populations may be altered in obese subjects possibly leading to a higher virulence of the periodontal pathogens in those patients (Fig 1-1).

Fig 1-1 Potential mechanism linking obesity to periodontitis. Obesity increases the levels of inflammatory cytokines, oxidative stress and levels of periodontal pathogens, and can lead to diabetes mellitus, increasing the prevalence and severity of periodontitis. Environmental and genetic factors modulate both diseases. (IL = interleukin; MCP-1 = monocyte chemoattractant protein-1; TNF-α = tumour necrosis factor alpha.)

Many studies have demonstrated that adipose tissue cells (adipocytes, pre-adipocytes and macrophages) secrete cytokines and over 50 other bioactive substances collectively known as adipokines, explaining the low-grade systemic inflammation observed in obesity 126. However, there are conflicting results regarding which cytokines play the main role in an obesity-periodontitis association. For example, high levels of TNF-α in plasma 127and gingival crevicular fluid (GCF) 128were found in obese subjects. On the other hand, Saxlin et al 129observed that serum IL-6, but not TNF-α, may mediate the possible inflammatory effect of body weight on the periodontium.