Perhaps the best reflection of the current knowledge potential risk factor for periodontal disease.^65,66 Obesity comes from a recent meta-analysis of 10 intervention was shown to be associated with periodontal disease in a trials showing that periodontal therapy without antibiot- cohort study of 241 patients, where the additional risk for ics reduced HbA1c levels 0.4% from baseline on aver- periodontitis was 3-fold higher in patients with BMI 25 to age, and the addition of systemic antibiotics resulted in 29. 9 kg/m² than in patients with BMI ≤ 20 kg/m².^{(ref 65)} Pa-an average reduction of 0.7%, neither of which reached tients with BMI ≤ 30 kg/m² had an 8.6-fold higher risk than statistical significance.⁶² Although the studies to date are controls. A recent study using data from 12,367 subjects conflicting, it appears that periodontal treatment may in the National Health and Nutrition Examination Survey have the ability to influence glycemic control in some pa- (NHANES III) showed that insulin resistance appears to tients, and those with poorer diabetic control and severe, mediate this relationship, ⁴⁷ which may begin to explain generalized periodontitis are likely to benefit the most. the association between periodontal disease and DM. The study further suggested that high plasma TNF-α levels

The exact mechanisms by which a reduction in periodon- associated with enhanced adipocyte secretion in obesity tal inflammation following treatment may affect insulin may account for further increases in insulin resistance. A resistance and glycemic control are not well established. model was proposed in which increased cytokine levels, It has been noted that local as well as systemic dissemi- along with additional cytokine production triggered by nation of inflammatory mediators, most notably the cy- advanced glycation end products (AGE) in DM patients, tokines TNF-α and IL- 6, may increase insulin resistance. create a systemic hyperinflammatory state and prime the IL- 6 itself acts to further stimulate TNF-α production, periodontal tissues to respond in an exaggerated manner which may lead to additional insulin resistance. Chronic to infecting microorganisms. Further data are needed to periodontal infection can contribute to insulin resistance substantiate this theory. However, periodontal therapy by up-regulating these cytokines.⁶³ In addition, mono- not only reduces local inflammation and cytokine levels cytes from DM patients produce up to 32 times more but also reduces TNF-α levels systemically, and this cor-TNF-α than monocytes from patients without DM when relates with a significant improvement in glycemic con-stimulated by periodontal pathogens, leading to higher trol in patients with type 2 DM, with a significant reduc-systemic cytokine levels.⁶⁴ tion in HbA1c levels from 8.0% to 7.1%.⁶⁷ Further work is needed to determine exactly how periodontal treatment

Obesity is a risk factor for type 2 DM and also may be a and the subsequent reduction in periodontal inflamma-

Obesity;
Acute
Illness;
Chronic ➡ Elevated Serum _α) ➡ ➡ Poor _{Periodontal Cytokine Levels Insulin Glycemic Inflammation (TNF- Resistance Control}

Weight Loss;
Resolution
of Acute
Illness; ➡ Decreased ➡ Improved ➡ _{Periodontal Systemic Insulin Improved}
Treatment Inflammation Sensitivity Glycemia

Figure 1 – Proposed model for effects of inflammation, infection, and obesity on glycemic control

Obesity, acute illness (such as upper respiratory tract infection), or chronic periodontal inflammation may result in a state of systemic inflammation, with increased serum levels of cytokines, such as TNF-α, that cause an increase in insulin resistance. The result is worsening of glycemic control. Weight loss, resolution of an acute illness, and periodontal treatment that reduces inflammation may improve the systemic inflammatory status of the patient, resulting in enhanced insulin sensitivity and better glycemic control.