Obesity, a common metabolic and nutritional disorder, is a complex multifactorial chronic disease that develops from an interaction of genotype and the environment 1. Obesity can be considered the fastest-growing health-related problem in the world at present 2. Although the fundamental mechanisms contributing toward the increase in obesity are not well understood, it has become clear that genetic and environmental factors and socioeconomic and behavioral influences leading to excess caloric intake, decreased physical activity, and metabolic and endocrine abnormalities are likely important factors 3.
Periodontitis is among the most common chronic disorders worldwide. It is initiated by gingival colonization by pathogenic bacteria, followed by the activation of defense mechanisms 4. It is generally known that much of the periodontal tissue destruction observed in periodontitis is host mediated through the release of proinflammatory cytokines by local tissues and immune cells in response to the bacteria and its products, especially lipopolysaccharides 5,6. Many factors are considered to be associated with the development of periodontal disease and its progression and aggressiveness. Augmented secretion of proinflammatory cytokines increases the probability of the appearance of lesions in the periodontal tissue 3,7.
Obesity has been suggested to be associated with periodontal infection in several studies 3,8. Through its impact on metabolic and immune parameters, obesity may increase the host’s susceptibility to periodontal disease 3,9. Many studies have shown that cytokines produced by adipose tissue could be one mechanism mediating the association between body weight and periodontal infection 10.
Adipose tissue is inflamed in obesity, with decreased expression of the anti-inflammatory adipokines adiponectin and increased secretion of a variety of proinflammatory cytokines such as tumor necrosis factor α (TNF-α) 11. TNF-α is a major signal for cellular apoptosis, bone resorption, matrix metalloproteinases secretion, and interleukin-6 production. Interleukin-6, once produced, stimulates the formation of osteoclasts and promotes osteoclastic bone resorption 12. Adiponectin is associated with the modulation of inflammatory responses. It attenuates the inflammatory response mediated by TNF-α and inhibits macrophage phagocytic activity and TNF-α production. Also, it inhibits the formation of osteoclasts stimulated by lipopolysaccharides from periodontal pathogenic bacteria 13,14.
This study was carried out to determine the effect of changes in the serum level of TNF-α and adiponectin because of obesity on the clinical outcome of periodontal treatment and to determine whether obese patients respond to periodontal treatment in a manner similar to normal-weight patients.
Participants and methods
Forty patients were selected from the out-patient clinic of the Department of Oral Diagnosis, Oral Medicine and Periodontology, Faculty of Dentistry, Ain Shams University. Patients fulfilled the following inclusion criteria:
All patients free from any systemic diseases were selected using a medical questionnaire guided by the Cornell medical index, nonsmokers, either men or women, age range 20–40 years. Patients were not receiving any systemic drugs at the time of the examination and for at least 4 weeks before the study. Patients did not receive any drugs during the follow-up period. Patients had at least 18 remaining teeth excluding third molars. Patients showed no marked changes in body weight at least 3 months before the start of the study. All the patients were willing to perform self-performed plaque control measures.
Patients who showed marked changes in body weight during the study period were excluded from the study. Also, patients who had taken any systemic drugs during the study period (3 months from starting the conventional periodontal therapy) were excluded from the study. The proposed nature of the study was explained to each patient.
Patient grouping and treatment protocol
The 40 patients were divided into three groups. Group 1 included 15 obese patients [according to: the BMI≥30 kg/m2 and waist circumference (WC) measures>102 cm in men and WC>88 cm in women (on the basis of Expert panel, 1998)] with moderate-to-severe chronic periodontitis (mean clinical attachment loss≥4 mm) and with a mean probing depth (PD) greater than or equal to 3 mm. This group of patients was subjected to conventional periodontal therapy, which included full-mouth supra and subgingival scaling, curettage and root planning, and instructions for oral hygiene measures. All other dental treatments were carried out before the completion of the periodontal treatment phase. Recall appointments were held every 3 weeks throughout the study period for professional prophylaxis and oral hygiene reinforcement. Group 2 included 15 patients whose weight was within normal limits [BMI=18.5–24.9 kg/m2 (on the basis of Expert panel, 1998) and WC≤102 in men and WC≤88 in women] with moderate-to-severe chronic periodontitis (mean clinical attachment loss≥4 mm) and with a mean PD greater than or equal to 3 mm. Group 3 included 10 obese patients [according to: the BMI≥30 kg/m2 and WC measures>102 cm in men and WC>88 cm in women (on the basis of Expert panel, 1998)] who had no chronic periodontitis (no clinical attachment loss) but had mild chronic gingivitis. Groups 2 and 3 were subjected to the same treatment protocol as group 1.
Periodontal assessment was carried out for the three groups at the baseline (at the initial visit before starting the conventional periodontal therapy) and at the end of the study (3 months after starting the conventional periodontal therapy). Periodontal assessment included plaque index 15, sulcus bleeding index 16, PD 17, and clinical attachment level (CAL) 17. PD and CAL were measured using Ash William’s graduated periodontal probe with a cross-sectional diameter of 0.8 mm. Four readings were recorded for each tooth: mesiobuccal, midbuccal, distobuccal, and midlingual excluding the third molars.
Laboratory tests and measures
Laboratory tests were carried out for the detection of serum level of TNF-α using a commercially available enzyme-linked immunosorbent assay (ELISA) kit [Quantikine Human TNF-α/TNFSF1A Immunoassay; R&D Systems (R&D SYSTEMS inc., Minneapolis, USA)]. The serum level of adiponectin was determined using a commercially available ELISA kit (Quantikine Human Adiponectin/Acrp30 Immunoassay; R&D Systems).
Measures for obesity assessment include BMI and WC (cm). Laboratory tests and measures were carried out for the three groups at the baseline and at the end of the study.
Statistical analyses were carried using the SPSS program Version 15 (SPSS, Chicago, Illinois, USA). Qualitative data were presented using the frequency and related percentage. Quantitative data were presented using the mean and SD. Comparison of qualitative data between groups was carried out using the χ2-test. Comparison of quantitative data between groups was carried out using analysis of variance with an least significant difference post-hoc analysis. Paired quantitative data were compared using the t-test for paired samples. Pearson correlation was used to measure the correlation between the different variables. A ‘P’ value of 0.05 was chosen as the level of statistical significance.
Group 1 included five men (33.3%) and 10 women (66.7%), group 2 included six men (40%) and nine women (60%), and group 3 included three men (30%) and seven women (70%). The demographic parameters of the three study groups are shown in Table 1.
In the three study groups, a high statistically significant difference (P<0.001) was found between the mean plaque index before and after the periodontal treatment, between the mean bleeding index before and after treatment, and on comparing the mean PD before and after periodontal treatment. Also, on comparing the mean attachment loss before and after treatment in groups 1 and 2, a high statistically significant difference was found (P<0.001). No significant difference was found between the mean TNF-α serum level before and after treatment in groups 1 and 3, whereas a statistically significant difference (P<0.05) was found between the mean TNF-α before and after the periodontal treatment in group 2.
No significant difference was found between the mean adiponectin level before and after periodontal treatment in the three study groups. Table 2 and Fig. 1 shows the effect of periodontal treatment on the changes in the periodontal parameters and the changes in TNF-α and adiponectin serum levels (the mean percentages of change). For the entire study population, the correlation was tested; a statistically significant negative correlation was found between the BMI or WC and changes in PD, CAL (P<0.01), and the serum TNF-α level. For the entire study population, a significant positive correlation was found between the changes in the TNF-α serum level and changes in the PD and CAL (P<0.05) (Tables 3 and 4).
The subclinical inflammatory response observed in obesity is characterized by elevated levels of proinflammatory cytokines, for example, TNF-α 18. In contrast to other adipose tissue-derived adipokines, the levels of adiponectin, an anti-inflammatory adipokine, are reduced in obese individuals 19. Considering the role played by TNF-α and adiponectin in the association of obesity with periodontal disease, TNF-α and adiponectin can be considered suitable serum parameters to study the effect of obesity on the clinical results of conventional periodontal treatment while monitoring the changes in their serum levels induced by the treatment. We hypothesized that the clinical response to conventional periodontal treatment in normal-weight patients will be better than that in obese patients in terms of PD and CAL because of the changes induced by obesity in the serum levels of TNF-α and adiponectin. It was found that the systemic effects in terms of obesity need to be fairly high before a relationship between TNF-α in gingival crevicular fluid and BMI can be demonstrated 20. Thus, obese individuals selected in the obese group of our study had BMI of more than 30. In a recent research, obesity in terms of high WC was especially associated with periodontal disease in 18–34-year-old individuals, but not in older adults, suggesting a closer correlation between high WC and periodontitis in younger adults; it is not clear as to why an increase in periodontal disease was not seen in older individuals 21. Therefore, our study population was restricted to patients who were 20–40 years of age. There were statistically significant differences between the BMI and WC of groups 1 and 2 and also between groups 3 and 2, which are important to illustrate the effect of obesity on the clinical outcome of conventional periodontal treatment.
The serum levels of adiponectin and TNF-α were examined using the ELISA kits according to the manufacturer’s protocol. The baseline serum level of TNF-α in group 1 was found to be higher than the baseline serum level of TNF-α in group 2, but the difference did not reach the level of significance. On comparing them statistically, the P value was 0.08, which is very close to 0.05 (the P value chosen as the level of significance in our study). The insignificant difference can be explained by the high value of SD or/and the small sample size. The higher level of TNF-α in group 1 than that in group 2 is in agreement with previous studies that have reported that obese individuals have elevated levels of circulating TNF-α compared with normal-weight patients and the levels of these cytokines decrease after weight loss 22. The baseline serum level of adiponectin in group 1 is less than the baseline serum level of adiponectin in group 2, but the difference did not reach the level of significance. On comparing them statistically, the P value was 0.1, which is very close to 0.05. The insignificant difference can be explained by the high value of SD or/and the small sample size. The lower adiponectin level in group 1 than that in group 2 is in agreement with previous studies that have shown that adiponectin serum level is reduced in obese individuals in contrast to other adipose tissue-derived hormones 19.
On comparing the obese groups (groups 1 and 3) regarding the serum level of TNF-α and adiponectin, the TNF-α serum level for group 1 (obese and chronic periodontitis) was higher than that for group 3 (obese with no chronic periodontitis) and the difference was statistically significant, whereas for adiponectin, the serum level in group 1 was significantly lower than that in group 3. These results were in agreement with the results of previous studies that have shown that serum TNF-α levels were elevated in periodontitis patients and that periodontal treatment reduces the levels of circulating TNF-α serum 23,24 and with the results that showed that there is a tendency toward decreased serum adiponectin levels in periodontitis patients 25. A highly statistically significant reduction in all periodontal parameters at P value of less than 0.001 was observed in our results in all three groups after the periodontal treatment.
The mechanical professional instrumentation reduces the number of pathogens populating the subgingival biofilm of the infected periodontium and eliminates the environment conductive to microbial colonization; in addition, 0.1% cholorohexidine gluconate exerts an antimicrobial effect. Thus, this conventional periodontal treatment helped reduce the bacterial load and local inflammation, which explained the significant improvement in all periodontal parameters after periodontal treatment in all the three groups. A reduction in the serum level of TNF-α was seen in the three groups after periodontal treatment. These results were in agreement with a previous study carried out by Nishimura and coworkers, which showed that periodontal patients with elevated TNF-α concentrations had reduced levels after periodontal therapy; thus, periodontal treatment reduces the circulating TNF-α level 23,24,26.
The reduction in the serum level of TNF-α after the periodontal treatment was statistically significant in group 2, but not in group 1.This can be as attributed to the fact that in group 1, the serum TNF-α level was affected concomitantly by obesity and periodontitis, whereas in group 2, the serum TNF-α was elevated mainly because of chronic periodontitis; thus, after periodontal treatment, the serum TNF-α level in group 1 decreased, but not significantly, as a result of the effect of obesity on the TNF-α serum level. In group 3, an insignificant reduction in the serum TNF-α level was observed after treatment owing to the limited effect of gingivitis on the TNF-α serum level; thus, the periodontal treatment of chronic gingivitis did not have a significant effect on the serum TNF-α level.
Insignificant changes were seen in the serum adiponectin level after the periodontal treatment in the three groups, which is in accordance with a previous study that demonstrated that periodontal treatment did not influence the circulating adiponectin level 27. In the current study, changes in serum TNF-α were not related to the serum adiponectin level and adiponectin levels did not change significantly. Therefore, at least in an inflammatory condition, TNF-α might be induced by mechanisms independent of adiponectin. However, in our study and in the study carried out by Iwamoto and colleagues in 2003, the number of patients is small and only a single timepoint after antimicrobial periodontal therapy was chosen to measure the adiponectin level. Therefore, the role of periodontal inflammation in the regulation of adiponectin still remains inconclusive. A significant difference (P<0.05) was found between groups 1 and 2 in the mean percent of change in PD and CAL, with the mean percent of change in group 2 being greater than that in group 1; this can be attributed to the significant difference between groups 1 and 2 in the mean percent of change in the serum level of TNF-α being significantly higher in group 2 (P<0.05). For the entire study population, a significant positive correlation was found between the changes in the TNF-α serum level and changes in PD and CAL (P<0.05). This means that the clinical response to periodontal treatment in terms of PD and CAL is better in group 2 compared with group 1 23,24.
The greater significant changes in TNF-α in group 2 than group 1 after periodontal treatment can be attributed to the fact that the TNF-α level in group 1 is affected by both obesity and periodontitis, whereas in group 2, it is affected by periodontitis but not obesity. Thus, treatment of periodontitis will exert a greater reducing effect on the TNF-α serum level in group 2 than in group 1.
No statistically significant difference was found between the percent of changes in PD or TNF-α in groups 1 and 3. This may suggest that the effect of obesity on the clinical outcome of periodontal treatment in terms of PD in obese patients with chronic periodontitis or chronic gingivitis may not differ. However, this result may also be because of significant differences in the baseline PD and TNF-α between the two groups or small sample sizes.
For the entire study population, the correlation was tested; a statistically significant negative correlation was found between the BMI and changes in PD, attachment loss (P<0.01), and serum TNF-α level. Also, a statistically significant negative correlation was found between the WC and changes in PD, attachment loss (P<0.01), and TNF-α serum level. Thus, the correlation between obesity and periodontal disease in our study does not differ in terms of BMI or WC.
The clinical outcome of periodontal treatment in terms of PD and CAL is better in patients with chronic periodontitis whose weight is within normal limits when compared with patients with chronic periodontitis who are obese.
The significantly greater reduction in the TNF-α serum level after periodontal treatment in patients with chronic periodontitis whose weight is within normal limits may play a role in enhancing the clinical outcome of periodontal treatment in this group of patients.
General and oral risk assessments in the dental office should include regular evaluations of BMI and WC. The relation between obesity and periodontal disease should be made clear to the patients in the dental office. Also, the effect of obesity on the outcome of periodontal treatment should always be taken into consideration.
Conflicts of interest
There are no conflicts of interest.
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