Association between Periodontal Disease and Obesity: Umbrella Review

Objective: Determine the association between periodontal disease (PD) and obesity through an umbrella review. Materials and Methods: A search for information until March 2024 was carried out in the following electronic databases: PubMed, Cochrane library, Scopus, SciELO, Web of Science, Google Scholar, Proquest Dissertations and Theses, and OpenGrey. We included studies that were systematic reviews (SR) with or without meta-analysis, without time or language restrictions, that evaluated primary studies that associated PD with obesity. Literary or narrative reviews, rapid reviews, intervention studies, observational studies, preclinical and basic research, summaries, comments, case reports, protocols, personal opinions, letters, and posters were excluded. The AMSTAR-2 tool was used to determine the quality and overall confidence of the included studies. Results: The preliminary search yielded a total of 419 articles, discarding those that did not meet the selection criteria, leaving only 14 articles. All studies reported that PD was associated with obesity, with an OR and RR ranging from 1.1 to 1.46 and 1.64 to 2.21, respectively. Conclusions: Based on the results and conclusions of the SR with a high overall confidence level, PD is associated with obesity.


Introduction
In recent years, evidence has accumulated on the relationships between oral diseases such as periodontitis and various systemic diseases, known as periodontal medicine [1].The strongest associations, supported by a significant amount of evidence, include cardiovascular disease, adverse pregnancy outcomes, respiratory disease, and diabetes mellitus [2][3][4][5].In 2013, the European Federation of Periodontology (EFP) and the American Academy of Periodontology (AAP) organized workshops focusing on these associations, especially cardiovascular disease, diabetes, and adverse pregnancy outcomes [6][7][8][9].However, Linden et al. [10] explored lesser-known associations, such as chronic kidney disease, rheumatoid arthritis, cognitive decline, inflammatory cancers, and obesity.Although some modest associations were found between periodontitis and obesity, connections with other diseases are weaker and are subject to limitations in the definition of periodontal disease (PD) and the control of confounding factors in the studies [10].A systematic mapping of clinical trial registries conducted in 2016 reported that 57 systemic conditions are currently being investigated for possible links to PDs [11].
Obesity and being overweight represent a significant public health challenge in the modern era [12], with prevalence steadily increasing globally since 1980 [13].This problem affects about a third of the world's population, with higher rates among men for overweight and among women for obesity [13,14].Furthermore, each year, obesity and being overweight cause the death of around 3.4 million people [13,15,16].The World Health Organization (WHO) defines an adult as overweight if the body mass index (BMI) is greater than or equal to 25 and obese if the BMI is greater than or equal to 30 [17], while, for children and adolescents, it defines that they will be overweight if the BMI is greater than or equal to the 85th percentile and obese if the BMI is greater than or equal to the 95th percentile [18].
Obesity is associated with an increased risk of serious diseases, such as heart disease, hypertension, type 2 diabetes, and several types of cancer, and contributes to increased medical costs [13,19,20].Despite genetic predisposition, environmental changes, availability of high-fat foods, and decreased physical activity have contributed to rising obesity rates worldwide [21].The BMI is a commonly used measure to assess the relative amount of body fat in a person [22][23][24] and has been associated with metabolism [25,26] and oral health [27].Obesity is associated with dental problems such as dental caries, periodontitis, and tooth loss, and inflammation is thought to play a key role in this relationship [27,28].
Only one umbrella systematic review [1] on the associations of PD with obesity has been published in the scientific literature.However, a general synthesis and evaluation of all systematic reviews taken together, including those published in recent years, has not yet been performed.Therefore, the purpose of this umbrella review was to summarize the available evidence and answer the following specific question: "What do we know so far about the association of PD and obesity?" and what is the overall confidence of systematic reviews assessing this topic?

Protocol and Registration
A protocol was carried out based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) [29] and registered in the Prospective Registry of Systematic Reviews (PROSPERO) [30].The registry is publicly available under the number CRD42024521090.In addition, the report of this study is based on the Preferred Reporting Items for Overview of Systematic Reviews Checklist (PRIO-harms) [31].Ethical approval was not required for this umbrella review.

Eligibility Criteria and Results of Interest
The included studies were systematic reviews (SR) with or without meta-analysis, without time and language restrictions, that evaluated primary studies that reported the association between PD and obesity.
Literature or narrative reviews, rapid reviews, intervention studies, observational studies, preclinical and basic research, abstracts, commentaries, case reports, protocols, personal opinions, letters, and posters were excluded.

Sources of Information, Search Strategy, and Additional Search for Primary Studies
An electronic search was performed on 5 March 2024 in five databases (Pubmed, Cochrane database, Scielo, Web of Science, and Scopus).Gray literature was also consulted through Google Scholar, Proquest Dissertations and Theses, and OpenGrey.In addition, the reference lists of the included studies were reviewed.The found articles were exported to reference management software (Zotero ® 6.0, Center for History and New Media, Fairfax, VA, USA) and duplicate articles were removed.The search strategy adopted for each database is shown in Table 1.

Data Management and Selection Process
The identified articles were entered into Rayyan ® Online Software https://www.rayyan.ai/,accessed on 4 April 2024 (Qatar Research Institute of Computing, Doha, Qatar).The selection of the studies was performed in 2 phases; in phase 1, two reviewers (F.C.O. and F.C.Z.) independently selected the studies by reading the title and abstract; then, phase 2 was carried out, which consisted of reading the full text, performed independently by the same two reviewers.A third reviewer (H.A.) was consulted in case of disagreement.

Data Collection Process
Data from the studies were independently collected in duplicate using a table previously formulated by two reviewers (F.C.O. and R.A.).The data were cross-checked and disagreements resolved by the third review author (H.A.).The following information was extracted from the selected articles: authors, year of publication, study design, design of the primary studies included, number of studies included in the qualitative and quantitative analysis, results, main conclusions, mentions of what was used or carried out: PRISMA, PROSPERO, and Grading of Recommendations Assessment, Development and Assessment (GRADE), and meta-analysis.

Assessment of Methodological Quality, Quality of Evidence, and Meta-Bias
The evaluation of the methodological quality of the included SRs was performed independently in duplicate by two reviewers (J.M. and S.L.), calibrated (Kappa 0.85), using the AMSTAR-2 checklist (A MeaSurement Tool to Assess Systemic Reviews) [32].The AMSTAR-2 evaluates the methodological quality of the SR through 16 questions that can be answered with three possible answers: "yes", "no", or "partially yes".The overall confidence rating (high, moderate, low, and critically low) in the studies was assessed as suggested by Shea et al. [32].

Summary of Measures
In the case of an SR without meta-analysis, the results shown in odds ratio (OR), hazard ratio (HR), incidence risk ratio (IRR), or prevalence ratio (PR) in ranges or intervals were considered.If the SR presents meta-analysis, we consider the results that were shown with OR, risk/rate ratio (RR), or standardized mean difference (SMD) for the association between PD and obesity.

Summary of Results
The main results of the included SRs were summarized, categorizing their findings into the following points: general association, by age, sex, countries, or continents, BMI, type of PD, smoking, and by periodontal clinical parameters (plaque index, gingival index, bleeding on probing, probing depth, and sub-and supragingival calculus).

Review and Selection of Primary Studies
The electronic database search retrieved 419 references, with 267 remaining after removal of duplicates.In phase 1, the title and abstract of the identified studies were assessed and 23 articles eligible for full-text reading were considered.Finally, 14 SRs remained for the qualitative synthesis.The reasons for the exclusion of the articles are shown in Table 2.The complete process of identification and selection of the studies is shown in Figure 1.

Overlapping
A total of 397 primary studies were identified in the SRs.Of these, approximately 41.81% of the primary studies were included in more than one SR.Thirty studies were included twice; twenty-three were included three times; twelve were included four times; seven were included five times; four were included six times; and one was included seven times.More information on the overlap and characteristics of the primary studies is available in Table 5.

Synthesis of Results
The syntheses of the results are presented in Table 6.AMSTAR = A MeaSurement Tool to Assess Systemic Reviews. 1 = Did the research questions and inclusion criteria for the review include the components of PICO? 2 = Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review and did the report justify any significant deviations from the protocol?3 = Did the review authors explain their selection of the study designs for inclusion in the review?4 = Did the review authors use a comprehensive literature search strategy?5 = Did the review authors perform study selection in duplicate?6 = Did the review authors perform data extraction in duplicate?7 = Did the review authors provide a list of excluded studies and justify the exclusions?8 = Did the review authors describe the included studies in adequate detail?9 = Did the review authors use a satisfactory technique for assessing the risk of bias (RoB) in individual studies that were included in the review?10 = Did the review authors report on the sources of funding for the studies included in the review?11 = If meta-analysis was performed, did the review authors use appropriate methods for statistical combination of results? 12 = If meta-analysis was performed, did the review authors assess the potential impact of RoB in individual studies on the results of the meta-analysis or other evidence synthesis?13 = Did the review authors account for RoB in primary studies when interpreting/discussing the results of the review?14 = Did the review authors provide a satisfactory explanation for, and discussion of, any heterogeneity observed in the results of the review?15 = If they performed quantitative synthesis, did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?16 = Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review?* = Critical domain.) Yes G = gingivitis; BOP = bleeding on probing; PD = probing depth; PI = plaque index; GI = gingival index; SBC = subgingival calculus; SPC = supragingival calculus; OR = odds ratio; RR = risk/rate ratio; HR = hazard ratio; PR = prevalence ratio; IRR = incidence risk ratio.

Sex
One SR [55] included reported that there was an association between PD and obesity according to sex.This study meta-analyzed its results and found that the OR was 1.50 (CI: 1.27 to 1.77) for men and 1.75 (CI: 1.26 to 2.43) for women.

Country or Continent
Two SRs [46,55] included reported that there was an association between PD and obesity depending on the country or continent.All of them meta-analyzed the results and found that the OR for the United States, Brazil, Korea, and Japan ranged from 0.59 (CI: 0.19 to 1.65) [46] to 1.75 (CI: 1.48 to 2.06) [46], while the OR for European countries, East Asia, Europe and the Middle East, and other Asian countries ranged from 0.98 (CI: 0.49 to 1.95) [46] to 2.46 (CI: 1.11 to 5.46) [46].

Smoker and Non-Smoker
One SR [55] included reported that there was an association between PD and obesity depending on whether the person did not smoke.This study meta-analyzed its results and found that the OR was 1.36 (CI: 0.98 to 1.88) for smokers and 2.08 (CI: 1.29 to 3.36) for non-smokers.

Bleeding on Probing
One SR [53] included reported that there was an association between PD and obesity when the BOP was greater than 25%, while one RS [43] reported that there was such an association when the BOP was from people with gingivitis and who were overweight.They all meta-analyzed their results and found that the OR was 5.41 (CI: 2.75 to 10.63) [53], while the SMD for the obese ranged from 0.03 (CI: −0.23 to 0.28) [43] to 0.64 (CI: −0.37 to 1.65) [43] and, for those who were overweight, it ranged from 0.13 (CI: −0.04 to 0.30) [43] to 0.78 (CI: 0.52 to 1.03) [43].
3.5.9.Gingival Index One SR [43] included reported that there was an association between PD and overweight people according to their gingival index.This study meta-analyzed its results and found that the SMD for the obese ranged from 0.35 (CI: −0.21 to −0.91) to 2.13 (CI: −1.51 to 5.77) and, for overweight people, it ranged from 0.97 (CI: 0.45 to 1.49) to 3.52 (CI: 2.32 to 4.71).

Plaque Index
One SR [53] included reported that there was an association between PD and obesity when the plaque index was greater than 25%.This study meta-analyzed its results and found that the OR was 4.75 (CI: 2.42 to 9.34).

Probing Depth
One SR [53] included reported that there was an association between PD and obesity when probing depth was greater than 4 mm.This study meta-analyzed its results and found that the OR was 14.15 (CI: 5.10 to 39.25).

Subgingival Calculus
One SR [53] included reported that there was an association between PD and obesity according to subgingival calculus.This study meta-analyzed its results and found that the OR was 3.07 (CI: 1.10 to 8.62).

Supragingival Calculus
One SR [53] included reported that there was no association between PD and obesity according to supragingival calculus.This study meta-analyzed its results and found that the OR was 1.08 (CI: 0.60 to 1.94).

Discussion
In recent years, there has been increasing interest in evaluating and analyzing the relationship between PD and obesity.Numerous studies have investigated this topic and found evidence to support this association.
Currently, obesity and overweight are considered global health problems of epidemic proportions, classified as chronic inflammatory diseases by the National Institutes of Health (NIH) and the World Health Organization (WHO) [1].The WHO has reported a significant increase in obesity rates worldwide in all age groups since 1975 [1].Although initially attributed primarily to an energy imbalance between calories consumed and calories expended, it is now recognized that the causes of obesity and overweight are much more complex and involve environmental and genetic factors [1,130].
For more than 20 years, oral health researchers have investigated the possible relationship between obesity and PD.Several potential mechanisms linking the two conditions have been identified, including an exaggerated immune response in obese individuals [128,131], differences in the oral microbiome [132], and the release of proinflammatory cytokines by adipose tissue cells [133].Other mechanisms include the role of several molecules, such as TNFα, leptin, and ghrelin, which are involved in inflammation and energy balance [130].These findings support the possibility of a biological connection between PD and obesity.
An umbrella review in 2018 [130] that included 14 SRs on the relationship between periodontitis and obesity highlighted that obese people are more likely to suffer from periodontitis than those of normal weight.Furthermore, Khan et al. [49] also found a positive association between obesity and periodontitis in young adults and adolescents.These findings were supported by a longitudinal cohort study in Taiwan, that included more than 12,000 people and found a slightly increased risk of periodontitis in obese people, with an even higher risk in obese people over 65 years of age [134].
Previous studies of the relationship between periodontitis and obesity have been conducted primarily in animals or through cross-sectional, case-control, or cohort studies.Recently, however, intervention studies have recently emerged.For example, Suvan et al. [130] analyzed six SRs that included intervention studies, but the results were contradictory.
Most studies found no differences in gingival inflammation between obese and nonobese individuals, but higher levels were observed in obese people with periodontitis.In addition, there were variations in the measurement of obesity, with some studies using different measures such as waist-hip ratio (WHR) and waist circumference (WC), indicating the need for consistency in measurement tools in future studies [43].It is also clear that there is a positive association between obesity and periodontitis at all age levels, although determination of a cause-effect relationship is premature at this time [1].
In the present study, a comprehensive literature search was conducted to summarize and analyze the available SRs on the association between PD and obesity, and 14 SRs were identified that met the selection criteria.Although SRs are a reliable source of scientific evidence, it is important to be cautious when interpreting their results due to the possibility of bias.The SRs included in this study showed certain limitations related to the selected primary studies: different types of study, different definition criteria for periodontal disease (gingivitis or periodontitis), and different population groups studied (children, adolescents, adults, and pregnant women).These limitations of the primary studies made it impossible to perform a meta-analysis.Some studies included in the analysis had a high level of confidence, which could strengthen the evidence for the results and conclusions of the current study.However, the persistence of systematic reviews with lower confidence levels highlights the need for greater rigor in conducting research on this topic.
The assessment of the methodological quality of the included SRs was performed using the AMSTAR-2 tool, which is current and widely recognized.Some studies were found to have deficiencies in critical domains 7, 9, and 13 of this tool.These deficiencies included failure to provide a list of excluded studies with justification, inadequate use of techniques to assess risk of bias, and failure to consider such risk when interpreting or discussing results.These findings highlight the importance of addressing these elements in future SRs.
Furthermore, caution should be taken when interpreting the results of systematic reviews, as about 50% of the included primary studies are repeated in multiple reviews, which may lead to repeated re-evaluation of the same data.This may distort the perception of the amount of work conducted in the field.Although, it would be beneficial to conduct new SRs to address the methodological limitations recommended by Moher [135] due to the high degree of overlap between existing reviews.

Evidence Summary
In this umbrella review, we sought to clarify the association between PD and obesity through the collection and analysis of SRs and meta-analysis on this topic, identifying the following results: The SRs included in this study suggest an overall positive and direct association between PD and obesity.This finding aligns with what was found by Suvan et al. [130] and Lavigne [1], who also reported on this association.
With regard to age, it was observed that the association between PD and obesity was stronger in young people.This may be due to the fact that young people today tend to adopt unhealthy eating habits, which may contribute to both obesity and oral health problems [136,137].
Regarding gender, it was observed that this association was more present in women.This may be because hormonal changes during the menstrual cycle, pregnancy, and menopause affect fat metabolism in women, generally resulting in a higher percentage of body fat in women compared to men [130,[138][139][140].
In relation to the country or continent, it was observed that the association was present in most countries and continents.This may be attributed to globalization and the adoption of Western lifestyles in many countries, which has led to the increase in unhealthy eating habits, smoking, and lack of physical activity [130,141].
In obese and overweight individuals, this association was found to be more pronounced in obese individuals.This may be due to unhealthy eating habits and lack of physical activity in this population group [130].
In relation to smoking, the association is more present in non-smokers.This may be explained by the tendency of smokers to have a weakened immune response and a greater propensity to inflammation, which could obscure this association.On the other hand, non-smokers may have a more pronounced inflammatory response to the inflammatory effects of obesity [52].
Regarding periodontal clinical indicators, the association was observed in all clinical aspects.This could be due to the fact that obesity is linked to modifications in the immune response and systemic inflammation, which negatively impacts periodontal health [1].

Implications for Clinical Practice
Oral health professionals have a responsibility to raise awareness and educate patients about how overweight and obesity can increase the risk of developing PD.Promoting good oral hygiene, including regular tooth brushing, flossing, and mouthwash, can help prevent plaque buildup and reduce the risk of PD.In the era of personalized medicine, it is suggested to incorporate BMI measurement as part of routine risk assessment and educate patients about the complex, multiorgan nature of obesity.It is crucial to implement preventive interventions to modify risk factors such as diet, exercise, and weight control, which may decrease the likelihood of obesity and PD.Additionally, a monitoring and followup plan should be established for patients with obesity, including frequent visits to the dentist and specific evaluations to detect PD early and provide intervention when necessary.Collaboration with endocrinologists, nutritionists and other specialists is essential for a comprehensive approach to the management of patients with obesity, allowing for coordinated medical and dental care.

Implications for Research
This review highlights the need to improve the presentation of SRs.The authors suggest the use of quality assessment tools to guide the development of future SRs.They also emphasize the importance of conducting primary studies with high methodological rigor to obtain more reliable results.
For future research on this topic, it is recommended to standardize the diagnostic criteria for both PD and obesity, conduct high-quality prospective studies with larger samples and consistent measures, and conduct more robust research to understand the precise mechanisms and the magnitude of the association between PD and obesity.

Conclusions
Based on the results and conclusions of the SRs with a high overall confidence, PD is associated with obesity in children, adolescents, adults, and pregnant women.

[ 38 ]Figure 1 .
Figure 1.PRISMA diagram showing the process of inclusion and exclusion of studies.

Figure 1 .
Figure 1.PRISMA diagram showing the process of inclusion and exclusion of studies.

Table 1 .
Database search strategy.

Table 2 .
Reason for exclusion of studies.

Table 2 .
Reason for exclusion of studies.

Table 3 .
Characteristics of included studies.

Table 4 .
Assessment of the methodological quality and the quality of the evidence of the included studies.

Table 6 .
Synthesis of the results of the included studies.