review article

Periodontal disease and obesity 1

Abstract Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health leading to reduced life ex-pectancy and/or increased health problems. As obesity is a multifaceted condition it has been implicated as a significant risk factor for numerous diseases, such as hy-pertension, cardiovascular disease and type 2 diabetes mellitus. Recently it has been found that obesity also ap-pears to participate in the multifactorial etiology of peri-odontitis through increased production of reactive oxy-gen species and an increase in inflammatory cytokines. The association between impaired lipid metabolism and periodontitis still needs to be established. This review explains the mechanisms that link hyperlipidemia to periodontitis, which is probably related to the exacer-bated proinflammatory changes in periodontal tissues.

Keywords: Hyperlipidemia, Interleukin 6, Tumor ne-crosis factor alpha, Adipocytokines

Introduction

Periodontitis is defined as an inflammatory disease of the supporting tissues of the teeth caused by specific micro-organisms or groups of specific microorganisms, result-ing in progressive destruction of periodontal ligament and alveolar bone with pocket formation, recession or both [1]. Periodontal diseases are generally chronic in nature and can persist in the absence of treatment [2]. Recent research results have suggested that periodontitis is a risk factor for systemic inflammation-related chronic diseases, such as cardiovascular disease, diabetes and chronic obstructive pulmonary disease (COPD) [3].

Obesity is an excess amount of body fat in proportion to lean body mass to the extent that health is impaired.

The most commonly used measure of body fat is the body mass index (BMI, also called the Quetelet index), which is defined as a person’s weight in kilograms divided by the square of the body height in meters [4].

The World Health Organization (WHO) estimated in 2005 that 1 billion people were overweight with a BMI > 25  kg/m2 or obese BMI > 30  kg/m2 and the num-ber would increase to 1.5 billion by 2015 if current trends continued. Recently, obesity has emerged as one of the risk indicators of periodontal disease [5].

The fundamental mechanism underlying the increase in obesity is not clearly understood but the probable important risk factors for obesity are genetic, environ-mental, socio-economic factors and behavior influences leading to excess calorie intake, decreased physical activ-ity, metabolic and endocrinal abnormalities. The World Health Organization (WHO) has recognized obesity as a predisposing factor to major chronic diseases ranging from cardiovascular disease to cancer [5].

A short-term high fat diet results in prolonged impair-ment in the antibacterial function of polymorphonuclear leukocytes (PMN) and an increased release of superox-ide anions in response to cell agonists (PMN priming). Activated or primed PMNs are linked to damage to the periodontal tissue [5, 6].

Obesity, adipose tissue-derived cytokines and oral health

Adipose tissue is a loose connective tissue composed of adipocytes which not only acts as a passive triglyceride reservoir but also produces high levels of cytokines and hormones collectively called adipokines or adipocyto-kines [7]. Adipokines play a number of different roles, such as hormone-like proteins (e.g. leptin and adiponec-tin), classical cytokines, e.g. tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), proteins involved in vascular hemostasis [e.g. plasminogen activator inhibi-tor-1 (PAI-1) and tissue factor], regulators of blood pres-sure (angiotensinogen), promoters of angiogenesis (e.g.

J. Stomat. Occ. Med. (2013) 6:1–5DOI 10.1007/s12548-012-0069-0

Periodontal disease and obesityP. Aravind Kumar, P. Mohan Kumar, A. Krishna Rao, G. Krishna Dileep

P. M. Kumar () · P. A. Kumar · A. K. Rao · G. K. DileepDepartment of Periodontics, St. Joseph Dental College and Hospital, Duggirala, Eluru, Andhra Pradesh, Indiae-mail: mosups@gmail.com

Received: 28 June 2012 / Accepted: 15 November 2012 / Published online: 22 January 2013© Springer-Verlag Wien 2012

2 Periodontal disease and obesity

review article

vascular endothelial growth factor) and acute phase respondents (e.g. C-reactive peptide; [7, 8]).

Leptin is the best known substance secreted from adi-pose tissue. It regulates food intake, energy donation [8] and stimulates the production of other proinflammatory cytokines [9, 10]. Leptin is present within healthy and marginally inflamed gingiva and decreases in concen-tration as the probing depth increases. Thus, leptin may play an important role in the development of periodon-titis [11].

Adiponectin is produced primarily by adipocytes and has anti-inflammatory and anti-atherogenic proper-ties. Plasma levels of adiponectin are decreased in obese individuals compared with normal weight individuals. Low levels of plasma adiponectin are associated with an increased risk of coronary artery disease and other features of the metabolic syndrome [12]. Furthermore, recent evidence suggests a reduced adiponectin function in periodontitis [13].

Obesity-associated TNF-α is primarily secreted from macrophages accumulated in abdominal (as opposed to peripheral) adipose tissue. It provides an evident link between obesity and inflammation [14] and seems to play an important role in the progression of periodontitis [15] (Fig. 1).

Interleukin 6 is secreted by human adipose tissue and is produced in greater amounts by deep abdominal (or visceral) fat than by subcutaneous fat. Elevated levels of IL-6 are associated with obesity [10] and periodontitis [15].

Plasminogen activator inhibitor 1 is produced both by adipocytes and stromal cells surrounding the adipocytes. The levels of PAI-1 are raised with increased accumula-tion of adipose tissue, especially in the abdominal area [16]. Plasminogen activator inhibitor 1 is thought to con-tribute directly to obesity complications, including the development of type 2 diabetes and coronary thrombi. It is also thought to decrease blood flow in the periodon-tium of obese subjects to promote the development of periodontal disease [16].

Obesity is associated with increased levels of the angiogenic factor vascular endothelial growth factor (VEGF), which also plays a role in hypertension and ath-

erogenesis [17]. Elevated C-reactive peptide levels are associated both with obesity and with increased risk of cardiovascular disease [18].

Recently a newly described adipocytokine, resistin which is also produced by inflammatory immune cells (in high levels) and was originally identified in adipose tissue (in low levels) is also related to the activation of inflammatory cells to secrete TNF-α and IL-6 [19] and impairs the anti-inflammatory effects of adiponectin [20]. Increased levels of serum resistin have also been implicated in periodontitis [21].

Obesity and periodontal disease

Obesity and host immunity

Obesity increases host susceptibility by altering the host immune and inflammatory system and by impairing cell-mediated immunity, decreasing the activity of lympho-cyte immune function and natural killer T-cell activity thus increasing the risk for periodontitis [22].

Obesity and reactive oxygen species

Reactive oxygen species (ROS) are products of normal cellular metabolism but excessive production induces damage by oxidizing DNA, lipids and proteins. Obesity increases the circulation of ROS which in turn causes oxi-dative damage and progression of periodontitis [19, 23].

The first report on the relationship between obesity and periodontal disease was given by Perlstein and Bis-sada in 1977 in an animal model [24]. They reported that obese hypertensive rats were more likely to have peri-odontitis than normal non-obese zucker rats and that the periodontal blood vessels of these rats showed intimal thickening, indicating diminished blood flow. As a high cholesterol diet directly leads to fat accumulation, an elevated serum cholesterol level may be a reason for the relationship between obesity and periodontal disease. In humans, Saito et al. [25] reported that obese Japanese

Fig. 1 A proposed model linking inflammation to obesity and periodontitis

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Periodontal disease and obesity 3

subjects were more likely to have periodontal disease than thin people.

The BMI and waist circumference (WC) were used as measures of overall body fat and upper body fat. Upper body obesity, i.e. abdominal adiposity, has greater adverse effects on health than lower body obesity. Vis-ceral fat accumulation, which is frequently observed in upper body obesity, increases the risk of cardiovascular disease [26] and type 2 diabetes [27]. This upper body obesity showed significant association with periodontal disease in 643 Japanese subjects in a study by Saito et al. [19]. Ito et al. [28] and Tessari [29] reported that aging is associated with an increased body fat mass meaning that some older subjects gain weight as part of aging process. In a study by Torrungruang et al. [30] BMI was not found to be associated with attachment loss in 2,005 subjects aged between 50 and 73 years. Studies by Al-Zahrani et al. [31] and Alabdulkarim et al. [32] reported that obesity was not associated with periodontal disease in subjects ≥ 35 or > 40 years of age.

The Forsyth Institute in the USA conducted an on-going case control study and reported that obesity was related to deep pockets, attachment loss, bleeding on probing and plaque accumulation and an increase in the proportion of Tannerella forsythia (Bacteroides for-sythus) that was marked in extremely obese subjects with a BMI > 35 [33].

As mentioned previously obesity is the important risk factor for type 2 diabetes and both obesity and type 2 dia-betes are increasing in prevalence [34]. Nishimura et al. [35] reported an association between BMI and periodon-tal disease in type 2 diabetes individuals (Fig. 2).

Saito et al. [23] conducted a community-based study of women and showed that deep pockets were signifi-cantly associated with obesity, after adjusting for oral glucose tolerance test (OGTT). As the OGTT results were closely associated with both periodontal condition and obesity, the relationship between obesity indices and deep pockets was more significant than that between

obesity indices and deep pockets. From these studies it can be concluded that obesity may be associated with periodontal disease independent of diabetes.

A study by Lundin et al. [36] in young adults showed that TNF-α in gingival crevicular fluid is correlated with BMI in subjects with a BMI ≥ 40. The level of TNF-α in gin-gival crevicular fluid was positively associated with BMI in subjects without periodontal disease suggesting that TNF-α in gingival crevicular fluid is derived from adipose tissue in obese subjects. This suggests that TNF-α from adipose tissue in young adults will cause deterioration of periodontal tissue in later life even if they did not have periodontal disease when they were young.

In a study by Kim et al. [37] in Korean adults the asso-ciation between periodontitis and obesity was deter-mined by measuring BMI and WC and it was found that a high WC was associated with periodontitis, whereas BMI was not. However, it is still not understood how obesity modifies the pathogenesis of periodontal disease at the molecular level. A recent study by Perri et al. [38] demon-strated that expression of specific microRNA (miRNAs) in obesity targets and post-transcriptionally modulates cytokine mRNA within periodontal tissues and affects disease expression.

Role of the dentist in managing obesity and periodontal disease

The diagnosis of obesity and obesity-related diseases, such as diabetes and atherosclerosis is important for physicians but dentists can evaluate the signs and symp-toms of obesity-related diseases. Dentists should have suitable knowledge of the signs, symptoms and diag-nostic tests for metabolic syndrome (MetS) and related diseases, such as obesity, insulin resistance, dyslipdemia and hypertension. Dentists do not usually come into contact with patients having diabetes mellitus and their physicians but a good communication among dentists, physicians and patients is an area ripe for improvement.

Dentists should refer overweight and obese periodon-tal patients for weight reduction interventions, such as diet therapy, behavioral therapy, pharmacotherapy and surgical procedures, so that they can have better con-trol over periodontal inflammation. Behavioral therapy, serving as a useful adjunct to dietary therapy, includes self-monitoring, i.e. recording dietary intake (e.g. food choices, amounts, time or daily weighing), stress man-agement, stimulus control (recognizing the social or environmental stimuli that seem to encourage undesired eating and then modifying them), problem solving, con-tingency management (the use of rewards for specific actions), cognitive restructuring (unrealistic goals and inaccurate beliefs about weight loss and body image are modified to help change self-defeating thoughts and feelings) and social support.

If lifestyle changes do not lead to weight loss in 6 months, pharmacotherapy should be considered but is only recommended for those patients who have a body

Fig. 2 Obesity as a significant risk factor for periodontal dis-ease. TNF-α tumor necrosis factor alpha, IL-6 interleukin 6, CRP C-reactive protein, C. pneumoniae Chlamydophila pneu-moniae, H. pylori Helicobacter pylori, CMV cytomegalovirus

4 Periodontal disease and obesity

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mass index of ≥ 30 or for those who have a body mass index of ≥ 27, if concomitant obesity-related risk factors or diseases exist. The two medications currently available for the treatment of obesity are sibutramine, a selective inhibitor of neuronal reuptake of norepinephrine and serotonin at the receptor sites that affect food intake and orlistat, a gastrointestinal lipase inhibitor that reduces fat absorption in the intestines.

Weight loss surgery is recommended for well informed and motivated patients who have clinically severe obe-sity (BMI ≥ 40) or a BMI of ≥ 35. The two types of opera-tions routinely performed are those that restrict gastric volume (banded gastroplasty) and those that, in addition to limiting food intake, also alter digestion (Roux-en-Y gastric bypass, [39]). Surgical complications, including anastomotic leakage, subphrenic abscess, splenic injury, pulmonary embolism, wound infection and stoma ste-nosis occur in approximately 10  % of all obese patients [40]. Late complications include the development of inci-sional hernias, gallstones and less commonly weight loss failure and dumping syndrome. Vitamin deficiencies are relatively common, especially for vitamin B12 and iron and require close monitoring [41]. In the future, if obesity is to be acknowledged as a multiple risk factor syndrome for overall and oral health, general and oral risk assess-ment in the dental practice should include the evalua-tion of BMI on a regular basis.

Conclusions

Obesity is a complex and multifactorial disease. Reports on the relationship between obesity and periodontal dis-ease are increasing and the relationship in young adults is likely to be major. It is quite difficult to tell whether obesity predisposes an individual to periodontal disease or periodontal disease affects lipid metabolism or both; however, all the studies so far are cross-sectional or case control studies and future longitudinal studies on large populations are required to clarify whether obesity is one of the risk factors for periodontal disease or simply a risk indicator. If this proves to be the case, periodon-tal disease prevention could be included in intervention campaigns designed to prevent obesity-related diseases. Conversely, the prevention and management of obesity may be an adjunctive approach to improving periodontal health.

Conflict of interestThe authors declare that there are no potential conflicts of interest in relation to this article.

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