Clinical trial NCT03470987: The Role of Visfatin in Obesity and Periodontal Disease
Official title: The Role of Visfatin Levels in Gingival Crevicular Fluid as Potential Biomarker in The Relationship Between Obesity and Periodontal Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Periodontitis
Keywords: obesity
periodontitis
cytokines
Lead sponsor: Gazi University
Sponsor class: OTHER
First posted: 2018-03-20
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The 195 patients diagnosed with obesity in the outpatient clinics of Endocrinology and Metabolic Diseases Department, Ataturk Hospital, Turkey, were potential candidates and were interviewed according to our case definition and invited to be included in the study. Thirty-one of 195 volunteers accepted and signed the informed study protocol and took part in the study. All individuals were thoroughly informed of the nature, potential risks, and benefits of their participation in the study before providing their informed consent.

In the same period, 100 consecutive non-obese patients were screened from the Department of Periodontology, Faculty of Dentistry, Gazi University, Turkey, who were systemically healthy and fulfilled the inclusion criteria, of which 19 agreed to participate.

Brief summary: Visfatin is an adipokine that plays an important role in immune functions as a growth factor, enzyme, and proinflammatory mediator. The investigators aimed to determine the levels of visfatin, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in gingival crevicular fluid (GCF) in both obese/non-obese patients, with/without generalized chronic periodontitis (GCP). Patients were categorized as obese (O) (n=31) or non-obese (nO) (n=19). Groups were divided into four subgroups according to periodontal conditions: (1) periodontally healthy without obesity (nO-Ctrl); (2) GCP without obesity (nO-CP); (3) periodontally healthy with obesity (O-Ctrl); and (4) GCP with obesity (O-CP). Demographic variables and anthropometric and laboratory data were recorded. Periodontal measurements were recorded at baseline and 3rd months after either non-surgical periodontal treatment or calorie restricted diet therapy. At the same time GCF samples were taken from patients to analyze TNF-alpha, IL-6, and visfatin levels.

Detailed description: Overweightness and obesity are defined as the accumulation of fat in body tissues that might impair overall health. Adults are considered overweight if their body mass index (BMI, calculated as weight in kg/\[height in meters\]2) is ≥ 25 and obese if BMI ≥ 30 kg/m2. The prevalence of overweightness and obesity has increased worldwide during recent decades.

Obesity is usually related to a chronic low-grade systemic inflammation resulting in significant changes in the concentrations of cytokines and hormones, which subsequently leads to the development of obesity-linked disorders, including insulin resistance, type II diabetes, cardiovascular diseases, dyslipidemia, and metabolic syndrome. Since the host response is among the most crucial factors affecting the pathogenesis of periodontal disease, multiple studies have addressed the possible associations between BMI, overweightness, obesity, diabetes, the serum level of lipids, cholesterol, and periodontal breakdown, with mixed results. Many studies have demonstrated a positive association between obesity and periodontitis and suggested that obesity-related inflammation might promote periodontitis by secretion of inflammatory markers by the adipose tissue, which might subsequently increase gingival inflammation. The association between obesity and periodontal disease is based on the amassing of white adipose tissue (WAT) and increased secretion levels of adipokines from WAT.

WAT is an energy storage organ with some metabolic activities, participating in the endocrine and secretory systems. WAT secretes several immune-modulatory adipokine molecules, such as adiponectin, leptin, visfatin, resistin, chemerin, tumor necrosis factor-alpha (TNF-alpha), interleukin-1β (IL-1β), and interleukin-6 (IL-6). It has been found that these molecules are involved in a wide range of physiologic and pathologic processes, including immunity and inflammation. Thus, cytokines and hormones released from adipose tissue might play a role in the destruction of periodontal tissue by inducing hyperinflammatory responses.

Visfatin is a multi-potential mediator that functions as a growth factor, cytokine, an enzyme with a role in energy metabolism, and as a proinflammatory mediator. It is mainly released from adipose tissue, especially from macrophages, and can also be released from lymphocytes, dendritic, muscle, and bone marrow cells. Visfatin has an important role in the regulation of the immune response. Visfatin inhibits neutrophil apoptosis during inflammation and increases TNF-alpha, IL-1β, and IL-6 levels. The expression of visfatin is increased under inflammatory conditions, such as rheumatoid arthritis, cardiovascular diseases, type-II diabetes mellitus, and periodontal disease.

Although several studies have demonstrated the relationship between periodontitis and obesity, no study has evaluated the levels of visfatin in gingival crevicular fluid (GCF) in obese individuals with periodontitis. Increased adipocytes levels, such as visfatin, cause secretion of cytokines, which are known to play an important role in periodontitis, and might trigger periodontitis formation and development.

Therefore, the main objective of this study was to analyze the levels of visfatin, IL-6, and TNF-alpha in obese and non-obese individuals, with or without generalized chronic periodontitis (GCP). Secondarily, the investigators aimed to evaluate metabolic and clinical periodontal parameters, and also clarify the relationship between these parameters and adipocytokines. The hypothesis is that adipocytokine molecules are involved in the pathogenesis of inflammatory diseases; if true, individuals who are obese with periodontitis would present increased levels of visfatin, IL-6, and TNF-alpha in their GCF.

Eligibility criteria: Inclusion Criteria:

* having \> 22 natural teeth
* no systemic diseases
* having good cooperation
* having BMI \> 30
* waist circumference \> 88 cm for females for obese patients
* waist circumference \> 102 cm for males for obese patients
* age \> 20 years

Exclusion Criteria:

* presence of localized chronic periodontitis
* received periodontal therapy/surgery in the previous 6 months
* pregnancy
* use of any hormone therapy
* history of antibiotic or anti-inflammatory drugs therapy within the previous 6 months
* current and former smoker
* lactation
* presence of aggressive periodontitis
* presence of periapical pathologies

Primary outcomes:
measure: Cytokine levels in Gingival crevicular fluid
timeFrame: Beginning of the study (baseline) and 3 months following Phase I periodontal therapy and metbolic control
Secondary outcomes:
measure: Clinical attachment level
timeFrame: Change from baseline clinical attachment level to 3rd month level
measure: Probing depth
timeFrame: Change from baseline probing depth value at 3rd month value
measure: Bleeding on probing
timeFrame: Change from baseline bleeding on probing score to 3rd month score
measure: Gingival index
timeFrame: Change from baseline gingival index score to 3rd month score
measure: Plaque index
timeFrame: Change from baseline plaque index score to 3rd month score
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Gazi University Faculty of Dentistry
Study officials:
affiliation: Gazi University Faculty of Dentistry Department of Periodontology
name: Deniz Cetiner, Prof
role: STUDY_CHAIR
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