Effect of Non-surgical Periodontal Treatment on Chemerin, Fetuin-A, IL-34 and IL-13 Levels in Type 2 Diabetic Periodontitis Patients

Type 2 diabetes (T2DM) increases the risk for severe periodontal disease by three times, making it a risk factor for the progression of periodontitis. Periodontitis works as a focus of local infection and a source of low-grade chronic inflammation. Periodontal therapy primarily targets the microbial component of the disease by mechanical debridement of tooth surfaces.

Chemerin, an adipose tissue-specific adipokine, influences the glucose pathway, lipid metabolism, inflammation levels, chemotaxis of immature dendritic cells, and integration of macrophage-phagocytic activity to extracellular matrix proteins and adhesion molecules. Fetuin-A impedes insulin receptor tyrosine kinase, thus affiliated with insulin resistance, metabolic syndrome, and an increased risk for type 2 diabetes mellitus. Interleukin (IL)-34 modulates myeloid cell differentiation, proliferation, and survival. Depending on the microenvironment, IL-34 can transform circulating monocytes into specific non-resident macrophages with a "pro-inflammatory" M1 phenotype or an "anti-inflammatory" M2 phenotype. IL-13 inhibits the release of inflammatory cytokines, such as IL-1, IL-6, and TNF-α, from monocytes and macrophages.

This study is the first controlled clinical study that examines the levels of chemerin, fetuin-A, IL-34, and IL-13 in saliva and serum in periodontitis with and without T2DM (well-controlled and poorly-controlled T2DM) and evaluates the situation before and after the treatment. The first hypothesis of this study is that in periodontitis groups, chemerin and IL-34 levels will be high in saliva and serum, and IL-13 and fetuin-A levels will be low in contrast to the non-periodontitis groups. The second hypothesis of this study is that in T2DM groups, fetuin-A and chemerin levels will be high compared to participants without T2DM. The third hypothesis of this study, after periodontal treatment, chemein and IL-34 levels will decrease, and IL-13 and fetuin-A will increase in saliva and serum. Based on these hypotheses, the study aims to compare the levels of chemerin, fetuin-A, IL-34, and IL-13 in saliva and serum of nonperiodontitis controls (NP), NP with T2DM (DM.NP), periodontitis (P), P with well-controlled T2DM (WDM.P) and P with poorly-controlled T2DM (PDM.P) subjects and to evaluate the effect of periodontal treatment.

A total of 110 participants, 22 NP, 22 DM.NP, 22 P, 22 WDM.P, and 22 PDM.P were included in this study. The whole mouth clinical periodontal examination included measurement of probing depth (PPD), clinical attachment level (CAL), presence of bleeding on probing (BOP), gingival index (GI), and plaque index (PI) at 6 sites per tooth, except the third molars. The presence and type of the alveolar bone loss were assessed on the digital panoramic radiograph in each participant, which was supplemented with periapical radiographs if necessary.

The periodontal status of each patient was evaluated by a single calibrated periodontist with a manual probe. The diagnosis of periodontitis or periodontally health was determined according to the 2017 World Workshop on Classification of Periodontal and Peri-Implant Diseases and Conditions. NP individuals (healthy and gingivitis) (n=22) in the control group had no sites with PD >3 mm and CAL >2 mm and no radiographic evidence of alveolar bone loss. NP group also exhibited no history of periodontitis. The periodontitis stage III/IV patients had a minimum of three teeth apart from the first molars and incisors showing CAL ≥5 mm and PD ≥6 mm. Radiographic bone loss extending from coronal to middle third or beyond. Bone loss %/age was higher than 1.0.