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      Effect of periodontal treatment in patients with periodontitis and diabetes: systematic review and meta-analysis

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          Abstract

          The evidence is inconclusive regarding the effect of periodontal treatment on glycemic control and systemic inflammation in patients with type 2 diabetes (T2D) and periodontitis

          Objective:

          To evaluate the effect of scaling and root planing (SRP) on the metabolic control and systemic inflammation of patients with type 2 diabetes (T2D).

          Methodology:

          A literature search was conducted using the MEDLINE database via PubMed and the Cochrane Central Register of Controlled Trials, from their oldest records up to July 2018. Only randomized clinical trials (RCT) were considered eligible for evaluating the effect of periodontal treatment on markers of metabolic control [glycated hemoglobin (HbA1C)] and systemic inflammation [C-reactive protein (CRP)] in patients with T2D. The quality of the studies was evaluated using the Cochrane Collaboration risk assessment tool. Meta-analyses were performed for HbA1c and CRP using random effects models. The size of the overall intervention effect was estimated by calculating the weighted average of the differences in means (DM) between the groups in each study. Heterogeneity was assessed using the Q-statistic method (x 2 and I²). The level of significance was established at p<0.05.

          Results:

          Nine RCT were included. SRP was effective in reducing HbA1c [DM=0.56 (0.36-0.75); p<0.01] and CRP [DM=1.89 (1.70-2.08); p<0.01]. No heterogeneity was detected (I 2=0%, p>0.05).

          Conclusions:

          SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D.

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          Most cited references83

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          A systematic review and meta-analyses on C-reactive protein in relation to periodontitis.

          Elevated plasma C-reactive protein (CRP) is regarded as a risk predictor for cardiovascular diseases. This systematic review explored the robustness of observations that CRP is elevated in periodontitis. Similarly, the effect of periodontal therapy on CRP levels was investigated. Selection of publications was based on: (1) cross-sectional (case-control) studies; (2) longitudinal (treatment) studies; (3) high-sensitivity CRP measurement; (4) median and/or mean (+/-SD) values presented; and (5) subjects with no systemic disorders. Screening of the initially 448 identified studies and reference checking resulted in 18 suitable papers. The majority of the studies showed that CRP levels are higher in patients than in controls. Often, studies showed that patients had CRP levels >2.1 mg/l. A meta-analysis of 10 cross-sectional studies showed that the weighted mean difference (WMD) of CRP between patients and controls was 1.56 mg/l (p<0.00001). Evidence from available treatment studies (n=6) showed lower levels of CRP after periodontal therapy. Eligible treatment studies in a meta-analysis demonstrated a WMD of reductions of CRP after therapy of 0.50 mg/L (95% CI 0.08-0.93) (p=0.02). There is strong evidence from cross-sectional studies that plasma CRP in periodontitis is elevated compared with controls. There is modest evidence on the effect of periodontal therapy in lowering the levels of CRP.
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            A proposed model linking inflammation to obesity, diabetes, and periodontal infections.

            Obesity is an important risk factor for diabetes, cardiovascular disease, and periodontal disease. Adipocytes appear to secrete proinflammatory cytokines which may be the molecules linking the pathogenesis of these diseases. We evaluated the relationship between obesity, periodontal disease, and diabetes mellitus insulin resistance as well as the plasma levels of tumor necrosis factor alpha (TNFalpha) and its soluble receptors (sTNFalpha) to assess the relationship of inflammation to obesity, diabetes, and periodontal infections. The relationship between periodontal disease, obesity, and insulin resistance was examined in the Third National Health and Nutrition Examination Survey (NHANES III). In a population of 12,367 non-diabetic subjects, the variable body mass index (BMI) was used as an assessment of obesity and periodontal disease was assessed by mean clinical attachment loss. The plasma levels of TNFalpha and sTNFalpha were assessed in subsets of 1,221 adults from Erie County, New York, who represented the highest and lowest quartile of BMI. These subjects had extensive periodontal and medical evaluations. In the NHANES III portion of the study, BMI was positively related to severity of periodontal attachment loss (P or=27 kg/m2) with high levels of insulin resistance (IR) exhibited an odds ratio of 1.48 (95% confidence interval 1.13 - 1.93) for severe periodontal disease as compared to overweight subjects with low IR. In the Erie County adult population, the highest levels of TNFalpha and sTNFalpha receptors were found in those individuals in the highest quartile of BMI. A positive correlation of TNFalpha levels with periodontal disease was found only in those in the lowest quartile of BMI. Obesity is a significant predictor of periodontal disease and insulin resistance appears to mediate this relationship. Furthermore, obesity is associated with high plasma levels of TNFalpha and its soluble receptors, which in turn may lead to a hyperinflammatory state increasing the risk for periodontal disease and also accounting in part for insulin resistance. Further studies of the molecular basis of insulin resistance and its relationship to diabetes, periodontal disease, and obesity are necessary to fully test the hypothesis that adipocyte production of proinflammatory cytokines is a pathogenic factor linking obesity to diabetes and periodontal infections.
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              Insulin resistance and chronic cardiovascular inflammatory syndrome.

              Insulin resistance is increasingly recognized as a chronic, low-level, inflammatory state. Hyperinsulinemia and insulin action were initially proposed as the common preceding factors of hypertension, low high-density lipoprotein cholesterol, hypertriglyceridemia, abdominal obesity, and altered glucose tolerance, linking all these abnormalities to the development of coronary heart disease. The similarities of insulin resistance with another inflammatory state, atherosclerosis, have been described only in the last few decades. Atherosclerosis and insulin resistance share similar pathophysiological mechanisms, mainly due to the actions of the two major proinflammatory cytokines, TNF-alpha and IL-6. Genetic predisposition to increased transcription rates of these cytokines is associated with metabolic derangement and simultaneously with coronary heart disease. Dysregulation of the inflammatory axis predicts the development of insulin resistance and type 2 diabetes mellitus. The knowledge of how interactions between metabolic and inflammatory pathways occur will be useful in future therapeutic strategies. The effective administration of antiinflammatory agents in the treatment of insulin resistance and atherosclerosis is only the beginning of a promising approach in the management of these syndromes.
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                Author and article information

                Journal
                J Appl Oral Sci
                J Appl Oral Sci
                jaos
                Journal of Applied Oral Science
                Faculdade De Odontologia De Bauru - USP
                1678-7757
                1678-7765
                17 December 2019
                2020
                : 28
                : e20190248
                Affiliations
                [1 ] Universidad de Chile, Facultad de Odontología, Departamento de Odontología Conservadora, Santiago, Chile.
                [2 ] Universidad de Chile, Facultad de Medicina, Escuela de Salud Pública, Santiago, Chile.
                [3 ] Universidad de Chile, Facultad de Odontología, Centro de Epidemiología y Vigilancia de las Enfermedades Orales (CEVEO), Santiago, Chile.
                [4 ] Universidad de Chile, Facultad de Odontología, Departamento de Prótesis, Santiago, Chile.
                Author notes
                Corresponding address: Jorge Gamonal, Facultad de Odontología - Universidad de Chile. Avenida Olivos, 943 - Comuna de Independencia - Santiago - Chile, Phone: 0056-2-9781700, e-mail: jgamonal@ 123456odontologia.uchile.cl
                Author information
                https://orcid.org/0000-0001-8910-4700
                https://orcid.org/0000-0003-1288-8855
                https://orcid.org/0000-0001-6148-5644
                https://orcid.org/0000-0002-6896-5744
                https://orcid.org/0000-0001-8411-423X
                https://orcid.org/0000-0001-8656-0989
                https://orcid.org/0000-0002-8264-0612
                https://orcid.org/0000-0001-7703-6587
                Article
                00801
                10.1590/1678-7757-2019-0248
                6919200
                31939522
                5b49b051-80fe-4fab-84eb-ede35d3c121d

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 07 May 2019
                : 29 August 2019
                : 19 September 2019
                Page count
                Figures: 7, Tables: 0, Equations: 0, References: 95
                Funding
                Funded by: FONDEF IDEA
                Award ID: ID18I10034
                Categories
                Systematic Review

                periodontitis,cardiovascular diseases,diabetes mellitus

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