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

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 (x2 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 (I2=0%, p>0.05). Conclusions: SRP has an impact on metabolic control and reduction of systemic inflammation of patients with T2D.


Introduction
Type 2 diabetes (T2D) and periodontitis are closely related noncommunicable diseases (NCDs) that present a high prevalence in the world, seriously compromising the quality of life of the affected population. 1,2 The number of people with diabetes has increased from 108 million in 1980 to 422 million in 2014 and is considerably higher in middle and lower income countries. 3 Diabetes has become a leading cause of death and disability in the region of the Americas, and if current trends continue, the burden of the disease will increase substantially over the next two decades. 4 In Mexico and in the majority of the countries of Central and South America and the Spanish-speaking Caribbean, diabetes prevalence has been reported between 8% and 10%. 4 In Chile, according to the last National Health Survey, 5 the prevalence of diabetes is 12.3%. In turn, the prevalence of periodontal destruction in Chile is greater than 85% in people over 35 years of age. 6 Despite the heterogeneity in the operational definition of the disease, most studies show that the prevalence of periodontitis in Latin America is high. 7 Although there are no epidemiological studies of simultaneity of both pathologies, a meta-analysis showed that people with T2D have twice the risk of developing periodontitis compared with those without diabetes. 8 These data show that almost all patients with T2D have periodontitis simultaneously.
T2D is characterized by an altered hyperglycemic metabolic state and is associated with a decrease in life expectancy of ten years and with long-term complications that may include cardiovascular disease, diabetic retinopathy, and kidney failure. 9 Periodontitis, however, is currently considered a noncommunicable chronic inflammatory pathology of infectious etiology.
The bidirectional pathogenic association between both diseases has been extensively documented. 10 Diabetic patients are more susceptible to severe periodontitis and it may increase the risk of poor glycemic control. 11 The effect of periodontitis on diabetes may be related to the penetration of the host tissues by bacteria or their degradation products into the systemic circulation.
Activation of an exaggerated systemic inflammatory response to subgingival bacteria leads to an acute phase protein burst and systemically elevated levels of proinflammatory mediators which facilitate insulin resistance. 12,13 Metabolic dysregulation in diabetes as a result of prolonged exposure to chronic hyperglycemia can lead to the glycosylation of proteins and lipids, called advanced glycation end-products (AGEs). They can explain many of the sequelae of diabetes, such as microvascular complications. Local periodontal tissue destruction may be a consequence of an exaggerated monocytic inflammatory response induced by AGEs accumulation and result in exaggerated secretion of local and systemic mediators leading to severe periodontitis. 14 The binding of AGEs to monocyte receptors induces production of interleukin-1 (IL-1), IL-6, insulin-like growth factor-1, tumor necrosis factor-alfa (TNF-a) and platelet-derived growth factor. 15 Those are some factors that initiate and maintain an inflammatory response and regulate the transcription of human Acute Phase Reactants, like C-reactive protein (CRP). CRP is a sensitive inflammatory marker and an independent predictor of cardiovascular diseases. 16 The poor glycemic control of diabetic patients, defined as glycated hemoglobin (HbA1c) values >7%, is associated with microvascular and macrovascular complications. 17 Macrovascular complications also known as cardiovascular diseases (CVD) are an important cause of morbidity and mortality among individuals with T2D. Patients with T2D have an increased risk of premature atherosclerotic plaque development, which is the central pathogenic mechanism of CVD. To a great extent, the endothelial dysfunction present in patients with poor glycemic control is associated with the high production of CRP as a result of systemic inflammation caused by AGEs. 18 The role of systemic inflammation and, consequently, of high levels of CRP has been described in all phases of atherosclerosis, from the onset and build-up of plaque to rupture. From the biological point of view, CRP participates in the atherogenic process, and its concentration predicts cardiovascular events. 19 The cardiovascular effects of CRP have been described no changes in the T2D treatment scheme during follow-up, except one that did not report these data. 35 The initial values, final values, and changes (delta) in HbA1c and/or CRP in each group of each study are presented in Figure 1.

Risk of bias in the included studies
To determine the validity of the included studies, a tool developed by the Cochrane Collaboration was

Inadequate evaluation and/or high risks of bias (n=6)
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