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Effect of Nonsurgical Periodontal Therapy on Metabolic Control and Systemic Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with Stage III Periodontitis
Rajashri Abhay Kolte, Abhay Pandurang Kolte, Pranjali Vijaykumar Bawankar, A Vinisha Bajaj
VSPM Dental College and Research Centre, Nagpur, Maharashtra, India
|Date of Submission||07-Jul-2021|
|Date of Decision||28-Jan-2022|
|Date of Acceptance||15-Feb-2022|
|Date of Web Publication||03-Nov-2022|
Rajashri Abhay Kolte,
104, Department of Periodontics and Implant Dentistry, VSPM Dental College and Research Centre, Digdoh Hills, Hingna, Nagpur - 440 019, Maharashtra
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: A reciprocal relationship is understood to exist between periodontal disease and type 2 diabetes mellitus (T2DM), and this intervention study aimed to evaluate the effects of nonsurgical periodontal therapy (NSPT) on metabolic control, systemic inflammation, and cytokines in patients of T2DM with Stage III periodontitis. Materials and Methods: Sixty patients of T2DM with Stage III periodontitis were divided equally into two groups: intervention group (IG) and control group. Clinical parameters such as bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded at baseline and 3 and 6 months, and the serum samples were collected and processed at baseline and 6 months following NSPT to evaluate fasting plasma glucose, Glycosylated hemoglobin (HbA1c), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), and high-sensitivity capsule-reactive protein (hs-CRP). Results: The results indicated a significant improvement in clinical parameters of PPD and CAL 6 months after NSPT (P = 0.005) in both the groups. However, a significant decrease (P < 0.0001) in the TNF-α, hs-CRP, blood glucose, and HbA1c levels was seen after NSPT. On the other hand, an increase in anti-inflammatory cytokine IL-10 was observed after NSPT in the IG. The changes in the pretreatment and posttreatment levels of all clinical, biochemical, and metabolic parameters, were found to be significant in both the groups except BOP. Conclusion: NSPT effectively improves periodontal condition, systemic inflammatory status, and glycemic control in patients of T2DM with Stage III periodontitis and decreases hs-CRP levels.
Keywords: C-reactive protein, diabetes mellitus, HbA1c tumor necrosis factor-α, nonsurgical periodontal therapy
|How to cite this URL:|
Kolte RA, Kolte AP, Bawankar PV, Bajaj A V. Effect of Nonsurgical Periodontal Therapy on Metabolic Control and Systemic Inflammatory Markers in Patients of Type 2 Diabetes Mellitus with Stage III Periodontitis. Contemp Clin Dent [Epub ahead of print] [cited 2022 Nov 29]. Available from: https://www.contempclindent.org/preprintarticle.asp?id=360375
| Introduction|| |
The global prevalence of type 2 diabetes mellitus (T2DM) among adults over 18 years of age rose from 4.7% in 1980 to 8.5% in 2014. Periodontal infection can cause indirect damage to the vascular system by releasing inflammatory mediators and eliciting different host immune reactions. Similarly, T2DM can cause major complications such as macrovascular and microvascular diseases. Intervention studies have shown a beneficial effect of periodontal treatment on the glycemic control as expressed by reduced glycosylated hemoglobin (HbA1c) levels.,
The inflammatory mediators released due to periodontitis exacerbate the prevailing metabolic dysfunction in cases of T2DM; on the other hand, the T2DM adversely affects the periodontal health. It is believed that nonsurgical periodontal therapy (NSPT) reduces the possibility of inducing bacteremia caused by periodontitis and has a positive effect on systemic inflammatory status and metabolic control.
In the management of T2DM, maintaining good glycemic control is imperative not only to reduce cardiovascular risks but also other complications which have an adverse bearing on the health of an individual and affect the quality of life. High-sensitivity capsule-reactive protein (hs-CRP) is one of the inflammatory markers commonly used to identify cardiovascular risk. The presence of acute and chronic-phase inflammatory mediators is common to periodontitis and T2DM. In particular, hs-CRP is of particular interest because of longitudinal studies linking it to cardiovascular disease as a risk predictor.,
Interleukin (IL)-10 is a cytokine which inhibits interferon production and has a pleiotropic effect in immune regulation and inflammation. It inhibits the release of pro-inflammatory mediators which includes tumor necrosis factor-α (TNF-α), IL-1β, IL-6, and IL-8 from monocytes/macrophages. Periodontal inflammation may involve both an increase in inflammatory stimulators such as IL-1 and a decrease in inflammatory inhibitors such as IL-10, and such a double impact may be the underlying factor in severe progressive changes inherent to periodontitis.
TNF-α has been associated with insulin resistance and reported to play a key role in the pathogenesis of T2DM. The correlation of this cytokine with insulin resistance has likewise been shown in the metabolic syndrome., The effect of TNF-α on insulin resistance is believed to be due to its ability to inhibit insulin-dependent autophosphorylation of the insulin receptor and the phosphorylation of insulin receptor substrate-1, the major substrate of the insulin receptor in vivo.
However, literature search examining the effects of periodontal therapy on the metabolic control, hs-CRP, and the pro-inflammatory mediator levels was found to be scarce. Hence, the present study was aimed to investigate the impact of NSPT on metabolic control as well as systemic inflammatory markers in patients of T2DM with Stage III periodontitis.
| Materials and Methods|| |
This clinical trial was conducted from January 2019 to October 2020 in the Department of Periodontics and Implant Dentistry and Department of General Medicine of our institute. The clinical trial was performed in accordance with the provisions of Helsinki Declaration 1975, as revised in 2013. The study was presented to and approval was sought from the Institutional Ethics Committee of our institute (VSPM'S DCRC/ETHICS COMMITTEE/16/2014, dated 20/08/2014). Subsequent to explanation of the study details to all the patients, written informed consent was obtained from all the participants.
The inclusion criteria were as follows: (a) patients with controlled T2DM (ADA 2014) and Stage III periodontitis (according to Papapanou et al., 2018) and (b) patients having a minimum of 15 natural teeth present and at least four teeth with one or more sites with probing pocket depth (PPD) ≥5 mm, clinical attachment level (CAL) ≥4 mm, and bleeding on probing (BOP).
Patients with a history of antibiotic therapy within the previous 6 months and anti-inflammatory drugs within the previous 3 months, pregnant female patients or having a history of contraceptive use and on any other form of hormonal therapy, current smokers or former smokers, and patients with a history of stroke, acute cardiovascular events, and renal or liver dysfunction were excluded from the study.
The sample size was calculated based on the results of a project by Correa et al. conducted using data relative to the mean difference and standard deviation (SD) for the clinical and biochemical parameters in patients of T2DM with Stage III periodontitis. It was projected that with a minimum of 20 patients of T2DM with Stage III periodontitis, significant differences in the clinical and biochemical parameters would be detected with 90% statistical power and a 95% confidence interval. Hence, a total of 60 patients of T2DM with Stage III periodontitis were recruited for the study. The study participants were randomized into two groups (30 patients each), the intervention group (IG) and the control group (CG) using computer-generated random number tables.
All patients included were under medication for T2DM which included oral hypoglycemic agents and/or insulin for the treatment and under the supervision of an endocrinologist, with no alteration in the T2DM treatment in the previous year before the study, and were authorized by their physician to undergo periodontal treatment.
A complete periodontal examination including PPD, CAL, and BOP was done using PCP UNC 15 (Hu-Friedy, Chicago, IL, USA) at baseline and 3 and 6 months.
Participants in IG received NSPT comprising oral hygiene instructions and full-mouth scaling and root planing (SRP) at baseline and 3 and 6 months, and participants in CG received oral prophylaxis with supragingival scaling at the same time intervals along with oral hygiene instructions. A thorough SRP was performed in CG after completion of the study (after 6 months) and was taken up for further surgical intervention wherever required. All the study patients were followed up for 6 months, with intermediate visit at 3 months. During the experimental period, any changes in medications related to T2DM therapy, use of anti-inflammatory or antibiotics, and alteration of lifestyle, including exercise and diet, were recorded. All the participants completed the study, and there were no dropouts as they were counseled properly at the beginning and in between the study at recall visits [Figure 1].
Blood samples were collected and analyzed at baseline and 6-month visit for estimation of fasting and postmeal plasma glucose levels using glucose oxidase–peroxidase method (glucose in vitro diagnostic kit; Siemens, Vadodara, Gujarat, India). Glycated hemoglobin (HbA1c) determination was based on latex agglutination inhibition assay using an autoanalyzer (Kone-Lab Clinical Chemistry Analyzers; Thermo Scientific, Milan, Italy). hs-CRP, TNF-α, and IL-10 were analyzed using enzyme-linked immunosorbent assay. In order to avoid any bias, the laboratory staff was masked to the allocation group.
All the descriptive data were expressed as mean and SD. Comparison of parameters before and after intervention in each group was done using paired t-test. Comparison of parameters between IG and CG before intervention was obtained using t-test for independent samples. Comparison of clinical parameters at baseline and 3 and 6 months in IG and CG was done using repeated measures analysis of variance independently. The data analysis were performed using a statistical package SPSS version 26.0 (IBM Corp. ARMONK,USA), and P < 0.05 was considered to be statistically significant.
| Results|| |
The study comprised 60 patients within the age range of 30–60 years who were equally divided into CG and IG. All the participants in the study were controlled diabetics for more than 10 years. [Table 1] provides the demographic details. The mean values of all the clinical parameters were estimated at baseline and 3 and 6 months post NSPT, while the biochemical parameters were estimated at baseline and 6 months for both IG and CG.
|Table 1: Demographic and clinical data of intervention and control groups at baseline|
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[Table 2] shows the comparison between pretreatment values of all clinical, biochemical, and metabolic parameters between IG and CG. The nonsignificant difference between these values demonstrates the proper selection of the patients and distribution of samples in both the groups. The mean PPD for IG was 6.59 ± 1.50 mm at baseline which declined 5.17 ± 1.46 mm at 3 months and 3.98 ± 1.47 mm at 6 months. The mean reduction in the PPD at 3 and 6 months in IG was 1.42 mm and 2.61 mm, respectively, which was found to be significant (P = 0.043). While the mean PPD for CG was 6.13 ± 0.83 mm at baseline, 6.14 ± 0.83 at 3 months, and 6.14 ± 0.83 at 6 months. The mean difference was not statistically significant for CG. The mean CAL for IG was 7.20 ± 1.60 mm at baseline which declined to 5.56 ± 1.39 mm at 3 months and 4.18 ± 1.71 mm at 6 months. The mean reduction in the CAL at 3 and 6 months in IG was 1.64 mm and 2.94 mm, respectively, which was found to be significant. For CG, the mean CAL was 6.52 ± 0.78 mm at baseline and 6.52 ± 0.77 mm at 3 months and 6.54 ± 0.76 mm at 6 months, respectively. The mean reduction in CAL from baseline to 6 months was statistically significant in the IG (P < 0.0001), whereas it was nonsignificant in CG (P = 0.0540). The differences for BOP from baseline to 6 months were not significant in both the groups [Table 3] and [Table 4].
|Table 2: Comparison of parameters between test and control groups before intervention|
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|Table 3: Comparison of clinical parameters with time in test and control groups independently|
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|Table 4: Comparison of parameters before and 6 months after intervention in each group|
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The mean baseline IL-10 level in IG was 5.64 ± 0.77 pg/ml which increased to 12.21 ± 1.30 pg/ml at 6 months after therapy. The mean increase in the IL-10 levels from baseline to 6 months was significant in IG (P < 0.0001), however, there was nonsignificant difference in the levels of IL-10 in CG from baseline (10.50 ± 1.00 pg/ml) to 6 months (11.68 ± 0.91 pg/ml) (P = 0.76) [Table 1]. The mean baseline TNF-α level in IG was 14.45 ± 1.09 pg/ml which declined to 10.25 ± 1.14 pg/ml at 6 months. The mean baseline TNF-α levels in CG were 13.66 ± 0.81 pg/ml and 13.64 ± 0.80 pg/ml at 6 months. The mean difference was statistically significant for IG, however, the difference was nonsignificant in CG [Table 4].
The mean hs-CRP level at baseline was 4.85 ± 0.58 mg/l in IG which was reduced to 3.05 ± 0.79 mg/l at 6 months. The mean difference was statistically significant. A nonsignificant difference was found between baseline (4.80 ± 0.36 mg/l) and 6-month (4.78 ± 0.37 mg/l) levels of hs-CRP in CG [Table 4].
The mean fasting blood glucose level at baseline was 150.36 ± 41.91 mg/dl which reduced to 124.31 ± 29.14 mg/dl at 6 months in IG and the difference was statistically significant (P < 0.0001), whereas in CG, the mean difference between baseline (135.63 ± 11.91 mg/dl) and 6 months (135.15 ± 12.19 mg/dl) for fasting blood glucose level was significant (P = 0.008).
Similarly, for postmeal blood glucose levels, the mean difference between baseline (245.45 ± 60.74 mg/dl) and 6-month (194.80 ± 40.41 mg/dl) levels was significant (P < 0.0001) in IG while it was found to be nonsignificant (P = 0.109) in CG [Table 4].
The mean baseline level for HbA1c (%) in IG was 6.83 ± 0.46 which was declined to 6.53 ± 0.48 at 6 months. The mean difference was statistically significant. However, the difference between baseline (6.68 ± 0.48) and 6-month (6.67 ± 0.47) levels of HbA1c was statistically nonsignificant in CG [Table 4].
When the comparison was made between IG and CG for changes in the pretreatment and posttreatment levels of all clinical, biochemical, and metabolic parameters, it was found to be significant except BOP [Table 5].
|Table 5: Comparison of differences from baseline to 6 months between test and control group|
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| Discussion|| |
Despite differing pathogenesis, T2DM and periodontitis share similar polygenic backgrounds wherein both the conditions can upregulate the systemic immune response with some degree of immune-inflammatory dysfunction. Impaired bacterial elimination and monocyte hyper-responsiveness in diabetic patients lead to persistent elevation of systemic inflammatory mediators. This process gives rise to prolonged and augmented exposure to inflammatory cytokines which interact with traditional risk factors having the capability of leading to initiation of endothelial dysfunction, the first phase of atherogenesis.
The results of the present study depicted that the periodontal and the biochemical parameters significantly reduced after 6 months in both the groups, however, the reduction in parameters was more robust in the IG. Similar results were found in a study by Correa et al. (2010) where the authors investigated the effect of periodontal therapy on the circulating concentrations of hs-CRP, fibrinogen, IL-4, IL-6, IL-8, IL-10, and TNF-α and on the metabolic control in T2DM patients. They concluded that NSPT tended to reduce systemic inflammation and the concentration of some circulating cytokines. The results were also consistent with the bacteriological results by Mauri-Obradors et al. where improvement was seen in all periodontal and metabolic parameters in the treatment group after NSPT.
Significant differences are seen in HbA1c levels from baseline to 6 months between the test group and CG which are in contrast with the study done by Kim et al. The present study confirmed the understanding that NSPT improves the glycemic control through reduction of hs-CRP which is a significant risk factor for both the CVD and progression of T2DM. Patients included in IG differed from that of CG in terms of the periodontal maintenance regimen (NSPT versus only supragingival prophylaxis), respectively. This study shows that the two regimens were comparable with respect to periodontal variables, however, the results indicated that NSPT at baseline and 3 months in IG brought a significant drop in the PPD and CAL. Similar results were found in a previous clinical trial by Chen et al. and D'Aiuto el al. The probable reason behind these extreme differences might be the positive effects of intensive subgingival debridement included in NSPT which gets rid or at least reduces the burden of microorganisms which otherwise are capable of inducing detrimental changes within the tissues and a further progression of the disease. In diabetic patients, the periodontal tissue destruction is more severe even with minimal presence of plaque due to the compromised host defense mechanism. With NSPT being accorded in patients of IG and patients in both the groups being placed on regular oral hygiene instructions, the subsequent plaque accumulation in the study population was found to be negligible which justifies the nonsignificant changes in BOP after treatment.
Similar significant differences were observed in the cytokine levels (IL-10 and TNF-α) in the IG at pre and post NSPT, suggesting that the diabetic patients responded well to the NSPT as compared to simple supragingival scaling. The main reason may be that NSPT can eliminate plaque, calculus, periodontal pathogens or their products, and other stimulating factors in the periodontal environment. The control of periodontal infection resulted in decreased production and activity of local pro-inflammatory mediators and might have positive effects by reducing systemic inflammatory markers in patients with T2DM.
The role of TNF-α in patients with T2DM and periodontitis remains debatable. Some intervention studies have reported that periodontal treatment could improve glycemic control in T2DM by reducing peripheral TNF-α concentrations,, whereas other studies have failed to find such a reduction in serum TNF-α levels after periodontal therapy.,,,, The possible differences in such variations in the results of these studies can be attributed to the fact that the glycemic levels in T2DM patients can vary drastically from each other. Furthermore, the duration of diabetic affliction would additionally have a cumulative unfavorable effect within the tissues which is reflected in the evaluated parameters.
IL-10 suppresses both immune-proliferative and inflammatory responses and contributes to the maintenance of bone mass by inhibition of osteoclastic bone resorption and stimulation of osteoblastic bone formation. In the IG, the IL-10 levels substantially increased after NSPT, while on the contrary, no significant differences were found in the case of CG. IL-10 can downregulate the synthesis of pro-inflammatory cytokines and chemokines, such as TNF-α,,, and this demonstrates that NSPT decreases the TNF-α levels and elevates IL-10 which in turn again suppresses the pro-inflammatory cytokine (TNF-α) levels. This in turn diminishes the systemic inflammatory burden resulting in the clinical improvements in the evaluated parameters. A positive relationship between the severity of periodontitis and initial systemic levels of hs-CRP has been observed in previous studies.
Limitations and future prospects
The present study has certain limitations: small sample size and possibility of the presence of any other unknown confounding factors which may have influenced the results of the study to a certain extent.
Patients with periodontal disease are candidates where the glycemic control may be a problem even with medications. In these patients, NSPT can be instituted to eliminate the present infection so that such patients respond to antidiabetic medications. There is also a possibility of reduction in the antidiabetic medication doses if the periodontal infection is treated. The findings of this study indicate that all diabetic patients should be mandatorily examined for their periodontal status.
| Conclusion|| |
This study underlines the importance of common pathophysiologic relationship of systemic inflammation in diseases such as T2DM, hs-CRP, and periodontitis. Within the limitations, it can be concluded that a thorough and successful NSPT tends to reduce inflammatory burden within the local and systemic tissues which is manifested in the concentrations of TNF-α, hs-CRP, blood glucose, and HbA1c and substantially increases the IL-10 levels which are important and critical for the health and well-being in patients of T2DM with Stage III periodontitis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]