Abstract
Aim:
Chronic periodontal disease (CPD) and type 2 diabetes mellitus (T2DM) share common pathogenic pathways involving the cytokine network resulting in increased susceptibility to both diseases, leading to increased inflammatory destruction, insulin resistance, and poor glycemic control. Periodontal treatment may improve glycemic control. The aim of this study was to evaluate the effect of scaling and root planing (SRP) of T2DM patients with CPD on hyperglycemia and the levels of serum interleukin-10 (IL-10).
Materials and Methods:
Forty-five subjects were divided into three groups comprising 15 subjects each as Group 1 (healthy controls), Group 2 (CPD patients), and Group 3 (T2DM patients with CPD). Plaque index, gingival index (GI), probing pocket depths (PPD), clinical attachment loss (AL), bleeding on probing (BoP), random blood sugar, glycosylated hemoglobin (HbA1C), and serum IL-10 were measured at baseline; SRP was performed on Groups 2 and 3 and the selected parameters recorded again at 6 months.
Results:
Statistically significant (P < 0.05) differences were observed in the variables at baseline and 6 months after SRP between the three groups using one-way ANOVA. The paired samples t-test for PPD and AL in Group 3 was statistically significant. Group 3 revealed positive correlations between PPD and HbA1C, BoP and IL-10, respectively, at 6 months and a predictable association of HbA1C with PPD and GI, and IL-10 levels with BoP, respectively, at 6 months.
Conclusion:
Scaling and root planing is effective in reducing blood glucose levels in T2DM patient with pocket depths and effective in elevating systemic IL-10 levels in CPD patients and CPD patients with T2DM.
Keywords: Chronic periodontitis, dental scaling, diabetes mellitus, glycosylated, hemoglobin A, interleukin-10, root planning, type 2
INTRODUCTION
The prevalence of chronic periodontal disease/periodontitis (CPD) and type 2 diabetes mellitus (T2DM) is high, and the association of these two as risk factors influencing each other has been recognized and documented.[1] Chapple and Genco, and on behalf of working Group 2 of the joint EFP/AAP workshop have stated that periodontal disease impacts diabetes control.[1]
Chronic periodontal disease may induce or perpetuate an elevated systemic chronic inflammatory state[2] and may also result in increased insulin resistance and poor glycemic control.[3] Treatment that reduces periodontal inflammation may restore insulin sensitivity, resulting in improved metabolic control. It is possible that CPD may serve as an initiator or propagator of insulin resistance, thereby, aggravating glycemic control. The literature has suggested that periodontal treatment in T2DM patients with CPD may lead to improved diabetic control as measured by serum glycosylated hemoglobin (HbA1C) levels.[4,5,6] These data are consistent with the hypothesis that hyperglycemia contributes to an increased inflammatory response, and suggest a proinflammatory mechanism to account for the observed associations between poor glycemic control and CPD, and the concept that untreated CPD hinders efforts to improve glycemic control.
Chronic periodontal disease and T2DM may share common inflammatory pathogenic pathways which result in increased susceptibility to both diseases, and both can be considered as distressed responses of the immune system to environmental events on a predisposed host. For example, the inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) contribute significantly to the pathogenesis of insulin resistance and development of DM via a number of direct and indirect pathways.[7] Thus, TNF-α and IL-6 inhibit pathways which mediate insulin signaling, but also have indirect effects via an increase in nonesterified fatty acids which in turn inhibit insulin action.[8]
Given the importance of cytokines such as TNF-α and IL-6 in both CPD and diabetes, it is important that more studies need to investigate the role of other systemic cytokines in T2DM subjects with CPD. In general, studies to date have focused on IL-1β, IL-6, and TNF-α, amongst others.
Interleukin-10 has long been recognized to have potent and broad-spectrum anti-inflammatory activity, which has been unequivocally established in various models of infection, inflammation, and even in cancer.[9] IL-10 is a fascinating cytokine first identified by its ability to stop the immune response by inhibiting the production of a number of cytokines.[10] IL-10 was originally identified by Fiorentino et al., and due to its suppressor and inhibitor ability, IL-10 was first called a cytokine synthesis inhibitory factor.[11,12] IL-10 also plays a role in proliferation and differentiation of B cells, T cells, and mast cells.
Based on its immunomodulating functions, IL-10 has been considered an attractive candidate for therapeutic applications for treatment of acute and chronic inflammation, autoimmunity, cancer, and infectious disease.[13]
Interleukin-10 is type 2 cytokine and the “founding” member of a family of cytokines that include IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29.[14] All of these cytokines have similar intron – exon genomic organization, bind to receptors with similar structures and in some cases shared components,[15] and all activate Janus kinase/signal transducer and activator of transcription (STAT) signaling pathways. Despite these commonalities, the cytokines in this family have very different biological activities, which are largely determined by the cells producing the cytokine, the cells responding to them, and the immune environment in which they are released. More detailed descriptions of each of these individual cytokines can be found in the literature.[16]
To the best of knowledge, not many studies have reported the effect of scaling and root planing (SRP) on glycemic control including an evaluation of systemic cytokines like IL-10 in T2DM.
Hence, this study aimed to investigate the effect of SRP of patients with CPD and T2DM patients having CPD on glycemic control and the serum levels of IL-10 in these patients.
MATERIALS AND METHODS
Forty-five subjects including healthy volunteers and patients visiting the Department of Periodontics and the Department of General Medicine of the associated hospital, as outpatients were recruited in this study. The study was conducted in full accordance with the ethical principles of the institution's ethical committee. Study purposes and procedures were fully explained to the participants, and written informed consent was obtained from all of them.
The inclusion criteria were age range of 30–55 years; minimum of 20 teeth; patients diagnosed with T2DM for at least over 1-year; random (casual) blood sugar (RBS) >200 mg/dl and HbA1C ≥7%; not smoking; body mass index (BMI) <30; total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides within normal limits.
The exclusion criteria were pregnancy; immunosuppressed subjects; any condition requiring prophylactic antibiotics prior to dental treatment; on any antibiotics; any medical condition that could compromise safe participation in the study; any subject/patient who has undergone nonsurgical therapy for CPD in the last 3 months.
The subjects were divided into three groups. Each group containing 15 subjects were as follows:
Group 1 (healthy controls) comprised of subjects who were nondiabetic, systemically and periodontally healthy, Group 2 (CPD) included patients who were diagnosed with moderate-severe pocket depths and were nondiabetic and systemically healthy, Group 3 (T2DM with CPD) contained patients diagnosed as T2DM (RBS >200 mg/dl and HbA1C ≥7%), with moderate-severe CPD. Moderate-severe CPD was defined as at least 4 teeth with probing depths ≥ 5 mm, together with attachment loss (AL) and alveolar bone loss as evidenced in prescribed radiographs. These patients were on oral hypoglycemic drugs or insulin, with no change in their T2DM treatment in the past 6 months without any major diabetic complications.
At screening, all groups received a full periodontal examination: Plaque index (PlI),[17] gingival index (GI),[18] probing pocket depths (PPD), clinical AL, bleeding on probing (BoP) using the sulcus bleeding index[19] and measurement of BMI. Radiographs were obtained as clinically indicated, and clinical and radiographic examinations were used to confirm the periodontal diagnosis.
Blood samples were obtained at screening. Total cholesterol, HDL, LDL, and triglycerides were measured. RBS was evaluated using Infinite STAT Glucose (Accurex Biomedicals Pvt. Ltd., New Delhi, India). Glycemic control was assessed by measuring HbA1C levels using NycoCard® HbA1C test kit (Axis-Shield, Oslo, Norway). Serum IL-10 was measured using a commercially available ELISA kit (Krishgen BioSystems, Mumbai, India). Following screening, SRP was performed on Groups 2 and 3 patients. The patients were recalled once a month after treatment for routine periodontal examinations and supplementary oral prophylaxes. None of the subjects were prescribed any chemical plaque controlling agent or any antibiotic.
Blood samples were again obtained at month 6, and RBS, HbA1C, and serum IL-10 was measured.
Statistical analysis
Based on our pilot study, a sample of 15 subjects/patients for each group was estimated to achieve a 95% power with an error of 5% in each of the groups. The Kolmogorov-Smirnov and Shapiro-Wilk tests were first performed to assess for normality of distribution of all the variables in all the groups. Having found a normal distribution, parametric tests were applied for the comparison of the variables which included one-way ANOVA for comparing all the variables between the three groups at baseline and at 6 months, Tukey's multiple post-hoc procedures for multiple comparisons and the pairwise comparison of the variables for each group using the t-test. The Karl Pearson's correlation coefficient was used to analyze for correlations. A multiple step-wise regression analysis was done to establish a relationship between IL-10, HbA1C, and clinical variables.
The statistical significance was set at P < 0.05. Data were analyzed using computer software, statistical package for social sciences (SPSS) 20 (SPSS Inc., Chicago, IL, USA).
RESULTS
Participants in the three groups were aged between 30 and 55 years with an average age being 40.8 years. The mean values of all the variables of the three groups at baseline and after SRP at 6 months were expressed as mean ± standard deviations [Table 1].
Table 1.
Mean±SD values of the Pl, GI, BoP, PPD, AL, HbA1c, RBS, and IL-10 in the three groups at baseline and 6 months
Interleukin-10 was detected (pg/ml) in all the three groups, lowest (10.50 ± 0.61) in Group 2 patients (CPD) at baseline, and highest (15.52 ± 1.29) in Group 3 patients (T2DM with CPD) after SRP at 6 months.
The one-way ANOVA showed a statistical significance for PlI, GI, BoP, PPD, AL, HbA1C, RBS, and IL-10 at baseline and 6 months between the three groups [Table 2].
Table 2.
Results of one-way ANOVA between the three groups for all the variables at baseline and 6 months
Tukey's multiple post-hoc procedure of all variables of each group against the other at baseline and at 6 months showed statistical significance except for PlI, BoP, and PPD at baseline and PPD at 6 months between Groups 2 and 3, RBS at baseline and 6 months between Groups 1 and 2. Table 3 illustrates the post-hoc procedure with regard to HbA1C.
Table 3.
Tukey's multiple post-hoc test for comparison of the three groups against each other with respect to HbA1c
The paired samples t-test in Group 2 showed GI, PPD and AL to be statistically significant, and in Group 3, only PPD and AL were statistically significant [Table 4].
Table 4.
Paired sample test of the variables in groups 1, 2, and 3 at baseline and 6 months
A statistically significant positive correlation of GI, BoP, PPD, and HbA1C with IL-10 levels at 6 months was observed in Group 2. A similar positive correlation was observed between PPD and HbA1C, BoP and IL-10, respectively, at 6 months in Group 3.
The multiple step-wise regression analysis with IL-10 and HbA1c used as dependent variables as against the other variables such as GI, PlI, BoP, PPD, and AL as independent variables, revealed statistically significant results for Group 3 after SRP at 6 months which was the predictability of the reduction of HbA1C by 32.5% with decrease in PPD (R2 = 0.325), and by 48.6% with decrease in GI (R2 = of 0.486), and an increase in IL-10 levels by 48.8% with reduction in BoP (R2 = 0.488) [Tables 5–7].
Table 5.
Step-wise regression analysis for HbA1c and PPD for group 3 at 6 months
Table 7.
Step-wise regression analysis for IL-10 and BoP for group 3 at 6 months
Table 6.
Step-wise regression analysis for HbA1C and GI for group 3 at 6 months
DISCUSSION
Severe periodontitis is associated with increased HbA1C in individuals with and without type 2 diabetes. In people without diabetes, progression of periodontitis over 5–10 years was associated with increasing HbA1C and impaired glucose tolerance.[1] Those with periodontitis at baseline and demonstrating periodontal disease progression had a larger HbA1C increase than those without periodontitis over a 5-year period (0.143% vs. 0.005%), and there is evidence that periodontitis in nondiabetics increases systemic levels of inflammatory mediators.[1]
This study evaluated the effect of SRP on glycemic control and the serum IL-10 levels. The results of this study show that nonsurgical periodontal treatment in the form of SRP of patients with chronic periodontitis and T2DM patients with periodontal disease are associated with significant improvement in their periodontal clinical parameters and glycemic control after 6 months. All the T2DM patients were on oral hypoglycemic agents and/or insulin regimen as prescribed by their physician or endocrinologist.
One-way ANOVA showed statistical significance with regard to all the variables between the groups. The SRP procedure on the two intervention groups, that is, Groups 2 and 3 showed statistically significant improvement in PlI, GI, PPD, and BoP at baseline and posttreatment at 6 months. The amount of gingival recession increased slightly in Group 3 after treatment, which can be attributed as a posttreatment consequence. PPD reduction after treatment when compared between Groups 2 and 3 were statistically not significant, but the reduction was significant when both these groups were compared to the PPD at baseline and in comparison with the healthy control subjects of Group 1.
Although several investigators[20,21,22] have reported that periodontal intervention does not show an improved glycemic control in T2DM patients with chronic periodontitis, this study revealed an observable improvement in the glycemic status of the T2DM subjects with chronic periodontitis. This is in agreement with studies by Stewart et al.,[4] Kiran et al.,[5] Jones et al.,[6] Singh et al.,[23] and other studies.[24,25,26,27]
In this study, antibiotics were not used as an adjunctive to nonsurgical periodontal disease treatment. Administration of antibiotics, especially systemic, can lead to controversial results regarding HbA1C, because they may affect other systemic sources of infection/inflammation, and potential reduction in HbA1C levels cannot be solely attributed to the local reduction in the infectious/inflammatory periodontal burden.[27] It has been accepted that HbA1C is affected by systemic inflammation.[28,29] Periodontal inflammation can result in increased levels of pro-inflammatory cytokines in the systemic circulation. Koromantzos et al.,[27] state that because the resolution of inflammation from the periodontal tissues as a result of periodontal disease treatment is a prerequisite for reducing the levels of HbA1C, patients with mild or no periodontal disease cannot be expected to exhibit a significant decrease in HbA1C after periodontal disease treatment. Taking this into account, only patients with moderate-to-severe periodontal disease as defined by probing depths ≥5 mm, together with AL and radiographic evidence of alveolar bone loss were included in this study. HbA1C was shown to be statistically significant between all groups at baseline and 6 months. HbA1C concentrations at 6 months correlated with improved PPD at 6 months in Group 3. The clinical effectiveness of nonsurgical periodontal disease treatment is shown in this study through the significant improvement of all periodontal parameters being consistent with the HbA1C improvement at baseline and posttreatment after 6 months in patients with T2DM with chronic periodontitis. Hyperglycemia was reduced in this group after SRP at 6 months. The multiple step-wise regression analysis in this study showed that the variation in the HbA1C concentration in Group 3 patients was influenced by PPD and GI by 32.5% and 48.6%, respectively, after SRP at 6 months.
The biologic rationale and the mechanisms underlying the effect that periodontal treatment has on glycemic control and chronic inflammation are not clarified completely, but there is evidence to support the hypothesis that resolution of inflammation from the periodontal tissues has a favorable effect on HbA1C levels.
Random blood sugar was observed to be statistical significant at baseline and 6 months between the groups. In Group 2, RBS at baseline correlated with PlI at 6 months, GI at baseline, BoP at baseline, and HbA1C at 6 months and in Group 3 RBS at baseline correlated with PPD at baseline with RBS at 6 months correlating with PlI at baseline and HbA1C at 6 months.
Interleukin-10 was chosen in this study for its potent anti-inflammatory characteristics.[30] The objective was only to estimate its levels at baseline and posttreatment at 6 months in the two intervention groups. This study did not plan to explain the role of IL-10 and its behavior with other proinflammatory and anti-inflammatory cytokines. A significant difference in the serum IL-10 levels was observed between Groups 1-3 at baseline. A comparison of IL-10 levels at 6 months for Groups 1 and 2, and for Groups 1 and 3 was also significant. Although there was a change in the levels of serum IL-10 at baseline and 6 months for Groups 2 and 3, it was not statistically significant.
Correa et al.,[31] in their study concluded that nonsurgical periodontal therapy tended to reduce systemic inflammation and the concentration of some circulating cytokines. In their results, all clinical parameters were significantly improved 3 months after the periodontal therapy. The univariate comparison employed by them showed a tendency toward a decrease of the measured biomarkers, most pronounced for TNF-α and fibrinogen (FIB), after therapy. Furthermore, in their investigation, the median value of IL-10 was 11.9 pg/ml at baseline and 8.6 pg/ml after 3 months posttherapy. This was not statistically significant and the present study showed the mean IL-10 levels in Groups 2 and 3 to be 10.50 pg/ml and 11.35 pg/ml, respectively, at baseline and 14.14 pg/ml and 15.52 pg/ml, respectively, after treatment at 6 months. Passoja et al.,[32] reported that IL-10 levels were higher in healthy controls as compared with chronic periodontitis patients and that a negative association exists between the serum level of IL-10 and the extent of BoP, PPD, and AL. They also proposed that the level of IL-10 was indicative of a dose-dependent association with chronic periodontitis. The lower level of IL-10 in aggressive periodontitis has been reported by Mattuella et al.[33] The inter-subject variability could also be one of the reasons for such a variation in the estimation of IL-10 in the studies.
In this study, serum IL-10 levels at 6 months correlated with GI at 6 months, BoP at 6 months, PPD at 6 months, AL at baseline and 6 months and HbA1C at 6 months in Group 2. In Group 3, serum IL-10 levels at baseline and 6 months correlated with BoP at 6 months. This can be interpreted as an increase in the IL-10 levels with a decrease in BoP after SRP, thus attributing an anti-inflammatory role of IL-10,[9] and also in concurrence with Passoja et al.[32] However, IL-10 levels at 6 months correlated with HbA1C at 6 months in Group 2 only.
This study was able to estimate the serum IL-10 level at baseline and 6 months after therapy in patients having chronic periodontitis and in T2DM patients with chronic periodontitis. The multiple step-wise regression analysis in this study showed that the variation in IL-10 levels in Group 3 patients was influenced by BoP by 48.8%, respectively, after SRP at 6 months.
As mentioned by Chapple and Genco,[1] there is evidence for change in systemic cytokine levels in nondiabetics with chronic periodontitis, and whether this occurs in diabetic patients remains to be clarified. The present study to a certain extent clarified this by providing evidence that serum IL-10 levels differ in T2DM subjects with chronic periodontitis before and after SRP. The present study has also shown that there is a positive outcome of SRP on glycemic control in T2DM patients with chronic periodontitis.
CONCLUSION
The aim of this study was to evaluate the effect of SRP on T2DM patients with CPD on glycemic control and the levels of serum IL-10. The results of the study indicate that SRP is effective on glycemic control and also has a role to play in the level of systemic IL-10 in periodontal health and disease and T2DM with CPD. The levels of IL-10 is indicative of its anti-inflammatory role.
Footnotes
Source of Support: Nil
Conflict of Interest: None declared.
REFERENCES
- 1.Chapple IL, Genco R. Working group 2 of joint EFP/AAP workshop. Diabetes and periodontal diseases: Consensus report of the Joint EFP/AAP Workshop on Periodontitis and Systemic Diseases. J Clin Periodontol. 2013;40(Suppl 14):S106–12. doi: 10.1111/jcpe.12077. [DOI] [PubMed] [Google Scholar]
- 2.Loos BG. Systemic markers of inflammation in periodontitis. J Periodontol. 2005;76:2106–15. doi: 10.1902/jop.2005.76.11-S.2106. [DOI] [PubMed] [Google Scholar]
- 3.Genco RJ, Grossi SG, Ho A, Nishimura F, Murayama Y. A proposed model linking inflammation to obesity, diabetes, and periodontal infections. J Periodontol. 2005;76:2075–84. doi: 10.1902/jop.2005.76.11-S.2075. [DOI] [PubMed] [Google Scholar]
- 4.Stewart JE, Wager KA, Friedlander AH, Zadeh HH. The effect of periodontal treatment on glycemic control in patients with type 2 diabetes mellitus. J Clin Periodontol. 2001;28:306–10. doi: 10.1034/j.1600-051x.2001.028004306.x. [DOI] [PubMed] [Google Scholar]
- 5.Kiran M, Arpak N, Unsal E, Erdogan MF. The effect of improved periodontal health on metabolic control in type 2 diabetes mellitus. J Clin Periodontol. 2005;32:266–72. doi: 10.1111/j.1600-051X.2005.00658.x. [DOI] [PubMed] [Google Scholar]
- 6.Jones JA, Miller DR, Wehler CJ, Rich SE, Krall-Kaye EA, McCoy LC, et al. Does periodontal care improve glycemic control? The Department of Veterans Affairs Dental Diabetes Study. J Clin Periodontol. 2007;34:46–52. doi: 10.1111/j.1600-051X.2006.01002.x. [DOI] [PubMed] [Google Scholar]
- 7.Stumvoll M, Goldstein BJ, van Haeften TW. Type 2 diabetes: Principles of pathogenesis and therapy. Lancet. 2005;365:1333–46. doi: 10.1016/S0140-6736(05)61032-X. [DOI] [PubMed] [Google Scholar]
- 8.Lau DC, Dhillon B, Yan H, Szmitko PE, Verma S. Adipokines: Molecular links between obesity and atheroslcerosis. Am J Physiol Heart Circ Physiol. 2005;288:H2031–41. doi: 10.1152/ajpheart.01058.2004. [DOI] [PubMed] [Google Scholar]
- 9.Mosser DM, Zhang X. Interleukin-10: New perspectives on an old cytokine. Immunol Rev. 2008;226:205–18. doi: 10.1111/j.1600-065X.2008.00706.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683–765. doi: 10.1146/annurev.immunol.19.1.683. [DOI] [PubMed] [Google Scholar]
- 11.Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse Thelper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170:2081–95. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Moore KW, Vieira P, Fiorentino DF, Trounstine ML, Khan TA, Mosmann TR. Pillars article: Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI. Science. 1990;248:1230–1234. doi: 10.1126/science.2161559. J Immunol 2012;189:2072-6. [DOI] [PubMed] [Google Scholar]
- 13.Asadullah K, Sterry W, Volk HD. Interleukin-10 therapy – Review of a new approach. Pharmacol Rev. 2003;55:241–69. doi: 10.1124/pr.55.2.4. [DOI] [PubMed] [Google Scholar]
- 14.Commins S, Steinke JW, Borish L. The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J Allergy Clin Immunol. 2008;121:1108–11. doi: 10.1016/j.jaci.2008.02.026. [DOI] [PubMed] [Google Scholar]
- 15.Donnelly RP, Sheikh F, Kotenko SV, Dickensheets H. The expanded family of class II cytokines that share the IL-10 receptor-2 (IL-10R2) chain. J Leukoc Biol. 2004;76:314–21. doi: 10.1189/jlb.0204117. [DOI] [PubMed] [Google Scholar]
- 16.Sabat R, Wallace E, Endesfelder S, Wolk K. IL-19 and IL-20: Two novel cytokines with importance in inflammatory diseases. Expert Opin Ther Targets. 2007;11:601–12. doi: 10.1517/14728222.11.5.601. [DOI] [PubMed] [Google Scholar]
- 17.Silness J, Loe H. Periodontal disease in pregnancy. II. Correlation between oral hygiene and periodontal condtion. Acta Odontol Scand. 1964;22:121–35. doi: 10.3109/00016356408993968. [DOI] [PubMed] [Google Scholar]
- 18.Loe H, Silness J. Periodontal disease in pregnancy. I. Prevalence and severity. Acta Odontol Scand. 1963;21:533–51. doi: 10.3109/00016356309011240. [DOI] [PubMed] [Google Scholar]
- 19.Mühlemann HR, Son S. Gingival sulcus bleeding – A leading symptom in initial gingivitis. Helv Odontol Acta. 1971;15:107–13. [PubMed] [Google Scholar]
- 20.Gustke CJ. Treatment of periodontitis in the diabetic patient. A critical review. J Clin Periodontol. 1999;26:133–7. doi: 10.1034/j.1600-051x.1999.260301.x. [DOI] [PubMed] [Google Scholar]
- 21.Talbert J, Elter J, Jared HL, Offenbacher S, Southerland J, Wilder RS. The effect of periodontal therapy on TNF-alpha, IL-6 and metabolic control in type 2 diabetics. J Dent Hyg. 2006;80:7. [PubMed] [Google Scholar]
- 22.Simpson TC, Needleman I, Wild SH, Moles DR, Mills EJ. Treatment of periodontal disease for glycaemic control in people with diabetes. Cochrane Database Syst Rev. 2010 doi: 10.1002/14651858.CD004714.pub2. CD004714. [DOI] [PubMed] [Google Scholar]
- 23.Singh S, Kumar V, Kumar S, Subbappa A. The effect of periodontal therapy on the improvement of glycemic control in patients with type 2 diabetes mellitus: A randomized controlled clinical trial. Int J Diabetes Dev Ctries. 2008;28:38–44. doi: 10.4103/0973-3930.43097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kudva P, Tabasum ST, Garg N. Evaluation of clinical and metabolic changes after non surgical periodontal treatment of type 2 diabetes mellitus patients: A clinico biochemical study. J Indian Soc Periodontol. 2010;14:257–62. doi: 10.4103/0972-124X.76933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Sun WL, Chen LL, Zhang SZ, Ren YZ, Qin GM. Changes of adiponectin and inflammatory cytokines after periodontal intervention in type 2 diabetes patients with periodontitis. Arch Oral Biol. 2010;55:970–4. doi: 10.1016/j.archoralbio.2010.08.001. [DOI] [PubMed] [Google Scholar]
- 26.Chen L, Wei B, Li J, Liu F, Xuan D, Xie B, et al. Association of periodontal parameters with metabolic level and systemic inflammatory markers in patients with type 2 diabetes. J Periodontol. 2010;81:364–71. doi: 10.1902/jop.2009.090544. [DOI] [PubMed] [Google Scholar]
- 27.Koromantzos PA, Makrilakis K, Dereka X, Katsilambros N, Vrotsos IA, Madianos PN. A randomized, controlled trial on the effect of non-surgical periodontal therapy in patients with type 2 diabetes. Part I: Effect on periodontal status and glycaemic control. J Clin Periodontol. 2011;38:142–7. doi: 10.1111/j.1600-051X.2010.01652.x. [DOI] [PubMed] [Google Scholar]
- 28.Moutsopoulos NM, Madianos PN. Low-grade inflammation in chronic infectious diseases: Paradigm of periodontal infections. Ann N Y Acad Sci. 2006;1088:251–64. doi: 10.1196/annals.1366.032. [DOI] [PubMed] [Google Scholar]
- 29.Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006;116:1793–801. doi: 10.1172/JCI29069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Prabhu A, Michalowicz BS, Mathur A. Detection of local and systemic cytokines in adult periodontitis. J Periodontol. 1996;67:515–22. doi: 10.1902/jop.1996.67.5.515. [DOI] [PubMed] [Google Scholar]
- 31.Correa FO, Gonçalves D, Figueredo CM, Bastos AS, Gustafsson A, Orrico SR. Effect of periodontal treatment on metabolic control, systemic inflammation and cytokines in patients with type 2 diabetes. J Clin Periodontol. 2010;37:53–8. doi: 10.1111/j.1600-051X.2009.01498.x. [DOI] [PubMed] [Google Scholar]
- 32.Passoja A, Puijola I, Knuuttila M, Niemelä O, Karttunen R, Raunio T, et al. Serum levels of interleukin-10 and tumour necrosis factor-a in chronic periodontitis. J Clin Periodontol. 2010;37:881–7. doi: 10.1111/j.1600-051X.2010.01602.x. [DOI] [PubMed] [Google Scholar]
- 33.Mattuella LG, Campagnaro MB, Vargas AE, Xavier LL, Oppermann RV, Chies JA, et al. Plasma cytokines levels in aggressive and chronic periodontitis. Acta Odontol Scand. 2013;71:683–8. doi: 10.3109/00016357.2012.715191. [DOI] [PubMed] [Google Scholar]