Effects of Scaling and Root Planing onClinical Response and Serum Levels ofAdipocytokines in Patients With Obesityand Chronic PeriodontitisTiago Eduardo Dias Goncxalves,* Magda Feres,* Glaucia Santos Zimmermann,* Marcelo Faveri,*Luciene Cristina Figueiredo,* Paloma Gralha Braga,* and Poliana Mendes Duarte*

Background: Despite several investigations suggesting thatobesity is a risk indicator for periodontitis, little is knownabout the effect of obesity on periodontal treatment re-sponse. The aim of this study is to evaluate the effects ofscaling and root planing (SRP) on clinical parameters andcirculating levels of leptin and adiponectin in patients withobesity with chronic periodontitis (CP).

Methods: Twenty-four patients with obesity and CP and24 patients without obesity with CP were submitted to SRP.Clinical parameters were assessed at baseline and 3 and6 months after therapy. Serum levels of leptin and adipo-nectin were evaluated at all time points, using enzyme-linkedimmunosorbent assay.

Results: SRP improved the clinical parameters of bothgroups at 3 and 6 months (P

possible link between obesity and periodontitis as aresult of altered inflammatory and immune responsesat systemic and/or periodontal levels. The obesityinduces a chronic systemic inflammatory state thatmay negatively affect the onset and progression ofperiodontal disease, whereas periodontitis may ad-versely influence the systemic levels of adipocyto-kines in favor of proinflammation.12-15

Despite numerous studies showing an associationbetween obesity and periodontal diseases, few in-vestigations to date have assessed the affect of obesityon periodontal treatment response.16-20 Some re-ports have shown that obesity does not have a neg-ative effect on the clinical response to periodontaltreatment in the short term.16,17,19 Conversely, Suvanet al.20 showed that BMI and obesity are predictorsof unfavorable responses to non-surgical periodontaltreatment after 2 months. Furthermore, patientswith obesity who had significant weight loss afterbariatric surgery presented a short-term better clin-ical response to non-surgical periodontal therapythan those who did not have bariatric surgery.18

Because the results of the few studies assessingobesity as a possible modifying factor in the re-sponse to periodontal therapy are contradictory,additional studies on this topic are still necessary.Therefore, the aim of this study is to evaluate theeffects of scaling and root planing (SRP) on clinicalresponse and circulating levels of leptin and adi-ponectin in patients with obesity and chronic peri-odontitis (CP) up to 6 months after therapy.

MATERIAL AND METHODS

Sample Size CalculationThe ideal sample size to ensure adequate power inthis study was calculated considering differences of0.5 mm between groups for full-mouth mean PDchange from baseline to 6 months and a standarddeviation of 0.5 mm.20 Based on these data, it wasdetermined that 18 patients per group would be nec-essary to provide an 85% power with an a of 0.05.However, based on an anticipated attrition rate of 25%,24 patients per group were included in this study.

PopulationPatients with and without obesity with CP (26 malesand 22 females, aged 33 to 70 years; mean age: 48.7years) were selected from the population referredto the Dental Clinic of Guarulhos University, SaoPaulo, Brazil. All eligible patients were invited toparticipate in the study, and detailed medical anddental records were obtained. Patients were in-formed of the nature, potential risks, and benefits oftheir participation in the study and signed an in-formed consent. The Guarulhos University EthicsCommittee in Clinical Research had previouslyapproved the study protocol.

Inclusion and Exclusion CriteriaInclusion criteria included: 1) aged >30 years; 2) 15teeth excluding third molars and teeth with advanceddecay indicated for exodontia; 3) diagnosis ofgeneralized CP21 (>30% of the sites with concom-itant PD and clinical attachment level [CAL] 4 mmand a minimum of six teeth distributed in the dif-ferent quadrants presenting at least one site withPD and CAL 5 mm and bleeding on probing [BOP]at baseline); 4) glycated hemoglobin A1c (HbA1c)

They were also instructed regarding brushing tech-nique and use of dental floss. A trained periodontist(GSZ) performed SRP in four to six appointmentslasting 1 hour each, using manual curets and anultrasonic device under local anesthesia. Peri-odontal therapy was completed in 14 days. Theendpoint for each SRP appointment was smooth-ness of the scaled roots. Local and systemic an-timicrobials were not used. All patients receivedperiodontal maintenance at 3 and 6 months aftertherapy, including: 1) professional plaque controlwith abrasive sodium carbonate air-powder system;2) reinstruction of oral hygiene; and 3) subgingivaldebridement of deep sites presenting BOP.

Clinical MonitoringPatients received clinical monitoring at baseline and3 and 6 months after therapy. One calibrated ex-aminer (TEDG) performed all the clinical examina-tions. After a calibration exercise, the standard errorof measurement was calculated. Intraexaminer var-iability was 0.22 mm for PD and 0.24 mm for CAL.The agreement for categorical variables (e.g., BOP)was >85%, as calculated by the k-light test. Thefollowing parameters were assessed at six sites(mesio-buccal, mid-buccal, disto-buccal, mesio-lingual,mid-lingual, and disto-lingual) per tooth, excludingthird molars, using a manual periodontal probei: 1)visible plaque accumulation (presence or absence);2) marginal bleeding (MB) (presence or absence);3) BOP (presence or absence); 4) suppuration (SUP)(presence or absence); 5) PD (distance between thegingival margin and the bottom of the sulcus/pocket[millimeters]); and 6) CAL (distance between thecemento-enamel junction and the bottom of thesulcus/pocket [millimeters]).

Leptin and Adiponectin MonitoringFasting peripheral blood was sampled on the daysof the clinical examinations into appropriate tubes.

Immediately after blood collection, the serum wasseparated from blood by centrifugation (10 min at1,300 rpm) and stored in aliquots at -80C.

Aliquots of serum were analyzed by enzyme-linkedimmunosorbent assay (ELISA) at baseline and 3and 6 months using commercially available kitsfor detecting adiponectin# and leptin**. ELISA pro-cedures were performed according to the recom-mendations of the manufacturer using humanrecombinant standards. According to the manu-facturer, the minimum detectable dose for adipo-nectin is 0.246 ng/mL and for leptin is

(P >0.05) (Table 1). As expected, BMI and WHR werehigher in the obese than in the non-obese group(P

response of patients with obesityand CP to non-surgical periodontaltherapy up to 6 months when com-pared with age- and sex-matchedpatients without obesity. Further-more, the possible effects of non-surgical periodontal therapy onserum levels of leptin and adipo-nectin were also assessed at 3 and6 months in both groups. Overall,the results demonstrated that SRPwas effective in improving clinicalparameters in patients with andwithout obesity. However, patientswith obesity exhibited lower reduc-tions in PD at 6 months after ther-apy, indicating that obesity may, tosome extent, negatively affect theclinical response to non-surgical peri-odontal therapy. In addition, peri-odontal treatment did not yield anychanges in adiponectin and leptinlevels in any group, suggesting thatSRP was not able to modulate theseadipocytokines at the systemic level.

Patients with obesity exhibitedsignificantly greater mean PD (Table2) and lower reduction in PD in thefull-mouth analysis and at initiallydeep sites compared with patientswithout obesity at 6 months aftertreatment (Table 3). Patients withoutobesity, but not those with obesity,presented statistically significant grad-ual improvements from baseline to3 and 6 months in mean PD and CALand in the number and percentageof sites with PD 5 mm (Table 2).To date, few studies16-20 have eval-uated the response of patients withobesity to periodontal therapy. Someinvestigations16,17,19 have shownthat patients with and without obe-sity did not differ in their clinical re-sponse to non-surgical periodontaltherapy. Conversely, a previousstudy18 showed an improved clini-cal response to SRP in patients withobesity that lost weight after bari-atric surgery when compared withobese controls not submitted to bari-atric surgery. Furthermore, a recentstudy20 reported that BMI and obe-sity were associated with meanPD and mean percentage of siteswith PD >4 mm at 2 months after

Table 2.

Mean 6 SDs of Full-Mouth Clinical Parameters forBoth Groups at Baseline and at Follow-Up Visits

Groups

Time Point

Without

Obesity (n = 21)With Obesity

(n = 18) P

% of sites with plaque accumulationBaseline 84.6 9.7a 83.3 22.1a 0.763 months 37.2 17.2b 35.2 18.4b 0.486 months 32.4 13.3b 39.4 16.5b 0.38

% of sites with MBBaseline 23.6 14.6a 17.3 23.0a 0.773 months 7.2 8.5b 7.7 8.0b 0.806 months 6.5 5.5b 3.7 5.4b 0.13

% of sites with BOPBaseline 51.6 17.7a 53.2 24.9a 0.813 months 30.4 17.5b 29.7 13.4b 0.766 months 21.8 8.2b 20.3 8.8b 0.55

% of sites with SUPBaseline 4.6 6.5a 4.3 8.1a 0.953 months 1.7 3.5b 2.0 2.8b 0.216 months 1.0 2.4b 1.6 3.0b 0.40

Mean PD (mm)Baseline 3.4 0.6a 3.6 0.6a 0.243 months 3.0 0.5b 3.3 0.6b 0.126 months 2.7 0.6c 3.0 0.5b 0.04

Mean CAL (mm)Baseline 4.4 0.8a 4.9 1.1a 0.183 months 4.2 0.8b 4.7 1.1b 0.136 months 3.9 0.8c 4.4 1.0b 0.08

Number of sites with PD 5 mmBaseline 30.3 15.1a 34.9 17.9a 0.403 months 19.2 15.0b 24.6 15.5b 0.256 months 13.5 13.7c 15.9 11.8b 0.34

% of sites with PD 5 mmBaseline 22.3 10.4a 25.4 11.8a 0.343 months 14.2 10.3b 18.0 10.7b 0.246 months 9.9 9.4c 11.6 8.2b 0.35

Number of sites with PD 7 mmBaseline 11.2 10.0a 11.5 7.8a 0.713 months 6.7 8.1b 9.7 8.2b 0.156 months 4.5 6.4b 5.1 6.3b 0.37

% of sites with PD 7 mmBaseline 8.3 7.0a 8.3 5.2a 0.683 months 5.0 5.5b 7.0 5.7b 0.156 months 3.3 4.5b 3.7 4.5b 0.34

Superscript letters indicate significant differences over time within the same group (Friedman test,P

non-surgical periodontal therapy. In that study20,patients with obesity had 3.2% more sites withPD >4 mm and 0.14 mm greater mean PD at 2months after therapy than patients with normal BMI.Unfortunately, significant methodologic differencesamong the studies hamper a more direct compar-ison with the results of the present study. First, all ofthe abovementioned investigations16-20 have limitedtheir clinical monitoring period to a maximum of3 months. In addition, studies differed considerably

regarding the non-surgical peri-odontal therapy protocol used (i.e.,quadrant-wise SRP or SRP within 24hours with or without local antimi-crobials), the parameter used to de-fine obesity (i.e., BMI and/or waistcircumference), the inclusion/exclusioncriteria used (e.g., smokers and pa-tients with diabetes), and the severityof obesity (e.g., inclusion or exclu-sion of Class III obesity). One couldargue that the worse mean PD ob-served in the patients with obesityafter therapy could be attributed totheir poorer compliance with oralhygiene and/or greater degree of

gingival inflammation. However, it is important toobserve that patients with and without obesity didnot differ in terms of plaque accumulation, MB, andBOP at any time point (Table 2).

Studies in the medical field have proposed thatpatients with obesity present altered immuneinflammatory responses and adipocytokine signaling,which may increase the susceptibility to infection andimpair would healing.24,25 However, at this stage,the mechanisms that could explain the worse clinical

Table 3.

Mean6 SEM PD Reduction and CAL Gain From Baseline to 3 and 6 Months for Full-Mouthand Initially Moderate and Deep Sites

Groups

PD Category Without Obesity (n = 21) With Obesity (n = 18) P

Reduction in PD (mm)Full-mouth sites0 to 3 months 0.44 0.06 0.30 0.06 0.080 to 6 months 0.73 0.07 0.54 0.07 0.04

Initially moderate sites (PD of 4 to 6 mm)0 to 3 months 0.87 0.12 0.70 0.13 0.310 to 6 months 1.38 0.14 1.10 0.15 0.16

Initially deep sites (PD 7 mm)0 to 3 months 1.86 0.25 1.22 0.26 0.070 to 6 months 3.00 0.23 2.30 0.24 0.04

Gain in CAL (mm)Full-mouth sites0 to 3 months 0.29 0.05 0.19 0.06 0.210 to 6 months 0.54 0.07 0.38 0.06 0.13

Initially moderate sites (PD of 4 to 6 mm)0 to 3 months 0.66 0.11 0.53 0.12 0.410 to 6 months 1.06 0.12 0.81 0.13 0.15

Initially deep sites (PD 7 mm)0 to 3 months 1.14 0.24 0.70 0.26 0.200 to 6 months 2.10 0.23 1.56 0.24 0.07

P

response of patients with obesity to periodontal ther-apy are still unknown. Additional evaluations perform-ing local immunologic and microbiologic analysesand longer follow-up periods are still needed toclarify this issue.

Adipose tissue acts as an endocrine organ by se-creting several proinflammatory and anti-inflammatoryfactors, called adipocytokines, that are able to stim-ulate molecular events in inflammatory and/or au-toimmune conditions.6,7 Leptin is an adipocytokinewith proinflammatory properties that has a funda-mental role in regulating appetite and energy ex-penditure but also in controlling immunity andinflammation.8,9,11 Recent evidence has suggestedthat leptin may play a role in the metabolism, defense,and regeneration of the dental and periodontaltissues.26 In addition, dental and periodontal tissuesseem to be important sources of leptin not only locallybut also systemically.26 Adiponectin is an adipo-cytokine with anti-inflammatory properties that isrelated to the improvement of insulin sensitivity,antiatherogenic actions, and regulation of metabolichomeostasis.10,11 In the present study, serum levelsof leptin are increased in patients with obesity at alltime points, corroborating previous evidence thatleptin concentrations are mostly higher in patientswith obesity compared with normal-weight patients,with or without periodontitis.12,27-29 Because previousstudies have linked periodontitis with high serumlevels of leptin and lower levels of adiponectin,12-15

changes in the circulating levels of these adipocy-tokines would be expected after periodontal treat-ment. However, in this study, although SRP yieldedclinical improvements, it did not affect the circu-latory levels of leptin and adiponectin in either group.Some studies have demonstrated a decrease in serumlevels of leptin in patients with19 or without obesity14

after SRP. Conversely, in agreement with the presentresults, other investigations29,30 have also failed toshow changes in the serum levels of leptin andadiponectin in patients with periodontitis after non-surgical periodontal therapy.

Although the patients of the present study wereengaged in a maintenance therapy at 3-month in-tervals, the majority of them still retained severalresidual pockets (PD 5 mm) after the proposed non-surgical periodontal therapy (Tables 2 and 4), whichreflects the failure of this therapy in promotinga periodontal condition comparable with that of theperiodontally healthy patients. Possibly these re-sidual infected/inflamed sites could be enough tomaintain a systemic load able to sustain the leptinand adiponectin levels unchanged despite peri-odontal treatment. Furthermore, a pre-existingsusceptibility for systemic inflammation, possiblyunrelated to periodontal infection, may be anotherexplanation for the unchanged levels of adipocy-tokines after therapy, because previous evidence hasidentified groups of patients that are resistant tosystemic anti-inflammatory effects after periodontaltherapy.30

The main strength of this study is to be the firstinvestigation, to the best of the authors knowledge,to follow the response of patients with obesity toSRP up to 6 months after therapy. In addition, someaspects related to participant selection could alsobe considered strengths of the present investigation.Patients with and without obesity were classifiedconsidering both WHR and BMI, which take intoconsideration body fat distribution and abdominalobesity. To avoid interference of other risk factorsfor periodontitis, patients with diabetes and smokerswere not included in this study, and all patientspresented low levels of CRP (

evidence has demonstrated that CRP directly bindsleptin in extracellular settings, impairing its biologicactions.31 Therefore, the chronic elevation of CRP,commonly observed in patients with obesity, mayworsen leptin resistance.31 Finally, anthropometricmeasurements were revised at all follow-up visits toensure that patients maintained their obese or non-obese status over the course of the study. Con-versely, this study has some limitations that shouldbe taken into consideration. First, four patients fellinto the BMI classification of overweight (BMI from26.7 to 27.8 Kg/m2), although their WHRs were belowthose determined for obesity. Second, there wasa pronounced dropout in the group with obesity,which ended up with 18 patients. Fortunately, thesample size calculation estimated that 18 patientsper group would be enough to provide an 85%statistical power. Furthermore, based on the peri-odontitis and obesity profiles of the present studypopulation, these results cannot be extrapolated topatients with milder periodontitis and Class IIIobesity (i.e., BMI 40 kg/m2). Finally, this study isnot considered masked. Because obesity is anobvious characteristic, both the operator and ex-aminer could certainly deduce the patient group,which may be a possible bias.

CONCLUSIONS

Patients with obesity presented a worse response toSRP than patients without obesity at 6 months aftertherapy. In addition, this treatment did not affect thecirculating levels of leptin and adiponectin in pa-tients with or without obesity and CP.

ACKNOWLEDGMENTS

This study was supported by Sao Paulo State Re-search Foundation Grant 2011/14875-3. The authorsreport no conflicts of interest related to this study.

REFERENCES1. Chaffee BW, Weston SJ. Association between chronic

periodontal disease and obesity: A systematic re-view and meta-analysis. J Periodontol 2010;81:1708-1724.

2. Suvan J, DAiuto F, Moles DR, Petrie A, Donos N.Association between overweight/obesity and peri-odontitis in adults. A systematic review. Obes Rev2011;12:e381-e404.

3. Gorman A, Kaye EK, Nunn M, Garcia RI. Changes inbody weight and adiposity predict periodontitis pro-gression in men. J Dent Res 2012;91:921-926.

4. Pataro AL, Costa FO, Cortelli SC, Cortelli JR, AbreuMH, Costa JE. Association between severity of bodymass index and periodontal condition in women.Clin Oral Investig 2012;16:727-734.

5. Palle AR, Reddy CM, Shankar BS, Gelli V, Sudhakar J,Reddy KK. Association between obesity and chronicperiodontitis: A cross-sectional study. J Contemp DentPract 2013;14:168-173.

6. Wozniak SE, Gee LL, Wachtel MS, Frezza EE.Adipose tissue: The new endocrine organ? A reviewarticle. Dig Dis Sci 2009;54:1847-1856.

7. Ouchi N, Parker JL, Lugus JJ, Walsh K. Adipokinesin inflammation and metabolic disease. Nat RevImmunol 2011;11:85-97.

8. Procaccini C, Jirillo E, Matarese G. Leptin as animmunomodulator. Mol Aspects Med 2012;33:35-45.

9. Zhou Y, Rui L. Leptin signaling and leptin resistance.Front Med 2013;7:207-222.

10. Fantuzzi G. Adiponectin in inflammatory and immune-mediated diseases. Cytokine 2013;64:1-10.

11. Conde J, Scotece M, Gomez R, et al. Adipokines:Biofactors from white adipose tissue. A complex hubamong inflammation, metabolism, and immunity.Biofactors 2011;37:413-420.

12. Zimmermann GS, Bastos MF, Dias Goncxalves TE,Chambrone L, Duarte PM. Local and circulatinglevels of adipocytokines in obese and normal weightindividuals with chronic periodontitis. J Periodontol2013;84:624-633.

13. Karthikeyan BV, Pradeep AR. Gingival crevicular fluidand serum leptin: Their relationship to periodontal healthand disease. J Clin Periodontol 2007;34:467-472.

14. Shimada Y, Komatsu Y, Ikezawa-Suzuki I, Tai H,Sugita N, Yoshie H. The effect of periodontal treat-ment on serum leptin, interleukin-6, and C-reactiveprotein. J Periodontol 2010;81:1118-1123.

15. Nagano Y, Arishiro K, Uene M, et al. A low ratio ofhigh molecular weight adiponectin to total adiponec-tin associates with periodontal status in middle-agedmen. Biomarkers 2011;16:106-111.

16. Zuza EP, Barroso EM, Carrareto AL, et al. The roleof obesity as a modifying factor in patients undergo-ing non-surgical periodontal therapy. J Periodontol2011;82:676-682.

17. Al-Zahrani MS, Alghamdi HS. Effect of periodontaltreatment on serum C-reactive protein level in obeseand normal-weight women affected with chronicperiodontitis. Saudi Med J 2012;33:309-314.

18. Lakkis D, Bissada NF, Saber A, et al. Response toperiodontal therapy in patients who had weight lossafter bariatric surgery and obese counterparts: Apilot study. J Periodontol 2012;83:684-689.

19. Altay U, Gurgan CA, Agbaht K. Changes in inflam-matory and metabolic parameters after periodontaltreatment in patients with and without obesity. JPeriodontol 2013;84:13-23.

20. Suvan J, Petrie A, Moles DR, et al. Body mass indexas a predictive factor of periodontal therapy outcomes.J Dent Res 2014;93:49-54.

21. Armitage GC. Development of a classification sys-tem for periodontal diseases and conditions. AnnPeriodontol 1999;4:1-6.

22. World Health Organization. Waist circumference andwaisthip ratio: Report of a WHO Expert Consulta-tion. Geneva: World Health Organization; 2008.

23. Lang NP, Tonetti MS. Periodontal risk assessment(PRA) for patients in supportive periodontal therapy(SPT). Oral Health Prev Dent 2003;1:7-16.

24. Wilson JA, Clark JJ. Obesity: Impediment to woundhealing. Crit Care Nurs Q 2003;26:119-132.

25. Karlsson EA, Beck MA. The burden of obesity oninfectious disease. Exp Biol Med (Maywood) 2010;235:1412-1424.

26. Li W, Zhu W, Hou J, Huang B, Liu K, Meng H. Leptinand its receptor expression in dental and periodontal

Response of Patients With Obesity to Periodontal Therapy Volume 86 Number 1

60

tissues of primates. Cell Tissue Res 2014;355:181-188.

27. El-Haschimi K, Lehnert H. Leptin resistance Orwhy leptin fails to work in obesity. Exp Clin Endo-crinol Diabetes 2003;111:2-7.

28. Considine RV. Human leptin: An adipocyte hormonewith weight-regulatory and endocrine functions.Semin Vasc Med 2005;5:15-24.

29. Teles FR, Teles RP, Martin L, Socransky SS, HaffajeeAD. Relationships among interleukin-6, tumor ne-crosis factor-a, adipokines, vitamin D, and chronicperiodontitis. J Periodontol 2012;83:1183-1191.

30. Behle JH, Sedaghatfar MH, Demmer RT, et al.Heterogeneity of systemic inflammatory responses

to periodontal therapy. J Clin Periodontol 2009;36:287-294.

31. Hribal ML, Fiorentino TV, Sesti G. Role of C reactiveprotein (CRP) in leptin resistance. Curr Pharm Des2014;20:609-615.

Correspondence: Dr. Poliana Mendes Duarte, UniversidadeGuarulhos, Centro de Pos-Graduacxao e Pesquisa, PracxaTeresa Cristina, 229, Centro, Guarulhos, Sao Paulo, Brazil07.023-070. Fax: 55-11-24641758; e-mail: pduarte@ung.br.

Submitted May 5, 2014; accepted for publication July 31,2014.

J Periodontol January 2015 Goncxalves, Feres, Zimmermann, et al.

61

mk1