9
Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study Rafael Paschoal Esteves Lima,* Luı ´s Ota ´ vio Miranda Cota,* and Fernando Oliveira Costa* Background: Some studies have reported an association between gestational diabetes mellitus (GDM) and peri- odontitis. The aim of the present study is to analyze this potential association and the influence of risk variables as- sociated with GDM. Methods: This case-control study includes 360 women, 90 with GDM and 270 controls. Participants received a full- mouth periodontal examination with a record of bleeding on probing (BOP), probing depth (PD), and clinical attach- ment level (CAL). Periodontitis is defined as the presence in 4 teeth of 1 sites with PD 4 mm and CAL 3 mm asso- ciated with BOP. The influence of risk variables in the occur- rence of GDM is tested through univariate analysis and multivariate logistic and multinomial regression. Odds ratio (ORs) and respective confidence intervals (CIs) are calcu- lated and reported. Results: The prevalence of periodontitis was 40% in the case group (GDM) and 46.3% in the control group. There was a lack of association between periodontitis and GDM (OR = 0.74; 95% CI = 0.40 to 1.38). The multivar- iate final logistic regression model retained the following as significant variables associated with GDM: maternal age (OR = 2.65; 95% CI = 1.97 to 3.56), chronic hyper- tension (OR = 3.16; 95% CI = 1.35 to 7.42), and body mass index (OR = 1.99; 95% CI = 1.41 to 2.81). Conclusions: A high prevalence of periodontitis was found among cases and controls, with no association be- tween periodontitis and GDM. The present study suggests the need for implementation of health policies directed to the periodontal care of pregnant women. J Periodontol 2013;84:1257-1265. KEY WORDS Diabetes mellitus; diabetes, gestational; oral health; periodontitis; pregnancy; risk factors. P eriodontitis is a chronic infection of bacterial etiology and multifacto- rial characteristics that causes breakdown of the supporting structures of the tooth. 1 Several studies have link- ed periodontitis to systemic events such as cardiovascular disease, 2 respiratory infections, 3 poorly controlled diabetes mellitus (DM), 4,5 prediabetes, 6 and ad- verse pregnancy outcomes. 7-9 Gestational DM (GDM) is a glucose intolerance of variable degrees with on- set during pregnancy. It affects ap- proximately 7% of pregnant women. 10 GDM represents a significant cause of maternal and infant morbidity, in- cluding macrosomia and maternal hy- pertensive disorders. 11 Risk factors for GDM include obesity, previous GDM, high maternal age, and family history of diabetes. 11,12 It has been suggested that inflammatory and infectious processes may play a role in the pathogenesis of GDM. The pre- sence of high levels of C-reactive pro- tein, tumor necrosis factor-a, and interleukin-6 can suggest an associa- tion between infection/inflammation and GDM. 13,14 DM has been extensively evaluated in numerous studies, and it was identified as a risk factor for periodontitis. 4,15-18 Changes in the immune-inflammatory response of individuals with DM are associated with a greater prevalence, extent, and severity of periodontitis. 4,19 In addition, periodontitis may have * Department of Periodontology, Dentistry School, Federal University of Minas Gerais, Belo Horizonte, Brazil. doi: 10.1902/jop.2012.120350 J Periodontol • September 2013 1257

Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

Embed Size (px)

Citation preview

Page 1: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

Association Between Periodontitisand Gestational Diabetes Mellitus:A Case-Control StudyRafael Paschoal Esteves Lima,* Luıs Otavio Miranda Cota,* and Fernando Oliveira Costa*

Background: Some studies have reported an associationbetween gestational diabetes mellitus (GDM) and peri-odontitis. The aim of the present study is to analyze thispotential association and the influence of risk variables as-sociated with GDM.

Methods: This case-control study includes 360 women,90 with GDM and 270 controls. Participants received a full-mouth periodontal examination with a record of bleedingon probing (BOP), probing depth (PD), and clinical attach-ment level (CAL). Periodontitis is defined as the presencein ‡4 teeth of ‡1 sites with PD ‡4 mm and CAL ‡3 mm asso-ciated with BOP. The influence of risk variables in the occur-rence of GDM is tested through univariate analysis andmultivariate logistic and multinomial regression. Odds ratio(ORs) and respective confidence intervals (CIs) are calcu-lated and reported.

Results: The prevalence of periodontitis was 40% in thecase group (GDM) and 46.3% in the control group. Therewas a lack of association between periodontitis andGDM (OR = 0.74; 95% CI = 0.40 to 1.38). The multivar-iate final logistic regression model retained the followingas significant variables associated with GDM: maternalage (OR = 2.65; 95% CI = 1.97 to 3.56), chronic hyper-tension (OR = 3.16; 95% CI = 1.35 to 7.42), and bodymass index (OR = 1.99; 95% CI = 1.41 to 2.81).

Conclusions: A high prevalence of periodontitis wasfound among cases and controls, with no association be-tween periodontitis and GDM. The present study suggeststhe need for implementation of health policies directed tothe periodontal care of pregnant women. J Periodontol2013;84:1257-1265.

KEY WORDS

Diabetes mellitus; diabetes, gestational; oral health;periodontitis; pregnancy; risk factors.

Periodontitis is a chronic infection ofbacterial etiology and multifacto-rial characteristics that causes

breakdown of the supporting structuresof the tooth.1 Several studies have link-ed periodontitis to systemic events suchas cardiovascular disease,2 respiratoryinfections,3 poorly controlled diabetesmellitus (DM),4,5 prediabetes,6 and ad-verse pregnancy outcomes.7-9

Gestational DM (GDM) is a glucoseintolerance of variable degrees with on-set during pregnancy. It affects ap-proximately 7% of pregnant women.10

GDM represents a significant cause ofmaternal and infant morbidity, in-cluding macrosomia and maternal hy-pertensive disorders.11

Risk factors for GDM include obesity,previous GDM, high maternal age, andfamily history of diabetes.11,12 It hasbeen suggested that inflammatory andinfectious processes may play a rolein the pathogenesis of GDM. The pre-sence of high levels of C-reactive pro-tein, tumor necrosis factor-a, andinterleukin-6 can suggest an associa-tion between infection/inflammationand GDM.13,14

DM has been extensively evaluated innumerous studies, and it was identifiedas a risk factor for periodontitis.4,15-18

Changes in the immune-inflammatoryresponse of individuals with DM areassociated with a greater prevalence,extent, and severity of periodontitis.4,19

In addition, periodontitis may have

* Department of Periodontology, Dentistry School, Federal University of Minas Gerais,Belo Horizonte, Brazil.

doi: 10.1902/jop.2012.120350

J Periodontol • September 2013

1257

Page 2: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

a significant impact on the metabolic status of in-dividuals with DM and may contribute to the sys-temic dissemination of inflammatory mediators, aswell as microorganisms and bacterial products,leading to a systemic inflammatory state that caninitiate and propagate insulin resistance.20-22

Therefore, based on this same reasoning, peri-odontitis in pregnant women may induce a systemicinflammatory response and lead to the developmentof insulin resistance with manifestation of GDM.23

However, studies that have evaluated the associa-tion between periodontitis and GDM23-28 show greatmethodologic variability and inconclusive results.

The objective of the present study is to evaluatethe potential association between periodontitis andGDM and analyze the influence of social, behav-ioral, and biologic risk variables associated withGDM.

MATERIALS AND METHODS

Study Design and Sampling StrategyThe sample for this unmatched (1:3) case-controlstudy consisted of pregnant women who underwentprenatal care in the Odete Valadares MaternityHospital, Belo Horizonte, Brazil. The ratio of casesto controls was 1:3 in an attempt to improve powerand validity of the study inferences. Sample sizewas based on the prevalence of GDM in the hospitalunit of the study. According to medical records, theprevalence was approximately 6%. The number ofindividuals in the case group was calculated basedon the 95% confidence interval (CI) of this preva-lence data and a variation of 5% adopted aroundthe prevalence rate. In this manner, a number of�87 women with GDM was determined to benecessary. Therefore, the total sample comprised360 pregnant women (aged 18 to 44 years; meanage: 27.20 – 6.31 years); 90 in the case group(women diagnosed with GDM) and 270 in thecontrol group (pregnant women without GDM).From February 2010 to November 2011, 120women diagnosed with GDM undergoing medicalmonitoring in the unit of the study were consideredeligible for the case group. During prenatal visits,these women underwent one complete periodontalexamination carried out at random (according tothe availability and accessibility of women in thematernity’s medical routine) up to the identificationof 90 women with GDM according to predefinedinclusion criteria. Women in the control group re-ceived prenatal care at the same hospital unit of thestudy and were examined in a previous cross-sectional study7 of this research group, comprising588 pregnant women. Periodontal examination ofwomen in the control group was conducted betweenFebruary 2004 and June 2004 at the same hospital

unit and with the same methodology of the presentstudy. Hence, 270 pregnant women who showed noendocrine disease were randomly assigned for thecontrol group. It is important to emphasize that thestudy sample did not differ from women who did nottake part in the study regarding demographics andsocioeconomic conditions, making the process ofrandomization valid.

Inclusion and Exclusion CriteriaThe established inclusion criteria were: 1) pregnantwomen older than 18 years; 2) single pregnancy;3) gestational age >28 weeks; 4) presence of ‡12teeth in the oral cavity; and 5) absence of con-traindications for the periodontal examination.Exclusion criteria included: 1) refusal of peri-odontal examination; 2) antibiotic or periodontaltherapy in 3 months prior to clinical examination;3) type 1 or type 2 DM (DM-1 or DM-2); and 4)serologically positive human immunodeficiencyvirus infection.7-9

Ethical GuidelinesThe present study was approved by the EthicsResearch Committees from the Federal Universityof Minas Gerais and the Hospital Foundation of theState of Minas Gerais. The participants were in-formed about the study and signed an informedconsent form. The present study followed theguidelines from Strengthening the Reporting ofObservational Studies in Epidemiology (STROBE),when applicable.29

Sociodemographic CharacteristicsSocial and demographic data including age, maritalstability, education, parity, smoking, self-reportedalcohol consumption, systemic diseases, andcomplications in previous pregnancies were col-lected using a structured questionnaire. Data re-garding smoking were recorded as presence/absence, duration, and frequency (cigarettessmoked/day). Women who reported consumptionof ‡100 cigarettes in their lives and smoked atthe time of examination were classified as smokers.Women who reported lifetime consumption of ‡100cigarettes and did not smoke at the time of theexamination were classified as former smokers.Women who reported lifetime consumption of <100cigarettes were classified as non-smokers.30

Medical DataThrough the analysis of medical records, data werecollected on gestational age, maternal weight,height, blood glucose, and diagnosis of GDM.Gestational age was established by the physicianduring prenatal visits considering the last menstrualperiod. When it was not possible to determinethe date of last menstrual period, gestational age

Gestational Diabetes and Periodontitis Volume 84 • Number 9

1258

Page 3: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

was determined by examination of obstetrical ul-trasound. Body mass index (BMI) was calculatedby dividing weight in kilograms by height in meterssquared. According to the relationship betweenBMI and gestational age, women were classifiedas underweight, normal weight, overweight, orobese.31

A fasting glucose test was performed to estab-lish the diagnosis of GDM and was recorded foreach participant in the case group. All pregnantwomen underwent oral glucose tolerance testing(OGTT) in the first prenatal visit for GDMscreening. When the initial examination showeda negative result for GDM, the test was performedagain in the period between 24 and 28 weeks ofgestation. The test was performed with standard-ized measures of fasting glucose, 1 and 2 hoursafter ingestion of 75 g anhydrous glucose. For theOGTT curve, the cutoff points were considered tobe 95 mg/dL in fasting analysis, 180 mg/dL for thesample taken 1 hour after the ingestion of glucoseloading, and 155 mg/dL for the sample taken after2 hours. A single abnormal value in OGTT wasconsidered sufficient for the diagnosis of GDM.Pregnant women with GDM were categorized intothree groups according to glucose level: 96 to 105,106 to 125, and ‡126 mg/dL.

Periodontal Clinical ExaminationClinical measures of periodontal conditions in-cluded bleeding on probing (BOP), probing depth(PD), and clinical attachment level (CAL) in foursites of all present teeth using a manual periodontalprobe.† Two specialists in periodontics (RL and LC)were responsible for the examinations of all par-ticipants. Inter- and intra-examiner reliability, as-sessed by weighted k coefficients, were 0.90 for PDand 0.88 for CAL.

The following exclusion criteria were used: 1)third molars; 2) teeth whose limit between cemen-tum and enamel was impossible to determine; 3)teeth with gingival morphology alterations; 4) teethwith extensive caries lesions; and 5) teeth with iat-rogenic restorative procedures.32

Periodontitis was defined as the presence of ‡4teeth having ‡1 sites with PD ‡4 mm and CAL ‡3mm33 associated with BOP.34

Statistical AnalysesDescriptive and univariate analyses were per-formed to compare variables of interest in relationto outcome (GDM; cases versus controls) as wellas exposure (periodontitis; diseased versus non-diseased). The normality of data was testedthrough Kolmogorov-Smirnov test with Lillieforscorrection. Groups were compared regarding thefollowing variables: 1) age group (18 to 25, 26 to

30, 31 to 35, 36 to 40, or ‡41 years); 2) educationlevel (illiterate or £8, 9 to 12, or >12 years); 3)marital stability (with or without partner or other);4) primiparity (yes or no); 5) smoking (yes or no);6) alcohol consumption (yes or no); 7) chronichypertension (yes or no); 8) BMI (underweight,normal weight, overweight, or obese); and 9)presence of periodontitis (yes or no) by Mann-Whitney U and x2 test when appropriate.

Characterization of the sample and comparisonsamong groups in relation to the clinical periodontalmeasures (BOP, PD, and CAL) were performedwith the Mann-Whitney U test. In the case group,Kruskal-Wallis and post hoc Dunn tests were usedto compare the different glucose level categories,and x2 test was used to determine the associationbetween periodontitis and glucose levels. Multi-variate logistic regression was performed to ex-amine the association between periodontitis andGDM, considering all variables categorized aspreviously mentioned. All variables, including first-order interactions among periodontitis, chronichypertension, and smoking, were selected to enterinto the models and were manually removed untilonly significant variables were retained. Interactionswere based on their biologic plausibility. All multi-variate models were evaluated in post hoc compat-ible tests to verify suitability. In addition, multinomialregression was performed, considering the cate-gories of glucose level. Odds ratios (ORs) andrespective 95% CIs were calculated and reported.

All data collected were stored in a database, andall analyses were performed by means of statisticalsoftware.‡ Results were considered significant fora probability lower than 5% (P <0.05).

RESULTS

Characteristics of the sample according to de-mographic, behavioral, and biologic variables ofinterest are shown in Table 1. The mean age of thetotal sample was 27.2 – 6.3 years. When evaluatingthe study sample according to outcome (GDM), thecase group showed a mean age of 31.9 – 5.3 years,significantly different from the control group (25.3 –5.8 years). Data such as education level, maritalstability, parity, smoking, and alcohol consumptionshowed no significant difference between case andcontrol groups. Women from the case group hadsignificantly higher BMI and higher occurrence ofchronic hypertension than women from the controlgroup. When evaluating the study sample accord-ing to exposure (periodontitis), women with peri-odontitis differed from those without periodontitis

† UNC-15, Hu-Friedy, Chicago, IL.‡ SPSS v.17.0, IBM, Chicago, IL.

J Periodontol • September 2013 Lima, Cota, Costa

1259

Page 4: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

regarding education level and primiparity. Thesefindings could provide some indication about poten-tial factors likely to confound the relation betweenexposure and outcome (Table 1). Periodontitis un-adjusted OR for GDM was 1.293 (95% CI = 0.796 to2.100; P = 0.298). The education level–adjusted ORwas 1.277 (95% CI = 0.784 to 2.079; P = 0.236), andthe primiparity-adjusted OR was 1.382 (95% CI =0.842 to 2.268; P = 0.201).

The prevalence of periodontitis and character-ization of the sample according to periodontal statusare reported in Table 2. A high prevalence of peri-odontitis was reported among cases (40%) andcontrols (46.3%). However, no significant differenceamong the groups was observed. Moreover, therewere no significant differences between cases and

controls regarding percentage of sites with BOP orsites with CAL ‡3 mm and PD 5 to 6 mm or ‡7 mm.

Table 3 presents the prevalence of periodontitisand periodontal status of the sample stratified byblood glucose levels. Controls and categories ofglucose level of 96 to 105, 106 to 125, and ‡126mg/dL showed prevalence rates of periodontitis of46.3%, 41.3%, 42.9%, and 31.3%, respectively (P =0.636). There were no significant differences amonggroups in relation to percentage of sites with BOPor sites with CAL ‡3 mm and PD 4 mm, 5 to 6 mm,or ‡7 mm.

The results of multivariate logistic regression areshown in Table 4. The variables that remainedsignificant in the final model for GDM were: 1)maternal age (OR = 2.65, P <0.001); 2) chronic

Table 1.

Characteristics of the Sample in Relation to Variables of Interest According to Outcome(GDM) and Exposure (periodontitis)

Outcome (GDM) Exposure (periodontitis)

Variable Total Sample Cases Controls P* Yes No P†

n 360 90 270 161 199

Age (years) <0.001 0.69018 to 25 161 (44.7) 10 (11.1) 151 (55.9) 74 (46.0) 87 (43.7)26 to 30 94 (26.1) 25 (27.8) 69 (25.6) 42 (26.1) 52 (26.1)31 to 35 66 (18.3) 34 (37.8) 32 (11.9) 25 (15.5) 41 (20.6)36 to 40 30 (8.3) 15 (16.7) 15 (5.6) 16 (9.9) 14 (7.0)‡41 9 (2.5) 6 (6.7) 3 (1.1) 4 (2.5) 5 (2.5)

Education level (years) 0.502 0.024Illiterate 5 (1.4) 0 (0.0) 5 (1.9) 4 (2.5) 1 (0.5)£8 197 (54.7) 50 (55.6) 147 (54.4) 92 (57.1) 105 (52.8)9 to 12 150 (41.7) 37 (41.1) 113 (41.9) 65 (40.4) 85 (42.7)>12 8 (2.2) 3 (3.3) 5 (1.9) 0 (0.0) 8 (4.0)

Marital stability 0.734 0.130With partner 267 (74.2) 68 (75.6) 199 (73.7) 117 (72.7) 150 (75.4)Without partner 84 (23.3) 19 (21.1) 65 (24.1) 37 (23.0) 47 (23.6)Other 9 (2.5) 3 (3.3) 6 (2.2) 7 (4.3) 2 (1.0)

Primiparity 125 (34.7) 27 (30.0) 98 (36.3) 0.277 39 (24.2) 86 (43.2) <0.001

Smoking 81 (22.5) 24 (26.7) 57 (21.1) 0.736 9 (5.6) 15 (7.5) 0.461

Alcohol consumption 22 (6.1) 5 (5.6) 17 (6.3) 0.799 10 (6.2) 12 (6.0) 0.943

Chronic hypertension 40 (11.1) 26 (28.9) 14 (5.2) <0.001 16 (9.9) 24 (12.1) 0.524

BMI‡ <0.001 0.254Underweight 27 (7.5) 5 (5.6) 22 (10.0) 8 (5.7) 19 (11.1)Normal weight 128 (35.6) 16 (17.8) 112 (50.7) 63 (45.0) 65 (38.0)Overweight 74 (20.6) 31 (34.4) 43 (19.5) 35 (25.0) 39 (22.8)Obese 82 (22.8) 38 (42.2) 44 (19.9) 34 (24.3) 48 (28.1)

Data are n (%).* Comparison between cases and controls through x

2 test.† Comparison between exposed and non-exposed through x

2 test.‡ Control group had 49 missing values.

Gestational Diabetes and Periodontitis Volume 84 • Number 9

1260

Page 5: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

hypertension (OR = 3.16, P = 0.008); and 3) BMI(OR = 1.99, P <0.001). Periodontitis did not remainsignificant in the initial model, with an OR of 1.29(95% CI = 0.80 to 2.10).

A multinomial regression model for blood glu-cose levels is shown in Table 5. It was found thatonly age and BMI were significantly associatedwith all altered blood glucose levels. Periodontitiswas not associated with altered blood glucose lev-els in pregnant women.

DISCUSSION

GDM is a metabolic disorder of the DM group thatoccurs in the presence of risk factors such as high

maternal age, high BMI, and history of previousGDM.11,12 Moreover, the possibility has been dis-cussed that a systemic infection can lead to thedevelopment of insulin resistance and manifesta-tion of GDM.13 Studies13,14,35 demonstrated thatwomen with GDM have elevated levels of in-flammatory mediators in the systemic circulation,suggesting that a source of infection in the bodycan have an important role in the developmentof this pregnancy complication. The link betweenGDM and periodontitis is guided by the fact thatperiodontitis, an infectious inflammatory disease,represents an important source of inflammatorymediators and bacterial products.

Table 2.

Prevalence of Periodontitis and Periodontal Status of the Sample

Variable Total Sample Cases (GDM) Controls P*

n 360 90 270

Periodontitis† 161 (44.7) 36 (40.0) 125 (46.3) 0.298‡

Teeth present (n) 25.66 – 3.02 (12 to 28) 25.20 – 2.90 25.82 – 3.04 0.005§

Sites with BOP (%) 25.29 – 23.44 (0 to 100) 26.08 – 19.25 25.04 – 24.70 0.130§

Sites with CAL ‡3 mm (%)and PD 4 mm 5.00 – 5.93 (0 to 31.25) 3.23 – 4.58 5.59 – 6.21 0.008§

and PD 5 to 6 mm 3.81 – 6.82 (0 to 52.50) 2.53 – 4.41 4.24 – 7.41 0.428§

and PD ‡7 mm 0.56 – 2.36 (0 to 27.27) 0.22 – 0.91 0.67 – 2.67 0.058§

Data are mean – SD (range) unless otherwise specified.* Comparisons between cases and controls.† n (%).‡ x2 test.§ Mann-Whitney U test.

Table 3.

Prevalence of Periodontitis and Periodontal Status of the Sample Stratified by BloodGlucose Level

Blood Glucose Level (mg/dL)

Variable Controls 96 to 105 106 to 125 ‡126 P

n 270 46 28 16

Periodontitis* 125 (46.3) 19 (41.3) 12 (42.9) 5 (31.3) 0.636†

Teeth present (n) 25.82 – 3.04 25.46 – 2.41 24.43 – 3.73 25.81 – 2.43 0.021‡,§

Sites with BOP (%) 25.04 – 24.70 24.36 – 18.74 29.32 – 16.84 25.34 – 24.61 0.242‡

Sites with CAL ‡3 mm (%)and PD 4 mm 5.59 – 6.21 3.27 – 5.20 2.94 – 2.91 3.64 – 5.26 0.068‡

and PD 5 to 6 mm 4.24 – 7.41 2.68 – 4.71 2.75 – 4.72 1.71 – 2.79 0.761‡

and PD ‡7 mm 0.67 – 2.67 0.28 – 0.99 0.23 – 1.03 0.06 – 0.22 0.291‡

Data are mean – SD unless otherwise specified.* n (%).† x

2 test.‡ Kruskal-Wallis test.§ Post hoc Dunn test; P <0.05 for all pair comparisons.

J Periodontol • September 2013 Lima, Cota, Costa

1261

Page 6: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

Based on this hypothesis and the biologic plau-sibility of the association, it has been speculatedthat periodontitis is more common among womenwith GDM. However, this study reported high prev-alence rates of periodontitis in both cases (40%)and controls (46.6%), with no significant differencesamong the groups, as well as a lack of associationbetween periodontitis and GDM (OR = 1.29; 95% CI =0.80 to 2.10). The prevalence rates of periodontitisreported in the present study were similar to thosereported by Dasanayake et al.26 among pregnantwomen. This prevalence can also be consideredsimilar to data for a non-pregnant Brazilian sam-ple, since it was demonstrated that prevalence ratescan vary from 40% to 80% among Brazilians ac-cording to the periodontitis definition applied.36 In-deed, when criteria similar to those used in thepresent study were applied, the prevalence ratewas around 39%.36

Some studies have assessed the association be-tween periodontitis and GDM.23-28 Two studies,Novak et al.24 and Dasanayake et al.,26 also reporteda similar lack of association between periodontitisand GDM. Conversely, three studies supported theassociation between periodontitis and GDM.23,25,27

The study from Novak et al.24 found a non-significant

OR of 2.0 (95% CI = 0.6 to 6.3), of great similarity to theOR and CI estimates reported in the present study.

Another study37 investigated the association be-tween gingivitis and GDM and demonstrated thatwomen with GDM had higher gingival indices thanpregnant women with adequate glucose blood lev-els. However, these women also had a higher plaquescore. In the view of the present authors, this resultcould be associated with a potential collinearity be-tween these two periodontal parameters.

The number of studies that have proposed to ex-amine the association between periodontitis andGDM can still be considered extremely low. Theavailable studies in the literature described datafrom distinct populations, presented small samples,and considered heterogeneous exposure to riskfactors. Therefore, the reported results are conflict-ing. Due to these methodologic differences amongstudies, comparison and discussion with this study’sresults are difficult. In addition, differences in criteriafor the diagnosis of GDM and the definition of peri-odontitis may also have caused great impact onthe study results. Regarding the criteria for diagno-sis of GDM, it can be observed that criteria varyfrom self-report to different blood test results, andthe same observation could be noted regardingperiodontitis. Studies24-26 used criteria of a lesserextent and severity in the PD and CAL parametersto define periodontitis (where one periodontal sitewith PD or CAL ‡3 or 4 mm was determinant of thediagnostic). It is difficult to establish a consensuscase definition of periodontitis that does not un-derestimate or overestimate the disease and thatreally reflects patterns of inflammation and infec-tion that may have systemic repercussions. A strongimpact of the robustness of a criterion on prevalencerates of the disease has been reported previously.36

On the other hand, it must be emphasized thatnumerous studies on the association between peri-odontitis and adverse pregnancy outcomes wereconducted with different criteria for periodontitis,mostly with low cut-off points for PD and/or CAL,as well as without including indicators of diseaseactivity such as BOP and/or suppuration.33,38-41

Currently, in studies of association between peri-odontitis and systemic events,3,21 it is recommendedto evaluate indicators of exposure or markers ofinflammation and infection of periodontitis. In thismanner, the present study used as a criterion fordefining periodontitis the presence of ‡4 teeth with‡1 sites with PD ‡4mm and CAL ‡3mm33 associatedwith BOP at the same site.34

Conversely, poorly controlled DM-2 has beenwidely investigated and associated with greaterprevalence, extent, and severity of periodontitis innumerous studies.5,15-18,42 In a recent meta-analysis,

Table 4.

Initial and Final Multivariate Logistic Modelfor GDM

Variable Coefficient OR (95% CI) P

Constant -5.801 NA <0.001

Initial modelAge 1.054 2.87 (2.07 to 3.97) <0.001Education level 0.167 1.18 (0.66 to 2.11) 0.573Marital stability 0.197 1.22 (0.67 to 2.23) 0.523Parity 0.281 1.32 (0.63 to 2.80) 0.464Smoking 0.070 1.07 (0.53 to 2.17) 0.845Alcoholconsumption

-0.555 0.57 (0.13 to 2.59) 0.470

Chronichypertension

1.043 2.84 (1.19 to 6.77) 0.019

BMI 0.701 2.02 (1.42 to 2.86) <0.001Periodontitis -0.304 0.74 (0.40 to 1.38) 0.339

Final modelAge 0.975 2.65 (1.97 to 3.56) <0.001Chronichypertension

1.153 3.16 (1.35 to 7.42) 0.008

BMI 0.689 1.99 (1.41 to 2.81) <0.001NA = not applicable.Sensitivity = 46.67%, specificity = 90.05%, positive predictive value =65.63%, negative predictive value = 80.57%, area under receiver operatorcharacteristic curve = 0.8417.

Gestational Diabetes and Periodontitis Volume 84 • Number 9

1262

Page 7: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

Chavarry et al.4 demonstrated that DM-2 is a riskfactor for periodontitis and that there is insufficientevidence to establish a relationship between DM-1and periodontitis. The low age of the patients withDM-1 usually involved in most studies may be re-sponsible for the lack of association between DM-1and periodontitis, since periodontitis affects moreindividuals >35 to 45 years old in different settings.32

Individuals with DM have impaired function ofneutrophils, whereas macrophages and monocytesare more reactive, which results in an overproductionof proinflammatory cytokines. However, the mech-anism by which DM influences the development ofperiodontitis is not expected to be the same forGDM. Hyperglycemia with onset during pregnancyoccurs in a relatively short period of time andtherefore is insufficient to cause the loss of peri-odontal supporting tissues seen in chronic peri-odontitis. Moreover, periodontitis, as an infectiousprocess, could contribute to the insulin resistanceobserved in women with GDM.

Results from the present study showed that ma-ternal age was strongly associated with GDM. Thisresult was different from the study of Dasanayakeet al.26 but consistent with others.23,27 It is note-worthy that increased maternal age has beenrecognized as an important risk factor for the de-velopment of GDM.11,43

It was also demonstrated that BMI showed a sig-nificant association with GDM in the present study.Other studies23,27 that included the evaluation ofBMI in their analyses similarly showed that a higherBMI was more prevalent in women with GDM com-

pared with pregnant women without endocrinopa-thies. These data solidify the results of other studiesthat establish high BMI as a risk factor for GDM.11,43

It is important to note that BMI for Brazilian womenin general is approximately 25 (normal weight),44

and it is similar to the values for most of the womenin the present study.

GDM has been associated with significant mater-nal morbidity and infant mortality. Women with GDMare at high risk for hypertension, preeclampsia,need for cesarean delivery, and development ofDM-2 after the gestational period.10 Similarly to thefindings from the present study, Bener et al.45 showeda significantly higher prevalence of chronic hyper-tension among women with GDM.

Deepening knowledge about GDM is crucial, be-cause this disorder represents a unique opportunityfor early intervention to prevent the development ofDM-2. In addition, GDM may have serious conse-quences for children and mothers. The limitednumber of studies regarding the association be-tween periodontitis and GDM, as well as their con-flicting results, points to the need for additionalstudies on this association. These studies shouldbe conducted in different population groups, com-prise large samples, and present different meth-odologic designs.

In addition to temporal and external validity is-sues of case-control studies, some limitations ofthe present study related to outcome and exposuredefinitions should be discussed. Regarding peri-odontitis definition, this issue is timely and con-troversial in periodontal research, since extension

Table 5.

Multinomial Regression Model for Blood Glucose Levels

Variable Coefficient OR (95% CI) P

Blood glucose 96 to 105 mg/dLConstant -5.610 NA <0.001Age 0.954 2.60 (1.84 to 3.67) <0.001Chronic hypertension 1.470 4.35 (1.69 to 11.21) 0.002BMI 0.604 1.83 (1.20 to 2.79) 0.005

Blood glucose 106 to 125 mg/dLConstant -6.580 NA <0.001Age 0.983 2.67 (1.79 to 3.98) <0.001Chronic hypertension 0.894 2.45 (0.77 to 7.70) 0.126BMI 0.784 2.19 (1.31 to 3.65) 0.003

Blood glucose ‡126 mg/dLConstant -7.076 NA <0.001Age 1.017 2.76 (1.70 to 4.50) <0.001Chronic hypertension 0.527 1.69 (0.38 to 7.54) 0.489BMI 0.758 2.13 (1.13 to 4.04) 0.020

NA = not applicable.Main effects model; reference category = controls.

J Periodontol • September 2013 Lima, Cota, Costa

1263

Page 8: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

and severity of PD and CAL parameters couldstrongly influence prevalence estimates re-ported.36,46 In this manner, the present researchgroup adopted a relatively robust criterion to avoidoverestimation of periodontitis. However, it is im-portant to highlight that the definition of peri-odontitis based on the presence of ‡4 teeth with ‡1sites with PD ‡4 mm and CAL ‡3 mm has beenextensively used in association studies investigat-ing adverse pregnancy outcomes.7-9,33 RegardingGDM definition, although the criteria adopted in thepresent study are currently recommended by theAmerican Diabetes Association, the normal glucoseblood level considered in pregnant women couldbe lower.47,48

Regardless of uncertainties and conflicting dataon the relationship between periodontitis and itsimpact on GDM, periodontitis has serious conse-quences for oral health and is responsible for highrates of edentulism. Therefore, it should not be ne-glected. In addition, other adverse effects on thesystemic condition have been positively associ-ated with periodontitis.3,49 Regarding the associa-tion between periodontitis and GDM, the potentialof women with GDM to develop DM-2 in the futurealso suggests the importance of preventive mea-sures for periodontitis.

CONCLUSIONS

The present study demonstrated no associationbetween maternal periodontitis and GDM. However,the high prevalence of periodontitis among casesand controls suggests the need for implementationof public and private health policies directed tothe periodontal care of pregnant women, especiallythose prioritizing preventive strategies for the main-tenance of periodontal health.

ACKNOWLEDGMENT

The authors report no conflicts of interest relatedto this study.

REFERENCES1. Kinane DF. Causation and pathogenesis of periodontal

disease. Periodontol 2000 2001;25:8-20.2. Tonetti MS. Periodontitis and risk for atherosclerosis:

An update on intervention trials. J Clin Periodontol2009;36(Suppl 10):15-19.

3. Scannapieco FA, Dasanayake AP, Chhun N. Doesperiodontal therapy reduce the risk for systemic dis-eases? Dent Clin North Am 2010;54:163-181.

4. Chavarry NG, Vettore MV, Sansone C, Sheiham A. Therelationship between diabetes mellitus and destruc-tive periodontal disease: A meta-analysis. Oral HealthPrev Dent 2009;7:107-127.

5. Javed F, Nasstrom K, Benchimol D, Altamash M,Klinge B, Engstrom PE. Comparison of periodontaland socioeconomic status between subjects with type

2 diabetes mellitus and non-diabetic controls. J Perio-dontol 2007;78:2112-2119.

6. Javed F, Al-Askar M, Al-Rasheed A, Babay N, Galindo-Moreno P, Al-Hezaimi K. Comparison of self-perceivedoral health, periodontal inflammatory conditions andsocioeconomic status in individuals with and withoutprediabetes. Am J Med Sci 2012;344:100-104.

7. Cota LO, Guimaraes AN, Costa JE, Lorentz TC, CostaFO. Association between maternal periodontitis andan increased risk of preeclampsia. J Periodontol 2006;77:2063-2069.

8. Siqueira FM, Cota LO, Costa JE, Haddad JP, Lana AM,Costa FO. Intrauterine growth restriction, low birthweight, and preterm birth: Adverse pregnancy out-comes and their association with maternal peri-odontitis. J Periodontol 2007;78:2266-2276.

9. Siqueira FM, Cota LO, Costa JE, Haddad JP, Lana AM,Costa FO. Maternal periodontitis as a potential riskvariable for preeclampsia: A case-control study. JPeriodontol 2008;79:207-215.

10. American Diabetes Association. Diagnosis and classi-fication of diabetes mellitus. Diabetes Care 2011;34(Suppl. 1):S62-S69.

11. Xiong X, Saunders LD, Wang FL, Demianczuk NN.Gestational diabetes mellitus: Prevalence, risk factors,maternal and infant outcomes. Int J Gynaecol Obstet2001;75:221-228.

12. Schneider S, Hoeft B, Freerksen N, et al. Neonatalcomplications and risk factors among women withgestational diabetes mellitus. Acta Obstet GynecolScand 2011;90:231-237.

13. Wolf M, Sauk J, Shah A, et al. Inflammation andglucose intolerance: A prospective study of gestationaldiabetes mellitus. Diabetes Care 2004;27:21-27.

14. Ategbo JM, Grissa O, Yessoufou A, et al. Modulationof adipokines and cytokines in gestational diabetesand macrosomia. J Clin Endocrinol Metab 2006;91:4137-4143.

15. Loe H. Periodontal disease. The sixth complication ofdiabetes mellitus. Diabetes Care 1993;16:329-334.

16. Taylor GW. The effects of periodontal treatment ondiabetes. J Am Dent Assoc 2003;134:41S-48S.

17. Kaur G, Holtfreter B, Rathmann W, et al. Associationbetween type 1 and type 2 diabetes with periodontaldisease and tooth loss. J Clin Periodontol 2009;36:765-774.

18. NewtonKM,ChaudhariM, BarlowWE, et al. A population-based study of periodontal care among those with andwithout diabetes. J Periodontol 2011;82:1650-1656.

19. Mealey BL, Oates TW; American Academy of Peri-odontology. Diabetes mellitus and periodontal dis-eases. J Periodontol 2006;77:1289-1303.

20. Taylor GW, Burt BA, Becker MP, et al. Non-insulindependent diabetes mellitus and alveolar bone lossprogression over 2 years. J Periodontol 1998;69:76-83.

21. Teeuw WJ, Gerdes VE, Loos BG. Effect of periodontaltreatment on glycemic control of diabetic patients: Asystematic review and meta-analysis. Diabetes Care2010;33:421-427.

22. Santos Tunes R, Foss-Freitas MC, Nogueira-Filho GR.Impact of periodontitis on the diabetes-related inflam-matory status. J Can Dent Assoc 2010;76:a35.

23. Xiong X, Elkind-Hirsch KE, Vastardis S, Delarosa RL,Pridjian G, Buekens P. Periodontal disease is associ-ated with gestational diabetes mellitus: A case-controlstudy. J Periodontol 2009;80:1742-1749.

Gestational Diabetes and Periodontitis Volume 84 • Number 9

1264

Page 9: Association Between Periodontitis and Gestational Diabetes Mellitus: A Case-Control Study

24. Novak KF, Taylor GW, Dawson DR, Ferguson JE 2nd,Novak MJ. Periodontitis and gestational diabetes mel-litus: Exploring the link in NHANES III. J Public HealthDent 2006;66:163-168.

25. XiongX, Buekens P, Vastardis S, Pridjian G. Periodontaldisease and gestational diabetes mellitus. Am J ObstetGynecol 2006;195:1086-1089.

26. Dasanayake AP, Chhun N, Tanner AC, et al. Periodon-tal pathogens and gestational diabetes mellitus. J DentRes 2008;87:328-333.

27. Ruiz DR, Romito GA, Dib SA. Periodontal disease ingestational and type 1 diabetes mellitus pregnantwomen. Oral Dis 2011;17:515-521.

28. Xie Y, Xiong X, Elkind-Hirsch KE, et al. Change ofperiodontal disease status during and after pregnancy[published online ahead of print August 8, 2012].J Periodontol. doi:10.1902/jop.2012.120235.

29. STROBE statement. Available at: http://www.strobe-statement.org/. Accessed June 30, 2012.

30. Tomar SL, Asma S. Smoking-attributable periodontitisin the United States: Findings from NHANES III.J Periodontol 2000;71:743-751.

31. Atalah ES, Castillo C, Castro R, Aldea A. Proposal ofa new standard for the nutritional assessment ofpregnant women (in Spanish). Rev Med Chil 1997;125:1429-1436.

32. Oliveira Costa F, Cota LO, Costa JE, Pordeus IA. Peri-odontal disease progression among young subjectswith no preventive dental care: A 52-month follow-upstudy. J Periodontol 2007;78:198-203.

33. Lopez NJ, Smith PC, Gutierrez J. Higher risk of pretermbirth and low birth weight in women with periodontaldisease. J Dent Res 2002;81:58-63.

34. Gomes-Filho IS, Cruz SS, Rezende EJ, et al. Exposuremeasurement in the association between periodontaldisease and prematurity/low birth weight. J Clin Perio-dontol 2007;34:957-963.

35. Wolf M, Sandler L, Hsu K, Vossen-Smirnakis K, EckerJL, Thadhani R. First-trimester C-reactive protein andsubsequent gestational diabetes. Diabetes Care 2003;26:819-824.

36. Costa FO, Guimaraes AN, Cota LOM, et al. Impact ofdifferent periodontitis case definitions on periodontalresearch. J Oral Sci 2009;51:199-206.

37. Mittas E, Erevnidou K, Koumantakis E, PapavasileiouS, Helidonis E. Gingival condition of women withgestational diabetes on a Greek island. Spec CareDentist 2006;26:214-219.

38. Canakci V, Canakci CF, Canakci H, et al. Periodontaldisease as a risk factor for pre-eclampsia: A casecontrol study. Aust N Z J Obstet Gynaecol 2004;44:568-573.

39. Toygar HU, Seydaoglu G, Kurklu S, Guzeldemir E,Arpak N. Periodontal health and adverse pregnancy

outcome in 3,576 Turkish women. J Periodontol 2007;78:2081-2094.

40. Lohsoonthorn V, KungsadalpipobK, Chanchareonsook P,et al. Is maternal periodontal disease a risk factorfor pretermdelivery?AmJEpidemiol2009;169:731-739.

41. Srinivas SK, Sammel MD, Stamilio DM, et al. Periodon-tal disease and adverse pregnancy outcomes: Is therean association? Am J Obstet Gynecol 2009;200:497.e1-8.

42. Westfelt E, Rylander H, BlohmeG, Joanasson P, LindheJ. The effect of periodontal therapy in diabetics. J ClinPeriodontol 1996;23:92-100.

43. Lapolla A, Dalfra MG, Bonomo M, et al; ScientificCommittee of GISOGD Group. Gestational diabetesmellitus in Italy: A multicenter study. Eur J ObstetGynecol Reprod Biol 2009;145:149-153.

44. Sichieri R, Moura EC. Amultilevel analysis of variationsin body mass index among adults, Brazil, 2006 (inPortuguese). Rev Saude Publica 2009;43(Suppl. 2):90-97.

45. Bener A, Saleh NM, Al-Hamaq A. Prevalence ofgestational diabetes and associated maternal andneonatal complications in a fast-developing commu-nity: Global comparisons. Int J Womens Health 2011;3:367-373.

46. Eke PI, Page RC, Wei L, Thornton-Evans G, Genco RJ.Update of the case definitions for population-basedsurveillance of periodontitis. J Periodontol 2012;83:1449-1454.

47. Metzger BE, Lowe LP, Dyer AR, et al.; HAPO StudyCooperative Research Group. Hyperglycemia and ad-verse pregnancy outcomes. N Engl J Med 2008;358:1991-2002.

48. Hiramatsu Y, Shimizu I, Omori Y, Nakabayashi M;JGA (Japan Glycated Albumin) Study Group. De-termination of reference intervals of glycated albuminand hemoglobin A1c in healthy pregnant Japanesewomen and analysis of their time courses and influ-encing factors during pregnancy. Endocr J 2012;59:145-151.

49. Seymour RA. Does periodontal treatment improvegeneral health? Dent Update 2010;37:206-208,210-212.

Correspondence: Dr. Fernando Oliveira Costa, Depart-ment of Periodontology, Federal University of MinasGerais, Antonio Carlos Avenue, 6627, Pampulha - POBox 359, 31270-901 Belo Horizonte, Minas Gerais, Brazil.Phone: 55 31 3409 2412 ext. 2427; fax: 55 31 3282 6787;e-mail: [email protected] and [email protected].

Submitted June 5, 2012; accepted for publication October4, 2012.

J Periodontol • September 2013 Lima, Cota, Costa

1265