Oral-Systemic Links Gestational Diabetes Mellitus

Periodontitis and MaternalFetal Outcomes

Karen Novak DDS MS PhD

Professor Department of Periodontics amp Dental Hygiene Associate Dean for Professional Development amp Faculty Affairs

University of Texas Health Science Center School of Dentistry at Houston

Interprofessional Collaboration for Collective Impact

bull Dr Jeff Ebersole Basic Scientist

bull Dr James E Ferguson OBGYN

bull Dr John Novak Periodontist and Basic Scientist

bull Dr George Taylor General Dentist Epidemiologist

Objectives

bull After this presentation participants will be able to ndash discuss the etiology of gestational diabetes mellitus (GDM)

ndash describe how periodontal disease (PD) GDM and negative pregnancy outcomes may be linked

ndash describe data linking PD GDM and negative pregnancy outcomes

Gestational Diabetes Mellitus (GDM)

bull Diabetes that has onset during pregnancy

bull Occurs in approximately 5-7 of pregnant women

bull Is the most common metabolic disorder of pregnancy

GDM Etiology

bull Women with GDM make sufficient amounts of insulin ndash Placental hormones block the effect of insulin leading to

ldquoinsulin resistancerdquo

ndash The larger the placenta grows the more these hormones are produced and the greater the insulin resistance becomes

GDM Risk Factors

bull Obesity

bull Previous history of GDM

bull Family history of diabetes

bull Having given birth previously to a very large infant a still birth or a child with a birth defect

bull Having too much amniotic fluid

bull Being gt25 years of age

bull Being African American HispanicLatina American American Indian

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Interprofessional Collaboration for Collective Impact

bull Dr Jeff Ebersole Basic Scientist

bull Dr James E Ferguson OBGYN

bull Dr John Novak Periodontist and Basic Scientist

bull Dr George Taylor General Dentist Epidemiologist

Objectives

bull After this presentation participants will be able to ndash discuss the etiology of gestational diabetes mellitus (GDM)

ndash describe how periodontal disease (PD) GDM and negative pregnancy outcomes may be linked

ndash describe data linking PD GDM and negative pregnancy outcomes

Gestational Diabetes Mellitus (GDM)

bull Diabetes that has onset during pregnancy

bull Occurs in approximately 5-7 of pregnant women

bull Is the most common metabolic disorder of pregnancy

GDM Etiology

bull Women with GDM make sufficient amounts of insulin ndash Placental hormones block the effect of insulin leading to

ldquoinsulin resistancerdquo

ndash The larger the placenta grows the more these hormones are produced and the greater the insulin resistance becomes

GDM Risk Factors

bull Obesity

bull Previous history of GDM

bull Family history of diabetes

bull Having given birth previously to a very large infant a still birth or a child with a birth defect

bull Having too much amniotic fluid

bull Being gt25 years of age

bull Being African American HispanicLatina American American Indian

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Objectives

bull After this presentation participants will be able to ndash discuss the etiology of gestational diabetes mellitus (GDM)

ndash describe how periodontal disease (PD) GDM and negative pregnancy outcomes may be linked

ndash describe data linking PD GDM and negative pregnancy outcomes

Gestational Diabetes Mellitus (GDM)

bull Diabetes that has onset during pregnancy

bull Occurs in approximately 5-7 of pregnant women

bull Is the most common metabolic disorder of pregnancy

GDM Etiology

bull Women with GDM make sufficient amounts of insulin ndash Placental hormones block the effect of insulin leading to

ldquoinsulin resistancerdquo

ndash The larger the placenta grows the more these hormones are produced and the greater the insulin resistance becomes

GDM Risk Factors

bull Obesity

bull Previous history of GDM

bull Family history of diabetes

bull Having given birth previously to a very large infant a still birth or a child with a birth defect

bull Having too much amniotic fluid

bull Being gt25 years of age

bull Being African American HispanicLatina American American Indian

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Gestational Diabetes Mellitus (GDM)

bull Diabetes that has onset during pregnancy

bull Occurs in approximately 5-7 of pregnant women

bull Is the most common metabolic disorder of pregnancy

GDM Etiology

bull Women with GDM make sufficient amounts of insulin ndash Placental hormones block the effect of insulin leading to

ldquoinsulin resistancerdquo

ndash The larger the placenta grows the more these hormones are produced and the greater the insulin resistance becomes

GDM Risk Factors

bull Obesity

bull Previous history of GDM

bull Family history of diabetes

bull Having given birth previously to a very large infant a still birth or a child with a birth defect

bull Having too much amniotic fluid

bull Being gt25 years of age

bull Being African American HispanicLatina American American Indian

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

GDM Etiology

bull Women with GDM make sufficient amounts of insulin ndash Placental hormones block the effect of insulin leading to

ldquoinsulin resistancerdquo

ndash The larger the placenta grows the more these hormones are produced and the greater the insulin resistance becomes

GDM Risk Factors

bull Obesity

bull Previous history of GDM

bull Family history of diabetes

bull Having given birth previously to a very large infant a still birth or a child with a birth defect

bull Having too much amniotic fluid

bull Being gt25 years of age

bull Being African American HispanicLatina American American Indian

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

GDM Risk Factors

bull Obesity

bull Previous history of GDM

bull Family history of diabetes

bull Having given birth previously to a very large infant a still birth or a child with a birth defect

bull Having too much amniotic fluid

bull Being gt25 years of age

bull Being African American HispanicLatina American American Indian

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

GDM Testing and Diagnosis

bull Non-fasting 50 gm glucose screening test (Glucola) ndash Negative (lt140 mgdL)

bull No further testing

ndash Positive (gt140 mgdL) bull Fasting 4 hour 100 gm glucose

tolerance test (GTT)

ndash Positive (gt200 mgdL) bull Diagnostic no further test needed

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

GDM Testing and Diagnosis bull GTT

ndash Overnight fast followed by 100 gm glucose administration

ndash Fasting 1 2 and 3 hour plasma levels obtained

ndash Two values gt normal are diagnostic bull Fasting 105 mgdL

bull 1 hour 190 mgdL

bull 2 hours 165 mgdL

bull 3 hours 145 mgdL

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

GDM Testing and Diagnosis

bull Average risk women

ndash Tested between 24-28 weeks gestation

bull High risk women

ndash Tested as soon as possible

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

GDM Potential Negative Outcomes

bull After pregnancy 5-10 of women with GDM develop type 2 diabetes mellitus

bull Women who have had GDM have a 20-50 chance of developing type 2 diabetes in the next 5-10 years

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Study 1 NHANES III Analysis

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Periodontal Disease and GDM bull 4244 women ages 20-59

ndash 113 had a history of GDM during pregnancy

bull Periodontal disease defined as one or more teeth with one or more sites with PDgt4mm LOA gt2mm and bleeding on probing

bull There was a trend for women with a history of GDM to have more periodontal disease than women without a history of GDM

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Hypothesis Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Novak KF Taylor G Ferguson JE and Novak MJ 2006 Periodontitis and Gestational Diabetes Mellitus

Exploring the Link in NHANES III J Pub Health Dent 66163-168

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Periodontal Disease and GDM bull Prior GDM higher pre-pregnancy BMI vaginal levels of Tannerella forsythia and C-

reactive protein were risk factors for developing GDM Periodontal disease was not statistically significant Dasanayakeet al 2008

ldquoNew Evidence of Periodontal Disease Leading to Gestational Diabetesrdquo

bull Further support for the hypothesis that there is an association between periodontal disease and GDM Xiong et al 2009

bull The presence of periodontal disease was significantly higher in women with either GDM or Type 2 diabetes during their pregnancy Age pregestational BMI and HbA1c) were related to clinical attachment loss in these two group Ruiz et al 2011

bull Women with both prior GDM and periodontal disease showed greater insulin resistance and altered Beta cell function potentially making them at greater risk for developing Type 2 diabetes Xiong et al 2012

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Study 2 NIH Cross-Sectional Analysis

NIHNCRR Center of Biomedical Research Excellence P20 RR020145

University of Kentucky CR-DOC

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Study Population

bull 306 matched pairs of pregnant women ndash Ages 16-45

ndash No history of type 1 or type 2 diabetes mellitus

ndash Minimum of 20 teeth

bull 153 with GDM 153 controls without GDM ndash Age raceethnicity and gestational age matched

bull Categorized by presenceabsence of periodontal disease (PD)

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Data Collection bull Enrollment

ndash Consent and HIPAA authorization

ndash Medical and dental histories

ndash Comprehensive periodontal examination

bull Plaque index probing pocket depths clinical

attachment levels bleeding index calculus index

ndash Periodontitis (PD)

bull At least 4 teeth with PD gt4mm LOA gt2mm and

BOP

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Data Collection

Laboratory samples

bull Serum ndash assessed by ELISA and Luminex

bull Subgingival plaque ndash biofilm microbiota assessed by qPCR

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Data collection bull Post-delivery maternal and fetal outcomes

ndash Maternal pre-eclampsia premature labor premature rupture of membranes urinary tract infections chorioamnionitisfunisitis induction of labor operative vaginal deliveries or unplanned cesarean

ndash Fetal IUGRLBW shoulder dystocia brachial plexus damage facial

nerve injury fractured bones other neonatal birth problems hypoglycemia hyperbilirubinemia respiratory distress syndrome transient tachypnea of the newborn polycythemia hypocalcemia intraventricular hemorrhage necrotizing enterocolitis congenital anomaly stay in NICU Apgars 1 or Apgars 5 lt7rsquo

Crowther et al 2005 Effect of Treatment of Gestational Diabetes

Mellitus on Pregnancy Outcomes NEJM 3522477-2486

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Analysis of 306 Matched Subjects

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Study Population Characteristics

Variable GDM=No GDM=Yes

Number of subjects 153 153

Age (sd) 284 (52)

293 (59)

Raceethnicity number and (column )

Asian (n=24) 12 (78) 12 (78)

African American (n=24) 12 (78) 12 (78)

Caucasian (n=96) 48 (314) 48 (314)

Hispanic (n=162) 81 (529) 81 (529)

Gestational age at enrollment 290 (84) 286 (85)

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Variable GDM+PD+

N=68

GDM+PD-

N=85

GDM-PD+

N=59

GDM-PD-

N=94

Difference

(p value)

Plaque index 065 (016) 047 (014) 064 (016) 046 (017) lt0001

Probing depth 326 (054) 250 (033) 314 (051) 247 (024) lt0001

Clinical

attachment loss

103 (061) 036 (025) 10 (065) 032 (020) lt0001

Calculus (0-3) 073 (032) 021 (021) 074 (033) 017 (019) lt0001

Bleeding (0-3) 057 (030) 020 (021) 045 (032) 016 (015) lt0001

Clinical Characteristics

Periodontal Evaluation

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Odds Ratios for Adverse Maternal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 23 106 48

PD+ GDM+ vs PD- GDM+ 197 088 44

PD+ GDM+ vs PD+ GDM- 177 085 37

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone

Fig 1

Gestational Diabetes Mellitus Periodontal Disease

Negative Maternal and Fetal Outcomes

Combined Effect

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Periodontal Variable

Adverse pregnancy outcomes

n=130

No adverse pregnancy outcomes

n=176

P- value (Wilcoxon test)

Plaque index 056 (019) 053 (017) 008

Probing depth 28 (051) 27 (056) 001

Clinical attachment loss

063 (055) 062 (055) 084

Calculus (0-3) 044 (037) 039 (037) 017

Bleeding (0-3) 036 (030) 033 (031) 007

Case Control Comparison

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Periodontal Variable

GDM + n=153

GDM ndash n=153

(P- value) (Wilcoxon

test)

Plaque index 055 (017) 053 (019) 026

Probing depth 28 (057) 27 (049) 008

Clinical attachment loss

066 (056) 058 (054) 021

Calculus (0-3) 044 (037) 039 (037) 020

Bleeding (0-3) 037 (031) 032 (030) 021

Case Control Comparison

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Conclusions bull Probing pocket depth independent of GDM

status was a significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Odds Ratios for Adverse Fetal Outcomes

Contrasts for PD and GDM status Odds Ratio 95 CI

PD+ GDM+ vs PD- GDM- 142 064 314

PD+ GDM+ vs PD- GDM+ 147 066 327

PD+ GDM+ vs PD+ GDM- 119 058 242

Multivariable logistic regression GEE adjusted for smoking and calculus Variables used for matching were not used as covariates in the GEE matched analysis regression

modeling These included age raceethnicity and gestational age at enrollment

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Conclusion bull Women in this study with the combination of GDM

plus periodontal disease had

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Conclusions bull Women in this study with the combination of GDM

plus periodontal disease had

ndash a 23-fold greater risk for developing adverse maternal outcomes than women with either GDM or periodontal disease alone bull Probing pocket depth independent of GDM status was a

significant predictor of adverse pregnancy outcomes (p=001)

bull Bleeding on probing was related to adverse pregnancy outcomes (p=007)

bull GDM status was related to probing pocket depth (p=008)

ndash no greater risk for adverse fetal outcomes than women with either GDM or periodontal disease alone

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Exploring the possible biology of an oral-systemic link

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

ldquoOral health is integral to general healthrdquo

A ldquosilent epidemic of oral diseases is affecting our most vulnerable citizensrdquo

Oral Health in America

A Report of the Surgeon General

2000

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Associations between oral and systemic conditions

bull type 2 diabetes

bull preterm birth

bull coronary heart disease atherosclerosis stroke

bull Alzheimerrsquos disease

bull chronic obstructive pulmonary disease

bull acute respiratory infections

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

How could periodontal disease contribute to systemic

conditions

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Defining periodontal disease

bull An inflammatory disease that is initiated by the

accumulation of Gram-negative bacteria around the

teeth and gums

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Potential mechanisms

bull Dissemination of periodontal infection

bull Dissemination of periodontal inflammation

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Is there evidence that periodontal bacteria play a major role

bull ldquoGuilt by associationrdquo

ndash Periodontal bacteria rarely found in systemic organs

ndash Case of fetal demise due to oral Fusobacterial infection extremely rare

ndash No cases of stroke or myocardial infarction due to periodontal infection

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Letrsquos look at inflammation as a potential culprit

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Inflammation

bull Initiates the host response to challenge

bull Brings immune cells and molecules to the site of challenge

bull A tightly regulated mechanism

bull When dysregulated leads to pathology

ndash Genetic (polymorphisms in gene structure)

ndash Environmental (smoking stress diet)

ndash Systemic (obesity type 2 diabetes hormonal)

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Including

Periodontal disease

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Periodontal disease and systemic disease

bull Risk indicator or risk factor

ndash Risk indicator ndash periodontal disease and the systemic condition share common etiologies

ndash Risk factor ndash oral infectioninflammation contributes to the genesis of the systemic condition Remove periodontal disease and the systemic condition improves

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

What is the evidence

bull Cross sectional studies

ndash periodontal disease may be a risk indicator for systemic inflammatory conditions in certain populations

bull Prospective multi-center randomized controlled intervention studies

ndash failed to show a causal effect suggesting that periodontal disease is not a risk factor for systemic disease

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

What is the answer

bull Periodontitis and systemic inflammatory conditions have complex etiologies

bull Influenced by

ndash Socio-economic status

ndash Lifestyle choicesbehaviors

bull Diet stress smoking drug abuse

ndash Genetics family history a good predictor

bull Infection

bull Inflammation

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

The answer may lie in complex interactions between multiple components of susceptibility This may make it very difficult to show a direct causal relationship between periodontal disease and systemic conditions

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

Thank you

KarenFNovakuthtmcedu

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422

References Dasanayake AP1 Chhun N Tanner AC Craig RG Lee MJ Moore AF Norman RG J Dent Res 2008 Periodontal pathogens and gestational diabetes mellitus 2008 Apr87(4)328-33 Xiong X1 Elkind-Hirsch KE Vastardis S Delarosa RL Pridjian G Buekens P Periodontal disease is associated with gestational diabetes mellitus a case-control study J Periodontol 2009 Nov80(11)1742-9 Ruiz DR1 Romito GA Dib SA Periodontal disease in gestational and type 1 diabetes mellitus pregnant women Oral Dis 2011 Jul17(5)515-21 Xiong X Elkind-Hirsch KE Xie Y Delarosa R Maney P Pridjian G Buekens P Periodontal disease as a potential risk factor for the development of diabetes in women with a prior history of gestational diabetes mellitus J Public Health Dent 2013 Winter73(1)41-9 Michalowicz BS Hodges JS DiANgelis AJ Lupo VR Novak MJ Ferguson JE et al Treatment of periodontal disease and the risk of preterm birth N Engl J Med 2006 3551885-94 Offenbacher S Beck JD Jared HL Maaureilllo SM Mendoza LC Couper DJ et al Effects of periodontal therapy on rate or preterm delivery a randomized controlled trial Maternal Oral Therapy to Reduce Obstetric Risk (MOTOR) Investigators Obstet Gynecol 2009 114551-9 Committee on Health Care for Underserved Women Committee Opinion Oral health care during pregnancy and through the lifespan 2013 122417-422