Volume 81 Number 4

A Cohort Study on the Association

Between Periodontal Disease and the
Development of Metabolic Syndrome
Toyoko Morita,* Yoji Yamazaki, Ayae Mita, Koji Takada, Misae Seto, Norihide Nishinoue,
Yoshiyuki Sasaki, Masafumi Motohashi,* and Masao Maeno*

Background: An association between periodontal disease

and metabolic syndrome based on cross-sectional and case-
control studies was recently reported, but their causal relation-
ship has not been fully clarified. The objective of this cohort
study is to investigate the association between periodontal dis-
ease and changes in metabolic-syndrome components to ac-
cumulate evidence of the causal relationship between the two

M
etabolic syndrome is a complex
conditions. collection of components that
Methods: The study subjects consisted of 1,023 adult em- are thought to arise from a vis-
ployees (727 males and 296 females; mean age: 37.3 years) ceral fat-type obesity involving hyper-
who underwent medical and dental checkups between 2002 tension and abnormal glucose and lipid
and 2006 and in whom all metabolic-syndrome components metabolism. Preventing metabolic syn-
were within the standard values in 2002. The association be- drome is of great medical importance
tween the presence of periodontal pockets and the positive because the presence of multiple com-
conversion of metabolic-syndrome components was investi- ponents increases the risk of develop-
gated using multiple logistic-regression analysis, odds ratios ing cardiovascular disease.1,2 Numerous
(ORs), and 95% confidence intervals (CIs). studies3-13 linked periodontal disease with
Results: The presence of periodontal pockets was associ- several serious risk factors for metabolic
ated with a positive conversion of one or more metabolic com- syndrome, including type 2 diabetes,3,4
ponents during the 4-year observation period (OR: 1.6; 95% obesity among community residents,5,6
CI: 1.1 to 2.2). The ORs for a positive conversion of one com- lipid abnormalities in patients with peri-
ponent and two or more components were 1.4 (95% CI: 1.0 to odontal disease7-11 and community res-
2.1) and 2.2 (95% CI: 1.1 to 4.1), respectively, and the differ- idents,12 and elevated blood-pressure
ence was significant for two or more positive components. Of levels.13 Studies on the association be-
the metabolic-syndrome components, positive conversions of tween periodontal disease and meta-
blood pressure and the blood-lipid index were significantly as- bolic syndrome in Japanese-community
sociated with the presence of periodontal pockets. residents and adults in Northern Jordan
Conclusion: The presence of periodontal pockets was asso- and China14-16 and analysis of results
ciated with a positive conversion of metabolic-syndrome com- from the United States National Health
ponents, suggesting that preventing periodontal disease may and Nutrition Examination Survey III17
prevent metabolic syndrome. J Periodontol 2010;81:512-519. were reported, and Morita et al.18 de-
scribed the association in industrial
KEY WORDS
workers. Previous studies14-18 of the as-
Cohort study; hyperglycemia; hypertension; lipid sociation of periodontal disease and meta-
metabolism; obesity; periodontal disease. bolic syndrome were cross-sectional or
case-control studies. The results pro-
* Department of Oral Health Sciences, Nihon University School of Dentistry, Tokyo, Japan. vided by these study designs is relatively
The Lion Foundation for Dental Health, Tokyo, Japan.
Health Care Center, Lion Corporation, Tokyo, Japan. weaker than in cohort studies.
Center for Education and Research in Oral Health Care, Faculty of Dentistry, Tokyo Elevated blood levels of inflammatory
Medical and Dental University, Tokyo, Japan.
markers, such as C-reactive protein (CRP)
and interleukin (IL)-6 were reported in
patients with periodontal disease,19,20

doi: 10.1902/jop.2010.090594

512
J Periodontol April 2010
suggesting that periodontal disease is a mild chronic
inflammatory disease affecting the systemic condi-
tion.21,22 Aggravation of glucose tolerance in people
with deep periodontal pockets was also shown
epidemiologically, suggesting that infection with
periodontal disease pathogens enhances tumor ne-
crosis factor-alpha (TNF-a) production, induces the
prediabetic condition, and leads to abnormal glucose
tolerance.23
Furthermore, negative influences by lipopolysac-
charide (LPS) and cytokines produced by inflamma-
tion, such as TNF-a and IL-1, on lipid metabolism
were reported,24 suggesting that Gram-negative an-
aerobe-induced periodontal disease has some influ-
ence on lipid metabolism.
Considering these findings, it is possible that peri-
odontal disease increases the risk of developing
metabolic syndrome as a Gram-negative anaerobe-
induced mild chronic inflammatory disease. The aim
of this cohort study is to evaluate the influence
of periodontal disease on the development of meta-
bolic syndrome in industrial workers. In this study,
exposure was the presence of a periodontal pocket
4 mm, and the outcome was a positive conversion
of metabolic-syndrome components.
MATERIALS AND METHODS
The subjects were industrial employees of a company
that manufacturers household products in Tokyo,
Japan. The subjects underwent periodic health and
dental checkups that were independently performed
by a health-insurance association in 2002 and 2006.
In 2002, 99.9% of the employees underwent systemic
medical checkups, 88.4% of them had dental exami-
nations, and 2,796 received both checkups. There
were 2,078 employees who had checkups in 2002
and 2006 and gave written informed consent to partic-
ipate in the present study. The study subjects included
1,023 industrial workers in whom all components of
metabolic syndrome were within the standard values
at baseline in 2002 (727 males and 296 females; age
range: 20 to 56 years; mean age: 37.3 years). The re-
maining 1,055 workers were excluded from the study
because one or more metabolic syndrome compo-
nents were not within standard values in 2002.
The presence of periodontal disease at the initiation
of follow-up was assessed according to the criteria of
the World Health Organization (WHO) Community
Periodontal Index (CPI) criteria.25 Dental hygienists
(AM et al.) examined 10 representative teeth in six
sextants under the supervision of dentists (Yoko
Ogawa et al.). Oral examinations were carried out us-
ing standard WHO probes after calibration of the pres-
sure (<20 g) of the probe using a sensor probe. The
subjects were divided into two groups: individuals with
CPI codes 2 (without a periodontal pocket) and the
Morita, Yamazaki, Mita, et al.
other individuals with at least one sextant with a CPI
code 3 (periodontal pocket 4 mm), and their re-
lationships with the positive conversion of each
metabolic-syndrome component were analyzed.
Additionally, oral examination was carried out by
dentists to assess dental caries experience and
periodontal disease excluding third molars. Blood
pressure was measured with an automatic hemoman-
ometer while the patients were in a sitting position.
Blood pressure was measured twice for only those
subjects with an abnormal value at the first measure-
ment. The data of blood pressure used in the present
study were based upon the first measurement only for
consistency in data collection across subjects. After
fasting from 9:00 pm to the following morning, blood
samples were collected from an arm vein. Triglycer-
ide, high-density lipoprotein (HDL) cholesterol, total
cholesterol, and fasting blood glucose levels were
measured from these samples. The body mass index
(BMI) was calculated from the heights and body
weights of each participant. The test values of hyper-
tension, lipid abnormality, and hyperglycemia were
based on the definition and diagnostic criteria for met-
abolic syndrome in Japan;26,27 a 130-mm/Hg sys-
tolic or 85-mm/Hg diastolic blood pressure was
equated with hypertension, 150 mg/dl triglycerides
or <40 mg/dl HDL cholesterol was considered an
abnormal lipid profile, and 110 mg/dl fasting blood
glucose was deemed positive for hyperglycemia. A
BMI 25 kg/m2 was regarded as positive for a meta-
bolic disorder. The health habits described by Belloc
and Breslow28 were surveyed using a self-completed
questionnaire. The items on the questionnaire were:
Do you have a smoking habit?, Are you doing phys-
ical exercise regularly?, and Are you controlling con-
sumption of food between meals? Subjects answered
the questions by selecting yes or no. Periodontal
pockets, age, gender, and smoking habit were deter-
mined at the baseline of the observational period.
This study was approved by the ethics committee
of the Nihon University School of Dentistry.
Statistical Methods
Multiple logistic regression analysis was used to eval-
uate the association between the presence of peri-
odontal pocket and the number of positively changed
components during 4 years (positive components)
and between the presence of periodontal pocket and
positive components. Dependent variable was the
positivity of each component and explanatory vari-
ables were the presence of periodontal pockets, carious
teeth, and missing teeth representing the oral condi-
tion in 2002. Odds ratios (ORs) and confidence intervals
(CIs) were calculated with adjustments for age, gen-
der, cigarette smoking, exercise, eating between
meals, and the maintenance of a healthy body weight
513
Cohort Study on Periodontal Disease and Metabolic Syndrome
in 2002. Statistical analysis softwarei Table 1.
was used, and the significance level
Association Between One or More Positivity of Metabolic-
was set at 5%.
Syndrome Components in 2006 and Oral Condition in 2002
RESULTS
Prevalence of Periodontal Pockets
and Subject Characteristics at
Baseline of Follow-Up Oral Condition
The CPI score was 2 (no periodontal in 2002
pocket) in 818 subjects (68.0%
male) and 3 (with periodontal Periodontal pockets
Without pockets
pockets) in 205 subjects (83.4%
With pockets
male). The average age of subjects
with the presence or absence of peri- Missing teeth
odontal pockets was 42.2 9.0 years None
and 36.1 8.5 years, respectively. One or more
The cigarette-smoking rate of sub- Carious teeth
jects with the presence or absence None
of periodontal pockets was 42% and One or more
28.6%, respectively. Age, gender, * Adjusted for age, gender, smoking habit, exercise, eating between meals, and healthy body weight.
and cigarette-smoking rate were sig- P <0.05.
nificantly associated with the pres-
ence of periodontal pockets (P <0.05).
Association Between Positive Conversion
of Metabolic-Syndrome Components and
Oral Condition
Table 1 shows the association between positivity of
one or more metabolic syndrome components and
oral conditions. Table 2 shows the association be-
tween each number of metabolic syndrome compo-
nents and oral conditions. The rate of subjects with
periodontal pockets in 2002 was higher in those with
many positive components in 2006. The OR of sub-
jects with periodontal pockets in 2002 who became
positive for metabolic-syndrome components after
4 years was 1.6 (95% CI: 1.1 to 2.2) higher (P <0.05)
than those with no periodontal pockets (Table 1).
The OR of subjects with periodontal pockets who be-
came positive for one component was 1.4 (95% CI:
1.0 to 2.1), and the OR of subjects who became pos-
itive for two or more components was 2.2 (95% CI: 1.1
to 4.1), showing that the OR rose as the number of
positive components increased, and the difference
was significant for two or more positive components
(Table 2). There was no association between the
presence of missing or carious teeth with a positive
conversion of metabolic-syndrome components.
Association Between Positive Conversion of Each
Metabolic-Syndrome Component and Oral
Condition
The association between changes in individual meta-
bolic-syndrome components after 4 years and oral
condition is shown in Tables 3 through 6. The indi-
ces of obesity, hypertension, lipid abnormality, and
hyperglycemia were positive after 4 years in 73
514
Volume 81 Number 4
Subjects in 2006 (n [%])
No Positive One or More
Components Positive Components
(n = 788 [77.0%]) (n = 235 [23.0%]) OR (95% CI)*
656 (80.2) 162 (19.8) 1
132 (64.4) 73 (35.6) 1.6 (1.1 to 2.2)
656 (78.2) 183 (21.8) 1
132 (71.7) 52 (28.3) 1.0 (0.6 to 2.0)
739 (77.1) 219 (22.9) 1
49 (75.4) 16 (24.6) 1.1 (0.7 to 1.6)
(7.1%), 140 (13.7%), 69 (6.7%), and 10 (1.0%) sub-
jects, respectively. The positive conversions of hy-
pertension and lipid abnormality after 4 years were
significantly associated with the presence of peri-
odontal pockets. There was no significant association
between positive conversions of obesity and hyper-
glycemia and the presence of periodontal pockets,
but there was a tendency toward an association with
obesity (P = 0.056). The presence of missing or cari-
ous teeth was not associated with the positive con-
version of any index of obesity, hypertension, lipid
abnormality, or hyperglycemia.
DISCUSSION
We previously performed a cross-sectional study18 in
Japanese adult male and female employees (age
range: 20 to 59 years) and found that individual com-
ponents of metabolic syndrome (i.e., obesity, hyper-
tension, lipid abnormality, and hyperglycemia) were
associated with periodontal disease. We also clarified
that the OR of having periodontal pockets markedly
rose as the number of positive metabolic-syndrome
components increased, showing that the risk for peri-
odontal disease increased as the number of positive
metabolic-syndrome components increased.18 In
the present study, we investigate whether the presence
of periodontal pockets influences the development of
metabolic syndrome after 4 years in subjects in whom
all metabolic-syndrome components were within
standard values in 2002. In this study, we analyze data
obtained from employees of one company; therefore,
we must be careful when generalizing the results.
i JMP, SAS Institute, Tokyo, Japan.
J Periodontol April 2010 Morita, Yamazaki, Mita, et al.

Table 2.
Association Between Each Number of Positive Components of Metabolic Syndrome
in 2006 and Oral Condition in 2002

Subjects in 2006 (n [%]) OR (95% CI)*

No Positive One Positive Two Positive Three Positive One Two or More
Oral Condition Components Component Components Components Positive Positive
in 2002 (n = 788 [ 77.0%]) (n = 186 [18.2%]) (n = 41 [4.0%]) (n = 8 [0.8%]) Component Components

Periodontal pockets
Without pockets 656 (80.2) 132 (16.1) 27 (3.3) 3 (0.4) 1 1
With pockets 132 (64.4) 54 (26.3) 14 (6.8) 5 (2.5) 1.4 (1.0 to 2.1) 2.2 (1.1 to 4.1)
Missing teeth
None 656 (78.2) 146 (17.4) 30 (3.6) 7 (0.8) 1 1
One or more 132 (71.7) 40 (21.7) 11 (6.0) 1 (0.6) 1.0 (0.6 to 1.5) 1.2 (0.4 to 3.6)
Carious teeth
None 739 (77.1) 174 (18.2) 37 (3.9) 8 (0.8) 1 1
One or more 49 (75.4) 12 (18.5) 4 (6.1) 0 (0) 1.3 (0.4 to 3.6) 1.1 (0.5 to 2.1)
* Adjusted for age, gender, smoking habit, exercise, eating between meals, and healthy body weight.
P <0.05.

Table 3. levels of triglycerides, HDL cholesterol,

Association Between Obesity in 2006 and Oral blood pressure, and fasting blood
Condition in 2002 glucose as those with metabolic syn-
drome.29 This definition is not obesity
based because the presence of non-
Subjects in 2006 (n [%])
obese cases with insulin resistance
Oral Condition Non-Obese Obese OR and other metabolic risk factors was
in 2002 (n = 950 [92.9%]) (n = 73 [ 7.1%]) (95% CI)* recognized, and placing special empha-
sis on a single pathology, visceral obe-
Periodontal pockets
sity, was considered inadequate. We
Without pockets 767 (93.8) 51 (6.2) 1
With pockets 183 (89.3) 22 (10.7) 1.7 (1.0 to 3.0) considered obesity as an index to in-
vestigate whether the presence of peri-
Missing teeth odontal pockets was associated with
None 779 (92.9) 60 (7.1) 1 the development of metabolic syn-
One or more 171 (92.9) 13 (7.1) 1.2 (0.6 to 2.3) drome and surveyed positive conver-
Carious teeth sions of obesity, hypertension, lipid
None 891 (93.0) 67 (7.0) 1 abnormality, and hyperglycemia to in-
One or more 59 (90.8) 6 (9.2) 1.3 (0.5 to 3.0) vestigate their associations with peri-
* Adjusted for age, gender, smoking habit, exercise, eating between meals, and healthy body odontal disease. The BMI was adopted
weight. as the obesity index because the waist-
circumference measurement specified
However, >3,000 employees work for the company, in- for metabolic syndrome was not performed on health
dicating that the data may be generalized in terms of checkups in 2002 and 2006. The metabolic-syn-
industrial workers. drome criteria26,27 regard conditions with three or
Metabolic syndrome was defined as an obesity more positive components as metabolic syndrome,
(waist circumference)-based condition with three or but subjects with two or more positive components
more of the following conditions: obesity, hypertension, were collectively handled in the analysis because
lipid abnormality, and hyperglycemia in Japan by only 0.8% of subjects became positive for three or
the Japanese Society of Internal Medicine in 2005;26,27 more components, whereas 18.2% and 4.0% became
whereas the American Heart Association and United positive for one and two components, respectively.
States National Heart, Lung, and Blood Institute re- The positive rate for any one of the metabolic-
gard persons with three or more of the following con- syndrome components was significantly higher in
ditions: obesity (waist circumference) and abnormal subjects with periodontal pockets than in subjects

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Cohort Study on Periodontal Disease and Metabolic Syndrome Volume 81 Number 4

Table 4. risk of becoming positive for meta-

bolic-syndrome components is higher
Association Between Hypertension in 2006 and Oral
in subjects with periodontal pockets.
Condition in 2002 Previous cross-sectional14,17,18 and
case-control15,16 studies showed the
Subjects in 2006 (n [%]) presence of a close association be-
Oral Condition Non-Hypertensive Hypertensive OR tween periodontal disease and meta-
in 2002 (n = 883 [86.3%]) (n = 140 [13.7%]) (95% CI)* bolic syndrome, and that patients with
metabolic syndrome may be at a higher
Periodontal pockets risk for periodontal disease. Further-
Without pockets 726 (88.8) 92 (11.3) 1
more, the present cohort study sug-
With pockets 157 (76.6) 48 (23.4) 1.5 (1.0 to 2.3)
gests that people with periodontal
Missing teeth pockets are at a higher risk for devel-
None 736 (87.7) 103 (12.3) 1 oping metabolic syndrome even when
One or more 147 (79.9) 37 (20.1) 1.3 (0.8 to 2.0) all metabolic-syndrome components
Carious teeth are within standard values. Periodontal
None 826 (86.2) 132 (13.8) 1 disease is considered a mild chronic
One or more 57 (87.7) 8 (12.3) 1.1 (0.5 to 2.7) inflammatory condition caused by
* Adjusted for age, gender, smoking habit, exercise, eating between meals, and healthy body
Gram-negative anaerobes inhabiting
weight. periodontal pockets,21,22 and the ele-
P <0.05. vation of the blood levels of cytokines,
such as CRP and IL-6, has been
reported.19,20 These inflammatory
Table 5.
substances induced by periodontal
Association Between Lipid Abnormality in 2006 disease may influence the whole
and Oral Condition in 2002 body and act toward the positive
conversion of metabolic-syndrome
Subjects in 2006 (n [%]) components. In contrast, a report33
found that the level of CRP increases
No Lipid With Lipid in the person with the metabolic
Oral Condition Abnormality Abnormality syndrome. Therefore, an increase
in 2002 (n = 954 [93.3%]) (n = 69 [6.7%]) OR (95% CI)* of CRP due to periodontitis is related
Periodontal pockets to the progression of the metabolic
Without pockets 774 (94.6) 44 (5.4) 1 syndrome.
With pockets 180 (87.8) 25 (12.2) 1.9 (1.1 to 3.2) Positive conversions of hyperten-
sion and lipid abnormality were
Missing teeth
significantly associated with the
None 782 (93.2) 57 (6.8) 1
One or more 172 (93.5) 12 (6.5) 1.4 (0.7 to 2.9) presence of periodontal pockets.
Negative influences of a Gram-nega-
Carious teeth tive bacterial cell component, LPS,
None 893 (93.2) 65 (6.8) 1 and cytokines, such as TNF-a and
One or more 61 (93.9) 4 (6.2) 1.3 (0.5 to 4.3) IL-1, on lipid metabolism were re-
* Adjusted for age, gender, smoking habit, exercise, eating between meals, and healthy body weight. ported,24 suggesting that the OR for
P <0.05.
the development of lipid abnormality
increases through these substances
without periodontal pockets in 2002 (OR: 1.6), even af- in subjects with periodontal pockets. Although an as-
ter adjustments for age, gender, and habits (cigarette sociation between hypertension and periodontal dis-
smoking, exercise, eating between meals, and the ease was reported,34 the reason for this association
maintenance of a healthy body weight). 18,30-32 These has not been clarified. However, thrombus formation
findings indicate that the maintenance of a healthy caused by Porphyromonas gingivalis from aggregat-
oral cavity to prevent periodontal pocket formation ing platelets,35 the elevation of risks of hypertension
is effective for maintaining metabolic-syndrome com- and coronary arterial heart disease because of an el-
ponents within standard values. After 4 years, the OR evated CRP level,36-38 and elevated CRP levels in pa-
rose as the number of positive components increased, tients with periodontal disease19,21 were reported. It is
and the difference was significant for two or more pos- quite possible that periodontal disease influences the
itive components (OR: 2.2), thus clarifying that the development of hypertension through inflammatory

516
J Periodontol April 2010
Table 6.
Association Between Hyperglycemia in 2006 and Oral
Condition in 2002
Subjects in 2006 (n[%])
Oral Condition Non-Hyperglycemic Hyperglycemic
in 2002 (n = 1,013 [99.0%]) (n = 10 [1.0%])
Periodontal pockets
Without pockets 810 (99.0)
With pockets 203 (99.0)
Missing teeth
None 832 (99.2)
One or more 181 (98.4)
Carious teeth
None 950 (99.2)
One or more 63 (96.9)
* Adjusted for age, gender, smoking habit, exercise, eating between meals, and healthy body
weight.
substances, such as CRP, which supports our finding
that the presence of periodontal pockets increases the
risk of developing hypertension.
In contrast, there was no significant association
between the presence of periodontal pockets and a
positive conversion of obesity or hyperglycemia, but
obesity showed a tendency toward an association
(P = 0.056); P value was approximated to P = 0.05.
It was reported that LPS stimulated fat deposition in
the liver and adipose tissue in mice, which led to
a weight increase.39 This result and our findings sug-
gest that periodontal disease affects obesity. A re-
duction in blood glucose levels after periodontal
treatment in patients with diabetes was reported in
studies40,41 on periodontal disease and diabetes inter-
vention. The OR for subjects with periodontal pockets
becoming hyperglycemic was 1.4, but the association
was not significant. In the 2006 National Nutrition Sur-
vey,42 the rate of people between 20 and 69 years of
age strongly suspected of having diabetes and in
whom the possibility of diabetes could not be ruled
out increased with advancing age, and the difference
between age groups classified as patients with and
suspected of having diabetes for 10 years was 3.0%
to 9.5%. However, the rate of subjects who became
positive for hyperglycemia within the next 4 years
was only 1% of all subjects, and this may have been
the reason for the absence of a significant difference.
The present study shows that adult employees,
ranging in age from 20 to 56 years, with periodontal
pockets were at a higher risk for the positive conver-
sion of metabolic-syndrome components. Accord-
ingly, the prevention of periodontal disease may
consequently prevent metabolic syndrome, and the
maintenance of a healthy oral cavity from a young
Morita, Yamazaki, Mita, et al.
age may be important to maintain
the health of the entire body. How-
ever, there is a limitation for the find-
ings of this study. Periodontal disease
and metabolic syndrome are con-
sidered to be related to a complex
lifestyle. To exclude confounding
OR (95% CI)* factors, habits (cigarette smoking,
exercise, eating between meals,
and the maintenance of a healthy
8 (1.0) 1
body weight) that are assumed
2 (1.0) 1.4 (1.0 to 2.1)
to affect periodontal disease and
metabolic syndrome18,30-32 were
7 (0.8) 1 adopted for adjustment, in addition
3 (1.6) 1.0 (0.6 to 1.5) to age and gender. However, it can-
not be ruled out that habits not in-
8 (0.8) 1 vestigated in this study may affect
2 (3.1) 4.6 (0.7 to 20.6) metabolic syndrome. Interventional
studies on periodontal treatment-in-
duced changes in the condition of
metabolic syndrome in patients with
periodontal disease and metabolic syndrome may be
necessary to further clarify the causal relationship be-
tween periodontal disease and metabolic syndrome.
CONCLUSION
The presence of periodontal pockets was associated
with positive conversions of metabolic-syndrome
components, suggesting that the prevention of peri-
odontal disease consequently prevents metabolic
syndrome.
ACKNOWLEDGMENTS
This work was supported by the Promotion and Mutual
Aid Corporation for Private Schools of Japan,Tokyo,
Japan. The authors report no conflicts of interest re-
lated to this study.
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Correspondence: Dr. Masafumi Motohashi, Department of
Oral Health Sciences, Nihon University School of Dentistry,
1-8-13 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310,
Japan. Fax: 81-3-3219-8138; e-mail: motohashi@dent.
nihon-u.ac.jp.
Submitted October 23, 2009; accepted for publication
December 11, 2009.
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