periodontal inflammatory conditions among smokers and never-smokers with and without type 2 diabetes...

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Periodontal inflammatory conditions among smokers and

never-smokers with and without type 2 diabetes mellitus

Journal: Journal of Periodontology

Manuscript ID: JOP-15-0120.R1

Manuscript Type: Original Article

Date Submitted by the Author: n/a

Complete List of Authors: Javed, Fawad; University of Rochester, Division of General Dentistry; Al-Kheraif, Abdulaziz A.; King Saud University, Applied Medical Sciences Lazo, Karem Salazar; University of Rochester, General Dentistry Fontenla, Virginia Yanez; University of Rochester, General Dentistry Aldosary, Khaled; King Saud University, Division of Restorative Dentistry Alshehri, Mohammed; King Saud University, Division of Restorative and

Implant Dentistry Malmstrom, Hans; University of Rochester, General Dentisry Romanos, Georgios; Stonybrook,

Key Words: Periodontal-systemic disease interactions, Smoking, Diabetes

Journal of Periodontology

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Title: Periodontal inflammatory conditions among smokers and never-smokers with and

without type 2 diabetes mellitus

Authors: Fawad Javed,* Abdulaziz A. Al-Kheraif,

† Karem Salazar Lazo,

* Virginia Yanez

Fontenla,* Khalid M. Aldosary,

‡ Mohammed Alshehri,

‡ Hans Malmstrom,

* Georgios E.

Romanosǁ

Affiliations:

* Division of General Dentistry, Eastman Institute for Oral Health, University of Rochester,

Rochester, NY;

† Dental Biomaterials Research Chair, Dental Health Department, College of Applied Medical

Sciences; King Saud University, Riyadh, Saudi Arabia;

‡ Dental Department, King Khalid University Hospital, King Saud University, Riyadh, Saudi

Arabia;

§ Department of Periodontology, School of Dental Medicine, Stony Brook University, NY.

Running title: Periodontal inflammation, smoking and T2DM

One sentence summary: Periodontal inflammatory conditions are comparable among smokers

and never-smokers with T2DM. Among controls, periodontal inflammation is worse among

smokers than never-smokers.

Correspondence: Dr. Fawad Javed, Division of General Dentistry, Eastman Institute for Oral

Health, University of Rochester, Rochester, NY 14642, USA. Email:

[email protected]

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ABSTRACT

Background: There is a dearth of studies regarding the influence of cigarette smoking on

periodontal inflammatory conditions among patients with type 2 diabetes mellitus (T2DM). The

aim of the present study was to assess periodontal inflammatory conditions among smokers and

never-smokers with and without T2DM.

Methods: One hundred individuals (50 patients with T2DM [25 smokers and 25 never-smokers]

and 50 controls [25 smokers and 25 never-smokers]) were included. Information regarding age,

gender, duration and daily frequency of smoking, duration and treatment of diabetes and oral

hygiene was recorded using a questionnaire. Periodontal parameters (plaque index [PI], bleeding

on probing [BOP], probing depth [PD], clinical attachment [CA] loss and marginal bone loss

[MBL]) were measured. Hemoglobin A1c (HbA1c) levels were also recorded.

Results: Mean age, monthly income status and education levels were comparable among

smokers and never-smokers with and without T2DM. Mean HbA1c Levels were significantly

higher among patients with T2DM (8.2±0.1%) compared to controls (4.4±0.3%) (P<0.05).

Smokers in the control group were smoking significantly greater number of cigarettes (15.5±2.5

cigarettes daily) compared to smokers with T2DM (6.2±2.1 cigarettes daily) (P<0.05).

Periodontal parameters were comparable among smokers and never-smokers with T2DM.

Among controls, periodontal parameters (PI [P<0.05], CA loss [P<0.05], PD≥4mm [P<0.05] and

MBL [P<0.05]) were significantly higher in smokers than never smokers. Never-smokers with

T2DM had worse periodontal status than smokers and never-smokers in the control group

(P<0.05).

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Conclusion: Periodontal inflammatory conditions are comparable among smokers and never-

smokers with T2DM. Among controls, periodontal inflammation is worse among smokers than

never-smokers.

Key words (MeSH): Alveolar bone loss; Bleeding on probing; Cigarette smoking; Dental

plaque; Inflammation; Type 2 Diabetes Mellitus;


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INTRODUCTION

It is well-established that chronic hyperglycemia is a significant risk factor for

periodontal inflammatory conditions.1-4

Studies3, 5, 6

have shown that clinical parameters of

periodontal inflammation (such as plaque index [PI], bleeding on probing [BOP], probing depth

[PD]≥4mm and clinical attachment [CA] loss are worse among patients with poorly-controlled

type 2 diabetes mellitus (T2DM) as compared to systemically healthy individuals (controls).

Moreover, marginal bone loss (MBL) around teeth, a radiographic marker of periodontal

inflammation is also higher among patients with poorly-controlled T2DM than controls.3, 7

An

explanation that has been posed in this regard is that persistent hyperglycemia increases the

formation and accumulation of advanced glycation endproducts (AGEs) in periodontal tissues,

which in turn impairs the chemotactic and phagocytic function of polymorphonuclear leukocytes

(PMNL) and produces proinflammatory cytokines in the serum and gingival crevicular fluid.8, 9

This leads to periodontal inflammation and MBL in patients with T2DM. Furthermore, function

of potential cells involved in immunoinflammatory responses is also sabotaged in a chronic

hyperglycemic state.10

The deleterious effects of tobacco smoking on oral and systemic health are well

documented.11-15

Habitual tobacco smoking has also been associated with an increased

expression of receptors of AGEs in the gingival tissues.16

This in turn jeopardizes the

chemotactic and phagocytic functions of PMNL and provokes a proinflammatory effect by

stimulating the secretion of cytokines and reactive oxygen species that directly cause destruction

of periodontal tissues.17-20

Clinical studies3, 14, 21

have also shown that habitual tobacco smokers

exhibit greater number of sites with plaque accumulation, CA loss and PD (≥ 4mm) as compared

to individual who had never used tobacco in any form. It is however, important to mention that


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BOP (a classical marker of periodontal disease activity22

), is masked in tobacco smokers than

never-smokers.3, 21

This most probably occurs as a result of the vasoconstrictive effect of

nicotine on gingival blood vessels.23

Therefore, tobacco smokers may remain unaware of

ongoing periodontal destruction until the inflammatory process reaches a stage where tooth

mobility becomes evident.

Since chronic hyperglycemia and habitual tobacco smoking are significant and

independent risk factors of periodontal disease;3, 21

it is hypothesized that periodontal

inflammatory conditions are more intense among smokers with T2DM as compared to never-

smokers with T2DM. Therefore, the aim of the present study was to assess the periodontal

inflammatory conditions among smokers and never-smoker with and without T2DM.

MATERIALS AND METHODS

Ethical guidelines

The study was approved by the Research Ethics Review committee of the College of

Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia (OR-114-2084). It was

mandatory for all study participants to have read and signed the consent form before being

included in the present investigation.

Eligibility Criteria

The inclusion criteria encompassed the following: (a) Patients with medically diagnosed

T2DM (HbA1c ≥ 6.5%)24

; (b) self-reported controls. The exclusion criteria were: (a) Individuals


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with self-reported systemic diseases other than T2DM (such as human immunodeficiency virus

infection/acquired immunodeficiency syndrome, cardiovascular diseases, renal disease, hepatic

disorder and epilepsy); (b) edentulous individuals; (c) crowding of teeth or occlusal trauma; (d)

habitual alcohol consumers; (e) lactating and/or pregnant individuals; (f) individuals who

reported to have consumed antibiotics, non-steroidal anti-inflammatory drugs and/or steroids

within the past three months; (g) bilateral maxillary and mandibular third molars.

Study participants and groups

Between November 2013 and July 2014, a convenience sample case-control study

involving smokers and never-smokers with and without T2DM was conducted at the College of

Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia. All participants were

recruited from a local residential area in Riyadh, South Arabia. Clinical and radiographic

examinations were performed at the College of Applied Medical Sciences, King Saud

University, Riyadh, South Arabia. All participants who reported to have T2DM were requested

to present their medical records in order to verify the diagnosis of T2DM. Smokers were defined

as individuals who reported to be smoking at least one cigarette daily since at least 1 year.3

Never-smokers were defined as individuals who reported to have never consumed tobacco in any

form.3


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Questionnaire

Information regarding gender, age, socioeconomic status (SES), education status

(graduate level education— post-4 year college degree), duration of smoking, number of

cigarettes smoked daily, duration of T2DM, treatment of T2DM recommended by healthcare

provider/s and daily oral hygiene maintenance protocols were collected using a questionnaire. A

trained interviewer (AAK) presented the questionnaire to all participants.

Clinical periodontal parameters

A calibrated and trained investigator (MA) blinded to the study groups performed the

periodontal clinical examinations. The overall k value for intraexaminer reliability was 0.91.

Full-mouth PI,25

BOP,26

PD27

, and CA loss28

were measured at six sites (mesiobuccal, mid-

buccal, distobuccal, distolingual/palatal, mid-lingual/palatal, and mesiolingual/palatal) on all

maxillary and mandibular teeth. A graded probeǁ was used to measure the probing depth to

nearest millimeter.3 Broken down teeth with embedded roots remnants were excluded.

Radiographic parameter

Full mouth digital bitewing radiographs¶ were taken and were viewed on a calibrated

computer screen# using a software program

**. MBL (defined as the vertical distance from 2 mm

below the cementoenamel junction (CEJ) to the most apical part of marginal bone3) was

measured on all teeth. Surfaces of teeth on which the CEJ or the bone crest were not visible due

to technical reasons (such as dental caries, dental restorations, malocclusion and/or poor


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radiography quality) were excluded. All radiographic assessments were performed by one trained

and calibrated investigator (MA). The overall k value for intraexaminer reliability was 0.89.

Hemoglobin A1c levels

In all groups, HbA1c levels were measured using ion-exchange high-performance liquid

chromatography and expressed as percentages.29

Statistical analysis

Statistical analysis was performed using a software program††

. Clinical and radiographic

periodontal parameters among smokers and never-smokers with and without T2DM were

assessed using one way analysis of variance. Multiple logistic regression analysis was also

performed using a software program††

. This was done evaluate the associations between

periodontal inflammation among smokers and never-smokers with and without T2DM (after

adjustment for tooth brushing habits-confounder). For multiple comparisons, Bonferroni post hoc

adjustment test was used. Power and sample sizes were calculated using a computer software‡‡

.

With inclusion of 50 patients individuals with T2DM [25 smokers and 25 never-smokers] and 50

controls [25 smokers and 25 never-smokers] (assuming a standard deviation of 1.0%), the study

power was estimated to be 85% with a two-sided significance level of 0.05. P-values < 0.05 were

considered statistically significant.


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RESULTS

General Characteristics of the study population

In total, 100 individuals (50 patients with T2DM and 50 controls) were included. All

participants were males. The mean age, monthly income status and education levels were

comparable among smokers and never-smokers with and without T2DM. Among patients with

diabetes, the duration of T2DM was 8.5±1.5 years. Among smokers and never-smokers with

T2DM the mean duration of T2DM was 4.6±1.1 years and 10.2±2.5 years, respectively. The

duration of smoking habit among patients with T2DM and controls was 12.6± 4.8 years and

16.4±5.1 years, respectively. Smokers in the control group were smoking significantly greater

number of cigarettes (15.5±2.5 cigarettes daily) compared to smokers with T2DM (6.2±2.1

cigarettes daily) (P<0.05). Seventy-eight percent individuals with T2DM and 88% controls

reported to brush their teeth once daily. None of the participants either with or without T2DM

reported to have ever used dental floss (Table 1).

Hemoglobin A1c

The mean HbA1c Levels were significantly higher among patients with T2DM

(8.2±0.1%) compared to controls (4.4±0.3%) (P<0.05). There was a statistically significant

difference in the mean HbA1c levels among smokers with (7.8±0.4%) and without T2DM

(4.3±0.1%) (P<0.05) (Table1). The mean HbA1c levels were significantly higher among patients

with T2DM (8.2±0.1%) as compared to never-smokers in the control group (4.5±0.1%) (P<0.05).

There was no statistically significance difference in mean HbA1c levels among smokers and

never-smokers with and without T2DM. Never-smokers with T2DM (8.7±0.2%) had a

significantly higher mean HbA1c Levels than smokers in the control group (4.3±0.1%) (P<0.05).


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Among never-smokers with and without T2DM, the mean HbA1c Levels were 8.7±0.2% and

4.5±0.1%, respectively (P<0.05). All patients with T2DM were prescribed conventional

allopathic medications for the management of hypoglycemia. Most of the individuals with and

without T2DM reported to brush their teeth once a day (Table 1).

Periodontal parameters among smokers and never smokers with and without T2DM

Periodontal parameters (PI [P<0.01], BOP [P<0.01], CA loss [P<0.01], PD≥4mm

[P<0.01] and MBL [P<0.01]) were significantly higher among patients with T2DM than

controls.

Periodontal parameters were significantly higher among smokers with T2DM than

smokers and never-smokers in the control group (PI [P<0.01], BOP [P<0.01], CA loss [P<0.01],

PD≥4mm [P<0.01] and MBL [P<0.01]). Never-smokers with T2DM had worse periodontal

status than smokers and never-smokers in the control group (PI [P<0.05], BOP [P<0.05], CA

loss [P<0.05], PD≥4mm [P<0.05] and MBL [P<0.05]). Among controls, periodontal parameters

(PI [P<0.05], CA loss [P<0.05], PD≥4mm [P<0.05] and MBL [P<0.05]) were significantly

higher in smokers than never-smokers. In the control group, never-smokers demonstrated

significantly greater sites with BOP than smokers (P<0.05). These results are summarized in

Table 2.

Periodontal parameters among smokers and never-smokers with T2DM after stratification for

brushing habits.

Periodontal parameters, PI, BOP, PD≥4mm, CA Loss and the MBL were comparable

among patients with T2DM who brushed their teeth once and twice a day (Figure 1A and 1B).


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Periodontal parameters among smokers and never smokers in the control group after

stratification for brushing habits.

Among individuals who brushed their teeth once and twice daily, PI (P<0.01), PD≥4mm

(P<0.01) and MBL (P<0.01) were significantly higher among smokers than never-smokers.

Never-smokers showed significantly greater number of sites with BOP (P<0.01) than smokers

regardless of their daily tooth brushing frequency (Figure 2A and 2B).

DISCUSSION

The present study was based on the hypothesis that periodontal inflammatory conditions

are worse among smokers with T2DM than never-smokers with T2DM. This was mainly

speculated due to the fact that both hyperglycemia and habitual smoking enhance the formation

and accumulation of AGEs in the periodontal tissues, which jeopardize periodontal health.9

16

Interestingly, in the present study, clinical and radiologic parameters of periodontal inflammation

(PI, BOP, PD [≥4mm], CA loss and MBL, respectively) were comparable among smokers and

never-smokers with T2DM. It is pertinent to note that all individuals with T2DM (smokers and

never-smokers) included in the present investigation had poorly-controlled T2DM (HbA1c

≥6.5%). It is known that persistent hyperglycemia is associated with increased formation and

accumulation of AGEs in the periodontal tissues. Therefore, it is likely that AGEs produced and

accumulated in the periodontal tissues of smokers and never-smokers with T2DM were

comparable. This could be an explanation for the similar periodontal inflammatory parameters

among smokers and never-smokers with T2DM.


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Among controls, PI, PD (≥4mm), CA loss and MBL were worse in smokers than never

smokers; however, sites with BOP were more often manifested in never-smokers as compared to

smokers. These results are in accordance with previous studies.3, 14

A precise mechanism by

which habitual smoking increases periodontal inflammation is poorly understood. However, it

has been reported that smoking induces endothelial dysfunction, which may initiate an

inflammatory response in the vascular walls.30

This inflammatory response is mediated by pro-

inflammatory cytokines (such as IL-6, and tumor necrosis factor alpha) and adhesion

molecules.30

Serum levels of immunoglobulin (Ig) G (particularly IgG2, an important antibody

against gram-negative periodontal microbes), have also been reported to be lower in smokers

than never-smokers, thereby making them more susceptible to develop periodontal disease. 31, 32

It is noteworthy that a suppressed BOP among smokers (most likely due to the vasoconstrictive

effect of nicotine on gingival blood vessels 23

) may make them unaware of the ongoing

periodontal destruction sometimes until the stage where tooth mobility becomes evident (as a

result of profound MBL). It is therefore imperative for healthcare providers to educate patients

about the detrimental effect of smoking on oral health. In addition, routine community-based

smoking awareness programs are also warranted for patient/community education purposes.

It is well-known that advancing age3, poor education status

3 and underprivileged SES

3

are significant risk-factors of periodontal inflammatory conditions. In this regard, these factors

may be considered as confounders while assessing periodontal inflammatory conditions among

smokers and never-smokers with and without T2DM. It is emphasized that in the present study,

mean age, graduate level education (post-four year college degree) status and SES were

comparable in smokers and never-smokers among individuals with and without T2DM. It was

therefore perceived that the only parameter that may have influenced the periodontal


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inflammatory conditions among smokers and never-smokers with and without T2DM was daily

tooth brushing frequency. After stratification of data with reference to daily tooth brushing

protocols (once and twice daily ), it was observed that periodontal parameters (PI, BOP, PD≥4

mm, CA loss and MBL) remained comparable among smokers and never-smokers with T2DM

(Figure 1A and 1B). This outcome also suggests that chronic hyperglycemia seems to be the

most likely factor that influenced periodontal inflammation in patients with T2DM and the role

of smoking in this regard was rather secondary. Among controls, there was no significant

difference in periodontal parameters in patients who either brushed their teeth once or twice daily

(Figure 2A and 2B). These results are in accordance with the study by Attin and Hornecker33

,

which reported that tooth brushing once daily is sufficient to maintain oral health and to prevent

periodontal inflammation.

A limitation of the present study is that all individuals that agreed to participate in the

present investigation were males. Although females were also invited to participate in the present

study; none of them volunteered. It is known that hormonal changes and postmenopausal state

influences periodontal health status. It is therefore likely that female smokers with T2DM in the

postmenopausal phase may exhibit variation in the expression of periodontal disease activity as

compared to male smokers with T2DM.34

Furthermore, in the present study, controls were

smoking almost twice as many cigarettes (~15 cigarettes daily) as compared to patients with

T2DM (~6 cigarettes daily). It is tempting to hypothesize that diabetic smokers who smoke

approximately 15 cigarettes a day may exhibit more intense periodontal inflammation as

compared to never-smokers with T2DM. However, further randomized controlled trials are

warranted to assess a dose-dependent relationship between smoking, periodontal disease and

T2DM.


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CONCLUSION

Periodontal inflammatory conditions are comparable among smokers and never-smokers

with T2DM. Among controls, periodontal inflammation is worse among smokers than never-

smokers.


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LEGENDS

Table 1. Sociodemographic characteristics of the study participants

Table 2. Clinical periodontal status among smokers and never-smokers with and without type 2

diabetes mellitus

Figure 1. (A) Plaque index (dark grey bars), bleeding on probing (light grey bars) and probing

depth (≥4mm) (striped bars) among smokers and never-smokers with type 2 diabetes mellitus

after stratification for brushing habits. (B) Clinical attachment loss (dark grey bars) and

marginal bone loss (light grey bars) among smokers and never-smokers with type 2 diabetes

mellitus after stratification for brushing habits.

Figure 2. (A) Plaque index (dark grey bars), bleeding on probing (light grey bars) and probing

depth (≥4mm) (striped bars) among smokers and never-smokers in the control group after

stratification for brushing habits. (B) Clinical attachment loss (dark grey bars) and marginal bone

loss (light grey bars) among smokers and never-smokers in the control group after stratification

for brushing habits. *P<0.01 †P<0.01 ‡P<0.01 §P<0.01 ǁP<0.01 ¶P<0.01


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FOOT NOTES

ǁ Hu-Friedy, Chicago, IL.

¶ Ektaspeed plus; Kodak, Rochester, NY.

# Samsung SyncMaster digital TV monitor, Suwon City, Gyeonggi-do, Korea.

** Image Tool 3.0, Department of Dental Diagnostic Science, University of Texas Health

Science Center, San Antonio, TX.

†† SPSS v.18, IBM, Chicago, IL.

‡‡ nQuery Advisor 6.0, Statistical Solutions, Saugas, MA.


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ACKNOWLEDGEMENTS

The authors extend their appreciation to the Research Center, College of Applied Medical

Sciences and Deanship of Scientific Research at King Saud University, Saudi Arabia for funding

this research. The authors also thank the Visiting Professor Program at King Saud University,

Saudi Arabia for supporting this research project.


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Conflict of interest and financial disclosure

The authors declare that they have no conflict of interest and there was no external source of

funding for the present study.


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Table 1. Sociodemographic characteristics of the study participants

Parameters

Patients with T2DM Controls

All

individuals

Smokers Never

smokers

All

individuals

Smokers Never

smokers

No. of patients (n) 50 25 25 50 25 25

Gender (Male) 50 25 25 50 25 25

Mean age (in years) 52.6±3.8 50.6±1.8 54.1±3.2 50.5±2.4 48.5±4.8 55.6±5.5

Duration of T2DM (in years) 8.5±1.5 4.6±1.1 10.2±2.5 — — —

Duration of smoking (in years) 12.6±4.8 12.6±4.8 — 16.4±5.1 16.4±5.1 —

No. of cigarettes smoked daily (n) 6.2±2.1

6.2±2.1* — 15.5±2.5 15.5±2.5 —

Monthly income (in USD) 525±85.4 498.7±90.6

598.5±75.5

585±88.6 530.6±54.7 627±58.8

Graduate level education status (%) 40% 16% 24% 41% 19% 22%

Mean Hemoglobin A1c (±SD) 8.2±0.1† 7.8±0.4

‡§ 8.7±0.2

ǁ¶ 4.4±0.3 4.3±0.1 4.5±0.1

Treatment of T2DM

Allopathic 100% 100% 100% — — —

Homeopathic — — — — — —

Others — — — — — —

Daily tooth brushing

Once daily 78% 80% 76% 88% 92% 84%

Twice daily 22% 20% 24% 12% 8% 16%

Three times or more — — — — — —

Have you ever used a dental floss?

Yes — — — — — —

No 100% 100% 100% 100% 100% 100% *Compared to smokers in the control group (P<0.05)

† Compared to all individuals in the control group (P<0.05)

‡ Compared to smokers in the control group (P<0.05)

§ Compared to never-smokers in the control group (P<0.05)

ǁ Compared to smokers in the control group (P<0.05) ¶ Compared to never-smokers in the control group (P<0.05)


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Table 2. Clinical periodontal status among smokers and never-smokers with and without type 2 diabetes mellitus

Parameters

Patients with T2DM Controls

All

individuals

Smokers Never

smokers

All

individuals

Smokers Never

smokers

No. of patients (n) 50 25 25 50 25 25

PI 69.4±5.1* 73.4±8.5

†‡ 61.7±3.5

§ǁ 26.2±4.6 30.5±5.2

¶ 18.2±4.8

BOP 62.6±4.9* 58.7±4.8

†‡ 69.5±6.1

§ǁ 18.4±6.5 9.2±2.7

¶ 28.5±3.3

CA loss 5.4±1.2* 6.3±0.8

†‡ 5.8±1.1

§ǁ 2.2±0.4 3.8±0.2

¶ 0.4±0.1

PD (≥4mm) 33.5±5.5* 36.3±4.2

†‡ 30.8±2.9

§ǁ 6.2±1.5 6.4±2.5

¶ 0.6±0.1

MBL 6.5±1.2*

7.1±0.5†‡

6.2±1.1§ǁ

2.4±0.3 4.5±0.4¶ 2.1±0.2

* Compared to all individuals in the control group (P<0.01)

† Compared to smokers in the control group (P<0.01)

‡ Compared to never-smokers in the control group (P<0.01)

§ Compared to smokers in the control group (P<0.05)

ǁ Compared to never-smokers in the control group (P<0.05)

¶ Compared to never-smokers in the control group (P<0.05)


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29x26mm (300 x 300 DPI)


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28x24mm (300 x 300 DPI)


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periodontal inflammatory conditions among smokers and never-smokers with and without type 2 diabetes...

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