Periodontal Disease in Habitual Cigarette Smokers
and Nonsmokers With and Without Prediabetes
Fawad Javed, PhD, Mansour Al-Askar, MSc, Lakshman P. Samaranayake, FRCPath
and Khalid Al-Hezaimi, MSc
Abstract: Introduction: Prediabetes and habitual cigarette smoking are
significant risk factors contributing to periodontal disease. The aim was
to assess the clinical and radiological markers of periodontal disease in
habitual cigarette smokers and nonsmokers with and without pre-
diabetes. Methods: Sixty-eight individuals with prediabetes (test group;
34 smokers and 34 nonsmokers) and 68 medically healthy individuals
(control group; 34 smokers and 34 nonsmokers) were included.
Sociodemographic information, duration of smoking habit and
number of cigarettes smoked daily were recorded through a ques-
tionnaire. Fasting blood glucose levels and periodontal inflammatory
conditions (plaque index [PI], bleeding on probing [BOP] and
probing pocket depth [PPD] of 4 to ,6 mm and $6 mm) were
recorded. In both groups, marginal bone loss (MBL) was measured
on digital panoramic radiographs. Results: Cigarette smokers and
nonsmokers in the test group had significantly higher fasting
blood glucose level when compared with cigarette smokers in the
control group (P , 0.001). In the test group, there was no significant
difference in PI, BOP, PPD (4 to ,6 mm and $6 mm) and MBL
among cigarette smokers and nonsmokers. Cigarette smokers in the
control group had significantly higher PI (P , 0.001), PPD (4 to ,6
mm; P , 0.001), PPD $6 mm (P , 0.01) and MBL (P , 0.05) than
nonsmokers. BOP was significantly reduced in smokers when
compared with nonsmokers in the control group (P , 0.001).
Conclusions: Cigarette smokers without prediabetes exhibit sig-
nificantly severe periodontal disease than nonsmokers. In subjects
with prediabetes, the severity of periodontal disease seems to be
over shadowed by the hyperglycemic state, obscuring the effect of
Key Indexing Terms: Impaired glucose tolerance;Inflammation; Periodon-
tal disease; Prediabetes; Smoking. [Am J Med Sci 2013;345(2):94–98.]
impaired glucose tolerance (IGT) or prediabetes worldwide.
The prediabetes designations of impaired fasting glucose and
IGT are defined by a fasting blood glucose level (FBGL) of
100 to 125 mg/dL and a postglucose challenge of 140 to
199 mg/dL correspondingly.1Although a number of studies2–7
have reported that periodontal inflammatory conditions are
severe in patients with poorly controlled diabetes when com-
pared with individuals with well-controlled diabetes and healthy
individuals, little is known about the severity of periodontal
he rapidly escalating global prevalence of diabetes implies
a concomitant increase in the number of individuals with
disease in patients with prediabetes. Nearly, 2 decades ago,
Sastrowijoto et al8investigated the relationship between peri-
odontal inflammatory parameters (gingival bleeding and dental
plaque index [PI]) and IGT. They concluded that in individuals
with IGT, the cumulative frequency and duration of increased
blood glucose values may be too short to induce periodontal
disease. In contrast, in an experimental study on Zucker rats,
Pontes Andersen et al9reported that prediabetes worsens peri-
odontal inflammation. In a recent study, Javed et al10also re-
ported that the clinical (PI, bleeding on probing [BOP] and
probing pocket depth [PPD 4 to ,6 mm]) and radiological
parameters of periodontal disease (marginal bone loss [MBL])
are aggravated in patients with prediabetes when compared with
medically healthy individuals.
The detrimental effects of cigarette smoking on oral and
systemic health are well documented.2,10–12Several stud-
ies2,10,11have shown that habitual cigarette smokers are more
susceptible to periodontal disease when compared with non-
smokers. It has been reported that tobacco smoking increases
the expression of receptors of advanced glycation end prod-
ucts (AGEs) in gingival tissues and impairs the chemotactic
and phagocytic functions of polymorphonuculear leuko-
cytes.13–17This in turn provokes a proinflammatory effect by
stimulating the secretion of cytokines and reactive oxygen
species which directly cause destruction of periodontal tis-
sues.15It is also noteworthy that gingival bleeding, a classic
sign of periodontal inflammation, is masked in habitual smok-
ers when compared with nonsmokers.2Because of this, habit-
ual smokers may be unaware of the periodontal destruction
until the disease progresses to a stage where tooth mobility
Because prediabetes and habitual cigarette smoking are
significant risk factors for periodontal disease, it is hypothesized
that habitual cigarette smokers with prediabetes experience
more intense periodontal disease when compared with habitual
cigarette smokers without prediabetes. The aim of this study
was to assess the clinical and radiological markers of periodon-
tal disease in habitual cigarette smokers and nonsmokers with
and without prediabetes.
MATERIALS AND METHODS
Individuals with medically diagnosed prediabetes (test
group) were recruited from the Diabetes Care Unit of a hospital
in Karachi, Pakistan; whereas subjects without prediabetes
(control group) were recruited from a residential area located
in the vicinity of the hospital. “Cigarette smokers” were defined
as individuals who smoked at least 1 cigarette per day for
a minimum of 12 months before the study period. “Non-
smokers” were defined as individuals who reported to have
never consumed tobacco in any form.2The medical records
from individuals in both groups were examined to ascertain
the presence or absence of prediabetes.
From the Growth Factors and Bone Regeneration (FJ, MA-A, KA-H), College
of Applied Medical Sciences; Department of Periodontics and Community
Dentistry (MA-A, KA-H), King Saud University, Riyadh, Saudi Arabia; and
Oral Biosciences (LPS), Faculty of Dentistry, Prince Philip Dental Hospital,
University of Hong Kong, Hong Kong.
Submitted January 6, 2012; accepted in revised form January 27, 2012.
Correspondence: Fawad Javed, PhD, Growth Factors and Bone
Regeneration, College of Applied Sciences, King Saud University, PO Box
60169, Riyadh 11545, Saudi Arabia (E-mail: firstname.lastname@example.org).
The American Journal of the Medical Sciences
? Volume 345, Number 2, February 2013
In total, 136 individuals (68 individuals in the test group
[34 smokers and 34 nonsmokers] and 68 individuals in the
control group [34 smokers and 34 nonsmokers]) were recruited.
The exclusion criteria were as follows: (a) self-reported
habitual alcohol and smokeless tobacco consumption; (b)
edentulism; (c) individuals who self-reported to have other
systemic disorders such as infection with human immunodefi-
ciency virus disease, acquired immune deficiency syndrome,
cardiovascular disorders, renal disease, hepatitis B and hepatitis
C and (d) individuals currently using or those with a recent
history of corticosteroid, antibiotic and/or nonsteroidal anti-
inflammatory drug use.
In the test and control groups, information regarding
age, gender, socioeconomic status, habitual cigarette smoking
(yes/no), duration of smoking habit and number of cigarettes
smoked daily was recorded through a questionnaire. Informa-
tion regarding the treatment of prediabetes was also recorded.
Measurement of FBGLs
FBGLs in the test and control groups were measured by
a digital glucometer (ACCU-CHEK ACTIV; Roche Diagnos-
tics, Mannheim, Germany). The participants were categorized
into 2 groups as follows: (a) healthy controls—individuals
with FBGL ,100 mg/dL (5.6 mmol/L) and (b) patients with
prediabetes—individuals with FBGL of $100 mg/dL but
,126 mg/dL (7.0 mmol/L).18
Clinical Periodontal Examination
A single investigator, blinded to the prediabetic or the
smoking status of individuals, performed all the clinical peri-
odontal examinations. The overall kappa value for intraexaminer
reliability was 0.78. A full-mouth PI, BOP and PPD (4 to ,6 mm
and $6 mm) were measured at 4 sites (mesial, distal, buccal and
lingual/palatal) on all maxillary and mandibular teeth (excluding
bilateral maxillary and mandibular third molars). PPD was mea-
sured to the nearest millimeters with a graded probe (Hu-Friedy
Manufacturing, Chicago, IL).2Fractured teeth with embedded
root remnants were considered missing.
Marginal Bone Loss
Digital panoramic radiographs were taken using a digital
panoramic tomography machine (KODAK 8000C System;
Carestream Dental LLC, Atlanta, GA) and viewed on a cali-
brated computer screen (Samsung SyncMaster Digital TV
Monitor, Korea) using a software program (Image Tool 3.0
Program; Department of Dental Diagnostic Science, University
of Texas Health Science Center, San Antonio, TX). MBL was
considered as the vertical distance from 2 mm below the
cementoenamel junction to the most apical part of marginal
bone.2MBL was measured on bilateral maxillary and mandib-
ular premolars and molars by a single investigator. Tooth sur-
faces at which the cementoenamel junction and/or the bone
crest were not visible because of technical reasons (including
dental restorations, interdental caries, overlapping of teeth
and/or poor radiographic quality) and bilateral maxillary and
mandibular third molars were excluded.
The statistical analysis was performed using SPSS,
Statistics 18.0, software program (Chicago, IL). One-way analysis
of variance was used to determine whether the dependent
variables (PI, BOP, PPD [4 to ,6 mm and $6 mm], MBL
and number of missing teeth) were statistically significant with
the independent variables. The independent variables were
transformed into dichotomous variables, for example, cigarette
smokers in individuals with prediabetes, 1 versus nonsmokers
in subjects with prediabetes, 0; cigarette smokers in individuals
without prediabetes, 1 versus nonsmokers in individuals without
prediabetes, 0. The Bonferroni adjustment post hoc test was per-
formed for multiple comparisons. P values ,0.05 were consid-
ered statistically significant. The power calculations performed
before the study showed that the sample size required to ascertain
the significance of association of periodontal disease in predia-
betic smokers and nonsmokers with an alpha value of 0.05 and
85% power was 34 prediabetic smokers, 34 prediabetic non-
smokers, 34 smokers without prediabetes and 34 nonsmokers
The study was approved by the research ethics review
committee of the Engineer Abdullah Bugshan Research Chair
for Growth Factors and Bone Regeneration, College of
Dentistry, King Saud University, Riyadh, Saudi Arabia. Written
consent was obtained from all individuals who agreed to
participate in this study.
Characteristics of the Study Population
There was no significant difference in the mean age of
cigarette smokers and nonsmokers in the test and control groups
(Table 1). The mean duration of prediabetes among cigarette
smokers and nonsmokers was 6.4 and 6.2 months, respectively.
There was no significant difference in the duration of the smok-
ing habit and the daily number of cigarettes per smoker among
smokers in the test and control groups. These results are sum-
marized in Table 1.
Fasting Blood Glucose Levels
The mean FBGL among individuals in the test group
and control group were 120 mg/dL (range, 114-124 mg/dL)
and 75.6 mg/dL (69-80 mg/dL) (P , 0.001). In the test and
control groups, there was no significant difference in FBGL
among smokers and nonsmokers (Table 1). Cigarette smok-
ers in the test group had significantly higher FBGL when
compared with cigarette smokers in the control group (P ,
0.05). Nonsmokers in the test group had significantly higher
FBGL when compared with cigarette smokers in the control
group (P , 0.01).
All patients with prediabetes were under a regimen
of dietary control as prescribed by their physicians for the
management of the metabolic state.
Periodontal Inflammatory Conditions
In the test group of prediabetics, there was no significant
difference in PI, BOP, PPD (4 to ,6 mm) and PPD ($6 mm)
among cigarette smokers and nonsmokers (Table 2).
Cigarette smoking prediabetics (test group) had a higher
PI (P , 0.001), BOP (P , 0.001), PPD (4 to ,6 mm; P ,
0.001) and PPD ($6 mm; P , 0.001) than cigarette smokers in
the healthy control group. PI (P , 0.001), BOP (P , 0.001),
PPD (4 to ,6 mm; P , 0.001) and PPD ($6 mm; P , 0.05)
were also significantly higher among subjects in the test group
compared with those in the control group (Table 2).
In the control group, cigarette smokers had signifi-
cantly higher PI (P , 0.001), PPD (4 to ,6 mm; P , 0.001)
Periodontal Disease Smoking and Prediabetes
? 2012 Lippincott Williams & Wilkins
and PPD ($6 mm; P , 0.01) when compared with
nonsmokers; however, BOP was significantly reduced in
smokers when compared with nonsmokers in this group
(P , 0.001).
Marginal Bone Loss
In the control group, MBL was significantly higher in
smokers when compared with nonsmokers (P , 0.01). In the
test group, there was no difference in MBL among smokers and
nonsmokers. Nonsmokers in the test group showed significantly
higher MBL when compared with smokers in the control group
(P , 0.05). These results are shown in Figure 1
The present results demonstrate that in individuals
without prediabetes, periodontal inflammatory conditions (PI,
PPD [4 to ,6 mm] and PPD [$6 mm]) were significantly
higher in smokers; however, gingival bleeding was reduced in
smokers when compared with nonsmokers. Although these
results are in agreement with previous studies2,10,11,19that
TABLE 1. Characteristics of the study population
TABLE 2. Clinical parameters of periodontal inflammation in habitual cigarette smokers and non-smokers with and without
Individuals with prediabetes (n 5 68)
Individuals without prediabetes (n 5 68)
Smokers (n 5 34)
(mean 6 SD)
(n 5 34)
Smokers (n 5 34)
(mean 6 SD)
(n 5 34)
PPD (4 mm , 6 mm) (%)28.7a
PPD ($ 6 mm) (%)12.2a
PI, Plaque index; BOP, Bleeding on probing; PPD, Probing pocket depth; mm, millimeters; SD, Standard deviation.
aP , 0.001.
bP , 0.001.
cP , 0.05.
dP , 0.01.
i indicates P , 0.05; j indicates P , 0.01.
Javed et al
Volume 345, Number 2, February 2013
assessed the effect of cigarette smoking on periodontal health,
the exact mechanisms by which cigarette smoking increases
periodontal inflammation remains poorly understood as yet.
Various explanations have been proposed in this regard.
Rezavandi et al20reported that the inflamed gingival tissues
of smokers exhibit significantly smaller number of vessels when
compared with nonsmokers. Similarly, Bergström et al21
reported that the vascular reaction associated with plaque-
induced gingivitis is suppressed in smokers when compared
with nonsmokers. Smoking induces endothelial dysfunction
that may lead to inflammatory activation within the vascular
wall, mediated by cytokines (including interleukin [IL] 6,
IL-8 and tumor necrosis factor-a) and adhesion molecules (par-
ticularly intercellular adhesion molecule-1).22The level of sol-
uble intercellular adhesion molecule-1 has been reported to be
higher in smokers when compared with nonsmokers.22Serum
concentrations of immunoglobulin G, mainly immunoglobulin
G2 (an important antibody against gram-negative periodontal
pathogens) are also decreased in smokers thereby making them
more susceptible to develop periodontal disease when com-
pared with nonsmokers.23,24According to the present results,
there was no difference in BOP in smokers and nonsmokers
with prediabetes. This suggests that the vasoconstrictive effect
of nicotine does not mask gingival bleeding in prediabetic
smokers and that there might be other mechanisms (such as
increased accumulation of AGEs in periodontal tissues) that
may play a role in augmenting BOP in smokers with prediabe-
tes when compared with nonsmokers. It may therefore be sug-
gested that increased gingival bleeding in smokers may be
indicative of a “latent hyperglycemic state” in undiagnosed
individuals. It is recommended that such individuals should
be referred to physicians for medical assistance. Our results
are in accordance with a recent study25in which the authors
reported that oral healthcare professionals have the opportunity
to identify undiagnosed diabetes and prediabetes in dental
patients and refer them to a physician for further evaluation
and care. However, further studies are warranted in this regard.
An interesting finding in this investigation was that the
nonsmoking individuals in the test group showed significantly
higher MBL when compared with cigarette smokers in the
control group. It therefore seems that the intensity of
periodontal inflammation induced by a hyperglycemic state
(in patients with prediabetes) is more intense than the
inflammatory response induced by cigarette smoking. Chronic
hyperglycemia has been associated with an increased forma-
tion and accumulation of glucose-mediated AGEs in the
gingival tissues, which in turn impairs the chemotactic and
phagocytic function of polymorphonuclear leukocytes and
produce proinflammatory cytokines, thereby leading to peri-
odontal disease and MBL.23Although smoking has also been
associated with an increased accumulation of AGEs in peri-
odontal tissues, it is tempting to speculate that the amount of
AGEs accumulation in hyperglycemic patients does not sig-
nificantly impact upon the inflammatory condition of the
periodontium, at least in the current cohort. This may perhaps
explain the similarity in periodontal inflammatory parameters
in prediabetic smokers and nonsmokers. Although the predi-
abetic individuals in the current cohort were recommended by
their physicians to control hyperglycemia through dietary
regimes both smokers and nonsmokers in this group had
impaired fasting plasma glucose levels when compared with
smokers and nonsmokers (without prediabetes).
It has been reported that increasing age, socioeconomic
status, daily oral hygiene maintenance regimes and number of
cigarettes smoked daily are directly associated with periodontal
inflammation;2,24however, in this investigation, there was no sig-
nificant difference in these variables among cigarette smokers and
nonsmokers with and without prediabetes. This suggests that in this
study, the severity of periodontal inflammation was mainly gov-
erned by hyperglycemia in prediabetic smokers and nonsmoker.
Furthermore, studies on prediabetic smokers and nonsmokers with
controlled glycemic statuses are warranted to assess the effect of
cigarette smoking on periodontal health in these individuals.
In subjects without prediabetes, cigarette smokers had
accentuated periodontal inflammation when compared with
nonsmokers. In subjects with prediabetes, the severity of
periodontal inflammatory parameters among smokers and non-
smokers was not significantly different implying that the
hyperglycemic state may have obscured the adverse effect of
habitual cigarette smoking on the periodontium.
1. Olson DE, Rhee MK, Herrick K, et al. Screening for diabetes and pre-
diabetes with proposed A1C-based diagnostic criteria. Diabetes Care
with and without prediabetes.
Marginal bone loss in smokers and nonsmokers
Periodontal Disease Smoking and Prediabetes
? 2012 Lippincott Williams & Wilkins
2. Javed F, Näsström K, Benchimol D, et al. Comparison of peri- Download full-text
odontal and socioeconomic status between subjects with type 2
diabetes mellitus and non-diabetic controls. J Periodontol 2007;
3. Hodge PJ, Robertson D, Paterson K, et al. Periodontitis in non-smoking
type 1 diabetic adults: a cross-sectional study. J Clin Periodontol 2012;39:
4. Javed F, Klingspor L, Sundin U, et al. Periodontal conditions, oral
Candida albicans and salivary proteins in type 2 diabetic subjects with
emphasis on gender. BMC Oral Health 2009;9:12.
5. Kim JB, Jung MH, Cho JY, et al. The influence of type 2 diabetes
mellitus on the expression of inflammatory mediators and tissue
inhibitor of metalloproteinases-2 in human chronic periodontitis.
J Periodontal Implant Sci 2011;41:109–16.
6. Javed F, Romanos GE. Impact of diabetes mellitus and glycemic
control on the osseointegration of dental implants: a systematic litera-
ture review. J Periodontol 2009;80:1719–30.
7. Javed F, Sundin U, Altamash M, et al. Self-perceived oral health and
salivary proteins in children with type 1 diabetes. J Oral Rehabil 2009;
8. Sastrowijoto SH, Abbas F, Abraham-Inpijn L, et al. Relation-
ship between bleeding/plaque ratio, family history of diabetes mel-
litus and impaired glucose tolerance. J Clin Periodontol 1990;17:
9. Pontes Andersen CC, Flyvbjerg A, Buschard K, et al. Periodontitis is
associated with aggravation of prediabetes in Zucker fatty rats.
J Periodontol 2007;78:559–65.
10. Javed F, Al-Askar M, Al-Rasheed A, et al. Comparison of self-
perceived oral health, periodontal inflammatory conditions and socio-
economic status in individuals with and without prediabetes [published
online ahead of print Nov 16, 2011]. Am J Med Sci doi: 10.1097/MAJ.
11. Javed F, Al-Rasheed A, Almas K, et al. Effect of cigarette smoking on
the clinical outcomes of periodontal surgical procedures. Am J Med Sci
12. Okoro CA, Balluz LS, Eke PI, et al. Tooth loss and heart disease:
findings from the behavioral risk factor surveillance system. Am J Prev
Med 2005;29(suppl 1):50–6.
13. Breitling LP, Yang R, Korn B, et al. Tobacco-smoking-related differ-
ential DNA methylation: 27K discovery and replication. Am J Hum
14. Katz J, Yoon TY, Mao S, et al. Expression of the receptor of advanced
glycation end products in the gingival tissue of smokers with general-
ized periodontal disease and after nornicotine induction in primary
gingival epithelial cells. J Periodontol 2007;78:736–41.
15. Katz J, Caudle RM, Bhattacharyya I, et al. Receptor for advanced
glycation end product (RAGE) upregulation in human gingival
fibroblasts incubated with nornicotine. J Periodontol 2005;76:1171–4.
16. Palmer RM, Scott DA, Meekin TN, et al. Potential mechanisms of
susceptibility to periodontitis in tobacco smokers. J Periodontal Res
17. Balaji SM. Tobacco smoking and surgical healing of oral tissues: a
review. Indian J Dent Res 2008;19:344–8.
18. James C, Bullard KM, Rolka DB, et al. Implications of alternative
definitions of prediabetes for prevalence in U.S. adults. Diabetes Care
19. Hugoson A, Rolandsson M. Periodontal disease in relation to smoking
and the use of Swedish snus: epidemiological studies covering 20 years
(1983-2003). J Clin Periodontol 2011;38:809–16.
20. Rezavandi K, Palmer RM, Odell EW, et al. Expression of ICAM-1 and
E-selectin in gingival tissues of smokers and non-smokers with periodon-
titis. J Oral Pathol Med 2002;31:59–64.
21. Bergström J, Persson L, Preber H. Influence of cigarette smoking on
vascular reaction during experimental gingivitis. Scand J Dent Res
22. Ojima M, Hanioka T. Destructive effects of smoking on molecular and
genetic factors of periodontal disease. Tob Induc Dis 2010;8:4.
23. Quinn SM, Zhang JB, Gunsolley JC, et al. The influence of smoking
and race on adult periodontitis and serum IgG2 levels. J Periodontol
24. Tomar SL, Asma S. Smoking-attributable periodontitis in the United
States: findings from NHANES III. National Health and Nutrition
Examination Survey. J Periodontol 2000;71:743–51.
25. Lalla E, Kunzel C, Burkett S, et al. Identification of unrecognized di-
abetes and pre-diabetes in a dental setting. J Dent Res 2011;90:855–60.
Javed et al
Volume 345, Number 2, February 2013