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ORIGINAL ARTICLE
SALIVARY BIOMARKER LEVELS AND PERIODONTAL HEALTH STATUS IN PATIENTS WITH
DIABETIC AND HEALTHY LIFESTYLE: A COMPARATIVE STUDY
Farooq Maqsood1, Huma Abid2, Nausheen Daud3, Naila Noreen4, Faizan Bilal Malik5, Tariq Ali Khan6
with Diabetic and Healthy Lifestyle: A
How to cite this article
Maqsood F, Abid H, Daud N, Noreen
N, Malik FB, Khan TA.
Salivary Biomarker Levels and
Periodontal Health Status in Patients
Comparative Study. J Gandhara Med
Dent Sci. 2025;12(1):15-19.doi:10.37762
Date of Submission:
Date Revised:
Date Acceptance:
21-08-2024
09-10-2024
21-11-2024
2Final Year Resident, Department of
Periodontology & Implant, Rehman
College of Dentistry, Peshawar
3Lecturer, Department of
Periodontology & Implant, Rehman
College of Dentistry, Peshawar
4Final Year Resident, Department of
Periodontology & Implant, Rehman
College of Dentistry, Peshawar
52nd Y ear Resident, Department of
Periodontology & Implant, Rehman
College of Dentistry, Peshawar
6Professor, Department of
Periodontology & Implant, Rehman
College of Dentistry, Peshawar
Correspondence
1Farooq Maqsood, Lecturer,
Department of Periodontology &
Implant, Rehman College of
Dentistry, Peshawar
+92-331-9813629
dr.farooqmaqsood@gmail.com
ABSTRACT
OBJECTIVES
To evaluate and compare the periodontal health status and salivary
biomarker levels in diabetic patients and non-diabetic individuals, thereby
determining the association between these factors.
METHODOLOGY
A comparative study included 100 participants divided into two groups: 50
diabetic patients and 50 healthy controls. Periodontal parameters such as the
gingival index (GI), probing pocket depth (PPD), and clinical attachment
level (CAL) were assessed. Salivary biomarkers, including interleukin-6 (IL-
6), tumor necrosis factor-alpha (TNF-α), and glucose levels, were measured
using enzyme-linked immunosorbent assay (ELISA) techniques. Statistical
analysis was conducted using SPSS software.
RESULTS
Diabetic patients exhibited signicantly higher periodontal parameters (GI,
PPD, CAL) compared to healthy controls (p < 0.05). Salivary biomarkers,
particularly IL-6 and TNF-α, were markedly elevated in the diabetic group (p
< 0.01). There was a strong positive correlation between salivary glucose
levels and periodontal parameters (p < 0.001).
CONCLUSION
Diabetic individuals show worse periodontal health and elevated salivary
inammatory biomarkers compared to non-diabetic controls. This suggests a
need for closer periodontal monitoring in diabetic patients to mitigate further
systemic complications.
KEYWORDS: Diabetic, Periodontal, Salivary Biomarkers, Hyperglycemia
INTRODUCTION
Periodontal disease, a chronic inammatory condition
affecting the supporting structures of the teeth, has
garnered signicant research attention due to its
systemic implications. Emerging evidence underscores
a bidirectional relationship between periodontal disease
and systemic conditions such as diabetes mellitus
(DM), a chronic metabolic disorder characterized by
hyperglycemia and associated vascular and immune
dysfunctions. DM aects more than 400 million
individuals globally, with type 2 diabetes being the
predominant form.1 Given the increasing prevalence of
DM and periodontal disease worldwide, understanding
their interrelationship through objective biomarkers is
essential for developing targeted diagnostic and
therapeutic strategies. Patients with diabetes are
predisposed to periodontal disease due to altered host
responses to microbial insults, impaired wound healing,
and dysregulated inammatory processes.2 Conversely,
periodontal inammation can exacerbate glycemic
control through systemic dissemination of inammatory
mediators such as tumor necrosis factor-alpha (TNF-α)
and interleukin-6 (IL-6).3 This interplay emphasizes the
need for robust comparative studies to delineate
dierences in periodontal parameters and associated
biomarkers between diabetic patients and healthy
individuals. Periodontal parameters, including clinical
attachment loss (CAL), probing depth (PD), bleeding
on probing (BOP), and plaque index (PI), serve as
clinical indicators of periodontal health, while salivary
biomarkers oer a non-invasive, dynamic assessment of
systemic and oral health. Saliva, a complex biological
fluid, reects both local and systemic
pathophysiological changes, making it a promising
medium for biomarker identication. In diabetic
patients, alterations in salivary glucose,
immunoglobulins, pro-inflammatory cytokines, and
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16 J Gandhara Med Dent Sci
January - March 2025
oxidative stress markers have been documented.4
Additionally, specic biomarkers such as matrix
metalloproteinase-8 (MMP-8), C-reactive protein
(CRP), and advanced glycation end products (AGEs)
have been implicated in both periodontal and diabetic
pathologies.5 Comparative analyses of these biomarkers
can elucidate shared mechanistic pathways, providing
insights into the pathogenesis of periodontal disease in
diabetic populations. Studies have highlighted
significant disparities in periodontal parameters
between diabetic and non-diabetic individuals. For
instance, diabetic patients consistently exhibit higher
CAL, PD, and BOP scores, suggesting increased
susceptibility to periodontal destruction.6 These clinical
findings are mirrored by elevated levels of pro-
inammatory mediators in saliva, indicative of
heightened inammatory burden in diabetes-associated
periodontal disease.7 However, discrepancies exist
regarding the extent of these dierences and their
correlation with systemic glycemic control,
necessitating comprehensive investigations. The
intricate relationship between diabetes and periodontal
disease is mediated by several mechanisms, including
advanced glycation, oxidative stress, and dysbiosis of
the oral microbiome. Hyperglycemia induces the
formation of AGEs, which interact with receptors on
immune cells to amplify inammatory responses.8
Additionally, oxidative stress, a hallmark of diabetic
complications, exacerbates periodontal tissue
destruction by promoting apoptosis and impairing tissue
repair mechanisms.9 Dysbiosis of the subgingival
microbiota further perpetuates inammation, creating a
vicious cycle that exacerbates both periodontal and
systemic health.10 Salivary biomarker analysis provides
a window into these pathophysiological processes,
enabling the identication of potential diagnostic and
prognostic indicators. Despite the wealth of research
linking diabetes and periodontal disease, signicant
knowledge gaps persist regarding the utility of salivary
biomarkers in clinical practice. While some studies
have demonstrated strong correlations between salivary
markers and periodontal parameters, others have
reported conicting ndings, highlighting the need for
standardized methodologies and larger cohort studies.11
Additionally, the inuence of confounding factors such
as smoking, age, and medication use must be carefully
considered in comparative analyses. This study aims to
provide a comparative analysis of periodontal
parameters and salivary biomarkers in patients with
diabetes mellitus and healthy controls. By synthesizing
findings, this work seeks to unravel the complex
interplay between diabetes and periodontal disease,
oering insights into shared pathophysiological
mechanisms and potential clinical applications.
Understanding these relationships is pivotal for the
development of integrated care models that address the
systemic and oral health needs of diabetic populations.
METHODOLOGY
This comparative study was conducted over six months
at the Department of Periodontology, Rehman College
of Dentistry, Peshawar. A total of 100 participants were
recruited, comprising 50 patients diagnosed with type 2
diabetes mellitus (DM) and 50 healthy controls
matched for age and gender. Patients diagnosed with
type 2 DM for at least ve years, healthy controls with
no history of systemic diseases, participants aged
between 30 to 65 years, and no use of antibiotics or
anti-inammatory drugs in the last three months were
included. The smokers or individuals with a history of
tobacco use, pregnant or lactating women, and patients
with other systemic conditions such as cardiovascular
disease, rheumatoid arthritis, or immunocompromised
states. Periodontal examination was conducted by a
calibrated periodontist using a UNC-15 periodontal
probe. The following periodontal parameters were
recorded: Gingival Index (GI): To assess the severity of
gingivitis. Probing Pocket Depth (PPD): To measure
the depth of periodontal pockets. Clinical Attachment
Level (CAL): To evaluate the extent of periodontal
attachment loss. Unstimulated saliva was collected
from each participant in the morning after an overnight
fast. The samples were centrifuged at 3000 rpm for 10
minutes, and the supernatant was stored at -80°C until
further analysis. The salivary levels of glucose, IL-6,
and TNF-α were measured using ELISA kits following
the manufacturer‟s instructions. Data were analyzed
using SPSS version 25.0. Descriptive statistics were
used to summarize the demographic and clinical
characteristics of the participants. The independent t-
test was used to compare the periodontal parameters
and salivary biomarkers between the two groups.
Pearson's correlation analysis was performed to assess
the relationship between salivary glucose levels and
periodontal parameters. A p-value of < 0.05 was
considered statistically significant.
RESULTS
The study included 100 participants, with a mean age of
52 ± 8 years. The demographic characteristics of the
study population are presented in Table 1. Diabetic
patients had signicantly higher mean values for GI,
PPD, and CAL compared to healthy controls (p < 0.05),
as shown in Table 2. Salivary levels of glucose, IL-6,
and TNF-α were significantly elevated in diabetic
patients compared to healthy controls (p < 0.01). The
results are presented in Table 3. There was a signicant
positive correlation between salivary glucose levels and
periodontal parameters (p < 0.001), as shown in Table
4.
Salivary Biomarker Levels and Periodontal Health Status
17
J Gandhara Med Dent Sci
January - March 2025
Table 1: Demographic Characteristics of Participants
Characteristics Diabetic Group
(n=50)
Healthy
Controls (n=50)
Age (mean ± SD) 53 ± 7 51 ± 9
Gender (Male/Female) 26/24 25/25
Duration of Diabetes (years) 10 ± 5 N/A
Table 2: Comparison of Periodontal Parameters
Periodontal Parameters Diabetic Group
(n=50)
Healthy
Controls (n=50)
Gingival Index (GI) 2.5 ± 0.4 1.8 ± 0.3
Probing Pocket Depth (PPD)
(mm)
5.2 ± 1.0 3.1 ± 0.8
Clinical Attachment Level
(CAL) (mm)
4.6 ± 0.7 2.9 ± 0.6
Table 3: Salivary Biomarker Levels
Salivary Biomarkers
Glucose (mg/dL)
IL-6 (pg/mL)
TNF-α (pg/mL)
Diabetic Group
(n=50)
Healthy
Controls (n=50)
20 ± 5 4 ± 1
35 ± 8 12 ± 4
42 ± 10 18 ± 5
Table 4: Correlation Between Salivary Glucose and Periodontal
Parameters
Parameter
Gingival Index (GI)
Probing Pocket Depth (PPD)
Clinical Attachment Level (CAL)
Correlation
Coefficient (r)
P-Value
0.76 < 0.001
0.82 < 0.001
0.79 < 0.001
DISCUSSION
The present study aimed to evaluate and compare
periodontal parameters and salivary biomarkers
between diabetic patients and healthy controls,
highlighting the correlations between salivary glucose
levels and periodontal health. The ndings
demonstrated signicantly higher gingival index (GI),
probing pocket depth (PPD), and clinical attachment
level (CAL) in diabetic patients compared to healthy
controls, alongside elevated salivary levels of glucose,
IL-6, and TNF-αin the diabetic group. These results
contribute to the growing body of evidence suggesting a
bidirectional relationship between diabetes mellitus
(DM) and periodontal disease through systemic
inammatory and metabolic pathways. The
signicantly higher periodontal parameter values (GI,
PPD, and CAL) in diabetic patients align with prior
studies that have demonstrated heightened periodontal
destruction in individuals with diabetes. Research by
Preshaw et al. (2012) reported similar increases in PPD
and CAL in diabetic patients, attributing these
dierences to the hyperinammatory state induced by
diabetes, which exacerbates periodontal tissue
destruction.12 Similarly, Khumaedi et al. (2020) found
increased GI and PPD in diabetic populations,
emphasizing the role of systemic hyperglycemia in
impairing immune responses and enhancing microbial
pathogenicity.13 This study’s ndings corroborate these
results, highlighting the global impact of diabetes on
periodontal health. The signicant elevation in salivary
glucose levels observed in diabetic patients is consistent
with studies by Jurysta et al. (2009) and Soares et al.
(2016), both of which reported higher salivary glucose
concentrations in diabetic individuals due to
compromised glycemic control and increased
transudation of glucose into the oral cavity.14,15
Elevated salivary glucose can foster a conducive
environment for pathogenic bacteria, further
exacerbating periodontal inammation. This study‟s
correlation analysis supports this mechanism, showing
a strong positive association between salivary glucose
levels and periodontal parameters, consistent with
findings by Nainggolan et al. (2017), who reported
similar correlations between salivary glucose and CAL
in diabetic patients.16 The pro-inammatory cytokines
IL-6 and TNF-α were signicantly higher in the
diabetic group compared to healthy controls, mirroring
findings in studies by Lalla et al. (2000) and
Engebretson et al. (2007), which identied elevated
levels of these biomarkers in both serum and saliva of
diabetic individuals with periodontal disease.17,18 These
cytokines play a critical role in the pathogenesis of
periodontal disease by amplifying local and systemic
inammation, promoting osteoclastogenesis, and
impairing tissue repair. Additionally, IL-6 and TNF-α
have been implicated in insulin resistance, further
linking periodontal inammation with systemic
glycemic control.19 The current study reinforces these
observations, suggesting that salivary cytokine levels
reect systemic inammation and periodontal status.
Contrastingly, while many international studies have
focused on serum biomarkers, this study highlights the
utility of salivary biomarkers, which oer a non-
invasive and cost-eective alternative for assessing
periodontal and systemic health. For instance,
Giannobile et al. (2016) emphasized saliva's diagnostic
potential, particularly for biomarkers like IL-6 and
TNF-α, which correlate well with periodontal
inammation and systemic conditions (20). However,
conflicting ndings exist in the literature, with some
studies reporting weaker correlations between salivary
cytokines and periodontal parameters, potentially due to
variations in sample collection, population
characteristics, and analytical methods.21 The ndings
regarding salivary TNF-α levels align with a study by
Belazi et al. (2017), which reported elevated salivary
TNF-α in diabetic patients with periodontitis, further
substantiating the cytokine‟s role as a biomarker of
inammation in diabetic and periodontal pathologies.22
However, unlike the current study, Belazi et al. noted a
stronger correlation with glycemic control than
periodontal parameters, indicating potential variations
Salivary Biomarker Levels and Periodontal Health Status
18 J Gandhara Med Dent Sci
January - March 2025
in biomarker dynamics between populations. This
highlights the need for standardized methodologies to
ensure comparability across studies. The signicant
correlations between salivary glucose levels and
periodontal parameters (GI, PPD, and CAL) observed
in this study suggest that salivary glucose may serve as
a valuable biomarker for predicting periodontal health
in diabetic patients. This is consistent with the ndings
of Panchbhai et al. (2012), who demonstrated that
salivary glucose is strongly associated with periodontal
indices and glycemic control.23 However, the lack of
significant correlations in some studies, such as by
Aoyama et al. (2012), underscores the inuence of
confounding factors such as age, medication use, and
oral hygiene practices on salivary biomarker levels.24
The ndings align with research conducted in similar
populations. For example, a study in India by Singh et
al.(2015) reported elevated periodontal parameters and
salivary IL-6 levels in diabetic patients, emphasizing
the role of inammation in periodontal destruction.25
However, the magnitude of dierences in biomarkers
and parameters varies across regions, potentially
reecting dierences in genetic, environmental, and
healthcare factors. Studies in diverse populations have
reported similar trends, further armed the
generalizability of these ndings while highlighting
regional variations in disease prevalence and severity.26
LIMITATIONS
Despite its strengths, this study has certain limitations
that warrant consideration. The relatively small sample
size and cross-sectional design limit the ability to
establish causal relationships between salivary
biomarkers and periodontal parameters. Moreover,
confounding factors such as dietary habits, medication
use, and smoking were not explicitly controlled, which
may inuence biomarker levels. Future longitudinal
studies with larger, diverse cohorts are necessary to
validate these ndings and explore the dynamic
interactions between diabetes, periodontal disease, and
salivary biomarkers over time.
CONCLUSIONS
This study underscores the significant disparities in
periodontal health and salivary biomarker levels
between diabetic patients and healthy controls,
reinforcing the bidirectional relationship between
diabetes and periodontal disease. The strong
correlations between salivary glucose and periodontal
parameters suggest that salivary biomarkers could serve
as non-invasive tools for monitoring periodontal and
systemic health in diabetic populations. However,
further research is needed to standardize biomarker
analysis methodologies, address confounding factors,
and explore the longitudinal dynamics of these
relationships. Such eorts will pave the way for
integrating salivary diagnostics into clinical practice,
enhancing the early detection and management of
periodontal disease in diabetic individuals.
Dec 30;6(2):1
CONFLICT OF INTEREST: None
FUNDING SOURCES: None
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CONTRIBUTORS
1. Farooq Maqsood- Concept & Design; Data Acquisition;Data
Analysis/Interpretation; Drafting Manuscript; Critical
Revision; Supervision; Final Approval
2. Huma Abid - Data Acquisition; Data Analysis/Interpretation;
Drafting Manuscript
3. Nousheen Daud - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Critical Revision
4. Naila Noreen - Data Acquisition; Data Analysis/Interpretation;
Drafting Manuscript; Critical Revision; Supervision; Final
Approval
5. Faizan Bilal Malik - Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Critical Revision
4. Naila Noreen - Data Acquisition; Data Analysis/Interpretation;
Drafting Manuscript; Critical Revision; Supervision
6. Tariq Ali Khan - Concept & Design; Data
Analysis/Interpretation; Critical Revision; Supervision; Final
Approval
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Salivary Biomarker Levels and Periodontal Health Status