A peer-reviewed journal that offers evidence-based clinical information and continuing education for dentists.

Impact of Systemic Conditions on Periodontal Health

Explore the intricate relationship between systemic conditions and periodontal diseases, revealing key biomarkers and pathways linking these conditions to oral health outcomes.


Systemic conditions and modifiers represent an increased risk factor for periodontal diseases. These conditions include, but are not limited to, diabetes mellitus, human immunodeficiency virus (HIV), obesity, atherosclerosis, and tobacco use. Diabetes is a multifactorial disease due to its disruption of the regulation of the endocrine and metabolic pathways.1 Both periodontal diseases and diabetes are inflammatory diseases that involve a variety of cells, including endothelial cells, adipocytes, and cytokines.1 It has been shown that periodontal diseases can lead to poor glycemic control, and play a role in severe alveolar bone loss.1 Studies demonstrate the levels of IL-1β, TNF-α, and prostaglandin in GCF are significantly higher compared to non-diabetic controls with a similar periodontal status.1 Moreover, studies that investigated glycemic control and IL-1β in GCF levels in patients with type 2 diabetes and periodontitis found a significant correlation in both periodontal measures and glycemic control measures, with increased IL-1β in GCF.1 Additionally, GCF levels of IL-1β and prostaglandin increased in individuals with diabetes as their severity of periodontal disease increased.1

Specific biomarkers in GCF taken from patients with HIV present a profile conducive to determining periodontal disease progression. Studies show an increase of the IgG antibody in the GCF, along with IL-1β in deep periodontal pockets.2 High levels of IL-1β and IL-6 are associated with periodontal diseases in patients with HIV, as opposed to patients without HIV, which suggests these high cytokine levels are responsible for the periodontal lesions observed in those with HIV.3 The presence of HIV in leukocytes found in GCF suggests these cells could be the intraoral source of the HIV virus.4 However, more studies are needed to verify this.

Nevertheless, biomarkers in GCF from patients with HIV affirm the role of cytokines in the advancement of periodontitis in seropositive patients.5

There is evidence in GCF of the relationship between obesity and periodontal diseases. Çetiner et al6 reported a positive correlation between periodontal diseases and visfatin levels in GCF. Visfatin is an adipocytokine that plays an important role in immune functions as a growth factor, enzyme, and pro-inflammatory mediator.Research also shows visfatin increases the number of sites with periodontitis.6 Additionally, the levels of visfatin and IL-6 in GCF are higher in patients with obesity as compared to individuals without obesity and in individuals with periodontitis, as compared to healthy periodontal sites.6 However, investigators also found that levels of visfatin can decrease in some groups with obesity, suggesting that obesity and periodontitis can independently, or together, change pro-inflammatory adipocytokines levels in GCF.Thus, levels of visfatin and IL-6 in GCF in relation to the pathogenesis of obesity and periodontal diseases serve as two markers that may be used to monitor the progression of both diseases.

Smoking is known to increase disease risk, including risk for periodontal diseases. In gingival tissue, microcirculation of gingival blood flow and GCF volume are greatly reduced in smokers, but have been found to recover after smoking cessation.7 The cytokine profiles in GCF suggest smoking impacts the cytokine network.Compared to nonsmokers, research shows smokers display higher levels of IL-8, but lower levels of IL-4.8 Levels of IL-6 were found to be elevated in patients with periodontitis who also smoked, and IL-1β concentration was also lower in smokers than nonsmokers.8

Although there are limited data, GCF levels of inflammatory mediators have been studied in relation to cerebrovascular diseases. Research suggests higher levels of leukotriene and cysteinyl-leukotrienes exist in GCF in patients with atherosclerosis.9Though more study is needed, these biomarkers can indicate inflammation that increases the risk for atherosclerosis associated with periodontal diseases.9


  1. Pooja S, Varghese S. Gingival crevicular fluid level of interleukin 1 in chronic periodontitis with diabetes mellitus. Drug Invention Today. 2019;12:1–4.
  2. Grbic JT, Lamster IB, Mitchell-Lewis D. Inflammatory and immune mediators in crevicular fluid from HIV-infected injecting drug users.J Periodonto 1997;68:249–255.
  3. Baqui AA, Meiller TF, Jabra‐Rizk MA, Zhang M, Kelley JI, Falkler WA Jr. Enhanced interleukin 1β, interleukin 6 and tumor necrosis factor αin gingival crevicular fluid from periodontal pockets of patients infected with human immunodeficiency virus 1. Oral Microbiol Immunol. 2000;15:67–73.
  4. Suzuk T, Tai H, Yoshie H, et al. Characterization of HIV‐related periodontitis in AIDS patients: HIV‐infected macrophage exudate in gingival crevicular fluid as a hallmark of distinctive etiology. Clin Exp Immunol.1997;108:254–259.
  5. Alpagot T, Font K, Lee A. Longitudinal evaluation of GCF IFN‐γlevels and periodontal status in HIV+ patients. J Clin Periodontol. 2003;30:944–948.
  6. Cetiner D, Uraz A, Öztoprak S, Akça G. The role of visfatin levels in gingival crevicular fluid as a potential biomarker in the relationship between obesity and periodontal disease. J Appl Oral Sci.2019;27:e20180365.
  7. Morozumi T, Kubota T, Sato T, Okuda K, Yoshie H. Smoking cessation increases gingival blood flow and gingival crevicular fluid. J Clin Periodontol. 2004;31:267–272.
  8. Kamma JJ, Giannopoulou C, Vasdekis VG, Mombelli A. Cytokine profile in gingival crevicular fluid of aggressive periodontitis: influence of smoking and stress. J Clin Periodontol. 2004;31:894–902.
  9. Bäck M, Airila-Månsson S, Jogestrand T, Söder B, Söder PO. Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis. Atherosclerosis. 2007;193:389–394.

This information originally appeared in Rivera M, Apolinar S, Smith M. Gingival crevicular fluid as a biomarker for periodontal disease. Decisions in Dentistry. 2021;7(4):40–43.


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