Mechanisms linking periodontitis and diabetes

Background + Aims

• Type 2 diabetes mellitus (DM) is characterised by insulin resistance and deficiencies in insulin secretion. It increases the prevalence and severity of periodontitis, a chronic inflammatory disease affecting gums and supporting structures of teeth.
• DM is a significant risk factor for periodontitis due to hyperglycaemia-induced inflammatory responses, leading to tissue damage and faster disease progression.
• Periodontitis may negatively impact blood glucose management, creating a bidirectional relationship.
• Limited data are available on the molecular mechanisms linking non-managed  diabetes and periodontal inflammation.
• Gingival crevicular fluid (GCF) contains biomarkers of inflammation, which provide insights into disease mechanisms but are challenging to analyse due to small sample volumes.
• This study aimed to evaluate a broad panel of inflammatory biomarkers (cytokines and chemokines) in the GCF of people with non-managed diabetes and chronic periodontitis compared to individuals living without diabetes.

Materials + Methods

• 26 individuals with non-managed type 2 DM (HbA1c >7.5%, fasting plasma glucose (FPG) >99 mg/dL) and 20 participants who did not live with diabetes.
• All participants were diagnosed with generalised chronic periodontitis.
• Inclusion criteria included:
  • > 35 years old
  • ≥15 teeth
  • > 30% of the sites with concomitant probing pocket depth (PPD) and clinical attachment level (CAL) ≥ 4 mm and ≥ 6 non- adjacent sites with PPD and CAL >5mm, distributed in different quadrants
  • Those with diabetes should have been formally diagnosed with diabetes for ≥5 years
• Exclusion criteria included:
  • Pregnancy or lactation
  • Current or recent cigarette smoking (within the past 5 years)
  • Recent periodontal or antibiotic treatments (within 6 months)
  • Use of antimicrobial mouthrinses in the past 2 months
  • Individuals with systemic conditions that could impact periodontal disease progression (such as immunological disorders or osteoporosis)
  • Individuals using anti-inflammatory or immunosuppressive medications.
  • Individuals with endodontic lesions or orthodontic appliances
  • Obesity (defined as BMI ≥30 and <40 kg/m², with specific waist-hip ratios for women and men).
• Clinical parameters such as bleeding on probing (BoP), suppuration (SUP), plaque index (PI), and marginal bleeding (MB) were assessed at 6 sites of all teeth, excluding third molars.
• The examiner was blinded to the subjects’ diabetic status.
• GCF was collected from healthy and diseased sites in each participant. Paper strips inserted into the gum pockets captured GCF, which was analysed using multiplex bead immunoassays.
• The collected samples were analyzed for 14 cytokines/chemokines using a multiplex bead immunoassay. Biomarkers included interleukins (IL-1β, IL-6, IL-10, etc.), tumour necrosis factor-α (TNF-α), and chemokines like eotaxin and macrophage inflammatory protein (MIP-1α).
• Statistical analysis:
  • Biomarker concentrations were compared between groups of people living with diabetes  and people living without diabetes.
  • Multivariable regression models assessed the relationship between diabetes and biomarker levels, adjusting for confounding factors.
  • A significance level of p < 0.0035 was set for comparisons between cytokine levels.

Results

• Clinical results revealed that the only significant difference between the 2 groups was the mean PPD which was higher in diabetic subjects (p < 0.05).
• Diabetic subjects had higher levels of HbA1c and FPG compared to non-diabetic individuals (p < 0.05).
• The mean duration of diabetes was 6.4 ± 0.9 years, with most diabetic subjects using oral hypoglycemic agents or insulin.
• No significant differences were observed in GCF volume, PPD, or CAL in both healthy and diseased sites (p > 0.05).
• Regarding cytokine/chemokine concentrations, higher levels of eotaxin, MIP-1a, GM-CSF, IL-6, TNF-α, and IL-12 were found in the diseased sites of those with diabetes compared to non-diabetics (p < 0.05), after adjusting for multiple comparisons (p < 0.0035).
• There was also a trend for higher IL-8 and lower IL-10 (anti-inflammatory) and IL-2 concentrations in those with diabetes.
• Multivariable logistic regression analysis revealed that those with diabetes had higher concentrations of eotaxin, IL-6, TNF-α, and IL-7 in diseased sites, whereas non-diabetic subjects had higher IL-10 and IL-2 levels in both healthy and diseased sites.
• Differences were observed even in healthy gum sites, indicating that hyperglycaemia exacerbates inflammation regardless of periodontal disease status.

Limitations