Impact of periodontitis on diabetic complications

Background + Aims

• Chronic kidney disease (CKD) involves impaired kidney function, increasing the risk of cardiovascular disease, infection, and mortality. Despite medical advances, CKD prevalence is rising globally.
• Periodontitis, a common inflammatory oral disease, is now recognised as a modifiable risk factor for CKD.
• Evidence suggests periodontal pathogens and inflammatory markers may impair kidney function by affecting endothelial cells in nephrons.
• Both diabetes and periodontitis are linked to CKD, with diabetes potentially mediating this relationship.
• This study aims to explore the causal pathways between periodontitis, diabetes, and CKD through mediation analysis to better understand their complex interactions.

Materials + Methods

• The study was an observational cohort design, utilising data from the Electric Generation Authority of Thailand (EGAT) project. The EGAT project is a prospective cohort study investigating non-communicable disease risk factors, with health surveys conducted every five years.
• Data from the 2003 survey (EGAT2/2) served as the baseline, with follow-ups in 2008 (EGAT2/3) and 2013 (EGAT2/4).
• Participants were included if they completed all three surveys. Exclusions applied to those with baseline kidney dysfunction (eGFR <60 ml/min/1.73 m²), refusal of periodontal examination, systemic conditions requiring antibiotic prophylaxis, or complete tooth loss.
• Baseline characteristics, health behaviours, and medical history were collected via self-administered questionnaires.
• Physical examinations and fasting blood tests were conducted by trained personnel from Ramathibodi Hospital.
• Periodontal health was assessed by calibrated periodontists from Chulalongkorn University using periodontal probing depth (PPD) and gingival recession (RE) measurements at six sites per tooth. Clinical attachment level (CAL) was calculated, and inter-examiner reliability was assessed using weighted kappa scores. Periodontitis severity was quantified as the percentage of proximal sites with CAL ≥5 mm, and the CDC/AAP case definition was also applied.
• Diabetes was diagnosed based on fasting blood glucose levels ≥126 mg/dl or the use of anti-diabetic medications.
• The outcome of interest was chronic kidney disease (CKD), defined as eGFR <60 ml/min/1.73 m², calculated using the CKD-EPI equation.
• Multiple imputation using chain equations (MICE) addressed missing data, assuming it was missing at random.
• Mediation analysis was performed using structural causal diagrams to explore two pathways:
  • Periodontitis as the independent variable, diabetes as the mediator, and CKD as the outcome
  • Diabetes as the independent variable, periodontitis as the mediator, and CKD as the outcome.
• The generalised structural equation model (GSEM) was used to account for within- and between-participant variability over time.
• The causal mediation effects were estimated using the product of coefficients method, with bootstrap analysis (1,000 replications) to generate bias-corrected confidence intervals.
• Statistical analyses were performed, with significance set at p < 0.05.

Results

• 2,635 participants were included in the final analysis
  • Mean age at baseline: 47.7 years
  • Gender at baseline: 73% male
  • Diabetes at baseline: 7.7%
  • Hypertension at baseline: 27.3%
  • Dyslipidaemia at baseline: 68.6%
  • Moderate periodontitis at baseline: Approximately 50%
  • Severe periodontitis at baseline: Approximately 30%
• Over the 10-year follow-up:
  • 272 new CKD cases were identified, with a cumulative incidence of 10.3 cases per 100 persons.
  • CKD incidence rates increased with periodontitis severity:
    • 2 cases per 100 persons in those with no/mild periodontitis
    • 6 cases in moderate periodontitis
    • 9 cases in severe periodontitis.
• Missing data ranged from 0.38% to 18.3%, and multiple imputation using the MICE method was applied to address this.
• Causal Diagram A (Periodontitis → Diabetes → CKD):
  • Periodontitis was significantly associated with diabetes incidence (p<0.001)
  • Both, diabetes and periodontitis independently increased CKD risk.
  • Mediation analysis found that 42.4% of periodontitis’ effect on CKD was mediated through diabetes.
  • Each 1% increase in severe periodontitis sites led to a 0.7% increased CKD risk via diabetes and a 1.0% direct risk increase.
• Causal Diagram B (Diabetes → Periodontitis → CKD):
  • Diabetes was linked to a higher extent of severe periodontitis (4.8% more sites)
  • The indirect pathway through periodontitis accounted for 6.5% of the total effect of diabetes on CKD.
  • The total odds ratio (OR) for CKD in subjects with diabetes was 2.09, with the direct effect contributing 93.5% and the periodontitis-mediated effect contributing 6.5%.
• Sensitivity analyses confirmed consistent mediation effects across different periodontitis definitions, supporting the robustness of the findings.

Limitations