Mechanisms linking periodontitis and diabetes

Background + Aims

• Emerging evidence suggests that periodontitis may increase the risk of developing type 2 diabetes.
• Cross-sectional studies, such as NHANES III in the US and KNHANES in Korea, have shown that periodontitis is associated with impaired fasting glucose and diabetes.
• Prospective studies in the US, Germany, and Japan further confirmed that individuals with periodontitis have poorer glycaemic control and higher risk of diabetes.
• Inflammation may be a key mechanism linking periodontitis to diabetes, as elevated systemic inflammatory markers like C-reactive protein (CRP) and white blood cell count (WBC) have been observed in both conditions.
• Research has begun to assess other inflammatory biomarkers, such as the neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR), known predictors of diabetes, although their link to periodontitis remains unclear.
• This study aims to investigate the relationship between periodontitis and impaired fasting glucose or diabetes in a Thai population and to explore whether CRP, WBC, NLR, and PLR mediate or modify these associations.

Materials + Methods

• This cross-sectional study analysed data from the Electricity Generating Authority of Thailand (EGAT) cohort between June and November 2003.
• Participants with ≥6 teeth and complete medical data were included, while those with conditions affecting inflammatory markers were excluded.
• Medical history, sociodemographic data, and physical exams were collected.
• Periodontal assessments, conducted by 6 calibrated periodontists, measured probing depth (PD) and clinical attachment level (CAL) at 6 sites per tooth.
• Participants were categorised into no/mild, moderate, or severe periodontitis based on CDC/AAP definitions.
• Glycaemic status was assessed using fasting plasma glucose (FPG) levels: normal (<100 mg/dl), impaired fasting glucose (100–126 mg/dl), or diabetes (≥126 mg/dl or on anti-diabetic medication).
• Blood samples were analysed for WBC, CRP, NLR, and platelet–lymphocyte ratio (PLR).
• CRP was measured using a high-sensitivity immunonephelometric assay.
• Covariates included age, gender, education, smoking and drinking status, exercise, body mass index (BMI), family history of diabetes, hypercholesterolemia, and hypertension.
• Multinomial logistic regression estimated the odds of IFG based on periodontitis severity.
• Mediation and effect modification analyses assessed whether inflammatory biomarkers influenced the association between periodontitis and glycaemic status.

Results

• Of the 2,036 participants analysed:
  • IFG: 16.3%
  • Diagnosed with diabetes: 7.4%
• Participants with diabetes were generally older, male, less educated, and had a higher prevalence of smoking, drinking, obesity, hypercholesterolemia, and hypertension.
• Periodontitis severity increased with worsening glycaemic status. Severe periodontitis was apparent in:
  • 50% of participants with diabetes
  • 2% of participants with IFG
  • 7% of normoglycaemic individuals
• Inflammatory biomarkers such as CRP and WBC increased with both periodontitis severity and worsening glycaemic status, while PLR decreased. NLR showed no significant difference across glycaemic groups.
• Multinomial logistic regression revealed that severe periodontitis was associated with an:
  • Increased likelihood of diabetes (OR = 2.4, p = .006)
  • Increased likelihood of IFG (OR = 1.6, p = .023).
• For every 1-mm increase in mean PD or CA, the odds of diabetes increased by 90% and 40%, respectively.
• Mediation analysis showed that CRP, WBC, and PLR partially mediated the association between severe periodontitis and glycaemic status, explaining up to 19.1% of the effect for IFG and 12.6% for diabetes. The NLR did not significantly mediate these associations.
• No inflammatory biomarkers tested were identified as effect modifiers of the periodontitis-diabetes relationship.

Limitations