Periodontitis and pre-diabetes

Background + Aims

• Prediabetes is increasingly recognised as a major public health issue, affecting about 35% of adults in the United States (US), or roughly 88 million people. While it serves as a significant indicator for developing diabetes, prediabetes is reversible, with around 13% of individuals returning to normal glucose levels. Managing risk factors during the prediabetic phase could alleviate the diabetes burden, a leading cause of morbidity and mortality.
• Periodontitis, a chronic inflammatory condition involving a microbial imbalance in the oral cavity, is speculated to be bidirectionally linked to diabetes via impaired glucose regulation and insulin resistance.
• Treatments for periodontitis have shown promise in improving glycaemic control in diabetic patients. However, the connection between periodontitis and prediabetes remains underexplored, with existing studies yielding mixed results. Some indicate a higher incidence of prediabetes among those with periodontitis, while others report no significant association. Most research has focused on older populations, leaving a gap in understanding the relationship in younger individuals without existing cardiometabolic diseases. Additionally, the categorisation of periodontitis in studies often fails to reflect its continuum or consider varying disease measures.
• The study aims to examine the relationship between various forms of periodontitis and the prevalence of prediabetes and cardiometabolic markers in young-to-middle-aged non-diabetic adults in the Oral Infections, Glucose Intolerance, and Insulin Resistance Study (ORIGINS). They hypothesise that poorer periodontal health will correlate with higher prediabetes prevalence and increased fasting glucose, HbA1c, and insulin resistance.

Materials + Methods

• Participants included in the study were aged 20 to 55 years, did not have diabetes mellitus (type 1 or 2) based on self-reported physician diagnosis, had fasting plasma glucose levels below 126 mg/dL and HbA1c below 6.5%, and reported no history of cardiovascular disease or chronic inflammatory conditions. A total of 1,071 participants (mean age = 32.2 years; 73% female) from the ORIGINS study were enrolled.
• Clinical assessments of full-mouth clinical attachment loss (CAL), probing pocket depth (PPD), and bleeding on probing (BOP) were conducted by calibrated examiners. Periodontitis was classified into four categories: healthy, mild, moderate, and severe. The mean CAL, PPD, and the percentage of sites with BOP were calculated for each participant across up to 192 probing sites and divided into tertiles. The extent and severity of full-mouth and interproximal CAL and probing depth were assessed by determining the % of sites with CAL of ≥3mm and probing depth of ≥3mm.
• Outcomes for glucose, HbA1c, insulin, and insulin resistance were measured from fasting blood samples. Prediabetes was defined according to American Diabetes Association guidelines, indicating fasting plasma glucose between 100 and 125 mg/dL or HbA1c between 5.7% and 6.4%.
• Covariates, including age, sex, race/ethnicity, education, income, smoking history, physical activity, blood pressure, lipid profile, BMI, and dietary habits, were self-reported or measured during visits.
• Prediabetes prevalence ratios and mean cardiometabolic biomarkers were analysed using multivariable robust variance Poisson regression or multivariable linear regression.

Results

• Moderate to severe periodontitis was linked to a 12% increase in prediabetes prevalence compared to healthy or mildly diseased individuals, though these results were not statistically significant. Glucose, HbA1c, insulin, and Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) levels were generally similar across different periodontitis categories.
• Increased CAL was associated with higher prediabetes prevalence; adjusted prevalence ratios (PRs) were significant across CAL tertiles:
  – Tertile 2: PR = 1.74
  – Tertile 3: PR = 2.42
• Fasting plasma glucose and HbA1c levels significantly increased with higher CAL tertiles. No significant trends were observed for insulin or HOMA-IR across CAL tertiles.
• Higher PPD tertiles showed elevated insulin and HOMA-IR levels, while prediabetes prevalence and glucose levels remained similar across PPD categories. A direct correlation was observed between the percentage of sites with significant PPD and insulin levels.
• BOP was not significantly associated with prediabetes or other metabolic markers, but it showed a linear decrease in HbA1c levels with increasing BOP severity.
• Obese individuals exhibited higher prediabetes prevalence and metabolic markers compared to non-obese participants. Associations between mean CAL measures and metabolic risks were consistent regardless of obesity status.

Limitations