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

• This cross-sectional analysis used baseline data from 1,071 ORIGINS participants recruited in New York during 2011–2020. Participants were aged 20–55 years (mean approximately 32 years; 72.5% female), had no diagnosed diabetes, fasting glucose <126 mg/dL and HbA1c <6.5%, and reported no cardiovascular disease or chronic inflammatory conditions.
• Calibrated examiners measured clinical attachment loss (CAL), probing pocket depth (PPD) and bleeding on probing (BOP) at six sites per tooth. CDC/AAP-defined moderate/severe periodontitis was compared with periodontal health/mild disease.
• The primary exposures were interproximal CAL and PPD, measured between teeth. Mean values were divided into tertiles (three groups), and the percentages of sites with CAL or PPD ≥3 mm were also examined. Full-mouth measurements and BOP were assessed separately.
• Fasting glucose, HbA1c and insulin were measured, and insulin resistance was estimated using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR). Prediabetes was defined as fasting glucose 100–125 mg/dL or HbA1c 5.7%–6.4%.
• Poisson regression estimated prediabetes prevalence ratios (PRs), while linear regression assessed biomarkers. Fully adjusted models included study wave, demographic factors, smoking, BMI, diet quality, HDL cholesterol and blood pressure. Multiple imputation addressed missing covariates.

Results

• Prediabetes was present in 134 participants (12.5%). Moderate/severe periodontitis was not significantly associated with prediabetes after full adjustment: PR 1.12 (95% CI 0.79–1.45). Glucose, HbA1c, insulin and HOMA-IR were also similar between the periodontal disease categories.
• Higher mean interproximal CAL was associated with greater prediabetes prevalence. Compared with the lowest tertile, adjusted PRs were 1.74 (95% CI 1.13–2.34) for the middle tertile and 2.42 (95% CI 1.77–3.08) for the highest tertile. These estimates describe existing prediabetes, not future diabetes risk.
• Adjusted mean fasting glucose was 83.29, 84.31 and 86.48 mg/dL across increasing interproximal CAL tertiles; corresponding HbA1c values were 5.23%, 5.28% and 5.35% (both trends p < .01 in Table 3). Although statistically significant, these group averages remained below prediabetes thresholds. Insulin and HOMA-IR trends were not significant.
• For mean interproximal PPD, fully adjusted trends were not significant for insulin (p = .12) or HOMA-IR (p = .20). However, a greater percentage of interproximal sites with PPD ≥3 mm was associated with higher insulin and HOMA-IR (p = .02 and .04, respectively). These different measures should not be treated as interchangeable.
• BOP was not significantly associated with prediabetes, fasting glucose, insulin or HOMA-IR, although greater BOP was associated with lower HbA1c.
• No statistically significant interaction between mean CAL and BMI was detected. This does not establish that associations are identical in people with and without obesity.

Limitations

• The cross-sectional design cannot determine which condition occurred first or establish causality. Higher glucose could contribute to periodontal changes rather than result from them.
• Residual confounding, including possible effects of biological ageing, remains despite adjustment for several shared risk factors.
• The relatively young, predominantly female cohort had limited severe periodontal destruction. Findings may not generalise to older adults or the wider population, and periodontal classification may miss early disease differences.
• Limited statistical power may have prevented detection of differences by obesity status.
• Different insulin assays were used across recruitment waves, potentially introducing measurement error into insulin resistance estimates.

Conclusion

• Greater interproximal attachment loss was associated with prevalent prediabetes and higher fasting glucose and HbA1c among younger adults without diabetes. However, categorically defined moderate/severe periodontitis was not significantly associated with prediabetes after adjustment.
• The extent of interproximal sites with PPD ≥3 mm was associated with insulin resistance, whereas the trend across mean PPD tertiles was not significant after full adjustment. The authors interpreted CAL as cumulative tissue damage and probing depth as reflecting current inflammation; this study did not demonstrate active disease progression.
• These findings support further longitudinal and intervention studies. They do not validate attachment loss as a diabetes screening test or demonstrate that periodontal treatment prevents prediabetes or diabetes.