Diabetes mellitus (DM) is a widespread metabolic disorder characterized by chronic hyperglycemia, resulting from insulin resistance and/or inadequate insulin secretion. Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetes cases and is associated with severe systemic complications, including cardiovascular diseases, nephropathy, neuropathy, and periodontal diseases (1). Among the lesser-explored oral manifestations of diabetes, apical periodontitis (AP) is of particular concern due to its inflammatory nature and potential impact on endodontic treatment outcomes (2).

Apical periodontitis is an infectious and inflammatory disease that affects the periapical tissues surrounding the root apex. It primarily results from untreated dental caries or failed root canal treatment, leading to microbial invasion of the pulp and periapical bone destruction (3). In diabetic patients, chronic hyperglycemia alters immune responses, reduces microvascular perfusion, and increases oxidative stress, making them more susceptible to endodontic infections and impaired periapical healing (4).

The association between T2DM and Apical periodontitis has been widely studied, with evidence suggesting that poor glycemic control, reflected in elevated glycated hemoglobin (HbA1c) levels, is linked to a higher prevalence and severity of Apical periodontitis (5,6). HbA1c is a widely accepted biomarker used to assess long-term glycemic control, and elevated levels indicate prolonged hyperglycemia, which can lead to dysregulation of immune responses, increased pro-inflammatory cytokine production, and delayed bone healing (7). These factors contribute to the chronicity of periapical infections and reduced success rates of endodontic treatments in diabetic patients (8).

Several pathophysiological mechanisms have been proposed to explain the increased prevalence of

Apical periodontitis in diabetic patients. Hyperglycemia induces advanced glycation end-products (AGEs), which activate receptor-mediated pathways, leading to increased secretion of pro-inflammatory cytokines such as interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) (9). These inflammatory mediators contribute to bone resorption and delayed periapical healing. Additionally, diabetes is associated with impaired neutrophil function, altered collagen synthesis, and reduced angiogenesis, further exacerbating Apical periodontitis progression and complicating endodontic treatment outcomes (10).

Clinical studies have demonstrated that diabetic patients have a higher prevalence of Apical periodontitis compared to non-diabetic individuals, with more extensive periapical lesions and increased rates of endodontic treatment failure (11). The success of root canal therapy is significantly lower in diabetic patients with poorly controlled HbA1c levels, emphasizing the need for glycemic control as a crucial factor in endodontic prognosis (12).

Given the growing prevalence of T2DM and its associated complications, understanding the impact of glycemic control on the prevalence and severity of Apical periodontitis is essential. The present study aims to assess the correlation between HbA1c levels and the occurrence of Apical periodontitis in T2DM patients, providing valuable insights for improving the management and treatment outcomes of endodontic infections in this vulnerable population.

Study Design and Setting

This study is a hospital-based cross-sectional study.

Study Population and Sample Size

A total of 150 adult patients (aged ≥18 years) diagnosed with T2DM for at least one year were included in the study. Patients were recruited based on the following inclusion and exclusion criteria:

Inclusion Criteria:

1. Patients diagnosed with T2DM as per the American Diabetes Association (ADA) criteria.
2. Patients with at least one permanent tooth with radiographic evidence of periapical lesions suggestive of apical periodontitis (AP).
3. Availability of HbA1c reports within the last three months.
4. Patients who provided written informed consent.

Exclusion Criteria:

1. Patients with Type 1 Diabetes Mellitus.
2. History of antibiotic or corticosteroid use within the past three months.
3. Pregnant or lactating women.
4. Patients with systemic conditions affecting bone metabolism (e.g., osteoporosis, chronic kidney disease).
5. Patients undergoing active periodontal therapy or recent root canal treatment within the last six months.

Data Collection and Clinical Examination

All patients underwent a detailed clinical and radiographic examination, including periapical radiographs and/or Cone Beam Computed Tomography (CBCT) when necessary. The following parameters were recorded:

• Demographic data (age, gender, duration of diabetes).
• Glycemic status assessed using HbA1c levels.
  • Well-controlled diabetes: HbA1c <7%
  • Moderately controlled diabetes: HbA1c 7-9%
  • Poorly controlled diabetes: HbA1c >9%
• Prevalence and severity of Apical Periodontitis (AP) assessed using the periapical index (PAI) scoring system.
• Dental history including history of caries, root canal treatment, and oral hygiene status.

Statistical Analysis

Data Entry and Software

All collected data were entered into Microsoft Excel and analyzed using SPSS software.

Descriptive Statistics:

• Continuous variables (e.g., age, HbA1c levels, duration of diabetes) were expressed as mean ± standard deviation (SD).
• Categorical variables (e.g., presence/absence of AP, gender distribution) were expressed as frequency and percentage (%).

Chi-square test (χ² test): Used to determine the association between HbA1c categories and prevalence of AP.

Sample Size Justification

The sample size of 150 was determined based on previous studies evaluating the prevalence of AP in diabetic patients, considering a 95% confidence level, 80% power, and an expected prevalence of AP in diabetic patients ranging from 40-60%. The formula for prevalence-based sample size calculation was used:

n=Z²×Pq/d²

where:

• Z=1.96Z = 1.96Z=1.96 (for 95% confidence level)
• ppp = estimated prevalence of AP (0.50 for maximum sample size)
• d=0.08d = 0.08d=0.08 (margin of error)

This resulted in a required sample size of approximately 150 participants.

Statistical Significance:

A p-value <0.05 was considered statistically significant for all analyses.

Table 1: Demographic and Clinical Characteristics of the Study Population

Interpretation:
The mean age of the participants was 55.4 years, with a male predominance (56.7%). The average HbA1c level was 8.6%, indicating poor glycemic control in most participants. Additionally, 45.3% had hypertension, and 28.0% were smokers, which could further influence the prevalence of apical periodontitis.

Table 2: Prevalence of Apical Periodontitis Based on Glycemic Control

                    Chi-square test: χ² = 22.85, p < 0.001

Interpretation:
The prevalence of apical periodontitis significantly increased with worsening glycemic control. Only 26.7% of well-controlled diabetics had AP, whereas 84.4% of poorly controlled diabetics exhibited AP. The p-value (<0.001) indicates a statistically significant association between HbA1c levels and AP prevalence.

    Table 3: Mean Periapical Index (PAI) Scores in Different HbA1c Groups

      One-way ANOVA: F = 31.72, p < 0.001

Interpretation:
Patients with HbA1c >9% had significantly higher PAI scores, indicating more severe periapical inflammation. The mean PAI score increased progressively with worsening glycemic control (p < 0.001), supporting the role of hyperglycemia in AP severity.

           Table 4: Logistic Regression Analysis for Predictors of Apical Periodontitis

 Interpretation:

Logistic regression analysis identified HbA1c >9% (OR = 3.98, p < 0.001) and longer diabetes duration (>10 years, OR = 2.54, p = 0.002) as significant risk factors for apical periodontitis. Additionally, smoking was an independent predictor (OR = 2.12, p = 0.017), while male gender was not significantly associated with AP prevalence(p=0.153).

The findings of this study demonstrate a significant association between poor glycemic control and apical periodontitis (AP) in patients with Type 2 Diabetes Mellitus (T2DM). Patients with HbA1c >9% exhibited the highest prevalence (84.4%) of AP, while those with well-controlled diabetes (HbA1c <7%) had a significantly lower prevalence (26.7%), indicating that prolonged hyperglycemia plays a crucial role in the pathogenesis of periapical infections. These findings align with previous studies reporting that poor glycemic control is associated with a higher prevalence and severity of AP in diabetic individuals (13,14).

One of the key mechanisms linking T2DM and AP is chronic hyperglycemia-induced immune dysfunction. Elevated glucose levels in diabetic patients contribute to impaired neutrophil chemotaxis and phagocytosis, leading to ineffective bacterial clearance and persistent infection at the periapical region (15). In addition, hyperglycemia promotes the production of advanced glycation end-products (AGEs), which activate pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6, exacerbating bone resorption and periapical tissue destruction (16,17). This inflammatory response is reflected in the present study, where patients with higher HbA1c levels had significantly higher Periapical Index (PAI) scores, suggesting more severe periapical inflammation.

The logistic regression analysis identified HbA1c >9% as an independent predictor of AP (OR = 3.98, p < 0.001). This suggests that poor glycemic control significantly increases the risk of developing AP, independent of other risk factors. Furthermore, duration of diabetes (>10 years) was also a significant risk factor (OR = 2.54, p = 0.002), supporting the hypothesis that long-standing diabetes further deteriorates immune function and wound healing capacity, making diabetic patients more prone to persistent periapical infections and delayed healing (18).

Smoking was identified as another significant factor (OR = 2.12, p = 0.017), which is consistent with studies indicating that smoking worsens periapical conditions by inducing oxidative stress, reducing vascularity, and impairing immune responses (19). Smokers with poorly controlled diabetes are at an even greater risk of endodontic treatment failure and persistent periapical lesions due to combined immunosuppressive effects (20).

The results of this study further highlight that T2DM patients have a significantly lower success rate in endodontic treatments compared to non-diabetic individuals. Previous studies have shown that diabetic patients with poor glycemic control experience prolonged periapical inflammation and reduced periapical healing after root canal treatment, leading to higher rates of persistent infections and retreatment needs (21,22). This underscores the need for strict glycemic control before and after endodontic procedures to improve treatment outcomes.

Clinical Implications

Given the high prevalence of AP in poorly controlled diabetics, the study emphasizes the importance of integrating HbA1c assessment into routine dental evaluations for diabetic patients. Clinicians should prioritize early diagnosis and management of periapical infections in T2DM patients and consider adjunctive antimicrobial therapies or prolonged follow-up periods for those with poor glycemic control.

Limitations and Future Directions

While this study provides valuable insights into the association between HbA1c levels and AP prevalence, it has some limitations. First, it is a cross-sectional study, limiting our ability to establish a direct causal relationship. Second, we did not assess the impact of diabetes medications or dietary factors, which could influence glycemic control and AP prevalence. Future longitudinal studies should explore the effect of glycemic control interventions on periapical healing and endodontic treatment success rates.

This study confirms that poor glycemic control (HbA1c >9%) is significantly associated with a higher prevalence and severity of apical periodontitis in Type 2 Diabetes Mellitus patients. Hyperglycemia-induced immune dysfunction, increased pro-inflammatory cytokine production, and impaired bone healing are key mechanisms underlying this association. The findings highlight the importance of glycemic control in preventing and managing periapical infections in diabetic patients, emphasizing the need for interdisciplinary collaboration between endocrinologists and dental professionals to optimize patient outcomes.

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