Cytokine levels in periodontitis among type 2 diabetes patients

Research Topic:

Background + Aims

Periodontitis and diabetes share a bidirectional relationship, where poor glycaemic control exacerbates periodontal disease and vice versa. The interplay between periodontal inflammation and glycaemic status is mediated by immune cells, primarily T-helper (Th) cells, which regulate pro- and anti-inflammatory cytokine production.
Key cytokines such as TNF-α, IFN-γ, IL-4, IL-17, and IL-23 play critical roles in maintaining or disrupting periodontal tissue homeostasis. IFN-γ and IL-17, for instance, are linked to tissue destruction, while IL-4 has anti-inflammatory effects. However, the specific impact of glycaemic control on these cytokines in individuals with diabetes and chronic periodontitis remains inadequately explored.
While prior research has established the relationship between periodontitis and diabetes, this study focuses on specific cytokine dynamics and the therapeutic impact of non-surgical periodontal therapy (NSPT) over six months. This study addresses a critical gap by analysing cytokine levels in gingival crevicular fluid (GCF) from patients with well-controlled and poorly controlled diabetes and chronic periodontitis, before and after NSPT. The findings aim to provide insights into how hyperglycaemia modulates immune responses, potentially influencing disease progression and treatment outcomes. Understanding these mechanisms is essential for tailoring periodontal care in patients with diabetes, ultimately improving both oral and systemic health outcomes.
The study aims to compare the levels of TNF-α, IFN-γ, IL-4, IL-17, and IL-23 in GCF from well-controlled and poorly controlled T2DM patients with chronic periodontitis before and after NSPT over 6 months, assessing the impact of glycaemic status on periodontal inflammation and cytokine expression.

Materials + Methods

The study involved 38 T2DM patients (20 poorly controlled, HbA1c > 8%; 18 well-controlled, HbA1c ≤ 8%) aged 40–67 years with chronic periodontitis.
Inclusion criteria included: diagnosis of T2DM for >5 years, presence of ≥15 teeth, and periodontitis with probing depth (PD) ≥4 mm in ≥30% of sites.
Exclusion criteria included: smoking, systemic illnesses (other than diabetes), recent periodontal/antibiotic treatments, or pregnancy.
Patients had scaling and root planing (SRP) conducted over 2–4 sessions under local anaesthesia. They then underwent maintenance therapy and oral hygiene instructions provided at 3 and 6 months.
Data collection involved:
GCF sampled at baseline, 3, and 6 months from two sites per patient (PD ≥ 5 mm).
Clinical parameters: PD, clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP).
Cytokine quantification (TNF-α, IFN-γ, IL-4, IL-17, IL-23) using ELISA.
Blood tests: HbA1c and fasting plasma glucose (FPG).
Group comparisons and correlations between cytokine levels, clinical parameters, and HbA1c were performed using non-parametric and parametric tests.

Results

At baseline patients those with poorly controlled T2DM had a higher plaque index (81.3%) and slightly higher bleeding on probing (53.2%) than the well-controlled T2DM group (52.9% and 49.9%, respectively).
At 3 months, PI reduced to 30.3% in the poorly controlled T2DM group and 21.3% in well-controlled T2DM group. BOP decreased to 7.8% and 11.5%, respectively. PD improved from 3.4 mm at baseline to 2.5 mm in poorly controlled T2DM group and to 2.7 mm in well-controlled T2DM group at both 3 and 6 months.
Cytokine levels at baseline demonstrated:
IL-17 was higher in poorly controlled T2DM group and positively correlated with HbA1c levels.
IFN-γ was higher in well-controlled T2DM group (0.75 pg/ml vs 0.50 pg/ml) and negatively correlated with HbA1c.
IL-4 levels were higher in poorly controlled T2DM group (0.20 pg/ml vs 0.15 pg/ml).

Cytokine Trends Post-Therapy:
- IFN-γ increased at 3 and 6 months in well-controlled T2DM group, correlating with improved PD and BOP.
- IL-17 levels remained elevated in the poorly controlled T2DM group despite clinical improvements.
Poorly controlled T2DM group maintained higher HbA1c levels (10.4% at baseline, 10.9% at 6 months) compared to well-controlled patients (7.0% at baseline, 8.3% at 6 months).

Limitations

The study’s small sample size may limit its generalisability.
The study did not include a non-diabetic control group, making it difficult to distinguish whether the observed cytokine patterns were solely attributable to glycaemic control or shared inflammatory mechanisms between diabetes and periodontitis.
The cytokine analysis was limited to specific markers, potentially overlooking other key mediators involved in periodontal inflammation and healing, such as IL-1β or matrix metalloproteinases (MMPs).
The study relied on GCF sampling, which, while useful for assessing local inflammation, does not fully capture systemic inflammatory changes or broader immune responses. GCF cytokine levels can be influenced by factors such as sampling techniques or localised variations in periodontal disease.
The study did not assess long-term outcomes beyond six months. Periodontitis is a chronic condition, and longer follow-up periods are necessary to evaluate the sustainability of clinical improvements and cytokine shifts.
Future studies should also account for potential confounders such as diet, medication changes, and patient adherence to oral hygiene practices, which could impact both glycaemic control and periodontal health.

Conclusion

Glycaemic control significantly influences cytokine expression in chronic periodontitis. Poorly controlled T2DM is associated with elevated IL-17 levels, indicating a pro-inflammatory Th17-dominant response, whereas well-controlled diabetes exhibits increased IFN-γ, suggesting a Th1 response.
NSPT effectively improved clinical outcomes, such as reduced PD, BOP, and PI, in both groups. However, cytokine levels, particularly IL-17, remained elevated in poorly controlled patients, indicating persistent inflammation despite therapy. Notably, unlike other studies, glycaemic control (HbA1c levels) did not improve following periodontal therapy.
This study underscores the importance of glycaemic control in managing periodontal inflammation. For clinicians, it highlights the need to consider diabetes status in periodontal treatment planning and supports multidisciplinary approaches to improve both metabolic and periodontal health.

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