Differential Association of Salivary Proinflammatory Mediators with Type 2 Diabetes: A Network Meta-Analysis

Background: Salivary compounds can be used as diagnostic markers for changes in the oral cavity that cause oral problems in type 2 diabetes mellitus (T2DM).

Methods: This meta-analysis searched PubMed/Medline, EMBASE, Scopus and Cochrane Library, and the Web of Science until Nov 2023. The observational studies included patients with T2DM and healthy controls aged > 18 yr with no oral health problems or systematic or periodontal diseases. The Quality in Prognostic Studies (QUIPS) tool was used to evaluate the risk of bias. The random-effects model was constructed using standardized mean differences (SMD).

Results: The meta-analysis analyzed 13 observational studies that included 519 patients with T2DM and 356 healthy controls. Non-fasting periods of 30 min to 8 h were used to measure salivary profiles. Overall, salivary proinflammatory mediators favored patients with T2DM (SMD: 1.66; CI_95%: 0.42, 2.91, P<0.01) compared with healthy subjects. Subgroup analysis revealed that interleukin-6 (SMD: 1.33; CI_95%: -0.04, 2.69, P<0.05), followed by interleukin-8 (SMD: 0.92; CI_95%: -0.71, 2.55, P<0.13), was greater in patients with T2DM than in healthy subjects. Among patients with T2DM, network analysis identified salivary factors most closely associated with male sex (i.e., tumor necrosis factor), female sex (i.e., interleukin-8), fasting plasma glucose (i.e., C-reactive protein), HbA1c (i.e., IL-8), and age (i.e., C-reactive protein).

Conclusion: Overall, salivary IL-6 levels were greater in patients with T2DM and might be considered for monitoring oral changes. Moreover, network analysis could identify different salivary components that were most closely associated with patient characteristics.