Impact of type 1 diabetes on the inflammatory response in periodontal disease

Ana Mendes-Frias^1,2Alexandra Viana Da Costa^3,4Filomena Salazar^5,6Ana Cristina Braga⁷Ricardo Silvestre^2,8*Marta Relvas⁶

• ¹Life and Health Sciences Research Institute, School of Medicine, University of Minho, Braga, Portugal
• ²Universidade do Minho Instituto de Investigacao em Ciencias da Vida e Saude, Braga, Portugal
• ³Institute for Health and Bioeconomy, Gandra, Portugal
• ⁴Instituto Universitario de Ciencias da Saude Unidade de Investigacao em Toxicologia & Uma So Saude, Gandra, Portugal
• ⁵Department of Medicine and Oral Surgery, University Institute of Health Sciences (IUCS-CESPU), Gandra, Portugal
• ⁶Instituto Universitario de Ciencias da Saude Unidade de Investigacao em Patologia Oral e Reabilitacao, Gandra, Portugal
• ⁷Universidade do Minho Centro ALGORITMI, Guimaraes, Portugal
• ⁸Laboratorio Associado ICVS 3B's, Guimaraes, Portugal

Type 1 diabetes mellitus (T1DM) is increasing globally and represents a significant public health concern. Periodontitis affects about 11% of the global population, particularly in its severe forms, and is 1.5 to 2 times more prevalent in individuals with poorly controlled T1DM. Both conditions are multifactorial, chronic, and inflammatory, sharing a bidirectional relationship: T1DM accelerates the onset and progression of periodontitis, while periodontal inflammation worsens glycemic control. This observational case-control study included adults with T1DM and metabolically healthy controls, stratified by periodontal status: healthy, gingivitis, or periodontitis. Cytokine profiles were assessed in both saliva and gingival crevicular fluid (GCF) to characterize the oral immune response. Significant associations were observed between T1DM and both the extent and severity of periodontal disease. T1DM patients with gingivitis exhibited increased bleeding on probing (BOP) and probing pocket depth (PPD), with BOP remaining significantly elevated in those with periodontitis. GCF analysis revealed a dysregulated immune profile in T1DM patients, characterized by elevated IL-1𝛽, IL-6, IL-8 and IL-17A, and reduced levels of IL-2, IL-4, IL-12p70 and IP-10. The salivary cytokine profile generally mirrored GCF findings, with higher IL-6 and IL-8 concentrations and strong correlations with key pro-inflammatory cytokines. Salivary IL-8 emerged as the most promising biomarker for distinguishing periodontal status in T1DM patients. Overall, these findings highlight the clinical potential of salivary immune profiling as a non-invasive tool for monitoring periodontal inflammation and assessing disease activity in individuals with T1DM.