Tumor Necrosis Factor-α, Matrix-Metalloproteinases 8 and 9 Levels in the Saliva Are Associated with Increased Hemoglobin A1c in Type 1 Diabetes Subjects

BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease resulting in the targeted destruction of pancreatic β-cells and permanent loss of insulin production. Proper glucose management results in better clinical outcomes for T1D and provides a strong rationale to identify non-invasive biomarkers indicative or predictive of glycemic control. Therefore, we investigated the association of salivary inflammation with HbA(1c) in a T1D cohort. METHODS: Unstimulated saliva was collected from 144 subjects with T1D at the USF Diabetes Center. BMI, duration of diabetes, and HbA(1c) were recorded during clinical visit. Levels of interleukin (IL)-1β, -6, -8, -10, IFN-γ, TNF-α, MMP-3, -8, and -9 were measured using multiplexing immunoassay analysis. To account for smoking status, salivary cotinine levels were also determined. RESULTS: Multiple linear (HbA(1c)) and logistic (self-reported gingival condition) regression analyses were performed to examine the relationships between the Principal Component Analysis (PCA) components and HbA(1c) and gingival condition (adjusted for age, duration of diabetes, BMI, and sex; model for HbA(1c) also adjusted for gingival condition and model for gingival condition also adjusted for HbA(1c)). PCA components 1 (MMP-8 and MMP-9) and 3 (TNF-α) were significantly associated with HbA(1c) (β = 0.28 ±0.14, p = 0.045; β = 0.31 ±0.14, p = 0.029), while PCA component 2 (IL-6, IL-1β, and IL-8) was significantly associated with gingival condition (OR 1.60 95% CI 1.09–2.34, p = 0.016). In general, increased salivary inflammatory burden is associated with decreased glycemic control and self-reported gingival condition. CONCLUSIONS: The saliva may represent a useful reservoir of novel noninvasive inflammatory biomarkers predictive of the progression and control of T1D.