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

Abstract

BackgroundType 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 HbA1c in a T1D cohort.MethodsUnstimulated saliva was collected from 144 subjects with T1D at the USF Diabetes Center. BMI, duration of diabetes, and HbA1c 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.ResultsMultiple linear (HbA1c) and logistic (self-reported gingival condition) regression analyses were performed to examine the relationships between the Principal Component Analysis (PCA) components and HbA1c and gingival condition (adjusted for age, duration of diabetes, BMI, and sex; model for HbA1c also adjusted for gingival condition and model for gingival condition also adjusted for HbA1c). PCA components 1 (MMP-8 and MMP-9) and 3 (TNF-α) were significantly associated with HbA1c (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.ConclusionsThe saliva may represent a useful reservoir of novel noninvasive inflammatory biomarkers predictive of the progression and control of T1D.

Dominant TNFα and impaired IL‐2 cytokine profiles of CD4+ T cells from children with type‐1 diabetes

“…In the LEW.1AR1‐ iddm rat animal model of T1D, treatment with anti‐TNFα only in combination with anti‐ T‐cell receptor antibodies restored normoglycemia, normalized C‐peptide and increased beta‐cell proliferation 36 . Furthermore, T1D patients studies identified increased TNFα plasma concentration associated with higher HbA1c 37 and lower C‐peptide levels 38 . In accordance, we found TNFα‐dominant T MEM responses especially at long‐term T1D stage.…”

Effects of Hypoxia during Continuous and Intermittent Exercise on Glycaemic Control and Selected Markers of Vascular Function in Type 1 Diabetes

“…It has been shown that one of the factors regulating the production of VEGF is a pro-inflammatory cytokine TNF-α [43,53]. Kuehl et al [69] demonstrated a positive correlation between the concentration of the cytokine and HbA1c in the saliva of patients with T1D. This result would indicate a role of the cytokine in maintaining inflammation process in the course of the disease.…”

“…Therefore, the observed in the present study tendency for TNF-α to decrease in response to hypoxia and interval exercise is an important finding. It has been shown that lower cytokine concentration can enhance angiogenesis [69,70], which can be beneficial in the organs, where the process is impaired (i. e., the skeletal muscles, the skin, the heart). ExC in hypoxia, on the other hand, caused an insignificant increase in TNF-α concentration.…”

Cytokine Regulation of Regenerative Processes in Pancreatic Gland in Alloxan-Induced Diabetic Rats, and It Correction by 1,3,4-Thiadiazine Composition and Lipoic Acid

“…Отмечают повышенный уровень TNFα также у грызунов с аллоксановым и стрептозотоциновым диабетом [20]. Увеличение содержания TNFα обнаружи-вают не только в плазме крови и слюне больных СД [26], но также в различных тканях диабети-ческих крыс, в том числе в сетчатке глаза [23]. IL-1 подавляет продукцию инсулина β-клетками и стимулирует их апоптоз [28].…”

“…По-вышенное содержание IL-6 выявлено у больных СД 1 и СД 2 типа в плазме крови [15,22], а также в плазме крови мышей с аллоксановым диабетом [20]. У больных CД 1 типа содержание IL-6 кор-релировало с повышением уровня гликирован-ного гемоглобина [26].…”