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 HbA1c in a T1D cohort.


METHODS
Unstimulated 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.


RESULTS
Multiple 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.


CONCLUSIONS
The saliva may represent a useful reservoir of novel noninvasive inflammatory biomarkers predictive of the progression and control of T1D.
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, the United States of America.
Melanie N
MN
Kuehl
Diabetes Center, College of Medicine, University of South Florida, Tampa, Florida, the United States of America.
Henry
H
Rodriguez
Department of Cell Biology, Microbiology and Molecular Biology, University of South Florida, Tampa, Florida, the United States of America; Diabetes Center, College of Medicine, University of South Florida, Tampa, Florida, the United States of America.
Brant R
BR
Burkhardt
Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, Florida, United States of America.
Amy C
AC
Alman
D015415:Biomarkers / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D016015:Logistic Models; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D025341:Principal Component Analysis; D012463:Saliva / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D015415:Biomarkers; D006442:Glycated Hemoglobin; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D014409:Tumor Necrosis Factor-alpha; C517652:hemoglobin A1c protein, human