Plasma fetuin-A/α2-HS-glycoprotein correlates negatively with inflammatory cytokines, chemokines and activation biomarkers in individuals with type-2 diabetes

Abstract

BackgroundFetuin-A/AHSH is a novel hepatokine that acts as a vascular calcification inhibitor and as an endogenous TLR-4 ligand. Fetuin-A may act as a positive or negative acute phase protein (APP) in disease conditions. The relationship between circulatory fetuin-A and inflammatory biomarkers in type-2 diabetes (T2D) remains controversial. Therefore, the purpose of this study was to determine the plasma fetuin-A levels in 53 T2D (BMI = 29.7 ± 4.5 kg/m2) and 72 non-diabetic individuals (BMI = 28.2 ± 5.8 kg/m2) using premixed 38-plex MAP human cytokine/chemokine magnetic bead immunoassays and the data (mean ± SEM) were statistically analyzed to determine Pearson’s correlation (r) between fetuin-A and detected analytes; P-values ≤0.05 were considered significant.ResultsThe data show that plasma fetuin-A levels were comparable in both groups (P = 0.27) and in T2D individuals, fetuin-A associated negatively (P ≤ 0.05) with a large number of proinflammatory cytokines/chemokines and activation biomarkers including TNF-α, IFN-α2, IFN-γ, IL-1α, IL-1β, IL-1RA, IL-3, IL-4, IL-7, IL-9, IL-12p40/p70, IL-15, CCL-2, CCL-4, CCL-11, CCL-22, CXCL-8, CX3CL-1, EFF-2, EGF, G-CSF, GM-CSF, GRO, sCD40L, and VEGF. In non-diabetics, fetuin-A also correlated positively with certain TH2 cytokines (IL-5, IL-13) and chemokines (CCL-3, CCL-5, CCL-7). Notably, in vitro fetuin-A production was significantly suppressed in HepG2 cells treated with TNF-α, IL-1β, and IFN-γ which supported the clinical findings of a negative association between fetuin A and inflammatory mediators.ConclusionsThe negative association between circulatory fetuin-A and systemic inflammatory mediators in T2D patients suggests that plasma fetuin-A may have predictive significance as a negative APP in metabolic disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12865-016-0171-y) contains supplementary material, which is available to authorized users.

Prediction of gestational diabetes mellitus in the first trimester: comparison of maternal fetuin-A, N-terminal proatrial natriuretic peptide, high-sensitivity C-reactive protein, and fasting glucose levels

“…Sindhu and cols. demonstrated a negative correlation between plasma levels of fetuin-A and systemic inflammatory markers in patients with type 2 diabetes (4). Serum levels of fetuin-A increase mid-trimester in normal pregnancies (5).…”

Fetuin‐A, serum amyloid A and tumor necrosis factor alpha levels in periodontal health and disease

“…In the current study, consideration of all groups simultaneously showed a negative and significant correlation between the total amount of fetuin‐A and SAA, TNF‐ α , CAL, and GI. There is evidence that fetuin‐A is negatively associated with systemic inflammatory mediators (Sindhu et al , ). To evaluate the relationship between fetuin‐A and inflammatory markers, we examined the correlations between fetuin‐A, TNF‐ α , and SAA.…”

Fetuin-A – Alpha2-Heremans-Schmid Glycoprotein: From Structure to a Novel Marker of Chronic Diseases Part 2. Fetuin-A – A Marker of Insulin Resistance and Related Chronic Diseases

“…Fetuin-A levels reveal a divergent correlation with pro-in ammatory markers in patients with T2DM. The investigation of in ammatory mediators or activation markers in T2DM patients by Sindhu et al (2016) demonstrated a reciprocal correlation between plasma levels of fetuin-A and interleukin (IL)-1 , IL-7, IL-15, tumor necrosis factor alpha (TNF-), chemokine ligand (CCL)-2, CCL4, soluble CD40L (sCD40L), growth related oncogene (GRO), elongation factor F (EFF) 2, and vascular endothelial growth factor (VEGF) [31]. The study provided evidence that fetuin-A levels are reciprocally associated with the pro-in ammatory cytokines and biomarkers that possess a predictive value of fetuin-A as a negative acute phase protein in patients with T2DM.…”