fetuin-A Levels Research Articles

Impact of Fetuin-A on progression of calcific aortic valve stenosis - The COFRASA - GENERAC study

BackgroundAortic stenosis (AS) is an active disease, but the determinants of AS progression remain largely unknown. Low levels of Fetuin-A, a powerful inhibitor of ectopic calcification, have been linked to ectopic calcium tissue deposition but its role in AS progression has not been clearly evaluated. MethodsIn our ongoing prospective cohort (COFRASA/GENERAC), serum Fetuin-A level was measured at baseline and AS severity was evaluated at baseline and yearly thereafter using echocardiography (mean pressure gradient (MPG)) and computed tomography (degree of aortic valve calcification (AVC)). Annual progression was calculated as [(final measurement-baseline measurement)/follow-up duration] for both MPG and AVC measurements. ResultsWe enrolled 296 patients (74 ± 10 years,73% men); mean follow-up duration was 3.0 ± 1.7 years. No correlation was found between baseline serum Fetuin-A (0.55 ± 0.15 g/L) and baseline AS severity (r = 0.25, p = 0.87 for MPG; r = 0.06, p = 0.36 for AVC). More importantly, there was no correlation between baseline serum Fetuin-A level and AS progression either assessed using MPG or AVC (both r = 0.01, p = 0.82). In bivariate analysis, after adjustment for age, gender, baseline AS severity, or valve anatomy, Fetuin-A was not associated with AS progression (all p > 0.20). The absence of link with AS progression was further confirmed by the absence of link betwen serum Fetuin-A and the occurrence of AS-related events (p = 0.17). ConclusionsIn a large prospective cohort of AS patients, serum Fetuin-A was not associated to hemodynamic or anatomic AS progression. Despite its capacity to inhibit ectopic calcium deposition, Fetuin-A serum level seemed to have minor influence on AS progression.

Correlation analysis of monocyte subsets and insulin resistance considering fetuin-A involvement in patients with type 2 diabetes

BackgroundFetuin-A is a multifunctional circulating glycoprotein that can induce insulin resistance. Lately, adipose tissue has gained prominence as an effector site of fetuin-A. Although fetuin-A—induced proinflammatory polarization and migration of macrophages plays a crucial role, it remains obscure whether monocyte subsets in circulation could simulate characteristics of macrophages in adipose tissues. This study aims to investigate the correlation between monocyte subsets with fetuin-A and its relevant insulin resistance.ResultsWe evaluated serum fetuin-A levels in 107 patients with type 2 diabetes (T2D). Using flow cytometry, we classified monocyte subsets into three subtypes: (a) classical, CD14++CD16−; (b) intermediate, CD14++CD16+, the most proinflammatory one; (c) and nonclassical, CD14+CD16++. We assessed the insulin resistance by the homeostasis model assessment for insulin resistance (HOMA-IR) in 68 patients without insulin injections. We observed no correlation between fetuin-A levels and classical (ρ = − 0.005; P = 0.959), intermediate (ρ = 0.022; P = 0.826), and nonclassical monocyte counts (ρ = 0.063; P = 0.516), respectively. In addition, no significant correlation was found between log (HOMA-IR) and classical (ρ = 0.052; P = 0.688), intermediate (ρ = 0.054; P = 0.676), and nonclassical monocyte counts (ρ = 0.012; P = 0.353), respectively. However, serum fetuin-A levels showed positive correlation with log (HOMA-IR) (ρ = 0.340; P = 0.007). Multiple regression analyses revealed a significant relationship between fetuin-A and log (HOMA-IR) (β = 0.313; P = 0.016), but not with monocyte subsets.ConclusionsMonocyte subsets in circulation, including proinflammatory intermediate monocytes, were not associated with fetuin-A and insulin resistance.

The relationship of IL-6, hs-CRP and Fetuin-A with cardiac valve calcification in maintenance hemodialysis

Objective To investigate the relationship of IL-6, hs-CRP and Fetuin-A with cardiac valve calcification(CVC) in maintenance hemodialysis(MHD). Methods A total of 163 ca-ses of MHD patients in our hospital from January 2014 to December 2016 were collected, according to the whether ornot CVC were divided into the CVC group(n=68) and the non-CVC group(n=95), and according to the number and extent of CVC were divided into the non-CVC group(n=95), one CVC group(n=37), two CVC group(n=31) and mild group (n=22), moderate group (n=31), severe group (n=15). The levels of IL-6, hs-CRP and Fetuin-A in each group were compared, the correlation between Fetuin-A and clinical data was analyzed. Results In the 163 patients, CVC was found in 68 patients(41.72%). The abdominal aorta calcification score, dialysis time, age, iPTH, hs-CRP, IL-6, serum phosphorus, calcium phosphorus product in the CVC group were higher than non-CVC group, the serum albumin, Fetuin-A were lower than non- CVC group(P 0, P<0.05), and negative correlation with abdominal aorta calcification score, CVC, IL-6, hs-CRP, iPTH, dialysis time and age reached significant level(r<0, P<0.05). Conclusions The severity of CVC in patients with CVC is correlated with abdominal aorta calcification score, IL-6, hs-CRP and Fetuin-A, and has some clinical value in evaluating the occurrence and development of CVC in patients with MHD. Key words: Renal Dialysis; Heart Valves; Calcinosis; Interleukin-6; C-Reactive Protein; alpha-Fetoproteins

Exploring Biological and Geological Age-related Changes through Variations in Intra- and Intertooth Proteomes of Ancient Dentine.

Proteomic analyses are becoming more widely used in archeology not only due to the greater preservation of proteins in ancient specimens than DNA but also because they can offer different information, particularly relating to compositional preservation and potentially a means to estimate biological and geological age. However, it remains unclear to what extent different burial environments impact these aspects of proteome decay. Teeth have to date been much less studied than bone but are ideal to explore how proteins decay with time due to the negligible turnover that occurs in dentine relative to bone. We investigated the proteome variability and deamidation levels of different sections of molar teeth from archeological bovine mandibles as well as their mandibular bone. We obtained a greater yield of proteins from the crown of the teeth but did not find differences between the different molars analyzed within each mandible. We also obtained the best variety of protein from a well-preserved mandible that was not the youngest one in terms of chronological age, showing the influence of the preservation conditions on the final proteomic outcome. Intriguingly, we also noticed an increase in abundance levels of fetuin-A in biologically younger mandibles as reported previously, but the opposite trend in tooth dentine. Interestingly, we observed higher glutamine deamidation levels in teeth from the geologically oldest mandible despite it being the biologically youngest specimen, showing that the archeological age strongly impacts on the level of deamidations observed, much more so than biological aging. This indicates that the glutamine deamidation ratio of selected peptides may act as a good predictor of the relative geochronological age of archeological specimens.

Association of fetuin-A with incident type 2 diabetes: results from the MONICA/KORA Augsburg study and a systematic meta-analysis

We investigated the association of circulating fetuin-A with incident T2D particularly examining potential sex differences. Additionally, we determined whether putative associations were independent of subclinical inflammation, adiponectin and liver fat content. Case-cohort study plus systematic meta-analysis. We investigated the association between baseline fetuin-A levels and incident T2D in the MONICA/KORA Augsburg study using Cox proportional hazards analyses. Furthermore, we conducted a systematic review within PubMed and EMBASE and pooled association estimates of eligible studies with the MONICA/KORA Augsburg data using a DerSimonian-Laird random effects model. Within MONICA/KORA Augsburg, 930 participants developed incident T2D (median follow-up: 14 years). We observed a significant association between fetuin-A and T2D risk after multivariable adjustment including C-reactive protein and adiponectin. The strength of the association was similar in males and females (P value for sex interaction >0.55). Seven eligible published studies were identified in addition to the MONICA/KORA Augsburg study for the meta-analysis. The pooled hazard ratio (95% CI) for incident T2D per 1 standard deviation (s.d.) increment of fetuin-A was 1.24 (1.14-1.34) for the multivariable adjusted model. Our sex-stratified meta-analysis yielded relative risk estimates per 1 s.d. of 1.19 (1.04-1.38) in males and 1.29 (1.15-1.46) in females. Further individual adjustment for subclinical inflammation, adiponectin and liver fat content had almost no impact on the strength of the association. Higher fetuin-A levels are associated with incident T2D in both males and females independently of subclinical inflammation, adiponectin and liver fat content.

Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification: A Role for GRP (Gla-Rich Protein).

Inhibition of mineral crystal formation is a crucial step in ectopic calcification. Serum calciprotein particles (CPPs) have been linked to chronic kidney disease (CKD) calcification propensity, but additional knowledge is required to understand their function, assemblage, and composition. The role of other circulating nanostructures, such as extracellular vesicles (EVs) in vascular calcification is currently unknown. Here, we investigated the association of GRP (Gla-rich protein) with circulating CPP and EVs and the role of CKD CPPs and EVs in vascular calcification. Biological CPPs and EVs were isolated from healthy and CKD patients and comparatively characterized using ultrastructural, analytic, molecular, and immuno-based techniques. Our results show that GRP is a constitutive component of circulating CPPs and EVs. CKD stage 5 serum CPPs and EVs are characterized by lower levels of fetuin-A and GRP, and CPPs CKD stage 5 have increased mineral maturation, resembling secondary CPP particles. Vascular smooth muscle cell calcification assays reveal that CPPs CKD stage 5 and EVs CKD stage 5 are taken up by vascular smooth muscle cells and induce vascular calcification by promoting cell osteochondrogenic differentiation and inflammation. These effects were rescued by incubation of CPPs CKD stage 5 with γ-carboxylated GRP. In vitro, formation and maturation of basic calcium phosphate crystals was highly reduced in the presence of γ-carboxylated GRP, fetuin-A, and MGP (matrix gla protein), and a similar antimineralization system was identified in vivo. Uremic CPPs and EVs are important players in the mechanisms of widespread calcification in CKD. We propose a major role for cGRP as inhibitory factor to prevent calcification at systemic and tissue levels.

Serum Fetuin-A Levels in Patients with Bilateral Basal Ganglia Calcification

Background and PurposeThe idiopathic basal ganglia calcification (Fahr syndrome) may occur due to senility. Fetuin-A is a negative acute phase reactant which inhibits calcium-phosphorus precipitation and vascular calcification. In this study, we aimed to evaluate whether serum fetuin-A levels correlate with bilateral basal ganglia calcification. MethodForty-five patients who had bilateral basal ganglia calcification on brain CT were selected according to the inclusion and exclusion criteria, and 45 age and gender-matched subjects without basal ganglia calcification were included for the control group. Serum fetuin-A levels were measured from venous blood samples. All participants were divided into two groups; with and without basal ganglia calcification. These groups were divided into subgroups regarding age (18–32 and 33–45 years of age) and gender (male, female). ResultsWe detected lower levels of serum fetuin-A in patients with basal ganglia calcification compared with the subjects without basal ganglia calcification. In all subgroups (female, male, 18–32 years and 33–45 years), mean fetuin-A levels were significantly lower in patients with basal ganglia calcification (p = 0.017, p = 0.014, p = 0.024, p = 0.026, p = 0.01 respectively). And statistically significantly lower levels of fetuin-A was found to be correlated with the increasing densities of calcification in the calcified basal ganglia group (p-value: <0.001). ConclusionConsidering the role of fetuin-A in tissue calcification and inflammation, higher serum fetuin-A levels should be measured in patients with basal ganglia calcification. We believe that the measurement of serum fetuin-A may play a role in the prediction of basal ganglia calcification as a biomarker.

Can Fetuin-A Be a Marker for Insulin Resistance and Poor Glycemic Control in Children with Type 1 Diabetes Mellitus?

Objective:Metabolic impairment in type 1 diabetes mellitus (T1DM) with poor glycemic control causes insulin resistance, non-alcoholic fatty liver disease (NAFLD), atherosclerosis, and increased carotid intima-media thickness (CIMT). Fetuin-A has a protective effect in cardiovascular disorders and is increased in hepatosteatosis. We aimed to investigate the reliability of fetuin-A levels in early detection of diabetic complications in children with T1DM and to identify a cut-off value that may show poor metabolic control.Methods:The study included 80 patients who had T1DM for at least 5 years and who had no chronic complications or an auto-immune disorder. Blood samples were drawn to measure hemoglobin A1c (HbA1c), biochemical parameters, and fetuin-A levels. Anthropometric parameters were also measured. Percent body fat was calculated. Hepatosteatosis and CIMT were assessed by sonography. Results:Mean age of the patients was 13.5 years. Grade 1 hepatosteatosis was detected in 10%. Patients were stratified into 2 groups based on presence of NAFLD. Fetuin-A level was increased in patients with NAFLD. We identified a fetuin-A cut-off value (514.28 ng/mL; sensitivity: 47.34; specificity: 96.72) that may predict NAFLD. HbA1c and total cholesterol levels were found to be higher in patients with fetuin-A levels above higher the cut-off value.Conclusion:Fetuin-A is a reliable parameter in the prediction of complications and poor glycemic control in patients with T1DM.

Serum fetuin-A levels in obese and non-obese subjects with and without type 2 diabetes mellitus

BackgroundHigher fetuin-A expression is linked to both obesity and type 2 diabetes mellitus (T2DM), However, studies in non-obese patients with T2DM are scarce. Methods345 newly diagnosed T2DM patients and 300 subjects with normal glucose tolerance (NGT) were divided into obese and non-obese subgroups, respectively. Serum fetuin-A and adiponectin levels and related parameters were measured. ResultsT2DM patients with obesity had higher fetuin-A levels compared with non-obese patients and obese NGT subjects (p<0.001). Significant correlations were observed between fetuin-A and most metabolic parameters in obese NGT and T2DM subjects, but which was not in non-obese patients with T2DM. The independent associations were found between fetuin-A and free fatty acids, HOMA-IR, C-reactive protein and adiponectin only in obese NGT and T2DM subjects (all p<0.05). The adjusted odds ratios for obesity were increased with increasing quartile of fetuin-A in both T2DM and NGT subjects in logistic regression models (p for trend<0.001), but which was more significant in T2DM patients. ConclusionHigher serum fetuin-A levels in obese T2DM patients compared with non-obese patients and obese NGT subjects supports the hypothesis that fetuin-A may be as a bridge connecting obesity and obesity-related T2DM.

Vascular calcification is not related to serum fetuin-A and osteopontin levels in hemodialysis patients.

Vascular calcification (VC) in hemodialysis (HD) patients is a sign of severe cardiovascular disease and can predict cardiovascular outcomes. Fetuin-A and osteopontin (OPN) inhibit VC. Serum fetuin-A levels are lower in patients with end-stage kidney disease (ESKD) and in those who are on chronic HD therapy. However, there are limited data concerning OPN in patients who are on dialysis. The aim of our study was to determine VC in HD patients, the relationship between VC and 25-OH-vitamin D, fetuin-A, and OPN levels, and independent predictors of VC. Ninety-three patients with ESKD on HD therapy were recruited. Among these patients, 44 were male and 49 were female. The patient group was compared with a group of 20 healthy controls of similar age and sex. A plain radiograph of the hand was taken using a mammography machine for the evaluation of VC. Serum fetuin-A, OPN, and 25-OH-vitamin D levels of both patients and controls were measured. VC was detected in 45 (48.4%) HD patients. When patients were compared with healthy controls, fetuin-A levels (p<0.029) were significantly lower in patients, whereas OPN (p<0.000) and VC (p<0.002) were significantly higher in the patient group. Age [odds ratio (OR) 1.036], the presence of diabetes mellitus (DM) (OR 17.527), and high parathyroid hormone (PTH) levels (OR 1.002) were independent predictors of VC in a logistic regression model including the following factors: age, the presence of DM, HD duration, and serum albumin, phosphate, PTH, 25-OH-vitamin D, fetuin-A, OPN, and calcium levels. No significant correlation was found between patients with VC and patients without VC in terms of fetuin-A, OPN, and 25-OH-vitamin D levels. VC is a frequent sign in patients undergoing HD and is not related to serum fetuin-A and osteopontin levels. Age, the presence of DM, and high PTH levels were independent predictors of VC in patients undergoing HD. Further studies are warranted to understand the mechanism underlying and the factors contributing to VC.

Fetuin-A levels and risk of type 2 diabetes mellitus: a systematic review and meta-analysis.

Fetuin-A has been linked to insulin resistance and obesity. Its role in the pathogenesis of type 2 diabetes (T2DM) has also been discussed. We aimed to investigate the prospective association of fetuin-A and the risk of T2DM in a systematic review and meta-analysis. A systematic search of studies from the MEDLINE, EMBASE, Pubmed and Web of Science using fetuin-A, diabetes and various synonyms was conducted up to June 5, 2017. Relevant studies were extracted by two reviewers independently. The quality of studies was assessed using Newcastle-Ottawa scales. Overall estimates were pooled using fixed effect with inverse variance meta-analysis. Subgroup analyses by gender, study population, techniques of assessing fetuin-A, diabetes ascertainment methods, follow-up duration and measures of association were conducted. Seven studies comprising a total of 11,497 individuals and 2176 cases of T2DM were included in the systematic review and meta-analysis. Overall, one SD increment of fetuin-A level was associated with a 23% greater risk of incident T2DM (RR: 1.23, 95% CI 1.16-1.31). No significant heterogeneity or publication bias was found. The association was relatively stable across different subgroups. However, the association seemed only evident in women, but not in men. Higher circulating fetuin-A levels were associated with increased risk of T2DM. However, the causality deserved further analysis.

Elevated serum fetuin-A levels are associated with grades of retinopathy in type 2 diabetic patients.

Fetuin-A is a physiological inhibitor of insulin receptor tyrosine kinase and thus associated with insulin resistance, metabolic syndrome, and an increased risk for type 2 diabetes mellitus (T2DM). This study aims to investigate the possible relation between the serum fetuin-A levels and the stages of diabetic retinopathy (DR) in patients with T2DM. This prospective study included 82 patients with T2DM and 19 age- and gender-matched healthy controls (HCs) (group 1). Diabetic patients were subclassified into three groups according to ocular findings: without DR (group 2; n=26); non-proliferative DR (group 3; n=29), and proliferative DR (group 4; n=27). Serum fetuin-A levels were determined by a spectrophotometric technique using an immulite chemiluminescent immunometric assay. The data were analyzed using a Mann-Whitney U test, and the results were expressed as mean±standard deviation. Mean fetuin-A values were 256.4±21.3μg/ml in group 1, 263.5±24.2μg/ml in group 2, 282.2±31.1μg/ml in group 3, and 296.3±26.2μg/ml in group 4. Group 2 had higher mean fetuin-A level compared with group 1, but the difference was not statistically significant (p>0.05). Serum fetuin-A levels were significantly higher in groups 3 and 4 compared with HCs (both p<0.05). Compared with group 2, both DR groups had higher fetuin-A levels with a significant difference (both p<0.05); and patients with proliferative DR had significantly higher serum fetuin-A levels compared with non-proliferative DR (p<0.05). The mean serum fetuin-A levels increased with the stage of DR, and the highest levels were found in patients with proliferative DR. Our findings suggest an association between fetuin-A levels and DR stage. In diabetic patients, the risk of retinopathy development increases with higher fetuin-A values. Fetuin-A may play an important role in the pathophysiology and progression of DR.

Serum Fetuin-A levels in obese children with biopsy proven nonalcoholic fatty liver disease

Background and aimsFetuin-A has been proposed as a marker of liver damage in adults with obesity-related NAFLD. The aim of this study was to test serum fetuin-A concentrations in obese children with NAFLD diagnosed either by ultrasonography or by liver biopsy and to determine its applicability as predictive tool in pediatric NAFLD. Methods and resultsMetabolic parameters and fetuin-A levels were investigated in 81 obese children with NAFLD diagnosed by biopsy, 79 obese children with NAFLD defined by liver ultrasonography and 23 lean subjects.Serum fetuin-A correlated significantly with age, waist circumference, systolic blood pressure, fasting insulin and 2-h postload insulin during OGTT, HOMA-IR, ISI, CRP, and apo B levels. Obese children with NAFLD detected by ultrasonography had significantly higher fetuin-A levels compared to those with normal liver. In obese children who underwent liver biopsy, no significant differences were detected in fetuin-A levels between subject with nonalcoholic steatohepatitis and those with simple steatosis. Fetuin-A was not different between obese and lean children. ConclusionFetuin-A is not related with the degree of liver damage in obese children with NAFLD and its routine measurement as marker of liver disease severity is therefore not recommended.

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery.

The elucidation of the changes of fetuin-A in the context of bariatric surgery. Twenty obese patients (8 males, 12 females; body mass index = 42.5±3.4 kg/m2) were studied at baseline and 6 months after bariatric surgery. Serum fetuin-A levels did not differ with regard to the presence of each individual component of the Metabolic Syndrome (MetS) at baseline, except for hypertriglyceridaemia [increased serum fetuin-A levels (p=0.011)]. Circulating fetuin-A was positively correlated with serum triglycerides (TG) (r=0.461, p=0.047) and negatively correlated with serum globulins (r=-0.477, p=0.033) and C-reactive protein (CRP) (r=-0.604, p=0.010), while it independently predicted TG at baseline. Circulating fetuin-A did not change during the 6 months either in the whole population or in the subgroups of patients who were positive for each individual component of MetS at baseline and negative for this component at 6 months of follow-up, except for hypertriglyceridaemia [reduction of serum fetuin-A levels (p=0.046)]. The subgroup of patients with a decrease in circulating fetuin-A during the 6 months was characterized by a smaller reduction of serum globulins (p=0.003) and CRP (p=0.049). The change in serum fetuin-A levels over the 6 months was positively correlated with the change in TG (r=0.592, p=0.006) and negatively correlated with the change in serum globulins (r=-0.523, p=0.018) and CRP (r=-.494, p=0.037). Circulating fetuin-A predicted serum triglycerides before as well as 6 months after bariatric surgery.

Serum Fetuin-A Evaluation in Chronic Hepatitis C-Virus Patients with Concomitant Type 2 Diabetes Mellitus

Background and study aim: Hepatitis C virus infection represents a potential public health problem worldwide. Many studies have shown markedly higher prevalence of insulin resistance (IR) and type 2 diabetes mellitus (T2DM) among patients with hepatitis C virus (HCV) infection compared to healthy subjects. Fetuin-A is one of the principal hepatokines regulating the human metabolism. This study aimed to estimate the level of Fetuin-A in HCV patients with concomitant T2DM, and its relation to insulin resistance. Patients and Methods: The study was conducted on 115 subjects, 87 patients had chronic HCV infection with and without T2DM, diabetic patients without HCV infection and 28 healthy control, they were subjected to full history taking thorough clinical examination, abdominal ultrasonography, routine laboratory investigation including fasting and post prandial blood glucose level and assessment of HOMA- IR, viral markers and serum Fetuin-A level by ELISA. Results Conclusion : There was high statistically significant increase of serum Fetuin-A level among HCV with DM patient group followed by HCV group when compared to DM and control groups. Serum Fetuin-A level was higher in HCV patients than non HCV subjects with statistically significant difference.Also,it was higher among diabetic patients than non diabetic subjects with statistically significant difference.Serum Fetuin-A level was positively correlated with glucose homeostasis parameters in both HCV and HCV&D.M patients with high statistically significant difference. At Cut-off value of serum Fetuin-A >5.2 mg/mL, Sensitivity was 54.84, Specificity was 96.30, positive PV 94.4 and negative PV was 65.0 for prediction of IR in HCV patients. While, at Cut-off value of serum Fetuin-A >4.9 mg/mL, sensitivity was 72.41, specificity was 79.31, positive PV was 77.8 and negative PV was 74.2 for prediction of DM in HCV patients. Conclusion: Fetuin-A may have role as a mediator in IR of either HCV or diabetes. However, Fetuin-A is more specific for evaluation of IR than DM in HCV patients as other factors may be incriminated in the pathogenesis of DM in HCV patients other than serum Fetuin-A level alone.

Lower Plasma Fetuin-A Levels Are Associated With a Higher Mortality Risk in Patients With Coronary Artery Disease.

The present study was designed to evaluate the association of circulating fetuin-A with cardiovascular disease (CVD) and all-cause mortality. We measured plasma fetuin-A in 1620 patients using an enzyme-linked immunosorbent assay kit. The patients were members of the Guangdong coronary artery disease cohort and were recruited between October 2008 and December 2011. Cox regression models were used to estimate the association between plasma fetuin-A and the risk of mortality. A total of 206 deaths were recorded during a median follow-up of 5.9 years, 146 of whom died from CVD. The hazard ratios for the second and third tertiles of the fetuin-A levels (using the first tertile as a reference) were 0.65 (95% confidence interval, 0.44-0.96) and 0.51 (95% confidence interval, 0.33-0.78) for CVD mortality (P=0.005) and 0.65 (95% confidence interval, 0.47-0.91) and 0.48 (95% confidence interval, 0.33-0.70) for all-cause mortality (P<0.001), respectively. Lower plasma fetuin-A levels were associated with an increased risk of all-cause and CVD mortality in patients with coronary artery disease independently of traditional CVD risk factors.

Serum osteoprotegerin in prevalent hemodialysis patients: associations with mortality, atherosclerosis and cardiac function

BackgroundTo assess whether serum osteoprotegerin (OPG) and/or fetuin-A predict mortality and cardiovascular (CV) morbidity and mortality in hemodialysis patients.MethodsMulticenter, observational, prospective study that included 220 hemodialysis patients followed up for up to 6 years. Serum OPG and fetuin-A levels were measured at baseline and their possible association with clinical characteristics, CV risk biomarkers, carotid ultrasonographic findings, as well as their association with overall and CV mortality and CV events were assessed.ResultsDuring a mean follow-up of 3.22 ± 1.91 years, there were 74 deaths (33.6%) and 86 new cardiovascular events. In the Kaplan-Meier survival analysis, the highest tertile of OPG levels was associated with higher overall mortality (p = 0.005), as well as a higher, although non-significant, incidence of CV events and CV mortality. In contrast, fetuin-A levels did not predict any of these events. OPG levels were directly associated with age, the Charlson comorbidity index (CCI), prevalent cardiovascular disease, carotid intima-media thickness, adiponectin, troponin-I and brain natriuretic peptide (BNP). OPG showed a negative correlation with left ventricular ejection fraction (LVEF) and phosphate levels. In the multivariate Cox proportional hazard analysis, all-cause mortality was associated with the highest tertile of OPG (HR:1.957, p = 0.018), age (HR:1.031, p = 0.036), smoking history (HR:2.122, p = 0.005), the CCI (HR:1.254, p = 0.004), troponin-I (HR:3.894, p = 0.042), IL-18 (HR:1.061, p < 0.001) and albumin levels (HR:0.886, p < 0.001). In the bootstrapping Cox regression analysis, the best cut-off value of OPG associated with mortality was 17.69 pmol/L (95%CI: 5.1–18.02).ConclusionsOPG, but not fetuin-A levels, are independently associated with overall mortality, as well as clinical and subclinical atherosclerosis and cardiac function, in prevalent hemodialysis patients.

Effect of a 12-Week Aerobic Exercise Training on Serum Fetuin-A and Adipocytokine Levels in Type 2 Diabetes.

We aimed to evaluate the effect of 12-week aerobic exercise training on fetuin-A levels in type 2 diabetes mellitus and examine the relationships between fetuin-A and adipocytokine levels and cardiovascular risk factors. The study included 32 patients with type 2 diabetes mellitus who were assigned to an exercise or a control group. The exercise group underwent 12 weeks of exercise (consisting of a 5-min warm-up, 60-min aerobic bicycle training performed at 70% of the maximal heart rate, a cool-down period, 5 times/week). Adiponectin, resistin, and fetuin-A serum levels were measured using enzyme-linked immunosorbent assay. Leptin serum levels were measured by a radioimmunoassay. Exercise for 12 weeks significantly reduced serum fetuin-A (643.1±109.4 to 448.7±92.5 μg/mL, P<0.05), leptin (11.9±7.2 to 8.6±5.7 ng/dL, P<0.05), and resistin (3.2±1.5 to 2.2±1.4 ng/mL, P<0.05) levels, but increased adiponectin (6.9±1.9 to 8.1±1.7 µg/mL, P<0.05) levels. In the exercise group, Δfetuin-A positively correlated with differences in weight (r=0.654, P=0.046), body mass index (r=0.725, P=0.002), waist circumference (r=0.898, P=0.013), and adiponectin levels (r=0.662, P=0.035). Aerobic exercise significantly decreased serum fetuin-A levels in type 2 diabetes mellitus, which can be attributed to weight loss and related to increased adiponectin levels.

Phase Angle Predicts Arterial Stiffness and Vascular Calcification in Peritoneal Dialysis Patients.

Fluid overload (FO) is frequently present in peritoneal dialysis (PD) patients and is associated with markers of malnutrition, inflammation, and atherosclerosis/calcification (MIAC) syndrome. We examined the relationships in stable PD patients between phase angle (PhA) and the spectrum of uremic vasculopathy including vascular calcification and arterial stiffness and between PhA and changes in serum fetuin-A levels. Sixty-one stable adult PD patients were evaluated in a cross-sectional study (ST1). Phase angle was measured by multifrequency bioimpedance analysis (InbodyS10, Biospace, Korea) at 50 kHz. Augmentation index (AI), a surrogate marker of arterial stiffness, was assessed by digital pulse amplitude tonometry (Endo PAT, Itamar Medical, Caesarea, Israel). Vascular calcification was assessed by simplified calcification score (SCS). Serum fetuin-A levels were measured by ELISA (Thermo scientific; Waltham, MA, USA). Serum albumin was used as a nutritional marker, and serum C-reactive protein (CRP) was used as an inflammatory marker. The same assessments were carried out longitudinally (ST2) in the first 33 patients who completed 1 year of evaluation in ST1. In ST1, patients with PhA < 6° had higher CRP levels, AI, and SCS and lower serum albumin and fetuin-A levels, in comparison with patients with PhA ≥ 6°. In addition, PhA was a predictor of both AI (β = -0.351, p = 0.023) and SCS ≥ 3 (EXP (B) = 0.243, p = 0.005). In ST2, the increase of PhA over time was associated with decreases in both AI (r = -0.378, p = 0.042) and CRP levels (r = -0.426, p = 0.021), as well as with the increase in serum fetuin-A levels (r = 0.411, p = 0.030). Phase angle predicts both arterial stiffness and vascular calcification in stable PD patients.

The association between circulating fetuin-A levels and type 2 diabetes mellitus risk: systematic review and meta-analysis of observational studies.

Fetuin-A is a liver-derived circulating protein that is associated with insulin resistance and diabetes. The objective of this systematic review and meta-analysis of published observational studies was to investigate mean levels of fetuin-A in T2D patients and the relationship between blood fetuin-A levels and T2D risk. PubMed, Embase, Google Scholar, Web of Science, and The Cochrane Library were systematically searched for potential relevant studies up to 1 December 2016. Natural logarithm-transformed estimate risks, standard mean differences on the basis of Hedges's adjusted g, and 95% confidence intervals (CIs) were calculated for all eligible studies and were combined to measure the pooled data using random-effects model. A total of 32 studies including 27 case-control and 5 cohort studies were included in the current study. Fetuin-A levels in T2D patients were significantly higher than control groups [Hedges' g=1.73, 95% CI (1.25-2.22), P<0.001], with significant heterogeneity across studies (P<0.001, I 2=98.46%). Findings from meta-analyses of cohort studies showed a statistically significant association between fetuin-A levels and T2D risk [rate ratio=1.62, 95% CI (1.26-2.08), P<0.001], with no significant heterogeneity (P=0.10, I 2=46.06%). We found a significant relationship between the fetuin-A levels with T2D risk. Although fetuin-A may be as a potential screening and prediction biomarker or a therapeutic target in T2D patients, further studies are required in this regard.