fetuin-A Levels Research Articles

Effect of circulating exosomes derived from normal-weight and obese women on gluconeogenesis, glycogenesis, lipogenesis and secretion of FGF21 and fetuin A in HepG2 cells

BackgroundIt is generally accepted that obesity can lead to metabolic disorders such as NAFLD and insulin resistance. However, the underlying mechanism has been poorly understood. Moreover, there is evidence to support the possible role of exosomes in the metabolic homeostasis regulation. Accordingly, we aimed to determine the effect of plasma circulating exosomes derived from obese and normal-weight women on insulin signaling and the secretion of hepatokines in human liver cells.MethodsPlasma exosomes isolated from four obese (O-Exo) women and four normal-weight (N-Exo) female candidates were characterized for size, zeta potential, and CD63 protein expression and were used for stimulation of HepG2 cells. Then, cell viability, as well as levels of glycogen and triglyceride (TG), were evaluated. Levels of fetuin-A and FGF21 were measured using the ELISA kit. Expression of glucose 6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) genes were determined using qRT-PCR. Western blot analysis was carried out to evaluating the phosphorylation of GSK3β.ResultsThe TG levels increased significantly in the cells treated with O-Exo than the control (vehicle) group (P = 0.005) and normal-weight group (P = 0.018). Levels of p-GSK3β and glycogen were significantly reduced by O-Exo in comparison with control (P = 0.002, P = 0.018, respectively). The mRNA expression of G6pase and PEPCK enzymes increased in the cells treated with O-Exo in comparison with the vehicle group (P = 0.017, P = 0.010, respectively). The levels of FGF21 in the supernatant of cells treated with O-Exo and N-Exo were significantly lower than the control group (P = 0.007).ConclusionIt appears that obesity-related circulating exosomes can impair insulin signaling pathways and associated components, increase intracellular TG content, and decrease FGF21 secretion in the hepatocytes.

Fetuin-a to adiponectin ratio is a sensitive indicator for evaluating metabolic syndrome in the elderly

BackgroundFetuin-A and adiponectin present significant associations, supported by recent evidence, with metabolic syndrome (MS) featuring hyperglycemia, central obesity and insulin resistance as the main components, but their biological functions are opposite. The aim of this study was to verify whether fetuin-A/adiponectin ratio (F/A ratio) is a more sensitive indicator for evaluation of MS than either fetuin-A or adiponectin.MethodsIn this cross-sectional study, 465 elderly subjects were selected from the physical examination database. Serum levels of fetuin-A and adiponectin were measured using an enzyme-linked immunosorbent assay (ELISA) method. Spearman’s rank correlation coefficient, linear regression and logistic regression analysis were adopted to estimate the correlations of fetuin-A, adiponectin and F/A ratio with MS and its components, and receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive values of the aforesaid indices.ResultsCompared with fetuin-A or adiponectin, F/A ratio was significantly associated with all the components of MS, and this correlation was significant even after adjusting potential confounding factors (P < 0.05). Logistic regression analysis indicated that F/A ratio presented a stronger correlation with incident MS (adjusted OR: 1.466; 95% CI: 1.189–1.808) than fetuin-A (adjusted OR: 1.100; 95% CI: 1.020–1.186) and adiponectin (adjusted OR: 0.760; 95% CI: 0.664–0.871) alone. ROC analysis revealed that F/A ratio achieved a larger area under curve (AUC) than fetuin-A and adiponectin, with their AUC values of 0.755, 0.709 and 0.708, respectively.ConclusionF/A ratio is a more sensitive index for evaluating MS than either fetuin-A or adiponectin in the elderly.

Fetuin-A as a Marker of Insulin Resistance in Type 2 Diabetic Patients in Zagazig University

Background: Fetuin-A is responsible for instigating insulin resistance by inhibiting tyrosine kinase receptors. Objective: To investigate the relationship of fetuin-A with and insulin resistance in type- II diabetics either obese or non-obese of Zagazig University, Shatkia Governorate, Egypt. Patients and Methods: This is a case-control study that was conducted at the Internal Medicine Department of Zagazig University. Seventy-five participants were divided into three groups. Group-A (n =25) normal healthy individual, Group-B (n =25) non-obese type 2 diabetic patients and Group C (n=25) obese type 2 diabetic patients. Type 2 diabetic patients with no morbidities. Serum fetuin-A and insulin levels were performed by ELISA kits while fasting blood glucose (FBG), 2HPP and HA1C were determined by the enzymatic kit method. A comparison of groups was done and correlation was achieved by using Spearman correlation. Results: The results demonstrated a significant difference in mean values of fetuin-A, BMI, WHR, fasting blood glucose (FBG), 2HPP, HA1C, insulin level and Homoeostasis Model Assessment of Insulin resistance (HOMAIR) in type-II diabetics when compared to normal healthy individuals and obese type-II diabetics (p<0.01). The fetuin-A level was higher in obese more than non-obese type II diabetics. Conclusion: The study concluded that fetuin-A might be accountable for insulin resistance in type-II diabetes mellitus either obese or non-obese. So the high levels of Fetuin-A responsible for insulin resistance.

Fetuin-A as a Marker of Insulin Resistance in Type 2 Diabetic Patients in Zagazig University

Background: Fetuin-A is responsible for instigating insulin resistance by inhibiting tyrosine kinase receptors. Objective: To investigate the relationship of fetuin-A with and insulin resistance in type- II diabetics either obese or non-obese of Zagazig University, Shatkia Governorate, Egypt. Patients and Methods: This is a case-control study that was conducted at the Internal Medicine Department of Zagazig University. Seventy-five participants were divided into three groups. Group-A (n =25) normal healthy individual, Group-B (n =25) non-obese type 2 diabetic patients and Group C (n=25) obese type 2 diabetic patients. Type 2 diabetic patients with no morbidities. Serum fetuin-A and insulin levels were performed by ELISA kits while fasting blood glucose (FBG), 2HPP and HA1C were determined by the enzymatic kit method. A comparison of groups was done and correlation was achieved by using Spearman correlation. Results: The results demonstrated a significant difference in mean values of fetuin-A, BMI, WHR, fasting blood glucose (FBG), 2HPP, HA1C, insulin level and Homoeostasis Model Assessment of Insulin resistance (HOMAIR) in type-II diabetics when compared to normal healthy individuals and obese type-II diabetics (p<0.01). The fetuin-A level was higher in obese more than non-obese type II diabetics. Conclusion: The study concluded that fetuin-A might be accountable for insulin resistance in type-II diabetes mellitus either obese or non-obese. So the high levels of Fetuin-A responsible for insulin resistance.

Fetuin A: Is a New Biomarker for Growth?

Vitamin D deficiency is common in the World and Turkey due to changing lifestyles. The association with autoimmune diseases such as obesity, metabolic syndrome, diabetes, cardiovascular diseases and important diseases such as cancer has made it important to prevent vitamin D deficiency. Fetuin-A is a glycoprotein produced in the liver and it is effective in the inhibition of bone mineralization, insulin resistance, obesity and calcification in smooth muscle. In the study conducted, it was aimed to investigate the relationship between the two substances in growth retardation, considering that Vitamin D and Fetuin-A are acting through similar mechanisms. The study was conducted with 50 healthy children with growth retardation. In short patients and underweight patients, vitamin D levels were found to be lower than control group (respectively p = 0,011 p = 0,036). As vitamin D value increased one unit, it was found that the risk of growth retardation decreased by 1,071 times (p = 0,21). Fetuin-A levels were higher in those with growth retardation (p = 0,035). In the preschool group, fetuin-A was higher than middle childhood (p &lt; 0,001). In short patients, fetuin-A levels were higher than control groups (p = 0,043). There was a poor correlation between vitamin D and fetuin-A levels in those with growth retardation (rho: 0,366 p = 0,009). Fetuin-A levels were higher in short children and there was a positive relationship between vitamin D and fetuin-A levels in those with growth retardation. Vitamin D levels were lower in those with growth retardation.

Apoptosis biomarkers (Apaf-1, sFa s, sFa s-L, and caspase-9), albumin, and fetuin-A levels in pulmonary thromboembolic patients

INTRODUCTION: Pulmonary thromboembolism (PE) is the third most common medical emergency with mortality due to ischemia and reperfusion lung injury. Lung ischaemia-reperfusion injury. Lung reperfusion damage is believed to cause cellular damage and apoptosis. The aim of the present study was to evaluate the levels of fetuin-A, albumin, and apoptosis biomarkers (Apaf-1, sFas, and sFasL) among pulmonary thromboembolic patients. MATERIAL AND METHODS: Blood samples were collected from 45 volunteer patients and 40 healthy control volunteers. Human apoptosis biomarkers (Apaf-1, sFas, sFasL, and caspase-9) and fetuin-A values were measured by ELISA device. Student’s t-test or Mann-Whitney U test were used for continuous variables, and categorical variables were compared with the chi-square test to assess the significance of intergroup differences. The mean values of apoptosis biomarkers and acute phase reactants between dead and survival patients were also compared. RESULTS: While the apoptosis mean values of Apaf-1, sFas, sFasL, and caspase-9 for the control group were 0.12 ± 0.01, 332.1 ± 28.0, 130.4 ± 34.6, and 74.3 ± 2.6, for the patient group they were 0.14 ± 0.02, 509.1 ± 67.6, 139.9 ± 23.7, and 79.4 ± 2.8, respectively. The group differences were significant for all the biomarkers (p = 0.01, p = 0.001, p = 0.19, and p = 0.01, respectively). The negative acute phase fetuin- A and albumin levels decreased significantly in the patient groups (p = 0.01 and p = 0.01, respectively). CONCLUSIONS: Intrinsic and extrinsic apoptosis pathways are stimulated during pulmonary embolism, and negative acute phase reactants are decreased. There was a correlation with the mortality and Apaf-1, sFas, caspase-9, fetuin, and albumin levels.

Recurrent implantation failure is associated with increased levels of fetuin-A/alpha2-Heremans-Schmid-glycoprotein

ObjectiveRecurrent implantation failure is defined as the absence of implantation, after two or three consecutive cycles of in-vitro fertilization (IVF), intracytoplasmic sperm injection or frozen embryo replacement. Human fetuin-A/alpha2-Heremans-Schmid-glycoprotein is a plasma protein secreted by the liver that modulates insulin action in adipocytes. Increased fetuin-A promotes adipocyte dysfunction which results in decreased adiponectin and increased fatty acids and inflammatory cytokines. Fatty acids and inflammatory cytokines were previously reported in implantation failure. Also, fetuin-A inhibits receptor tyrosine kinase activity in trophoblast growth factors which decrease trophoblast viability and invasion. In this study, we aimed to find the association between fetuin-A and implantation failure. Study designA total of 78 women were included in this case-control study. Serum fetuin-A concentrations were measured in 42 women with recurrent IVF failure and 36 healthy women with regular cycles. ResultsThe mean serum fetuin-A levels of implantation failure and control women were 257.77 ± 32.18 and 219.59 ± 48.86 respectively with a p-value <0.001 (independent samples t-test). Our results showed a statistically significant difference between serum fetuin-A levels of implantation failure women and controls. ConclusionSo far reasons for implantation failure are only partially understood. The current study reveals the association between implantation failure and fetuin-A. Further studies with large population sizes are needed to investigate whether fetuin-A can be used as a marker before controlled ovarian stimulation began or regulation of fetuin-A levels with treatment or lifestyle interventions can improve implantation success.

Serum Fetuin-A and Insulin Levels in Classic Congenital Adrenal Hyperplasia.

Androgens play a pivotal role in non-reproductive organs such as the kidney, heart, liver, and pancreas. As androgen receptors are expressed in pancreatic and liver cells, excess testosterone can result in hypersecretion of insulin and fetuin-A, a protein produced in the liver. The expression of fetuin-A, a natural inhibitor of tyrosine kinase activity in muscle and liver, leads to insulin resistance. In addition, insulin and fetuin-A levels are thought to be affected by drugs such as glucocorticoids (GCs) and fludrocortisone. However, whether fetuin-A and insulin levels are affected by androgens and GCs in patients with classic congenital adrenal hyperplasia (CAH) is unknown. This cross-sectional study included 56 CAH patients and 70 controls. Analyses were stratified by sex and prepubertal/pubertal status to control for potential changes in serum metabolic/inflammatory markers associated with the production of sex steroids. Fasting blood glucose, insulin, triglyceride, total cholesterol, high density lipoprotein-cholesterol, aspartate aminotransferase, alanine aminotransferase, fetuin-A, and high-sensitivity C-reactive protein (hs-CRP) levels were measured in blood samples. In addition, 17α-hydroxyprogesterone, androstenedione, total testosterone, free testosterone, and dehydroepiandrosterone sulfate levels were measured before medication was administered. Insulin and fetuin-A levels were significantly higher in CAH patients than in controls. The unfavourably high levels of these substances exhibited a positive correlation with total and free testosterone. Regression analysis revealed that fetuin-A and free testosterone were the only independent predictors of the insulin level, while insulin and free testosterone levels significantly predicted the fetuin-A level (R2=42.7% and 59.8%). Differences were also observed in triglyceride and hs-CRP levels between the pubertal and prepubertal groups. We conclude that serum fetuin-A and insulin levels may be associated with androgens in CAH patients.

Effect of liraglutide therapy on serum fetuin A in patients with type 2 diabetes and non-alcoholic fatty liver disease

We aimed to compare the effectiveness of liraglutide vs. pioglitazone on hepatic fat content and serum fetuin A levels in patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease. This was a single-center, open-label, prospective, and randomized trial using a parallel design and lasting 24 weeks. Sixty patients with type 2 diabetes mellitus and non-alcoholic fatty liver disease were randomly assigned to the liraglutide and pioglitazone groups on a 1:1 basis using a computer-generated sequence. Fetuin-A levels were determined using enzyme-linked immunosorbent assay. Hepatic fat content was measured using proton 1H-MRS on a 1.5T whole-body MRI scanner. All analyses were performed with SPSS version 13.0. In the liraglutide group, fetuin-A levels decreased after 24 weeks (666.1±109.4 vs. 443.7±90.5μg/mL, P<0.05). In the pioglitazone group, fetuin-A levels also decreased after 24 weeks (659.3±111.8 vs. 538.1± 101.0μg/mL, P<0.05) but not to the level of the liraglutide group. The liraglutide treatment resulted in a decrease in 1H-MRS (24.1±3.0 vs. 20.1±3.8, P<0.05). After 24 weeks, ΔFetuin-A was positively correlated with Δweight (r=0.756, P=0.035), ΔBMI (r=0.653, P=0.006), Δwaist circumference (r=0.767, P=0.010), and Δ1H-MRS (r=0.732, P=0.004) in the liraglutide group. Liraglutide treatment resulted in a decrease in hepatic fat content and fetuin-A compared with pioglitazone treatment in patients with T2DM and NAFLD. Fetuin-A is positively correlated with weight and hepatic fat content. The reduction in the hepatic fat content may be attributed to weight loss rather than reduction of glucose.

Association of serum FGF-23, klotho, fetuin-A, osteopontin, osteoprotegerin and hs-CRP levels with coronary artery disease

Environmental, genetic, oxidative and biochemical factors play an important role in the atherosclerotic process. We investigated the association of serum fibroblast growth factor (FGF-23), klotho, fetuin-A, osteoprotegerin (OPG), osteopontin (OPN) and high-sensitive-CRP (Hs-CRP) markers with coronary artery disease and whether one was superior to others or not. A study group of 52 patients with coronary artery disease (CAD) and a control group of 30 patients with angiographically normal epicardial coronary arteries were included in the study. Serum FGF-23, klotho, fetuin-A, OPN, OPG and Hs-CRP marker levels were studied. Patients with CAD were classified in two groups as low (SYNTAX ≤22, n = 29) and moderate-high (SYNTAX ≥ 23, n = 23) according to anatomic SYNTAX score. FGF-23 (p = .033), klotho (p < .001), fetuin-A (p = .005) and OPG (p = .001) serum marker levels were significantly lower in CAD patients than the control group. Serum levels of FGF-23 (p = .012), klotho (p = .001), fetuin-A (p = .015) and OPG (p = 0.002) were significantly different between SYNTAX tertiles and control group. Klotho (p = .025, odd ratio (OR) = 0.542, 95% confidence interval (CI): 0.317–0.926) and HT (p = .004, OR = 34.598, 95%CI:1.054–1135.657) were the independent predictors of CAD presence. Serum klotho levels of 91.48 pmol/L predicts the presence of CAD with 60% sensitivity and 96.55% specificity (p < .001, area under curve = 0.864, 95% CI = 0.768, 0.931). We found that serum klotho level is an independent predictor of presence, extent and severity of CAD.

Microvasculopathy and soft tissue calcification in mice are governed by fetuin-A, magnesium and pyrophosphate.

Calcifications can disrupt organ function in the cardiovascular system and the kidney, and are particularly common in patients with chronic kidney disease (CKD). Fetuin-A deficient mice maintained against the genetic background DBA/2 exhibit particularly severe soft tissue calcifications, while fetuin-A deficient C57BL/6 mice remain healthy. We employed molecular genetic analysis to identify risk factors of calcification in fetuin-A deficient mice. We sought to identify pharmaceutical therapeutic targets that could be influenced by dietary of parenteral supplementation. We studied the progeny of an intercross of fetuin-A deficient DBA/2 and C57BL/6 mice to identify candidate risk genes involved in calcification. We determined that a hypomorphic mutation of the Abcc6 gene, a liver ATP transporter supplying systemic pyrophosphate, and failure to regulate the Trpm6 magnesium transporter in kidney were associated with severity of calcification. Calcification prone fetuin-A deficient mice were alternatively treated with parenteral administration of fetuin-A dietary magnesium supplementation, phosphate restriction, or by or parenteral pyrophosphate. All treatments markedly reduced soft tissue calcification, demonstrated by computed tomography, histology and tissue calcium measurement. We show that pathological ectopic calcification in fetuin-A deficient DBA/2 mice is caused by a compound deficiency of three major extracellular and systemic inhibitors of calcification, namely fetuin-A, magnesium, and pyrophosphate. All three of these are individually known to contribute to stabilize protein-mineral complexes and thus inhibit mineral precipitation from extracellular fluid. We show for the first time a compound triple deficiency that can be treated by simple dietary or parenteral supplementation. This is of special importance in patients with advanced CKD, who commonly exhibit reduced serum fetuin-A, magnesium and pyrophosphate levels.

Exercise plus caloric restriction lowers soluble RAGE in adults with chronic kidney disease.

SummaryIntroductionThe incidence of chronic kidney disease (CKD) has increased in recent years. CKD is associated with obesity, type 2 diabetes, and cardiovascular disease, although the mechanism remains unclear. Elevated soluble form of the receptor for advanced glycation end products ( RAGE) is related to proinflammatory signaling pathways that may promote diabetic nephropathy and vascular dysfunction. Because lifestyle modification reduces systematic inflammation in adults with obesity and hyperglycaemia, the hypothesis that exercise plus caloric restriction would lower soluble RAGE in adults with CKD was tested in this study.MethodsEight adults (n = 6 females; age: 56.3 ± 2.8 y; BMI: 43.7 ± 2.2 kg/m2; 2‐h OGTT glucose: 215 ± 9.8 mg/dL; eGFR: 49.6 ± 3.3 mL/min/1.73 m2) were enrolled in a 12‐week pilot lifestyle intervention (supervised aerobic exercise [5 d/wk, up to 60 min/d at approximately 65%‐85% HRmax] plus low‐fat dietary counseling). Body composition (DXA), aerobic fitness (VO2max), insulin sensitivity (120 min 75 g OGTT; Matsuda Index), plasma levels of soluble RAGE and fetuin‐A were measured before and after the intervention.ResultsExercise reduced body weight, fasting glucose, and fetuin‐A as well as increased VO2max, glucose tolerance, and insulin sensitivity (all P < .05). Lifestyle intervention decreased plasma soluble RAGE (pre: 1018.1 ± 163 vs post: 810.6 ± 119.6 ng/mL; P = .02), and the decrease was associated with a lower 2‐hour blood glucose (r = 0.76, P = .03) and with increased insulin sensitivity (r = −0.90, P < .01).ConclusionsExercise and caloric restriction are effective at lowering soluble RAGE in relation to glucose regulation in patients with CKD.

Fetuin-A and fetal growth in gestational diabetes mellitus

ObjectiveFetuin-A is a glycoprotein produced by hepatocytes and has been associated with insulin resistance and bone growth in postnatal life. Gestational diabetes mellitus (GDM) is a condition characterized by insulin...

Association of AHSG gene polymorphisms with serum Fetuin-A levels in individuals with cardiovascular calcification in west of Iran.

Fetuin-A (AHSG) is a multifunctional secretory protein and acts as an ectopic valve and artery calcification inhibitor. We assessed the correlation between serum levels of Fetuin-A and both exon 6 (248 C/T) and exon 7 (256 C/G) mutations in patients with coronary artery calcification (CAC), mitral annular calcification (MAC), and aortic valve calcification (AVC). 184 patients and 184 healthy individuals as control group were included. The genetic variants of rs4917 and rs4918 for the AHSG gene were determined by PCR-RFLP and T-ARMS PCR techniques. Fetuin-A levels, fasting blood sugar (FBS), urea, creatinine, calcium phosphorus, and lipid profile were measured. Fetuin-A levels were remarkedly lower in individuals with AVC, MAC, and CAC comparing to the control group (p < 0.001). The CT + TT genotypes and the T allele (AHSG Thr248Met) were associated with the risk of calcification of heart valves and coronary artery by 1.31 and 1.27 times in the patient group, respectively. The frequency of CT genotype and T allele was considerably higher in the patient group comparing to the control group. Patients with T allele (CT + TT) had higher levels of FBS, urea, low-density lipoproteins (LDL)-C, phosphorus, systolic blood pressure (SBP), diastolic blood pressure (DBP) while decreased levels of triglyceride, high-density lipoproteins (HDL)-C, calcium and fetuin-A in comparison to control group. Additionally, there was a positive correlation between serum FBS, urea, creatinine, HDL-C, calcium with fetuin-A, and a negative correlation between phosphorous level, SBP, and DBP with fetuin-A. T allele in rs4917 Single nucleotide polymorphism (SNP) is the risk allele of calcification of heart valves and coronary arteries and fetuin-A levels correlates negatively with the occurrence of the disease.

Effects of dynamic change in fetuin-A levels from the first to the second trimester on insulin resistance and gestational diabetes mellitus: a nested case–control study

ObjectiveTo examine the effects of dynamic change in fetuin-A levels before the diagnosis of gestational diabetes mellitus (GDM) on insulin resistance and GDM.Research design and methodsA total of 135 women...

Association of low fetuin-A levels with periodontitis in community-dwelling adults

Fetuin-A is a liver-secreted glycoprotein isolated from fetal bovine serum. Recent reports of its several pathological functions suggest an association between fetuin-A and systemic diseases. This study therefore examined the correlation between serum fetuin-A level and periodontal status. Data from 356 middle-aged and elderly adults who underwent health examinations in Goto, Japan, during the period from 2008 through 2010 were analyzed. Systemic and periodontal measurements were recorded, and serum fetuin-A level was determined by using an enzyme-linked immunosorbent assay. Fetuin-A levels for participants with moderate to severe periodontitis were significantly lower than those for participants with no or mild periodontitis. Additionally, fetuin-A level negatively correlated with periodontal clinical attachment loss. Moderate to severe periodontitis was significantly correlated with low serum fetuin-A levels (odds ratio, 1.69; 95% confidence interval, 1.01-2.69) in logistic regression analysis. Low serum fetuin-A level was correlated with worse periodontal status and could thus potentially serve as a marker of periodontitis.

Studying Some Novel Biochemical and Immunological Markers in a Sample of Iraqi Women with Polycystic Ovarian Syndrome

Polycystic ovarian syndrome (PCOS) considers as the most common disorder among women during reproductive age. Till now, the pathogenesis of PCOS stay unknown, and there is evidence considered PCOS as a low-grade inflammatory disease. The present study was designed to find out relationship of new biochemical markers, like fetuin-A, and immunological markers, like sirtuin-1, auto-antibodies (anti-histone antibody (AHA),anti-ovarian antibody (AOA)), and interleukins (IL-17, IL-23) with PCOS in studied patients when compared with healthy control group. Also, the study aimed to find the possible relationship between PCOS and autoimmunity.A total of 60 PCOS women and 30 healthy women, matching in average age and body mass index (BMI), were enrolled in this study. Women with PCOS were attend to AL -Nahrain University High Institute for Infertility Assisted Reproductive Technology, in Baghdad between Septembers to December/2018. Blood samples were aspirated from both groups to study the biochemical and immunological markers byusing enzyme linked immunosorbent assay (ELISA). The obtained results showed highly significant elevation (P<0.01) in luteinizing hormone (LH) serum levels of patients group. Regarding the results of serum fetuin-A, sirtuin-1, auto-antibodies, and interleukins levels, highly significant differences were noticed between patients and control group (P<0.01). On the other hand, the LH recorded a direct correlation at highly significant level with sirtuin-1 and auto-antibodies (AH, AOA). Also LH showed a direct correlation at significant level with ILs (17, 23). Sirtuin-1 showed a direct correlation at highly significant level with auto-antibodies (AHA, AOA) and ILs (17, 23). Both auto-antibodies have direct correlation at highly significant level with ILs (17, 23) and with each other, in addition to their correlation with sirtuin-1, auto-antibodies (AHA, AOA) and LH. The current study showed that the studied markers were elevated significantly in patients group when compared with control. These findings confirm the possibility that PCOS may attributed to an autoimmune disease.

Body composition and serum fetuin-A levels in patients with rheumatoid arthritis

Background. Rheumatoid cachexia is a pathological condition which appears in patients with rheumatoid arthritis with low fat-free mass and normal or high body mass index. Bone mass loss is one of the components of rheumatoid cachexia. Fetuin-A, a major noncollagen protein of bone tissue, regulates bone remodeling. Aim of the study was to investigate the prevalence of rheumatoid cachexia and the association of serum fetuin-A level with body composition components in patients with rheumatoid arthritis. Material and methods. 110 patients (8 male and 102 female) with rheumatoid arthritis were enrolled in our study. Serum fetuin-A level was determined by ELISA. Dual-energy X-ray absorptiometry with Total Body program was performed. The diagnosis of rheumatoid cachexia was based on the next criteria: fat-free mass index less than 10th percentiles with fat mass index above 25th percentiles. Results and discussion. We observed rheumatoid cachexia in 25 patients (22,7 %). According to the literature, such patients have an increased risk of developing metabolic syndrome, arterial hypertension and mortality. Positive significant ( p < 0,05) correlations were observed between serum fetuin-A levels and right and left lower limb, trunk, gynoid region, both lower limbs and total body bone mass. No statistically significant relationships with other indicators were identified. Fetuin-A negative dynamic in patients with rheumatoid arthritis may be accompanied by the loss of bone mass, which requires the improvement of therapeutic approach. Conclusions. Almost a quarter of patients with rheumatoid arthritis have rheumatic cachexia. Positive correlation between serum fetuin-A levels and lower limbs, trunk, gynoid region and total body bone mass was observed.

Reduced plasma Fetuin-A is a promising biomarker of depression in the elderly.

Depression affects 7% of the elderly population, and it often remains misdiagnosed or untreated. Peripheral biomarkers might aid clinicians by allowing more accurate and well-timed recognition of the disease. We sought to determine if plasma protein levels predict the severity of depressive symptomatology or distinguish patients from healthy individuals. The severity of depressive symptoms and global cognitive functioning were assessed by the Geriatric Depression Scale (GDS) and Mini-Mental State Examination (MMSE) in 152 elderly subjects, 76 of which with major depressive disorder (MDD). Plasma levels of 24 proteins were measured by multiplexing and analyzed as continuous predictors or dichotomized using the median value. The association between individual plasma proteins and MDD risk or depressive symptoms severity was investigated using multiple logistic and linear regressions including relevant covariates. Sensitivity analyses were performed excluding cognitively impaired individuals or non-acute patients with MDD. After adjusting for possible confounders and false discovery rate (FDR) correction, we found lower Fetuin-A levels in MDD patients vs. controls (pFDR = 1.95 × 10-6). This result was confirmed by the sensitivity and dichotomized analyses. Lower prolactin (PRL) levels predicted more severe depressive symptoms in acute MDD patients (pFDR = 0.024). Fetuin-A is a promising biomarker of MDD in the elderly as this protein was negatively associated with the disorder in our sample, regardless of the global cognitive functioning. Lower PRL levels may be a peripheral signature of impaired neuroprotective processes and serotoninergic neurotransmission in more severely depressed patients.

Evaluation of fetuin-A as a predictor of outcome after surgery for osteoporotic fracture of the proximal femur.

In the elderly, osteoporotic fractures of the femur are associated with high morbidity and mortality. At the time of hospitalization and during pre-operative care identification of patients at risk for poor outcome despite an otherwise good clinical condition is challenging. We hypothesized that the serum concentration of fetuin-A during post-operative recovery might serve as a biomarker. During a 15months period patients admitted to our hospital for treatment of a femur fracture were registered on a voluntary basis and irrespective of age, underlying diseases and therapy. For all patients enrolled in this registry, blood was sampled for additional laboratory analysis. Patients with osteoporotic fractures were invited for follow-up examination about 2years later. At this time, the functional outcome and clinical performance together with the handgrip strength as a surrogate measure of overall strength were assessed and the occurrence of additional fractures was recorded. Results from these assessments and the absence or presence of subsequent fractures were combined as summary score of outcome (SSO) and overall physical performance (oPP), a score derived by principal component analysis and relying on normally distributed data, only. 39 of 96 eligible patients were deceased during the follow-up period, while 45 consented to participate in the study. Patients with a SSO ≥ 17pts were younger and had higher fetuin-A serum concentrations (each p < 0.05) during hospitalization compared to those with a SSO below 8pts. Age at follow-up together with total serum protein and fetuin-A levels during post-operative recovery had significant influence on SSO and oPP. Fetuin-A at time of follow-up examination was not associated with outcome. Our results are in favor of fetuin-A as an important factor for fracture healing but do not support an association between fetuin-A at time of follow-up examination and either SSO or oPP.