Association Of fetuin-A Research Articles

Fetuin-A in newly detected type 2 diabetes mellitus as a marker of non-alcoholic fatty liver disease.

Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. Numerous studies have shown the association between levels of fetuin-A in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic (NDD)patients and its relationship with the presence of NAFLD have not been studied. To study the fetuin-A levels in patients with NDD and its relationship with NAFLD. A total of 60 NDD patientswere studied. The diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. The percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, systolic and diastolic blood pressure, fasting blood sugar (FBS), hemoglobin (Hb)A1c, fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/mL could predict the development of NAFLD with odds ratio (OR) of 4.33 (95%CI: 1.364-13.77), which remained significant after adjustment for various confounding factors. Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with insulin resistance (IR). The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.

Association of Fetuin-A with Thr256Ser exon polymorphism of α2-Heremans Schmid Glycoprotein (AHSG) gene in type 2 diabetic patients with overt nephropathy

BackgroundCirculatory Fetuin-A has been well reported to elevate the risk for Diabetic Nephropathy (DN) and is associated with many vascular complications. Compelling reports have well documented that the circulatory levels of Fetuin-A directly have an impact on its AHSG (α2- Heremans- Schmid Glycoprotein) gene single nucleotide polymorphisms (SNP). Thus, in this study among the South Indian T2DM population, we aim to explore the association of AHSG Thr256Ser (rs4918) SNP in subjects with DN and correlate with the circulatory levels of Fetuin-A at various stages of DN patients. MethodsA total of 975 subjects were recruited, such as Group-I, consisting of Controls (n = 300), Group-II, with normoalbuminuria (n = 300), Group-IIIa, with incipient microalbuminuria (n = 195), Group-IIIb, with persistent macroalbuminuria (n = 180)] and were subjected for genotyping using PCR-Restriction Fragment Length Polymorphism (RFLP). Circulatory Fetuin-A was measured using sandwich enzyme-linked immunosorbent assay (ELISA). ResultsThe ‘G’ allele of AHSG exon-7 (C/G) SNP is significantly concomitant and conferred significant risk for normoalbuminuria subjects. In the DN subjects, the ‘G' allele showed the risk for persistent macroalbuminuria. A noticeable stepwise decrease was evidenced in the circulatory Fetuin-A among persistent macroalbuminuria over incipient microalbuminuria from normoalbuminuria. Further, the circulatory Fetuin-A was lowered in DN subjects with mutant GG genotype than the wild CC. ConclusionAHSG Thr256Ser (rs4918) SNP was associated with renal complications among South Indian T2DM subjects.

Fetuin-A as a Marker of NAFLD

Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. There are numerous studies which have shown the association between levels of fetuin-A in Type 2 diabetes mellitus (T2DM) and Nonalcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic patients (NDD) and its correlation with presence of NAFLD has not been studied. Objective: To study the fetuin-A levels in patients with NDD and its correlation with NAFLD. Methods: A total of 60 newly diagnosed type 2 diabetes (NDD) were studied. Diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. Results: Percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, both systolic and diastolic blood pressure, FBS, HbA1c, fasting insulin, HOMA-IR, QUICKI and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/ml could predict the development of NAFLD with OR of 4.33 (95%CI:1.364–13.77) which remained significant after adjustment for various confounding factors. Conclusion: Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with IR. The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.

Association of fetuin-A with dyslipidemia and insulin resistance in type-II Diabetics of Pakistani population.

Background & Objective:Fetuin-A, hepatokine is responsible for instigating insulin resistance by inhibiting tyrosine kinase receptors. Our objective was to investigate the relationship of fetuin-A with dyslipidemia and insulin resistance in type-II diabetics of Pakistani population.Methods:In this cross sectional study which was conducted at Basic Medical Sciences Institute, Jinnah Postgraduate Medical Centre, Karachi between October 2013 to March 2014, a total of 330 participants were selected and divided into two groups. Group-A (n = 165) normal healthy individual and Group-B (n = 165) Type-II diabetes mellitus mellitus with no comorbidities. Serum fetuin-A and insulin levels were determined by commercially prepared ELISA kits while fasting blood glucose (FBG) and lipid profile were performed by enzymatic kit method. Employing independent t-test, comparison of groups was done and correlation was achieved by using spearman correlation.Results:The results demonstrate a significant difference in mean values of fetuin-A, lipid profile, glucose, insulin and Homoeostasis Model Assessment of Insulin resistance (HOMA-IR) in type-II diabetics when compared to normal healthy individuals (p<0.01). A positive correlation was found between serum fetuin-A levels and FBG(r= 0.495, p< 0.001), insulin(r= 0.227, p< 0.001), HOMA-IR(r= 0.336, p<0.001, triglycerides(r= 0.197, p< 0.001) and LDL-cholesterol(r= 0.170, p= 0.002), while negative correlation with HDL-cholesterol(r= -0.251, p< 0.001).Conclusion:The study concludes that fetuin-A might be accountable for dyslipidemia and insulin resistance in type-II diabetes mellitus mellitus. So the high levels of Fetuin-A responsible for insulin resistance might alters endothelium and causes inflammation, vasoconstriction and thrombosis and ultimately atherosclerosis.

Association of fetuin-A with kidney disease; a review on current concepts and new data

Fetuin-A (α2Heremans-Schmid glycoprotein) is a glycoprotein which is synthesized in the liver and secreted into the bloodstream. It belongs to a large group of binding proteins mediating the transport and availability of a wide variety of cargo substances in the bloodstream. The aim of this study is to summarize the available results of studies on the association of fetuin-A with chronic kidney disease and end-stage renal disease, type 2 diabetes, non-alcoholic fatty liver, and yield the end results. The databases including PubMed, Google Scholar, Scopus, and Science-Direct were searched with the purpose of finding the related studies. The articles were assessed in terms of repeatability of title, type of study, population, study variables and the quality of reporting. Finally, 37 articles, which were published between the years 2002 and 2018, were selected to be overviewed completely. The studies showed that fetuin-A can function as a protective inhibitor of vascular calcification in patients with chronic kidney disease and end-stage renal disease, and is reduced during acute inflammation. The deficiency of this protein is associated with an increase in the morbidity and mortality of patients with cardiovascular diseases. Fetuin-A can be useful as a vascular disease marker in patients with type 2 diabetes. In fact, it is an independent predictor of type 2 diabetes due to its high concentration in insulin resistance. Fetuin-A is a good indicator of liver cells function and its level will be increased in non-alcoholic fatty liver disease. Fetuin-A, as a multi-functional protein, performs many tasks. However, studies in this area are very limited and based on its multiple and complex functions, further studies are recommended.

Do Nonalcoholic Fatty Liver Disease and Fetuin-A Play Different Roles in Symptomatic Coronary Artery Disease and Peripheral Arterial Disease?

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is strongly associated with both atherosclerotic cardiovascular disease (CVD) and Fetuin-A. However, the association of Fetuin-A with atherosclerosis is more controversial. We hypothesized that the pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis varies based on arterial site. Accordingly, we aimed to assess NAFLD prevalence, Fetuin-A values and their relationship with symptomatic atherosclerosis occurring in different localizations: coronary artery disease (CAD) vs. peripheral arterial disease (PAD). Methods: One hundred and forty-nine consecutive patients with symptomatic atherosclerotic CVD were recruited: 45 with CAD diagnosed by coronary angiography and 104 with PAD detected by doppler-ultrasound and/or computed tomography angiography and/or angiography. NAFLD was diagnosed based on both ultrasonography and exclusion of competing etiologies. Serum Fetuin-A was measured with ELISA. Results: NAFLD was detected in 54% of the overall group, with higher rates in PAD (59%) than CAD (42%) patients. Median Fetuin-A values were 256 (111–662) μg/mL, higher in patients with CAD (378 (124−662) μg/mL) than those with PAD (236 (111−461) μg/mL). The main findings were: (1) CAD patients had higher Fetuin-A values and less frequently NAFLD than PAD patients; (2) NAFLD was positively associated with Fetuin-A values; however, this association was limited to CAD patients only; (3) Fetuin-A values were positively associated with both CAD and NAFLD. Conclusion: The pathogenic interplay of NAFLD, Fetuin-A and atherosclerosis probably varies according to the arterial site.

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.

Fetuin-A, glycemic status, and risk of cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis

AimsFetuin-A is a hepatic secretory protein that both promotes insulin resistance and inhibits arterial calcification. Previous studies have suggested that the association of fetuin-A with incident cardiovascular disease (CVD) might be modified by glycemic status. Methods and resultsWe conducted a case-cohort study of fetuin-A and incident non-fatal CVD nested in the Multi-Ethnic Study of Atherosclerosis with follow-up from 2000 to 2007. Fetuin-A concentrations were measured from baseline serum samples among 2505 randomly selected subcohort members and 142 incident cases. In weighted multivariable Cox regression models, no association was observed between fetuin-A and incident CVD in the total study population (HR per SD = 1.01; 95% CI: 0.84, 1.23). Although associations with CVD events were not statistically significant within categories of glycemic status, our results tended to support the interaction with glycemic status observed in other studies, with a positive trend restricted to participants with impaired fasting glucose or diabetes (HR per SD = 1.20; 95% CI: 0.89, 1.63) and an inverse trend among normoglycemic individuals (HR = 0.89; 95% CI: 0.69-1.13) (p-interaction = 0.04). In addition, we observed significant interaction between fasting glucose and fetuin-A when both were treated continuously in the subset of participants not using diabetes medication (p-interaction = 0.006). ConclusionOur results suggest that fetuin-A is not associated with an overall risk of CVD, but support prior evidence indicating that the association might be modified by glycemic status.

Abstract MP45: Liver Fat Content Does Not Account for the Strong Association of Fetuin-A with Diabetes Risk in Women: The Multi-Ethnic Study of Atherosclerosis

Introduction: Fetuin-A, a hepatic secretory protein, has been associated with risk of diabetes. However, liver fat content may be an important confounder or effect modifier not fully accounted for in previous studies. Further, it remains unclear whether associations differ between women and men. Aim: In an ethnically diverse cohort of women and men, we assessed the association of fetuin-A with risk of diabetes and investigated the role of liver fat in this association. Methods: We conducted a case-cohort study nested in the Multi-Ethnic Study of Atherosclerosis among 1,957 subcohort members and 455 cases (265 of whom belonged to the subcohort) with follow-up from 2000-2012. Fetuin-A was measured from baseline plasma samples by enzyme-linked immunosorbent assay, and liver fat was assessed via computed tomography. Associations were estimated using multivariable-adjusted Cox models, with weighting to account for the case-cohort design. Results: The association of fetuin-A with risk of diabetes differed between women and men (p-interaction = 0.001). Each standard deviation (SD) higher fetuin-A concentration (0.10 g/L) was associated with a hazard ratio (HR) of 1.51 (95% CI: 1.32-1.74, p &lt;0.0001) among women and an HR of 1.12 (95% CI: 0.94-1.32, p = 0.20) among men. With additional adjustment for liver fat, associations were slightly attenuated in both women (HR per SD fetuin-A = 1.37, 95% CI: 1.19-1.59, p&lt;0.0001) and men (HR = 1.06, 95% CI: 0.90-1.24, p = 0.40). Additional adjustment for other clinical variables had minimal impact on multivariable-adjusted estimates (Figure). Associations did not differ by degree of liver fat content (p-heterogeneity &gt;0.25 for both women and men). Conclusions: Fetuin-A was associated with diabetes risk, particularly in women, even after adjustment for liver fat.

THU0088 Fetuin-A and Its Association with Disease Activity in Psoriatic Arthritis

BackgroundIncreased risk of cardiovascular morbidity and mortality has been reported in psoriatic arthritis (PsA), a member of a spondyloarthropathy. Fetuin-A is a novel biomarker related with vascular calcification and atherosclerosis....

Abstract P025: Associations of Fetuin-A with Incident Heart Failure in Participants with and without Diabetes and Insulin Resistance: The Cardiovascular Health Study

Background: In animal models, the hepatic secretory protein fetuin-A simultaneously inhibits arterial calcification and causes insulin resistance. Increased calcification and insulin resistance lead to arterial stiffness, an important risk factor for heart failure (HF). The relationship between serum fetuin-A concentrations and HF, and whether it is modified by diabetes or insulin resistance has not been extensively studied. Research Design, Methods, and Objectives: In a prospective study of 4182 community-dwelling participants aged ≥ 65 years, Cox proportional hazards models were used to determine the association of fetuin-A (measured in 1992) with incident HF (followed up through June 2008). Multiplicative interaction terms determined whether diabetes or insulin resistance status modified the association. Results: Mean age was 75 ∓ 5 years, fetuin-A levels were 0.47 ∓ 0.10 g/L, and 1,186 incident HF events occurred during follow-up. In multivariable models adjusting for demographics and CVD risk factors, fetuin-A was not significantly associated with incident HF [HR per SD fetuin-A: 0.97, 95% CI (0.91, 1.04), p-value=0.40] and was not modified by prevalent diabetes status (p-interaction=0.54). However, when prevalent insulin resistant status was defined as previously by the presence of diabetes, or HOMA IR &gt; median (2.22), or obesity (body mass index, kg/m 2 &gt; 30), a significant interaction was observed (p-interaction=0.03). In 1,679 participants with no evidence of insulin resistance by the definition, each SD greater fetuin-A level was associated with a 12% lower risk of HF (95% CI: 2-22%) in a fully adjusted model (Table 1). Conclusions: Future studies should consider the presence of insulin resistance when evaluating the relationship between serum fetuin-A with adverse health outcomes.

Association of AHSG Gene Polymorphisms with Ischemic Stroke in a Han Chinese Population

Previous studies have shown associations of fetuin-A (alpha2-Heremans-Schmid glycoprotein, AHSG) with various disorders, including insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and atherosclerosis. In this study, genotype and allele frequencies of the rs4918 SNP in the AHSG gene were examined in 380 patients with ischemic stroke and 350 healthy controls from a Northern Han Chinese population via the PCR-RFLP technique. Frequencies of the GG genotype and the G allele in AHSG (rs4918) were significantly higher in patients with ischemic stroke or atherosclerotic cerebral infarction than those in the control group (P < 0.05). Logistic regression analysis demonstrated the significance of rs4918 in these patients, after adjustment for confounding factors (P < 0.05). These findings suggest that rs4918 SNPs of the AHSG gene are associated with a risk for ischemic stroke in a Northern Han Chinese population.

Associations of fetuin-A and osteoprotegerin with arterial stiffness and early atherosclerosis in chronic hemodialysis patients

BackgroundCardiovascular morbidity and mortality remains excessive in patients with chronic kidney disease. The association of vascular changes with regulators of extraosseous calcification in this patient population is still under investigation. The aim of the present study was to investigate the associations of the calcification inhibitor fetuin-A, and the anti-osteoclastic factor osteoprotegerin (OPG) with vascular pathology in chronic hemodialysis patients.MethodsIn this cross-sectional study including 81 stable chronic hemodialysis patients, we measured carotid-to-femoral pulse wave velocity (cfPWV) with applanation tonometry, reflecting arterial stiffness, and common carotid intima-media thickness (ccIMT), a surrogate of early atherosclerosis, as well as serum levels of fetuin-A and OPG. Co-morbidities, traditional cardiovascular risk factors, inflammatory markers and mineral-bone disease serology parameters were also recorded.ResultscfPWV correlated inversely with fetuin-A (r=−0.355, p=0.001) and positively with OPG (r=0.584, p<0.001). In multilinear regression analysis including age, gender, diabetes, cardiovascular disease, hypertension, pulse pressure, LDL, logCRP, both fetuin-A and OPG were independently associated with cfPWV (p=0.024 and p=0.041 respectively). ccIMT was negatively associated with fetuin-A (r=−0.312, p=0.005) and positively with OPG (r=0.521, p<0.0001); however these associations lost statistical significance after adjustment for age.ConclusionIn chronic hemodialysis patients both fetuin-A and OPG levels are independently associated with arterial stiffness but not with early atherosclerotic vascular changes.

Fetuin-A, Type 2 Diabetes, and Risk of Cardiovascular Disease in Older Adults

OBJECTIVEFetuin-A, a hepatic secretory protein that simultaneously inhibits arterial calcification and insulin action, is associated with type 2 diabetes, but its association with cardiovascular disease (CVD) is uncertain. Preliminary studies suggest that the association of fetuin-A with CVD might differ among individuals with or without type 2 diabetes.RESEARCH DESIGN AND METHODSThis was a prospective study of 3,810 community-living individuals older than 65 years (511 with type 2 diabetes) and free of CVD in 1992 when fetuin-A levels were measured. Participants were followed-up for incident CVD through June 2008.RESULTSMean age was 75 years, and 61% were women; 1,456 participants had an incident CVD event (248 among individuals with type 2 diabetes). The association of fetuin-A with CVD was modified by type 2 diabetes (P interaction = 0.02). Higher fetuin-A was associated with lower CVD risk among persons without type 2 diabetes [hazard ratio per SD 0.1 g/L higher fetuin-A, 0.93 (95% CI, 0.88–0.99)], whereas a trend in the opposite direction was observed among individuals with type 2 diabetes, although it was not statistically significant [1.07 (0.93–1.22)]. Among individuals without type 2 diabetes, similar effect modification was observed by obesity and insulin resistance. Consistently, higher fetuin-A was associated with lower CVD risk only in the subgroups without obesity or with HOMA-IR below the median [0.91 (0.85–0.97) and 0.87 (0.79–0.95), respectively].CONCLUSIONSThe association of fetuin-A with risk of CVD differs among elderly individuals with and without insulin resistance or type 2 diabetes.

Serum Fetuin-A Levels, QT Dispersion and P Dispersion in Dialysis Patients

Background: This study aims to find association of fetuin-A with serum lipids, QT dispersion (QT-d), and P dispersion (P-d) in dialysis patients. Methods: Fetuin-A serum levels were assessed in 50 dialysis patients. Results: Serum fetuin-A levels were significantly associated with QT-d (r = 0.289, p = 0.044), P-d (r = 0.39, p = 0.005), total cholesterol (r = 0.526, p = 0.000), low-density lipoprotein cholesterol (LDL-C) (r = 0.456, p = 0.00), triglyceride (r = 0.360, p = 0.011) and highly sensitive C-reactive protein (hsCRP) (r = −0.347, p = 0.030). In step-wise multiple regression analysis including being on hemodialysis (HD), presence of diabetes mellitus (DM), total cholesterol, LDL-C, triglycerides, hsCRP, only total cholesterol (b = 0.419, p = 0.03), and hsCRP (b = −0.316, p = 0.03) proved to be independent predictors of serum fetuin-A levels. QT-d showed a linear correlation with total cholesterol (r = 0.309, p = 0.029), LDL-C (r = 0.304, p = 0.038), P-d (r = 0.390, p = 0.005), and fetuin-A levels (r = 0.289, p = 0.044). In multiple regression analyses, the independent predictor of QT-d was being on HD (b = −0.417, p = 0.004), whereas total cholesterol, LDL-C, presence of DM, serum fetuin-A levels, and P-d had no independent effect on corrected QT (QT-C). Being on HD and age were important determinants of P-d whereas presence of DM, total cholesterol, LDL-C, fetuin-A, and QT-d had no independent effect on P-d. Conclusions: Lower fetuin-A levels are associated with high hsCRP and low cholesterol levels in dialysis patients.

The Association of Fetuin-A With Cardiovascular Disease Mortality in Older Community-Dwelling Adults: The Rancho Bernardo Study

The goal of this study was to evaluate the prospective association of fetuin-A levels with cardiovascular disease (CVD) mortality. Fetuin-A is a circulating inhibitor of calcium deposition in the vasculature and of insulin action in muscle and fat, and may be involved in the pathogenesis of CVD. This is a population-based prospective study of 633 men and 1,025 women (median age = 73 years) who had fetuin-A levels and CVD risk factors evaluated in 1992 to 1996 and were followed for vital status through 2010. Plasma fetuin-A (g/l ± SD) was highest in women using oral estrogens (0.55 ± 0.12), intermediate for women not using oral estrogens (0.51 ± 0.10), and lowest for men (0.50 ± 0.10), p < 0.001. Lower fetuin-A levels were associated with older age, but with lower levels of other CVD risk factors including adiposity, blood pressure, lipids, triglycerides, and insulin resistance (all p < 0.01). During the median 12-year follow-up, 273 deaths were attributed to CVD. The association of fetuin-A with CVD mortality differed by diabetes status (p for interaction = 0.003). Adjusting for age, sex, oral estrogens, and lifestyle, the hazard ratio for CVD mortality comparing the lowest fetuin-A quartile with all higher values was 1.76 (95% confidence interval [CI]: 1.34 to 2.31; p < 0.001) for participants without diabetes and 0.43 (95% CI: 0.19 to 0.98; p = 0.046) for participants with diabetes. Low fetuin-A levels predicted greater risk for CVD mortality in older adults without diabetes, but were associated with reduced risk of CVD death in those with diabetes. Fetuin-A may provide novel insight into mechanisms leading to CVD death in those with versus without diabetes.

Abstract MP036: The Sex-Specific Association of Fetuin-A with Diabetes in Older Adults: The Rancho Bernardo Study

Fetuin-A is a hepatic-secretory protein that induces insulin resistance in animals and is elevated in humans with insulin resistance and fatty liver disease. In population-based studies, higher fetuin-A has been shown to predict the development of type 2 diabetes; however, the sex-specific nature of the fetuin-A-diabetes link is unclear. This study tested the hypothesis of a sex-specific association of fetuin-A with prevalent and incident diabetes in a population of 1742 older community-dwelling adults (mean age 71.4 years). Fetuin-A levels (mean, SD in ng/ml) were highest in women using oral estrogen therapy (ET) (55.5, 11.6), intermediate in women not using ET (51.4, 10.2), and lowest in men (50.2, 9.6) (P&lt;.001 for all). At baseline, 14% (n=129) of women and 19% (n=113) of men had prevalent diabetes; during the median 9.1 year follow-up, 32 women and 53 men developed incident diabetes. In combined analyses, there was a significant interaction by sex for the fetuin-A association with both prevalent (P=.007) and incident (P=.020) diabetes. Table 1 presents odds ratios for prevalent diabetes and hazards ratios for incident diabetes per sex-specific SD increase in fetuin-A. Among women, a 1 SD increase in fetuin-A was associated with 79% increased odds of prevalent diabetes and 66% increased risk of incident diabetes adjusting for age and oral ET. Risk estimates for women were only modestly attenuated by additional adjustment for lifestyle, body size, lipids, blood pressure, fasting plasma glucose and insulin resistance. In contrast, among men, although a minor association was suggested in age-adjusted models, risk estimates were attenuated to one in multivariate models. In conclusion, higher fetuin-A levels predict type 2 diabetes in older women independent of established risk factors, but are not related to diabetes risk in older men. Whether these sex-specific associations are relevant to the observation that diabetes is a stronger risk factor for cardiovascular mortality in women than men merits further investigation. Table 1. Odds of Prevalent Diabetes and Risk of Incident Diabetes per SD increase in Fetuin-A Prevalent Diabetes, OR (95% CI) Women (n=1043) Men (n=672) Model 1 1.79 (1.47, 2.17) 1.15 (0.94, 1.41) Model 2 1.69 (1.38, 2.07) 1.14 (0.92, 1.41) Model 3 1.54 (1.25, 1.90) 1.05 (0.83, 1.31) Model 4 1.60 (1.26, 2.03) 1.14 (0.83, 1.56) Model 5 1.54 (1.24, 1.91) 1.02 (0.80, 1.32) Incident Diabetes, HR (95% CI) Women (n=782) Men (n=477) Model 1 1.66 (1.18, 2.34) 1.24 (0.93, 1.65) Model 2 1.64 (1.16, 2.32) 1.12 (0.81, 1.53) Model 3 1.53 (1.04, 2.25) 0.96 (0.69, 1.33) Model 4 1.51 (1.02, 2.23) 0.94 (0.66, 1.34) Model 5 1.51 (1.03, 2.22) 0.91 (0.65, 1.27) Funding(This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont)

Association of fetuin-A and heat shock protein 70 with arterial calcification in patients with peripheral vascular disease

Abstract Atherosclerosis may present with arterial calcification, which is associated with increased cardiovascular morbidity and mortality. Fetuin-A plays a role in the inhibition of extraosseal calcification, and heat shock protein 70 (Hsp70) is elevated in peripheral artery disease. The aim of our study was to examine the potential role of fetuin-A and Hsp70 in the inhibition of arterial calcification in atherosclerotic patients. Classical risk factors of atherosclerosis as well as the severity of arterial calcification and atherosclerosis were assessed by ultrasound, angiography, and serum analysis in a cross-sectional study of patients with carotid stenosis, aortic aneurysm, and lower extremity atherosclerosis. We demonstrate that there is an inverse correlation between serum fetuin-A levels and the severity of arterial calcification in patients with chronic atherosclerotic lower extremity disease without renal disease or infection. Our data suggest that it is not end-stage renal disease and dialysis that explains the earlier reported association of low fetuin-A level and arterial calcification. The novel finding of our study is the significantly different serum fetuin-A levels in patients with aortic aneurysm of different etiologies (atherosclerosis and Marfan syndrome). Our results suggest that there is an association between serum fetuin-A levels and the severity of arterial calcification also in patients without renal failure.

The Associations of Fetuin-A With Subclinical Cardiovascular Disease in Community-Dwelling Persons: The Rancho Bernardo Study

The aim of this study was to determine the association of fetuin-A with subclinical cardiovascular disease (CVD) in community-living individuals. Fetuin-A is a hepatic secretory protein that inhibits arterial calcium deposition in vitro. Lower fetuin-A levels are associated with arterial calcification and death in end-stage renal disease populations. The association of fetuin-A with subclinical CVD in the general population is unknown. Among 1,375 community-living individuals without prevalent clinical CVD, we measured plasma fetuin-A concentrations. Peripheral arterial disease (PAD) was defined by ankle brachial index &amp;amp;amp;amp;lt;0.90, coronary artery calcification (CAC) was measured by computed tomography, and common and internal intima-media thickness (cIMT) were measured by carotid ultrasound. PAD was measured concurrent with fetuin-A, and CAC and cIMT were measured 4.6 years (mean) later. Mean age was 70 ± 11 years, and 64% were women. Fetuin-A levels were inversely associated with CAC severity. When evaluated as CAC categories (0, 1 to 100, 101 to 300, &amp;amp;amp;amp;gt;300) with ordinal logistic regression, each SD higher fetuin-A was associated with 31% lower odds of CAC severity (proportional odds ratio: 0.69; 95% confidence interval: 0.46 to 0.92; p = 0.008) in models adjusted for demographic data, lifestyle factors, traditional CVD risk factors, and kidney function. In contrast, no association of fetuin-A was observed with PAD or high common or internal cIMT in adjusted models. Lower fetuin-A levels are independently associated with greater CAC severity but not PAD or cIMT. If confirmed, fetuin-A might mark calcium deposition within the vasculature but not atherosclerosis per se.

Fetuin-A, coronary artery calcification and outcome in maintenance hemodialysis patients

Previous studies have suggested that serum fetuin-A, a calcification inhibitor, predicts mortality in dialysis patients. This study investigated the relationships between fetuin-A, vascular calcification, and outcome in such patients. 58 patients on maintenance hemodialysis underwent multirow spiral computed tomography to determine baseline coronary artery calcification (CAC) score. Serum fetuin-A was measured repeatedly over time. Time-averaged fetuin-A inversely correlated with age and baseline CAC score. After partial correlation analysis controlling for age, the association between fetuin-A and CAC became insignificant. During the study, 27 of 58 patients died and 26 experienced at least one cardiovascular event. Low fetuin-A was associated with a significant increase in all-cause mortality and the occurrence of a cardiovascular event. The association of fetuin-A with mortality and cardiovascular event remained significant even when adjusting for confounding factors, including age and CAC score. Time-averaged fetuin-A was associated with survival and cardiovascular outcome, independent of vascular calcification.