Serum levels of the adipokine vaspin in relation to metabolic and renal parameters.

CONTEXT: Recently, vaspin was identified as an insulin-sensitizing adipokine. However, regulation of this adipocyte-secreted factor in human disease has not been determined. OBJECTIVE: We investigated vaspin serum concentrations in diabetic and nondiabetic patients on chronic hemodialysis (CD) as compared with controls with a glomerular filtration rate (GFR) above 50 ml/min. DESIGN: Vaspin was quantified by ELISA in control (n = 60) and CD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation, in both groups. RESULTS: Mean serum vaspin concentrations were not significantly different between CD patients and controls. Circulating vaspin was significantly lower in males (0.6 +/- 0.9 microg/liter) as compared with females (1.3 +/- 1.5 microg/liter) and was decreased in insulin-treated subjects. In univariate analyses, vaspin levels positively correlated with age and high-density lipoprotein cholesterol and negatively with waist-to-hip ratio and GFR in control patients, whereas the adipokine was negatively associated with GFR and C-reactive protein (CRP) in CD patients. In multivariate analyses, age and gender were independently associated with vaspin in controls, whereas gender, GFR, and CRP independently predicted circulating vaspin in CD patients. CONCLUSIONS: Vaspin levels are significantly higher in women, and gender is an independent predictor of circulating vaspin in both control and CD patients. In addition, age independently predicts vaspin in control patients, whereas GFR and CRP are independently associated with this adipokine in CD patients. In contrast, circulating vaspin is not independently associated with markers of glucose and lipid metabolism.

Endogenous soluble receptor for advanced glycation endproducts is increased in preeclampsia.

OBJECTIVE: Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular risk for both mother and newborn. Recently, low levels of endogenous soluble receptor for advanced glycation endproducts (esRAGE) have been associated with increased cardiovascular risk. In the current study, we investigated esRAGE serum levels in patients with preeclampsia as compared to healthy gestational age-matched controls. METHODS: esRAGE was quantified by enzyme-linked immunosorbent assay in controls and patients with preeclampsia during pregnancy (control: n = 20, preeclampsia: n = 16) and 6 months after delivery (control: n = 19, preeclampsia: n = 15). Furthermore, esRAGE was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. RESULTS: During pregnancy, median maternal serum esRAGE concentrations were more than three-fold higher in patients with preeclampsia (200 ng/l) than in controls (63 ng/l) (P < 0.01). Furthermore, esRAGE levels positively correlated with age, blood pressure, creatinine, adiponectin, and C-reactive protein, whereas a negative correlation existed with fasting insulin and the homeostasis model assessment of insulin resistance index. In multivariate analyses, homeostasis model assessment of insulin resistance and C-reactive protein independently predicted esRAGE serum levels and explained 44% of the variation in esRAGE concentrations. Surprisingly, median esRAGE concentrations 6 months after delivery were significantly lower in former patients with preeclampsia (270 ng/l) than in controls (342 ng/l) in contrast to the results obtained during pregnancy. CONCLUSION: We showed that maternal esRAGE concentrations are significantly increased in patients with preeclampsia during pregnancy. Here, insulin sensitivity and inflammatory status independently predict serum esRAGE levels.

Serum levels of the adipokine visfatin are increased in pre-eclampsia.

OBJECTIVE: Pre-eclampsia (PE) is a serious cardiovascular complication in pregnancy which shares risk factors with the metabolic syndrome including insulin resistance and obesity. Recently, visfatin was introduced as a novel insulin-mimetic adipokine which is up-regulated when weight is gained. In the current study, we investigated visfatin serum levels in pre-eclamptic patients as compared to healthy gestational age-matched controls. PATIENTS AND MEASUREMENTS: Visfatin was quantified by ELISA in control (n = 20) and PE (n = 15) patients. Furthermore, visfatin was correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation. RESULTS: Mean maternal visfatin serum levels adjusted for maternal age were about twofold up-regulated in PE (31.1 +/- 23.4 microg/l) as compared to controls (15.7 +/- 23.1 microg/l). Furthermore, visfatin concentrations correlated positively with age, blood pressure, creatinine, free fatty acids (FFA), IL-6 and C reactive protein (CRP), whereas a negative correlation was found with fasting insulin and the HOMA-insulin resistance index (HOMA-IR). In multivariate analyses, HOMA-IR and CRP remained independently associated with visfatin serum levels and explained 58% of the variation in visfatin concentrations. CONCLUSIONS: We show that maternal visfatin levels are significantly increased in PE patients. Furthermore, insulin sensitivity and inflammatory status independently predict serum visfatin levels.

Serum levels of the adipokine adipocyte fatty acid-binding protein are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious complication of pregnancy which is associated with an increased future metabolic and cardiovascular risk for both mother and newborn. Recently, adipocyte fatty acid-binding protein (AFABP) was introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In this study, we investigated serum concentrations of the adipokine AFABP in patients with PE as compared to healthy controls of similar gestational age. METHODS: AFABP serum levels were quantified by enzyme-linked immunosorbent assay (ELISA) in control (n = 20) and PE (n = 16) patients. Furthermore, AFABP was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Mean maternal AFABP concentrations were significantly elevated in PE (24.5 +/- 9.7 microg/l) as compared to controls (14.8 +/- 7.1 microg/l). Furthermore, AFABP serum levels correlated positively with age, body mass index (BMI), blood pressure, serum creatinine, free fatty acids (FFAs), leptin, and C-reactive protein (CRP). In multivariate analyses, BMI and serum creatinine remained independently associated with AFABP concentrations and explained 58% of the variation in AFABP levels. CONCLUSION: We demonstrate that maternal AFABP serum concentrations are significantly increased in PE. Furthermore, BMI and serum creatinine are independent predictors of circulating AFABP.

Serum levels of the atherosclerosis biomarker sTWEAK are decreased in type 2 diabetes and end-stage renal disease.

Recently, circulating soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) was introduced as a potential biomarker which is downregulated in atherosclerosis. In the current study, we hypothesized that sTWEAK serum levels are decreased in end-stage renal disease and in patients with type 2 diabetes mellitus (T2DM) since both conditions are high-risk states for atherosclerotic disease. Soluble TWEAK was quantified by ELISA in control patients (n=60) with a glomerular filtration rate above 50 ml/min and patients on chronic hemodialysis (CD, n=60) and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. 30 control patients and 32 CD patients presented with T2DM. Mean serum sTWEAK concentrations were significantly lower in CD and T2DM patients with lowest concentrations seen when both conditions were present (control/-T2DM: 669 +/- 201 microg/l; control/+T2DM: 516 +/- 187 microg/l; CD/-T2DM: 402 +/- 128 microg/l; CD/+T2DM: 317 +/- 132 microg/l; all comparisons between groups p<0.05). In univariate analyses, sTWEAK was negatively correlated with fasting glucose in both, control and CD patients. In multivariate analyses, CD and T2DM remained independently associated with circulating sTWEAK. Taken together, circulating sTWEAK concentrations are decreased in end-stage renal disease and T2DM. Furthermore, both conditions have an additive and independent negative effect on sTWEAK levels. Our results support the view that circulating sTWEAK might be a novel biomarker of atherosclerosis.

Adipokines influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis.

Adipokines including leptin, adiponectin, visfatin, resistin, and interleukin (IL)-6 significantly influence energy metabolism, insulin sensitivity, and cardiovascular health. In the current study, we investigated serum levels of these adipokines in diabetic and nondiabetic patients on maintenance hemodialysis (MD) as compared with controls with a glomerular filtration rate greater than 50 mL/min. Serum leptin, adiponectin, high-molecular-weight (HMW) adiponectin, visfatin, resistin, and IL-6 were determined by enzyme-linked immunosorbent assay in control (n = 60) and MD (n = 60) patients and correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. Adiponectin, visfatin, resistin, and IL-6 were significantly elevated in MD patients as compared with controls. In multivariate analyses, sex and body mass index were independently correlated with serum leptin levels in both controls and MD patients. Furthermore, insulin resistance was independently and negatively associated with adiponectin and HMW adiponectin in both groups. Moreover, circulating resistin levels were independently correlated with serum visfatin concentrations in control and MD patients. However, various independent associations were only found in either controls or patients on MD. Thus, serum IL-6 levels were strongly and independently associated with C reactive protein and resistin in MD patients but not control subjects. We show that levels of various adipokines are significantly increased in MD patients. Furthermore, regulation of adipokines in vivo strongly depends on renal function. Regulation of HMW adiponectin is similar as compared with total adiponectin in the patients studied.

Circulating high-molecular-weight adiponectin is upregulated in preeclampsia and is related to insulin sensitivity and renal function.

OBJECTIVE: Preeclampsia (PE) is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, a paradoxical upregulation of the insulin-sensitizing and anti-atherogenic adipokine adiponectin has been shown in PE. Furthermore, high-molecular-weight (HMW) adiponectin has been suggested as the biologically active form of this adipokine. DESIGN AND METHODS: HMW adiponectin and total adiponectin serum concentrations were quantified by ELISA in PE (n=16) patients and pregnant control women without PE (n=20). Furthermore, HMW adiponectin and total adiponectin were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Median maternal HMW adiponectin and total adiponectin levels were significantly and independently upregulated almost twofold in PE when compared with controls. HMW adiponectin and total adiponectin correlated positively with creatinine and negatively with fasting insulin in univariate and multivariate analyses. CONCLUSIONS: We show that maternal HMW adiponectin and total adiponectin serum concentrations are significantly increased in PE and are positively associated with markers of insulin sensitivity and renal dysfunction. Adiponectin might be part of a physiological feedback mechanism improving insulin sensitivity and cardiovascular health in PE.

Serum levels of adipokine retinol-binding protein-4 in relation to renal function.

OBJECTIVE: Retinol-binding protein (RBP)-4 was recently identified as an adipokine that induces insulin resistance. In the current study, we investigated RBP-4 serum levels in diabetic and nondiabetic patients on chronic hemodialysis (CD) compared with control subjects with a glomerular filtration rate >50 ml/min. The majority of the diabetic subjects used oral hypoglycemic agents or insulin. RESEARCH DESIGN AND METHODS: RBP-4 was determined by enzyme-linked immunosorbent assay in control subjects (n = 59) and CD patients (n = 58) and correlated with clinical and biochemical measures of renal function, glucose and lipid metabolism, and inflammation in both groups. RESULTS: Mean serum RBP-4 levels were almost fourfold higher in CD patients (102 +/- 30 mg/l) compared with control subjects (28 +/- 8 mg/l). Furthermore, serum creatinine independently predicted RBP-4 concentrations in multiple regression analyses in both control subjects and CD patients. In addition, C-reactive protein and systolic blood pressure independently and negatively correlated with RBP-4 serum concentrations in CD patients but not control subjects. In contrast, markers of glucose and lipid metabolism were not independently related to serum RBP-4 in control subjects or CD patients. CONCLUSIONS: We show that markers of renal function are independently related to serum RBP-4 levels.