Susanne Schrey

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.

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 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 irisin in gestational diabetes mellitus during pregnancy and after delivery

OBJECTIVE Irisin has recently been introduced as a novel an exercise-inducible myokine which improves glucose metabolism in mice. However, regulation of circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal period has not been assessed so far. METHODS Circulating irisin was quantified in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls. In a subset of these patients (44 GDM, 41 controls), postpartum follow-up data were also available. In a second study population of 40 healthy women with singleton pregnancies undergoing elective Cesarean section, irisin was assessed in maternal serum before and within 24h after delivery, as well as in umbilical cord blood and in placental tissue. RESULTS In the first study population, median [interquartile range] irisin levels were significantly higher in GDM patients as compared to controls after delivery (previous GDM: 446.3 [146.9]μg/l; controls: 378.0 [111.4]μg/l) but not during pregnancy (GDM: 482.1 [132.1]μg/l; controls: 466.6 [178.0]μg/l). Interestingly, fasting insulin (FI) was independently and positively associated with serum irisin in multivariate analysis during pregnancy. In agreement with these findings, relative changes (ratio) of FI independently and positively predicted relative changes of irisin (ratio) in the second study population. CONCLUSIONS The myokine irisin is independently associated with FI in pregnancy. The physiological significance of these findings needs to be assessed in future experiments.

Preliminary report: circulating levels of the adipokine vaspin in gestational diabetes mellitus and preeclampsia

The objective of the study was to investigate serum levels of the insulin-sensitizing adipokine vaspin in patients with gestational diabetes mellitus (GDM) and preeclampsia (PE) as compared with healthy controls of similar gestational age. Vaspin serum levels were quantified by enzyme-linked immunosorbent assay in control (n = 102), GDM (n = 40), and PE (n = 22) subjects. Median maternal vaspin concentrations were not significantly different in GDM, PE, and control subjects. Furthermore, vaspin did not significantly correlate to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. Circulating vaspin levels are not significantly different between GDM, PE, and control subjects and do not correlate with insulin sensitivity in pregnant subjects.

Serum levels of the adipokine fibroblast growth factor-21 are increased in preeclampsia

BACKGROUND Preeclampsia (PE) is a serious cardiovascular complication in pregnancy, which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Fibroblast growth factor (FGF)-21 was recently introduced as a novel adipokine improving glucose metabolism in vitro and in vivo. MATERIAL AND METHODS We investigated serum FGF-21 levels in patients with PE (n=51) as compared to healthy, age-matched controls (n=51) during and 6 months after pregnancy. Furthermore, association of FGF-21 with markers of renal function, glucose and lipid metabolism, as well as inflammation, was elucidated in all individuals. RESULTS Median maternal FGF-21 serum concentrations adjusted for body mass index and gestational age at blood sampling were significantly, almost 3-fold increased in PE patients (309.6 ng/l) as compared to healthy, age-matched pregnant women (105.2 ng/l) (p<0.001). Furthermore, FGF-21 concentrations were independently and positively correlated with triglycerides whereas an independent and negative association was observed with glomerular filtration rate and low density lipoprotein (LDL) cholesterol in pregnant women. Moreover, FGF-21 serum levels significantly decreased in former PE patients 6 months after pregnancy approaching levels found in control patients. CONCLUSIONS Maternal FGF-21 serum concentrations are significantly increased in PE during pregnancy. Furthermore, triglycerides, glomerular filtration rate, and LDL cholesterol are independent predictors of circulating FGF-21 in pregnant women.

Preliminary report: Serum levels of retinol-binding protein 4 in preeclampsia.

The objective of the study was to investigate serum levels of the adipokine retinol-binding protein 4 (RBP4) in patients with preeclampsia (PE) as compared with healthy controls of similar gestational age. Retinol-binding protein 4 serum levels were quantified by enzyme-linked immunosorbent assay in control (n = 20) and PE (n = 16) patients. Mean maternal RBP4 concentrations were not significantly different in PE (24.5 mg/L) as compared with controls (22.3 mg/L). Furthermore, RBP4 did not correlate to clinical and biochemical measures of pregnancy outcome, renal function, glucose, and lipid metabolism, as well as inflammation. Our results do not support a role of RBP4 in the pathogenesis of PE.

Serum levels of angiopoietin-related growth factor are increased in preeclampsia.

BACKGROUND Preeclampsia is a serious complication in pregnancy with an increased future cardiovascular and metabolic risk for both mother and newborn. Recently, angiopoietin-related growth factor (AGF) was introduced as a novel liver-derived protein with proangiogenic and insulin-sensitizing effects. In the current study, we hypothesized that serum levels of AGF would be lower in preeclamptic patients as compared to healthy controls. METHODS AGF was quantified by enzyme-linked immunosorbent assay (ELISA) in control and preeclamptic patients during pregnancy ( CONTROL n =22, Preeclampsia: n =22) and 6 months after delivery ( CONTROL n =20, Preeclampsia: n =20). Furthermore, circulating AGF was correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS During pregnancy, median maternal AGF concentrations were significantly higher in preeclampsia (191.6 microg/l) as compared to control subjects (136.3 microg/l) (P = 0.004). Furthermore, preeclampsia and systolic blood pressure (SBP) were associated with AGF levels in multivariate analyses independent of maternal age. However, higher circulating AGF concentrations in preeclampsia did not persist 6 months after delivery. CONCLUSIONS Maternal AGF serum levels are significantly and paradoxically higher in preeclampsia during pregnancy. However, median postpartum circulating AGF levels are similar in preeclampsia and normal pregnancies.

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 sclerostin in cardiometabolic disorders during pregnancy.

OBJECTIVE Sclerostin has recently been introduced as a novel osteocyte-secreted factor which is associated with an adverse metabolic profile. However, regulation of circulating sclerostin in cardiometabolic disorders during pregnancy including gestational diabetes mellitus (GDM) and preeclampsia (PE) has not been comprehensively assessed, so far. METHODS Serum levels of sclerostin were quantified in 72 women with GDM and in 72 healthy, pregnant, gestational age-matched controls (study population 1). Furthermore, circulating sclerostin was assessed in 51 women with PE as compared to 51 pregnant controls in a second cohort (study population 2). RESULTS In the first study population (GDM), median [interquartile range] sclerostin levels were not significantly different in women with GDM as compared to controls (GDM: 19.2 [8.1]pmol/l; controls: 18.6 [7.1]pmol/l; p=0.906). Interestingly, C reactive protein was a negative and independent predictor of circulating sclerostin in the GDM cohort in multivariate analysis. In study population 2 (PE), serum levels of sclerostin were not different between women with PE and controls (PE: 18.8 [9.2]pmol/l; controls: 19.3 [8.8]pmol/l; p=0.504). Furthermore, the osteocyte-secreted factor was not related to any metabolic and gestational parameter in this cohort. CONCLUSIONS Sclerostin serum levels are not associated with an adverse metabolic profile during pregnancy in women with GDM and PE. The physiological significance of different associations of circulating sclerostin between pregnancy and non-pregnant status needs to be determined in future experiments.