leptin and Hypertension--Pregnancy-Induced

The article presents information about leptin as the major metabolic hormone. The structure, localization of the hormone and its receptor have been described focusing on maturation and fertility processes. Several polymorphisms of leptin gene and its receptor have been described as potential developmental factors of pregnancy complications such as diabetes mellitus or pregnancy induced hypertension.

Topics: Diabetes, Gestational; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Polymorphism, Genetic; Pregnancy; Pregnancy Complications, Cardiovascular; Receptors, Leptin

In previously apparently healthy women, glucose intolerance and high blood pressure during pregnancy are common and frequently occur together. This article reviews the role of these gestational disorders as markers of vascular dysfunction and its pathophysiology. Mechanisms include alterations to function of large arteries and resistance vessels and to capillary blood flow. Much of the vessel pathology is seen in both gestational diabetes and hypertension. In women who have had transient diabetes during pregnancy and later redeveloped overt diabetes, cardiovascular risk is already elevated nearly fourfold before diagnosis, which is almost as high as the average risk after a clinical diagnosis of diabetes is made. This key finding suggests that vascular risk in such women is at least partly independent of overt hyperglycemia.

Topics: Adiponectin; Brachial Artery; Cardiovascular Diseases; Diabetes, Gestational; Endothelium, Vascular; Female; Glucose Intolerance; Humans; Hypertension, Pregnancy-Induced; Leptin; Pregnancy; Risk Factors; Vasodilation

Pregnancy - induced hypertension (PIH), preeclampsia (PE), and gestational diabetes (GDM) are common adverse outcomes in pregnancy.. To find out whether preconceptual leptin levels differ in subsequent pregnancy between control vs. GDM and hypertensive pregnancy groups.. Data was from The Cardiovascular Risk in Young Finns Study and The Medical Birth Register of Finland. Of 293 subjects 71 developed GDM, 27 PIH/PE and 201 were controls.. Leptin was higher in GDM (p < 0.0001) and PIH/PE (p = 0.0002) groups compared to control. GDM group was robust to BMI matching (p = 0,0081).

Topics: Diabetes, Gestational; Female; Finland; Humans; Hypertension, Pregnancy-Induced; Leptin; Pre-Eclampsia; Pregnancy

Exercise has profound effects on cardiovascular function and metabolism in both physiological and pathophysiological states. The present study tested whether voluntary exercise would protect male offspring against maternal gestational hypertension-induced hypertensive response sensitization elicited by post-weaning high-fat diet (HFD).. On low-lard-fat diet, offspring of both normotensive and hypertensive dams had comparable resting blood pressure, but HFD feeding elicited an enhanced increase in blood pressure (ie, hypertensive response sensitization) in sedentary offspring of hypertensive dams when compared with sedentary offspring of normotensive dams. The HFD fed sedentary offspring of hypertensive dams displayed greater sympathetic activity, enhanced pressor responses to centrally administered ANG II (angiotensin II) or leptin, and greater mRNA expression of proinflammatory cytokines, leptin, and a marker of blood-brain barrier leakage in the hypothalamic paraventricular nucleus. The enhanced blood pressure and central sympathetic activity in HFD-fed sedentary offspring of hypertensive dams were significantly reduced by exercise but fell only to levels comparable to HFD-fed exercising offspring of normotensive dams. HFD-induced increases in plasma IL-6 (interleukin-6) and sympathetic activity and greater pressor responses to central TNF (tumor necrosis factor)-α in offspring from both normotensive and hypertensive dams were also maintained after exercise. Nevertheless, exercise had remarkably beneficial effects on metabolic and autonomic function, brain reactivity to ANG II and leptin and gene expression of brain prohypertensive factors in all offspring.. Voluntary exercise plays a beneficial role in preventing maternal hypertension-induced hypertensive response sensitization, and that this is associated with attenuation of enhanced brain reactivity and centrally driven sympathetic activity.

Topics: Animals; Blood Pressure; Diet, High-Fat; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley

The study of adipokines and oxidative stress has aided in understanding pre-eclampsia physiopathology. Therefore, our group aimed to evaluate the correlation between the adipokines (adiponectin and leptin) and the oxidative stress marker malondialdehyde-thiobarbituric acid reactive substances (MDA-TBARS) and antioxidant activity of plasma [ferric reducing ability of plasma (FRAP)] in healthy pregnant women and patients with gestational hypertension and pre-eclampsia. We found a significant negative correlation between MDA-TBARS and adiponectin (r = -0.40, p = 0.0042), suggesting a relationship between antioxidant levels and this adipokine in healthy pregnancies which is altered in patients with gestational hypertension or pre-eclampsia.

Topics: Adiponectin; Adult; Antioxidants; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Malondialdehyde; Oxidative Stress; Pregnancy; Thiobarbituric Acid Reactive Substances; Young Adult

Impaired angiogenesis of the developing placenta in the early pregnancy is one etiology of preterm delivery. Vascular endothelial growth factor (VEGF) is a key regulator of normal angiogenesis. Leptin stimulates other angiogenic factors, including VEGF. In this study, we aimed to investigate whether levels of VEGF and leptin in amniotic fluid during the second trimester could serve as markers for preterm delivery.. This study was conducted on second trimester amniotic fluid samples obtained from women undergoing genetic amniocentesis at 16-20 weeks of gestation. VEGF and leptin levels were measured by enzyme-linked immunosorbent assay in every case of delivery at <37 weeks' gestation (n = 36) and in 36 matched controls who delivered at ≥ 37 weeks' gestation.. Amniotic fluid VEGF levels in the preterm group (32.24 ± 4.87 pg/ml) were significantly higher than those in the control group (23.49 ± 2.09 pg/ml) (p < 0.05). Leptin levels in the amniotic fluid were higher in the preterm group (6.64 ± 0.68 ng/ml) compared to the control group (5.35 ± 0.59 ng/ml), but this difference was not significant. Amniotic fluid VEGF and leptin levels were highest in women with placenta previa and were lowest in women with intrauterine growth retardation and pregnancy-induced hypertension.. These results show that amniotic fluid VEGF levels in the second trimester are more predictive of preterm delivery than leptin levels. This study also demonstrates that VEGF levels vary depending on the cause of preterm delivery.

Topics: Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension, Pregnancy-Induced; Infant, Newborn; Leptin; Male; Pregnancy; Pregnancy Trimester, Second; Premature Birth; Vascular Endothelial Growth Factor A

Leptin is known to be elevated in pre-eclampsia/ pregnancy induced hypertension (PE/PIH). However the reports on the association of leptin receptor (LEPR) c.668A>G polymorphism with PE/PIH are inconsistent.. LEPR c.668A>G polymorphism was studied in a cohort of women with PE/PIH (N = 61) and normotensive pregnancies (N = 40) by polymerase chain reaction / restriction fragment length polymorphism. Genotype and allele frequencies were in Hardy-Weinberg equilibrium within both groups (Chi square test). Allele and genotype frequencies were not significantly different between PE/PIH and normotensive pregnancies (Chi square test). Leptin levels (Kruskal Wallis analysis of variance) and leptin/body mass index (one way analysis of variance) were not significantly different between genotypes within each group. However, leptin (Mann Whitney U test) and leptin normalised to body mass index (unpaired t test) were significantly higher in PE/PIH women homozygous and heterozygous for the G668 allele than in respective normotensives.. Whether the leptin receptor c.668A>G polymorphism increases the risk of developing PE/PIH in Sri Lankan women remains inconclusive in view of the smaller sample studied. However leptin levels in PE/PIH appeared to be modulated by this polymorphism.

Topics: Body Mass Index; Case-Control Studies; Cohort Studies; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension, Pregnancy-Induced; Leptin; Polymorphism, Single Nucleotide; Pre-Eclampsia; Pregnancy; Receptors, Leptin; Sri Lanka

This study was designed to evaluate maternal levels of leptin and interferon-gamma (IFN-gamma) in pregnancy complicated with hypertension and to assess the role of cytokines in predicting the risk of cesarean section.. This was a cohort study with a prospective follow-up. After proportional sampling procedure, the study included the follow-up of 40 women with hypertensive disorders of pregnancy (pregnancy-induced hypertension [PIH] or preeclampsia [PE]) and 40 uncomplicated pregnancies. Women were followed from the time of admission to the delivery. Levels of leptin and interferon-gamma were measured in serum samples from all women. A p-value <0.05 was considered as significant.. Significant increase in IFN-gamma and leptin concentration in women with pre-eclampsia was observed. We found a significant 1.4-fold increase in the risk of birth by cesarean section associated with the increase of the IFN-gamma concentration by 0.1 pg/ml and almost 3-fold increase in the risk associated with the increase of the leptin concentration.. IFN-γ and leptin might be risk markers of cesarean section in hypertension disorders of pregnancy, but further studies supporting this evidence are needed.

Topics: Adult; Apgar Score; Case-Control Studies; Cesarean Section; Female; Humans; Hypertension, Pregnancy-Induced; Interferon-gamma; Labor, Obstetric; Leptin; Linear Models; Pregnancy

Pregnancy-induced hypertension (PIH) affects up to 15% of all pregnancies. Disturbed placentation is one factor associated with PIH. Leptin and peroxisome proliferator activator receptors (PPAR) seem to play an important role in placentation, fetal development, and blood pressure regulation. Therefore, we investigated polymorphisms in the genes encoding leptin, the leptin receptor, and PPARgamma2 in patients with PIH.. In this retrospective case-control study, 103 patients with PIH [gestational hypertension (GH) n = 39; preeclampsia n = 27; eclampsia n = 5; HELLP n = 32] and 100 controls were analyzed for the LEP tetranucleotide repeat (TTTC)(n) and the leptin receptor (LEPR) R223Q and PPARgamma2 P12A substitutions. Statistical analysis was performed using the chi-square, Mann-Whitney U-, and Kruskal-Wallis tests (P < 0.05 significant).. The frequency of the three possible genotypes did not differ significantly between patients and controls [LEP (TTTC)(n): P = 0.43; LEPR R223Q: P = 0.94; PPARgamma2 P12A: P = 0.94]. However, postpartal diastolic blood pressure of PIH patients was significantly higher in homozygous carriers of the LEPR Q223-encoding allele as compared with patients carrying the wild-type allele (P < 0.01).. Hypertensive disorders in pregnancy were not associated with the LEP, LEPR, and PPARgamma2 polymorphisms studied. The role of other variations in the LEP and PPAR genes in the pathophysiology of PIH and in exacerbations are the objective of ongoing research.

Topics: Adult; Blood Pressure; Case-Control Studies; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Microsatellite Repeats; Polymorphism, Genetic; PPAR gamma; Pregnancy; Receptors, Leptin; Retrospective Studies

To investigate −2548 G/A polymorphism of LEP gene, plasma leptin and soluble leptin receptor in preeclampsia/pregnancy induced hypertension.. Sixty-two patients and 63 controls (normal pregnancies) studied in the third trimester. Leptin and soluble leptin receptor measured by enzyme immunosorbent assay and −2548 G/A polymorphism by polymerase chain reaction followed by restriction enzyme digestion.. Frequency of the AA genotype was significantly (p < 0.001) higher in patients. The A allele conferred a relative risk of 1.67 for the disease (p < 0.0001). Preeclampsia/pregnancy induced hypertension significantly (p < 0.001 to 0.0001) affected leptin and soluble leptin receptor concentrations, free leptin index and leptin normalized to body mass index. Genotype significantly (p < 0.05) influenced only the soluble leptin receptor concentrations.. Preeclampsia/pregnancy induced hypertension appears to be associated with higher circulating leptin and lower SLR levels, and with the AA genotype of −2548 G/A polymorphism of the leptin gene.

Topics: Adult; Alleles; Analysis of Variance; Female; Gene Frequency; Humans; Hypertension, Pregnancy-Induced; Leptin; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Receptors, Leptin; Statistics, Nonparametric

To evaluate the role of the adipokines, visfatin and leptin in the pathophysiology of pre-eclampsia and how their concentrations correlate with the severity of the disease and abnormal Doppler velocimetry.. A cross-sectional study was carried out in 72 pregnant women (30 patients with mild pre-eclampsia, 20 patients with severe pre-eclampsia and 22 healthy normotensive pregnant women) during the third trimester of pregnancy. The maternal levels of plasma visfatin and serum leptin were determined in all cases by enzyme immunoassay and enzyme-linked immunosorbent assay, respectively. The uterine artery and umbilical artery RI were determined by Doppler analysis in all cases.. Plasma visfatin levels and serum leptin levels were higher in patients with pre-eclampsia than in the normotensive pregnant women. Six patients with mild pre-eclampsia and five patients with severe pre-eclampsia had abnormal Doppler velocimetry. Visfatin and leptin levels of pre-eclamptic patients with abnormal Doppler velocimetry were significantly higher than they were in those with normal Doppler velocimetry. Serum leptin levels were positively correlated with plasma visfatin level in cases of pre-eclampsia.. These findings suggest that increased maternal levels of leptin and visfatin may be involved in the pathogenesis of pre-eclampsia, and measurement of these adipokines may be useful in assessment of the severity of disease.

Topics: Adult; Blood Flow Velocity; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Nicotinamide Phosphoribosyltransferase; Pre-Eclampsia; Pregnancy; Pregnancy Trimester, Third; Severity of Illness Index; Ultrasonography, Doppler; Ultrasonography, Prenatal; Up-Regulation; Young Adult

To compare cord blood leptin concentrations between normal pregnancy, pregnancy induced hypertension (PIH), and gestational diabetes mellitus (GDM).. Cross-sectional study.. Academic institutes and a tertiary care maternal hospital.. 48 newborns of normal pregnancies (N=18), pregnancy induced hypertension (N=16), and gestational diabetes mellitus (N=14) were studied. Cord blood samples were collected and newborn anthropometric indices recorded at delivery. Leptin concentrations were measured using an enzyme immunoassay.. Cord blood leptin levels were significantly different between the 3 groups (Kruskal-Wallis ANOVA; P=0.0064), and the difference resulted mainly from higher levels in GDM than in PIH [geometric mean (95% CI) for GDM: 10.89 (6.30, 18.84) vs PIH: 3.49 (2.14, 5.69) ng/ml (Dunn's multiple comparison: P<0.01). This pattern persisted even when leptin levels were normalized to the ponderal index (Kruskal-Wallis ANOVA P=0.0035; Dunn's multiple comparison: P<0.01). Leptin levels significantly and positively correlated with the ponderal index in normal pregnancy (Spearman r=0.506, p<0.05) and with birth weight in PIH (r=0.5463, p<0.05).. In GDM cord blood leptin levels are significantly higher, and a source other than fetal adipocytes appears to contribute to this.

Topics: Birth Weight; Body Height; Cross-Sectional Studies; Diabetes, Gestational; Female; Fetal Blood; Humans; Hypertension, Pregnancy-Induced; Infant, Newborn; Leptin; Pregnancy

Insulin resistance syndrome has been observed in women with hypertensive disease of pregnancy, but few studies evaluated the presence of the syndrome a few years after delivery. The objective of this study was to evaluate the presence of insulin resistance and its metabolic alterations in these women compared with those who had a normal pregnancy. We performed an observational study in 168 women with previous hypertensive disease of pregnancy and 168 control subjects with normal pregnancy contacted, on average, 7.8 years after their first delivery (mean age: 34.8 years). Complete blood lipid profile, insulin, glucose, homocysteine, adipokins, and markers of inflammation were measured. Also, an oral glucose tolerance test was performed in 146 case and 135 control subjects. Case subjects were more overweight compared with control subjects. We found significantly lower high-density lipoprotein cholesterol and adiponectin levels and higher apolipoprotein (apo) apoB/apoA1 ratio, homocysteine, leptin, and insulin levels among case subjects compared with control subjects (P

Topics: Adiponectin; Adult; Apolipoprotein A-I; Apolipoproteins B; Biomarkers; Body Mass Index; Cholesterol, HDL; Female; Glucose Tolerance Test; Humans; Hypertension, Pregnancy-Induced; Insulin; Insulin Resistance; Leptin; Medical Records; Overweight; Pre-Eclampsia; Pregnancy; Time Factors

To identify parameters that may assist clinicians in predicting which women will develop preeclampsia (PE) after initially presenting with gestational hypertension (GH).. 118 women were recruited to the study with GH or PE. They were divided into three groups based on their diagnosis at delivery- (1) GH, (2) PE from the time of presentation, (3) those with an initial diagnosis of GH who progressed to PE. Women underwent 24 hour ambulatory blood pressure monitoring (ABPM) and had serum estrogen, progesterone, beta-HCG, leptin and adiponectin measured as possible predictors of transformation of GH to PE.. Women who presented with GH, and progressed to PE, presented four weeks earlier (33 vs 37 weeks, p < 0.001) than those who did not progress. Women with PE, either as their initial diagnosis or after progression from GH, were delivered earlier (p < 0.001) and had more small for gestational age (SGA) babies than women with GH at delivery (p < 0.05). Those who developed PE after presenting with GH generally had higher blood pressures than those who remained as GH, significant for awake and 24 hour systolic blood pressures (p < 0.05). beta-HCG, estrogen, progesterone or leptin values were similar across the groups. Adiponectin was higher in women with established PE at presentation compared to women with GH (p = 0.02) but adiponectin failed to discriminate those women with an initial diagnosis of GH who progressed to PE.. 24 hr ABPM may provide a non-invasive method of identifying this 'at risk' GH population, particularly in the case of early presentation.

Topics: Adiponectin; Adult; Blood Pressure Monitoring, Ambulatory; Disease Progression; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Sensitivity and Specificity

Leptin is a proteic hormone, isolated in 1994, mainly synthetized in the white adipose tissue. Aim of this study was to compare leptin concentrations in normal pregnancies with those measured in pregnancies complicated by gestational diabetes or gestational hypertension or pre-eclampsia.. We enrolled 48 pregnant women: 18 with uncomplicated pregnancy, 11 with gestational diabetes, 19 with gestational hypertension or pre-eclampsia. Leptin concentrations were measured in maternal serum at enrollment, together with insulin and cortisol, at delivery and in the immediate postpartum. At delivery serum leptin was calculated in the cord blood too.. Fasting plasma leptin and insulin were higher in the group of patients with gestational hypertension, than in the other groups. Third-trimester maternal leptin concentrations correlated significantly with insulin levels in the group of women with gestational diabetes and in the group with gestational hypertension or pre-eclampsia, but not in the women with an uncomplicated pregnancy.. Leptin concentrations in pregnancies complicated by hypertensive disorders are significantly higher than in normal pregnancies. The increased leptin concentrations are independent of associated proteinuria, as women with simple gestational hypertension and preeclampsia showed comparable third-trimester leptin concentrations. In both women with gestational diabetes and women with hypertensive disorders, serum leptin correlated closely with serum insulin, suggesting that the association between leptin and insulin resistance is preserved in pregnancy. Whatever the reasons for an increased maternal leptin production in pregnancies complicated by hypertension, maternal leptin homeostasis does not seem to influence foetal serum leptin concentrations, which seems to be mainly related to birth weight.

Topics: Adult; Biomarkers; Diabetes, Gestational; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Pregnancy; Risk Factors

To determine serum leptin levels in hypertensive disorder of pregnancy.. In this prospective, cross-sectional, case control study, we measured serum leptin levels of 58 hypertensive pregnant women and 54 normal pregnant women. We also did blood and urine analysis for the evaluation of the severity of hypertensive disorder of pregnancy. The patients were followed until after delivery and information about labour was recorded. We analysed the difference and correlation between anthropometric measures, hormonal and biochemical parameters, and serum leptin levels in two groups.. In the study group, serum leptin levels were determined to be higher than the control group. Neonatal birth weight was significantly lower in the hypertensive group. While the serum uric acid, urea, aspartate aminotransferase, fibronectin, and fasting blood glucose levels were found to be higher, serum total protein and albumin levels were significantly lower among the hypertensive pregnant women. Hypertensive pregnant women were more insulin resistant. Serum leptin levels were highly and positively correlated with serum fibronectin, and C peptide levels. A negative significant correlation was observed between maternal serum leptin levels and neonatal birth weight among the pregnant women having the hypertensive disorders.. Serum leptin levels in hypertensive pregnant women appear to be higher. The determination of serum leptin levels may be as important as serum fibronectin and C peptide levels in the management of hypertensive disorder of pregnancy. C peptide and insulin may be due to hyperinsulinemia which leads to increased stimulation of leptin production by fatty tissue. Insulin resistance which appears in late pregnancy is more significant especially in pregnancies complicated by preeclampsia.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cross-Sectional Studies; Female; Fibronectins; Humans; Hypertension, Pregnancy-Induced; Insulin Resistance; Leptin; Logistic Models; Pregnancy; Prospective Studies; Proteinuria; Skinfold Thickness

Topics: Adult; Female; Humans; Hypertension, Pregnancy-Induced; Leptin; Placenta; Pregnancy; Tumor Necrosis Factor-alpha