leptin and Diabetes--Gestational

Topics: Cytokines; Diabetes, Gestational; Female; Humans; Interleukin-6; Leptin; Pregnancy; Tumor Necrosis Factor-alpha

Gestational diabetes mellitus (GDM) is the most frequent pathophysiological state of pregnancy, which in many cases produces fetuses with macrosomia, requiring increased nutrient transport in the placenta. Recent studies by our group have demonstrated that leptin is a key hormone in placental physiology, and its expression is increased in placentas affected by GDM. However, the effect of leptin on placental nutrient transport, such as transport of glucose, amino acids, and lipids, is not fully understood. Thus, we aimed to review literature on the leptin effect involved in placental nutrient transport as well as activated leptin signaling pathways involved in the expression of placental transporters, which may contribute to an increase in placental nutrient transport in human pregnancies complicated by GDM. Leptin appears to be a relevant key hormone that regulates placental transport, and this regulation is altered in pathophysiological conditions such as gestational diabetes. Adaptations in the placental capacity to transport glucose, amino acids, and lipids may underlie both under- or overgrowth of the fetus when maternal nutrient and hormone levels are altered due to changes in maternal nutrition or metabolic disease. Implementing new strategies to modulate placental transport may improve maternal health and prove effective in normalizing fetal growth in cases of intrauterine growth restriction and fetal overgrowth. However, further studies are needed to confirm this hypothesis.

Topics: Amino Acids; Diabetes, Gestational; Female; Fetal Macrosomia; Glucose; Humans; Leptin; Lipids; Membrane Transport Proteins; Nutrients; Placenta; Pregnancy

Gestational diabetes mellitus (GDM) is a serious complication of pregnancy and is defined as a state of glucose intolerance that is first diagnosed and arises during gestation. Although the pathophysiology of GDM has not yet been thoroughly clarified, insulin resistance and pancreatic β-cell dysfunction are considered critical components of its etiopathogenesis. To sustain fetus growth and guarantee mother health, many significant changes in maternal metabolism are required in normal and high-risk pregnancy accompanied by potential complications. Adipokines, adipose tissue-derived hormones, are proteins with pleiotropic functions including a strong metabolic influence in physiological conditions and during pregnancy too. A growing number of studies suggest that various adipokines including adiponectin, leptin, visfatin, resistin and tumor necrosis factor α (TNF-α) are dysregulated in GDM and might have pathological significance and a prognostic value in this pregnancy disorder. In this review, we will focus on the current knowledge on the role that the aforementioned adipokines play in the development and progression of GDM.

Topics: Adipokines; Adiponectin; Adipose Tissue; Cytokines; Diabetes, Gestational; Female; Gene Expression; Gene Expression Regulation; Glucose Intolerance; Humans; Insulin Resistance; Insulin-Secreting Cells; Leptin; Nicotinamide Phosphoribosyltransferase; Pregnancy; Resistin; Tumor Necrosis Factor-alpha

Maternal pregestational obesity is a well-known risk factor for offspring obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes. The mechanisms by which maternal obesity can induce alterations in fetal and later neonatal metabolism are not fully elucidated due to its complexity and multifactorial causes. Two adipokines, leptin and adiponectin, are involved in fetal and postnatal growth trajectories, and both are altered in women with pregestational obesity. The placenta synthesizes leptin, which goes mainly to the maternal circulation and in lesser amount to the developing fetus. Maternal pregestational obesity and hyperleptinemia are associated with placental dysfunction and changes in nutrient transporters which directly affect fetal growth and development. By the other side, the embryo can produce its own leptin from early in development, which is associated to fetal weight and adiposity. Adiponectin, an insulin-sensitizing adipokine, is downregulated in maternal obesity. High molecular weight (HMW) adiponectin is the most abundant form and with most biological actions. In maternal obesity lower total and HMW adiponectin levels have been described in the mother, paralleled with high levels in the umbilical cord. Several studies have found that cord blood adiponectin levels are related with postnatal growth trajectories, and it has been suggested that low adiponectin levels in women with pregestational obesity enhance placental insulin sensitivity and activation of placental amino acid transport systems, supporting fetal overgrowth. The possible mechanisms by which maternal pregestational obesity, focusing in the actions of leptin and adiponectin, affects the fetal development and postnatal growth trajectories in their offspring are discussed.

Topics: Adipokines; Adiponectin; Diabetes, Gestational; Female; Fetal Development; Humans; Insulin Resistance; Leptin; Molecular Weight; Obesity, Maternal; Placenta; Pregnancy; Pregnancy Complications; Receptors, Adiponectin; Receptors, Leptin

Leptin is highly expressed in the placenta, mainly by trophoblastic cells, where it has an important autocrine trophic effect. Moreover, increased leptin levels are found in the most frequent pathology of pregnancy: gestational diabetes, where leptin may mediate the increased size of the placenta and the fetus, which becomes macrosomic. In fact, leptin mediates the increased protein synthesis, as observed in trophoblasts from gestational diabetic subjects. In addition, leptin seems to facilitate nutrients transport to the fetus in gestational diabetes by increasing the expression of the glycerol transporter aquaporin-9. The high plasma leptin levels found in gestational diabetes may be potentiated by leptin resistance at a central level, and obesity-associated inflammation plays a role in this leptin resistance. Therefore, the importance of anti-inflammatory nutrients to modify the pathology of pregnancy is clear. In fact, nutritional intervention is the first-line approach for the treatment of gestational diabetes mellitus. However, more nutritional intervention studies with nutraceuticals, such as polyphenols or polyunsaturated fatty acids, or nutritional supplementation with micronutrients or probiotics in pregnant women, are needed in order to achieve a high level of evidence. In this context, the Mediterranean diet has been recently found to reduce the risk of gestational diabetes in a multicenter randomized trial. This review will focus on the impact of maternal obesity on placental inflammation and nutrients transport, considering the mechanisms by which leptin may influence maternal and fetal health in this setting, as well as its role in pregnancy pathologies.

Topics: Anti-Inflammatory Agents; Diabetes, Gestational; Diet, Mediterranean; Female; Fetal Macrosomia; Humans; Leptin; Nutrition Therapy; Nutritional Status; Obesity; Placenta; Pregnancy; Pregnancy Complications; Trophoblasts

Nowadays, it is well-known that the deregulation of epigenetic machinery is a common biological event leading to the development and progression of metabolic disorders. Moreover, the expression level and actions of leptin, a vast adipocytokine regulating energy metabolism, appear to be strongly associated with epigenetics. Therefore, the aim of this review was to summarize the current knowledge of the epigenetic regulation of leptin as well as the leptin-induced epigenetic modifications in metabolic disorders and associated phenomena. The collected data indicated that the deregulation of leptin expression and secretion that occurs during the course of metabolic diseases is underlain by a variation in the level of promoter methylation, the occurrence of histone modifications, along with miRNA interference. Furthermore, leptin was proven to epigenetically regulate several miRNAs and affect the activity of the histone deacetylases. These epigenetic modifications were observed in obesity, gestational diabetes, metabolic syndrome and concerned various molecular processes like glucose metabolism, insulin sensitivity, liver fibrosis, obesity-related carcinogenesis, adipogenesis or fetal/early postnatal programming. Moreover, the circulating miRNA profiles were associated with the plasma leptin level in metabolic syndrome, and miRNAs were found to be involved in hypothalamic leptin sensitivity. In summary, the evidence suggests that leptin is both a target and a mediator of epigenetic changes that develop in numerous tissues during metabolic disorders.

Topics: Adipogenesis; Animals; Diabetes, Gestational; DNA Methylation; Epigenesis, Genetic; Female; Fetal Development; Histone Code; Humans; Hypothalamus; Leptin; Metabolic Diseases; Metabolic Syndrome; MicroRNAs; Obesity; Pregnancy

Accurate early risk prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated novel biomarker predictors to develop a first-trimester risk prediction model in a large multiethnic cohort.. Maternal clinical, aneuploidy and pre-eclampsia screening markers (PAPP-A, free hCGβ, mean arterial pressure, uterine artery pulsatility index) were measured prospectively at 11-13+6 weeks' gestation in 980 women (248 with GDM; 732 controls). Nonfasting glucose, lipids, adiponectin, leptin, lipocalin-2, and plasminogen activator inhibitor-2 were measured on banked serum. The relationship between marker multiples-of-the-median and GDM was examined with multivariate regression. Model predictive performance for early (< 24 weeks' gestation) and overall GDM diagnosis was evaluated by receiver operating characteristic curves.. Glucose, triglycerides, leptin, and lipocalin-2 were higher, while adiponectin was lower, in GDM (p < 0.05). Lipocalin-2 performed best in Caucasians, and triglycerides in South Asians with GDM. Family history of diabetes, previous GDM, South/East Asian ethnicity, parity, BMI, PAPP-A, triglycerides, and lipocalin-2 were significant independent GDM predictors (all p < 0.01), achieving an area under the curve of 0.91 (95% confidence interval [CI] 0.89-0.94) overall, and 0.93 (95% CI 0.89-0.96) for early GDM, in a combined multivariate prediction model.. A first-trimester risk prediction model, which incorporates novel maternal lipid markers, accurately identifies women at high risk of GDM, including early GDM.

Topics: Adiponectin; Adult; Arterial Pressure; Biomarkers; Blood Glucose; Case-Control Studies; Chorionic Gonadotropin; Diabetes, Gestational; Female; Health Status Indicators; Humans; Leptin; Lipids; Lipocalin-2; Models, Theoretical; Multivariate Analysis; Plasminogen Activator Inhibitor 2; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Pulsatile Flow; ROC Curve; Uterine Artery

Gestational diabetes mellitus (GDM) is a serious pregnancy complication, in which women without previously diagnosed diabetes develop chronic hyperglycemia during gestation. In most cases, this hyperglycemia is the result of impaired glucose tolerance due to pancreatic β-cell dysfunction on a background of chronic insulin resistance. Risk factors for GDM include overweight and obesity, advanced maternal age, and a family history or any form of diabetes. Consequences of GDM include increased risk of maternal cardiovascular disease and type 2 diabetes and macrosomia and birth complications in the infant. There is also a longer-term risk of obesity, type 2 diabetes, and cardiovascular disease in the child. GDM affects approximately 16.5% of pregnancies worldwide, and this number is set to increase with the escalating obesity epidemic. While several management strategies exist-including insulin and lifestyle interventions-there is not yet a cure or an efficacious prevention strategy. One reason for this is that the molecular mechanisms underlying GDM are poorly defined. This review discusses what is known about the pathophysiology of GDM, and where there are gaps in the literature that warrant further exploration.

Topics: Adiponectin; Adipose Tissue; Animals; Diabetes, Gestational; Female; Glucose; Humans; Insulin Resistance; Insulin-Secreting Cells; Leptin; Oxidative Stress; Pregnancy; Risk Factors

Universal oral glucose tolerance-based screening is employed to identify pregnant women with gestational diabetes mellitus (GDM), as treatment of this condition decreases the risk of associated complications. A simple and accurate blood test which identifies women at low or high risk for GDM in the first trimester would have the potential to decrease costs and improve outcomes through prevention or treatment. This review summarizes published data on early pregnancy biomarkers which have been tested as predictors of GDM.. A large number of first-trimester biochemical predictors of GDM have been reported, mostly in small case-control studies. These include glycemic markers (fasting glucose, post-load glucose, hemoglobin A1C), inflammatory markers (C-reactive protein, tumor necrosis factor-alpha), insulin resistance markers (fasting insulin, sex hormone-binding globulin), adipocyte-derived markers (adiponectin, leptin), placenta-derived markers (follistatin-like-3, placental growth factor, placental exosomes), and others (e.g., glycosylated fibronectin, soluble (pro)renin receptor, alanine aminotransferase, ferritin). A few large studies suggest that first-trimester fasting glucose or hemoglobin A1C may be useful for identifying women who would benefit from early GDM treatment. To translate the findings from observational studies of first-trimester biomarkers for GDM to clinical practice, trials or cost-effectiveness analyses of screening and treatment strategies based on these novel biomarkers are needed.

Topics: Adiponectin; Adult; Biomarkers; Blood Glucose; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Leptin; Pregnancy; Tumor Necrosis Factor-alpha

Our purpose was to review relations between physical activity during pregnancy, gestational diabetes, and other maternal metabolic markers (i.e., lipids, tumor necrosis factor alpha (TNFα), interleukin six (IL-6), leptin, and adiponectin). While observational studies indicate a protective effect of physical activity on gestational diabetes, interventions that promote recommended levels of physical activity during pregnancy (i.e., 150+ min/week) have failed to show significant effects. However, interventions have been often underpowered and with low protocol adherence. Maternal lipids, TNFα, IL-6, and leptin all increase and adiponectin decreases with a healthy pregnancy. Although the evidence base is small, preliminary results indicate a beneficial effect of physical activity on lowering triglycerides, TNFα, and leptin levels while increasing muscle-derived IL-6 levels during pregnancy. Future studies are needed to examine relationships among prospectively measured physical activity and metabolic markers throughout pregnancy, as well as theoretically based physical activity interventions to prevent gestational diabetes.

Topics: Adiponectin; Adult; Biomarkers; Diabetes, Gestational; Female; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Lipids; Motor Activity; Patient Compliance; Practice Guidelines as Topic; Pregnancy; Tumor Necrosis Factor-alpha

We aimed to systematically review available literature linking adipokines to gestational diabetes mellitus (GDM) for a comprehensive understanding of the roles of adipokines in the development of GDM.. We searched PubMed/MEDLINE and EMBASE databases for published studies on adipokines and GDM through October 21, 2014. We included articles if they had a prospective study design (i.e., blood samples for adipokines measurement were collected before GDM diagnosis). Random-effects models were used to pool the weighted mean differences comparing levels of adipokines between GDM cases and non-GDM controls.. Of 1523 potentially relevant articles, we included 25 prospective studies relating adipokines to incident GDM. Our meta-analysis of nine prospective studies on adiponectin and eight prospective studies on leptin indicated that adiponectin levels in the first or early second trimester of pregnancy were 2.25 μg/ml lower (95% CI: 1.75-2.75), whereas leptin levels were 7.25 ng/ml higher (95% CI 3.27-11.22), among women who later developed GDM than women who did not. Prospective data were sparse and findings were inconsistent for visfatin, retinol binding protein (RBP-4), resistin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and vaspin. We did not identify prospective studies for several novel adipokines, including chemerin, apelin, omentin, or adipocyte fatty acid-binding protein. Moreover, no published prospective studies with longitudinal assessment of adipokines and incident GDM were identified.. Adiponectin levels in the first or second trimester of pregnancy are lower among pregnant women who later develop GDM than non-GDM women, whereas leptin levels are higher. Well-designed prospective studies with longitudinal assessment of adipokines during pregnancy are needed to understand the trajectories and dynamic associations of adipokines with GDM risk.

Topics: Adipokines; Adiponectin; Adult; Biomarkers; Diabetes, Gestational; Female; Humans; Leptin; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Risk

This paper presents current data on the pathophysiology of gestational diabetes mellitus, classification and new diagnostic methods. Gestational Diabetes Mellitus (GDM) is defined as carbohydrate intolerance first detected during pregnancy. It is the most common metabolic disorder of pregnant women. The frequency of its occurrence depends on inter alia body weight, belonging to a particular ethnic group and diagnostic methods. GDM reveals usually between 24 and 28 weeks of gestation. The development of diabetes in pregnancy poses a threat to both the mother and the fetus. It is associated with an increased incidence of birth defects in newborns, impaired intrauterine fetal growth, higher incidence of premature births and greater percentage of the intrauterine fetus death. Amongst women complicated by gestational diabetes arterial hypertension more often unfolds. In the development of gestational diabetes mellitus important role apart from maternal and fetal hyperinsulinemia play: antagonistic to insulin placental hormones, TNFα, placental pro-inflammatory cytokines, resistin, leptin ghrelin.

Topics: Congenital Abnormalities; Cytokines; Diabetes, Gestational; Female; Fetal Death; Humans; Infant, Newborn; Infant, Premature; Insulin; Leptin; Pregnancy; Prenatal Exposure Delayed Effects

Gestational diabetes is characterised by glucose intolerance with onset or first recognition during pregnancy. The disease shows facets of the metabolic syndrome including obesity, insulin resistance, and dyslipidaemia. Adipokines are a group of proteins secreted from adipocytes, which are dysregulated in obesity and contribute to metabolic and vascular complications. Recent studies have assessed the role of various adipokines including leptin, adiponectin, tumour necrosis factor α (TNFα), adipocyte fatty acid-binding protein (AFABP), retinol-binding protein 4 (RBP4), resistin, NAMPT, SERPINA12, chemerin, progranulin, FGF-21, TIMP1, LCN2, AZGP1, apelin (APLN), and omentin in gestational diabetes. This Review provides an overview of these key adipokines, their regulation in, and potential contribution to gestational diabetes. Based on the evidence so far, the adipokines adiponectin, leptin, TNFα, and AFABP seem to be the most probable candidates involved in the pathophysiology of gestational diabetes.

Topics: Adipokines; Adiponectin; Blood Glucose; Diabetes, Gestational; Fatty Acid-Binding Proteins; Female; Humans; Insulin Resistance; Leptin; Pregnancy; Tumor Necrosis Factor-alpha

Gestational diabetes mellitus (GDM) is defined as a glucose intolerance of varying severity with onset or first recognition during pregnancy. The prevalence of GDM is growing rapidly worldwide, resulting in numerous and serious complications for both mother and foetus. Two major metabolic disorders, insulin resistance and β cells dysfunction, are currently linked to the pathogenesis of GDM, although the cellular mechanisms involved in the development of GDM are not yet completely understood. Increasing evidence from clinical and experimental studies indicates that adipose tissue dysfunction, characterised by abnormal production of adipokines, is an essential factor linked to insulin resistance and GDM. To date, several adipose tissue-derived hormones have been identified, including leptin, adiponectin, resistin, visfatin, apelin, retinol-binding protein 4 (RBP-4), vaspin, and omentin. The relationship of leptin and adiponectin to insulin resistance in GDM is relatively well documented, but the molecular mechanisms by which these hormones affect insulin resistance are not yet fully known. The other aforementioned adipokines appear to be also important players in the pathophysiology of GDM, although their precise function in this complex process remains to be established. The aim of this article is to review the literature concerning the relationship between the above-mentioned adipokines and GDM, and to clarify their role in the pathophysiology of GDM.

Topics: Adipokines; Adiponectin; Apelin; Diabetes, Gestational; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Nicotinamide Phosphoribosyltransferase; Pregnancy; Resistin; Retinol-Binding Proteins, Plasma; Serpins

Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications. Inflammation may play a role in the pathogenesis of GDM. We performed a systematic review and meta-analysis to determine whether maternal serum concentration of tumor necrosis factor-alpha (TNF-α), leptin, and adiponectin were associated with GDM. A systematic search of PubMed and Medline was undertaken. In total, 27 trials were evaluated by meta-analyses using the software Review Manager 5.0. The results showed that maternal TNF-α (P = 0.0003) and leptin (P < 0.00001) concentrations were significantly higher in GDM patients versus controls. However, maternal adiponectin (P < 0.00001) concentration was significantly lower in GDM patients compared with controls. Subgroup analysis taking in consideration the effect of obesity on maternal adipokine levels showed that circulating levels of TNF-α and leptin remained elevated in GDM patients compared to their body mass index (BMI) matched controls, and adiponectin level remained depressed in GDM individuals. Our findings strengthen the clinical evidence that GDM is accompanied by exaggerated inflammatory responses.

Topics: Adiponectin; Case-Control Studies; Diabetes, Gestational; Female; Humans; Leptin; Pregnancy; Publication Bias; Tumor Necrosis Factor-alpha

Proteins secreted from adipocytes - so-called adipokines - influence metabolic and vascular function. Recent data suggest that various adipokines are dysregulated in gestational diabetes mellitus (GDM) and pre-eclampsia (PE) and might be of pathophysiological and prognostic significance in these complications of pregnancy. This review gives an overview on the regulation and pathophysiology of leptin and adiponectin in GDM and PE. Furthermore, data on novel adipokines including resistin, visfatin, retinol-binding protein 4 and vaspin are summarized.

Topics: Adiponectin; Diabetes, Gestational; Female; Humans; Leptin; Pre-Eclampsia; Pregnancy

Diabetes mellitus complicates 1-2% of all pregnancies but is associated with high perinatal morbidity and mortality. Gestational diabetes affects up to 4% of pregnancies and is associated with fetal macrosomia (large for dates). Fetal growth is a complex process influenced by determinants such as genetics, maternal factors, uterine environment and maternal and fetal hormones. Infants of pre-gestational diabetic mothers have an additional influence of maternal fluctuations in glycaemia. The purpose of this paper is to review maternal and fetal growth factors, including insulin, in the aetiology of macrosomia in diabetic pregnancy. Placental Growth Hormone is the major growth hormone secreted during human pregnancy. Leptin may have a role in satiety. Resistin was originally proposed as the link between obesity and diabetes but is now thought to have a more complex role. These hormones and their actions on human in-utero growth are reviewed in depth with particular reference to both pre-gestational (type 1 and type 2 diabetes) and gestational diabetes. Previously increased fetal weight in infants of diabetic mothers was thought to be as a result of maternal hyperglycaemia. It is now evident that control of fetal growth, in normal as well as diabetic pregnancies, is far more complex than previously thought.

Topics: Adult; Birth Weight; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Macrosomia; Fetus; Growth Hormone; Humans; Hyperglycemia; Infant; Insulin; Leptin; Placental Hormones; Pregnancy; Pregnancy in Diabetics; Resistin

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

During pregnancy, a number of maternal metabolic changes occur early and continue throughout pregnancy which help optimize the transfer of nutrients to the fetus. During normal pregnancy, there are a decrease in insulin sensibility which is physiological, progressive and reverse. For glucose tolerance to be maintained in pregnancy it is necessary for maternal insulin secretion to increase sufficiently to counteract the fall in insulin sensitivity. The metabolic characteristic of women with gestational diabetes is insufficient insulin secretion to counteract the pregnancy related fall in insulin sensitivity. There are a lot of factors that could explain the mechanism of insulin secretion and insulin sensitivity during normal pregnancy and gestational diabetes mellitus. Although glucose tolerance normalizes shortly after pregnancy with gestational diabetes in the majority of women, the risk of developing overt diabetes, especially type 2 diabetes is markedly increased. The mechanisms which could explain gestational diabetes are the same as type 2 diabetes mellitus. We could speculate that these two diseases are identical for alterations in carbohydrate metabolism, but at different stages.

Topics: Diabetes, Gestational; Female; Humans; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Pregnancy

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose; Humans; Leptin; Obesity; Pregnancy

Leptin, a hormone produced by adipose tissue and the placenta, is enhanced in the maternal circulation throughout pregnancy in both the human and the baboon ( Papio sp.), a proven nonhuman primate model for the study of human pregnancy. The presence of both leptin and its receptor in the fetus implies a role for the polypeptide as a regulator of in utero development, although localization in the placental trophoblast may relate to autocrine and/or paracrine regulatory functions in this important endocrine tissue. Although regulatory mechanisms remain incompletely defined, it has been suggested that cross talk occurs between the fetus, placenta, and maternal adipose stores. Placental estrogen, which is present in increasing concentrations with advancing gestation, is suggested to influence leptin synthesis in a tissue- and cell type-specific fashion. In this capacity, cellular hypoxia, diabetes, and preeclampsia are conditions that appear to be intimately linked to leptin dynamics. A better understanding of regulatory mechanisms will have direct clinical significance, as leptin has been proposed to impact on those causes of human perinatal morbidity and mortality that are associated with anomalies of fetal maturity and development, general conceptus growth, trophoblast endocrinology, and placental sufficiency.

Topics: Animals; Cell Hypoxia; Diabetes, Gestational; Embryonic and Fetal Development; Estrogens; Female; Gene Expression; Humans; Leptin; Papio; Pre-Eclampsia; Pregnancy; Receptors, Cell Surface; Receptors, Leptin; Trophoblasts

Gestational diabetes mellitus (GDM) is linked to the dysregulation of inflammatory markers in women with GDM compared to women without. It is unclear whether the intensity of glycemic control influences these biomarkers. We aimed to assess whether different glycemic targets for women with GDM and compliance influence maternal and infant biomarkers.. Maternity hospitals caring for women with GDM were randomized in the TARGET Trial to tight or less tight glycemic targets. Maternal blood was collected at study entry, 36 weeks' gestation, and 6 months postpartum, and cord plasma after birth. We assessed compliance to targets and concentrations of maternal serum and infant biomarkers.. Eighty-two women and infants were included in the study. Concentrations of maternal and infant biomarkers did not differ between women assigned to tighter and less tight glycemic targets; however, concentrations were altered in maternal serum leptin and CRP and infant cord C-peptide, leptin, and IGF in women who complied with tighter targets.. Use of tighter glycemic targets in women with GDM does not change the concentrations of maternal and infant biomarkers compared to less tight targets. However, when compliance is achieved to tighter targets, maternal and infant biomarkers are altered.. The use of tighter glycemic targets in gestational diabetes does not result in changes to maternal or cord plasma biomarkers. However, for women who complied with tighter targets, maternal serum leptin and CRP and infant cord C-peptide, leptin and IGF were altered compared with women who complied with the use of the less tight targets. This article adds to the current evidence base regarding the impact of gestational diabetes on maternal and infant biomarkers. This article highlights the need for further research to assess enablers to meet the tighter target recommendations and to assess the impact on relevant biomarkers.

Topics: Biomarkers; C-Peptide; Diabetes, Gestational; Female; Glycemic Control; Humans; Infant; Leptin; Pregnancy

To compare body composition, visceral adiposity, adipocytokines, and low-grade inflammation markers in prepubertal offspring of mothers who were treated with metformin or insulin for gestational diabetes mellitus (GDM).. 172 offspring of 311 mothers randomized to receive metformin (n = 82) or insulin (n = 90) for GDMwere studied at 9 years of age (follow-up rate 55%). Measurements included anthropometrics, adipocytokines, markers of the low-grade inflammation, abdominal magnetic resonance imaging (MRI), magnetic liver spectrometry (MRS), and whole body dual-energy X-ray absorptiometry (DXA).. Serum markers of low-grade inflammation, visceral adipose tissue volume, total fat percentage, and liver fat percentage were similar between the study groups. Serum adiponectin concentration was higher in children in the metformin group compared to insulin group (median 10.37 vs 9.50 µg/ml, p = 0.016). This difference between groups was observed in boys only (median 12.13 vs 7.50 µg/ml, p < 0.001). Leptin/adiponectin-ratio was lower in boys in the metformin group than in the insulin group (median 0.30 vs 0.75; p = 0.016).. Maternal metformin treatment for GDM had no effects on adiposity, body composition, liver fat, or inflammation markers in prepubertal offspring compared to maternal insulin treatment but was associated with higher adiponectin concentration and lower leptin/adiponectin-ratio in boys.

Topics: Adipokines; Adiponectin; Adiposity; Child; Diabetes, Gestational; Female; Humans; Inflammation; Insulin; Insulin, Regular, Human; Leptin; Male; Metformin; Obesity; Pregnancy

Vitamin D deficiency is a common finding in overweight/obese pregnant women and is associated with increased risk for adverse pregnancy outcome. Both maternal vitamin D deficiency and maternal obesity contribute to metabolic derangements in pregnancy. We aimed to assess the effects of vitamin D3 supplementation in pregnancy versus placebo on maternal and fetal lipids. Main inclusion criteria were: women <20 weeks’ gestation, BMI ≥ 29 kg/m2. Eligible women (n = 154) were randomized to receive vitamin D3 (1600 IU/day) or placebo. Assessments were performed <20, 24−28 and 35−37 weeks and at birth. Linear regression models were used to assess effects of vitamin D on maternal and cord blood lipids. In the vitamin D group significantly higher total 25-OHD and 25-OHD3 levels were found in maternal and cord blood compared with placebo. Adjusted regression models did not reveal any differences in triglycerides, LDL-C, HDL-C, free fatty acids, ketone bodies or leptin between groups. Neonatal sum of skinfolds was comparable between the two groups, but correlated positively with cord blood 25-OH-D3 (r = 0.34, p = 0.012). Vitamin D supplementation in pregnancy increases maternal and cord blood vitamin D significantly resulting in high rates of vitamin D sufficiency. Maternal and cord blood lipid parameters were unaffected by Vitamin D3 supplementation.

Topics: Body Fat Distribution; Cholecalciferol; Cholesterol, LDL; Diabetes, Gestational; Dietary Supplements; Fatty Acids, Nonesterified; Female; Humans; Infant, Newborn; Ketone Bodies; Leptin; Life Style; Obesity; Overweight; Pregnancy; Pregnancy Outcome; Pregnant Women; Triglycerides; Vitamin D; Vitamin D Deficiency; Vitamins

C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration.. For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration.. In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 - 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 - 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 - 0.42, p < 0.001; and Coef.= 0.34, 95% CI: 0.06 - 0.63, p = 0.02, respectively).. UC blood concentration of C-peptide is significantly associated with the incidence of maternal GDM and neonatal macrosomia. Using stratification for maternal BMI and gestational weight gain (GWG) and investigating molecular markers like Leptin and IGF-1 in the future might lay the ground to better understand the link between metabolic disturbances of pregnancy and UC blood C-peptide concentration.

Topics: Birth Weight; Body Mass Index; C-Peptide; Cesarean Section; Child; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Iran; Leptin; Pregnancy; Pregnancy Outcome; Weight Gain

Alpha-lipoic acid (ALA) is a short chain fatty acid and is known as a universal antioxidant. The aim of the current clinical trial study was to explore the effects of ALA supplementation on maternal circulating values of adiponectin (A), leptin (L); and A/L, L/A, adiponectin/homeostatic model assessment for insulin resistance (A/H), and malondialdehyde/total antioxidant capacity (MDA/TAC) ratios in pregnant women with gestational diabetes mellitus (GDM). Sixty women diagnosed as GDM during 24 and 28 weeks of pregnancy were randomly divided into drug (n = 30) and placebo (n = 30) groups. They consumed ALA (100 mg) and cellulose acetate (100 mg) respectively for 8 weeks, per day. The biochemical variables were evaluated before and after the trial. Maternal fasting serum values of glucose (p < .001), HOMA-IR (p < .001), MDA/TAC (p < .001), and L/A (p = .008) were decreased while values of adiponectin (p = .011), A/L (p = .001), and A/H (p < .001) were increased in the drug group after the intervention. In summary, current study had shown that after daily supplementation with 100 mg of ALA for 8 weeks in women with GDM, maternal circulating values of adiponectin, A/L, and A/H were increased while values of L/A and MDA/TAC were decreased.

Topics: Adiponectin; Adult; Antioxidants; Blood Glucose; Diabetes, Gestational; Dietary Supplements; Double-Blind Method; Female; Humans; Insulin Resistance; Leptin; Malondialdehyde; Oxidative Stress; Pregnancy; Thioctic Acid; Treatment Outcome

To discriminate the effect of maternal obesity and gestational diabetes on birth weight and adipose tissue of the newborn.. Normal BMI women (group N, n = 243; 18.5≤ BMI<25 kg/m2) and obese women (group Ob, n = 253; BMI≥30 kg/m2) were recruited in a prospective study between 15 and 18 weeks of gestation. All women were submitted to a 75g oral glucose tolerance test in the second and third trimester. First trimester fasting blood glucose was also obtained from Ob women. All women with one measurement above normal values were considered positive for gestational diabetes and first treated by dietary intervention. When dietary measures were not efficient, they were treated by insulin. Neonatal anthropometrics, sum of skinfolds and cord serum hormones were measured.. 222 N and 226 Ob mothers and their newborns were included in the analysis. Diabetes was diagnosed in 20% and 45.2% of N and Ob women, respectively. Birth weight was not statistically different between groups (boys: 3456g±433 and 3392g±463; girls: 3316g±402 and 3391g±408 for N and Ob, respectively). Multivariate analysis demonstrated that skinfold thickness and serum leptin concentrations were significantly increased in girls born to women with obesity (18.0mm±0.6 versus 19.7mm±0.5, p = 0.004 and 11.3ng/mL±1.0 versus 15.3ng/mL±1.0, p = 0.02), but not in boys (18.4mm±0.6 versus 18.5mm±0.5, p = 0.9 and 9.3ng/mL±1.0 versus 9.0ng/mL±1.0, p = 0.9). Based on data from 136 N and 124 Ob women, maternal insulin resistance at 37 weeks was also positively related to skinfold in girls, only, with a 1-point increase in HOMA-IR corresponding to a 0.33mm±0.08 increase in skinfold (p<0.0001).. Regardless of gestational diabetes, maternal obesity and insulin resistance were associated with increased adiposity in girls only. Persistence of this sexual dimorphism remains to be explored during infancy.

Topics: Adiposity; Anthropometry; Birth Weight; Body Mass Index; Diabetes, Gestational; Female; Humans; Infant, Newborn; Leptin; Male; Multivariate Analysis; Obesity; Placenta; Pregnancy; Skinfold Thickness

To evaluate the value of third trimester ultrasound (estimated fetal weight, cheek-to-cheek diameter, sectional Wharton's jelly area, sectional areas and fractional volumes in extremities) to predict birth weight and cord biochemical markers at birth (leptin, insulin, c-peptide, IGF1, erythropoietin and ferritin) in diabetic pregnancies.. Prospective study in 49 patients with gestational diabetes. An ultrasound was performed between 32 and 34 weeks. Clinical data were collected, and a blood sample was obtained from cord after birth. ROC curve models were evaluated for 75(th) and 90(th) birth weight percentile. Univariate and multivariate models were used to assess the association between ultrasound and neonatal outcomes.. Sectional areas and fractional volumes showed significant differences and highest AUC values for predicting birth weight. A significant association was found for extremities measurements with total birth weight and its percentile. The only marker which showed a significant association to estimated fetal weight was erythropoietin. Sectional areas and fractional volumes related to cord leptin, erythropoietin, insulin and c-peptide.. Sectional areas and fractional volumes improve the predictive value of estimated fetal weight in diabetic pregnancies. They also show a predictive association to biochemical changes in cord (leptin, insulin and erythropoietin) related to increased adiposity and risk of fetal hypoxia. © 2015 John Wiley & Sons, Ltd.

Topics: Adult; Birth Weight; Body Fat Distribution; C-Peptide; Diabetes, Gestational; Erythropoietin; Female; Fetal Blood; Humans; Insulin; Leptin; Pregnancy; Prospective Studies; Ultrasonography, Prenatal

This study was designed to compare glucose, lipids, and C-reactive protein (CRP) in women with gestational diabetes mellitus treated with metformin or insulin and in cord plasma of their offspring and to examine how these markers relate to infant size at birth.. Women with gestational diabetes mellitus were randomly assigned to metformin or insulin in the Metformin in Gestational Diabetes trial. Fasting maternal plasma glucose, lipids, and CRP were measured at randomization, 36 weeks' gestation, and 6-8 weeks postpartum as well as in cord plasma. Women with available cord blood samples (metformin n = 236, insulin n = 242) were included.. Maternal plasma triglycerides increased more from randomization to 36 weeks' gestation in women treated with metformin (21.93%) versus insulin (9.69%, P < 0.001). Maternal and cord plasma lipids, CRP, and neonatal anthropometry did not differ between treatments. In logistic regression analyses adjusted for confounders, the strongest associations with birth weight >90th centile were maternal triglycerides and measures of glucose control at 36 weeks.. There were few differences in circulating maternal and neonatal markers of metabolic status and no differences in measures of anthropometry between the offspring of women treated with metformin and the offspring of women treated with insulin. There may be subtle effects of metformin on maternal lipid function, but the findings suggest that treating gestational diabetes mellitus with metformin does not adversely affect lipids or CRP in cord plasma or neonatal anthropometric measures.

Topics: Adult; Blood Glucose; C-Peptide; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Leptin; Metformin; Pregnancy; Risk Factors; Triglycerides

Mild gestational diabetes is a common complication of pregnancy, affecting up to 9% of pregnant women. Treatment of mild GDM is known to reduce adverse perinatal outcomes such as macrosomia and associated birth injuries, such as shoulder dystocia, bone fractures and nerve palsies. This study aimed to compare the plasma glucose concentrations and serum insulin, leptin and adiponectin in cord blood of babies of women (a) without gestational diabetes mellitus (GDM), (b) with mild GDM under routine care, or (c) mild GDM with treatment.. 95 women with mild GDM on oral glucose tolerance testing (OGTT) at one tertiary level maternity hospital who had been recruited to the ACHOIS trial at one of the collaborating hospitals and randomised to either Treatment (n = 46) or Routine Care (n = 49) and Control women with a normal OGTT (n = 133) were included in the study. Women with mild GDM (treatment or routine care group) and OGTT normal women received routine pregnancy care. In addition, women with treated mild GDM received dietary advice, blood glucose monitoring and insulin if necessary. The primary outcome measures were cord blood concentrations of glucose, insulin, adiponectin and leptin.. Cord plasma glucose was higher in women receiving routine care compared with control, but was normalized by treatment for mild GDM (p = 0.01). Cord serum insulin and insulin to glucose ratio were similar between the three groups. Leptin concentration in cord serum was lower in GDM treated women compared with routine care (p = 0.02) and not different to control (p = 0.11). Adiponectin was lower in both mild GDM groups compared with control (Treatment p = 0.02 and Routine Care p = 0.07), while the adiponectin to leptin ratio was lower for women receiving routine care compared with treatment (p = 0.08) and control (p = 0.05).. Treatment of women with mild GDM using diet, blood glucose monitoring and insulin if necessary, influences the altered fetal adipoinsular axis characteristic of mild GDM in pregnancy.

Topics: Adiponectin; Blood Glucose; Diabetes, Gestational; Diet Therapy; Female; Fetal Blood; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Leptin; Pregnancy

An adverse proinflammatory milieu contributes to abnormal cellular energy metabolism response. Gestational diabetes mellitus (GDM) is closely related to an altered maternal inflammatory status. However, its role on lipid metabolism regulation in human placenta has not yet been assessed. The aim of this study was to examine the impact of maternal circulating inflammatory mediators ([TNF]-α, [IL]-6, and Leptin) on placental fatty acid metabolism in GDM pregnancies.. Fasting maternal blood and placental tissues were collected at term deliveries from 37 pregnant women (17 control and 20 GDM). Molecular approach techniques as radiolabeled lipid tracers, ELISAs, immunohistochemistry and multianalyte immunoassay quantitative analysis, were used to quantify serum inflammatory factors' levels, to measure lipid metabolic parameters in placental villous samples (mitochondrial fatty acid oxidation [FAO] rate and lipid content [Triglycerides]), and to analyze their possible relationships. The effect of potential candidate cytokines on fatty acid metabolism in. Enhanced maternal proinflammatory cytokines levels (essentially IL-6) is closely associated with an altered placental fatty acid metabolism in pregnancies with GDM, which may interfere with adequate delivery of maternal fat across the placenta to the fetus.

Topics: Cytokines; Diabetes, Gestational; Fatty Acids; Female; Humans; Inflammation; Interleukin-6; Leptin; Placenta; Pregnancy; Triglycerides; Tumor Necrosis Factor-alpha

Well-regulated placental palmitic acid (PA) and oleic acid (OA) metabolism is vital for optimal placental function and fetal development, but dysregulation occurs with gestational diabetes (GDM). We hypothesized that such dysregulation might arise from increased maternofetal glucose, leptin or insulin concentrations present in GDM, and that dysregulated PA and OA lipid metabolism could be moderated by myo-inositol, a natural polyol and potential GDM intervention. Placental explants from 21 women were incubated with stable isotope-labelled

Topics: Diabetes, Gestational; Female; Glucose; Humans; Insulin; Leptin; Oleic Acid; Palmitic Acid; Phosphatidylethanolamines; Placenta; Pregnancy

Children of mothers with gestational diabetes mellitus (GDM) are more prone to acquire type 2 diabetes and obesity as adults. Due to this link, early intervention strategies that alter the gut microbiome may benefit the mother and kid long-term. This work uses metagenomic and transcriptome sequencing to investigate how probiotics affect gut microbiota dysbiosis and inflammation in GDM.. GDM and control metagenomic sequencing data were obtained from the SRA database. This metagenomic data helped us understand gut microbiota abundance and function. KEGG detected and extracted functional pathway genes. Transcriptome sequencing data evaluated GDM-related gene expression. Finally, GDM animal models were given probiotics orally to evaluate inflammatory response, regulatory immune cell fractions, and leptin protein levels.. GDM patients had more Fusobacteria and Firmicutes, while healthy people had more Bacteroidetes. Gut microbiota composition may affect GDM by altering the L-aspartate and L-asparagine super pathways. Mannan degradation and the super pathway of L-aspartate and L-asparagine synthesis enhanced in GDM mice with leptin protein overexpression. Oral probiotics prevent GDM by lowering leptin. Oral probiotics increased Treg, Tfr, and Breg cells, which decreased TNF-α and IL-6 and increased TGF-β and IL-10, preventing inflammation and preserving mouse pregnancy.. Dysbiosis of the gut microbiota may increase leptin expression and cause GDM. Oral probiotics enhance Treg, Tfr, and Breg cells, which limit the inflammatory response and assist mice in sustaining normal pregnancy. Thus, oral probiotics may prevent GDM, enabling targeted gut microbiota modulation and maternal and fetal health.

Topics: Animals; Asparagine; Aspartic Acid; B-Lymphocytes, Regulatory; Diabetes Mellitus, Type 2; Diabetes, Gestational; Dysbiosis; Female; Humans; Inflammation; Leptin; Mice; Pregnancy; T-Lymphocytes, Regulatory

Interactions between polymorphisms of the melatonin receptor 1B (MTNR1B) gene and lifestyle intervention for gestational diabetes have been described. Whether these are specific for physical activity or the healthy eating intervention is unknown.. The aim was to assess the interaction between MTNR1B rs10830962 and rs10830963 polymorphisms and lifestyle interventions during pregnancy.. Women with a BMI (in kg/m2) of ≥29 (n = 436) received counseling on healthy eating (HE), physical activity (PA), or both. The control group received usual care. This secondary analysis had a factorial design with comparison of HE compared with no HE and PA compared with no PA. Maternal outcomes at 24-28 wk were gestational weight gain (GWG), maternal fasting glucose, insulin, insulin resistance (HOMA-IR), disposition index, and development of GDM. Neonatal outcomes were cord blood leptin and C-peptide and estimated neonatal fat percentage. The interaction between receiving either the HE or PA intervention and genotypes of both rs10830962 and rs10830963 was assessed using multilevel regression analysis.. GDM risk was increased in women homozygous for the G allele of rs10830962 (OR: 2.60; 95% CI: 1.34, 5.06) or rs10830963 (OR: 2.83; 95% CI: 1.24, 6.47). Significant interactions between rs10830962 and interventions were found: in women homozygous for the G allele but not in the other genotypes, the PA intervention reduced maternal fasting insulin (β: -0.16; 95% CI: -0.33, 0.02; P = 0.08) and HOMA-IR (β: -0.17; 95% CI: -0.35, 0.01; P = 0.06), and reduced cord blood leptin (β: -0.84; 95% CI: -1.42, -0.25; P = 0.01) and C-peptide (β: -0.62; 95% CI: -1.07, -0.17; P = 0.01). In heterozygous women, the HE intervention had no effect, whereas in women homozygous for the C allele, HE intervention reduced GWG (β: -1.6 kg; 95% CI: -2.4, -0.8 kg). No interactions were found.. In women homozygous for the risk allele of MTNR1B rs10830962, GDM risk was increased and PA intervention might be more beneficial than HE intervention for reducing maternal insulin resistance, cord blood C-peptide, and cord blood leptin.

Topics: Adult; Alleles; Blood Glucose; C-Peptide; Diabetes, Gestational; Diet, Healthy; Exercise; Female; Fetal Blood; Genotype; Gestational Weight Gain; Humans; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Life Style; Polymorphism, Genetic; Pregnancy; Pregnancy Outcome; Prenatal Care; Receptor, Melatonin, MT2

Cord blood leptin and adiponectin are adipokines known to be associated with birth weight and overall infant adiposity. However, few studies have investigated their associations with abdominal adiposity in neonates. We examined maternal factors associated with cord blood leptin and adiponectin, and the association of these adipokines with neonatal adiposity and abdominal fat distribution measured by magnetic resonance imaging (MRI) in an Asian mother-offspring cohort.. Growing Up in Singapore Towards healthy Outcomes (GUSTO), is a prospective mother-offspring birth cohort study in Singapore. Cord blood plasma leptin and adiponectin concentrations were measured using Luminex and Enzyme-Linked Immunosorbent Assay respectively in 816 infants. A total of 271 neonates underwent MRI within the first 2-weeks after delivery. Abdominal superficial (sSAT), deep subcutaneous (dSAT), and intra-abdominal (IAT) adipose tissue compartment volumes were quantified from MRI images. Multivariable regression analyses were performed.. Indian or Malay ethnicity, female sex, and gestational age were positively associated with cord blood leptin and adiponectin concentrations. Maternal gestational diabetes (GDM) positively associated with cord blood leptin concentrations but inversely associated with cord blood adiponectin concentrations. Maternal pre-pregnancy body mass index (BMI) showed a positive relationship with cord blood leptin but not with adiponectin concentrations. Each SD increase in cord blood leptin was associated with higher neonatal sSAT, dSAT and IAT; differences in SD (95% CI): 0.258 (0.142, 0.374), 0.386 (0.254, 0.517) and 0.250 (0.118, 0.383), respectively. Similarly, each SD increase in cord blood adiponectin was associated with higher neonatal sSAT and dSAT; differences in SD (95% CI): 0.185 (0.096, 0.274) and 0.173 (0.067, 0.278), respectively. The association between cord blood adiponectin and neonatal adiposity was observed in neonates of obese mothers only.. Cord blood leptin and adiponectin concentrations were associated with ethnicity, maternal BMI and GDM, sex and gestational age. Both adipokines showed positive association with neonatal abdominal adiposity.

Topics: Abdominal Fat; Adipokines; Adiponectin; Cohort Studies; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Leptin; Obesity; Obesity, Abdominal; Pregnancy; Prospective Studies

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

Diabetes during pregnancy is associated with elevated maternal insulin, leptin and IL-6. Within the placenta, IL-6 can further stimulate leptin production. Despite structural similarities and shared roles in inflammation, leptin and IL-6 have contrasting effects on neurodevelopment, and the relative importance of maternal diabetes or chorioamnionitis on fetal hormone exposure has not been defined. We hypothesized that there would be a positive correlation between IL-6 and leptin with progressively increased levels in pregnancies complicated by maternal diabetes and chorioamnionitis. To test this hypothesis, cord blood samples were obtained from 104 term infants, including 47 exposed to maternal diabetes. Leptin, insulin, and IL-6 were quantified by multiplex assay. Factors independently associated with hormone levels were identified by univariate and multivariate linear regression. Unlike IL-6, leptin and insulin were significantly increased by maternal diabetes. Maternal BMI and birth weight were independent predictors of leptin and insulin with birth weight the strongest predictor of leptin. Clinically diagnosed chorioamnionitis and neonatal sepsis were associated with increased IL-6 but not leptin. Among appropriate for gestational age infants without sepsis, IL-6 and leptin were strongly correlated (R=0.6, P<0.001). In summary, maternal diabetes and birth weight are associated with leptin while chorioamnionitis is associated with IL-6. The constraint of the positive association between leptin and IL-6 to infants without sepsis suggests that the term infant and placenta may have a limited capacity to increase cord blood levels of the neuroprotective hormone leptin in the presence of increased cord blood levels of the potential neurotoxin IL-6.

Topics: Chorioamnionitis; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Interleukin-6; Leptin; Pregnancy

Gestational diabetes mellitus (GDM) is a significant pregnancy-related condition, which showed effect on the development of fetal. Anti-inflammatory and antioxidant therapy commonly used for the treatment of GDM. Nimbolide already confirmed their anti-inflammatory and anti-oxidant effect against various animal disease model. Our objective in this research is to investigate the protective effect of nimbolide against STZ induced GDM and elucidate the mechanism.. In this experimental study, pregnant female Wistar rats were used and STZ (40 mg/kg) was used to induce the GDM. Blood glucose level (BGL), body weight and plasma insulin were assessed at regular time (gestational day 0, 9, and 18). Water intake, food intake, fecal and urine output were also estimated. In the female rats, hemoglobin (Hb), glycalated hemoglobin (HbA1c), hepatic glycogen, fructosamine, adiponectin, leptin, lipid, antioxidant and inflammatory cytokines parameters were estimated. In the fetuses, the fetues weight, implementation loss, and fetal weight were estimated. At the completion of the protocol, biochemical parameters were calculated. Gut microbiota was estimated in end of the study.. Nimbolide treatment significantly (p < .001) improved the fetuses level and suppressed the fetal weight and implantation loss. Nimbolide treatment significantly (p < .001) suppressed the BGL and enhanced the body weight, insulin level. Nimbolide treatment suppressed the water intake, food intake, urinary and fecal output. Nimbolide significantly (p < .001) suppressed the fructosamine, leptin and enhanced the adiponectin level. Nimbolide treatment significantly (p < .001) decreased the malonaldehyde (MDA) level and boosted the total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and catalase (CAT); suppressed the level of TNF-α, IL-1β, IL-6, and boosted the level of IL-10. Furthermore, nimbolide treatment reversed the gut microbiota alteration induced via STZ in female rats. At the phylum level, the Firmicutes and Bacteroidetes relative abundance was altered via nimbolide treatment. The ratio of F/B boosted in GDM group and nimbolide treatment significantly (p < .001) suppressed. Nimbolide considerably suppressed the firmicutes and enhanced the Bacteroidetes, CAG-352, Lacnospirace.. Based on the findings, we may conclude that nimbolide protects the pregnant rats from GDM via alteration of inflammation, oxidative stress, and gut microbiota.

Topics: Adiponectin; Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Diabetes, Gestational; Female; Fetal Weight; Fructosamine; Gastrointestinal Microbiome; Humans; Inflammation; Insulins; Leptin; Limonins; Oxidative Stress; Pregnancy; Rats; Rats, Wistar; Streptozocin; Water

Leptin is an adipocytokine secreted by adipocytes which positively correlates with obesity. It is considered as a potential mediator for precipitating Gestational diabetes mellitus (GDM) which is more evident during 24-28 weeks of gestation. This study was conducted to see serum leptin level during 24-28 weeks of gestation in GDM at the Department of Endocrinology, BSMMU, Bangladesh from March 2019 to August 2020. Pregnant women (N=108) were challenged with 75gm oral glucose (OGTT) at 24-28 weeks of gestation and divided into GDM [n=45, age: 27.80±3.98 years, mean±SD; BMI: 27.88 (24.46-30.43) kg/m², median Interquartile range (IQR)] and normal glucose tolerance [NGT; n=62, age: 26.19±5.30 years, mean±SD; BMI: 25.80 (23.65-28.42) kg/m², median (IQR)] on basis of WHO-2013 diagnostic criteria. Fasting serum leptin and glucose were measured by ELISA and glucose oxidase method respectively. No statistically significant difference was found between GDM and NGT for leptin [26.05(16.92-50.55) vs. 23.50(14.95-38.30) median (IQR), p=0.360]. It was also not different statistically between GDM and NGT either for age groups (p=NS for all) or for Asian categories of BMI subgroups (p=NS for all). However, it was higher in subjects with BMI ≥23kg/m² than that with BMI ≤23kg/m² for both GDM [16.65 (6.39, 35.75) vs. 28.35 (19.60, 51.10) median (IQR), p=0.114] and NGT [14.65(9.19, 19.60) vs. 26.00 (17.30, 43.40) median (IQR), p=0.002]. It was also statistically similar in the GDM subgroups divided by Asian BMI cut-off (p=NS). BMI correlated with leptin in NGT (r=0.495, p<0.001) but not in GDM (r=0.177, p=0.251) and regression analysis revealed BMI (kg/m²) as predictor for high leptin (p=0.008). ROC curve analysis for leptin showed AUC for GDM was 0.553 (p=0.360) suggesting it as a poor predictor. It is concluded that fasting leptin in 24-28 weeks of gestation better relates with BMI but does not differ between GDM and NGT anddoes not seem to be a good predictor for GDM. Further study is required to make a comment on its prediction over GDM.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Female; Glucose; Glucose Tolerance Test; Humans; Leptin; Obesity; Pregnancy; Young Adult

Recently, we proposed two pathophysiologic subtypes of type 2 diabetes mellitus (T2DM), one related and one unrelated to metabolic syndrome. To begin to understand the pathophysiology of the subtype unrelated to metabolic syndrome, we now measured selected hormones and signaling molecules in affected individuals. In this cross-sectional analysis, we examined 138 women out of the monocenter, post gestational diabetes study PPSDiab. Of these women, 73 had prediabetes or screening-diagnosed T2DM, 40 related to metabolic syndrome and 33 unrelated. The remaining 65 women were normoglycemic controls. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, and cardiopulmonary exercise testing. In addition, plasma proinsulin/insulin ratio, growth hormone (hGH) nadir during oral glucose tolerance testing, Insulin-like Growth Factor I (IGF-I), Leptin, Resistin, Adiponectin, Fetuin-a, FGF21, and myostatin were measured. Compared to controls, women with prediabetes or screening-diagnosed T2DM unrelated to metabolic syndrome depicted higher plasma Leptin [10.47(6.6-14.57) vs. 5.52(3.15-10.02); p<0.0001] and IGF-I [193.01(171.00-213.30) vs. 167.97(138.77-200.64); p=0.0008], as well as a lower hGH nadir [0.07(0.05-0.15) vs. 0.14(0.08-0.22; p<0.0001]. These differences were independent of body adiposity. Women with prediabetes or T2DM related to metabolic syndrome, in comparison to controls, displayed elevated Leptin, Fetuin-a, and FGF21, as well as reduced Adiponectin and hGH nadir. Based on our study, altered Leptin and hGH/IGF-I signaling could potentially contribute to the pathophysiology of prediabetes and T2DM unrelated to metabolic syndrome. Further mechanistic investigations of these signaling pathways in the context of lean T2DM are necessary to test causal relationships.

Topics: Adiponectin; alpha-2-HS-Glycoprotein; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Insulin-Like Growth Factor I; Leptin; Metabolic Syndrome; Prediabetic State; Pregnancy

Topics: Adipokines; Adiposity; Bone Density; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant; Infant, Newborn; Leptin; Obesity; Pregnancy; Prospective Studies; Vascular Endothelial Growth Factor A

Gestational diabetes mellitus (GDM) "program" an elevated risk of metabolic syndrome in the offspring. Epigenetic alterations are a suspected mechanism. GDM has been associated with placental DNA methylation changes in some epigenome-wide association studies. It remains unclear which genes or pathways are affected, and whether any placental differential gene methylations are correlated to fetal growth or circulating metabolic health biomarkers. In an epigenome-wide association study using the Infinium MethylationEPIC Beadchip, we sought to identify genome-wide placental differentially methylated genes and enriched pathways in GDM, and to assess the correlations with fetal growth and metabolic health biomarkers in cord blood. The study samples were 30 pairs of term placentas in GDM vs. euglycemic pregnancies (controls) matched by infant sex and gestational age at delivery in the Shanghai Birth Cohort. Cord blood metabolic health biomarkers included insulin, C-peptide, proinsulin, IGF-I, IGF-II, leptin and adiponectin. Adjusting for maternal age, pre-pregnancy BMI, parity, mode of delivery and placental cell type heterogeneity, 256 differentially methylated positions (DMPs,130 hypermethylated and 126 hypomethylated) were detected between GDM and control groups accounting for multiple tests with false discovery rate <0.05 and beta-value difference >0.05. WSCD2 was identified as a differentially methylated gene in both site- and region-level analyses. We validated 7 hypermethylated (CYP1A2, GFRA1, HDAC4, LIMS2, NAV3, PAX6, UPK1B) and 10 hypomethylated (DPP10, CPLX1, CSMD2, GPR133, NRXN1, PCSK9, PENK, PRDM16, PTPRN2, TNXB) genes reported in previous epigenome-wide association studies. We did not find any enriched pathway accounting for multiple tests. DMPs in 11 genes (CYP2D7P1, PCDHB15, ERG, SIRPB1, DKK2, RAPGEF5, CACNA2D4, PCSK9, TSNARE1, CADM2, KCNAB2) were correlated with birth weight (z score) accounting for multiple tests. There were no significant correlations between placental gene methylations and cord blood biomarkers. In conclusions, GDM was associated with DNA methylation changes in a number of placental genes, but these placental gene methylations were uncorrelated to the observed metabolic health biomarkers (fetal growth factors, leptin and adiponectin) in cord blood. We validated 17 differentially methylated placental genes in GDM, and identified 11 differentially methylated genes relevant to fetal growth.

Topics: Adiponectin; Biomarkers; China; Diabetes, Gestational; DNA Methylation; Female; Fetal Blood; Fetal Development; Humans; Infant; Leptin; Parity; Placenta; Pregnancy; Proprotein Convertase 9

To explore the differences of serum fibroblast growth factor-21 (FGF-21) levels in pregnant women with normal glucose tolerance and gestational diabetes mellitus (GDM), and to analyze the relationship between FGF-21 and glucose and lipid metabolic indicators, leptin, retinol binding protein 4 (RBP-4) and adiponectin in GDM, in order to provide basis for the prevention and treatment of GDM.. Total of 120 women were included, and divided into normal glucose tolerance group (58 cases) and GDM group (62 cases) according to the 75 g oral glucose tolerance test results. General information were recorded; height, weight and blood pressure, blood glucose, lipids, insulin, FGF-21, leptin, RMP-4, and adiponectin were measured, and body mass index (BMI), homeostasis model assessment-IR, homeostasis model assessment-β and area under glucose curve were calculated. The t-test, Pearson analysis and multiple linear regression analysis were used to evaluate the differences and related factors of FGF-21 in GDM.. The pre-pregnancy BMI, pregnancy BMI, weight gain during pregnancy and FGF-21 levels were higher in GDM group, whereas there were no statistically significant differences in leptin, RBP-4 and adiponectin. Correlation analysis suggested that FGF-21 level was correlated with age, pre-pregnancy BMI, weight gain during pregnancy, high-density lipoprotein cholesterol, leptin, RBP-4 and adiponectin, and the results of multiple linear regression showed that serum FGF-21 was related to pre-pregnancy BMI, weight gain during pregnancy, leptin, RBP-4 and adiponectin in GDM.. There were higher serum FGF-21 levels in GDM, which might be related to pre-pregnancy BMI, weight gain during pregnancy, leptin, RBP-4 and adiponectin.

Topics: Adipokines; Adiponectin; Blood Glucose; Body Mass Index; Diabetes, Gestational; Female; Fibroblast Growth Factors; Humans; Leptin; Pregnancy; Weight Gain

Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine, which, in animal studies, improves insulin sensitivity and increases energy expenditure to counteract insulin resistance.. Evaluate in a human population, the role of serum ANGPTL6 in gestational diabetes mellitus (GDM) or its presence in fetal circulation.. A total of 190 women (115 controls and 75 GDM) and their offspring were studied. Insulin, glucose, ANGPTL6, retinol binding protein 4 (RBP4), and retinol, as well as leptin and adiponectin, were determined in maternal serum obtained at term and from umbilical artery blood at delivery.. At term, pregnant women with GDM showed higher serum concentrations of ANGPTL6, insulin, homeostatic model assessment, and apo-RBP4 (free RBP4) than controls but not of glucose, which remained similar in both groups. Also, in arterial cord serum, ANGPTL6 concentration was increased in GDM neonates with respect to the control group (201 ± 12 ng/mL vs 119 ± 8 ng/mL, respectively). No effect of maternal insulin treatment of some GDM mothers in neonates of either sex on ANGPTL6 levels was observed. In GDM, circulating ANGPTL6 showed no correlation with glucose or insulin concentration or with neonatal adiposity. However, in control pregnancies, the variation in glucose concentration was positively correlated with ANGPTL6 concentration, both in maternal and in cord samples, and cord ANGPTL6 was negatively correlated with neonatal fat mass. Furthermore, in control pregnant women, serum concentrations of ANGPTL6 and apo-RBP4 were negatively correlated.. Serum ANGPTL6 levels are associated with maternal glucose homeostasis and fetal adiposity in normal pregnancy. ANGPTL6 levels in maternal and cord serum GDM pregnancy at term are increased, although its mechanism and physiological role are unknown yet.

Topics: Adiponectin; Angiopoietin-Like Protein 6; Angiopoietin-like Proteins; Animals; Blood Glucose; Diabetes, Gestational; Female; Glucose; Homeostasis; Humans; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Pregnancy; Retinol-Binding Proteins, Plasma; Vitamin A

To examine the associations of serum concentrations of adiponectin and leptin and leptin/adiponectin ratio (LAR) in early pregnancy with risk of gestational diabetes mellitus (GDM) in Chinese women. The predictive ability of those biomarkers for GDM was also assessed.. Within the Tongji-Shuangliu Birth Cohort, a nested case-control study was established with 332 GDM cases and 664 matched controls at 1:2 ratio on age (±3 years) and gestational age (±4 weeks). Serum adiponectin and leptin levels were measured in early pregnancy (median gestational week, 11; range, 6-15). Conditional logistic regression models with adjustment for potential covariates were used to evaluate the associations.. Multivariable-adjusted odds ratios (ORs) comparing extreme quartiles of adiponectin, leptin and LAR were 0.55 (95 % CI, 0.35, 0.85), 1.96 (95 % CI, 1.19, 3.24), and 2.72 (95 % CI, 1.63, 4.54) for GDM, respectively (All P-trend < 0.02). Adding adiponectin and leptin to a conventional prediction model (including traditional risk factors and fasting glucose) increased the C-statistics from 0.708 (95 % CI, 0.674, 0.741) to 0.728 (95 % CI, 0.695, 0.760), and achieved a net reclassification improvement of 0.292.. Our findings indicate that adiponectin is inversely associated with GDM, while leptin and LAR are positively associated with GDM in Chinese pregnant women.

Topics: Adiponectin; Biomarkers; Case-Control Studies; China; Diabetes, Gestational; Female; Glucose; Humans; Infant, Newborn; Leptin; Pregnancy; Prospective Studies

The San Carlos Gestational Diabetes Mellitus (GDM) prevention study, a nutritional intervention RCT based on a Mediterranean Diet (MedDiet), has been shown to reduce the incidence of GDM. The objective of this study is to investigate the relationship of leptin, adiponectin, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), insulin and HOMA-IRand circulating miRNAs (miR-29a-3p, miR-103a-3p, miR-132-3p, miR-222-3p) with the appearance of GDM and with MedDiet-based nutritional intervention, at 24−28 gestational weeks (GW), and in glucose regulation 2−3 years post-delivery (PD). A total of 313 pregnant women, 77 with GDM vs. 236 with normal glucose tolerance (NGT), 141 from the control group (CG, MedDiet restricting the consumption of dietary fat including EVOO and nuts during pregnancy) vs. 172 from the intervention group (IG, MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios during pregnancy) were compared at Visit 1 (8−12 GW), Visit 2 (24−28 GW) and Visit 3 (2−3 years PD). Expression of miRNAs was determined by the Exiqon miRCURY LNA RT-PCR system. Leptin, adiponectin, IL-6 and TNF-α, were measured by Milliplex® immunoassays on Luminex 200 and insulin by RIA. Women with GDM vs. NTG had significantly higher leptin median (Q1−Q3) levels (14.6 (9.2−19.4) vs. 9.6 (6.0−15.1) ng/mL; p < 0.05) and insulin levels (11.4 (8.6−16.5) vs. 9.4 (7.0−12.8) µUI/mL; p < 0.001) and lower adiponectin (12.9 (9.8−17.2) vs. 17.0 (13.3−22.4) µg/mL; p < 0.001) at Visit 2. These findings persisted in Visit 3, with overexpression of miR-222-3p (1.45 (0.76−2.21) vs. 0.99 (0.21−1.70); p < 0.05)) and higher levels of Il-6 and TNF-α. When the IG is compared with the CG lower levels of insulin, HOMA-IR-IR, IL-6 levels at Visit 2 and 3 and leptin levels only at Visit 2 were observed. An overexpression of miR-222-3p and miR-103a-3p were also observed in IG at Visit 2 and 3. The miR-222-3p and miR103a-3p expression correlated with insulin levels, HOMA-IR, IL-6 and TNF-α at Visit 2 (all p < 0.05). These data support the association of leptin, adiponectin and insulin/HOMA-IR with GDM, as well as the association of insulin/HOMA-IR and IL-6 and miR-222-3p and miR-103a-3p expression with a MedDiet-based nutritional intervention.

Topics: Adipokines; Adiponectin; Diabetes, Gestational; Diet, Mediterranean; Female; Glucose; Humans; Insulin; Interleukin-6; Leptin; MicroRNAs; Olive Oil; Pregnancy; Tumor Necrosis Factor-alpha

Fetal overgrowth "programs" an elevated risk of type 2 diabetes in adulthood. Epigenetic alterations may be a mechanism in programming the vulnerability. We sought to characterize genome-wide alterations in placental gene methylations in fetal overgrowth and the associations with metabolic health biomarkers including leptin, adiponectin and fetal growth factors.. Comparing genome-wide placental gene DNA methylations in large-for-gestational-age (LGA, an indicator of fetal overgrowth, n = 30) versus optimal-for-gestational-age (OGA, control, n = 30) infants using the Illumina Infinium Human Methylation-EPIC BeadChip, we identified 543 differential methylation positions (DMPs; 397 hypermethylated, 146 hypomethylated) at false discovery rate < 5% and absolute methylation difference > 0.05 after adjusting for placental cell-type heterogeneity, maternal age, pre-pregnancy BMI and HbA1c levels during pregnancy. Twenty-five DMPs annotated to 20 genes (QSOX1, FCHSD2, LOC101928162, ADGRB3, GCNT1, TAP1, MYO16, NAV1, ATP8A2, LBXCOR1, EN2, INCA1, CAMTA2, SORCS2, SLC4A4, RPA3, UMAD1,USP53, OR2L13 and NR3C2) could explain 80% of the birth weight variations. Pathway analyses did not detect any statistically significant pathways after correcting for multiple tests. We validated a newly discovered differentially (hyper-)methylated gene-visual system homeobox 1 (VSX1) in an independent pyrosequencing study sample (LGA 47, OGA 47). Our data confirmed a hypermethylated gene-cadherin 13 (CDH13) reported in a previous epigenome-wide association study. Adiponectin in cord blood was correlated with its gene methylation in the placenta, while leptin and fetal growth factors (insulin, IGF-1, IGF-2) were not.. Fetal overgrowth may be associated with a large number of altered placental gene methylations. Placental VSX1 and CDH13 genes are hypermethylated in fetal overgrowth. Placental ADIPOQ gene methylations and fetal circulating adiponectin levels were correlated, suggesting the contribution of placenta-originated adiponectin to cord blood adiponectin.

Topics: Adiponectin; Adult; Carrier Proteins; Diabetes Mellitus, Type 2; Diabetes, Gestational; DNA Methylation; Female; Fetal Blood; Fetal Development; Fetal Macrosomia; Gestational Age; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Membrane Proteins; Placenta; Pregnancy

To evaluate a level of expression of endoglin (Eng), leptin (Lep), placental growth factor (PlGF), and hypoxia-inducible factor-1alpha (HIF-1α) in placenta among women with pre-eclampsia and diabetes mellitus (DM), considering the method of glycemia correction and preconception care.. A retrospective cohort study was conducted. A total of 124 women were divided into following groups: type 1 DM (. The highest level of placental expression of Eng was observed in the PE group (20.34%). The same trend was also typical for T1DM (not planned) and insulin-treated groups: T2DM and GDM. An amount of cell with an PlGF expression was significantly higher in the control group (12.2%), while the lowest was observed in the pre-eclampsia group (1.18%) and T1DM (not planned) (1.26%). The placental leptin expression within each DM group was increased among the patients with unplanned pregnancy and those who received insulin therapy. We observed the lowest Lep expression in the PE group (6.3%). High level of HIF-1α expression was detected in T1DM (not planned) (30.44%) and PE (29.64%) as compared to the control group (11.62%). In T2DM and GDM insulin groups, the HIF-1α expression was significantly higher as compared to diet groups.. The obtained data show that DM and pre-eclampsia are associated with changes in angiogenic and metabolic placental factor expressions. The degree of changes depends on preconception care and the control of glycemia level during pregnancy.

Topics: Adult; Diabetes, Gestational; Endoglin; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Leptin; Placenta; Placenta Growth Factor; Pre-Eclampsia; Pregnancy; Retrospective Studies

To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m. Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study.. Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only.. Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity.

Topics: Adiposity; Adolescent; Adult; Belgium; Birth Weight; C-Peptide; Cohort Studies; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Fetus; Humans; Infant, Newborn; Leptin; Lipids; Male; Middle Aged; Pregnancy; Pregnancy Outcome; Prognosis; Prospective Studies; Sex Characteristics; Skinfold Thickness; Young Adult

We aimed to examine prospective associations between circulating fatty acids in early pregnancy and incident gestational diabetes mellitus (GDM) among Chinese pregnant women.. Analyses were based on two prospective nested case-control studies conducted in western China (336 GDM cases and 672 matched controls) and central China (305 cases and 305 matched controls). Fasting plasma fatty acids in early pregnancy (gestational age at enrollment: 10.4 weeks(s.d., 2.0)) and 13.2 weeks (1.0), respectively) were determined by gas chromatography-mass spectrometry, and GDM was diagnosed based on the International Association of Diabetes in Pregnancy Study Groups criteria during 24-28 weeks of gestation. Multiple metabolic biomarkers (HOMA-IR (homeostatic model assessment for insulin resistance), HbA1c, c-peptide, high-sensitivity C-reactive protein, adiponectin, leptin, and blood lipids) were additionally measured among 672 non-GDM controls at enrollment.. Higher levels of saturated fatty acids (SFAs) 14:0 (pooled odds ratio, 1.41 for each 1-s.d. increase; 95% CI: 1.25, 1.59) and 16:0 (1.19; 1.05, 1.35) were associated with higher odds of GDM. Higher levels of n-6 polyunsaturated fatty acid (PUFA) 18:2n-6 were strongly associated with lower odds of GDM (0.69; 0.60, 0.80). In non-GDM pregnant women, higher SFAs 14:0 and 16:0 but lower n-6 PUFA 18:2n-6 were generally correlated with unfavorable metabolic profiles.. We documented adverse associations of 14:0 and 16:0 but a protective association of 18:2n-6 with GDM among Chinese pregnant women. Our findings highlight the distinct roles of specific fatty acids in the onset of GDM.

Topics: Adiponectin; Adult; Blood Glucose; C-Peptide; C-Reactive Protein; Case-Control Studies; China; Diabetes, Gestational; Fasting; Fatty Acids; Fatty Acids, Monounsaturated; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Female; Glycated Hemoglobin; Humans; Insulin Resistance; Leptin; Pregnancy; Prospective Studies; Risk Factors; Young Adult

This study aimed to: (1) identify metabolite patterns during late childhood that differ with respect to exposure to maternal gestational diabetes mellitus (GDM); (2) examine the persistence of GDM/metabolite associations 5 years later, during adolescence; and (3) investigate the associations of metabolite patterns with adiposity and metabolic biomarkers from childhood through adolescence.. This study included 592 mother-child pairs with information on GDM exposure (n = 92 exposed), untargeted metabolomics data at age 6-14 years (T1) and at 12-19 years (T2), and information on adiposity and metabolic risk biomarkers at T1 and T2. We first consolidated 767 metabolites at T1 into factors (metabolite patterns) via principal component analysis (PCA) and used multivariable regression to identify factors that differed by GDM exposure, at α = 0.05. We then examined associations of GDM with individual metabolites within factors of interest at T1 and T2, and investigated associations of GDM-related factors at T1 with adiposity and metabolic risk throughout T1 and T2 using mixed-effects linear regression models.. Of the six factors retained from PCA, GDM exposure was associated with greater odds of being in quartile (Q)4 (vs Q1-3) of 'Factor 4' at T1 after accounting for age, sex, race/ethnicity, maternal smoking habits during pregnancy, Tanner stage, physical activity and total energy intake, at α = 0.05 (OR 1.78 [95% CI 1.04, 3.04]; p = 0.04). This metabolite pattern comprised phosphatidylcholines, diacylglycerols and phosphatidylethanolamines. GDM was consistently associated with elevations in a subset of individual compounds within this pattern at T1 and T2. While this metabolite pattern was not related to the health outcomes in boys, it corresponded with greater adiposity and a worse metabolic profile among girls throughout the follow-up period. Each 1-unit increment in Factor 4 corresponded with 0.17 (0.08, 0.25) units higher BMI z score, 8.83 (5.07, 12.59) pmol/l higher fasting insulin, 0.28 (0.13, 0.43) units higher HOMA-IR, and 4.73 (2.15, 7.31) nmol/l higher leptin.. Exposure to maternal GDM was nominally associated with a metabolite pattern characterised by elevated serum phospholipids in late childhood and adolescence at α = 0.05. This metabolite pattern was associated with greater adiposity and metabolic risk among female offspring throughout the late childhood-to-adolescence transition. Future studies are warranted to confirm our findings.

Topics: Adiposity; Adolescent; Adult; Biomarkers; Child; Diabetes, Gestational; Female; Humans; Leptin; Linear Models; Phospholipids; Pregnancy; Prenatal Exposure Delayed Effects; Principal Component Analysis; Prospective Studies; Young Adult

This study aimed to determine, in women with gestational diabetes (GDM), the changes in insulin sensitivity (Matsuda Insulin Sensitivity Index; IS. IS. A total of 27 women completed all assessments. Compared with T1, IS. In women with GDM, delivery was associated with improvement in both insulin sensitivity and insulin production within the first few days. Improvement in insulin production persisted for 6-12 weeks, but insulin sensitivity deteriorated slightly. These changes in glucose metabolism were not associated to changes in lipids, leptin, inflammation markers or body weight.. ClinicalTrials.gov NCT02082301.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; C-Reactive Protein; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Postpartum Period; Pregnancy; Young Adult

While human milk composition is characterised by marked dynamicity, we are far from having a clear picture of what factors drive this variation. Hormones in human milk are known to vary according to specific maternal phenotypes, but limited evidence shows the infant also has a role in determining milk composition. The present study aimed to investigate the interplay between maternal and infant characteristics in relation to human milk hormonal profile. In total, 501 human milk samples from mothers recruited in the Finnish STEPS cohort study (Steps to the healthy development) were analysed. Pre-pregnancy and pregnancy maternal data, socioeconomic status and infant characteristics at birth were collated. Leptin, adiponectin, insulin-like growth factor-1 and cyclic Glycine-Proline in milk were measured. Multivariate analysis of variance (MANOVA) and linear regression were utilised for statistical analysis. Sex-specific interactions with maternal factors were observed, as the infant sex mediated associations between gestational diabetes and milk adiponectin (

Topics: Adiponectin; Adult; Body Mass Index; Body Weight; Breast Feeding; Cesarean Section; Diabetes, Gestational; Female; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Lactation; Leptin; Male; Milk, Human; Mothers; Obesity; Peptides, Cyclic; Pregnancy; Proteins; Sex Factors; Socioeconomic Factors

Changes in fetal DNA methylation (DNAm) of the leptin (

Topics: Adiposity; Adult; Child, Preschool; Diabetes, Gestational; DNA Methylation; Epigenesis, Genetic; Female; Fetal Blood; Genetic Loci; Humans; Hyperglycemia; Infant, Newborn; Leptin; Male; Obesity; Placenta; Pregnancy; Young Adult

To evaluate the difference in maternal circulating leptin profile between pregnant women with and without gestational diabetes mellitus (GDM).. This is a nested case-control study embedded in the Born in Guangzhou Cohort Study in Guangzhou Women and Children's Medical Center, with 198 GDM cases and 192 controls included. Maternal plasma leptin profile was defined as leptin concentrations measured at early (baseline) and late pregnancy, as well as a ratio of concentration at late to that at early pregnancy (RL1L0). General linear regression was used to assess the associations between GDM and log-transformed leptin measurements.. Women with GDM had a higher baseline leptin concentration and lower RL1L0 compared to those without GDM. The log leptin concentration at baseline (β: 0.19, 95%CI: 0.04, 0.34) and the log RL1L0 (β: -0.22, 95%CI: -0.41, -0.03) were associated with GDM status. The RL1L0 decreased significantly along with the increase of 1-hour glucose and the difference between 1-hour and fasting glucose levels in both GDM and non-GDM women.. Women with GDM had a certain profile of circulating leptin, with higher baseline concentration but less increase during pregnancy, suggesting an impaired compensatory response to increasing insulin resistance along with the progress of pregnancy.

Topics: Adolescent; Adult; Case-Control Studies; Diabetes, Gestational; Female; Humans; Leptin; Middle Aged; Pregnancy; Young Adult

Oral glucose tolerance testing (OGTT) is the recommended approach for the diagnosis of gestational diabetes mellitus (GDM). Leptin and chemerin are two examples of hormones from adipokine family, which mostly takes part in glucose metabolism and inflammatory processes. We aim to find a possible new and tolerable screening technique for GDM using salivary levels of leptin and chemerin.. Saliva samples of pregnant patients, on their 24-28th weeks of gestation, are collected. ELISA study for leptin showed an insignificant difference between patients with GDM and patients without where the values were 0.44 ± 0.33 and 0.34 ± 0.24 respectively (. Leptin and chemerin can be detected in saliva. Chemerin levels are significantly higher in patients with GDM, thus this knowledge can be used to develop a new screening method for OGTT.

Topics: Adult; Case-Control Studies; Chemokines; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Leptin; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Prospective Studies; Saliva

Several adipokines are implicated in the pathophysiology of gestational diabetes mellitus (GDM), however, longitudinal data in early pregnancy on many adipokines are lacking. We prospectively investigated the association of a panel of adipokines in early and mid-pregnancy with GDM risk.. Within the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons cohort (n=2802), a panel of 10 adipokines (plasma fatty acid binding protein-4 (FABP4), chemerin, interleukin-6 (IL-6), leptin, soluble leptin receptor (sOB-R), adiponectin, omentin-1, vaspin, and retinol binding protein-4) were measured at gestational weeks (GWs) 10-14, 15-26, 23-31, and 33-39 among 107 GDM cases (ascertained on average at GW 27) and 214 non-GDM controls. Conditional logistic regression was used to estimate ORs of each adipokine and GDM, controlling for known GDM risk factors including pre-pregnancy body mass index.. Throughout pregnancy changes in chemerin, sOB-R, adiponectin, and high-molecular-weight adiponectin (HMW-adiponectin) concentrations from 10-14 to 15-26 GWs were significantly different among GDM cases compared with non-GDM controls. In early and mid-pregnancy, FABP4, chemerin, IL-6 and leptin were positively associated with increased GDM risk. For instance, at 10-14 GWs, the OR comparing the highest versus lowest quartile (ORQ4-Q1) of FABP4 was 3.79 (95% CI 1.63 to 8.85). In contrast, in both early and mid-pregnancy adiponectin (eg, ORQ4-Q1 0.14 (0.05, 0.34) during 10-14 GWs) and sOB-R (ORQ4-Q1 0.23 (0.11, 0.50) during 10-14 GWs) were inversely related to GDM risk. At 10-14 GWs a model that included conventional GDM risk factors and FABP4, chemerin, sOB-R, and HMW-adiponectin improved the estimated prediction (area under the curve) from 0.71 (95% CI 0.66 to 0.77) to 0.77 (95% CI 0.72 to 0.82).. A panel of understudied adipokines including FABP4, chemerin, and sOB-R may be implicated in the pathogenesis of GDM with significant associations detected approximately 10-18 weeks before typical GDM screening.

Topics: Adipokines; Adiponectin; Chemokines; Child; Diabetes, Gestational; Female; Humans; Leptin; Longitudinal Studies; Pregnancy

Evaluation of serum concentration of leptin, adiponectin, resistin, and MCP-1 in pregnant patients with different types of diabetes mellitus (DM) considering preconception planning and method of DM correction in 11-14th and 30-34th weeks of pregnancy.. Longitudinal, prospective study included 130 pregnant women divided into the following comparison groups: type 1 DM (T1DM, n = 40), type 2 DM (T2DM, n = 35), GDM (n = 40), and the control group (n = 15). The ELISA method defined the levels of leptin, resistin, adiponectin, and MCP-1 concentration in serum, which was assessed in 11-14th and 30-34th weeks of pregnancy. Statistical analysis was accomplished using SPSS 23.0 and "Prism 8-GraphPad" software.. The leptin level in the 1st trimester was the highest in T2DM insulin group compared to the control due to gestational age, hence in the 3rd trimester in all groups its serum concentrations appeared higher than in healthy patients (p = 0.0001). In the 1st trimester leptin levels directly correlated with women's BMI, newborns' weight and macrosomia rate, in the 3rd trimester - with OGTT levels, HbA1c, gestational hypertension, and preeclampsia rates. Resistin levels in the 1st and 3rd trimesters were increased in almost all DM groups compared to the control group (p = 0.0001). The study established direct positive correlation between resistin and HbA1c, birth weight, and preeclampsia. In the 1st trimester, adiponectin demonstrated the lowest levels in T2DM insulin compared to T1DM and the control group (p = 0.0001) while in the 3rd trimester, adiponectin levels declined alongside gestational age in DM patients and all the groups compared to the control group (p < 0.05). Adiponectin negatively correlated with BMI, OGTT levels, and preeclampsia rate. MCP-1 levels in T2DM appeared higher than in T1DM patients and the control group in the 1st trimester, whereas in the 3rd trimester MCP-1 declined, correlating with BMI, preeclampsia and OGTT levels.. High rate of adverse perinatal outcomes in diabetic pregnancy might be developed due to more severe metabolic failures and further disturbances of adipokines expression.

Topics: Adipokines; Adiponectin; Chemokine CCL2; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Infant, Newborn; Leptin; Pregnancy; Prospective Studies; Resistin

The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM).. In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70-90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC).. First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02-0.68). The AUC of this model was 0.699 (95%CI 0.605-0.793).. In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study.

Topics: Adipokines; Adiponectin; Adult; Area Under Curve; Biomarkers; Blood Glucose; Body Mass Index; Case-Control Studies; Chemokines; Diabetes, Gestational; Female; Humans; Leptin; Maternal Age; Netherlands; Odds Ratio; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Proto-Oncogene Proteins; ROC Curve

Fetal exposure to gestational diabetes mellitus (GDM) increases the risk of metabolic diseases in the offspring. Leptin, adiponectin, and fibroblast growth factor 21 (FGF21) may play potential roles in the underlying disease mechanisms. We investigated the impact of fetal exposure to GDM on leptin, adiponectin, and FGF21 concentrations and their associations with measures of adiposity and metabolic traits during childhood/adolescence.. The follow-up study included 504 GDM and 540 control offspring aged 9-16 from the Danish National Birth Cohort. Anthropometric measurements, fasting blood samples, puberty status and fat percentages by dual-energy X-ray absorptiometry were examined. Serum concentrations of leptin, adiponectin, and FGF21 were measured by validated immune assays.. GDM offspring had 38% (95% CI: 22-55%) higher leptin, 0.6 mg/L (95% CI: -1.2, -0.04 mg/L) lower adiponectin, and 32% (95% CI: -47%, -12%) lower FGF21 concentrations than control offspring (P < 0.05). After adjustment for confounders including maternal pre-pregnancy BMI, GDM offspring had borderline higher leptin (P = 0.06) and significantly lower FGF21 concentrations (P = 0.006). When accounting for offspring BMI z-score, GDM exposure had no significant independent effect on leptin or adiponectin concentrations, whereas FGF21 was still significant. In univariate analyses, leptin and adiponectin were associated with fasting insulin, HOMA-IR, and adiposity, and FGF21 with total fat percentage.. GDM offspring had higher leptin, lower adiponectin and FGF21 concentrations than control offspring. Elevated leptin and decreased adiponectin concentrations associated with adverse metabolic traits and were most likely driven by higher obesity prevalence among GDM offspring. The functional implications of decreased FGF21 concentrations among GDM offspring need to be further explored.

Topics: Adiponectin; Adolescent; Birth Weight; Body Mass Index; Breast Feeding; Child; Diabetes, Gestational; Female; Fibroblast Growth Factors; Humans; Immunoassay; Leptin; Maternal Inheritance; Pregnancy

Lipids and adipokines including leptin, resistin and visfatin play various roles in the pathophysiology of Gestational Diabetes Mellitus (GDM). This study was aimed at determining whether serum leptin, resistin and visfatin are significantly altered during the first trimester of pregnancies that subsequently develop GDM and whether such changes are useful in predicting the disease.. This was a case-case control study which compared first trimester biochemical and anthropometric parameters in 70 pregnant women who subsequently developed GDM and 70 pregnant women without GDM at the Volta Regional Hospital, Ho, Ghana. Lipid profile and some selected adipokines were analyzed and first trimester body mass index (BMI) was determined.. There were significant differences (p < 0.05) in leptin, resistin, and visfatin as well as significant dyslipidemia among those with GDM compared to those without GDM. Furthermore, the area under the Receiver Operating Characteristic Curves (AUCs) for leptin, resistin and visfatin were; 0.812, 0.836 and 0.799 respectively. Increased first trimester leptin (OR = 1.166; CI = 1.104-1.233; p < 0.0001), resistin (p < 0.0001) and visfatin (p < 0.0001) were associated with GDM.. Hyperleptinemia, hyperesistinemia and hypervisfatinemia precede GDM and can serve as good predictive indices for gestational diabetes mellitus.

Topics: Adult; Body Mass Index; Case-Control Studies; Diabetes, Gestational; Female; Humans; Leptin; Lipids; Nicotinamide Phosphoribosyltransferase; Pregnancy; Pregnancy Trimester, First; Resistin

Maternal, cord blood and childhood adipokines have been associated with childhood obesity. We investigated whether postpartum maternal adipokines are associated with increased weight at 1 year of age in children of women with gestational diabetes (GDM).. Plasma leptin and adiponectin concentrations were measured in 160 women at approximately 12 weeks following pregnancy with GDM and compared with infant weight for length z-score at 1 year of age after adjustment for maternal and infant demographic variables.. No association was demonstrated between maternal postpartum leptin and adiponectin concentrations and infant weight for length z-score at 1 year of age.

Topics: Adiponectin; Adult; Birth Weight; Body Weight; Diabetes, Gestational; Female; Humans; Infant; Infant, Newborn; Leptin; Pediatric Obesity; Postpartum Period; Pregnancy

The study of adipokines in overweight women with early-onset (diagnosed before 20 weeks) gestational diabetes mellitus (GDM) could help to understand the ethiopathological mechanisms of this disorder. Our aim was to assess adipokine levels in overweight pregnant women with early-onset GDM compared to patients with standard-onset (diagnosed at 24-28 weeks) GDM and to glucose-tolerant women at the same gestational ages.. This nested case-control study included 133 overweight pregnant women: 33 with early-onset (diagnosed < 20 weeks) GDM; 40 with standard-onset (diagnosed ≥ 24 weeks) GDM and 60 glucose-tolerant (normal oral glucose tolerance tests < 20 and ≥ 24 weeks). Adiponectin, leptin, resistin, visfatin and ghrelin serum levels were measured by ELISA.. Adiponectin serum levels were significantly lower in early-onset GDM women than in standard-onset GDM patients or controls matched for gestational age. Leptin serum levels were significantly higher in women with early-onset GDM than in controls. Women with early-onset GDM had lower adiponectin/leptin ratio than those with standard-onset GDM. There were no significant differences in resistin, ghrelin and visfatin serum levels among the participants.. Our results suggest that, compared to overweight glucose-tolerant women and patients with standard-onset GDM, overweight women with early-onset GDM have unbalanced adipokine levels, suggesting that they have a more inflammatory profile.

Topics: Adiponectin; Adult; Case-Control Studies; Diabetes, Gestational; Female; Ghrelin; Humans; Leptin; Nicotinamide Phosphoribosyltransferase; Overweight; Pregnancy; Resistin

This study aimed to evaluate the longitudinal association of vitamin D status with glycaemia, insulin, homoeostatic model assessment of insulin resistance, adiponectin and leptin. A prospective cohort with 181 healthy, pregnant Brazilian women was followed at the 5th-13th, 20th-26th and 30th-36th gestational weeks. In this cohort, 25-hydroxyvitamin D (25(OH)D) plasma concentrations were analysed using liquid chromatography-tandem MS. Vitamin D status was categorised as sufficient or insufficient using the Endocrine Society Practice Guidelines (≥75/<75 nmol/l) and the Institute of Medicine (≥50/<50 nmol/l) thresholds. Linear mixed-effect regression models were employed to evaluate the association between vitamin D status and each outcome, considering interaction terms between vitamin D status and gestational age (P<0·1). At baseline, 70·7 % of pregnant women had 25(OH)D levels <75 nmol/l and 16 % had levels <50 nmol/l. Women with sufficient vitamin D status at baseline, using both thresholds, presented lower glycaemia than those with insufficient 25(OH)D. Pregnant women with 25(OH)D concentrations <75 nmol/l showed lower insulin (β=-0·12; 95 % CI -0·251, 0·009; P=0·069) and adiponectin (β=-0·070; 95 % CI -0·150, 0·010; P=0·085) concentrations throughout pregnancy than those with 25(OH)D levels ≥75 nmol/l. Pregnant women with 25(OH)D <50 nmol/l at baseline presented significantly higher leptin concentrations than those with 25(OH)D levels ≥50 nmol/l (β=-0·253; 95 % CI -0·044, 0·550; P=0·095). The baseline status of vitamin D influences the biomarkers involved in glucose metabolism. Vitamin D-sufficient women at baseline had higher increases in insulin and adiponectin changes throughout gestation than those who were insufficient.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Brazil; Cohort Studies; Diabetes, Gestational; Diet; Female; Gestational Age; Humans; Insulin; Insulin Resistance; Leptin; Pregnancy; Pregnancy Complications; Prospective Studies; Vitamin D; Vitamin D Deficiency

To investigate the cord blood levels of adipokine and to assess their association with the fetal insulin resistance and fetal outcomes in newborns of gestational diabetic women (GDM). Methods: This cross-sectional study was performed in 40 GDM women and 40 healthy pregnant women (HPW) in the Department of Obstetrics and Gynecology at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) hospital in Puducherry, India, during the period from May 2016 to December 2017. Cord blood samples were collected at delivery from GDM and HPW groups. Cord plasma biochemical parameters such as insulin, C-peptide, adiponectin, leptin, resistin, and visfatin concentrations were measured. Leptin/adiponectin ratio (L/A), homeostasis model assessment of insulin resistance (HOMA2-IR), insulin sensitivity (HOMA2-%S) and beta cell function (HOMA2-%B) were calculated. The pregnancy outcomes such as birth weight (BW), Ponderal index and Apgar scores of the baby were measured. Results: The BW and Ponderal index of the baby were found to be significantly higher in GDM newborns compared to HPW newborns. Cord plasma insulin, C-peptide, HOMA2 -IR, visfatin, leptin, and L/A ratio were significantly higher whereas adiponectin level was lower in GDM compared to HPW. A significant positive correlation was observed between L/A ratio and fetal HOMA2-IR. Conclusion: Altered adipokine levels with increased L/A ratio was observed among the new-borns of Indian gestational diabetic mothers. There was an association between increased L/A ratio, insulin resistance and increased Ponderal index among the new-borns.

Topics: Adipokines; Apgar Score; Biomarkers; Birth Weight; C-Peptide; Cross-Sectional Studies; Diabetes, Gestational; Female; Fetal Blood; Humans; India; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Pregnancy; Pregnancy Outcome; Resistin

Gestational diabetes mellitus (GDM) is a common disorder characterized by abnormal glucose metabolism during pregnancy, affecting 2% to 5% of pregnant women. Currently, clinical treatment for GDM is very limited. The present study was designed to investigate the effect and underlying molecular mechanism of tertiary butylhydroquinone (TBHQ) in a pregnant C57BL/KsJ-Lep db/+ (referred to as db+) GDM mouse model. The results showed that nonpregnant db/+ mice did not show a diabetic phenotype, and TBHQ had no effect on glucose and insulin tolerance in these mice. Moreover, in db/+ pregnant mice exhibiting typical diabetes symptoms, such as hyperglycemia and hypoinsulinemia, TBHQ could remarkably decrease the blood glucose level, increase insulin level, and improve glucose and insulin intolerance. The results also revealed that TBHQ could inhibit oxidative stress in pregnant db/+ mice. Furthermore, TBHQ greatly improved offspring survival rate, glucose metabolism, and insulin tolerance. In addition, TBHQ inhibited oxidative stress by reducing malondialdehyde (MDA) and reactive oxygen species (ROS) levels and increased superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities. Moreover, we found that TBHQ activated the nuclear factor erythroid 2-related factor 2 (Nrf2), thereby increasing the levels of Nrf2, and ultimately upregulating the expression of heme oxygenase 1 (NO-1) and superoxide dismutase 2 (SOD2). In conclusion, our findings demonstrated that TBHQ alleviated GDM via Nrf2 activation.

Topics: Animals; Antioxidants; Blood Glucose; Diabetes, Gestational; Disease Models, Animal; Female; Hydroquinones; Leptin; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; Oxidative Stress; Pregnancy; Reactive Oxygen Species; Up-Regulation

This study aimed to examine changes in the insulin secretory response in early pregnancy, while accounting for changes in insulin sensitivity.. This is a secondary analysis of a previously conducted longitudinal physiological study. In 34 women, insulin secretory response (by IVGTT) and insulin sensitivity (by euglycaemic clamp) were assessed prior to pregnancy, in early pregnancy (12-14 weeks gestation) and in late pregnancy (34-36 weeks gestation). Using mixed-effects models, we compared insulin secretory response and sensitivity in early pregnancy to the same variables prior to pregnancy and in late pregnancy, with adjustment for age, obesity status and gestational diabetes mellitus (GDM). We examined changes in insulin secretory response after adjustment for insulin sensitivity using both multivariate modelling and the disposition index (DI). We explored the relationship between insulin secretory response and circulating hormones.. The insulin secretory response increased from prior to pregnancy to early pregnancy (unadjusted mean [SD] first-phase insulin response 465.1 [268.5] to 720 [358.2], p < 0.0001) and from early pregnancy to late pregnancy (to 924 [494.6], p = 0.01). Insulin sensitivity increased from prior to pregnancy to early pregnancy (insulin sensitivity index 0.10 [0.04] to 0.12 [0.05], p = 0.001) and decreased in late pregnancy (to 0.06 [0.03], p < 0.0001). Accounting for changes in insulin sensitivity, using either multivariate modelling or the DI, did not attenuate the early-pregnancy augmentation of insulin secretory response. Leptin was positively associated with insulin secretory response, independent of insulin sensitivity and adiposity (p = 0.004). Adjustment for leptin attenuated the observed augmentation of insulin secretory response in early pregnancy (adjusted mean change 121.5, p = 0.13).. The insulin secretory response increases markedly in early pregnancy, prior to and independent of changes in insulin sensitivity. Circulating hormones may mediate this metabolic adaptation. Identifying mediators of this physiological effect could have therapeutic implications for treating hyperglycaemia during and outside of pregnancy.

Topics: Adult; Age Factors; Blood Glucose; Body Mass Index; Cytokines; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Leptin; Longitudinal Studies; Multivariate Analysis; Obesity; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Third; Prospective Studies; Tumor Necrosis Factor-alpha

Women with gestational diabetes (GDM) are a high risk group for early type 2 diabetes (T2D). Depression is a risk factor for T2D in the general population. We investigated in women after a recent pregnancy with GDM and without a clinical diagnosis of depression, whether mild to moderate depressive symptoms associate with pathologic glucose metabolism. In a cross-sectional analysis, we examined 173 women, 9 ± 3 months after delivery with several psychopathological assessments, 5-point oral glucose tolerance test with insulin, anthropometrics, and laboratory chemistry. In a subgroup of 101 women, abdominal visceral fat was quantified by magnetic resonance imaging (MRI). A total of 22 women (13%) showed mild to moderate depressive symptoms, and the proportion of women with pathologic glucose metabolism (impaired fasting glucose, impaired glucose tolerance, or T2D) was higher in this group than in the women without depressive symptoms (59.1% vs. 33.1%, p = 0.018). Women with depressive symptoms also had higher body mass index (BMI), systolic blood pressure, plasma leptin, plasma resistin, and abdominal visceral fat volume. Pathologic glucose metabolism (OR = 2.594, 95% CI: 1.021-6.592), systolic blood pressure (OR = 1.076, 95% CI: 1.027-1.128), and abdominal visceral fat volume (OR = 2.491, 95% CI: 1.142-5.433) remained, even after adjustment for BMI, associated with the presence of depressive symptoms. Taken together, we found depressive symptoms at a level not generally diagnosed in clinical practice in a subgroup of women with recent GDM. This subgroup also showed an unfavorable metabolic profile. Mild to moderate depressive symptoms may therefore help to identify this special subgroup.

Topics: Adult; Biomarkers; Blood Pressure; Cross-Sectional Studies; Depression; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Intra-Abdominal Fat; Leptin; Pregnancy; Resistin

To assess the association of serum leptin and its receptor (SLeptinR) with the risk of gestational diabetes mellitus (GDM) and to evaluate the longitudinal circulation of these peptides in pregnancy.. This study consisted of 53 subjects diagnosed with GDM and 43 normal glucose tolerance (NGT) pregnant women. Serum leptin and SLeptinR were measured at 24-28 weeks, prior and after delivery, and post-puerperium.. Lower levels of leptin and SLeptinR were observed in GDM compared to NGT. Leptin [OR 0.97 (95% CI 0.94-1.0)] and SLeptinR [OR 0.86 (95% CI 0.79-0.93]) were inversely associated with GDM. Participants in the lowest tertile for leptin and SLeptinR had a 2.8-fold (95% CI 1.0-7.6) and a 5.7-fold (95% CI 1.9-17.3) higher risk of developing GDM compared with the highest tertile, respectively. These relationships were attenuated after adjustment for covariates. In both the groups, peak leptin was observed at 24-28 weeks, decreasing continuously during pregnancy (p > 0.05) and after delivery (p < 0.017). SLeptinR level increased (p < 0.001) during pregnancy and decreased (p < 0.005) after delivery in GDM, however, levels remained the same in NGT. In GDM, leptin and SLeptinR was positively and inversely correlated with BMI and HOMA-IR at 24-28 weeks and post-puerperium, respectively. The cord levels of both leptin and SLeptinR were lower than maternal levels. There were no significant differences in serum cord leptin and SLeptinR levels between the groups.. Leptin and SLeptinR are independently and inversely associated with GDM. Lower levels of these peptides may play an important role in the pathophysiology of GDM and pre-diabetic state in post-puerperium.

Topics: Adult; Case-Control Studies; Diabetes, Gestational; Female; Glucose; Humans; Leptin; Middle Aged; Postpartum Period; Pregnancy; Prospective Studies; Receptors, Leptin

We have shown that some markers of oxidative stress were higher in women with gestational diabetes mellitus (GDM). This study examines the relationship between adipokines and oxidative stress and their potential effects in pregnant women.. Three markers of oxidative stress (malondialdehyde, 8-isoprostane and xanthine oxidase) and three adipokines (leptin, adiponectin and resistin) were measured in maternal plasma, cord plasma and placenta of 208 pregnant women.. Among all these women, 105 were diagnosed with GDM while the other 103 were controls. Leptin, resistin, malondialdehyde, xanthine oxidase and 8-isoprostane in maternal plasma, cord plasma and placenta were significantly higher while maternal adiponectin significantly lower in women with GDM (P < 0.05). Adipokines in maternal plasma, cord plasma and placenta were positively correlated with markers of oxidative stress. Both markers of oxidative stress and adipokines were correlated inversely with homeostasis model assessment of insulin resistance whereas positively with quantitative insulin sensitivity check index (P < 0.01). Adiponectin is negatively correlated with leptin and resistin. Placental/cord leptin and cord resistin levels were higher in the macrosomia while maternal adiponectin level was lower (P < 0.05) than normal birthweight newborns. Both markers of oxidative stress and adipokines in maternal and cord plasma are negatively correlated with newborn birthweight (P < 0.05).. Adipokines interact with markers of oxidative stress, both of which lead to insulin resistance, GDM and macrosomia. It has long been known that placenta involves in the development of GDM. Adipokines might participate in this process and need to be confirmed by further studies.

Topics: Adiponectin; Adult; Diabetes, Gestational; Dinoprost; Female; Fetal Blood; Fetal Macrosomia; Humans; Infant, Low Birth Weight; Infant, Newborn; Leptin; Male; Malondialdehyde; Placenta; Pregnancy; Resistin; Xanthine Oxidase

Both gestational diabetes mellitus (GDM) as well as overweight/obesity during pregnancy are risk factors for detrimental anthropometric and hormonal neonatal outcomes, identified to 'program' adverse health predispositions later on. While overweight/obesity are major determinants of GDM, independent effects on critical birth outcomes remain unclear. Thus, the aim of the present study was to evaluate, in women with GDM, the relative/independent impact of overweight/obesity vs. altered glucose metabolism on newborn parameters.. The prospective observational 'Early CHARITÉ (EaCH)' cohort study primarily focuses on early developmental origins of unfavorable health outcomes through pre- and/or early postnatal exposure to a 'diabetogenic/adipogenic' environment. It includes 205 mother-child dyads, recruited between 2007 and 2010, from women with treated GDM and delivery at the Clinic of Obstetrics, Charité - Universitätsmedizin Berlin, Germany. Recruitment, therapy, metabolite/hormone analyses, and data evaluation were performed according to standardized guidelines and protocols. This report specifically aimed to identify maternal anthropometric and metabolic determinants of anthropometric and critical hormonal birth outcomes in 'EaCH'.. Group comparisons, Spearman's correlations and unadjusted linear regression analyses initially confirmed that increased maternal prepregnancy body-mass-index (BMI) is a significant factor for elevated birth weight, cord-blood insulin and leptin (all P < 0.05). However, consideration of and adjustment for maternal glucose during late pregnancy showed that no maternal anthropometric parameter (weight, BMI, gestational weight gain) remained significant (all n.s.). In contrast, even after adjustment for maternal anthropometrics, third trimester glucose values (fasting and postprandial glucose at 32nd and 36th weeks' gestation, HbA1c in 3rd trimester and at delivery), were clearly positively associated with critical birth outcomes (all P < 0.05).. Neither overweight/obesity nor gestational weight gain appear to be independent determinants of increased birth weight, insulin and leptin. Rather, 3rd trimester glycemia seems to be crucial for respective neonatal outcomes. Thus, gestational care and future research studies should greatly consider late pregnancy glucose in overweight/obese women with or without GDM, for evaluation of critical causes and interventional strategies against 'perinatal programming of diabesity' in the offspring.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Diabetes, Gestational; Female; Fetal Blood; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Leptin; Male; Obesity; Pregnancy; Pregnancy Trimester, Third; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Factors

Determine the metabolic profile and identify risk factors of women transitioning from gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM).. 237 women diagnosed with GDM underwent an oral glucose tolerance test (OGTT), anthropometrics assessment, and completed lifestyle questionnaires six years after pregnancy. Blood was analysed for clinical variables (e.g., insulin, glucose, HbA1c, adiponectin, leptin, and lipid levels) and NMR metabolomics. Based on the OGTT, women were divided into three groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM.. Six years after GDM, 19% of subjects had T2DM and 19% IGT. After BMI adjustment, the IGT group had lower HDL, higher leptin, and higher free fatty acid (FFA) levels, and the T2DM group higher triglyceride, FFA, and C-reactive protein levels than the NGT group. IGT and T2DM groups reported lower physical activity. NMR measurements revealed that levels of branched-chain amino acids (BCAAs) and the valine metabolite 3-hydroxyisobyturate were higher in T2DM and IGT groups and correlated with measures of insulin resistance and lipid metabolism.. In addition to well-known clinical risk factors, BCAAs and 3-hydroxyisobyturate are potential markers to be evaluated as predictors of metabolic risk after pregnancy complicated by GDM.

Topics: Adiponectin; Adult; Amino Acids, Branched-Chain; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Progression; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hydroxybutyrates; Insulin Resistance; Leptin; Pregnancy; Risk Factors

Breast milk (BM) hormones have been hypothesised as a nutritional link between maternal and infant metabolic health. This study aimed to evaluate hormone concentrations in BM of women with and without gestational diabetes mellitus (GDM), and the relationship between maternal factors, BM hormones and infant growth. We studied ninety-six nulliparous women with (n 48) and without GDM and their exclusively breastfed term singletons. Women with GDM received dietary therapy or insulin injection for euglycaemia during pregnancy. Hormone concentrations in BM, maternal BMI and infant growth were longitudinally evaluated on postnatal days 3, 42 and 90. Mothers with GDM had decreased concentrations of adiponectin (P colostrum<0·001; P mature-milk=0·009) and ghrelin (P colostrum=0·011; P mature-milk<0·001) and increased concentration of insulin in BM (P colostrum=0·047; P mature-milk=0·021). Maternal BMI was positively associated with adiponectin (β=0·06; 95 % CI 0·02, 0·1; P=0·001), leptin (β=0·16; 95 % CI 0·12, 0·2; P<0·001) and insulin concentrations (β=0·06; 95 % CI 0·02, 0·1; P<0·001), and inversely associated with ghrelin concentration in BM (β=-0·08; 95 % CI -0·1, -0·06; P<0·001). Among the four hormones, adiponectin was inversely associated with infant growth in both the GDM (β weight-for-height=-2·49; 95 % CI -3·83, -1·15; P<0·001; β head-circumference=-0·39; 95 % CI -0·65, -0·13; P=0·003) and healthy groups (β weight-for-height=-1·42; 95 % CI -2·38, -0·46; P=0·003; β head-circumference=-0·15; 95 % CI -0·27, -0·03; P=0·007). Maternal BMI and GDM are important determinants of BM hormone concentrations. Milk-borne adiponectin is determined by maternal metabolic status and plays an independent down-regulating role in early infant growth.

Topics: Adiponectin; Anthropometry; Blood Glucose; Body Mass Index; Body Weight; Breast Feeding; Colostrum; Diabetes, Gestational; Down-Regulation; Female; Ghrelin; Glucose Tolerance Test; Humans; Infant; Infant, Newborn; Insulin; Leptin; Longitudinal Studies; Male; Milk, Human; Mothers; Nutritional Sciences; Pediatric Obesity; Pregnancy

To analyze the concentrations of nesfatin-1 in maternal and cord serum, to evaluate the expression of nesfatin-1 in subcutaneous adipose tissue (SAT) from pregnant women with gestational diabetes mellitus (GDM) and those with normal glucose tolerance (NGT).. We studied a total of 50 GDM and 50 NGT subjects. The clinical features, serum nesfatin-1, homeostasis model assessment of insulin resistance (HOMA-IR), lipid profiles were measured at the third trimester of pregnancy. The expression of nesfatin-1 in the SAT was determined by western blot.. Compared with the NGT group, the GDM group showed greater levels of serum nesfatin-1, adipocyte fatty acid binding protein (AFABP), and leptin; a greater level of cord blood nesfatin-1; and a higher level of expression in SAT (p < 0.05 or p < 0.01). Fasting insulin (FI) (b = 0.317, p= 0.022) and body mass index (BMI) before delivery (b = 0.367, p=0.008) were independently associated with serum nesfatin-1. Nesfatin-1 was the independent risk factor for GDM.. The GDM group had higher levels of maternal serum and cord blood nesfatin-1, and greater nesfatin-1 expression in SAT. Nesfatin-1 is closely related to obesity and IR in pregnancy.

Topics: Adult; Asian People; Biomarkers; Blood Glucose; Body Mass Index; Calcium-Binding Proteins; China; Diabetes, Gestational; DNA-Binding Proteins; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Female; Fetal Blood; Humans; Insulin; Insulin Resistance; Leptin; Nerve Tissue Proteins; Nucleobindins; Pregnancy; Subcutaneous Fat, Abdominal; Up-Regulation; Young Adult

Leptin (LEP), a protein that plays a fundamental role in the metabolism of energy reserves, and the solute carrier family 30 A8 zinc transporter (SLC30A8) have been consistently associated with diabetes. Women with gestational diabetes are at moderate risk of developing diabetes type 1 and 2 after pregnancy, in addition to complications to the fetus. We investigated the association of the polymorphisms rs7799039 (LEP) and rs13266634 (SLC30A8) in a case-control study in Euro-Brazilians with gestational diabetes (GDM, N = 134) and healthy pregnant women (control, N = 180). Real-time PCR with fluorescent probes (TaqMan system) was applied to genotyping. All polymorphisms were in Hardy-Weinberg equilibrium. The minor allele frequencies, for healthy and GDM, respectively, for the A-allele (LEP gene rs7799039) were 40.3% (95%CI = 35-45%) vs 36.6% (95%CI = 31-42%), P = 0.345; and for the T-allele (SLC30A8 gene rs13266634) were 27.8% (95%CI = 23-32%) vs 23.5% (95%CI = 18-29%), P = 0.227. Genotype comparisons for both polymorphisms showed no significant difference (P > 0.05). The polymorphisms rs7799039 and rs13266634 were not associated with GDM in the population studied (P > 0.05). The minor allele frequencies for both polymorphisms were similar to those of other Caucasian populations.

Topics: Adult; Alleles; Brazil; Carrier Proteins; Case-Control Studies; Cation Transport Proteins; Diabetes, Gestational; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Leptin; Polymorphism, Single Nucleotide; Pregnancy

Compared to O-BP, we found elevated plasma leptin and resistin levels in O-T1DM, decreased gene expression of all adipokines in O-GDM, decreased. In conclusion, offspring of women with diabetes in pregnancy exhibit increased

Topics: Adiponectin; Adult Children; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; DNA Methylation; Epigenesis, Genetic; Female; Follow-Up Studies; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Leptin; Maternal Exposure; Pregnancy; Resistin; Subcutaneous Fat

Gestational diabetes mellitus is a significant risk factor for metabolic syndrome and cardiovascular disease.. To assess the relationships between components of the metabolic syndrome and cytokine and adhesion molecule levels in women with GDM during pregnancy and after delivery.. A prospective case-control study on a sample of 126 pregnant women (63 with and 63 without gestational diabetes mellitus). In an intra-subject analysis, 41 women with history of gestational diabetes mellitus and 21 controls were re-assessed in the postpartum period. Clinical data and levels of cytokines and adhesion molecules were recorded during weeks 24-29 of pregnancy and 12 months after delivery.. In the postpartum period, there were significantly higher levels of tumor necrosis factor alpha in both cases and controls, and of adiponectin in controls. Cases showed higher leptin levels, with no significant differences during and after pregnancy. No significant differences were seen in adhesion molecules and interleukin-6 between cases and controls during pregnancy and in the postpartum period, but levels of both were higher in cases. During pregnancy and after delivery, adiponectin decreased in cases and increased in controls. Significant positive correlations were seen between adiponectin and fasting blood glucose levels and vascular cell adhesion molecule-1, and also between leptin and tumor necrosis factor alpha levels.. The results suggest that increased inflammation and transient hyperglycemia during pregnancy would represent a latent form of metabolic syndrome, with an increased risk for type 2 diabetes mellitus and future cardiovascular disease.

Topics: Adiponectin; Adult; Blood Glucose; Cardiovascular Diseases; Case-Control Studies; Cell Adhesion Molecules; Cytokines; Diabetes, Gestational; Disease Susceptibility; Female; Humans; Hyperglycemia; Inflammation; Leptin; Metabolic Syndrome; Postpartum Period; Prediabetic State; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha; Young Adult

Low physical fitness (PF) is a risk factor for type 2 diabetes mellitus (T2D). Women with a history of gestational diabetes (GDM) are at risk for T2D at a young age, but the role of PF in this population is not clear. PF has also been found to correlate inversely with plasma leptin in previous studies. Here, we examine whether women who had GDM have lower PF than women after a normoglycemic pregnancy and, second, whether PF is associated with plasma leptin, independently of body fat mass.. Cross-sectional analysis of 236 participants in the PPSDiab Study (cohort study of women 3-16 months after delivery, 152 after gestational diabetes (pGDM), 84 after normoglycemic pregnancy (control subjects); consecutively recruited 2011-16); medical history, physical examination with bioelectrical impedance analysis (BIA), whole body magnetic resonance imaging (MRI) (n = 154), 5-point oral glucose tolerance test, cardiopulmonary exercise testing, clinical chemistry including fasting plasma leptin; statistical analysis with Mann-Whitney U and t -test, Spearman correlation coefficient, multiple linear regression.. Women pGDM had lower maximally achieved oxygen uptake (VO2peak/kg: 25.7(21.3-29.9) vs. 30.0(26.6-34.1)ml/min/kg; total VO2peak: 1733(1552-2005) vs. 1970(1767-2238)ml/min; p<0.0001 for both), and maximum workload (122.5(105.5-136.5) vs. 141.0(128.5-159.5)W; p<0.0001). Fasting plasma leptin correlated inversely with PF (VO2peak/kg ρ = -0.72 p<0.0001; VO2peak ρ = -0.16 p = 0.015; max. load ρ = -0.35 p<0.0001). These associations remained significant with adjustment for body mass index, or for body fat mass (BIA and MRI).. Women with a recent history of GDM were less fit than control subjects. Low PF may therefore contribute to the risk for T2D after GDM. This should be tested in intervention studies. Low PF also associated with increased leptin levels-independently of body fat. PF may therefore influence leptin levels and signaling. This hypothesis requires further investigation.

Topics: Adult; Blood Glucose; Body Mass Index; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Leptin; Linear Models; Oxygen Consumption; Physical Fitness; Pregnancy; Prospective Studies; Risk Factors

Gestational diabetes is a risk factor for perinatal complications; include shoulder dystocia, birth injuries such as bone fractures and nerve palsies. It is associated with later development of type 2 diabetes, the risk of macrosomia and other long-term health effects of infants born to diabetic mothers. The study assesses placental peptides and maternal factors as potential predictors of gestational diabetes among pregnant women.. A total of 200 pregnant women were recruited for the study, 150 pregnant women without pre gestational diabetes including 50 women with low risk factors of diabetes as controls and 50 other pregnant women with pregestational diabetes as control. Fasting blood glucose and the lipid profile were determined by enzymatic methods using Envoy® 500 reagents (Vital Diagnostics, USA). Glycated haemoglobin was assessed using the Cation Exchange resin method. Leptin and the Human Placenta Lactogen were assayed using the Sandwich-ELISA technique. Beta chorionic gonadotrophin, insulin, progesterone and estradiol were determined using chemilumiscence imunoassay technique on MAGLUMI 600 analyzer. Anthropometry, including BMI and blood pressure were also measured.. Fasting plasma glucose (FBG), insulin, insulin resistance, glycated haemoglobin and Human Placenta Lactogen(HPL)were significantly (p<0.0001) increased in the pregestational diabetic women whereas progesterone and estradiol were significantly decreased. In the second trimester however, there was no significant difference (p>0.05) in estradiol, insulin, insulin resistance and HPL between the pregnant women who developed gestational diabetes and those who did not. Leptin, progesterone and FBG were significantly increased in those who developed GDM. The risk of developing gestational diabetes increased with overweight (OR = 1.76, P = 0.370) and family history of diabetes (OR = 2.18, P = 0.282).. Leptin, progesterone, estradiol estimated in this study were increased in the gestational diabetes mellitus women and fairly predicted gestational diabetes in the non-diabetics pregnant women. Obesity, aging and family history of diabetes were strongly predictive of gestational diabetes.

Topics: Adult; Blood Glucose; Case-Control Studies; Cross-Sectional Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Obesity; Overweight; Peptides; Placenta; Pregnancy; Risk Factors

Gestational diabetes mellitus (GDM) is increasing partly due to the obesity epidemic. Adipocytokines have thus been suggested as first trimester screening markers for GDM. In this study we explore the associations between body mass index (BMI) and serum concentrations of adiponectin, leptin, and the adiponectin/leptin ratio. Furthermore, we investigate whether these markers can improve the ability to screen for GDM in the first trimester.. A cohort study in which serum adiponectin and leptin were measured between gestational weeks 6+0 and 14+0 in 2590 pregnant women, categorized into normal weight, moderately obese, or severely obese.. Lower concentrations of adiponectin were associated with GDM in all BMI groups; the association was more pronounced in BMI<35 kg/m2 (p=0.30 for interaction). Leptin was inversely associated with GDM in severely obese (p=0.033), but showed no association in women with BMI<35 kg/m2. The adiponectin/leptin ratio was associated with GDM in women with BMI<35 kg/m2 but not in severely obese women (p=0.79). In regard to predicting GDM, maternal characteristics combined with adiponectin alone, adiponcetin and leptin, and adiponcetin/leptin ratio had the strongest associations in women with BMI<35 kg/m2. These models had a detection rate of 77.3%-80.3% when the false positive rate was fixed at 25%.. Low adiponectin measured in the first trimester is associated with the development of GDM; higher BMI was associated with lower performance of adiponectin, though this was insignificant. Leptin had an inverse relationship with GDM in severely obese women and did not improve the ability to predict GDM.

Topics: Adiponectin; Adult; Area Under Curve; Biomarkers; Body Mass Index; Cohort Studies; Diabetes, Gestational; Enzyme-Linked Immunosorbent Assay; Female; Humans; Leptin; Obesity; Pregnancy; Pregnancy Trimester, First; Regression Analysis; ROC Curve

BACKGROUND Gestational diabetes mellitus (GDM) is common all over the world. GDM women are with inflammatory and metabolisms abnormalities. However, few studies have focused on the association of IL-65-72C/G and TNF-α -857C/T single nucleotide polymorphisms (SNPs), inflammatory biomarkers, and metabolic indexes in women with GDM, especially in the Inner Mongolia population. The aim of this study was to investigate the associations of IL-65-72C/G and TNF-α -857C/T SNPs, and inflammation and metabolic biomarkers in women with GDM pregnancies. MATERIAL AND METHODS Blood samples and placentas from 140 women with GDM and 140 women with healthy pregnancies were collected. Matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) and MassARRAY-IPLEX were performed to analyze IL-65-72C/G and TNF-α -857C/T SNPs. Enzyme linked immunosorbent assay (ELISA) was performed to analyze inflammatory biomarkers and adipokines. RESULTS Distribution frequency of TNF-α -857CT (OR=3.316, 95% CI=1.092-8.304, p=0.025) in women with GDM pregnancies were obviously higher than that in women with healthy pregnancies. Women with GDM were of older maternal age, had higher BMI, were more nulliparous, and had T2DM and GDM history, compared to women with healthy pregnancies (p<0.05). Inflammatory biomarkers in serum (hs-CRP, IL-6, IL-8, IL-6/IL-10 ratio) and placental (NF-κB, IL-6, IL-8, IL-6/IL-10 ratio, IL-1b, TNF-α) were significantly different (p<0.05) between women with GDM and women with healthy pregnancies. Differences were found for serum FBG, FINS, HOMA-IR, and HOMA-β, and placental IRS-1, IRS-2, leptin, adiponectin, visfatin, RBP-4, chemerin, nesfatin-1, FATP-4, EL, LPL, FABP-1, FABP-3, FABP-4, and FABP-5. CONCLUSIONS TNF-α -857C/T SNP, hs-CRP, IL-6, IL-8, and IL-6/IL-10 were associated with GDM in women from Inner Mongolia, as was serious inflammation and disordered lipid and glucose metabolisms.

Topics: Adipokines; Adult; Biomarkers; Blood Glucose; China; Diabetes, Gestational; Female; Humans; Inflammation; Insulin; Insulin Resistance; Interleukin-6; Leptin; Placenta; Polymorphism, Single Nucleotide; Pregnancy; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tumor Necrosis Factor-alpha

Cytokines produced by adipose and placental tissues (adipokines) have been implicated in the development of gestational diabetes mellitus (GDM). There is, however, limited research regarding the relationship between advancing pregnancy, maternal adipokine profile, insulin resistance and the development of GDM. Furthermore, no studies have investigated these parameters in women with a history of GDM who are at the highest risk of recurrence. This study examined the circulating concentrations of a number of adipokines associated with insulin resistance at two points in pregnancy, and determined whether they were altered in women who developed GDM.. Non-diabetic women with a history of GDM in a previous pregnancy (n=123) had blood drawn at 14 and 28weeks of pregnancy for GDM diagnosis, together with assessment of a range of adipokine concentrations by multiplex assay (fatty acid-binding protein 4 [FABP4], leptin, chemerin, adiponectin and resistin).. With advancing pregnancy, maternal adiponectin concentrations decreased, while leptin and resistin levels increased (p<0.05). In women who developed GDM at 28weeks of pregnancy (42%), fasting and postprandial glucose levels were already significantly elevated by 14weeks (p<0.05), while adiponectin concentrations were lower (p<0.05). Adiponectin remained lower at the time of GDM diagnosis (p<0.05), while the other adipokines were similar between groups at each timepoint.. Maternal glucose and adipokine profile is altered early in pregnancy in women with a history of GDM who subsequently develop recurrent disease.

Topics: Adipokines; Diabetes, Gestational; Female; Humans; Insulin Resistance; Leptin; Mothers; Pregnancy; Recurrence; Resistin; Risk Assessment

We aimed to assess the levels of adipokine and their relation to gestational diabetic related clinical phenotypes and fetal growth parameters.. International Association of the Diabetes and Pregnancy Study criteria was used to classify gestational diabetic cases (n = 208) and euglycemic controls (n = 300). ELISA assays were performed for insulin, chemerin, leptin, and interleukin-18 (IL-18). Mann-Whitney U test, Chi-square/Fisher exact test, multiple regression analyses, and ROC curves were applied with significant p values of <0.05.. Levels of chemerin, IL-18, and leptin were seven-, four-, and five-folds higher in cases versus controls, respectively (p < 0.01). The adipokine showed strong positive correlation with fasting blood glucose, homeostasis model assessment of insulin resistance, and fetal weight (p < 0.01). Odds of GDM association remained significant for chemerin (OR 1.522; 1.097-2.110) and leptin (OR 2.579; 1.503-4.425) while all associations were lost for IL-18 (p > 0.05) after multiple adjustments. Raised chemerin levels were identified in 96% cases (n = 201) employing the proposed cut off value >15.49 ng/ml.. High chemerin and leptin levels are seen in GDM which may be associated with subclinical inflammation suggesting a role in development of insulin resistance.

Topics: Adult; Biomarkers; Case-Control Studies; Chemokines; Diabetes, Gestational; Enzyme-Linked Immunosorbent Assay; Female; Fetal Weight; Humans; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-18; Leptin; Pregnancy; Pregnancy Trimester, Second; ROC Curve; Young Adult

This study aimed to investigate the relationship between skinfold thickness and serum leptin, ghrelin, adiponectin, and resistin levels in infants of diabetic mothers. Biochemical parameters were also similar for the two groups (infants of diabetic mothers and controls) (p > 0.05). We confirmed that there was a negative correlation between birth weight and serum ghrelin level (p < 0.05) in the two groups. When it was evaluated for control newborns, a positive correlation between abdominal circumference and serum resistin level was found in the controls (p < 0.05). Our results indicate that gestational diabetes by appropriate diet or insulin treatment may be effective in the protection of fetuses of diabetic mothers from the negative effects of gestational diabetes. Ghrelin alone was negatively correlated with birth weight. This negative correlation could be potentially advantageous to infants, because a reduction in appetite might prevent excessive food intake and postnatal weight gain.

Topics: Adiponectin; Adipose Tissue; Anthropometry; Birth Weight; Case-Control Studies; Diabetes, Gestational; Feeding Behavior; Female; Gestational Age; Ghrelin; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Resistin; Skinfold Thickness; Weight Gain

Gestational diabetes mellitus (GDM) is the glucose intolerance occurring during pregnancy. The prevalence of GDM is increased in obese women. Leptin and adiponectin are adipokines that play an important role in the regulation of insulin secretion and glucose and lipid metabolism. The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and the development of GDM.. This case-control study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation. To discriminate the ADIPOQ rs266729, rs1501299 and LEP rs2167270 alleles, TaqMan® Pre-Designed SNP Genotyping Assays were used.. There was a statistically significant association between the ADIPOQ rs266729 gene polymorphism and GDM. Among women with GDM, a higher prevalence of the G allele was observed (GG and CG genotypes). Multivariate logistic regression analysis, taking into account age, BMI before pregnancy, past pregnancies and the ADIPOQ rs266729 gene polymorphism, revealed that the presence of a G allele is an independent risk factor for GDM. Moreover, there was the association between the LEP rs2167270 polymorphism and the requirement for daily insulin, which was significantly higher in women with the A allele (AA and GA genotypes).. The results of our study suggest an association between adiponectin gene rs266729 as well as leptin gene rs2167270 polymorphisms and GDM.

Topics: Adiponectin; Adult; Alleles; Diabetes, Gestational; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Glucose Tolerance Test; Humans; Insulin; Leptin; Polymorphism, Single Nucleotide; Pregnancy

Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. Adipokine imbalance in the presence of metabolic dysfunction may be a key event in promoting CVD. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma adiponectin, leptin and the leptin/adiponectin (L/A) ratio in pregnancy and at 5 years after the index pregnancy.. This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy X-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting adiponectin and leptin levels were measured four times during pregnancy and at follow-up.. We found the L/A ratio higher in GDM women both during pregnancy and follow-up compared to non-GDM women. A high L/A ratio during pregnancy was associated with CV risk based on lipid ratios at follow-up, especially the TG/HDL-C ratio. Further, interaction analysis indicated that an increase in the L/A ratio of 1 unit was associated with a higher CV risk in GDM compared to normal pregnancy. Finally, low adiponectin levels independently predicted increased lipid ratios at follow-up.. Taken together, our findings suggest that high L/A ratio in pregnancy and in particularly in those with GDM are associated with an unfavorable CVD risk profile during follow-up. Future studies should investigate if a dysregulated leptin and adiponectin profile during pregnancy is associated with atherosclerotic disease during long-term follow-up.

Topics: Absorptiometry, Photon; Adiponectin; Adult; Atherosclerosis; Biomarkers; Case-Control Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Leptin; Lipids; Longitudinal Studies; Pregnancy; Prognosis; Prospective Studies; Pulse Wave Analysis; Risk Assessment; Risk Factors; Time Factors

Cinnamon has a history of use for medicinal purposes and its major benefits have been linked to cinnamaldehyde. The present study aimed to investigate the hypoglycemic action of cinnamaldehyde against fatty-sucrosed diet/streptozotocin (FSD/STZ)-rat model of gestational diabetes. Female albino rats were divided into three groups. Group I fed with normal diet (ND) while group II and III were fed with FSD for eight weeks (five weeks pre-gestational and three weeks gestational). Rats of group III were administered with a daily oral dose of 20mg/kg cinnamaldehyde one week before mating onward. At the 7th day of gestation, FSD-fed rats were injected intraperitoneally with STZ (25mg/kg b.wt.) to induce gestational diabetes. Pre-mating treatment of cinnamaldehyde controls hyperphagia and glucose intolerance during the gestational period than in diabetic rats. It also reduced levels of fructosamine, total cholesterols, triglycerides, leptin, tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA) and nitric oxide (NO), while it significantly increased levels of high-density lipoprotein (HDL)-cholesterol, adiponectin, liver glycogen, reduced glutathione (GSH) and catalase activity at term pregnancy. In addition, cinnamaldehyde administration up-regulated the mRNA expression of peroxisome proliferated activated receptor-gamma (PPARγ) and also ameliorated the number of viable fetuses, implantation loss sites, fetal glucose and insulin levels. In conclusion, cinnamaldehyde has safe hypoglycemic action on gestational diabetes by potentiating insulin secretion and sensitivity through activating the antioxidant defense system, suppressing pro-inflammatory cytokines production, upregulating PPARγ gene expression and alleviating the reproductive performance.

Topics: Acrolein; Adipose Tissue; Animals; Antioxidants; Biomarkers; Blood Glucose; Body Weight; Cholesterol; Cytokines; Diabetes, Gestational; Feeding Behavior; Female; Fetus; Fructosamine; Glucose Tolerance Test; Glycogen; Hyperglycemia; Inflammation Mediators; Insulin; Leptin; Liver; Oxidative Stress; PPAR gamma; Pregnancy; Pregnancy Outcome; Rats; RNA, Messenger; Triglycerides

Insulin and leptin receptors are known to share signaling pathways, such as JAK2/STAT-3 (Janus kinase2/signal transduction and activator of transcription3), MAPK (Mitogen activated protein kinase), and PI3K (phosphoinositide 3-kinase). Both positive and negative cross-talk have been previously found in different cellular systems. Gestational diabetes (GDM) is a pathophysiological state with high circulating levels of both insulin and leptin. We have previously found that these 3 signaling pathways are activated in placenta from GDM patients to promote translation, involving the activation of leptin receptor. Now, we have tested the hypothesis that both leptin and insulin receptors might contribute to this activation in a positive way that may become negative when the system is overactivated. We studied the activation of leptin and insulin receptors in placenta from GDM and healthy pregnancies. We have also performed in vitro studies with insulin and leptin stimulation of trophoblast explants from healthy placenta. We have found that both leptin and insulin receptors are activated in placenta from GDM. In vitro stimulation of trophoblast explants with both leptin and insulin at submaximal doses (0.1 nM) potentiated the activation of signaling, whereas preincubation with maximal concentrations of insulin (10 nM) and further stimulation with leptin showed negative effect. Trophoblastic explants from GDM placenta, which presented high signaling levels, had a negative signaling effect when further incubated in vitro with leptin. In conclusion, insulin and leptin receptors have positive effects on signaling, contributing to high signaling levels in GDM placenta, but insulin and leptin have negative effects upon overstimulation.

Topics: Adult; Case-Control Studies; Diabetes, Gestational; Dose-Response Relationship, Drug; Down-Regulation; Female; Humans; Immunohistochemistry; Insulin; Insulin Receptor Substrate Proteins; Leptin; Models, Biological; Phosphorylation; Placenta; Pregnancy; Receptor, Insulin; Receptors, Leptin; Signal Transduction

In mice, undercarboxylated osteocalcin (ucOC) improves beta-cell function and insulin sensitivity through adiponectin. In humans, levels of total osteocalcin (OC) and ucOC were negatively correlated with insulin resistance (IR) indices in patients with type 2 diabetes. Whether ucOC plays a role in glucose homeostasis and whether its effect is mediated through adiponectin during pregnancy is unclear. Serum levels of total OC, ucOC, and adiponectin were measured in 130 pregnant women with varying degrees of IR [gestational diabetes mellitus (GDM), n = 74 and non-GDM, n = 56]. In all participants, total OC and ucOC levels were positively correlated with HOMA-IR and HOMA-%B, and negatively correlated with QUICKI. In contrast, adiponectin levels were negatively correlated with HOMA-IR and positively correlated with QUICKI (P < 0.01, both). However, neither total OC nor ucOC was associated with adiponectin. Although none of these markers could help distinguish women with and without GDM, total OC and ucOC levels were significantly higher in non-GDM women who had 1 abnormal OGTT value than those who had all normal OGTT values. Total OC and ucOC levels were significantly correlated with insulin secretion and IR indices, but not adiponectin levels, in pregnant women. Changes in OC might be a sensitive response to increased IR during pregnancy, which was not mediated through adiponectin.

Topics: Adiponectin; Adult; Blood Glucose; Diabetes, Gestational; Female; Humans; Insulin; Insulin Resistance; Leptin; Osteocalcin; Pregnancy

The objective was to determine the value of clinical and analytical maternal factors to predict birth weight and umbilical cord biochemical markers of diabetic fetopathy.. Prospective evaluation of gestational diabetes pregnancies (n = 50). Maternal weight-related clinical and analytical factors were collected during pregnancy. After birth, an umbilical cord sample was taken.. Univariate linear regression analysis showed relationship between maternal weight, glycated hemoglobin (HbA1c) and insulin-like growth factor 1 (IGF1) with birth weight percentile. A significant association was found between maternal weight and cord insulin and C-peptide. Maternal HbA1c, leptin and insulin during pregnancy showed a positive linear association to cord leptin, insulin and C-peptide. In multivariate analysis models, final maternal BMI showed an independent positive association with cord C-peptide.. Maternal weight-related and analytical parameters show diagnostic value to birth weight and cord markers.

Topics: Adult; Birth Weight; Body Weight; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Diseases; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Leptin; Pregnancy

The purposes of this study were to examine concentrations of leptin and biochemical parameters in gestational diabetes mellitus (GDM) patients and normal glucose tolerance (NGT) individuals, and also to explore the links of leptin (LEP) G2548A and leptin receptor (LEPR) Gln223Arg polymorphisms with leptin levels and GDM risk among Chinese. Our study included 357 GDM and 355 NGT individuals who were at 24~30 gestational weeks. Plasma leptin and insulin levels were analyzed by ELISA. Gene polymorphisms were genotyped using TaqMan real-time polymerase chain reaction assay. The results showed that plasma leptin levels were significantly higher in the impaired fasting glucose (IFG) group than NGT group (34.35 (26.54, 56.48) ng/mL vs 26.31 (17.99, 37.87) ng/mL, P < 0.05). Plasma leptin levels correlated with plasma fasting insulin levels, pre-pregnant body mass index, homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index both in GDM and NGT group (P < 0.05). However, neither LEP G2548A nor LEPR Gln223Arg polymorphisms were significantly associated with GDM risk and plasma leptin levels (P > 0.05). Our findings showed that high leptin level was associated with GDM. And larger and more rigorous researches were needed to further explore the association of LEP and LEPR gene polymorphisms and GDM among Chinese population.

Topics: Adult; Asian People; Blood Glucose; Diabetes, Gestational; Fasting; Female; Gene Frequency; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Insulin; Leptin; Polymorphism, Single Nucleotide; Pregnancy; Real-Time Polymerase Chain Reaction; Receptors, Leptin; Young Adult

The objective of this study is to evaluate third-trimester fetal liver biometry, to predict birth weight and cord markers at birth in diabetic pregnancies.. Fetal liver biometry (liver diameters, area and volume) was obtained between 32 and 34 weeks. A blood sample was obtained from cord after birth. Receiver operating characteristic (ROC) curve models were evaluated for 75th and 90th birth weight percentile. Univariate and multivariate models were used.. All the hepatic diameters, area and sectional volume demonstrated significant differences in both birth weight percentile ⩾75 and ⩾90. All ROC curves showed significant values. A significant association was observed for all measurements with birth weight. In multivariate model, liver area volume gave significant values for predicting birth weight. Cord leptin, c-peptide and ferritin were related to fetal hepatic size.. The hepatic changes in gestational diabetes were valid to predict birth weight and metabolic changes at birth.

Topics: Adult; Biomarkers; Biometry; Birth Weight; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Weight; Fetus; Humans; Leptin; Linear Models; Liver; Multivariate Analysis; Organ Size; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Third; Prospective Studies; ROC Curve; Spain; Ultrasonography, Prenatal

Children exposed to gestational diabetes mellitus (GDM) are at a higher risk of developing obesity and type 2 diabetes. This susceptibility might involve brown adipose tissue (BAT), which is suspected to protect against obesity. The objective of this study is to assess whether fetal exposure to maternal hyperglycemia is associated with DNA methylation variations in genes involved in BAT genesis and activation.. DNA methylation levels at the PRDM16, BMP7, CTBP2, and PPARGC1α gene loci were measured in placenta samples using bisulfite pyrosequencing in E-21 (n = 133; 33 cases of GDM) and the HumanMethylation450 array in Gen3G (n = 172, all from non-diabetic women) birth cohorts. Glucose tolerance was assessed in all women using an oral glucose tolerance test at the second trimester of pregnancy. Participating women were extensively phenotyped throughout pregnancy, and placenta and cord blood samples were collected at birth.. We report that maternal glycemia at the second and third trimester of pregnancy are correlated with variations in DNA methylation levels at PRDM16, BMP7, and PPARGC1α and with cord blood leptin levels. Variations in PRDM16 and PPARGC1α DNA methylation levels were also correlated with cord blood leptin levels. Mediation analyses support that DNA methylation variations at the PPARGC1α gene locus explain 0.8 % of the cord blood leptin levels variance independently of maternal fasting glucose levels (p = 0.05).. These results suggest that maternal glucose in pregnancy could produce variations in DNA methylation in BAT-related genes and that some of these DNA methylation marks seem to mediate the impact of maternal glycemia on cord blood leptin levels, an adipokine regulating body weight.

Topics: Adult; Diabetes, Gestational; DNA Methylation; Epigenesis, Genetic; Female; Fetal Blood; Glucose Tolerance Test; Humans; Infant, Newborn; Leptin; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Placenta; Pregnancy; Pregnancy Trimesters

Leptin and insulin levels are key factors regulating fetal and neonatal energy homeostasis, development and growth. Both biomarkers are used as predictors of weight gain and obesity during infancy. There are currently no prediction algorithms for cord blood (UCB) hormone levels using Artificial Neural Networks (ANN) that have been directly trained with anthropometric maternal and neonatal data, from neonates exposed to distinct metabolic environments during pregnancy (obese with or without gestational diabetes mellitus or lean women). The aims were: 1) to develop ANN models that simulate leptin and insulin concentrations in UCB based on maternal and neonatal data (ANN perinatal model) or from only maternal data during early gestation (ANN prenatal model); 2) To evaluate the biological relevance of each parameter (maternal and neonatal anthropometric variables).. We collected maternal and neonatal anthropometric data (n = 49) in normoglycemic healthy lean, obese or obese with gestational diabetes mellitus women, as well as determined UCB leptin and insulin concentrations by ELISA. The ANN perinatal model consisted of an input layer of 12 variables (maternal and neonatal anthropometric and biochemical data from early gestation and at term) while the ANN prenatal model used only 6 variables (maternal anthropometric from early gestation) in the input layer. For both networks, the output layer contained 1 variable to UCB leptin or to UCB insulin concentration.. The best architectures for the ANN perinatal models estimating leptin and insulin were 12-5-1 while for the ANN prenatal models, 6-5-1 and 6-4-1 were found for leptin and insulin, respectively. ANN models presented an excellent agreement between experimental and simulated values. Interestingly, the use of only prenatal maternal anthropometric data was sufficient to estimate UCB leptin and insulin values. Maternal BMI, weight and age as well as neonatal birth were the most influential parameters for leptin while maternal morbidity was the most significant factor for insulin prediction.. Low error percentage and short computing time makes these ANN models interesting in a translational research setting, to be applied for the prediction of neonatal leptin and insulin values from maternal anthropometric data, and possibly the on-line estimation during pregnancy.

Topics: Adult; Anthropometry; Biomarkers; Body Mass Index; Body Weight; Computer Simulation; Diabetes, Gestational; Female; Fetal Blood; Humans; Insulin; Leptin; Maternal Age; Neural Networks, Computer; Obesity; Pregnancy; Young Adult

Soluble leptin receptor (sOb-R), a potential marker of leptin resistance, is inversely associated with risk of type 2 diabetes, independently of leptin concentrations. We have previously shown that ethnic difference in leptin concentration may partly explain the increased risk of gestational diabetes (GDM) in South Asians.. Our objective was to investigate whether sOb-R concentrations are associated with risk of GDM, whether concentrations of sOb-R differ across ethnic groups, and whether ethnic differences in sOb-R explain the ethnic differences in GDM risk.. The STORK Groruddalen study; a prospective cohort study of pregnant women living in Oslo, Norway, between May 2008 and May 2010.. Of the total sample (n = 823), 680 (47.1% Europeans) had sOb-R measured in pregnancy week 15 and an oral glucose tolerance test performed in week 28.. GDM was diagnosed according to World Health Organization 2013 criteria.. sOb-R was inversely associated with GDM (odds ratio, 0.76 [95% confidence interval, 0.69-0.83] per ng/ml increase in sOb-R, P < .001) in crude analysis. The association was attenuated after adjustments for covariates and leptin (0.85 [0.77-0.95], P = .004). Compared to women with sOb-R higher than 5 ng/ml, the odds ratio of GDM was 0.29(0.11-0.78; P = .014) among women with sOb-R greater than 10 ng/ml and 0.59 (0.37-0.94; P = .026) among women with sOb-R 5-10 ng/ml, in adjusted analysis. sOb-R levels did not differ across ethnic groups, and sOb-R did not explain ethnic differences in GDM risk.. There was an independent, inverse association between sOb-R and GDM, with the lowest risk of GDM observed among higher sOb-R concentrations.

Topics: Adult; Diabetes, Gestational; Europe; Female; Humans; Iraq; Leptin; Morocco; Norway; Pakistan; Pregnancy; Prospective Studies; Receptors, Leptin; Risk; Sri Lanka; Turkey; Young Adult

To explore serum vaspin, leptin, and adiponectin levels and their correlation with insulin resistance (IR) in pregnant women with and without gestational diabetes mellitus (GDM) and healthy non-pregnant women. A total of 262 individuals, including pregnant women with GDM (n = 86), those without GDM (n = 92), and age-matched healthy non-pregnant women (n = 84) were enrolled in this case-control study. Vaspin, leptin, adiponectin, glucose, insulin, hemoglobin A1C (HbA1c), and lipid parameters were measured. The homeostasis model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and body mass index were calculated. Data inferred higher concentrations of vaspin (2.72 ± 2.20 vs. 1.84 ± 1.57 vs. 0.81 ± 1.02) in GDM than during normal pregnancy and in non-pregnant women, higher leptin (23.42 ± 12.18 vs. 22.19 ± 10.55 vs. 12.10 ± 11.26), and lower adiponectin (4,164.83 ± 2,650.39 vs. 4,871.66 ± 2,803.51 vs. 7,202.85 ± 4,893.13) in GDM and normal pregnancy as compared to non-pregnant women (p < 0.05). Vaspin was positively correlated to leptin (r = 0.273, p = 0.012), HOMA-IR (r = 0.387, p = 0.000), and triglycerides (TG, r = 0.218, p = 0.046) in GDM. In addition, leptin was negatively correlated to adiponectin in GDM (r = -0.336, p = 0.002) and normal pregnancy (r = -0.256, p = 0.014). Furthermore, vaspin was significantly correlated to GDM and HOMA-IR, and the weight gain might play a vital role in the occurrence of GDM. During pregnancy, high vaspin concentration is significantly associated with IR in GDM.

Topics: Adiponectin; Adult; Diabetes, Gestational; Female; Humans; Insulin Resistance; Leptin; Pregnancy; Serpins

To measure serum osteocalcin (OC), under-carboxylated osteocalcin (ucOC), osteopontin (OPN), and leptin in pregnant women with gestational diabetes mellitus (GDM) and in healthy pregnant women during pregnancy and after birth and relate these markers to glucose metabolism.. This was a prospective study including 60 women with GDM and 60 subjects with normal gestation who were evaluated at gestational week 30 and 6 weeks postpartum. Serum OC, ucOC, OPN, leptin, insulin and insulin resistance were evaluated during the study.. Bone biomarkers and leptin were similar between GDM and normal pregnancy. After delivery, OC, ucOC and OPN increased in both groups, while leptin decreased only in healthy controls. Bone markers did not correlate with insulin and insulin resistance in the two groups, but leptin was positively correlated with insulin and insulin resistance and negatively correlated with bone biomarkers only in healthy women. Furthermore, the women who developed diabetes postpartum had lower levels of OC than women with normal glucose tolerance.. GDM is not associated with OC, ucOC, OPN, and leptin and does not correlate with insulin resistance. At postpartum, women who develop diabetes have lower osteocalcin concentrations. Leptin correlates with insulin resistance and bone biomarkers in non-diabetic women.

Topics: Adult; Biomarkers; Diabetes, Gestational; Female; Humans; Leptin; Osteocalcin; Osteopontin; Postpartum Period; Pregnancy

To explore the differences between Europeans and South Asians in BMI, subcutaneous fat, and serum leptin (s-leptin) levels during and after pregnancy and their relationship with gestational diabetes (GDM).. Multi-ethnic population-based cohort study, whereof 353 Europeans (93.1% of the included) and 190 South Asians (95.0% of the included).. S-leptin, BMI, and subcutaneous fat (sum of triceps, subscapular, and suprailiac skinfolds) were measured at 14 and 28 weeks of gestation, and 14 weeks after delivery. GDM was diagnosed with the WHO criteria 2013.. South Asians had similar thickness of the triceps and suprailiac skinfolds, thicker subscapular skinfold, and higher s-leptin than Europeans in early pregnancy, despite lower BMI. South Asians retained more subcutaneous fat (mean (95% CI) 10.0 (7.4-12.7) mm vs 3.8 (1.9-5.8) mm) and BMI (1.5 (1.2-1.8) kg/m(2) vs 0.1 (-0.1 to 0.3) kg/m(2)) than Europeans 14 weeks after delivery and s-leptin decreased less in South Asians than Europeans (-0.13 (-0.27 to -0.00) μg/l vs -0.47 (-0.57 to -0.37) μg/l, P<0.001 for all). The prevalence of GDM was 23.8% (n=84) in Europeans and 42.6% (n=81) in South Asians. BMI, subcutaneous fat, and s-leptin were all positively associated with GDM, also after adjustment for covariates.. The relatively high amounts of subcutaneous fat and s-leptin in South Asians in early pregnancy contributed to their increased risk of GDM. South Asians retained more weight and subcutaneous fat after delivery, potentially increasing their risk of adiposity and GDM in future pregnancies.

Topics: Body Mass Index; Diabetes, Gestational; Female; Humans; Leptin; Norway; Pakistan; Postpartum Period; Pregnancy; Risk; Sri Lanka; Subcutaneous Fat

This study aimed to determine whether third-trimester adipokines during gestational diabetes (GDM) are associated with higher metabolic risk.. A total of 221 women with GDM (according to IADPSG criteria) were enrolled between 2011/11 and 2013/6 into a prospective observational study (IMAGE), and categorized as having elevated fasting blood glucose (FBG) or impaired fasting glucose (IFG, n = 36) if levels were ≥ 92 mg/dL during a 75-g oral glucose tolerance test (OGTT), impaired glucose tolerance (IGT, n = 116) if FBG was < 92 mg/dL but with elevated 1-h or 2-h OGTT values, or impaired fasting and stimulated blood glucose (IFSG, n = 69) if both FBG was ≥ 92 mg/dL and 1-h or 2-h OGTT values were elevated.. Pre-gestational body mass index (BMI) was higher in women with IFG or IFSG compared with IGT (P < 0.001), as were leptin levels in women with IFG vs IGT [34.7 (10.5-119.7) vs 26.6 (3.56-79.4) ng/L; P = 0.008]. HOMA2-IR scores were higher in women with IFG or IFSG vs IGT (1.87 ± 1.2 or 1.72 ± 0.9 vs 1.18 ± 0.8, respectively; P < 0.001). Also, those with IFSG vs those with IGT had significantly lower HOMA2-B scores (111.4 ± 41.3 vs 127.1 ± 61.6, respectively; P < 0.05) and adiponectin levels [5.00 (1.11-11.3) vs 6.19 (2.11-17.7) μg/mL; P < 0.001], and higher levels of IL-6 [1.14 (0.33-20.0) vs 0.90 (0.31-19.0); P = 0.012] and TNF-α [0.99 (0.50-10.5) vs 0.84 (0.45-11.5) pg/mL; P = 0.003]. After adjusting for age, parity, and pre-gestational and gestational BMI, the difference in adiponectin levels remained significant.. Diagnosing GDM by IADSPG criteria results in a wide range of heterogeneity. Our study has indicated that adipokine levels in addition to FBG may help to select women at high metabolic risk for appropriate monitoring and post-delivery interventions (ClinicalTrials.gov number NCP02133729).

Topics: Adiponectin; Biomarkers; Body Mass Index; Cohort Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; France; Humans; Insulin Resistance; Leptin; Overweight; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Prenatal Diagnosis; Prospective Studies; Risk Factors; Severity of Illness Index

To study the adipokines concentration and glucose homoeostasis in the early-second trimester of women who will develop gestational diabetes mellitus (GDM).. Maternal plasma and fetal amniotic fluid samples were prospectively collected between 2006 and 2007 at the time of mid-trimester amniocentesis. Eight patients found to be affected by GDM were compared with 10 control patients with a normal pregnancy course. Adipokines leptin and adiponectin, as well as insulin and glucose concentration both in amniotic fluid and maternal plasma were compared between cases and controls. HOMA-IR (homeostatic model assessment for insulin resistance) was also calculated both for amniotic fluid and maternal serum.. The amniotic fluid adiponectin concentration was higher in women who would develop GDM than in controls (29.9 ng/ml, 95% CI 26.7-49.8 ng/ml, versus 14.9 ng/ml, 95% CI 13.5-18.8 ng/ml), p < 0.05). No difference was shown for leptin both in amniotic fluid and maternal serum. Insulin concentrations in the amniotic fluid were found to be lower in GDM than in controls, while HOMA-IR-index resulted lower in amniotic fluid and higher maternal serum (p < 0.05).. Our data suggests that an earlier alteration in the fetal glucose metabolism will precede the glucose dysmetabolism in pregnancies later complicated by GDM.

Topics: Adipokines; Adiponectin; Adult; Amniocentesis; Amniotic Fluid; Blood Glucose; Case-Control Studies; Diabetes, Gestational; Female; Fetus; Glucose; Humans; Insulin; Insulin Resistance; Leptin; Pregnancy; Pregnancy Trimester, Second; Prospective Studies

Early-pregnancy short sleep duration is predictive of gestational diabetes and preeclampsia; mechanisms for these associations are unknown. Leptin, an adipocyte-derived peptide involved in regulating food intake and energy expenditure, may play a role in these observed associations. Given inconsistent reports linking short sleep duration with leptin, and absence of studies among pregnant women, we examined the association of maternal sleep duration with plasma leptin in early pregnancy.. This cross-sectional study included 830 pregnant women. Plasma leptin was measured in samples collected around 13 weeks gestation. Sleep duration was categorized as: ≤5, 6, 7-8 (reference), and ≥9 hours. Differences in leptin concentrations across categories were estimated using linear regression. Analyses were completed for lean and overweight/obese women.. Overall, women with long sleep duration had elevated plasma leptin (p-value = 0.04). However, leptin concentrations were not statistically significantly elevated in women with a short sleep duration. There was no association of leptin with sleep duration among lean women. Among overweight/obese women, a U-shaped relation between leptin and sleep duration was observed: Mean leptin was elevated (β = 21.96 ng/ml, P < 0.001) among women reporting ≤5 hour of sleep compared with reference group; and women reporting ≥9 hours of sleep also had elevated leptin (β = 4.29 ng/ml, P = 0.09).. Short sleep duration, and to a lesser extent long sleep duration, were associated with elevated leptin among overweight/obese women. These data add some evidence to help understand mechanistic relationships of sleep duration with pregnancy complications.

Topics: Blood Glucose; Blood Pressure; Circadian Rhythm; Comorbidity; Cross-Sectional Studies; Diabetes, Gestational; Female; Humans; Leptin; Obesity; Overweight; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Second; Risk Factors; Secretory Rate; Sleep Initiation and Maintenance Disorders; Thinness; Washington

Lactation may influence future progression to type 2 diabetes after gestational diabetes mellitus (GDM). However, biomarkers associated with progression to glucose intolerance have not been examined in relation to lactation intensity among postpartum women with previous GDM. This study investigates whether higher lactation intensity is related to more favorable blood lipids, lipoproteins and adipokines after GDM pregnancy independent of obesity, socio-demographics and insulin resistance.. The Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT) is a prospective cohort study that recruited 1035 women diagnosed with GDM by the 3-h 100g oral glucose tolerance tests (OGTTs) after delivery of a live birth in 2008-2011. Research staff conducted 2-h 75 g OGTTs, and assessed lactation intensity, anthropometry, lifestyle behaviors and socio-demographics at 6-9 weeks postpartum (baseline). We assayed fasting plasma lipids, lipoproteins, non-esterified free fatty acids, leptin and adiponectin from stored samples obtained at 6-9 weeks postpartum in 1007 of the SWIFT participants who were free of diabetes at baseline. Mean biomarker concentrations were compared among lactation intensity groups using multivariable linear regression models.. Increasing lactation intensity showed graded monotonic associations with fully adjusted mean biomarkers: 5%-8% higher high-density lipoprotein cholesterol (HDL-cholesterol), 20%-28% lower fasting triglycerides, 15%-21% lower leptin (all trend P-values < 0.01), and with 6% lower adiponectin, but only after adjustment for insulin resistance (trend P-value = 0.04).. Higher lactation intensity was associated with more favorable biomarkers for type 2 diabetes, except for lower plasma adiponectin, after GDM delivery. Long-term follow-up studies are needed to assess whether these effects of lactation persist to predict progression to glucose intolerance.

Topics: Adiponectin; Adult; Biomarkers; Cohort Studies; Diabetes Mellitus, Type 2; Diabetes, Gestational; Disease Progression; Fatty Acids, Nonesterified; Female; Humans; Insulin Resistance; Lactation; Leptin; Lipids; Lipoproteins; Middle Aged; Postpartum Period; Prediabetic State; Pregnancy; Young Adult

In this study, we aimed to investigate relationships between maternal prepregnancy obesity and gestational diabetes mellitus and placental leptin DNA methylation.. This study comprises data on 535 mother-infant dyads enrolled in the Rhode Island Child Health Study, a prospective cohort study of healthy term pregnancies. Prepregnancy body mass index was calculated from self-reported anthropometric measures and gestational diabetes mellitus diagnoses gathered from inpatient medical records. DNA methylation of the leptin promoter region was assessed in placental tissue collected at birth using quantitative bisulfite pyrosequencing.. In a multivariable regression analysis adjusted for confounders, infants exposed to gestational diabetes mellitus had higher placental leptin methylation (β = 1.89, P = .04), as did those demonstrating prepregnancy obesity (β = 1.17, P = .06). Using a structural equations model, we observed that gestational diabetes mellitus is a mediator of the effects of prepregnancy obesity on placental leptin DNA methylation (β = 0.81, 95% confidence interval, 0.27-2.71).. Our results suggest that the maternal metabolic status before and during pregnancy can alter placental DNA methylation profile at birth and potentially contribute to metabolic programming of obesity and related conditions.

Topics: Adult; Body Mass Index; Cohort Studies; Diabetes, Gestational; DNA Methylation; Female; Humans; Infant, Newborn; Leptin; Linear Models; Logistic Models; Male; Multivariate Analysis; Obesity; Placenta; Pregnancy; Pregnancy Complications; Promoter Regions, Genetic; Prospective Studies; Young Adult

Studies in both humans and rodents suggest that maternal diabetes leads to a higher risk of the fetus developing impaired glucose tolerance and obesity during adulthood. However, the impact of hyperinsulinemia in the mother on glucose homeostasis in the offspring has not been fully explored. We aimed to determine the consequences of maternal insulin resistance on offspring metabolism and endocrine pancreas development using the LIRKO mouse model, which exhibits sustained hyperinsulinemia and transient increase in blood glucose concentrations during pregnancy. We examined control offspring born to either LIRKO or control mothers on embryonic days 13.5, 15.5, and 17.5 and postpartum days 0, 4, and 10. Control offspring born to LIRKO mothers displayed low birth weights and subsequently rapidly gained weight, and their blood glucose and plasma insulin concentrations were higher than offspring born to control mothers in early postnatal life. In addition, concentrations of plasma leptin, glucagon, and active GLP-1 were higher in control pups from LIRKO mothers. Analyses of the endocrine pancreas revealed significantly reduced β-cell area in control offspring of LIRKO mothers shortly after birth. β-Cell proliferation and total islet number were also lower in control offspring of LIRKO mothers during early postnatal days. Together, these data indicate that maternal hyperinsulinemia and the transient hyperglycemia impair endocrine pancreas development in the control offspring and induce multiple metabolic alterations in early postnatal life. The relatively smaller β-cell mass/area and β-cell proliferation in these control offspring suggest cell-autonomous epigenetic mechanisms in the regulation of islet growth and development.

Topics: Animals; Animals, Newborn; Blood Glucose; Cell Proliferation; Diabetes, Gestational; Disease Models, Animal; Female; Glucagon; Glucagon-Like Peptide 1; Hyperglycemia; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Secreting Cells; Islets of Langerhans; Leptin; Mice; Organ Size; Phenotype; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Weight Gain

To determine the extent to which gestational fasting and postload levels of glucose explain differences in infant fat mass between UK-born Pakistani and white British infants.. Analyses were undertaken in a prospective pregnancy cohort study of 1,415 women and their singleton live-born infants (629 white British and 786 Pakistani). Infant fat mass was assessed by cord-blood leptin levels and fetal insulin secretion by cord-blood insulin levels. Maternal OGTTs were completed at 26-28 weeks of gestation.. Pakistani women had higher fasting and postload glucose levels and greater incidence of gestational diabetes than white British women. Higher fasting and postload glucose levels were associated with higher cord-blood levels of insulin and leptin in all participants, irrespective of ethnicity. Cord-blood leptin levels were 16% (95% CI 6, 26) higher in Pakistani than in white British infants. After adjustment for fasting glucose levels, this difference attenuated to 7% (-3, 16), and with additional adjustment for cord-blood insulin levels it attenuated further to 5% (-4, 14). Path analyses supported the hypothesis that fasting glucose levels mediate the relationship of Pakistani ethnicity to greater fat mass at birth, as measured by cord-blood leptin levels; on average, 19% of this mediation involved fetal insulin secretion. Postload glucose levels did not act as an important mediator of ethnic differences in cord-blood leptin levels. Results were very similar when 130 women with gestational diabetes were removed.. These novel findings suggest a role of maternal pregnancy glycaemia in mediating differences in fat mass between Pakistani and white British infants.

Topics: Blood Glucose; Body Mass Index; Diabetes, Gestational; Ethnicity; Fasting; Female; Fetal Blood; Glucose Tolerance Test; Humans; Incidence; Infant; Insulin; Leptin; Pakistan; Pregnancy; Prospective Studies; United Kingdom

Adipocytokines participate in the regulation of glucose metabolism and fetal development. The transcription factor activating protein 2B (TFAP2β) has been associated with adipocytokine regulation, and gene variations with type 2 diabetes and obesity. This study investigated associations between maternal TFAP2B variation, adipocytokine levels, and maternal and neonatal anthropometric characteristics.. A population-based sample of women was followed from delivery to 6 months postpartum. Adiponectin, leptin, and interleukin-6 levels at delivery, and maternal as well as neonatal anthropometric variables were assessed. The TFAP2β intron 1 variable number tandem repeat (VNTR) was genotyped.. Maternal interleukin-6 correlated positively with leptin at delivery, with peripartum weight changes and weight of newborn males, adjusted for potential confounders. Leptin at delivery was associated with TFAP2β intron 1 VNTR genotype, adjusted for confounders, maternal weight and negatively with birth weight among female neonates. A path model suggested a link between TFAP2β genotype, leptin levels, and newborn females' weight.. The present results stress a role for the TFAP2 β in adiposity-related conditions and intrauterine growth. The association between neonatal birth weight and maternal adipocytokine levels, together with the observed sex effect, call for further studies on the mechanisms behind neuroendocrine fetal programming.

Topics: Adipokines; Adiposity; Adult; Birth Weight; Blood Pressure; Body Mass Index; Body Weight; Diabetes, Gestational; Female; Genetic Variation; Humans; Infant, Newborn; Interleukin-6; Leptin; Longitudinal Studies; Male; Minisatellite Repeats; Pregnancy; Risk Factors; Transcription Factor AP-2

Gestational diabetes mellitus (GDM) is associated with adverse metabolic outcomes after delivery. Physical activity practice improves the inflammatory profile; however, whether this association exists in women with prior GDM remains unknown. Our objective was to examine the cardiometabolic and inflammatory risk factors associated with accelerometer-based measures of physical activity in women with prior GDM.. Ninety-six women who had GDM between 2003 and 2010 were tested 2.9 ± 2.2 yr after delivery. The physical activity practice was measured with ActiGraph GT3X (ActiGraph™, Pensacola, FL) accelerometers worn ≥ 5 d, and the time spent weekly in moderate to vigorous physical activity (MVPA) was derived. The waist circumference was measured and the inflammatory marker or cytokine concentrations were measured in fasting plasma by the xMAP technology using the Bio-Plex 200 system. The lipid profile was also measured from fasting blood samples.. Only 31% of women accumulated at least 150 min of MVPA per week. No association was observed between the MVPA practice and any of the metabolic measurements in the whole group of women. The MVPA did not differ in groups stratified by waist circumference <88 or ≥ 88 cm. In women with waist circumference <88 cm, the MVPA was negatively correlated with circulating concentrations of C-reactive protein (r = -0.51, P = 0.006), leptin (r = -0.40, P = 0.008), plasminogen activator inhibitor-1 (r = -0.32, P = 0.04), and triglycerides (r = -0.44, P = 0.003). No association was seen with plasma interleukin-6; tumor necrosis factor-α; and total, LDL, or HDL cholesterol concentrations.. These analyses suggest that in the years after delivery, longer time spent in MVPA practice is associated with a lower cardiometabolic risk only in women with prior GDM who do not have abdominal obesity.

Topics: Accelerometry; Adolescent; Adult; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Cohort Studies; Cytokines; Diabetes, Gestational; Female; Humans; Inflammation; Leptin; Lipids; Metabolic Diseases; Motor Activity; Obesity, Abdominal; Plasminogen Activator Inhibitor 1; Pregnancy; Risk Factors; Young Adult

Previous studies have shown markedly lower birth weight among infants of South Asian origin compared with those of White European origin. Whether such differences mask greater adiposity in South Asian infants and whether they persist across generations in contemporary UK populations is unclear. Our aim was to compare birth weight, skinfold thickness and cord leptin between Pakistani and White British infants and to investigate the explanatory factors, including parental and grandparental birthplace.. We examined the differences in birth weight and skinfold thickness between 4649 Pakistani and 4055 White British infants born at term in the same UK maternity unit and compared cord leptin in a subgroup of 775 Pakistani and 612 White British infants.. Pakistani infants were lighter (adjusted mean difference -234 g 95% CI -258 to -210) and were smaller in both subscapular and triceps skinfold measurements. The differences for subscapular and triceps skinfold thickness (mean z-score difference -0.27 95% CI -0.34 to -0.20 and -0.23 95% CI -0.30 to -0.16, respectively) were smaller than the difference in birth weight (mean z-score difference -0.52 95% CI -0.58 to -0.47) and attenuated to the null with adjustment for birth weight (0.03 95% CI -0.03 to 0.09 and -0.01 95% CI -0.08 to 0.05, respectively). Cord leptin concentration (indicator of fat mass) was similar in Pakistani and White British infants without adjustment for birth weight, but with adjustment became 30% higher (95% CI 17% to 44%) among Pakistani infants compared with White British infants. The magnitudes of difference did not differ by generation.. Despite being markedly lighter, Pakistani infants had similar skinfold thicknesses and greater total fat mass, as indicated by cord leptin, for a given birth weight than White British infants. Any efforts to reduce ethnic inequalities in birth weight need to consider differences in adiposity and the possibility that increasing birth weight in South Asian infants might inadvertently worsen health by increasing relative adiposity.

Topics: Adipose Tissue; Adult; Birth Weight; Body Mass Index; Diabetes, Gestational; Female; Fetal Blood; Gestational Age; Glucose Intolerance; Hospitals, Maternity; Humans; Infant, Newborn; Leptin; Pakistan; Pre-Eclampsia; Pregnancy; Pregnant Women; Prospective Studies; Regression Analysis; Skinfold Thickness; Surveys and Questionnaires; United Kingdom; White People

Our aim was to investigate the influence of gestational diabetes mellitus (GDM) and GDM-associated conditions upon the placental uptake of (14)C-l-methionine ((14)C-l-Met). The (14)C-l-Met uptake by human trophoblasts (TBs) obtained from normal pregnancies (normal trophoblast [NTB] cells) is mainly system l-type amino acid transporter 1 (LAT1 [L])-mediated, although a small contribution of system y(+)LAT2 is also present. Comparison of (14)C-l-Met uptake by NTB and by human TBs obtained from GDM pregnancies (diabetic trophoblast [DTB] cells) reveals similar kinetics, but a contribution of systems A, LAT2, and b(0+) and a greater contribution of system y(+)LAT1 appears to exist in DTB cells. Short-term exposure to insulin and long-term exposure to high glucose, tumor necrosis factor-α, and leptin decrease (14)C-l-Met uptake in a human TB (Bewo) cell line. The effect of leptin was dependent upon phosphoinositide 3-kinase, extracellular-signal-regulated kinase 1/2 (ERK/MEK 1/2), and p38 mitogen-activated protein kinase. In conclusion, GDM does not quantitatively alter (14)C-l-Met placental uptake, although it changes the nature of transporters involved in that process.

Topics: Adaptor Proteins, Signal Transducing; Adult; Biological Transport; Case-Control Studies; Cell Line; Diabetes, Gestational; Female; Glucose; Humans; Insulin; Kinetics; Large Neutral Amino Acid-Transporter 1; Leptin; Methionine; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; p38 Mitogen-Activated Protein Kinases; Phosphatidylinositol 3-Kinase; Pregnancy; RNA, Messenger; Trophoblasts; Tumor Necrosis Factor-alpha

This study aims to explore the changes in maternal serum adipocytokines during pregnancy and post partum in normal and complicated with gestational diabetes (GDM) pregnancies and to investigate the relationship between serum adipocytokines and some of major metabolic parameters.. 236 pregnant women (127 with GDM and 109 control group) and 50 postpartum women (30 with GDM during pregnancy and 20 controls). Using ELISA and EIA kits, serum levels of adipocytokines were tested during pregnancy and post partum. Maternal adipocytokines levels were correlated with some metabolic parameters.. Women with GDM had lower values of adiponectin and higher values of leptin during pregnancy (p<0.001; 0.0001) and post partum (p<0.002; 0.0001). Serum apelin was significantly lower in GDM group (p<0.009). However, we did not find significance for resistin (p<0.317) and apelin (p<0.218). Positive correlation for leptin and negative for adiponectin was found for pre-pregnancy and pregnancy body mass index, glycated hemoglobin and homeostasis model assessment of insulin resistance index. Using cut point of 8.2 μg/ml for adiponectin and 28.7 ng/ml for leptin could exclude GDM with a sensitivity of 83.6%/81.2% and specificity of 56.6%/64.2% (area under the curve 0.702 and 0.827).. There are constant differences in adiponectin and leptin levels between GDM and control group during pregnancy and post partum. Apelin was decreased in our GDM group and no differences were found for resistin and visfatin. Further studies are required to verify the mechanism of this alteration and whether the adipocytokines can be predictors for GDM at an early stage of pregnancy.

Topics: Adipokines; Adiponectin; Adult; Apelin; Blood Glucose; Body Mass Index; Diabetes, Gestational; Female; Humans; Intercellular Signaling Peptides and Proteins; Leptin; Postpartum Period; Pregnancy

Offspring of women with gestational diabetes (GDM) exhibit an adverse cardiovascular risk factor profile by as early as age 5 years. Recently, maternal glycemia has been associated with epigenetic modification of genes on the fetal side of the placenta, including those encoding emerging risk factors (adiponectin, leptin), suggesting that vascular differences may emerge even earlier in life. Thus, we sought to evaluate cardiovascular risk factors and determinants thereof in 1-year-old infants of women with and without GDM.. Traditional (glucose, lipids) and emerging (C-reactive protein (CRP), adiponectin, leptin) risk factors were assessed in pregnancy in 104 women with (n = 36) and without GDM (n = 68), and at age 1-year in their offspring. In pregnancy, women with GDM had higher triglycerides (2.49 vs 2.10 mmol/L, p = 0.04) and CRP (5.3 vs 3.6 mg/L, p = 0.03), and lower adiponectin (7.3 vs 8.5 μg/mL, p = 0.04) than did their peers. At age 1-year, however, there were no differences in cardiovascular risk factors (including adiponectin) between the infants of women with and without GDM. Of note, maternal and infant adiponectin levels were associated in the non-GDM group (r = 0.39, p = 0.001) but not in the GDM group (r = 0.07, p = 0.67). Furthermore, on multiple linear regression analyses, maternal adiponectin emerged as an independent predictor of infant adiponectin in the non-GDM group only (beta = 776.1, p = 0.0065).. Infants of women with and without GDM have a similar cardiovascular risk factor profile at age 1-year. However, there are differences in their early-life determinants of adiponectin that may be relevant to the subsequent vascular risk of GDM offspring.

Topics: Adiponectin; Blood Glucose; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Diabetes Complications; Diabetes, Gestational; Female; Humans; Infant; Leptin; Male; Pregnancy; Prospective Studies; Risk Factors; Triglycerides

The mechanisms whereby gestational diabetes mellitus (GDM) increases the risk of fetal overgrowth and development of metabolic diseases later in life are likely to involve changes in nutrient supply to the fetus. Hence, in this work, we hypothesize that GDM may affect folic acid (FA) supply to the placenta and fetus.. We compared (3)H-FA uptake by human cytotrophoblasts isolated from normal pregnancies (normal trophoblasts; NTB cells) and GDM pregnancies (diabetic trophoblasts; DTB cells) and investigated the effect of GDM hallmarks on (3)H-FA uptake by BeWo cells.. (3)H-FA uptake by NTB and DTB cells was time dependent and acidic pH stimulated. When compared with NTB, (3)H-FA uptake by DTB cells was more sensitive to acidic pH changes and to 5-methyltetrahydrofolate and pemetrexed (PTX) inhibition, indicating a proportionally greater involvement of the proton-coupled folate transporter (PCFT). A 4-h exposure of BeWo cells to lipopolysaccharide (LPS, 1-10 μg/ml) or to high levels of tumor necrosis factor-α (TNF-α, 300 ng/l) significantly reduced (3)H-FA uptake. Moreover, hyperleptinemic conditions (100 ng/ml leptin) decreased (3)H-FA uptake by BeWo cells in a time-dependent manner when compared with normoleptinemic conditions (1 ng/ml leptin).. GDM modulates (3)H-FA uptake by the syncytiotrophoblast, and leptin as well as TNF-α downregulate it.

Topics: Adult; Biological Transport; Case-Control Studies; Cells, Cultured; Diabetes, Gestational; Female; Folic Acid; Glutamates; Guanine; Humans; Hydrogen-Ion Concentration; Inflammation Mediators; Kinetics; Leptin; Lipopolysaccharides; Pemetrexed; Pregnancy; Proton-Coupled Folate Transporter; Recombinant Proteins; Signal Transduction; Tetrahydrofolates; Trophoblasts; Tumor Necrosis Factor-alpha

Placentas from gestational diabetes (GDM) suffer from structural and functional changes including overgrowth. That is why we aimed to study [³H]-leucine incorporation into protein in addition to translation signaling in placenta from GDM. Thus, we investigated the expression of leptin and leptin receptor (LEPR), as well as the activation state of signaling proteins regulating protein synthesis, such as mTOR, S6 Kinase, EIF4E-BP1, EIF4E, and eEF2 by measuring protein phosphorylation by immunoblot. [³H]-Leucine incorporation into protein also was determined in trophoblastic placenta explants from GDM and control pregnancy. We found that leptin and LEPR expression are increased in placentas from GDM and the translation machinery activity as well as [³H]-leucine incorporation into protein were higher in placentas from GDM compared with placentas from control pregnancy. In conclusion, protein synthesis rate is increased in placenta from GDM patients, and this may be due, at least in part, by the activation of translation signaling. The increased expression of leptin and LEPR may contribute to these effects. These results may provide a possible mechanism for the previously observed increase in placenta growth in GDM.

Topics: Adult; Case-Control Studies; Diabetes, Gestational; Female; Humans; Leptin; Placenta; Pregnancy; Receptors, Leptin; Signal Transduction; Young Adult

Leptin is an adipokine which has a direct relationship to obesity. Our aim was to measure this hormone in pregnant women at three months intervals throughout their pregnancies to determine the serum value of those who developed preeclampsia.. We followed 19 women (median age 24.8 +/- 5.7 years) with pre-gestational Body Mass Index (BMI) less than 25 kg/m2, 21 (median age 26.1 +/- 4.6 years) with BMI higher than 25 kg/m2 and 16 (median age 30.9 +/- 5.8 years) with Gestational Diabetes Mellitus (GDM) (median age 30.9 +/- 5.8 years), recruited in the 1st trimester of pregnancy. Serum levels of leptin were measured with radioimmunoassay (RIA) technique.. In the first trimester of pregnancy leptin levels showed statistically significant differences between normal weight and overweight-obese women (p < 0.001), diabetic women (p < 0.05) and the subgroup of preeclamptic women (p < 0.001). For those women with PGBMI > or = 40 kg/m2 and leptin > or = 40 ng/ml in the second trimester, the Odds Ratio (OR) to develop preeclampsia was of 47.95% CI (4.1-527.2). Analyzing leptin values with ROC curves, the greatest area under the curve (AUC) was for leptin in the second trimester (0.773, CI: 0.634-0.911).. Women with morbid obesity (BMI > or = 40 kg/m2) had significantly higher levels of serum leptin (p < 0.01) and a value of 40 ng/ml of this hormone seems to be predictive of developing preeclampsia in this group of patients.

Topics: Adult; Body Mass Index; Diabetes, Gestational; Female; Humans; Leptin; Obesity; Overweight; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Prognosis; Risk Factors; Sensitivity and Specificity

Inflammation is an important component of the metabolic syndrome (MetS) which could be the link between the metabolic and the cardiovascular consequences of this condition. Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for MetS and an inflammation component has been described in this disease. The aim of the study was to evaluate the relationships between cytokine concentrations, components of MetS and cardiovascular risk markers in women with late-onset GDM. Women (n=63) with late-onset GDM and 63 controls were enrolled. Clinical variables, and obstetrics and perinatal outcomes were recorded. Relationships between cytokines (TNF-α, leptin, IL6, adiponectin) and endothelial injury markers (VCAM, ICAM and selectine) were analyzed. Control vs. patient data indicated: pre-gestational body mass index (BMI) 23.46±3.73 vs. 26.97±5.07kg/m(2) (p=0.001); TNF-α 2.2±0.8 vs. 3.1±1.5pg/mL (p=0.002); leptin 18714.78±8859.08 vs. 27365.79±16209.67pg/mL (p=0.001); adiponectin 162.42±34.19 vs. 141.54±41.33ng/mL (p=0.04). Multivariate analyses showed that adiponectin had a protective effect (OR=0.9; p=0.02) and BMI carried a significant risk (OR=8.4; p=0.01) for GDM. No differences were found in endothelial injury markers. In conclusion, the cytokine profile in women with late-onset GDM is characterized by high concentrations of TNF-α and leptin and low adiponectin. This profile is related, in large extent, to an increased pregravid BMI which, potentially, may be linked to the future development of both metabolic and cardiovascular disease.

Topics: Adiponectin; Adult; Body Mass Index; Cardiovascular Diseases; Diabetes, Gestational; Female; Humans; Leptin; Metabolic Syndrome; Pregnancy; Pregnancy Trimester, Third; Risk; Tumor Necrosis Factor-alpha

Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for metabolic syndrome and CVD. The aim of the study was to evaluate the relationships between levels of cytokines, components of metabolic syndrome and cardiovascular risk markers in women with previous gestational diabetes.. Women (n = 41) with gestational diabetes background (cases) and 21 healthy women (controls) in the postpartum period were enrolled. Demographic and clinical data, lipid and carbohydrate metabolism and uric acid and adipokine levels (TNF-α, IL-6, leptin and adiponectin) were compared and their relationships analysed. Metabolic syndrome prevalence was calculated by WHO and NCEP-ATPIII definitions.. There were significant differences between cases and controls: body mass index (kg/m(2) ) 27.4 ± 5.6 vs 23.9 ± 3.6 (p = 0.013), waist circumference (cm) 85.2 ± 12.9 vs 77.5 ± 9.0 (p = 0.017), metabolic syndrome (WHO definition) 14.6% vs 0% (p = 0.012), metabolic syndrome (NCEP-ATPIII definition) 22% vs 0% (p = 0.002), low HDL 36.6% vs 9.5% (p = 0.024), fasting glucose (mmol/L) 5.4 ± 0.6 vs 4.9 ± 0.2 (p < 0.001), glucose 120' oral glucose tolerance test (mmol/L) 5.8 ± 1.7vs 4.7 ± 0.8 (p = 0.007), fasting insulin (μU/mL) 13.4 ± 8.1 vs 8.4 ± 4.3 (p = 0.004), HOMA index 3.3 ± 2.3 vs 1.8 ± 1.0 (p = 0.002), HbA(1c) (%) 5.4 ± 0.2 vs 5.2 ± 0.2 (p = 0.021), uric acid (mg/dL) 4.1 ± 1 vs 3.5 ± 0.6 (p = 0.009), leptin (ng/mL) 32 025.5 ± 19 917.3 vs 20 258.9 ± 16 359.9 (p = 0.023), respectively.. Women with previous gestational diabetes have central adiposity, atherogenic lipid profile, carbohydrate intolerance and adverse adipokine profile, all of which are risk factors for the future development of metabolic disease and CVD.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Body Mass Index; Cardiovascular Diseases; Diabetes, Gestational; Fasting; Female; Humans; Insulin; Leptin; Lipids; Metabolic Syndrome; Postpartum Period; Pregnancy; Prevalence; Risk Factors

Gestational diabetes mellitus is characterized by progressive insulin resistance. Adipocytokines are thought to be associated with insulin resistance. This cross-sectional study evaluated the associations between serum concentrations of several adipocytokines and insulin resistance at different stages of glucose tolerance in pregnancy, using the homeostasis model assessment of insulin resistance (HOMA-IR) as a reference.. According to oral glucose tolerance test results, 74 pregnant women were divided into three groups: normal glucose tolerance (n = 25); intermediate glucose tolerance (n = 19); gestational diabetes mellitus (n = 30). Adiponectin, leptin, resistin, visfatin and retinol-binding protein 4 (RBP4) concentrations were measured using enzyme-linked immuno sorbent assays.. Groups were comparable regarding age, week of gestation and body mass index before gestation. There were statistically significant between-group differences in HOMA-IR, but no significant differences regarding serum adipocytokine concentrations.. Adipo nectin, leptin, resistin, visfatin and RBP4 were not associated with the degree of glucose tolerance in pregnancy. Concentrations of these adipocytokines are not sufficiently sensitive to replace HOMA- IR in pregnancy.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Cross-Sectional Studies; Diabetes, Gestational; Female; Glucose; Glucose Clamp Technique; Humans; Insulin; Insulin Resistance; Leptin; Nicotinamide Phosphoribosyltransferase; Pregnancy; Resistin; Retinol-Binding Proteins, Plasma

To investigate the relationship between inflammatory factors, including C-reactive protein(CRP), tumor necrosis factor alpha (TNF-α), adiponectin, leptin and gestational diabetes mellitus (GDM) and their changes in puerperium.. From June 2008 to May 2010, 40 cases with gestational diabetes mellitus, 40 cases of normal pregnancy were enrolled in this study. Fasting venous blood were obtained at early pregnancy (10 - 12 weeks), late pregnancy (36 - 38 weeks) and day 3 and 42 of postpartum. Serumal adiponectin, leptin and TNF-α were measured by ELISA, and serumal CRP were measured by particle enhanced immunoturbidimetric method. The levels of those 4 cytokines and homeostasis model assessment insulin resistance (HOMA-IR) index were compared between two groups. And the changes of 4 cytokines were calculated in puerperium. The receiver operating characteristic (ROC) for TNF-α predicting GDM was designed.. (1) The relationship between cytokines and HOMA-IR: the levels of adiponectin of (5.7 ± 1.8) mg/L in the GDM group were significantly lower than (8.1 ± 2.7) mg/L in control group in early pregnancy, and the level of adiponectin was negatively correlated with HOMA-IR (r = -0.333, P < 0.05). The levels of (28 ± 10) µg/L of leptin, (10.0 ± 3.4) ng/L of TNF-α and (4.7 ± 1.1) mg/L of CRP in GDM group were significantly higher than (20 ± 8) µg/L of leptin, (4.6 ± 2.7) ng/L of TNF-α, (2.4 ± 1.2) mg/L of CRP in control group, which were positively correlated with HOMA-IR (r = 0.411, 0.529, 0.308, all P < 0.05). In late pregnancy, the level of adiponectin (3.9 ± 2.2) mg/L in the GDM group was significantly lower than (6.6 ± 2.7) mg/L in control group, and the level of adiponectin was negatively correlated with HOMA-IR (r = -0.344, P < 0.05). The levels of (37 ± 13) µg/L of leptin, (12.7 ± 2.6) ng/L of TNF-α and (6.7 ± 3.6) mg/L of CRP in the GDM group were significantly higher than (30 ± 13) µg/L of leptin, (5.8 ± 2.1) ng/L of TNF-α, (4.4 ± 3.1) mg/L of CRP in control group, which were positively correlated with HOMA-IR (r = 0.414, 0.487, 0.285, all P < 0.05). Multiple linear regression analysis showed that the level of TNF-α at early and late pregnancy was most correlated with HOMA-IR (r = 0.390, 0.284, all P < 0.05). (2) The level of the cytokines and HOMA-IR in puerperium: at day 3 of postpartum, the level of adiponectin of (3.3 ± 1.1) mg/L in the GDM group was significantly lower than (6.2 ± 1.5) mg/L in control group, which was negatively correlated with HOMA-IR (r = -0.283, P < 0.05). The levels of (31 ± 13) µg/L of leptin, (10.1 ± 5.7) ng/L of TNF-α and (35.1 ± 6.5) mg/L of CRP in the GDM group were significantly higher than (21 ± 15) µg/L of leptin, (5.6 ± 3.0) ng/L of TNF-α, (30.5 ± 8.5) mg/L of CRP in control group. And leptin and TNF-α levels were positively correlated with HOMA-IR (r = 0.372, 0.494, all P < 0.05). At day 42 of postpartum, the level of adiponectin in GDM group was negatively correlated with HOMA-IR (r = -0.299, P < 0.05), and the levels of leptin and TNF-α were positively correlated with HOMA-IR (r = 0.401, 0.442, all P < 0.05). Multiple linear regression analysis showed that the level of TNF-α at day 3 and day 42 was most correlated with HOMA-IR (r = 0.363, 0.274, all P < 0.05). (3) ROC analysis of data from early pregnancy showed that the threshold for TNF-α to predict GDM was 5.45 ng/L.. TNF-α might be the index to predict GDM and evaluate prognosis.

Topics: Adiponectin; Blood Glucose; C-Reactive Protein; Case-Control Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Postpartum Period; Predictive Value of Tests; Pregnancy; ROC Curve; Tumor Necrosis Factor-alpha

Several previous studies have investigated circulating levels of the adipokine leptin in relation to gestational diabetes mellitus (GDM). However, these studies have yielded markedly conflicting results, including increased, decreased, and unchanged leptin levels in women with GDM as compared with their peers.. We sought to evaluate the metabolic determinants of serum leptin in a well-characterized cohort reflecting the full spectrum of glucose intolerance in pregnancy.. Metabolic characterization, including oral glucose tolerance test (OGTT) and measurement of serum leptin, insulin, lipids, adiponectin, and C-reactive protein, was performed in 817 pregnant women. The OGTT identified 198 women with GDM, 142 with gestational impaired glucose tolerance, and 477 with normal glucose tolerance.. Median leptin (ng/ml) did not differ between the normal glucose tolerance (33.7), gestational impaired glucose tolerance (36.3), and GDM (36.4) groups (P = 0.085). On univariate correlation analysis, leptin was most strongly associated with prepregnancy body mass index (BMI) (r = 0.54, P < 0.0001), fasting insulin (r = 0.60, P < 0.0001), and C-reactive protein (r = 0.38, P < 0.0001) but only weakly associated with area under the glucose curve (AUC(glucose)) on the OGTT (r = 0.10, P = 0.0066). On multiple linear regression analysis, the strongest independent determinant of leptin was prepregnancy BMI (t = 11.55, P < 0.0001), whereas AUC(glucose) was not a significant predictor (t = -0.95, P = 0.34). Furthermore, although its respective associations with fasting insulin, triglycerides, and adiponectin varied across tertiles of prepregnancy BMI, leptin was not significantly associated with AUC(glucose) in any BMI tertile.. Pregravid BMI, rather than gestational glucose tolerance, is the primary determinant of serum leptin concentration in pregnancy.

Topics: Adiponectin; Adult; Blood Glucose; Body Weight; C-Reactive Protein; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Lipids; Pregnancy

To determine the extent to which known prenatal and perinatal predictors of childhood obesity also predict weight gain in early infancy.. We studied 690 infants participating in the prospective cohort Project Viva. We measured length and weight at birth and at 6 months. Using multivariable linear regression, we examined relationships of selected maternal and infant factors with change in weight-for-length z-score (WFL-z) from 0 to 6 months.. Mean (standard deviation) change in WFL-z from 0 to 6 months was 0.23 (1.11), which translates to 4500 grams gained from birth to 6 months of life in an infant with average birth weight and length. After adjustment for confounding variables and birth weight-for-gestational age z-score (-0.28 [95% confidence interval, -0.37, -0.19] per unit), cord blood leptin (-0.40 [95%confidence interval, -0.61, -0.19] per 10 ng/mL), and gestational diabetes -0.50 [95%confidence interval, -0.88, -0.11] versus normal glucose tolerance)were each associated with slower gain in WFL-z from 0 to 6 months.. Higher neonatal leptin and gestational diabetes predicted slower weight gain in the first 6 months of life. The hormonal milieu of the intrauterine environment may determine growth patterns in early infancy and thus later obesity.

Topics: Biomarkers; Blood Glucose; Body Height; Body Mass Index; Child Development; Cohort Studies; Confidence Intervals; Diabetes, Gestational; Female; Fetal Blood; Follow-Up Studies; Gestational Age; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant; Infant, Newborn; Leptin; Male; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Pregnancy; Prospective Studies; Regression Analysis; Sensitivity and Specificity; Time Factors; Weight Gain

There is conflicting data regarding leptin in gestational diabetes mellitus (GDM). The aim of the present study was to compare serum leptin levels between individuals with GDM and normal pregnancy.. This case-control study was performed on 26 GDM and 22 healthy pregnant women. Leptin concentrations were measured using an enzyme immunoassay.. The level of serum leptin was not significantly different between GDM (9.890 ± 7.764 ng/ml) and normal pregnant women (13.80 ± 10.32 ng/ml) (p = 0.14).. There are no significant differences between GDM and normal pregnant women regarding leptin levels.

Topics: Adult; Body Mass Index; Case-Control Studies; Diabetes, Gestational; Female; Humans; Iran; Leptin; Pregnancy; Statistics, Nonparametric; Young Adult

Recent studies have provided evidence that intrauterine exposure to maternal diabetes has lifelong effects on adult offspring, including increased risks of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to assess the relationship between exposure to maternal diabetes in utero and cardiovascular risk factors in healthy children and to investigate whether these associations are independent of maternal prepregnancy BMI and offspring attained BMI.. Data were from a retrospective cohort of children aged 6-13 years born during 1994-2002. Multiple linear regression was used to examine the associations between exposure and cardiovascular risk factors with adjustment for demographic factors and pubertal stage and additionally for maternal prepregnancy BMI and offspring attained BMI.. Ninety-nine offspring of diabetic pregnancies had significantly increased E-selectin, vascular adhesion molecule 1 (VCAM1), leptin, waist circumference, BMI and systolic blood pressure and decreased adiponectin levels compared with 422 offspring of non-diabetic pregnancies after adjustment for age, sex and race/ethnicity (p < 0.05 for each risk factor). Additional adjustment for maternal prepregnancy BMI substantially attenuated group differences in the risk factors except for E-selectin, VCAM1 and waist circumference, which remained significantly higher in exposed children.. Compared with unexposed children, healthy offspring exposed to maternal diabetes in utero have a worse cardiovascular risk profile. In particular, offspring have substantially increased levels of circulating cellular adhesion molecules, which are biomarkers of adverse endothelium perturbation and may be related to the earliest preclinical stages of atherosclerosis and diabetes.

Topics: Adiponectin; Adolescent; Amine Oxidase (Copper-Containing); Cardiovascular Diseases; Cell Adhesion Molecules; Child; Diabetes, Gestational; E-Selectin; Female; Humans; Leptin; Linear Models; Male; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Waist Circumference

Improved glycaemic control during pregnancy in mothers with type 1 diabetes (T1DM) and gestational diabetes (GDM) has resulted in a marked reduction of perinatal mortality and morbidity, but the prevalence of macrosomia is usually high.. We used non-invasive anthropometric methods to estimate the body composition and the thickness of the interventricular heart septum in 18 infants of mothers with well-controlled T1DM, 10 infants of mothers with GDM and 28 infants of healthy control mothers matched for gestational age and mode of delivery.. Skinfold measurements were obtained with a Harpenden calliper within 48 h after delivery. Echocardiography was also performed to measure the thickness of the interventricular septum. Cord blood was sampled for assays of C-peptide, leptin and IGF-I.. The rates of macrosomia (gestational age-adjusted birth weight >2 standard deviation score, SDS) were 56 and 30% in infants of mothers with T1DM and GDM, respectively, compared to 10% in control infants. The body fat content was 40% (0.2 kg) higher and the interventricular heart septum thickness was increased by 20% in both groups of infants of diabetic mothers. We found no associations between maternal levels of HbA1c during pregnancy and body composition or interventricular heart septum thickness. Cord levels of C-peptide and leptin were significantly higher in infants of T1DM mothers than in control infants. Cord leptin level was associated with birth weight SDS and percent body fat in infants of T1DM mothers. IGF-I was associated with percent body fat in infants of GDM mothers and control mothers. A multiple-regression analysis showed that 50% of the variation in body weight SDS could be determined, with IGF-I, leptin and C-peptide as independent variables.. Both fat mass and cardiac septal thickness are increased in newborn infants of women with T1DM and GDM in spite of efforts to achieve good glycaemic control during pregnancy.

Topics: Adipose Tissue; Adult; Blood Glucose; Body Composition; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Macrosomia; Glycated Hemoglobin; Heart Septum; Humans; Hypertrophy; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Pregnancy; Prevalence; Regression Analysis

Pregnancy in the diabetic woman has long been associated with an increased risk of cognitive deficit in the offspring, which might be associated with the poor intrauterine environment for the developing fetal brain. Leptin, as an important hormone regulating the intrauterine and early extrauterine life growth and development, greatly elevated during diabetic pregnancy. The current results indicate that leptin exerts neurotrophic actions during the critical period of development of hippocampus, and acts as a cognitive enhancer. Leptin resistance was a common phenomenon in diabetic pregnancies resulting reduced leptin receptors and signaling. With sudden withdrawal of placenta-derived leptin after birth, neonatal leptin levels declined sharply. The declined leptin could not work normally with the reduced leptin receptor and thus affected the newborn's brain development, which at least partly accounted for later cognitive deficits of offspring of GDM mother. Our hypothesis provides an alternative strategy to decrease the risk of cognitive deficit of offspring of diabetic mother, by exogenously supplementing leptin after birth for some period.

Topics: Child; Cognition Disorders; Diabetes, Gestational; Female; Humans; Leptin; Pregnancy

To explore the relationships between serum levels of adiponectin, leptin, TNF-alpha and CRP (c-reactive protein) versus insulin resistance in early pregnancy.. A total of 342 pregnant women delivering at our hospital were recruited from October 2007 to July 2008. Their clinical data were collected and analyzed. According to the 50-g 1-hour oral glucose screening test, they were divided into 3 groups: gestational diabetes, gestational impaired glucose tolerance and normal pregnancy. The serum levels of adiponectin, leptin, TNF-alpha and CRP were determined by ELISA (enzyme-linked immunosorbent assay) and multivariate correlation analysis was used to analyze their relationships with the indices of insulin resistance.. Among them, there were gestational diabetes (n = 13) and gestational impaired glucose tolerance (n = 19). Thirty-five normal pregnant women were selected as the control group. The result of analysis of variance indicted that adiponectin, leptin and TNF-alpha had significant statistical differences among three groups. Through the multivariate correlation analysis, adiponectin had a adverse correlation with the indices of insulin resistance. Leptin, CRP, TNF-alpha and BMI (body mass index) had positive correlations with the indices of insulin resistance.. Adiponectin, leptin, TNF-alpha and CRP are correlated with the indices of insulin resistance. And TNF-alpha may become an important predictor of gestational diabetes in early pregnancy.

Topics: Adiponectin; Adult; C-Reactive Protein; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Pregnancy; Pregnancy Trimester, First; Tumor Necrosis Factor-alpha

The aim of this study was to compare pregnant women with and without gestational diabetes (GDM) with regard to third trimester adiponectin, leptin and insulin resistance, as well as to investigate their relation to fetal growth and macrosomia. 134 pregnant women were enrolled in the study: 86 with GDM and 48 controls. Maternal plasma adiponectin, leptin, fasting insulin, glucose and fetal biometry were measured between 27 and 32 weeks of gestation. Birthweight and delivery data were also assessed. Adiponectin in GDM patients was lower when compared to non-diabetic women while mean leptin concentration was not different. In GDM group only mothers' weight gain until third trimester was significantly different between the groups of patients with normal and accelerated fetal growth. No correlation of adiponectin and leptin with fetal growth was shown. Mothers' weight gain until third trimester and mean fasting glucose between 33 and 34 weeks of gestation were associated with neonatal macrosomia. There were no differences in adiponectin and leptin between mothers of macrosomic and non-macrosomic neonates. Fetal growth seems not to be related to third trimester adiponectin and leptin concentrations, while increased third trimester fasting glucose may be an independent risk factor of macrosomia.

Topics: Adiponectin; Adult; Blood Glucose; Diabetes, Gestational; Female; Humans; Insulin; Leptin; Pregnancy; Pregnancy Trimester, Third

Women with gestational diabetes mellitus (GDM) have an enhanced cardiovascular risk factor profile at 3-months postpartum and an elevated risk of future cardiovascular disease, as compared to their peers. Recently, it has emerged that even mild dysglycemia on antepartum oral glucose tolerance test (OGTT) predicts an increased risk of future cardiovascular disease, although it is not known whether there exists an identifiable high-risk subgroup within this patient population. Since gestational impaired glucose tolerance (GIGT) due to isolated hyperglycemia at 1-h during the OGTT (1-h GIGT) bears metabolic similarity to GDM, we hypothesized that, like GDM, 1-h GIGT may predict a high-risk postpartum cardiovascular phenotype.. In this prospective cohort study, 485 women underwent antepartum OGTT, followed by cardiovascular risk factor assessment at 3-months postpartum. The antepartum OGTT identified 4 gestational glucose tolerance groups: GDM (n = 137); 1-h GIGT (n = 39); GIGT at 2- or 3-h (2/3-h GIGT)(n = 50); and normal glucose tolerance (NGT)(n = 259). After adjustment for age, ethnicity, breastfeeding and waist circumference, mean levels of the following cardiovascular risk factors progressively increased from NGT to 2/3-h GIGT to 1-h GIGT to GDM: LDL cholesterol (p = 0.0026); total cholesterol:HDL (p = 0.0030); apolipoprotein B (p = 0.004); apolipoprotein B:apolipoprotein A1 (p = 0.026); leptin (p = 0.018); and C-reactive protein (p = 0.011).. Amongst women without GDM, 1-h GIGT predicts an enhanced postpartum cardiovascular risk factor profile. It thus emerges, that amongst young women with mild dysglycemia in pregnancy, those with 1-h GIGT may comprise an unrecognized patient population at risk for future cardiovascular disease.

Topics: Adult; Apolipoproteins B; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperglycemia; Leptin; Postpartum Period; Pregnancy; Prospective Studies; Risk Factors

To determine the concentrations of adipocyte fatty acid-binding protein (AFABP) and other adipocytokines in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) and of control subjects and to relate them to indexes of insulin sensitivity.. In 86 control and 98 GDM pregnant women, venous blood was collected before vaginal delivery and arterial blood from cord immediately after delivery. Serum insulin and adipocytokines were measured by enzyme-linked immunosorbent assay (ELISA).. GDM women had higher prepregnancy BMI, and data were adjusted for it. Maternal serum insulin, insulin-to-glucose ratio, homeostasis model assessment (HOMA), AFABP, and retinol-binding protein 4 (RBP4) were higher and adiponectin was lower in GDM than in control subjects, whereas serum glucose, insulin, insulin-to-glucose ratio, HOMA, nonesterified fatty acids, and RBP4 were higher and glycerol, AFABP, and adiponectin were lower in cord blood serum of GDM than of control subjects. AFABP and adiponectin in cord serum of control subjects were higher than in maternal serum; in GDM women no difference was found for AFABP in cord versus maternal serum, although adiponectin remained higher in cord. Values of leptin in both groups were lower in cord than in maternal serum, and those of RBP4 were lower in only GDM women.. It is suggested that fetal tissues are the main source of cord arterial serum AFABP, and in GDM fetuses AFABP values correlate with adiposity markers. A downregulation of adiponectin and upregulation of RBP4 in GDM mothers and their fetuses may be related to their insulin-resistant condition, whereas changes in AFABP do not seem to be related.

Topics: Adipokines; Adiponectin; Adult; Diabetes, Gestational; Enzyme-Linked Immunosorbent Assay; Fatty Acid-Binding Proteins; Female; Fetal Blood; Humans; Insulin; Leptin; Pregnancy

The aim of this study was to evaluate fasting serum leptin concentration and its relation to insulin resistance in women with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (IGT).. This case-control study, at 28 weeks of gestation, measured serum concentration of fasting leptin, insulin, and homeostatic model assessment index in three groups, GDM, IGT, and normal control, and compared them with each other.. The serum leptin level was significantly higher in women with GDM than in the two other groups (p=0.03). In women with GDM and IGT, leptin was significantly positively related with insulin and homeostatic model assessment index (r=0.221, p=0.03) and (r=0.246, p=0.03), respectively. In all of the participants, there was a significant correlation between leptin and body mass index before pregnancy (r=0.416, p=0.001).. Our data showed that serum leptin level was higher in GDM and had a positive correlation with insulin resistance. Our findings suggest that high leptin levels might be a risk factor for GDM and IGT in pregnant women.

Topics: Adult; Body Mass Index; Case-Control Studies; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Leptin; Pregnancy; Young Adult

We undertook this study to assess the relationship between circulating adipokines and insulin resistance during pregnancy and postpartum in women with gestational diabetes mellitus (GDM).. This was a prospective study including 60 women with GDM and 60 subjects with normal gestation who were evaluated at gestational week 30, 6 weeks and 6 months postpartum. Circulating adipokines that were evaluated during the study were leptin, adiponectin, retinol-binding protein-4 (RBP4), and tumor necrosis factor-alpha (TNF-α).. Women with GDM showed higher insulin resistance measured by HOMA-IR than subjects with normal gestation (2.3 ± 2.3 vs. 1.3 ± 0.95). There was no difference between groups in adipokines; however, in women with a healthy pregnancy, RBP4 was associated with insulin resistance (r = 0.47, p <0.05). At 6 weeks and 6 months postpartum, women with previous GDM exhibited persistent elevated leptin and insulin resistance. RBP4 was associated with insulin resistance only in women with a previous healthy pregnancy (r = 0.51, p <0.05). In addition, progressively impaired glucose tolerance was observed after delivery in women with previous GDM.. It was demonstrated that GDM is associated with greater insulin resistance than observed in normal pregnancy; however, adipokines are similar in both groups. RBP4 levels are significantly associated with insulin resistance in healthy women during pregnancy and postpartum. After a pregnancy complicated by GDM, leptin and insulin resistance remain elevated and glucose tolerance worsens.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Postpartum Period; Pregnancy; Prospective Studies; Retinol-Binding Proteins, Plasma; Tumor Necrosis Factor-alpha

This study addressed the hypothesis that placental endothelial lipase (EL) expression is affected by pregnancies complicated by obesity and gestational diabetes mellitus (GDM).. EL expression in placental tissues from pregnancies complicated by obesity, GDM, or obesity combined with GDM (obese-GDM) was analyzed by quantitative RT-PCR. Moreover, primary placental cells were isolated and treated with insulin, glucose, leptin, or tumor necrosis factor (TNF)-α, and EL expression was measured. Inhibitors of nuclear factor (NF)-κB or mitogen-activated protein kinase (MAPK) signaling were used to detect potential pathways of EL regulation in primary placental endothelial cells (ECs).. In placentas from obese-GDM pregnancies, EL expression was upregulated by 1.9-fold (P < 0.05) compared with lean pregnancies, whereas obesity or GDM alone had no significant effect. Analyses of metabolic parameters in maternal venous and umbilical venous plasma revealed significantly increased insulin and leptin as well as slightly increased glucose and TNF-α values in the obese and obese-GDM groups. Cell culture experiments identified TNF-α and leptin, but not glucose or insulin, as regulators of EL expression in ECs. Induction of EL expression by these mediators occurred in a para/endocrine manner, since only leptin and TNF-α receptors, but not the cytokines themselves, were expressed in ECs. Inhibitor experiments suggested that TNF-α and leptin-mediated upregulation of EL may occur via two different routes. Whereas TNF-α induced EL upregulation in ECs by activation of the NF-κB pathway, leptin did not stimulate NF-κB or MAPK signaling pathways in these cells.. Metabolic inflammation with high leptin and locally increased TNF-α concentrations at the fetal-placental interface regulates placental EL expression.

Topics: Adult; Cells, Cultured; Diabetes, Gestational; Endothelial Cells; Female; Gene Expression Profiling; Gene Expression Regulation; Humans; Leptin; Lipase; Obesity; Placenta; Pregnancy; Protein Array Analysis; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Tumor Necrosis Factor-alpha; Up-Regulation; Young Adult

Maternal diabetes is a common complication of pregnancy, and the offspring of diabetic mothers have a higher risk of developing obesity and type 2 diabetes later in life. Despite these observations, the precise biological processes mediating this metabolic programming are not well understood. Here, we explored the consequences of maternal diabetes on the organization of hypothalamic neural circuits involved in the regulation of energy balance. To accomplish this aim, we used a mouse model of maternal insulin deficiency induced by streptozotocin injections. Maternal diabetes was found to be associated with changes in offspring growth as revealed by a significantly higher pre- and postweaning body weight in the offspring of insulin-deficient dams relative to those of control mice. Mice born to diabetic dams also showed increased fasting glucose levels, increased insulin levels, and increased food intake during their adult lives. These impairments in metabolic regulation were associated with leptin resistance during adulthood. Importantly, the ability of leptin to activate intracellular signaling in arcuate neurons was also significantly reduced in neonates born to diabetic dams. Furthermore, neural projections from the arcuate nucleus to the paraventricular nucleus were markedly reduced in the offspring of insulin-deficient dams. Together, these data show that insulin deficiency during gestation has long-term consequences for metabolic regulation. They also indicate that animals born to diabetic dams display abnormally organized hypothalamic feeding pathways that could result from the attenuated responsiveness of hypothalamic neurons to the neurotrophic actions of leptin during neonatal development.

Topics: Adipose Tissue; Animals; Diabetes Mellitus, Type 2; Diabetes, Gestational; Eating; Female; Hypothalamus; Insulin; Leptin; Maternal Nutritional Physiological Phenomena; Mice; Nerve Net; Neurons; Obesity; Phosphorylation; Pregnancy; STAT3 Transcription Factor

Topics: Animals; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Hypothalamus; Leptin; Maternal Nutritional Physiological Phenomena; Nerve Net; Neurons; Pregnancy

To evaluate whether serum RBP4 correlates with gestational diabetes mellitus (GDM) in a cohort of borderline obese (BMI>30) pregnant women.. Serum RBP4 and retinol were measured in pregnant women with (n=12) and without (n=10) GDM.. RBP4, retinol and RBP4:retinol molar ratio were not different between the groups and were not associated with markers of insulin resistance.. GDM is not associated with RBP4 or retinol among borderline obese pregnant women.

Topics: Adult; Animals; Blood Glucose; Diabetes, Gestational; Female; Humans; Insulin; Leptin; Obesity; Pregnancy; Retinol-Binding Proteins, Plasma; Vitamin A; Young Adult

To identify factors associated with declining beta-cell compensation for insulin resistance.. In a cohort of Hispanic women with recent gestational diabetes mellitus, oral glucose tolerance tests (OGTTs), intravenous glucose tolerance tests (IVGTTs), and bioelectrical impedance measurements were performed at 15-month intervals for up to 5 years, or until fasting plasma glucose exceeded 140 mg/dl (7.8 mmol/l). Data were analyzed to identify predictors of declining beta-cell compensation for insulin resistance (the disposition index [DI]) and to examine the mechanism of weight gain and changes in circulating levels of selected adipokines and inflammatory markers on beta-cell compensation decline.. A total of 60 nondiabetic women had a median of four sets of OGTT + IVGTT during a median follow-up of 52 months. Fourteen of the women developed diabetes. None of the baseline characteristics were significantly predictive of a decline in DI. There were significant univariate associations between declining DI and weight gain (specifically fat gain), declining adiponectin and rising C-reactive protein. Multivariate analysis showed that the weight gain was the most significant factor associated with declining DI. The amount of association between weight gain and declining DI was explained 31% by changes in adiponectin and C-reactive protein and 40% by changes in insulin resistance.. These results identify weight gain as the strongest factor associated with declining beta-cell compensation for insulin resistance in Hispanic women at high risk for type 2 diabetes. Such effect may be mediated through at least two effects: alterations in adipokine levels and increasing insulin resistance.

Topics: Adiponectin; Adipose Tissue; Adult; Body Weight; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Diabetes, Gestational; Electric Impedance; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Insulin-Secreting Cells; Leptin; Pregnancy; Triglycerides

The postpartum phase following gestational diabetes (GDM) is characterised by subtle metabolic defects, including the beta cell dysfunction that is believed to mediate the increased future risk of type 2 diabetes in this patient population. Low circulating levels of adiponectin and increased leptin and C-reactive protein (CRP) have recently emerged as novel diabetic risk factors, although their relevance to GDM and subsequent diabetes has not been characterised. Thus, we sought to determine whether adiponectin, leptin and CRP levels during pregnancy relate to the postpartum metabolic defects linking GDM with type 2 diabetes.. Metabolic characterisation, including oral glucose tolerance testing, was undertaken in 487 women during pregnancy and at 3 months postpartum. Based on the antepartum OGTT, there were 137 women with GDM, 91 with gestational impaired glucose tolerance and 259 with normal glucose tolerance.. Adiponectin levels were lowest (p < 0.0001) and CRP levels highest (p = 0.0008) in women with GDM. Leptin did not differ between the glucose tolerance groups (p = 0.4483). Adiponectin (r = 0.41, p < 0.0001), leptin (r = -0.36, p < 0.0001) and CRP (r = -0.30, p < 0.0001) during pregnancy were all associated with postpartum insulin sensitivity (determined using the insulin sensitivity index of Matsuda and DeFronzo [IS(OGTT)]). Intriguingly, adiponectin levels were also related to postpartum beta cell function (insulinogenic index/HOMA of insulin resistance; r = 0.16, p = 0.0009). Indeed, on multiple linear regression analyses, adiponectin levels during pregnancy independently predicted both postpartum insulin sensitivity (t = 3.97, p < 0.0001) and beta cell function (t = 2.37, p = 0.0181), even after adjustment for GDM. Furthermore, adiponectin emerged as a significant negative independent determinant of postpartum fasting glucose (t = -3.01, p = 0.0027).. Hypoadiponectinaemia during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia, and hence may be relevant to the pathophysiology relating GDM with type 2 diabetes.

Topics: Adiponectin; Adult; Blood Glucose; Breast Feeding; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetes, Gestational; Ethnicity; Female; Glucose Tolerance Test; Humans; Insulin Resistance; Insulin-Secreting Cells; Leptin; Parity; Postpartum Period; Pregnancy; Racial Groups; Risk Factors; Weight Gain

The aim of the study was to compare the regulation of ghrelin, leptin, and adiponectin by insulin and glucose during the second and third trimesters of pregnancy in women with diabetes. We studied 9 pregnant women with diabetes. All women were treated with insulin and omitted the morning dose on the day of the test. After collection of baseline fasting samples, we performed 3 successive glucose clamps: 2 euglycemic clamps (glucose, 5 mmol/L; insulin infusion at 20 and 40 mU m(-2) min(-1)) and 1 hyperglycemic clamp (glucose, 10 mmol/L; insulin infusion at 40 mU m(-2) min(-1)). We determined concentrations of acyl and desacyl ghrelin (using a double-antibody sandwich assay that recognizes the full-length molecule), leptin, and adiponectin. Fasting desacyl ghrelin concentrations decreased, whereas insulin and leptin concentrations increased, between the second and third trimesters of pregnancy (P < or = .011). During the clamp studies, desacyl ghrelin concentrations decreased by 33% (second trimester, P = .004) and 27% (third trimester, P = .09) with increasing glucose and insulin concentrations, whereas acyl ghrelin, leptin, and adiponectin concentrations were unaffected. Glucose and insulin regulate desacyl ghrelin concentrations in pregnant women with diabetes. Impaired desacyl ghrelin regulation may affect energy metabolism in pregnant women with poorly controlled diabetes.

Topics: Adiponectin; Adult; Blood Glucose; Diabetes, Gestational; Female; Ghrelin; Glucose; Glucose Clamp Technique; Humans; Hypoglycemic Agents; Insulin; Leptin; Pregnancy

Whether the placenta contributes to some of the abnormal hormonal profiles in gestational diabetes mellitus (GDM) pregnancies and whether GDM affects placental endocrine signaling pathways are yet to be established. The objective of this study was to investigate differences in the expression of the placental steroid and peptide hormone synthesis-related factors, enzymes and their receptors between normal and GDM pregnancies. Nine term placentae from GDM pregnancies and twelve from healthy pregnancies were collected. The results of immunohistochemistry, Western blotting and semiquantitative RT-PCR indicated that mRNA and protein levels of leptin, leptin receptors, androgen receptor and FGF2 were significantly higher in the GDM placentae than non-GDM placentae; while NRIH3, NRIH2, StARD3, CYP11A1, HSD3B, HSD11B, HSD17B, ERalpha, ERbeta, progesterone receptor, FGF receptor-2, insulin receptor-alpha and -beta showed no differences. Interestingly, Western blotting and immunohistochemistry revealed that aromatase protein concentrations in the GDM placentae were significantly reduced without a change in mRNA levels. Moreover, androgen upregulated FGF2 expression in the placental villous explants. These findings suggest that the placentae of GDM pregnancies contribute to elevated testosterone and leptin levels due to a decrease in the conversion of testosterone to estrogens and to an increase in leptin production. The androgen and leptin signaling pathways may be over-activated by the presence of excessive ligands and overexpressed receptors in GDM placentae. Dysregulation of these two endocrine networks may contribute to placental abnormalities eventually increasing the frequency of maternal and fetal complications associated with GDM.

Topics: Androgens; Diabetes, Gestational; Dihydrotestosterone; Female; Fibroblast Growth Factor 2; Humans; Leptin; Placenta; Pregnancy; Receptors, Androgen; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Testosterone

Maternal insulin sensitivity have strong correlation with fetal growth. The dysregulation of adiponectin and leptin is found in insulin resistance. The aim of this study was to determine whether there is an association between ultrasound fetal biometry and the maternal plasma cytokines and insulin concentrations at the beginning of gestational diabetes treatment.. 121 women with gestational diabetes diagnosed between 26th and 30th weeks, were included to the study. Plasma levels of adiponectin, leptin, insulin and glucose were quantified with the measurements and percentiles of the biparietal diameter, head circumference and abdominal circumference , estimated fetal weight and the actual birthweight.. Associations between both of the adipokines and fetal biometry measurements were not evident. There were also no differences in their serum concentrations between groups of women with and without accelerated fetal growth . Adiponectin negatively correlated with pre-pregnancy BMI (r=-0.366, p=0.01). Leptin positively correlated with pre - pregnancy BMI (r=0.42, p=0.002), fasting insulin (r=0.51, p=0.0006) and HOMA-IR (r=0.43, p=0.005). No association was found between adiponectin, leptin, fasting insulin, HOMA-IR and neonatal birth weight or birth weight percentile.. The results of this study imply that adiponectin, leptin and insulin maternal plasma concentrations in the third trimester do not have influence on fetal growth in gestational diabetes.

Topics: Adiponectin; Blood Glucose; Diabetes, Gestational; Female; Fetal Development; Fetal Weight; Humans; Insulin; Insulin Resistance; Leptin; Pregnancy

The purpose of the study was to clarify the alterations in serum leptin and soluble leptin receptor levels at term and early postpartum in gestational diabetes mellitus (GDM). Twenty women with normal pregnancy and 20 with GDM were recruited and blood samples were taken on the day of delivery and Days 1, 3 and 5 after delivery. Serum leptin levels were significantly higher in women with GDM than in the controls before delivery and decreased significantly after delivery (p < 0.001). After delivery there were no significant differences in serum leptin concentrations between women with GDM and the controls. Serum soluble leptin receptor concentrations did not differ neither between the two groups, nor before or after delivery. Leptin may play a role in GDM through a positive correlation with insulin resistance.

Topics: Adult; Analysis of Variance; Biomarkers; Blood Glucose; Cross-Sectional Studies; Diabetes, Gestational; Female; Follow-Up Studies; Gestational Age; Humans; Leptin; Peripartum Period; Pregnancy; Receptors, Leptin; Reference Values; Sensitivity and Specificity; Solubility; Term Birth; Time Factors; Young Adult

Adipocyte fatty acid binding protein (AFABP) was recently introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In the current study, we investigated serum concentrations of AFABP in patients with gestational diabetes mellitus (GDM) as compared with healthy pregnant controls matched for gestational age and fasting insulin.. AFABP was determined by ELISA in controls (n=80) and GDM patients (n=40) and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation, in both groups.. Median serum AFABP concentrations were significantly elevated in subjects with GDM (22.9 microg/l) as compared with healthy pregnant controls (18.3 microg/l; P<0.05). Furthermore, GDM was independently associated with AFABP concentrations in multiple regression analysis (P<0.05). In addition, markers of adiposity (body mass index, serum leptin), triglycerides and serum creatinine were independently associated with circulating AFABP (P<0.05).. Maternal AFABP concentrations are significantly increased in GDM. The adipokine might contribute to the increased metabolic and cardiovascular risk of the disease.

Topics: Adiponectin; Adolescent; Adult; C-Reactive Protein; Cholesterol; Creatinine; Diabetes, Gestational; Fatty Acid-Binding Proteins; Female; Humans; Insulin; Leptin; Linear Models; Middle Aged; Multivariate Analysis; Pregnancy; Resistin; Triglycerides; Young Adult

Acylated (octanoylated) ghrelin stimulates food intake and growth hormone secretion and is deacylated into desacyl ghrelin by butyrylcholinesterase. Acylated and desacyl ghrelin both promote adipogenesis. Ghrelin concentrations decrease with hyperglycemia and hyperinsulinism. We hypothesized that 1) acylated ghrelin increases during pregnancy, contributing positively to energy balance, but is lower in women with gestational diabetes and 2) butyrylcholinesterase activity is inversely correlated with acylated ghrelin concentrations. In a first group of subjects, using two-site sandwich ghrelin assays that specifically detect full-length forms, we investigated women with and without gestational diabetes (n = 14/group) during pregnancy and after delivery. We examined whether changes in ghrelin during a test meal were correlated with changes in pituitary growth hormone [assessed through calculation of the area under the curve (AUC) during the test meal]. In postpartum subjects, the percent of total ghrelin that is acylated was four to five times higher than previously observed using single antibody assays. During pregnancy, acylated ghrelin concentrations (mean +/- SE) were lower compared with the postpartum period throughout the meal (AUC 1.2 +/- 0.2 vs. 10.2 +/- 1.9 ng.ml(-1).90 min(-1), P < 0.001). In the postpartum, acylated ghrelin and growth hormone were positively correlated (r = 0.50, P = 0.007). Desacyl (but not acylated) ghrelin was increased in subjects with gestational diabetes during and after pregnancy (AUC 15.4 +/- 1.9 vs. 8.6 +/- 1.2 ng.ml(-1).90 min(-1), P = 0.005). In a second group of subjects (n = 13), acylated ghrelin was similarly suppressed during pregnancy. Circulating octanoate concentrations (3.1 +/- 0.5 vs. 4.5 +/- 0.6 microg/ml, P = 0.029) and cholinesterase activity (705 +/- 33 vs. 1,013 +/- 56 U/ml, P < 0.001) were lower during pregnancy compared with the postpartum period. In conclusion, acylated ghrelin markedly decreases during pregnancy, likely because of a decrease in the acylation process. Desacyl ghrelin increases in gestational diabetes, possibly reflecting resistance to the inhibitory effect of insulin on ghrelin secretion.

Topics: Acylation; Adiponectin; Adult; Blood Glucose; Cholinesterases; Diabetes, Gestational; Enzyme-Linked Immunosorbent Assay; Female; Ghrelin; Human Growth Hormone; Humans; Infant, Newborn; Insulin; Leptin; Postpartum Period; Pregnancy; Pregnancy Trimester, Third; Prospective Studies

Topics: Bone Density; Bone Diseases; Collagen; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Fractures, Bone; Homeostasis; Humans; Hypoglycemic Agents; Leptin; Metformin; Osteoporosis; Pregnancy; Thiazolidinediones

Gestational diabetes mellitus (GDM) is glucose intolerance diagnosed during pregnancy. Previous work suggested that women with GDM showed exaggerated preferences for sweet taste, but data were limited to a single time point during pregnancy. This study longitudinally assessed sweet taste changes across pregnancy in women who developed GDM (n = 15) as compared with women with normal glucose tolerance (NGT; n = 93) and nonpregnant controls (n = 19). A second objective was to relate sweet taste changes in GDM to fasting leptin and insulin profiles. Following an overnight fast, subjects evaluated strawberry-flavored milks varying in sucrose and fat content, as well as glucose solutions. Evaluations were made at 3 time points during pregnancy and during early postpartum. At 34-38 weeks gestation, women with GDM gave higher liking ratings to moderately sweetened (5% and 10% sucrose) strawberry milks than women with NGT. These differences were not related to alterations in the perception of the samples. At 24-28 weeks gestation, and in women with GDM only, fasting insulin was correlated with liking of the glucose solutions (R(2) = 0.63, P = 0.004) and fasting leptin was correlated with sweetness liking of the 10% sucrose milk (R(2) = 0.42, P = 0.017). These data suggest that women with GDM exhibit higher liking ratings for a sweet fat milk drink late in pregnancy. Also, higher hedonic ratings for sweet taste in GDM may be related to elevated leptin and insulin concentrations at midpregnancy. GDM may increase the desire for sweet taste that could influence dietary management of this disease.

Topics: Adolescent; Adult; Diabetes, Gestational; Fasting; Female; Humans; Insulin; Leptin; Middle Aged; Pregnancy; Prospective Studies; Taste Perception; Young Adult

It is generally accepted that the metabolic effects of leptin are diminished in the obese due to leptin resistance. Hormone resistance may develop if diurnal (including meal-related) changes in hormone levels are disrupted. We sought to describe leptin changes after a 75 g oral glucose tolerance test (OGTT) in women with a prior diagnosis of gestational diabetes mellitus (a high risk group for the metabolic syndrome) compared to that in healthy controls.. In 2000 a retrospective cohort study was performed on women who had been diagnosed with gestational diabetes mellitus (WHO criteria 1985, n = 57) between 1996 and 1998 and on a healthy control female group (n = 36) all of whom had had a prior pregnancy without any diagnosis of diabetes. All the women underwent a standard 75 g OGTT. Serum leptin was measured by radioimmunoassay before and 90 min after the OGTT.. Using multilevel models of change, fasting leptin levels were shown to be associated with body mass index; 10.1% (95% CI 8.1-12.1%) increase per 1 kg/m(2) increase in body mass index), homeostasis model assessment insulin sensitivity; 0.4% (95% CI 0.2-0.7%) decrease per 1% increase in insulin sensitivity); abnormal glucose tolerance (24% decrease, 95% CI 8-37%); and smoking (31% decrease, 95% CI 16-44%). Postload (90 min) leptin levels decreased significantly in women with normal glucose tolerance by 13% (95% CI 8-18%), while no significant change in postload leptin level was apparent in women with abnormal glucose tolerance (3% increase, 95% CI -4% to 29%).. Disturbed leptin changes were found following an OGTT in women with abnormal glucose tolerance that might be either a cause or a consequence of leptin resistance.

Topics: Adult; Body Mass Index; Cohort Studies; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Models, Statistical; Pregnancy; Retrospective Studies; Smoking; Time Factors

We investigated whether the increase of leptin expression in preeclamptic placentas is additionally influenced by soluble maternal factors under hypoxic and nonhypoxic conditions.. Term trophoblast cells were isolated and stimulated with sera from preeclamptic women under normoxic or hypoxic conditions. Levels of leptin mRNA and protein were evaluated by real-time RT-PCR or ELISA and Western blot analysis.. Leptin concentrations were increased in the serum of patients with preeclampsia and gestational diabetes. Hypoxia, insulin, and dexamethasone induced leptin expression in trophoblast cells. The incubation with sera from preeclamptic women led to a small, though, significant, increase of leptin gene expression. The effect of preeclamptic serum on leptin gene expression in trophoblast cells was lost under hypoxia. The serum of women with gestational diabetes did not increase leptin expression neither in normoxic nor hypoxic primary trophoblast cells.. Our results can not exclude a soluble maternal factor in the serum of women with preeclampsia accounting for increased leptin expression in placental tissue in addition to hypoxia. However, an important biological role of this small increase in nonhypoxic conditions does not seem very likely.

Topics: Adult; Case-Control Studies; Cells, Cultured; Diabetes, Gestational; Female; Humans; Hypoxia; Leptin; Pre-Eclampsia; Pregnancy; Trophoblasts

Many cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokines or the abnormal glucose metabolism.. This nested case-control study was undertaken from January 2004 to March 2005. Twenty-two women with gestational diabetes mellitus (GDM), 10 with gestational impaired glucose tolerance (GIGT), and 20 healthy pregnant women were chosen from the women who had visited the antenatal clinics and had blood samples prospectively taken and kept during their visit. The levels of tumor necrosis factor-alpha (TNF-alpha), leptin and adiponectin were determined. One-way ANOVA analysis and bivariate correlation analysis were used to assess the laboratory results and their relationship with body mass index (BMI).. Women with GDM have the highest values of TNF-alpha and leptin and the lowest value of adiponectin compared with those with GIGT and the healthy controls (P < 0.01) at 14-20 weeks of gestation. This was also found when these women progressed to 24-32 weeks. The significantly increased levels of TNF-alpha and leptin and the decreased level of adiponectin were found at the different periods of gestation within the same group. Positive correlation was shown between the levels of TNF-alpha and leptin at the two periods of gestation with the BMI at 14-20 weeks, while adiponectin was negatively correlated (P < 0.05).. The concentrations of TNF-alpha, leptin and adiponectin may change before the appearance of the abnormal glucose level during pregnancy. Further studies are required to verify the mechanism of this alteration and whether the three cytokines can be predictors for GDM at an early stage of pregnancy.

Topics: Adiponectin; Case-Control Studies; Diabetes, Gestational; Female; Glucose Intolerance; Humans; Leptin; Pregnancy; Prospective Studies; Tumor Necrosis Factor-alpha

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

To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg).. Cross-sectional case control study.. Acylated ghrelin levels were significantly increased (p<0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p<0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups.. Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Cross-Sectional Studies; Diabetes, Gestational; Female; Ghrelin; Humans; Insulin Resistance; Leptin; Multivariate Analysis; Peptide Hormones; Pregnancy; Pregnancy Trimesters; Receptors, Tumor Necrosis Factor; Resistin; Tumor Necrosis Factor-alpha

To evaluate midtrimester amniotic fluid leptin levels in pregnancies subsequently complicated by gestational diabetes.. We studied 32 pregnant women with gestational diabetes and a control group of 43 normal pregnancies with an adequate gestational age fetus. All underwent a midtrimester amniocentesis: leptin and insulin were measured in the amniotic fluid. Data were compared with the Mann-Whitney U-test.. Median leptin concentrations in the amniotic fluid of the gestational diabetes mellitus patients were significantly higher than in the control group (15.1 vs. 7.9 ng/ml) (p = 0.001); amniotic insulin concentrations were also higher in the gestational diabetes mellitus than in the control group (0.67 vs. 0.38 microU/ml) (p = 0.02). Furthermore, amniotic fluid leptin levels were directly correlated with amniotic insulin concentrations; instead, there was no correlation with maternal BMI and birth weight.. Our data suggest that in pregnancies subsequently complicated by gestational diabetes, amniotic fluid leptin and insulin levels are higher in the early fetal period.

Topics: Adult; Amniocentesis; Amniotic Fluid; Biomarkers; Birth Weight; Body Mass Index; Case-Control Studies; Diabetes, Gestational; Female; Gestational Age; Humans; Infant, Newborn; Insulin; Leptin; Male; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, Second; Risk Assessment

Intrauterine exposure to maternal diabetes and large size at birth are known risk factors for the subsequent development of insulin resistance and metabolic syndrome. Although Hispanic youth have been shown to have a high prevalence of metabolic syndrome, it is unknown whether metabolic abnormalities and a predisposition for glucose intolerance are present at birth.. The objective of the study was to determine whether abnormalities in insulin sensitivity exist at or soon after birth in large-for-gestational-age neonates born to Hispanic women with and without gestational diabetes. DESIGN/PATIENTS/SETTING: Forty-two term Hispanic neonates were enrolled for cross-sectional studies at 24-48 h after birth and included nine large-for-gestational-age neonates delivered of women with gestational diabetes (large-for-gestational-age-IDM), 12 large-for-gestational-age but not IDM neonates, 11 poorly grown (at the fifth to 10th percentile), and 10 appropriate-for-gestational-age neonates. Insulin sensitivity and secretion were measured by shortened fasting iv glucose tolerance test.. Insulin sensitivity index was measured within 48 h of birth.. Neonates were studied at 36 +/- 11 h postnatally, and all groups were euglycemic at the time of study. However, insulin sensitivity was significantly lower (P < 0.05, ANOVA) in large-for-gestational-age-IDM [3.0 +/- 0.7 (sem) mU/liter.min] and large-for-gestational-age-non-IDM (2.2 +/- 0.4 mU/liter.min) cohorts in comparison with poorly grown (5.0 +/- 0.7 mU/liter.min) and appropriate-for-gestational-age controls (5.4 +/- 0.8 mU/liter.min). Insulin secretion did not differ between groups.. Reduced insulin sensitivity is present soon after birth in Hispanic large-for-gestational-age neonates born to mothers with and without gestational diabetes, demonstrating the onset of insulin resistance before birth and evidence of altered fetal programming.

Topics: Adult; Birth Weight; Blood Glucose; Cross-Sectional Studies; Diabetes, Gestational; Female; Fetal Macrosomia; Gestational Age; Hispanic or Latino; Humans; Infant, Newborn; Insulin; Insulin Resistance; Leptin; Lipids; Male; Pregnancy; Prevalence; Risk Factors

Available evidences suggest that leptin has inhibitory role on insulin secretion. The aim of the work was to examine the association between plasma leptin concentrations and insulin resistance in patients with gestational diabetes mellitus. As a cross-sectional study we recruited 741 pregnant women. The universal screening was performed with an oral glucose challenge test-50 g. The recruits with plasma glucose levels of > or = 7.2 mmol/l were diagnosed as having gestational diabetes mellitus if they had an impaired oral glucose tolerance test-100 g based on Carpenter and Coustan criteria. In all pregnancies plasma insulin and leptin concentrations were measured. Gestational diabetes mellitus developed in 7% (52) of pregnancies. Elevated leptin concentrations were positively associated with insulin levels, BMI, and HOMA index while it was negatively associated with Quicky index. After adjusting for age and BMI before pregnancy, gestational diabetes mellitus had independent direct correlation with leptin concentration. Indeed, leptin level equal to or more than 20 ng/ml could help to predict the developing gestational diabetes mellitus. Measurement of leptin together with the assessment of other risk factors could help identifying women at risk of developing GDM.

Topics: Adult; Diabetes, Gestational; Female; Humans; Insulin Resistance; Leptin; Pregnancy

Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). In this study we examined the association between changes in expression of these genes in placental tissue and GDM risk. We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. Tissues were collected from uncomplicated pregnancies (n=28) and those complicated by GDM (n=19). Gene expression was normalized to three endogenous housekeeping genes. Relative gene expression values were reported as fold change between groups. Adiponectin gene expression was out of the sensitive range of our assay. There were increases in leptin mRNA expression in GDM cases compared with controls for maternal-side (p=0.06), and fetal-side (p=0.09) placental biopsies. No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). Finally, we noted that absence or presence of GDM was a major factor in leptin mRNA expression after adjusting for maternal age, mode of delivery, parity and smoking status. In conclusion, increases in leptin mRNA expression in term placenta, but not that of its receptors, are associated with the diagnosis of GDM. Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis.

Topics: Adult; Diabetes, Gestational; Female; Gene Expression; Humans; Leptin; Placenta; Pregnancy; Protein Isoforms; Receptors, Adiponectin; Receptors, Cell Surface; Receptors, Leptin; Regression Analysis

The recently discovered adipocytokine visfatin has insulin-like properties. It lowers blood glucose and improves insulin sensitivity; however, clinical data on visfatin are limited. To evaluate the role of visfatin in GDM (gestational diabetes mellitus), we determined visfatin levels in women with GDM and in healthy pregnant controls. Furthermore, visfatin concentrations were investigated longitudinally during pregnancy and after delivery in a subgroup of women with GDM. Blood for measurement of visfatin and metabolic parameters was obtained from 64 women with GDM [median week of gestation, 34 (interquartile range, 27-36) weeks] and 30 healthy pregnant controls [median week of gestation, 34 (interquartile range, 28-36) weeks]. In a subgroup of 24 women with GDM, visfatin, leptin and metabolic parameters were investigated twice during pregnancy (28-30 and 38-40 weeks of gestation) and 2 weeks after delivery. In the cross-sectional analysis, median visfatin levels were significantly elevated in women with GDM [64.0 (interquartile range, 50.9-74.8) ng/ml] compared with controls [46.0 (interquartile range, 36.9-54.6) ng/ml; P<0.0001]. In women with GDM, visfatin correlated with week of gestation at the time of blood draw (R=0.35, P=0.005). No association with fasting glucose, insulin, homoeostasis model assessment-insulin resistance or body mass index was observed. According to the longitudinal analysis, visfatin increased during pregnancy (P=0.002) and rose further after delivery (P=0.014), whereas leptin and insulin levels decreased after parturition (both P<0.001). In conclusion, visfatin is elevated in women with GDM and increases during the course of pregnancy as well as after delivery. Furthermore, visfatin shows no association with insulin and leptin in women with GDM.

Topics: Adult; Cross-Sectional Studies; Cytokines; Diabetes, Gestational; Female; Humans; Insulin; Insulin Resistance; Leptin; Longitudinal Studies; Nicotinamide Phosphoribosyltransferase; Postpartum Period; Pregnancy; Pregnancy Proteins

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

Not much is known about the implication of adipokines and different cytokines in gestational diabetes mellitus (GDM) and macrosomia. The purpose of this study was to assess the profile of these hormones and cytokines in macrosomic babies, born to gestational diabetic women.. A total of 59 women (age, 19-42 yr) suffering from GDM with their macrosomic babies (4.35 +/- 0.06 kg) and 60 healthy age-matched pregnant women and their newborns (3.22 +/- 0.08 kg) were selected.. Serum adipokines (adiponectin and leptin) were quantified using an obesity-related multiple ELISA microarray kit. The concentrations of serum cytokines were determined by ELISA.. Serum adiponectin levels were decreased, whereas the concentrations of leptin, inflammatory cytokines, such as IL-6 and TNF-alpha, were significantly increased in gestational diabetic mothers compared with control women. The levels of these adipocytokines were diminished in macrosomic babies in comparison with their age-matched control newborns. Serum concentrations of T helper type 1 (Th1) cytokines (IL-2 and interferon-gamma) were decreased, whereas IL-10 levels were significantly enhanced in gestational diabetic mothers compared with control women. Macrosomic children exhibited high levels of Th1 cytokines and low levels of IL-10 compared with control infants. Serum IL-4 levels were not altered between gestational diabetic mothers and control mothers or the macrosomic babies and newborn control babies.. GDM is linked to the down-regulation of adiponectin along with Th1 cytokines and up-regulation of leptin and inflammatory cytokines. Macrosomia was associated with the up-regulation of Th1 cytokines and the down-regulation of the obesity-related agents (IL-6 and TNF-alpha, leptin, and adiponectin).

Topics: Adiponectin; Adult; Blood Glucose; Cytokines; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Interferon-gamma; Interleukin-2; Interleukin-4; Interleukin-6; Leptin; Lipids; Male; Pregnancy; Tumor Necrosis Factor-alpha

To determine the concentration of plasma leptin and other metabolic hormones in offspring of diabetic and none diabetic mothers after 2 weeks of age. The relationship between leptin and metabolic hormones was also investigated.. Included in the study were 79 newborns from the Neonatal Unit at King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia from January 2004-January 2005. The newborns were categorized into 3 main groups: the control group, consisting of 32 infants of non-diabetic mothers; the gestational diabetes mothers (GDM) group, consisting of 26 infants; and the frank diabetic mothers (FDM), consisting of 21 infants. Infants of diabetic mothers were further subdivided into those of dietary (d) or insulin (i) dependent mothers. Plasma leptin, insulin, cortisol and free thyroxin levels were measured by enzyme link immunosorbent assay.. No significant difference in plasma leptin was observed between the studied groups. The GDM-d and FDM-d showed lower glucose versus controls (p<0.001 and p<0.05). There was significant correlation between leptin and glucose in the GDM group (r=0.18, p< 0.05) and with insulin in GDM-d on diet control (r=0.37, p< 0.01).. After 2 weeks of life, no difference in plasma leptin between infants of diabetic and non-diabetic mothers was observed, which may be important for the stimulation of feeding behavior and acquisition of energy homeostasis. Significant association between plasma leptin and insulin in offspring of GDM supports the hypothesis that functional adipoinsular axis might exist in term newborns.

Topics: Anthropometry; Blood Glucose; Diabetes, Gestational; Female; Humans; Hydrocortisone; Infant, Newborn; Insulin; Leptin; Male; Mothers; Pregnancy; Pregnancy in Diabetics; Thyroxine

To assess the relationship between plasma leptin concentration during third trimester of pregnancy and blood pressure, independent of body mass index at examination and other potential confounders.. A cross-sectional study was performed including 95 women (61 non-diabetic women, 34 women with gestational diabetes (GD)) in their third trimester of pregnancy. The relationship between plasma leptin and blood pressure was investigated using multiple linear regression analysis.. Independent of body mass index (BMI), leptin was positively correlated to systolic (P = 0.024) and diastolic blood pressure (P = 0.002). Stepwise linear regression identified leptin as the only variable independently associated with systolic blood pressure (P = 0.003), while leptin (P < 0.001) and age (P = 0.024) were the only variables independently correlated to diastolic blood pressure.. This study reports for the first time that, independent of BMI at examination, presence of GD or other confounders, plasma leptin is positively correlated with blood pressure in pregnant women.

Topics: Blood Pressure; Body Mass Index; Cross-Sectional Studies; Diabetes, Gestational; Female; Humans; Leptin; Linear Models; Pregnancy; Pregnancy Trimester, Third

To investigate whether maternal serum leptin level can be used as a predictor of gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT).. Five hundred and eighty-three pregnant women were screened for GDM by the 50g oral glucose challenge test. At the same time, serum leptin levels were determined by radioimmunoassay, then the relationship between maternal serum leptin level and the incidence of GIGT and GDM was analyzed. According to the screening result, all the pregnant women were divided into three groups, the normal glucose group (NGT group), the gestational impaired glucose tolerance group (GIGT group), and gestational diabetes mellitus group (GDM group). GIGT group and GDM group were named as glucose intolerant group as a whole.. (1) The serum leptin concentration of normal pregnant women ascended gradually from (7.0 +/- 1.8) microg/L in 24 gestational week to (9.4 +/- 2.1) microg/L during 34 - 36 gestational week, and then declined slightly but still maintained high level till delivery. (2) The serum leptin concentration of the glucose intolerant pregnant women ranged from (11.3 +/- 3.1) microg/L to(14.5 +/- 4.3) microg/L, and showed no difference among different gestational weeks (P > 0.05). (3) Serum leptin level of glucose intolerant women was (12.5 +/- 3.5) microg/L on average, much higher than that of NGT group, (8.5 +/- 2.6) microg/L (P < 0.05), and this difference remained in any gestational week (P < 0.05). (4) Most of the GDM clustered in the higher leptin level groups and 66.7% GDM had a serum leptin level higher than 14.0 microg/L. Moreover, 64.7% of women whose serum leptin level was above 17.0 microg/L had different degree of glucose intolerance. Serum leptin level positively correlated with the incidence of GIGT and GDM.. Serum leptin level is correlated with glucose tolerance during pregnancy. Its abnormal increase during pregnancy might have a predictive value for GDM and GIGT.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Female; Glucose Intolerance; Humans; Leptin; Pregnancy; Prenatal Diagnosis

The aim of this study was to determine the release and regulation of leptin, resistin and adiponectin from human placenta and fetal membranes, and maternal subcutaneous adipose tissue and skeletal muscle obtained from normal and gestational diabetes mellitus (GDM)-complicated pregnancies at the time of Cesarean section. Tissue explants were incubated in the absence (basal control) or presence of 10 mug/ml lipopolysaccharide (LPS), 10, 20 or 40 ng/ml tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, 1 microM phorbol myristate acetate, 10, 20 and 40 mM glucose, 0.1, 1 and 10 microM insulin and 0.1 1 and 10 microM dexamethasone, progesterone and estrogen. After an 18-h incubation, the medium was collected and the release of leptin, resistin and adiponectin was quantified by ELISA. Human gestational tissues and maternal tissues released immunoreactive leptin, resistin and adiponectin; however, there was no difference in the release of either resistin or adiponectin between normal pregnant women and women with gestational diabetes. The release of leptin was significantly higher in placenta, amnion and choriodecidua obtained from normal pregnant women compared with women with GDM. However, in maternal tissues, the situation was reversed, with adipose tissue and skeletal muscle obtained from women with GDM releasing significantly greater amounts of leptin. In adipose tissue and skeletal muscle the release of leptin was significantly greater in insulin-controlled GDM compared with diet-controlled GDM, and leptin release from adipose tissue was significantly correlated with maternal body mass index. In all tissues tested, there was no effect of incubation with LPS, IL-6, IL-8 or TNF-alpha on leptin, resistin or adiponectin release. PMA significantly increased the release of resistin from placenta and adipose tissue. Insulin increased placental resistin release, whereas the hormones dexamethasone, progesterone and estrogen significantly decreased placental resistin release. The data presented in this study demonstrate that dysregulation of leptin metabolism and/or function in the placenta may be implicated in the pathogenesis of GDM. Furthermore, resistin release is greatly affected by a variety of inflammatory mediators and hormones.

Topics: Adiponectin; Adipose Tissue; Adult; Anti-Inflammatory Agents; Case-Control Studies; Cytokines; Dexamethasone; Diabetes, Gestational; Estrogens; Extraembryonic Membranes; Female; Glucose; Hormones; Hormones, Ectopic; Humans; Insulin; Intercellular Signaling Peptides and Proteins; Leptin; Lipopolysaccharides; Muscle, Skeletal; Organ Culture Techniques; Placenta; Pregnancy; Progesterone; Resistin; Tetradecanoylphorbol Acetate

Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus (GDM). We examined the association between plasma leptin concentration and GDM risk.. Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95% confidence intervals.. GDM developed in 5.7% of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend <.001). After adjusting for maternal prepregnancy adiposity and other confounders, women with leptin concentrations of 31.0 ng/mL or higher experienced a 4.7-fold increased risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10-ng/mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3).. Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy.. II-2

Topics: Adult; Body Mass Index; Diabetes, Gestational; Female; Follow-Up Studies; Humans; Leptin; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Prospective Studies; Risk Factors

Our primary objective was to evaluate changes in energy expenditure and body composition in women with normal glucose tolerance (NGT) and gestational diabetes mellitus (GDM). A secondary objective was to examine the relationship between maternal leptin and nutrient metabolism. Fifteen obese women, eight with NGT and seven with GDM, were evaluated before conception (P), at 12-14 wk (E), and at 34-36 wk (L). Energy expenditure and glucose and fat metabolism were measured using indirect calorimetry. Basal hepatic glucose production was measured using [6,6-2H2]glucose and insulin sensitivity by euglycemic clamp. There was a significant increase (6.6 kg, P = 0.0001) in fat mass from P to L. There was a 30% (P = 0.0001) increase in basal O2 consumption (VO2, ml/min). There were no significant changes in carbohydrate oxidation during fasting or storage from P to L. There was, however, a significant (P = 0.0001) 150% increase in basal fat oxidation (mg/min) from P to L. Under hyperinsulinemic conditions, there were similar 25% increases in VO2 (P = 0.0001) from P to L in both groups. Because of the significant increases in insulin resistance from P to L, there was a significant (P = 0.0001) decrease in carbohydrate oxidation and storage. There was a net change from lipogenesis to lipolysis, i.e., fat oxidation (30-40 mg/min, P = 0.0001) from P to L. Serum leptin concentrations had a significant positive correlation with fat oxidation at E (r = 0.76, P = 0.005) and L (r = 0.72, P = 0.009). Pregnancy in obese women is associated with significant increases in fat mass and basal metabolic rate and an increased reliance on lipids both in the basal state and during the clamp. These modifications are similar in women with NGT and GDM. The increased reliance on fat metabolism is accompanied by a concomitant decrease in carbohydrate metabolism during hyperinsulinemia. The increase in fat oxidation may be related to increased maternal serum leptin.

Topics: Adult; Body Composition; Diabetes, Gestational; Energy Metabolism; Female; Glucose; Glucose Intolerance; Humans; Insulin; Leptin; Lipid Metabolism; Longitudinal Studies; Obesity; Osmolar Concentration; Oxidation-Reduction; Pregnancy; Pregnancy Complications; Prospective Studies

To determine the levels of leptin in pregnant females during different stages of pregnancy and to correlate these levels to maternal weight, body mass index (BMI), neonate weight and neonate BMI.. A case control study was carried out in which 60 pregnant females were enrolled, but only 36 completed the study and 30 non-pregnant females were used as controls. Blood samples were collected at the 1st trimester, 2nd trimester and 3rd trimester, and after delivery. Serum was used for the estimation of leptin (by radioimmunoassay).. The results showed that the levels of leptin were significantly higher in pregnant females compared to non-pregnant females, but significantly decreased after delivery. In pregnant females with gestational diabetes the leptin level was insignificantly higher.. The increase of leptin levels may be due to the stimulatory effect of insulin on leptin secretion from adipose tissue.

Topics: Adult; Birth Weight; Body Mass Index; Case-Control Studies; Diabetes, Gestational; Female; Humans; Infant, Newborn; Leptin; Organ Size; Placenta; Postpartum Period; Pregnancy; Pregnancy Trimesters

Women with previous gestational diabetes (pGDM) are frequently insulin-resistant, which could relate to intramyocellular lipid content (IMCL). IMCL were measured with (1)H nuclear magnetic resonance spectroscopy in soleus (IMCL-S) and tibialis-anterior muscles (IMCL-T) of 39 pGDM (32 +/- 2 years, waist-to-hip ratio 0.81 +/- 0.01) and 22 women with normal glucose tolerance (NGT; 31 +/- 1 years, 0.76 +/- 0.02) at 4-6 months after delivery. Body fat mass (BFM) was assessed from bioimpedance analysis, insulin sensitivity index (S(I)), and glucose effectiveness (S(G)) from insulin-modified frequently sampled glucose tolerance tests. pGDM exhibited 45% increased BFM, 35% reduced S(I) and S(G) (P < 0.05), and 40% (P < 0.05) and 55% (P < 0.005) higher IMCL-S and IMCL-T, respectively. IMCL related to body fat (BFM P < 0.005, leptin P < 0.03), but only IMCL-T correlated (P < 0.03) with S(I) and glucose tolerance index independent of BMI. Insulin-resistant pGDM (n = 17) had higher IMCL-S (+66%) and IMCL-T (+86%) than NGT and insulin-sensitive pGDM (+28%). IMCL were also higher (P < 0.005, P = 0.05) in insulin-sensitive pGDM requiring insulin treatment during pregnancy and inversely related to the gestational week of GDM diagnosis. Thus, IMCL-T reflects insulin sensitivity, whereas IMCL-S relates to obesity. IMCL could serve as an additional parameter of increased diabetes risk because it identifies insulin-resistant pGDM and those who were diagnosed earlier and/or required insulin during pregnancy.

Topics: Adult; Blood Glucose; Body Constitution; Body Mass Index; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin Resistance; Leptin; Lipid Metabolism; Lipids; Magnetic Resonance Imaging; Muscle, Skeletal; Pregnancy; Receptors, Cell Surface; Receptors, Leptin; Regression Analysis

To investigate the changes in leptin levels and the relationship between the substance and insulin and glucose in pregnant women with gestational diabetes mellitus (GDM) and gestational impaired glucose tolerance (GIGT).. Radio immunoassay was used to measure the leptin levels at fasting and 3 h after oral glucose load (50 g) in 36 patients with GDM and GIGT, and also in 24 normal pregnant women. In each pregnant women, fasting serum insulin levels and glycosylated haemoglobin values were measured by electrochemiluminescent immunoassays and pressure liquid chromatography (LPLC) respectively, glucose levels 1 h after the administration of glucose by glucose oxidase method.. The serum leptin levels in pregnant women with GDM and GIGT and normal pregnant women were (14.9 +/- 4.3) micro g/L and (10.0 +/- 1.8) micro g/L, respectively, suggesting the serum leptin levels were significantly higher in pregnant women with GDM and GIGT than in normal controls. The levels of fasting serum insulin, glycosylated haemoglobin values and plasma glucose levels obtained 1h after oral administration of 50 g glucose were (12.9 +/- 4.3) mU/L, (6.1 +/- 1.1)%, (11.0 +/- 1.4) mmol/L, respectively, whereas the corresponding values in normal controls were (8.6 +/- 3.2) mU/L, (4.5 +/- 1.0)%, (7.8 +/- 1.2) mmol/L. A positive correlation was found between maternal serum leptin levels and fasting serum insulin levels in pregnant women with GDM and GIGT (r = 0.835, P < 0.01). A positive correlation was also found between maternal leptin concentrations and glycosylated haemoglobin values, as well as between leptin levels and plasma glucose levels obtained 1 h after the administration of 50g glucose in women with GDM and GIGT (r = 0.758, P < 0.01; r = 0.561, P < 0.01).. Leptin levels are elevated in pregnant women with GDM and GIGT compared with healthy pregnant women, a positive and significant correlation was found between the maternal leptin levels and fasting insulin levels, as well as between the maternal leptin levels and plasma glucose levels obtained 1 h after the administration of 50 g glucose in women with GDM and GIGT.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Fasting; Female; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Leptin; Pregnancy; Reference Values

Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes.. One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study.. Serum AHSG was determined by radial immunodiffusion.. We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns.. AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

Topics: alpha-2-HS-Glycoprotein; Blood Glucose; Blood Proteins; Body Height; Body Weight; C-Peptide; Cephalometry; Diabetes, Gestational; Female; Gestational Age; Humans; Infant, Newborn; Insulin Resistance; Leptin; Pregnancy; Tumor Necrosis Factor-alpha

To compare umbilical cord leptin concentrations in different ethnic groups and between pregnancies with and without gestational diabetes mellitus (GDM) in Auckland, New Zealand.. A cross-sectional study of 116 European, Polynesian, and South Asian women and their infants with and without GDM. Maternal metabolic measures were recorded at 36 weeks' gestation, umbilical cord samples were collected at birth, and neonatal anthropometric measures were recorded 24 h after delivery.. Compared with Europeans and South Asians, samples of Polynesian umbilical cords had higher leptin concentrations (8.7 and 9.5 vs. 14.9 ng/ml, respectively; P = 0.026). Umbilical cord samples from pregnancies complicated by GDM had higher leptin concentrations than those from normal pregnancies (22.3 vs. 13.8 ng/ml, respectively; P = 0.022). Maternal leptin concentrations at 36 weeks were similar across ethnic groups and with and without GDM. Cord leptin correlated with birth weight, measures of fetal size, and cord insulin in normal pregnancies and those complicated by GDM. In multivariate analyses, cord leptin was related to birth weight (P < 0.001), gestation at delivery (P = 0.038), and ethnic group (P = 0.017) in normal pregnancies and to birth weight (P < 0.001), gestation at delivery (P < 0.001), and sex (P = 0.003) but not maternal diabetes status (P = 0.909) in pregnancies complicated by GDM.. Offspring of Polynesian women are relatively hyperleptinemic, independent of birth size. Offspring of women with GDM are also relatively hyperleptinemic at birth, but this was associated with their increased birth weight. We speculate that this GDM-associated relative hyperleptinemia may be due to fuel-mediated teratogenesis affecting the adipoinsular axis, which in turn could also lead to leptin resistance and obesity in adult life. The reason for the ethnic difference in hyperleptinemia is unclear.

Topics: Adult; Asian People; Birth Weight; Cross-Sectional Studies; Diabetes, Gestational; Female; Humans; Hyperglycemia; Infant Nutritional Physiological Phenomena; Infant, Newborn; Insulin; Leptin; Male; Pregnancy

The purpose of this study was to determine the relationship of neonatal sex and gestational diabetes mellitus on cord leptin concentration and to determine whether cord leptin has a stronger correlation with fat mass compared with birth weight or lean body mass. We hypothesized that there are no significant differences in fetal leptin concentration between male and female or between neonates of mothers with gestational diabetes mellitus and control neonates, when adjusted for body composition.. Cord blood leptin concentrations were measured in newborn infants of 78 women (44 control neonates and 34 gestational diabetes mellitus). Of the 78 neonates, 32 babies were female, and 46 babies were male. Birth weights were measured with a calibrated scale, and body compositions were measured by total body electrical conductivity.. Estimated mean gestational age at delivery was 39.1 +/- 1.1 weeks for control neonates versus 38.6 +/- 1.3 weeks for neonates of mothers with gestational diabetes mellitus (P =.01). The fat mass for the control neonates and neonates of mothers with gestational diabetes mellitus was 0.36 +/- 0.15 kg versus 0.48 +/- 0.21 kg (P =.01); the percent body fat for the control neonates and neonates of mothers with gestational diabetes mellitus was 10.5% +/- 3.8% versus 13.2% +/- 4.3% (P =.006), respectively. There was no significant difference in cord leptin concentration between male and female neonates (16.0 +/- 13.8 ng/dL vs 12.7 +/- 12.8 ng/dL, P =.24). Cord leptin concentrations (18.1 +/- 16.2 ng/dL vs 10.9 +/- 9.5 ng/dL, P =.02) were significantly greater in neonates of mothers with gestational diabetes mellitus than in control neonates. In all subjects, cord leptin was significantly correlated with percent body fat (r = 0.51, P <.0001), fat mass (r = 0.49,P <.0001), and birth weight (r = 0.25, P =.03). After the adjustment for fat mass, there was no significant difference in cord leptin concentration between control neonates and neonates of mothers with gestational diabetes mellitus (P =.20), but there was a significant difference between male and female neonates (P =.04). However, when an adjustment was made for both fat mass and lean body mass, there was no longer a significant difference between male and female neonates (P =.12). The differences in cord leptin concentration between male and female neonates and between infants of women with gestational diabetes mellitus and control neonates are related to differences in body composition.

Topics: Diabetes, Gestational; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Sex Factors

To investigate the fetoplacental leptin circulation in gestational diabetes, we compared cord leptin and insulin levels in 17 healthy pregnant women and 17 women with gestational-onset diabetes. Leptin levels in the umbilical arteries (mean+/-SD 1.80+/-0.76 ng/ml) were significantly (P<0.006) lower than those in umbilical veins (2.67+/-0.98 ng/ml) in normal pregnancies. Similarly, leptin levels in umbilical veins (mean+/-4.59+/-1.60 ng/ml) were significantly (P<0.001) higher than those in umbilical arteries (mean+/-SD 2.08+/-0.90 ng/ml) in gestational diabetes. However, leptin levels in umbilical veins were significantly higher (P<0.002) in gestational diabetes than those in controls. Additionally, in women with diabetes but not in controls, the birth weight and the cord leptin concentrations were positively related to cord insulin levels. We conclude that there is a hyperleptinaemia in the fetoplacental circulation in pregnant women with carbohydrate intolerance and in these cases insulin and leptin may have antagonist roles regarding fetal development.

Topics: Adult; Birth Weight; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Leptin; Placental Circulation; Pregnancy

The contribution of the tumor necrosis factor (TNF) system and leptin was studied in insulin resistance and neonatal development during the course of normal pregnancy and gestational diabetes mellitus (GDM). Thirty patients with GDM and their neonates (n = 30), 35 healthy pregnant women (15 in the first, nine in the second and 11 in the third trimester) and their neonates (n = 20), and 25 healthy matched non-pregnant women participated in the study. Significantly elevated levels of maternal TNF-alpha, sTNF receptor (R)-1 and R-2, leptin (detected by enzyme-linked immunosorbent assay) and fasting C-peptide (measured by radioimmunossay and raised body mass index (BMI) were found in GDM patients and in the third trimester of normal pregnancies. TNF-alpha, sTNFR-2, C-peptide, leptin concentrations and BMI positively correlated with each other in GDM. An inverse relationship between the body length, head circumference and body weight of the newborns, and maternal TNF-alpha, leptin and C-peptide concentrations was shown in GDM. In healthy pregnancies the maternal serum leptin level was in a negative linear correlation with the head circumference of the newborns. In conclusion, increased TNF-alpha and leptin levels may contribute to insulin resistance in GDM and in the third trimester of normal pregnancy and may negatively influence the anthropometric parameters of the newborns.

Topics: Adult; Anthropometry; Antigens, CD; Birth Weight; Body Height; C-Peptide; Cephalometry; Diabetes, Gestational; Female; Humans; Infant, Newborn; Insulin Resistance; Leptin; Pregnancy; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

Obesity is a state of relative leptin resistance, and obesity in childhood is associated with an increased incidence of type 2 diabetes in later life. Offspring of mothers with gestational diabetes mellitus (GDM) are at increased risk of obesity. A cohort consisting of 64 mothers, 33 GDM and 31 controls screened for diabetes during the index pregnancy together with their 9-year-old offspring were studied. Our hypotheses were: 1) an elevated child leptin is associated with elevated maternal leptin in GDM mothers 9 years post delivery; and 2) child leptin at 9 years serves as a marker for incipient insulin resistance. By univariate analyses, child leptins were only significantly correlated with maternal leptins among the offspring of GDMs (OGDM) (r = 0.59; p = 0.001). By multivariate analyses, child leptin for the total study group was significantly associated with child body mass index (BMI) (R(2) = 0.65; p < 0.0001), child fasting insulin (R(2) = 0.08; p = 0.03), and female gender (R(2) = 0.28; p = 0.001). In addition, among OGDM child leptin was associated with maternal leptin (R(2) = 0.14; p = 0.005). Our results suggest that there is an association between maternal and child leptin levels 9 years after a pregnancy complicated by gestational diabetes.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Child; Cholesterol; Cohort Studies; Diabetes, Gestational; Female; Follow-Up Studies; Humans; Insulin; Insulin Resistance; Leptin; Linear Models; Male; Multivariate Analysis; Obesity; Pregnancy

Historically, insulin resistance during pregnancy has been ascribed to increased production of placental hormones and cortisol. The purpose of this study was to test this hypothesis by correlating the longitudinal changes in insulin sensitivity during pregnancy with changes in placental hormones, cortisol, leptin, and tumor necrosis factor (TNF)-alpha. Insulin resistance was assessed in 15 women (5 with gestational diabetes mellitus [GDM] and 10 with normal glucose tolerance) using the euglycemic-hyperinsulinemic clamp procedure, before pregnancy (pregravid) and during early (12-14 weeks) and late (34-36 weeks) gestation. Body composition, plasma TNF-alpha, leptin, cortisol, and reproductive hormones (human chorionic gonadotropin, estradiol, progesterone, human placental lactogen, and prolactin) were measured in conjunction with the clamps. Placental TNF-alpha was measured in vitro using dually perfused human placental cotyledon from five additional subjects. Compared with pregravid, insulin resistance was evident during late pregnancy in all women (12.4 +/- 1.2 vs. 8.1 +/- 0.8 10(-2) mg. kg(-1) fat-free mass. min(-1). microU(-1). ml(-1)). TNF-alpha, leptin, cortisol, all reproductive hormones, and fat mass were increased in late pregnancy (P < 0.001). In vitro, most of the placental TNF-alpha (94%) was released into the maternal circulation; 6% was released to the fetal side. During late pregnancy, TNF-alpha was inversely correlated with insulin sensitivity (r = -0.69, P < 0.006). Furthermore, among all of the hormonal changes measured in this study, the change in TNF-alpha from pregravid to late pregnancy was the only significant predictor of the change in insulin sensitivity (r = -0.60, P < 0.02). The placental reproductive hormones and cortisol did not correlate with insulin sensitivity in late pregnancy. Multivariate stepwise regression analysis revealed that TNF-alpha was the most significant independent predictor of insulin sensitivity (r = -0.67, P < 0.0001), even after adjustment for fat mass by covariance (r = 0.46, P < 0.01). These observations challenge the view that the classical reproductive hormones are the primary mediators of change in insulin sensitivity during gestation and provide the basis for including TNF-alpha in a new paradigm to explain insulin resistance in pregnancy.

Topics: Adult; Blood Glucose; Body Composition; Chorionic Gonadotropin; Diabetes, Gestational; Female; Gestational Age; Glucose Clamp Technique; Glucose Intolerance; Humans; Hydrocortisone; Infusions, Intravenous; Insulin; Insulin Resistance; Leptin; Placenta; Placental Lactogen; Predictive Value of Tests; Pregnancy; Prolactin; Reference Values; Regression Analysis; Tumor Necrosis Factor-alpha

To investigate the changes in leptin levels and the relationship between this substance and insulin and glucose in pregnant women with gestational-onset diabetes, we measured plasma leptin levels in the maternal peripheral vein of 17 healthy and 17 diabetic women at 29 and 33 weeks of gestation. We also correlated maternal plasma leptin levels in diabetic women with fasting plasma insulin levels and plasma glucose levels obtained 1 h after oral administration of 50 g of glucose. Maternal serum leptin levels in women with gestational diabetes (mean +/- SD 16.52 +/- 5.07 ng/ml, range 10.84-27.4 ng/ml) were significantly higher (p < 0.001) than those found in uncomplicated pregnancies (10.61 +/- 1.47 ng/ml, range 7.28-13.4 ng/ml). A positive correlation was found between maternal serum leptin levels and glycosylated haemoglobin values in diabetic pregnant women (r = 0.94, p < 0.001). A positive correlation was also found between maternal leptin concentrations and fasting serum insulin levels, as well as between leptin concentrations and plasma glucose levels obtained 1 h after the administration of 50 g of glucose in women with gestational diabetes (r = 0.84, p < 0.001, and r = 0.92, p < 0.001, respectively). We conclude that leptin levels are elevated in pregnant women with gestational diabetes, and its metabolism depends on insulin levels and the severity of diabetes.

Topics: Adult; Blood Glucose; Diabetes, Gestational; Fasting; Female; Gestational Age; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Leptin; Pregnancy; Reference Values

Insulin resistance as well as marked changes in body weight and energy metabolism are associated with pregnancy. Its impact on plasma leptin is not known and was determined in this longitudinal study in both diabetic and normal pregnancy.. At 28 gestational weeks plasma concentrations of leptin and B-cell hormones were measured at fasting and after an oral glucose load (OGTT:75 g) in women with gestational diabetes and pregnant women with normal glucose tolerance and compared with women who were not pregnant (C).. Plasma leptin (ng/ml) was higher (p < 0.001) in women with gestational diabetes (24.9 +/- 1.6) than in women with normal glucose tolerance (18.2 +/- 1.5) and increased in both groups when compared with the non-pregnant women (8.2 +/- 1.3; p < 0.0005). No change in plasma leptin concentrations was induced by OGTT in any group. Basal insulin release was higher (p < 0.05) in women with gestational diabetes compared with the pregnant women with normal glucose tolerance. Marked insulin resistance was confirmed by a 20 % lower (p < 0.05) insulin sensitivity in subgroup analysis and a decrease of almost 40% in fasting glucose/insulin ratio (p < 0.005) in women with gestational diabetes. Leptin correlated in women with gestational diabetes with basal plasma concentrations of glucose (p < 0.02), insulin (p < 0.004) and proinsulin (p < 0.01) as well as with BMI (p < 0.001) and overall pregnancy induced maternal weight gain (p < 0.009). With normalisation of blood glucose 8 weeks after delivery in women with gestational diabetes their plasma leptin decreased (p < 0.0005) to 17.3 +/- 1.9 ng/ml but did not completely normalize (p < 0.05 vs non-pregnant women).. Our data show that women with gestational diabetes without any change in plasma leptin upon oral glucose loading have increased plasma leptin concentrations during and after pregnancy, a clear association of plasma leptin with the respective concentration of glucose and insulin resistance as well as with changes in body weight, and a failure to normalize spontaneously BMI to the same extent as pregnant women with normal glucose tolerance when compared with matched control subjects.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Diabetes, Gestational; Fasting; Female; Gestational Age; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Insulin Resistance; Insulin Secretion; Leptin; Postpartum Period; Pregnancy; Proinsulin; Regression Analysis; Weight Gain

The aim was to investigate the relationship between body mass index (BMI), plasma leptin, glucose, insulin and C-peptide levels in the offspring of diabetic mothers (DM) and non-diabetic healthy mothers (HM).. Seventy-two offspring (37 girls and 35 boys, age 4-20 years) of DM were investigated in a prospective study. Those 14-16 years old (Tanner stage II-IV) were compared with age-matched offspring of HM (33 girls and 33 boys).. BMI strongly correlated with plasma leptin concentration in the offspring of both DM and HM children. There were higher BMI and plasma leptin and glucose levels in DM than in HM children. There was no difference in plasma insulin or C-peptide levels between HM and age-matched DM children. There was a highly significant positive correlation between plasma leptin and C-peptide in boys of DM.. The higher plasma leptin found in the offspring of DM reflects their higher BMI. A moderately high but still normal glycemia might be a preclinical sign of insulin resistance or other disturbance of glucoregulation.

Topics: Adolescent; Adult; Blood Glucose; Body Mass Index; C-Reactive Protein; Child; Child, Preschool; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Humans; Insulin; Leptin; Longitudinal Studies; Male; Pregnancy; Pregnancy in Diabetics; Prospective Studies

Gestational diabetes mellitus (GDM) results from an interaction between susceptibility genes and the diabetogenic effects of pregnancy. During pregnancy, mice heterozygous for the lepin receptor (db/+) gain more weight, are glucose intolerant, and produce macrosomic fetuses compared with wild-type (+/+) mothers, suggesting that an alteration in leptin action may play a role in GDM and fetal overgrowth. To investigate whether leptin administration or pair-feeding can reduce adiposity and thereby prevent GDM and neonatal overgrowth, we examined energy balance, glucose and insulin tolerance, and fetal growth in pregnant db/+ and +/+ mice treated with recombinant human leptin-IgG during late pregnancy. Leptin reduced food intake and adiposity in pregnant db/+ mice to levels similar to pregnant +/+ mice and significantly reduced maternal weight gain. Maternal glucose levels were markedly lower during glucose and insulin challenge tests in leptin-treated db/+ mice relative to db/+ and pair-fed controls. Despite reduced energy intake and improved glucose tolerance, leptin administration did not reduce fetal overgrowth in offspring from db/+ mothers. Fetal and placental leptin levels were 1.3- to 1.5-fold higher in offspring from db/+ mothers and remained unchanged with leptin administration, whereas leptin treatment in +/+ mothers or pair-feeding decreased placental leptin concentration and reduced fetal birth weight. Our results provide evidence that leptin administration during late gestation can reduce adiposity and improve glucose tolerance in the db/+ mouse model of spontaneous GDM. However, fetal and placenta leptin levels are higher in db/+ mothers and are subject to reduced negative feedback in response to leptin treatment. These data suggest that alterations in placenta leptin may contribute to the regulation of fetal growth independently of maternal glucose levels.

Topics: Animals; Carrier Proteins; Diabetes, Gestational; Embryonic and Fetal Development; Female; Fetus; Glucose Intolerance; Heterozygote; Humans; Insulin; Leptin; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Placenta; Pregnancy; Pregnancy Complications; Receptors, Cell Surface; Receptors, Leptin; Recombinant Proteins; Signal Transduction

To evaluate the effect of maternal diabetes on the concentrations of free and bound leptin at birth and during postnatal adaptation.. Total, bound, and free leptin concentrations and the percentage of free leptin were measured in cord plasma and plasma at 3 days of age of 13 term infants of mothers with gestational diabetes mellitus (GDM) and 13 term infants of healthy mothers. Gestational age was 40.2 (1.4) weeks, and birth weight was 3693 (549) g (means (SD)).. At birth, infants of mothers with GDM had significantly higher concentrations of total, bound, and free leptin and a higher percentage of free leptin (all p < 0.05). In all infants, these concentrations were significantly lower at 3 days of age than at birth (all p < 0.003), and the differences in concentrations of total, bound, and free leptin between the two groups were no longer significant. In infants of mothers with GDM, the percentage of free leptin remained unchanged, and was higher (p<0.05) than in infants of healthy mothers; in the latter group the percentage of free leptin significantly declined (p = 0.02).. GDM appears to influence fetoplacental leptin metabolism. This effect may be mediated through altered maternal glucose metabolism, or insulinaemia, or both.

Topics: Anthropometry; Chromatography, High Pressure Liquid; Diabetes, Gestational; Female; Fetal Blood; Humans; Infant, Newborn; Leptin; Maternal-Fetal Exchange; Pregnancy

Infants of diabetic mothers have been characterized by macrosomia due to hyperinsulinism. A relation has been observed between circulating levels of leptin and the intrauterine growth pattern.. We studied the leptin and insulin concentrations in the cord blood of 29 newborn infants of mothers with type 1 diabetes (iT1DM), 70 newborn infants of mothers with gestational diabetes and 105 newborn infants of nondiabetic mothers.. There were significant differences (p < 0.001) between the 3 groups with the highest leptin levels 24.9 microg/l (range 1.7-94.1) in infants of mothers with iT1DM and the second-highest levels 14.0 microg/l (range 2.6-74.9) in infants of mothers with gestational diabetes (iGDM), whereas the control infants had the lowest leptin levels 10.0 microg/l (range 0.10-45.9). Girls had higher leptin concentrations than boys among the iT1DM and control infants. The insulin concentrations were 18.1 mU/l (range 1.9-123.3), 6.1 mU/l (range 1.1-51.4) and 3.6 mU/l (range 0.5-21.5) in the 3 groups (p < 0.001), respectively. A significant correlation was observed between leptin and insulin concentrations in iGDM and control infants (r = 0.51; p < 0.001 and r = 0.25; p < 0.05). Both absolute and relative birth weights correlated with leptin levels in all 3 groups (r = 0.60, p = 0.01 and r = 0.51, p = 0.05 in iT1DM; r = 0.51 and 0.56, p < 0.001 in iGDM and r = 0.42 and 0.59, p < 0.001 in control infants).. Our results confirm the relation between leptin concentrations and birth weight. They also suggest that leptin may be involved in the increased accumulation of adipose tissue characteristic of infants of diabetic mothers.

Topics: Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Insulin; Leptin; Male; Pregnancy

To investigate the effect of maternal diabetes on leptin in term newborns and to determine whether leptin correlates with insulin and its associated biochemical parameters in support of the hypothesis that a functional "adipoinsular axis" might exist at this stage of development.. A total of 116 term newborns were prospectively enrolled and categorised into three groups: 44 were infants of non-diabetic mothers (control group C); 41 were infants born to mothers with gestational diabetes on dietary treatment (group D); and 31 were infants born to mothers with gestational or pregestational diabetes on insulin treatment (group I).. No significant difference in serum leptin was observed between the three groups; the results of the study population were therefore pooled and analysed. Serum leptin correlated significantly with serum insulin, insulin:glucose ratio, birth weight, body length, body mass index, placenta weight, and maternal HbA(1c). Female infants had significantly higher serum leptin than male infants. All parameters except placenta weight and body length remained significantly associated with serum leptin when multivariate stepwise regression analysis was applied. Subgroup analysis revealed a significant correlation between serum leptin and cortisol in group D.. There was no significant difference in serum leptin between infants born to diabetic and non-diabetic mothers, though infants born to mothers requiring insulin treatment had the highest median serum leptin concentrations. The significant association between serum leptin and insulin or insulin:glucose ratio supports the hypothesis that a functional adipoinsular axis might exist in term newborns. Furthermore, the significant correlation between maternal HbA(1c) and circulating leptin of the studied infants suggests that the clinical control of maternal diabetes could affect the regulation of serum leptin in these infants.

Topics: Blood Glucose; Case-Control Studies; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Infant, Newborn; Insulin; Leptin; Male; Multivariate Analysis; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Sex Factors

The relationship between in utero fetal growth and fetal leptin concentrations was investigated between 19 and 41 wk in 40 normal (appropriate for gestational age, AGA) fetuses, in 25 intrauterine growth-restricted (IUGR) fetuses, and in 18 fetuses from gestational diabetic mothers (GDM), representing different intrauterine growth patterns. Umbilical venous plasma leptin concentrations were determined at the time of either in utero fetal blood sampling or delivery. Plasma leptin was measurable as early as 19 wk of gestation. A significant difference was observed between umbilical venous and arterial plasma leptin concentrations (0.6+/-0.6 ng/mL; p<0.01). In AGA and in IUGR fetuses, significant positive relationships were found between fetal leptin concentrations and both gestational age (p<0.001) and fetal weight (p<0.001). Leptin concentrations were significantly higher in AGA than IUGR only after 34 wk (p<0.05), but leptin per kilogram fetal weight (leptin/kg) was not significantly different. In IUGR with abnormal umbilical arterial Doppler velocimetry and fetal heart rate, leptin/kg significantly higher than in IUGR with normal biophysical and biochemical parameters was found (p<0.05). Both circulating plasma leptin and leptin/kg were significantly higher in GDM than in normal fetuses (p<0.001) and correlated with abdominal fat mass measured by ultrasound. No gender differences were observed in any group of fetuses. These findings indicate a clear relationship between fetal leptin concentrations and fetal fat mass. Data in severe IUGR suggest the presence of increased leptin concentrations associated with in utero signs of fetal distress.

Topics: Diabetes, Gestational; Embryonic and Fetal Development; Female; Fetal Blood; Fetal Growth Retardation; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Pregnancy; Reference Values

There is increasing evidence suggesting that leptin plays a major role in the regulation of energy homeostasis, as well as in the neuroendocrine and reproductive systems. Leptin is synthesized in the human placenta. The aim of this study was to relate serum leptin levels during pregnancy to glucose tolerance, body mass index (BMI) and specific metabolic variables, such as specific insulin and proinsulin.. A 2-h 75 g oral glucose tolerance test was performed in 221 pregnant women at 22-29 weeks of gestation (median 25th week). Serum leptin was measured using a radioimmunoassay. In 49 women, sequential leptin measurements were performed (during pregnancy and post partum (median 5 months)).. During pregnancy serum leptin was significantly related to body weight (r = 0.49), BMI (r = 0.51), fasting immunoreactive insulin (r = 0.46), specific insulin (r = 0.43) and proinsulin (r = 0.29) (all P-values <0.0001). In women with mild gestational diabetes (GDM, n = 55), leptin levels were lower compared to women with normal glucose tolerance (n = 166) after adjusting for BMI and fasting insulin (26.9 vs. 19.4 ng/ml, P = 0.0001). Leptin was significantly higher during pregnancy compared to post partum (mean +/- SE: 24.3+/-1.5 vs. 19.6+/-1.6 ng/ml, P = 0.0003), even after adjustment for changes in BMI and changes in fasting insulin (P = 0.013).. Leptin levels are elevated in pregnancy. Women with mild GDM presented with relative hypoleptinaemia compared to women with normal glucose tolerance.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Insulin; Leptin; Placenta; Postpartum Period; Pregnancy; Proteins; Reference Values

Leptin has been implicated in the regulation of body weight and energy balance; Leptin is produced by adipocytes and placental tissue. Chronic fetal hyperinsulinemia and accelerated fetal growth with increased amounts of body fat are frequent findings in the offspring of diabetic mothers. In this study, we examined whether leptin levels in cord blood of infants of type 1 diabetic mothers (n = 29), gestational diabetic mothers (n = 6 and controls (n = 96) correlated with level of maternal glucose control, maternal leptin level at delivery, gender, fetal and placental size, and C-peptide in cord blood at birth. Leptin was significantly elevated in infants of type 1 diabetic (24.7 ng/ml) and gestational diabetic mothers (29.3 ng/ml) as compared to controls (7.9 ng/ml). C-peptide was also significantly higher in infants of type 1 diabetic (0.91 nmol/l) and gestational diabetic mothers (0.99 nmol/l) vs controls (0.34 nmol/l). Infants of type 1 diabetic mothers with a leptin level in cord blood above the upper normal range, i.e. > 30 ng/ml (n = 13), had an average maternal HbA1c level of 5.4% (normal < 5.5%) that was not different from 5.2% in infants with a leptin level < 30 ng/ml (n = 15). In both neonatal groups of diabetic mothers, leptin in cord blood did not correlate with maternal leptin concentrations, placental weight, birthweight, gender and cord blood C-peptide. In controls, leptin in cord blood was higher in girls than in boys (p = 0.044) and correlated significantly with birthweight (p = 0.41, p < 0.001) and cord blood C-peptide (p = 0.44, p < 0.001) but not with maternal leptin level or placental weight. The 3-4 times higher leptin levels in the offspring of diabetic mothers than normal could reflect increased adipose tissue mass and/or increased contribution from other sources such as placental tissue.

Topics: Birth Weight; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Organ Size; Placenta; Pregnancy; Pregnancy in Diabetics; Proteins; Sex Characteristics

Leptin is a 16-kD protein encoded by the ob/ob (obesity) gene. In rodents it plays a role in obesity, diabetes, fertility, and neuroendocrine function. In humans serum concentrations of leptin correlate with total body fat in both adults and children. We measured cord blood leptin in 186 neonates that included 82 appropriate for gestational age (AGA), 47 large for gestational age (LGA), 20 infants of diabetic mothers, 52 preterm infants, and 15 intrauterine growth-retarded (IUGR) infants. There were 16 pairs of twins. The mothers of 17 preterm infants were treated with steroids before delivery. Leptin (mean +/- SD) concentration in term, AGA infants (39.4 +/- 1.1 wk) with birth weight (BW) of 3.2 +/- 0.3 kg, body mass index (BMI) of 12.6 +/- 1.1 was 4.01 +/- 3.5 ng/mL. BW correlated with cord leptin (p = 0.002) in a multivariate analysis controlling for potential confounders. Both LGA infants and infants of diabetic mothers had higher cord leptin concentration 7.3 +/- 3.8 and 6.1 +/- 4.8 ng/mL, respectively, compared with AGA infants (p < 0.05). Preterm infants had a mean leptin level of 1.8 +/- 0.97 ng/mL and a 3-fold elevation was seen if mothers received steroids antenatally (p = 0.006). IUGR infants had increased leptin (6.5 +/- 3.9 ng/mL, p = 0.03). Concerning the twin pairs, the smaller had a higher leptin level compared with larger twin (4.1 +/- 9.51 versus 2.8 +/- 5.14, p = NS). Neonatal cord leptin concentrations correlate well with BW and BMI. No gender differences were found in cord blood leptin. Maternal obesity had no effect on cord leptin, whereas exogenous maternal steroids increased neonatal leptin concentrations.

Topics: Adult; Birth Weight; Body Mass Index; Child; Diabetes, Gestational; Female; Fetal Blood; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Premature; Leptin; Maternal-Fetal Exchange; Obesity; Pregnancy; Proteins; Steroids

Leptin can be considered as a peripheral signal which informs the centers about the mass of energy stores. Studies done on the human adult population have demonstrated that degree of adiposity and insulin levels play a major role as determinants of leptin circulating levels. The aim of this study was to evaluate which factors may influence leptin levels at birth. We examined the role played by baby size and by the metabolic environment the fetus was exposed to during pregnancy. We considered 85 newborns from normal (n = 60), gestational (GDM, n = 17) and pregestational (IDDM = 8) diabetes mellitus mothers. At delivery, blood was taken from the umbilical cord vein. Babies from normal and GDM mothers were subdivided into AGA (appropriate for gestational age) and LGA (large for gestational age). There was no difference in leptin levels between babies from normal or GDM mothers belonging to the same weight category, but leptin levels were always higher in LGA than in AGA newborns, and highly correlated with birth weight (r = 0.34, P = 0.001). Moreover, IDDM mothers gave birth to newborns with significantly higher levels of leptin and insulin when compared with normal and GDM mothers. Diabetes of both GDM and IDDM mothers was clinically well controlled (HbA1c was 4.0 and 7.2, respectively). The correlation between leptin and insulin was significant only when newborns from IDDM mothers were included in the regression analysis (r = 0.39, P = 0.0002). Our results suggest that degree of adiposity is one of the main regulators of leptin concentration in the human newborn and that babies exposed to an altered, though clinically controlled, metabolic environment, as in IDDM mothers, have increased levels of leptin.

Topics: Adipose Tissue; Adult; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Leptin; Multivariate Analysis; Pregnancy; Proteins; Regression Analysis; Testosterone