Prenatal development is currently recognized as a critical period in the etiology of human diseases. This is particularly so when an unfavorable environment interacts with a genetic predisposition. The fetal programming concept suggests that maternal nutritional imbalance and metabolic disturbances may have a persistent and intergenerational effect on the health of offspring and on the risk of diseases such as obesity, diabetes, and cardiovascular diseases.

There is ample scientific evidence to suggest a link between the fatty acid-binding protein 4 (FABP4) and insulin resistance, gestational (GDM), and type 2 (T2DM) diabetes mellitus. This novel proinflammatory adipokine is engaged in the regulation of lipid metabolism at the cellular level. The molecule takes part in lipid oxidation, the regulation of transcription as well as the synthesis of membranes. An involvement of FABP4 in the pathogenesis of obesity and insulin resistance seems to be mediated via FABP4-dependent peroxisome proliferator-activated receptor γ (PPARγ) inhibition. A considerable number of studies have shown that plasma concentrations of FABP4 is increased in obesity and T2DM, and that circulating FABP4 levels are correlated with certain clinical parameters, such as body mass index, insulin resistance, and dyslipidemia. Since plasma-circulating FABP4 has the potential to modulate the function of several types of cells, it appears to be of extreme interest to try to develop potential therapeutic strategies targeting the pathogenesis of metabolic diseases in this respect. In this manuscript, representing a detailed review of the literature on FABP4 and the abovementioned metabolic disorders, various mechanisms of the interaction of FABP4 with insulin signaling pathways are thoroughly discussed. Clinical aspects of insulin resistance in diabetic patients, including women diagnosed with GDM, are analyzed as well.

The fetus may be exposed to increased endogenous or synthetic glucocorticoid (GS) exposure in late gestation. Approximately 7% of pregnant women in Europe and North America are treated with synthetic GSs to promote lung maturation in fetuses at risk of preterm delivery. Maternal steroid treatment before preterm delivery is one of the best documented and most cost effective life saving treatments in prenatal medicine but, in certain circumstances, the price of accelerated lung maturity may be loss of brain cells, increased neurodevelopmental disability, intra-uterine growth restriction (IUGR), and an increased risk of preterm delivery, of programming of post-natal hypertension, and of increased post-natal activity in the hypothalamo-pituitary-adrenal (HPA) axis. Placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) is the key enzyme which protects the fetus from overexposure to GSs by their oxidation into inactive derivates. We review the evidence for the metabolism of GSs during pregnancy and how endogenous and synthetic GSs cause other changes in the placenta which affect fetal development.

Gestational diabetes mellitus (GDM) is considered to be one of the most frequent medical complication observed among pregnant women. The role of adipokines in the pathogenesis of GDM remains strictly unknown. Different adipokines have been studied throughout gestation, and they have been proposed as biomarkers of GDM and other pregnancy-related complications; however, there is no biomarker reported for GDM screening at present. The aim of this study was to evaluate serum nesfatin-1 and vaspin levels in GDM and non-GDM women, to characterize the correlation between these adipokines, and to assess the potential role of circulating adipokines in the prediction of risk of gestational diabetes mellitus. Serum concentrations of nesfatin-1 and vaspin were measured in 153 women with GDM, and in 84 patients with uncomplicated pregnancy by enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer’s instructions. Circulating levels of nesfatin-1 and vaspin were significantly lower in the GDM group than in the control group. Nesfatin-1 levels were negatively correlated with vaspin levels. The results of this study point out the possible role of nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of GDM. Further studies are necessary to evaluate the influence of nesfatin-1 and vaspin on glucose metabolism in the early stages of GDM.

The exact roles of adipokines in the pathogenesis of type 2 diabetes and obesity are still unclear. The aim of the study was to evaluate fatty acid binding protein 4 (FABP4) concentrations in the serum and urine of women with excessive gestational weight gain (EGWG) and gestational diabetes mellitus (GDM) in the early post-partum period, with reference to their laboratory test results, body composition, and hydration status. The study subjects were divided into three groups: 24 healthy controls, 24 mothers with EGWG, and 22 GDM patients. Maternal body composition and hydration status were evaluated by the bioelectrical impedance analysis (BIA) method. Concentrations of FABP4, leptin, and ghrelin were determined via enzyme-linked immunosorbent assay (ELISA). Healthy women were characterized by the lowest serum leptin concentrations and by a negative correlation between the serum and urine FABP4 levels. Serum FABP4 levels were the highest in the GDM group. Serum FABP4 and leptin concentrations correlated positively in the GDM group. The EGWG group had the highest degree of BIA disturbances in the early puerperium and positive correlations between the urine FABP4 and serum leptin and ghrelin concentrations. The physiological and pathological significance of these findings requires further elucidation.

Two-thirds of pregnant women exceed gestational weight gain recommendations. Excessive gestational weight gain (EGWG) appears to be associated with offspring’s complications induced by mechanisms that are still unclear. The aim of this study was to investigate whether umbilical cord leptin (UCL) and ghrelin (UCG) concentrations are altered in full-term neonates born to EGWG mothers and whether neonatal anthropometric measurements correlate with UCL and UCG levels and maternal serum ghrelin and leptin as well as urine ghrelin concentrations. The study subjects were divided into two groups, 28 healthy controls and 38 patients with EGWG. Lower UCL and UCG levels were observed in neonates born to healthy mothers but only in male newborns. In the control group UCG concentrations correlated positively with neonatal birth weight, body length and head circumference. In the control group maternal serum ghrelin levels correlated negatively with neonatal birth weight, body length and head circumference as well as positively with chest circumference. In the EGWG group UCG concentrations correlated negatively with neonatal birth weight and birth body length. UCL correlated positively with birth body length in EGWG group and negatively with head circumference in the control group. In conclusion, EGWG is associated with disturbances in UCL and UCG concentrations.

Gestational diabetes mellitus (GDM) is traditionally defined as hyperglycemia first detected in pregnancy. The risk of GDM is much higher among obese women than in their lean counterparts. An excess of adipose tissue leads to immune and inflammatory responses of both white adipose tissue and the placenta, contributing to systemic inflammation. Although the significance of both obesity and inflammation is relatively well characterized in GDM, the molecular mechanisms involved are not fully defined and require further study. In recent years huge progress has been made in identifying the intracellular signaling pathways involved in the pathophysiology of GDM. However, currently available data regarding inflammation and obesity in women with GDM are still conflicting or incomplete. We discuss selected aspects of the problem and propose future directions for research in the hope of achieving a better understanding of the disease. In particular, this review highlights recent studies exploring molecular alterations related to insulin resistance, inflammation of the adipose tissue and the placenta, lipotoxicity or endotoxemia.

Fetuses exposed to gestational diabetes mellitus (GDM) have a higher risk of abnormal glucose homeostasis in later life. The molecular mechanisms of this phenomenon are still not fully understood. Fatty acid binding protein 4 (FABP4) appears to be one of the most probable candidates involved in the pathophysiology of GDM. The main aim of the study was to investigate whether umbilical cord serum FABP4 concentrations are altered in term neonates born to GDM mothers. Two groups of subjects were selected—28 healthy controls and 26 patients with GDM. FABP4, leptin, and ghrelin concentrations in the umbilical cord serum, maternal serum, and maternal urine were determined via an enzyme-linked immunosorbent assay. The umbilical cord serum FABP4 levels were higher in the GDM offspring and were directly associated with the maternal serum FABP4 and leptin levels, as well as the prepregnancy body mass index (BMI) and the BMI at and after delivery; however, they correlated negatively with birth weight and lipid parameters. In the multiple linear regression models, the umbilical cord serum FABP4 concentrations depended positively on the maternal serum FABP4 and negatively on the umbilical cord serum ghrelin levels and the high-density lipoprotein cholesterol. There are many maternal variables that can affect the level of FABP4 in the umbilical cord serum, thus, their evaluation requires further investigation.