Correction to: Pregnant women with gestational diabetes and with well controlled glucose levels have decreased concentrations of individual fatty acids in maternal and cord serum.

The authors regret that the incorrect figure was shown in Fig. 3d. The corrected figure is reproduced here.

Pregnant women with gestational diabetes and with well controlled glucose levels have decreased concentrations of individual fatty acids in maternal and cord serum.

AIMS/HYPOTHESIS: Both arachidonic acid (AA, 20:4 n-6) and docosahexaenoic acid (DHA,22:6 n-3), long-chain polyunsaturated fatty acids (LCPUFA), are involved in fetal development and, based on their percentage compositions, appear to be specifically accumulated in fetal circulation in a proposed phenomenon known as biomagnification. Discrepancies exist in the literature concerning the effect of gestational diabetes mellitus (GDM) on circulating fatty acids. Our objective was to analyse individual fatty acid concentrations in a large cohort of maternal and cord paired serum samples from pregnant women with and without GDM. METHODS: Overnight fasted maternal and cord blood paired samples from 84 women with GDM and well controlled blood glucose levels and 90 healthy pregnant women (controls) were drawn at term. Individual fatty acids within total serum lipids were analysed by gas chromatography and expressed both as concentrations of fatty acid (mmol/l) and as a percentage of total fatty acids. RESULTS: In the serum of overnight fasted pregnant women with GDM, the concentrations of most fatty acids were lower than in control women, except for AA and DHA, which remained the same. The concentrations of most fatty acids in cord serum were also lower in the GDM group than in the control group, except for α-linolenic acid (ALA,18:3 n-3), which was higher in the GDM group. In both groups, the concentrations of all fatty acids were lower in cord serum than in maternal serum. In GDM participants only, a positive and significant correlation between cord and maternal serum concentration of AA and DHA was observed. CONCLUSIONS/INTERPRETATION: The expression of fatty acids in molar concentrations reveals that GDM decreases the concentration of most fatty acids in both maternal and cord serum. There is a high fetal dependence on maternal AA and DHA, but our findings do not support the existence of a fetal biomagnification of those two LCPUFA.

Implications of Lipids in Neonatal Body Weight and Fat Mass in Gestational Diabetic Mothers and Non-Diabetic Controls.

PURPOSE OF REVIEW: Maternal lipid metabolism greatly changes during pregnancy and we review in this article how they influence fetal adiposity and growth under non-diabetic and gestational diabetic conditions. RECENT FINDINGS: In pregnant women without diabetes (control), maternal glycemia correlates with neonatal glycemia, neonatal body weight and fat mass. In pregnant women with gestational diabetes mellitus (GDM), maternal glucose correlates with neither neonatal glycemia, neonatal birth weight nor fat mass, but maternal triacylglycerols (TAG), non-esterified fatty acids (NEFA) and glycerol do correlate with birth weight and neonatal adiposity. The proportions of maternal plasma arachidonic (AA) and docosahexaenoic (DHA) acids decrease from the first to the third trimester of pregnancy, and at term these long-chain polyunsaturated fatty acids are higher in cord blood plasma than in mothers, indicating efficient placental transfer. In control or pregnant women with GDM at term, the maternal concentration of individual fatty acids does not correlate with neonatal body weight or fat mass, but cord blood fatty acid levels correlate with birth weight and neonatal adiposity-positively in controls, but negatively in GDM. The proportion of AA and DHA in umbilical artery plasma in GDM is lower than in controls but not in umbilical vein plasma. Therefore, an increased utilization of those two fatty acids by fetal tissues, rather than impaired placental transfer, is responsible for their smaller proportion in plasma of GDM newborns. In control pregnant women, maternal glycemia controls neonatal body weight and fat mass, whereas in mothers with GDM-even with good glycemic control-maternal lipids and their greater utilization by the fetus play a critical role in neonatal body weight and fat mass. We propose that altered lipid metabolism rather than hyperglycemia constitutes a risk for macrosomia in GDM.

Maternal adipose tissue becomes a source of fatty acids for the fetus in fasted pregnant rats given diets with different fatty acid compositions.

PURPOSE: The utilization of long-chain polyunsaturated fatty acids (LCPUFA) by the fetus may exceed its capacity to synthesize them from essential fatty acids, so they have to come from the mother. Since adipose tissue lipolytic activity is greatly accelerated under fasting conditions during late pregnancy, the aim was to determine how 24 h fasting in late pregnant rats given diets with different fatty acid compositions affects maternal and fetal tissue fatty acid profiles. METHODS: Pregnant Sprague-Dawley rats were given isoenergetic diets containing 10% palm-, sunflower-, olive- or fish-oil. Half the rats were fasted from day 19 of pregnancy and all were studied on day 20. Triacylglycerols (TAG), glycerol and non-esterified fatty acids (NEFA) were analyzed by enzymatic methods and fatty acid profiles were analyzed by gas chromatography. RESULTS: Fasting caused increments in maternal plasma NEFA, glycerol and TAG, indicating increased adipose tissue lipolytic activity. Maternal adipose fatty acid profiles paralleled the respective diets and, with the exception of animals on the olive oil diet, maternal fasting increased the plasma concentration of most fatty acids. This maintains the availability of LCPUFA to the fetus during brain development. CONCLUSIONS: The results show the major role played by maternal adipose tissue in the storage of dietary fatty acids during pregnancy, thus ensuring adequate availability of LCPUFA to the fetus during late pregnancy, even when food supply is restricted.

Fate of orally administered radioactive fatty acids in the late-pregnant rat.

To investigate the biodisponibility of placental transfer of fatty acids, rats pregnant for 20 days were given tracer amounts of [(14)C]palmitic (PA), oleic (OA), linoleic (LA), α-linolenic (LNA), or docosahexaenoic acid (DHA) orally and euthanized at 0.5, 1.0, 2.0, or 8.0 h thereafter. Maternal plasma radioactivity in lipids initially increased only to decline at later times. Most of the label appeared first as triacylglycerols (TAG); later, the proportion in phospholipids (PhL) increased. The percentage of label in placental lipids was also always highest shortly after administration and declined later; again, PhL increased with time. Fetal plasma radioactivity increased with time, with its highest value at 8.0 h after DHA or LNA administration. DHA initially appeared primarily in the nonesterified fatty acids (NEFA) and PA, OA, LA, and LNA as TAG followed by NEFA; in all cases, there was an increase in PhL at later times. Measurement of fatty acid concentrations allowed calculation of specific (radio)activities, and the ratio (fetal/maternal) of these in the plasmas gave an index of placental transfer activity, which was LNA > LA > DHA = OA > PA. It is proposed that a considerable proportion of most fatty acids transferred through the placenta are released into the fetal circulation in the form of TAG.

Dietary Implications of Polyunsaturated Fatty Acids during Pregnancy and in Neonates.

Certain limitations exist for animals to modify fatty acid changes. Besides the role of arachidonic acid (AA), docosahexaenoic acid (DHA) and other 20-carbon long-chain polyunsaturated fatty acids (LCPUFAs) for the synthesis of inflammatory mediators as eicosanoids, different LCPUFAs have many other effects, including their abilities to regulate gene expression and downstream events. LCPUFAs are susceptible to autoxidation, which is prevented by the action of antioxidants in the form of enzymes like superoxide dismutases, catalases and peroxidases, as well as antioxidant compounds that protect against oxidation or repair the damage caused. Under normal conditions, the fetus needs both essential fatty acids (EFAs) and LCPUFAs, which are obtained from its mother by placental transfer. In early pregnancy, dietary derived fatty acids are accumulated in maternal adipose tissue. However, during late pregnancy, corresponding to the period of the highest fetal growth, maternal adipose tissue becomes catabolic and LCPUFAs are released into the circulation by adipose lipolytic activity. The released LCPUFAs are taken up by maternal liver to be esterified and released back to the circulation as triacylglycerides (TAGs) in very-low-density lipoprotein (VLDL) that become available to the placenta to be transferred to the fetus in the form of non-esterified fatty acids (NEFAs). An enhanced adipose tissue lipolysis is maintained around parturition and esterified LCPUFAs are diverted to mammary glands thanks to an increased activity of lipoprotein lipase for milk production. Throughout this process, LCPUFAs become available to the newborn during suckling. The important role of both DHA and AA for the development of the nervous system and for growth has motivated their dietary supplement during different postnatal stages. This has been especially important in preterm infants both because under normal conditions, the fetus acquires most of these fatty acids during late pregnancy, and because the immaturity of the enzyme systems for the synthesis of AA and DHA from their respective EFAs.

Foetal hyperinsulinaemia and increased fat mass correlate negatively with circulating fatty acid concentrations in neonates of gestational diabetic mothers with dietary-controlled glycaemia.

BACKGROUD: Higher accretion of prenatal fat is associated with a higher proportion of obesity in children. However, most of the data on regulatory factors involved in fetal adipogenesis come from animal studies; in humans there is no evidence on how fetal insulin affects fatty acid concentrations and fetal adiposity. OBJECTIVE: We evaluate the relationship between fetal adipose tissue accretion with insulin and fetal consumption of circulating fatty acid (FA). METHODS: In fasting maternal blood at term and cord samples, from 41 gestational diabetes mellitus women (GDM) and 68 non-diabetic controls, serum compounds were determined. Individual FA were analyzed and expressed as concentrations of FA (mmol/L). RESULTS: Both groups had similar maternal serum glucose, insulin, triacylglycerol (TAG), non-esterified FA (NEFA), glycerol and leptin concentrations, but most individual maternal serum FA were lower in GDM than controls. Neonatal fat mass (FM) was higher in the GDM group even though neonatal birth weights were similar. In GDM cord serum glucose, insulin, NEFA and leptin were higher than controls, but glycerol and all individual FA were lower. In GDM neonates only, a negative correlation was found between each FA and FM, and there was a strong negative correlation between the concentrations of umbilical blood insulin and five major FA. CONCLUSION: Our results show for the first time that hyperinsulinemia in fetuses of GDM women increases FA utilization, which may contribute to to their increased adiposity.

Relationship of ANGPTL6 With Neonatal Glucose Homeostasis and Fat Mass Is Disrupted in Gestational Diabetic Pregnancies.

CONTEXT: Angiopoietin-like protein 6 (ANGPTL6) is a hepatokine, which, in animal studies, improves insulin sensitivity and increases energy expenditure to counteract insulin resistance. OBJECTIVE: Evaluate in a human population, the role of serum ANGPTL6 in gestational diabetes mellitus (GDM) or its presence in fetal circulation. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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 ±â€…12 ng/mL vs 119 ±â€…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. CONCLUSION: 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.

Leptin Concentration, Obesity, and Plasma Non-esterified Fatty Acid Levels in Children.

The association between obesity and higher non-esterified fatty acid (NEFA) levels has been established in adults. In contrast, lower NEFA levels have been described in children with obesity although the reason behind this association remains unclear. Leptin, which regulates body weight and plays a role in lipolysis, could be involved in this relationship. We evaluated the influence of leptin in the association between obesity and NEFA concentrations in children, analyzing two cohorts including 684 6- to 8-year-olds and 836 12- to 16-year-old children, respectively. After adjusting by leptin, insulin levels remained significantly higher in adolescents with obesity as compared with levels in those without obesity. However, insulin levels showed no differences between prepubertal children with and without obesity. The significantly lower NEFA concentrations observed in 6- to 8-year-old girls with obesity disappeared when comparing NEFA levels between girls with and without obesity after adjusting by leptin. We report an influence of leptin levels on the association between obesity and insulin and NEFA in young children that is not observed in adolescents. Our findings add information about factors that may contribute to explain the lower NEFA levels described in prepubertal children with obesity.

Enhanced circulating retinol and non-esterified fatty acids in pregnancies complicated with intrauterine growth restriction.

IUGR (intrauterine growth restriction) increases the incidence of perinatal complications and, although several placental transport functions have been shown to be altered in pregnancies complicated by IUGR, the mechanism behind it is not well understood. The aim of the present study was to investigate factors in maternal and cord blood plasma from normal and IUGR-complicated pregnancies associated with the body weight of newborns. At the time of Caesarean section, 24 women with IUGR pregnancies were compared with a group of 30 normal controls with AGA (appropriate gestational age) fetuses who were studied at Caesarean section, which took place 5 weeks later than IUGR pregnancies, and also to a group of 25 non-delivered gestational age-matched control pregnant women (AGA-35wk). Maternal plasma retinol, gamma- and alpha-tocopherol, NEFAs (non-esterified fatty acids), and palmitic, palmitoleic, gamma-linolenic and arachidonic acids were higher in women with IUGR pregnancies than in AGA-35wk controls, whereas stearic and alpha-linolenic acids were lower. Smaller differences were found when comparing these variables for IUGR and AGA women. However, umbilical vein plasma gamma-tocopherol, cholesterol, triacylglycerols and NEFAs were higher in the IUGR group than in the AGA group, whereas arachidonic acid was lower. Maternal plasma retinol and NEFAs were the only variables negatively correlated with birthweight when multiple linear regressions were analysed. In conclusion, the increased levels of circulating retinol and NEFAs in maternal plasma are negatively associated with birth and placental weights, which may reflect an impaired placental transfer in IUGR pregnancies. As retinoids are involved in the control of gene transcription, it is proposed that a decrease in placental transfer of retinol could underlie the metabolic dysfunction of IUGR pregnancies.

Relationship of NEFA concentrations to RBP4 and to RBP4/retinol in prepubertal children with and without obesity.

BACKGROUND: The regulation of adipose tissue metabolism in early childhood obesity is not well understood. Insulin levels are higher and insulin resistance seems to be present in prepubertal children with obesity but, differing from their behavior in adults with obesity, non-esterified fatty acid (NEFA) concentrations are not increased. Retinol-binding protein (RBP)-4 concentration is associated with obesity and insulin resistance conditions, but the means of this relationship remain unclear, and few studies have taken retinol values into account to evaluate it. OBJECTIVE: To analyze the relationship between RBP4 concentration and lipolytic products in plasma in 141 prepubertal children aged 6 to 8 years, with and without obesity. METHODS: Plasma glucose, insulin, triacylglycerols, NEFA, glycerol, leptin, RBP4, and retinol were analyzed in obese and in their normal-weight counterparts. Homeostatic model assessment, quantitative insulin sensitivity check index, and fasting glucose to insulin ratio were calculated as indicators of insulin resistance. RESULTS: Fasted plasma NEFA concentrations were lower in children with obesity than in their normal weight counterparts, despite leptin, insulin resistance indices, RBP4, retinol, and RBP4/retinol (an index of free-RBP4) being higher. NEFA and glycerol concentrations were inversely correlated with RBP4/retinol in children with obesity but not in those without obesity. In normal weight children, total RBP4 correlated negatively with NEFA and glycerol concentrations and positively with insulin and homeostasis model assessment for insulin resistance. These results indicate that a low saturation of RBP4 with retinol, which implies a higher concentration of free-RBP4, may preserve the antilipolytic function of insulin in adipose tissue in children with obesity. CONCLUSION: Our findings suggest that, in prepubertal children with obesity and insulin resistance, the amount of RBP4/retinol correlates with the antilipolytic response of the adipose tissue to insulin rather than the total RBP4 concentration.

Angiopoietin-like protein 4 (ANGPTL4) is related to gestational weight gain in pregnant women with obesity.

Angiopoietin-like protein 4 (ANGPTL4) is a circulating protein involved in the regulation of adipose tissue metabolism. However, its role in obesity and pregnancy is unknown. To evaluate the relationship between gestational weight gain (GWG) and circulating concentrations of ANGPTL4 in pregnant women with overweight and obesity, weight gain and fasting maternal blood samples of thirty-one pregnant women was drawn at 15, 24 and 32 weeks of gestation. ANGPTL4 concentrations continuously rose throughout gestation, whereas VEGF and leptin did not show the same trend. NEFA and glycerol concentrations remained stable during pregnancy. In contrast, total concentrations of saturated, monounsaturated and n-6 fatty acids, but not n-3 fatty acids, increased with pregnancy. In multiple regression analysis, the increase in plasma ANGPTL4 and decrease in linoleic acid concentrations were the most significant predictors of GWG, although only ANGPTL4 was significantly associated with the weight gain from early pregnancy (area under the ROC curve was 0.80 p < 0.01(95% CI 0.61-0.99)). In conclusion, in pregnant women with overweight and obesity, an increase in plasma ANGPTL4 concentrations throughout pregnancy is positively associated with GWG and could be used as an early marker of increased susceptibility to excess gestational weight gain.

Plasma Retinol Levels and High-Sensitivity C-Reactive Protein in Prepubertal Children.

The relationship between C-reactive protein (CRP) levels and plasma antioxidants has been established in adults. However, the association has been rarely investigated in healthy children. Thus, we examined the cross-sectional association of high-sensitivity CRP (hs-CRP) levels with fat-soluble plasma antioxidant concentrations in a cohort of healthy prepubertal children. We determined hs-CRP levels in 543 healthy six⁻eight-year-old children using a high-sensitivity CRP enzyme-linked immuno sorbent assay (ELISA) kit. The plasma concentrations of lipids, apolipoproteins and lipid-soluble antioxidants (α-tocopherol, γ-tocopherol, lycopene, α-carotene, ß-carotene and retinol) were determined using standardized methods. Pearson correlation analysis showed significant correlations between plasma hs-CRP and α-carotene and retinol concentrations. After adjusting by sex, body mass index (BMI) and lipid levels, only the association with retinol remains significant, with children in the highest hs-CRP tertile group (hs-CRP ≥ 0.60 mg/dL) showing significantly lower levels of retinol than those from the tertiles 1 and 2. A stepwise linear regression selected retinol, BMI, apo A-I and sex as predictors of hs-CRP levels, in a model explaining 19.2% of the variability of hs-CRP. In conclusion, in healthy prepubertal children, after adjusting by sex, BMI and lipid levels, hs-CRP concentrations were highly associated with plasma retinol, which is transported in blood bound to retinol-binding protein but were not associated with the lipoprotein-bound antioxidants.

Lipid metabolism during pregnancy and its implications for fetal growth.

More glucose crosses the placenta than any other substrate, but correlations between its concentration in maternal plasma and fetal growth are not found consistently. The accumulation of maternal fat depots and hyperlipidemia are the two principal changes in lipid metabolism during pregnancy. Although lipids cross the placenta with difficulty, maternal plasma triacylglycerols (TAG) and non-esterified fatty acids (NEFA) correlate with fetal lipids, fetal growth and fat mass under certain conditions. In intrauterine growth restriction, impaired placental transfer of lipophilic compounds (long-chain polyunsaturated fatty acids and lipophilic vitamins) seems to underpin metabolic dysfunction and decreased birth weight. In gestational diabetes mellitus (GDM), maternal TAG and NEFA levels correlate with neonatal anthropometric measures. In GDM, adipocyte fatty acid-binding protein in fetuses correlated with neonatal fat mass; changes in maternal or cord blood leptin, retinol binding protein 4 and adiponectin concentrations have been related to neonatal fat mass or birth weight, although their importance remains to be investigated. The angiopoietin-like protein 4 (ANGPTL-4) is secreted from adipose tissue, liver and placenta, and irreversibly inhibits lipoprotein lipase (LPL) activity. Maternal plasma ANGPTL-4 is decreased in GDM, and it has been proposed to be responsible for an increase in placental LPL activity, which would facilitate a greater fatty acid placental transfer, contributing to the higher fetal fat accumulation. Thus, while evidence suggesting major involvement of maternal lipid metabolism in fetal adiposity and growth exists, the precise mechanisms remain to be elucidated.

Decreased concentrations of the lipoprotein lipase inhibitor angiopoietin-like protein 4 and increased serum triacylglycerol are associated with increased neonatal fat mass in pregnant women with gestational diabetes mellitus.

CONTEXT: Angiopoietin-like protein 4 (ANGPTL4) is an extracellular inhibitor of lipoprotein lipase (LPL) activity. No studies have been done in pregnancy in which hypertriglyceridemia and tissue-specific changes in LPL activity are present. OBJECTIVE: The objective of the study was to determine the relationship between neonatal fat mass (FM) and concentrations of ANGPTL4 and triacylglycerols (TAG) in maternal and cord serum of pregnant women with gestational diabetes mellitus (GDM) compared with controls. DESIGN: Maternal blood samples (control, n = 90, and GDM, n= 80) and umbilical cord blood were drawn before and after vaginal delivery, respectively. Control and GDM subjects were grouped separately into 3 subgroups, according to neonatal FM: 0-25th percentiles, 25th-75th percentiles, and 75th-100th percentiles. OUTCOME MEASURES: Glucose, insulin, TAG, nonesterified fatty acids (NEFAs), and ANGPTL4 were determined in maternal and neonatal serum. RESULTS: Age and pregestational body mass index did not differ between GDM and control women in any subgroups. Maternal serum of GDM pregnant women who delivered the newborn with the highest FM showed the highest concentrations of TAG and NEFAs and lowest concentration of ANGPTL4, despite glucose and insulin concentrations being independent of changes in neonatal FM. However, cord serum of neonates of GDM patients with the highest FM showed higher concentrations of insulin and lower concentrations of TAG than those with lower neonatal FM but no significant differences in NEFAs or ANGPTL4 concentrations. CONCLUSIONS: In well-controlled GDM pregnancies, decreased maternal ANGPTL4 concentrations and a gradient of TAG toward the fetus are related with higher neonatal FM. However, in GDM fetuses with the highest FM, the potential effect of ANGPTL4 inhibiting adipose tissue LPL activity could be overcome by their hyperinsulinemia.

Lack of relationship between cord serum angiopoietin-like protein 4 (ANGPTL4) and lipolytic activity in human neonates born by spontaneous delivery.

BACKGROUND: Ligands of peroxisome-proliferator activated receptors (PPARs), such as non-esterified fatty acids (NEFAs), induce expression of angiopoietin-like protein 4 (ANGPTL4). Recently ANGPTL4 has been reported to be a mediator of intracellular adipose lipolysis induced by glucocorticoids. OBJECTIVE: To determine the concentrations of ANGPTL4 in cord serum of neonates born by spontaneous vaginal delivery (SVD) and by pre-labor cesarean section (CS) from healthy women, and to relate them to parameters of neonatal lipolytic activity at birth. MEASUREMENTS: In 54 neonates born by SVD and in 56 neonates born by CS, arterial cord blood was drawn to determine insulin, cortisol, triacylglycerols (TAGs), glycerol, non-esterified fatty acids (NEFAs), individual fatty acids, ANGPTL4, adiponectin, retinol binding protein 4 (RBP4) and leptin. RESULTS: Birth weight and neonatal fat mass in SVD and CS showed no difference, but the concentrations of glycerol, adiponectin, RBP4, NEFAs and most individual fatty acids were higher in cord serum of neonates born by SVD compared to CS, indicating a higher adipose tissue breakdown in the SVD group. The concentrations of TAG and cortisol were also higher and that of insulin was lower in cord serum of SVD compared to the CS group. However, the concentration in cord serum of ANGPTL4 did not differ between the two groups and no positive correlation with either NEFA or glycerol concentrations were detected. CONCLUSION: ANGPTL4 is known to stimulate lipolysis in adults, but does not appear to mediate the increased activity in SVD, indicating the presence of different regulatory inputs.

Gestational diabetes mellitus causes changes in the concentrations of adipocyte fatty acid-binding protein and other adipocytokines in cord blood.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Disturbances in lipid metabolism in diabetic pregnancy - Are these the cause of the problem?

The most common neonatal complication of gestational diabetes (GDM) is macrosomia. During early pregnancy an accumulation of maternal fat depots occurs followed by increased adipose tissue lipolysis and subsequent hyperlipidaemia, which mainly corresponds to increased triglycerides (TG) in all circulating lipoproteins. In GDM women, the enhanced insulin resistance and decreased oestrogens are responsible for the reported wide range of dyslipidaemic conditions. In GDM, decreased proportion of long chain polyunsaturated fatty acids in fetus plasma could result from decreased supply, impaired placental transfer or even altered intrauterine metabolism. A positive correlation between maternal TG and neonatal body weight or fat mass has been found in GDM. Augmented oxidative stress and altered adipokines have also been found, with an adverse outcome even in normoglycaemic conditions. Thus, although additional studies are required, overall these findings indicate that altered maternal lipid metabolism rather than hyperglycaemia constitutes a risk for macrosomia in GDM.

Gestational diabetes mellitus upsets the proportion of fatty acids in umbilical arterial but not venous plasma.

OBJECTIVE: Neonates of women with gestational diabetes mellitus (GDM) have reduced levels of arachidonic acid (AA) (20:4 n-6) and docosahexaenoic acid (DHA) (22:6 n-3). To assess whether this is the result of impaired placental transfer or endogenous fetal metabolism, fatty acids in umbilical venous and arterial plasma were analyzed in neonates of GDM women. RESEARCH DESIGN AND METHODS: Fatty acids were analyzed by gas chromatography in the plasma of 15 subjects with GDM and 30 healthy control subjects undergoing elective cesarean section and in vein and artery cord blood collected separately. RESULTS: The percentages of AA (20:4 n-6), DHA (22:6 n-3), and total n-6 or n-3 polyunsaturated fatty acids (PUFAs) as well as total PUFAs were lower in umbilical arterial but not in venous plasma of neonates of the GDM versus the control group. CONCLUSIONS: An altered handling or metabolism of long-chain PUFAs by the fetus rather than impaired placental transfer seems to be responsible for the lower proportion of those fatty acids in the plasma of neonates of GDM mothers.