Adropin as a potential protective factor of metabolic complications in obese pregnant women with hyperglycaemia diagnosed in early pregnancy.

Adropin is a hormone which increases insulin sensitivity. It enhances the oxygenation of glucose in the muscles. The 91 obese pregnant women (BMI >30 kg/m2) with gestational diabetes mellitus (GDM) diagnosed in the first half of pregnancy has been recruited to the study group. The control group consisted of 10 age matched and homogeneous pregnant women with BMI <25 kg/m2. Blood samples were collected on visit V1 - between the 28th and 32nd week and on visit V2 - between the 37th and 39th week of gestation. The ELISA test was used to measure the adropin level. The results in the study group and the control group were compared. Blood samples were collected at the same visits. The median concentration of adropin was 442.2 pg/ml on V1 and 453.1 pg/ml on V2. The increase was significant (p<0.05). Results were significantly lower in the control group's patients, i.e. 57.0 pg/ml (p<0.001) on V1 and 107.9 pg/ml on V2 (p<0.001). The higher adropin level on the V1 and V2 visits were related to patients' lower BMI and better metabolic control. The increase in the adropin level in the third trimester may have been involved in the weight gain reduction, whereas better dietary adherence might have had a compensatory effect on increasing insulin resistance. However, the small control group is a limitation of this study.

Significance of multiple myeloma oncogene 1 immunohistochemistry in chronic endometritis detection in patients with recurrent pregnancy losses: an observational study.

The most reliable chronic endometritis diagnosis is based on immunohistochemistry plasma cell identification in endometrial samples. Our study aimed to compare multiple myeloma oncogene 1 (MUM1) and syndecan-1/CD138 immunohistochemistry staining for chronic endometritis diagnosis among patients with recurrent pregnancy loss. We evaluated the presence of endometrial stromal changes. Fifty-four patients with a history of at least two intrauterine pregnancy losses underwent diagnostic hysteroscopy in the follicular phase of the cycle with endometrial aspiration biopsy. In all 54 cases, three successive sections were cut from each paraffin-embedded tissue block for hematoxylin and eosin (H&E), CD138 and MUM1 staining. The goal was to evaluate the level of agreement between the MUM1 and CD138 results and plasma cell detection rate in assessing the endometrial stromal changes. The concordance analysis between CD138 and MUM1 immunohistochemistry staining showed consistent results in 43 of 54 (79.6%) cases. The level of agreement was moderate, based on a Kappa value of 0.60. MUM1 immunostaining was positive for CE in more cases than CD138 staining, and this difference was statistically significant, showing a higher sensitivity of MUM1 in plasma cell detection (p=0.01). Endometrial stromal changes were observed in the majority of cases - 49/54 (90%). Samples without stromal changes were consistently negative for plasma cells using both CD138 and MUM1 staining. We demonstrated that MUM1 staining, used in conjunction with assessing endometrial stromal changes, contributes to a more accurate and comprehensive diagnosis of chronic endometritis.

Leptin and vascular endothelial growth factor A: a cross-talk in obese women with gestational diabetes and with diabetes in pregnancy - a cohort study.

Vascular endothelial growth factor A (VEGF A) synthesis is intensified by leptin in: hypoxia-inducible factor 1 alpha (HIF-1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NfκB)-dependent manners. The study aimed to investigate the association between leptin and VEGF A serum levels in obese women with hyperglycaemia in the third trimester of pregnancy. Sixty obese pregnant women with hyperglycaemia were divided into groups according to body mass index (BMI): group 1: BMI 30.0-34.9 kg/m2; group 2: BMI 35.0-39.9 kg/m2; group 3: BMI ≥40 kg/m2. On the enrolment visit, waist circumference, body mass and height were measured. At visit 1 (V1; gestational week (GW) 28-32) and visit 2 (V2; GW 36-38), anthropometric, blood pressure and heart rate measurements, and blood sample collection were performed. Blood levels of leptin, VEGF A, VEGF receptor 2, HIF-1A, NfκB, interleukin 1 alpha, protein delta homolog 1, nitric oxide and glycated haemoglobin were determined. To analyse the predictors of the biochemical parametres involved in leptin and VEGF A cross-talk, multivariate logistic regression was implemented. Positive correlations between serum levels of leptin and VEGF A were found. Serum level of HIF-1A at V1 was a predictor for the highest quartile of the serum levels of VEGF A at V1 and V2. Leptin serum level at V1 was a predictor for the highest quartile of HIF-1A serum concentration at V2. In group 3 HIF-1A level was higher at V2 compared to V1. We conclude that in obese women with hyperglycaemia in the third trimester of pregnancy there is a significant positive influence of serum leptin on VEGF A synthesis and serum level and HIF-1A seems to play more important role in leptin and VEGF A cross-talk than NfκB.

Low placental angiotensin-converting enzyme expression is related to fetal small for gestational age but not to metabolic control in type 1 diabetic pregnancies.

The maternal renin-angiotensin system is involved in blood pressure control and plays a crucial role in fetoplacental nutrition. Pre-gestational type 1 diabetes (PGDM) leads to serious pregnancy complications. We thus performed a longitudinal study to analyse the association of maternal angiotensin-converting enzyme (ACE) serum levels and placental mRNA expression with fetal newborns gestational weight in type 1 diabetes mellitus (T1DM) women. We recruited 65 singleton pregnant women with T1DM. Placental mRNA ACE gene expression was examined using quantitative real-time PCR. Serum ACE levels were measured in the first, second and third trimesters of pregnancy by ELISA commercial kits. Placental expression of ACE mRNA was significantly lower in small for gestational age (SGA) than appropriate for gestational age (AGA) and large for gestational age (LGA) mothers (0.55±0.06 vs 0.78±0.06 and 0.85±0.07 respectively, p=0.003). In the SGA group, the mRNA expression of ACE positively correlated with maternal body mass index (BMI) in the third trimester (r=0.49; p=0.04). In all study groups maternal ACE level was significantly higher in the third trimester (mean 139.91±SD 69.64) compared to the first and second trimesters of pregnancy (13.57±4.32 and 15.69±15.92 respectively). Our data suggest that lower placental ACE gene mRNA expression may have a vital role in the etiology of SGA babies.

The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

A core outcome set for the treatment of pregnant women with pregestational diabetes: an international consensus study.

OBJECTIVE: To develop a core outcome set (COS) for randomised controlled trials (RCTs) evaluating the effectiveness of interventions for the treatment of pregnant women with pregestational diabetes mellitus (PGDM). DESIGN: A consensus developmental study. SETTING: International. POPULATION: Two hundred and five stakeholders completed the first round. METHODS: The study consisted of three components. (1) A systematic review of the literature to produce a list of outcomes reported in RCTs assessing the effectiveness of interventions for the treatment of pregnant women with PGDM. (2) A three-round, online eDelphi survey to prioritise these outcomes by international stakeholders (including healthcare professionals, researchers and women with PGDM). (3) A consensus meeting where stakeholders from each group decided on the final COS. MAIN OUTCOME MEASURES: All outcomes were extracted from the literature. RESULTS: We extracted 131 unique outcomes from 67 records meeting the full inclusion criteria. Of the 205 stakeholders who completed the first round, 174/205 (85%) and 165/174 (95%) completed rounds 2 and 3, respectively. Participants at the subsequent consensus meeting chose 19 outcomes for inclusion into the COS: trimester-specific haemoglobin A1c, maternal weight gain during pregnancy, severe maternal hypoglycaemia, diabetic ketoacidosis, miscarriage, pregnancy-induced hypertension, pre-eclampsia, maternal death, birthweight, large for gestational age, small for gestational age, gestational age at birth, preterm birth, mode of birth, shoulder dystocia, neonatal hypoglycaemia, congenital malformations, stillbirth and neonatal death. CONCLUSIONS: This COS will enable better comparison between RCTs to produce robust evidence synthesis, improve trial reporting and optimise research efficiency in studies assessing treatment of pregnant women with PGDM. TWEETABLE ABSTRACT: 165 key stakeholders have developed #Treatment #CoreOutcomes in pregnant women with #diabetes existing before pregnancy.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

Low placental visfatin expression is related to impaired glycaemic control and fetal macrosmia in pregnancies complicated by type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is still related to altered fetal growth and severe maternal complications. We studied the possible role of placental visfatin/nicotinamide phosphoribosyltransferase (NAMPT) in fetal development in T1DM pregnancies, the possible role of placental visfatin in fetal macrosomia. Sixty five pregnant women with T1DM and singleton pregnancy were qualified into the study. Placental visfatin expression was by analysed by RT-PCR. We demonstrated the lowest expression of placental visfatin in women who delivered neonates with birth weight NBW > 4000 g (0.76 ± 0.05, P < 0.055). The highest placental visfatin/nicotinamide phosphoribosyltransferase (NAMPT) expression was found in the women who delivered small for gestational age (SGA) and large for gestational age (LGA) newborns (1.09 ± 0.95 vs. 0.87 ± 0.67, P < 0.05, respectively). There was also significant negative correlation between placental visfatin (NAMPT) expression and metabolic status in the 3rd trimester of pregnancy in T1DM LGA group, defined as long-term glycaemic control (3rd trimester HbA1C) - Pearson rank R - 08667654, P < 0.034. We conclude that the low placental visfatin (NAMPT) expression and poor metabolic control in the 3rd trimester of pregnancy may have a role in stimulating fetal overgrowth in T1DM pregnancy.

Maternal first trimester parameters in the prediction of excessive fetal growth in pregnant women with metabolic syndrome.

Metabolic syndrome (MS) and obesity is an important risk factor for fetal complications like excessive fetal growth manifested by large for gestational age (LGA) and macrosomia, which is a consequence of metabolic disturbances present in the first trimester of pregnancy. The aim of this prospective observational study is to analyze the relationship between the first trimester biochemical and anthropometric parameters of fetuses with the incidence of their macrosomia and LGA so to early predict such complications in women with symptoms of MS. A total of 124 Caucasian women in singleton pregnancies who fulfilled MS criteria were enrolled into the study group and compared to 30 healthy pregnant controls. Patients' blood was drawn and sampled for analysis at 11 - 13+6 weeks of gestation. Specific factors were analyzed in terms of influence on fetal growth and perinatal morbidity in both pregnancy groups. The maternal parameters obtained at first trimester that with respect to controls proved influential towards macrosomia defined as > 4000 g were: BMI and weight (28.0 versus 22 m/kg2; P < 0.001), (77.9 kg versus 60.8 kg; P < 0.001), fasting glucose (87.2 versus 82.1 mg/dl; P < 0.042), significantly higher s-E-selectin concentration (32.0 versus 24.5 ng/ml; P < 0.011) and lower adiponectin: (5.6 versus 9.1 µg/ml; P < 0.001). Similarly, the parameters for LGA fetuses were found to be: maternal weight (80.3 versus 60.8 kg; P < 0.001), BMI (28.7 versus 21.6 kg/m2; P < 0.001), fasting glucose (87.2 versus 82.4mg/dl; P < 0.022), increased s-E-selectin (30.8 versus 24.5 ng/ml; P < 0.022) and decreased adiponectin (6.3 versus 8.2 µg/ml; P < 0.024). We concluded that: 1) first trimester BMI with cut-off of 25.5 was significant risk factor for excessive fetal growth; 2) maternal glycemia, as well as adiponectin and soluble E-selectin serum concentration in the first trimester of pregnancy could be predictive of LGA and fetal macrosomia; 3) maternal weight at 11 - 13+6 weeks of pregnancy cut-off 67 kg had high sensitivity and specificity in detecting LGA and fetal macrosomia.

Short-term antidiabetic treatment with insulin or metformin has a similar impact on the components of metabolic syndrome in women with gestational diabetes mellitus requiring antidiabetic agents: results of a prospective, randomised study.

Gestational diabetes mellitus (GDM) is associated with an increased prevalence of fetal and maternal complications primarily caused by maternal hyperglycemia, which results in abnormal fetal growth. Diet modification is a common first step in the treatment of GDM, followed by antidiabetic pharmacotherapy if this approach fails. Insulin therapy is generally accepted; however, oral hypoglycemic agents have been used in this population. In this prospective, randomised study, we compared maternal metabolic status after treatment with insulin or metformin. Pregnant women (gestational age: ≥ 20 weeks) with GDM requiring medical hypoglycemic treatment were randomly allocated to the Metformin (n = 35) or Insulin (n = 43) Groups. Maternal metabolic status - assessed by glycated hemoglobin (HBA1c) level, glycemic profile, insulin concentration, Homeostatic Model Assessment - Insulin Resistance index, and lipids - was recorded at booking and throughout pregnancy. The characteristics of the study group were: maternal age 33.5 ± 5.9 years, gestational age at baseline 28.5 ± 3.5 weeks, prepregnancy body mass index (BMI) 32.2 ± 3.5 kg/m(2), HbA1c at baseline 5.6 ± 0.6%, and average daily glycemia 5.9 ± 0.6 mmol/dl. Fasting glycemia at term was significantly lower in the Insulin Group but there were no significant differences in mean daily glycemia, HbA1c and BMI at term between the groups. Longitudinally, there was a small but significant increase in BMI and a significant increase in high-density lipoprotein-cholesterol in the Insulin Group and a significant increase in the atherogenic index of plasma (AIP) and a trend towards higher triglycerides in the Metformin Group. Both fasting and average daily glycemia were significantly reduced following treatment in both groups. No such change was evident for HbA1c. In a relative risk analysis, metformin treatment was associated with an insignificant elevated risk of HbA1c, triglycerides and lipid indices falling within the highest quartile at term. The risk of gestational weight gain and total cholesterol falling within the highest quartile at term was insignificantly reduced in the Metformin Group. In conclusion, short-term antidiabetic treatment with insulin or metformin has a similar impact on markers of metabolic syndrome in women with GDM requiring antidiabetic treatment. Secondly, treatment with metformin is associated with increased triglyceride levels and higher AIP in the third trimester in pregnant women with GDM.

Placental vascular endothelial growth factor expression in pregnancies complicated by type 1 diabetes.

UNLABELLED: Type 1 diabetes mellitus (T1DM) is still associated with increased risk of severe maternal and foetal complications but their pathomechanism remains unclear. OBJECTIVES: we investigated the possible role of placental vascular endothelial growth factor (VEGF) and VEGF single nucleotide polymorphisms (SNP) in foetal development in T1DM pregnancies. Sixty seven pregnant women with T1DM and singleton pregnancy were enrolled into the study. Results demonstrated higher expression of placental VEGF in women who delivered neonates with birth weight (NBW)>4000g. No such correlation was found in the overall T1DM group and in women who delivered appropriate for gestational age (AGA) and small for gestational age (SGA) newborns. We also demonstrated a significant correlation between 3(rd) trimester mean blood glucose, HbA1C and placental VEGF. No such correlation was found for the 1(st) and 2(nd) trimesters. Top placental VEGF expression and placental mass were found in women who delivered large for gestational age (LGA) newborns. We also found a statistically significant difference in homozygous and heterozygous frequency variants of VEGF SNPs in study groups. We conclude that the increased placental VEGF together with impaired metabolic control may have a role in stimulating foetal overgrowth in T1DM pregnancy.

Concentrations of endothelial nitric oxide synthase, angiotensin-converting enzyme, vascular endothelial growth factor and placental growth factor in maternal blood and maternal metabolic status in pregnancy complicated by hypertensive disorders.

Hypertensive disorders of pregnancy (HDPs) are associated with altered maternal metabolism, impaired perinatal outcome and increased risk for remote maternal complications. The aim of our study was to analyse associations between circulating levels of angiogenic factors and markers of oxidative stress and metabolic status in women with HDP. Forty-six women in singleton pregnancies complicated by HDP and 30 healthy controls were enrolled in a prospective observational study. Serum concentrations of endothelial nitric oxide synthase (eNOS), angiotensin-converting enzyme, vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) were measured in the third trimester and correlated with maternal anthropometrics and metabolic status. We found significantly lower eNOS levels in patients with severe hypertension vs controls, a strong association between eNOS and PlGF in the study group, a significant association between maternal prepregnancy body mass index (BMI) and VEGF levels and an inverse correlation between VEGF and PlGF. Maternal prepregnancy BMI was the only independent predictor for VEGF concentrations. We noted reduced levels of PlGF and eNOS and increased VEGF levels in women with severe hypertension/preeclampsia. First, different forms of HDP are associated with different alteration patterns in concentrations of angiogenic factors and markers of oxidative stress. Second, maternal prepregnancy BMI, but not body weight, is a significant predictor for VEGF levels in late pregnancy.

Placental leptin and its receptor genes expression in pregnancies complicated by type 1 diabetes.

Type 1 diabetes mellitus (T1DM) is still associated with increased risk for severe maternal and fetal complications but their pathomechanism remains unclear. We investigated into possible role of placental leptin (LEP) and its receptor gene (LEPR) in T1DM pregnancies. Fourty nine pregnant women with T1DM and singleton pregnancy were enrolled into the study. Control group consisted of 15 healthy pregnant women in uncomplicated, singleton gestation. We observed higher expression of LEP and LEPR in T1DM placentas in comparison to healthy subjects. We also noticed greater expression of LEP and LEPR in T1DM pregnancies with large for gestational age (LGA) and appropriate for gestational age (AGA) fetuses in comparison to small for gestational age (SGA) diabetic fetuses and controls. We found a significant positive correlation between placental LEP and LEPR expression and neonatal birthweight in overweight T1DM subjects. No such a correlation was found in T1DM subjects with normal weight and controls. We conclude that increased placental LEP and LEPR expression may have a role in stimulating fetal overgrowth in T1DM pregnancy.

Metabolic syndrome in type 1 diabetes mellitus. Does it have any impact on the course of pregnancy?

UNLABELLED: To determine whether the symptoms of metabolic syndrome (MS), if accompanied by oxidative stress (OS), in type 1 diabetes mellitus (DM) patients could affect the course of pregnancy and the perinatal outcome. Oxidized low density lipoproteins (ox-LDL) and total lipid peroxides (TLP) were studied in 98 pregnant women with type 1 DM in the I(st) and III(rd) trimesters. 24% of the participants met the criteria of MS. Vascular complications were significantly more frequent in the MS-group (41.9% vs. 17.4% in the non-MS group, p<0.05). No differences in the markers of OS between the MS and the non-MS groups were noted in either the I(st) or the III(rd) trimester. A significant gestational rise in Per-Ox was found in both groups. Chronic hypertension was associated with significant differences in ox-LDL levels in both the I(st) and III(rd) trimester. No differences in perinatal outcome, as measured by abnormal birth weight or poor neonatal status (Apgar score<6, umbilical venous and/or arterial pH<7.20), were found. CONCLUSIONS: 1) MS in type 1 DM is associated with some changes in markers of oxidative stress, but it poses no additional risk to the course of pregnancy and perinatal outcome in properly controlled and treated pregnant women with type 1 DM. 2) Maternal hypertension is the only component of MS in diabetic pregnancy that is associated with significant changes in markers of oxidative stress. 3) MS is significantly more frequent in diabetic pregnant women with co-existing vascular complications and obesity.

Maternal endothelial dysfunction and its association with abnormal fetal growth in diabetic pregnancy.

AIMS: Some authors consider the vascular endothelium to be a target organ in diabetes. However, there have only been a few studies of the function of the maternal endothelium during pregnancy in women with diabetes. We analysed the relationship between maternal vascular endothelial dysfunction and fetal growth in such pregnancies. METHODS: Markers of endothelial dysfunction (serum concentration of sE-selectin and sVCAM-1) were measured at admission (baseline) and before delivery in 97 women with pregestational diabetes and a singleton pregnancy,. After delivery, the group with pregestational diabetes was divided retrospectively according to neonatal birthweight into three groups-appropriate, small and large for gestational age- and the maternal variables were analysed in relation to birthweight. RESULTS: The baseline concentration of sE-selectin was significantly higher in the large-for-gestational-age group vs. the small-for-gestational-age group (median: 53.1 vs. 39.0 ng/ml, P<0.05). The concentration of sVCAM-1 at baseline was significantly higher in the small-for-gestational-age vs. the appropriate- and large-for-gestational-age groups (median: 846.2 vs. 576.8 and 524.1 ng/ml, respectively; P<0.01 and P<0.001, respectively). The concentration of sE-selectin at baseline and gestational changes in the concentration of sVCAM-1 were related to birthweight. The baseline concentrations of sE-selectin and sVCAM-1 and the gestational change in sVCAM-1 concentration were predictive factors for large for gestational age (cut-off values: 45.0, 644.6 and 38.4 ng/ml; sensitivity: 67.7, 89.3 and 34.4%; specificity: 65.5, 39.7 and 85.5%, respectively). CONCLUSIONS: Our study showed a relationship between maternal endothelial dysfunction and fetal growth disturbances during pregnancy in women with diabetes that was not associated with maternal metabolic control. Higher levels of maternal sE-selectin in early pregnancy were associated with increased risk of the large-for-gestational-age condition. High levels of maternal sVCAM-1 in early pregnancy were characteristic of gestation complicated by the small-for-gestational-age condition. Further studies in larger groups are warranted to determine whether markers of maternal endothelial dysfunction are of use in the prediction of abnormal birthweight (large or small for gestational age) in pregnant women with diabetes.

Components of metabolic syndrome and their impact on fetal growth in women with gestational diabetes mellitus.

UNLABELLED: Gestational diabetes mellitus (GDM) is associated with increased maternal insulin resistance. Maternal hyperglycemia is a well known risk factor for fetal overgrowth. However, despite improved glycemia control, macrosomia complicates a significant proportion of diabetic pregnancies, resulting in increased perinatal risk. The aim of our retrospective study was to investigate the association between fetal growth and different maternal metabolic characteristics in women with GDM. The study group included 357 women (singleton pregnancy, and GDM diagnosed following WHO criteria). The following parameters were studied: maternal pre-pregnancy BMI, 75 g OGTT results, HbA(1c), triglycerides (TAG), total, HDL- and LDL-cholesterol levels at admission. Neonatal birth weight and the prevalence of being large for gestational age birth weight (LGA) was an end-point. We found a significant association between birth weight and HbA(1c), TAG, fasting OGTT glycemia, BMI and a birth weight of a large child born previously. BMI and birth weight of a large child was the strongest independent predictors for LGA. A significant increase in birth weight and the prevalence of LGA (from 10.5% to 83.3%) was related to a number of altered maternal metabolic features. CONCLUSIONS: Fetal growth in a diabetic pregnancy is a complex process and maternal metabolic parameters other than glucose levels should be addressed to reduce the risk of macrosomia in these groups of patients.

Leptin gene, leptin gene polymorphisms and body weight in pregnant women with diabetes mellitus type I.

UNLABELLED: There have been several genetic causes of obesity discussed by past authors, among others leptin, that have provided information regarding signaling pathways in energy expenditure in humans. Genetic variants of the leptin gene and its receptor may influence body weight. AIM: To investigate the role of the leptin gene's polymorphism promotion region (2548 G/A) and the leptin gene receptor polymorphism (668 A/G) and its associations with body weight in pregnant women with type 1 diabetes (PGDM-1). METHODS: 78 PGDM-1 were qualified to the study group (SG) which was divided into normal and over-weight individuals according to BMI criteria. The control group (CG) consisted of first trimester healthy pregnant women with normal body weight. Genetic variants of the leptin gene and its receptor were analyzed using PCR-RFLP assays. Within the SG, the following metabolic parameters were estimated: MBG, HbA1C, insulin dose, LDL, HDL, T-CHOL, creatinine, creatinine clearance and blood pressure. RESULTS: There was a trend found among the majority of homozygous A and G variants in LEP -2548 G/A and LEPR 668 A/G in over-weight and obese individuals in comparison to normal-weight subjects (CG). There were no specific differences found in selected first trimester metabolic parameters in relation to patients' genotypes.

Acylation stimulating protein is associated with pregnancy weight gain.

Among the proteins secreted by adipocytes, acylation stimulating protein (ASP), which plays a crucial role in energetic balance regulation, merits particular attention. ASP is a protein of the C3 complement system, responsible for glucose and lipids metabolism in an insulin-independent mechanism. ASP's role during pregnancy and its interactions with pregnancy hormones remains unknown. The lipogenic character of ASP may impose a question as to what extent this hormone participates in pregnant women lipogenesis, and what is the basal and postprandial ASP secretion during the second trimester of pregnancy. The results of the examinations of 26 pregnant women during the second trimester of their first pregnancy were analyzed. Due to the limited data available in the literature, a control group was examined. The group consisted of 8 healthy non-pregnant patients within similar age ranges. Blood samples were collected in order to determine ASP, total cholesterol, HDL, LDL and triglyceride levels. Basal ASP levels present in obese pregnant women (group OBP; 30.20 +/- 2.13 ng/mL) were significantly higher than those in the healthy control group (group LnP; 20.49 +/- 1.97 ng/mL), P<0.05. Mann-Whitney U test- analysis of these group differences indicated that OBP patients had significantly higher ASP levels than controls at 30 (P<0.01), 60 (P<0.01), and 120 (P<0.01) min after a meal. After a meal, the incremental ASP area under the curve in group OBW patients was significantly higher from that observed in control group LnP (718,9 +/- 263,9 ng/mL x 2h vs. 35,1 +/- 14,6 ng/mL x 2h, P<0.05). Basal concentration of triglycerides, total cholesterol and LDL cholesterol were significantly higher in all pregnant women compared to the group of non-obese non-pregnant women. It was found that lipid parameters were highly dependent upon body mass gain during pregnancy. Group OBP demonstrated significantly higher basal concentrations of all parameters of lipid metabolism in comparison with the remaining groups of pregnant patients. In conclusion, we found abnormalities of ASP and lipid profiles in lean, overweight, and obese pregnant women strictly connected with obesity. Acylation stimulating protein correlated with lipid parameters, suggesting increased risk of dyslipidemia in obese pregnant women.

Concentration of chemokines in peripheral blood in first trimester of diabetic pregnancy.

BACKGROUND: Several types of regulators (i.e. chemokines and metalloproteinases) are considered to play a crucial role in pregnancy by local modulation of the immune system at the level of peripheral leukocytes. The aim of this study was to determine whether changes in chemokines (interferon-gamma-inducible protein (IP-10), monocyte chemotactic peptide-1(MCP-1), cytokines regulated upon activation normal T cell expressed and secreted (RANTES) and matrix metalloproteinase-9 (MMP-9)) concentrations in diabetic patients could affect the course of pregnancy. METHODS: The study group consisted of 65 diabetics in the first trimester of pregnancy. Some 47 pregnancies were successfully continued to delivery, 18 were terminated with spontaneous miscarriages. Twenty healthy women matched for gestational age served as a control group. RESULTS: Glycated haemoglobin (HbA1C), vascular complications and lipoproteins (cholesterol, HDL-cholesterol, low density lipoprotein (LDL)-cholesterol and triglicerides) concentrations in maternal blood did not influence the chemokines concentrations. Lower RANTES level and higher MMP-9 concentrations were found in diabetic women. MCP-1 and RANTES levels differed significantly between pregnancies with good and poor perinatal outcome. A logistic regression model revealed that not only duration of diabetes, age of patients, HbA1C and insulin requirements, but also MMP-9,RANTES, MCP-1 and LDL-cholesterol levels seem to be involved in first trimester metabolism. CONCLUSIONS: Our results suggest the possible role of chemokines in early pregnancy development, especially in well-controlled diabetic patients, when hyperglycaemia is unlikely to be the main reason for an unfavourable outcome. Our results show that MCP-1 and RANTES might serve as predictive factors for an unfavourable outcome in diabetic pregnancy, whereas MMP-9 seems to be a marker of immunological changes related to mild hyperglycaemia. However, the open question of how the modulation of chemokines concentrations might be applied to prevent miscarriage in diabetic patients remains.