c-peptide and Birth-Weight

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

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

Gender plays a role in the development of a number of cardiovascular and metabolic diseases and it has been suggested that females may be more insulin resistant in utero. We sought to assess the relationship between infant gender and insulin resistance in a large pregnancy cohort.. This is a secondary analysis of a cohort from the ROLO randomized control trial of low GI diet in pregnancy. Serum insulin, glucose and leptin were measured in early pregnancy and at 28 weeks. At delivery cord blood C-peptide and leptin were measured. A comparison of maternal factors, fetal biometry, insulin resistance and leptin was made between male and female offspring. A multivariate regression model was built to account for the possible effects of maternal BMI, birthweight and original study group assignment on findings.. A total of 582 women were included in this secondary analysis, of whom 304 (52.2%) gave birth to male and 278 (47.8%) gave birth to female infants. Compared to male infants at birth, female infants were significantly lighter, (3945 ± 436 vs. 4081± 549g, p<0.001), shorter in length (52.36 ± 2.3 vs. 53.05 ± 2.4cm, p<0.001) and with smaller head circumferences (35.36 ± 1.5 vs. 36.10 ± 1.1cm, p<0.001) than males. On multiple regression analysis, women pregnant with female fetuses were less insulin resistant in early pregnancy, i.e. had lower HOMA indices (B = -0.19, p = 0.01). Additionally female fetuses had higher concentrations of both cord blood leptin and C-peptide at birth when compared to male offspring (B = 0.38, p<0.001 and B = 0.31, p = 0.03 respectively).. These findings suggest gender is a risk factor for insulin resistance in-utero. Additionally, carrying a female fetus decreases the risk of insulin resistance in the mother, from as early as the first trimester.

Topics: Birth Weight; Body Mass Index; C-Peptide; Female; Fetal Blood; Fetal Development; Humans; Infant; Insulin Resistance; Leptin; Male; Pregnancy; Risk Factors; Sex Factors

Large for gestational age infants have an increased risk of obesity, cardiovascular and metabolic complications during life. Knowledge of the key predictive factors of neonatal adiposity is required to devise targeted antenatal interventions. Our objective was to determine the fetal metabolic factors that influence regional neonatal adiposity in a cohort of women with previous large for gestational age offspring.. Data from the ROLO [Randomised COntrol Trial of LOw Glycaemic Index in Pregnancy] study were analysed in the ROLO Kids study. Neonatal anthropometric and skinfold measurements were compared with fetal leptin and C-peptide results from cord blood in 185 cases. Analyses were performed to examine the association between these metabolic factors and birthweight, anthropometry and markers of central and generalised adiposity.. Fetal leptin was found to correlate with birthweight, general adiposity and multiple anthropometric measurements. On multiple regression analysis, fetal leptin remained significantly associated with adiposity, independent of gender, maternal BMI, gestational age or study group assignment, while fetal C-peptide was no longer significant.. Fetal leptin may be an important predictor of regional neonatal adiposity. Interventional studies are required to assess the impact of neonatal adiposity on the subsequent risk of childhood obesity and to determine whether interventions which reduce circulating leptin levels have a role to play in improving neonatal adiposity measures.

Topics: Adiposity; Adult; Anthropometry; Birth Weight; Body Mass Index; C-Peptide; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Leptin; Male; Pediatric Obesity; Pregnancy; Weight Gain

To compare maternal characteristics, obstetric outcomes and insulin resistance in a cohort of women subdivided into those who did and those who did not exceed the Institute of Medicine (IOM) gestational weight gain guidelines.. This is a prospective study of 621 women without diabetes. Concentrations of glucose, insulin and leptin were measured in early pregnancy and at 28 weeks. Ultrasound at 34 weeks assessed fetal anthropometry including abdominal wall width (AAW). At delivery birthweight was recorded and fetal glucose, C-peptide and leptin measured in cord blood. Insulin resistance was calculated using the HOMA equation. Outcomes in those who did and did not exceed IOM guidelines were compared.. Overall, 267 women (43%) exceeded IOM guidelines and 354 (57%) did not. On 34-week ultrasound women with excessive weight gain had higher fetal weights (2681 ± 356 g vs. 2574 ± 331, P = 0.001) and fetal adiposity (AAW) (5.29 ± 1.3 vs. 4.8 ± 1.2, P = 0.001). Infant birthweight and birthweight centiles were also higher in those who exceeded the guidelines. There was no difference between the two groups in maternal insulin resistance in early pregnancy, but by 28 weeks those with excessive weight gain had higher maternal HOMA indices and higher maternal leptin concentrations.. Excessive maternal gestational weight gain has significant implications for infant growth and adiposity, with potential implications for later adult health.

Topics: Adiposity; Adult; Birth Weight; Body Mass Index; C-Peptide; C-Reactive Protein; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Leptin; Pregnancy; Prospective Studies; United States; Weight Gain

To compare the ability of customized versus normalized population fetal growth norms in identifying neonates at risk for adverse perinatal outcomes (APOs) associated with fetal overgrowth and gestational diabetes (GDM).. Secondary analysis of a multicenter treatment trial of mild GDM. The primary outcome was a composite of neonatal outcomes associated with fetal overgrowth and GDM. Birth weight percentiles were calculated using ethnicity- and gender-specific population and customized norms (Gardosi).. Two hundred three (9.8%) and 288 (13.8%) neonates were large for gestational age by population (LGApop) and customized (LGAcust) norms, respectively. Both LGApop and LGAcust were associated with the primary outcome and neonatal hyperinsulinemia, but neither was associated with hypoglycemia or hyperbilirubinemia. The ability of customized and population birth weight percentiles for predicting APOs were poor (area under the receiver operating characteristic curve < 0.6 for six of eight APOs).. Neither customized nor normalized population norms better identify neonates at risk of APOs related to fetal overgrowth and GDM.

Topics: Adult; Area Under Curve; Birth Weight; Blood Glucose; C-Peptide; Confidence Intervals; Diabetes, Gestational; Female; Fetal Macrosomia; Gestational Age; Humans; Hyperbilirubinemia, Neonatal; Hyperinsulinism; Hypoglycemia; Infant, Newborn; Odds Ratio; Pregnancy; Pregnancy Outcome; Reference Values; ROC Curve; Young Adult

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study is a trial on a high evidence level that included 25,000 women recruited in 15 centers all over the world who underwent a 75-gram oral glucose tolerance test (oGTT) at 24-32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was below 105 mg/dl (5.8 mmol/l) and the 2-hour plasma glucose level was below 200 mg/dl (11.1 mmol/l). The aim of the study was to clarify whether maternal hyperglycemia less severe than that in diabetes mellitus is associated with increased risks of adverse pregnancy outcomes. The results indicate a continuous association of maternal glucose levels below those diagnostic of diabetes with an adverse outcome, with the strongest risk for increased birth weight and cord blood serum C peptide levels indicating fetal hyperinsulinism. Additionally an increased risk for maternal complications like preeclampsia was seen. Like in many biological processes, there were no obvious thresholds at which risks increased. An international expert committee proposed how to transfer the HAPO data into criteria for the oGTT in pregnancy for the future diagnosis of gestational diabetes mellitus (GDM) which will be based on acute pregnancy problems in contrast to the recent Carpenter and Coustan criteria. The availability of uniform, internationally accepted and applied GDM criteria will provide more clinical and legal security for the caregivers which will be a big advantage also in Germany where a wide diversity of GDM criteria is used. Beside the threshold discussion, the HAPO data are of enormous relevance for Germany. The HAPO data will significantly influence the decision of the German Health Authorities whether to finally establish a general screening for GDM as obligatory part of prenatal care. A report from the German Institute for Quality and Efficiency in Health Care (IQWiG) which was ordered from the German Health Authorities describes--mainly based on the HAPO Study--an indirect benefit of blood glucose screening for GDM for all pregnant women.

Topics: Birth Weight; C-Peptide; Diabetes, Gestational; Double-Blind Method; Female; Fetal Blood; Fetal Death; Fetal Macrosomia; Germany; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Mass Screening; National Health Programs; Obstetric Labor Complications; Pregnancy; Pregnancy Outcome; Quality Assurance, Health Care; Reference Values; Risk Factors

Macrosomia occurs in infants of diabetic mothers in spite of "nearly normal maternal blood glucose levels" with insulin treatment. Insulin antibodies may carry bound insulin into the fetal blood and thus may be associated with fetal hyperinsulinemia and macrosomia in these infants. Our objective was to test the hypothesis that human insulin is associated with lower insulin antibody levels and less macrosomia than is animal species insulin.. Forty-three insulin-requiring pregnant (< 20 weeks' gestation) women, previously treated with animal insulin, were randomized to human and animal insulins and studied at weeks 10 through 20, 24, 28, 32, 36, and 38, at delivery, and at 3 months post partum. Infant blood was drawn at delivery (cord) and at 1 day and 3 months post partum 1 hour after a glucose-amino acid challenge.. Women receiving human insulin required significantly less insulin per kilogram of body weight and showed significant dampening of glucose excursions (p < 0.05 for each comparison). Infants born to mothers receiving human insulin weighed 2880 +/- 877 gm compared with 3340 +/- 598 gm for infants of women treated with animal insulin (p < 0.05). There was no difference in insulin antibody levels between groups for either mothers or infants. Infants born to mothers receiving human insulin had a 1 hour C-peptide level after the glucose-amino acid challenge at 3 months of age of 0.21 +/- 0.13 pmol/ml compared with 0.32 +/- 0.13 pmol/ml (p = 0.01).. Administration of human insulin to pregnant diabetic women has a therapeutic advantage over animal insulin, with less maternal hyperglycemia or hypoglycemia, fewer larger-for-gestational-age infants, and less neonatal hyperinsulinemia. Our data do not support the hypothesis that maternal antibodies to insulin influence infant birth weight.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Macrosomia; Humans; Infant, Newborn; Insulin; Insulin Antibodies; Pregnancy; Pregnancy in Diabetics; Recombinant Proteins

Obesity during pregnancy is associated with neonatal adiposity, which is a risk factor for childhood obesity. Maternal physical activity (PA) and sedentary behaviours during pregnancy might modify this risk. We therefore studied associations between maternal PA and sedentary time (ST) during pregnancy and neonatal anthropometry and cord blood parameters and investigated whether associations differed by offspring sex.. Participants of the Vitamin D And Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) study with a BMI  ≥ 29 kg/m. Almost all women decreased MVPA levels and increased ST throughout gestation. Both higher maternal mean MVPA and increasing MVPA were associated with lower offspring FM% in males (-0.520%; 95% CI: -1.011%, -0.031% and -4.649%; -7.876%, -1.432% respectively). In female offspring, mean ST was associated with lower cord blood C-peptide (-0.145 µg/l; -0.279 µg/l, -0.005 µg/l). No associations were found with birthweight or other cord blood parameters.. Maternal MVPA is associated with neonatal fat mass, but not birthweight, in male offspring. Our findings underline the importance of physical activity throughout pregnancy.

Topics: Adiposity; Bayes Theorem; Birth Weight; Body Mass Index; C-Peptide; Child; Exercise; Female; Fetal Blood; Humans; Infant, Newborn; Male; Pediatric Obesity; Pregnancy; Sedentary Behavior

Fibroblast growth factor 19 (FGF19) has been implicated in glucose homeostasis. Gestational diabetes mellitus (GDM) enhances fetal insulin secretion and fetal growth. Girls weigh less and are more insulin resistant than boys at birth. We sought to assess whether FGF19 is associated with GDM and fetal growth and explore potential sex dimorphic associations. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns of GDM versus euglycemic mothers matched by infant's sex and gestational age at birth. Cord plasma FGF19, insulin, C-peptide, proinsulin, IGF-I and IGF-II concentrations were measured. Cord plasma FGF19 concentrations were similar in GDM versus euglycemic pregnancies (mean ± SD: 43.5 ± 28.2 versus 44.5 ± 30.2 pg/mL, P=0.38). FGF19 was not correlated with IGF-I or IGF-II. FGF19 concentrations were positively correlated with birth weight (r=0.23, P=0.01) and length (r=0.21, P=0.02) z scores, C-peptide (r=0.27, P=0.002) and proinsulin (r=0.27, P=0.002) concentrations in females. Each SD increment in cord plasma FGF19 was associated with a 0.25 (0.07-0.43) increase in birth weight z score in females. In contrast, FGF19 was not correlated with birth weight or length in males. These sex dimorphic associations remained after adjusting for maternal and neonatal characteristics. The study is the first to demonstrate that GDM does not matter for cord blood FGF19 concentrations. The female specific positive correlation between FGF19 and birth weight is suggestive of a sex-dimorphic role of FGF19 in fetal growth. The observations call for more studies to validate the novel findings and elucidate the underlying mechanisms.

Topics: Birth Weight; C-Peptide; Case-Control Studies; Diabetes, Gestational; Female; Fetal Blood; Fetal Development; Fibroblast Growth Factors; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male; Pregnancy; Proinsulin

We aimed to examine associations of newborn anthropometric measures with childhood glucose metabolism with the hypothesis that greater newborn birthweight, adiposity and cord C-peptide are associated with higher childhood glucose levels and lower insulin sensitivity.. Data from the international, multi-ethnic, population-based Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and the HAPO Follow-Up Study were used. The analytic cohort included 4155 children (mean age [SD], 11.4 [1.2] years; 51.0% male). Multiple linear regression was used to examine associations of primary predictors, birthweight, newborn sum of skinfolds (SSF) and cord C-peptide, from HAPO with continuous child glucose outcomes from the HAPO Follow-Up Study.. In an initial model that included family history of diabetes and maternal BMI during pregnancy, birthweight and SSF demonstrated a significant, inverse association with 30 min and 1 h plasma glucose levels. In the primary model, which included further adjustment for maternal sum of glucose z scores from an oral glucose tolerance test during pregnancy, the associations were strengthened, and birthweight and SSF were inversely associated with fasting, 30 min, 1 h and 2 h plasma glucose levels. Birthweight and SSF were also associated with higher insulin sensitivity (Matsuda index) (β = 1.388; 95% CI 0.870, 1.906; p < 0.001; β = 0.792; 95% CI 0.340, 1.244; p < 0.001, for birthweight and SSF higher by 1 SD, respectively) in the primary model, while SSF, but not birthweight, was positively associated with the disposition index, a measure of beta cell compensation for insulin resistance (β = 0.034; 95% CI 0.012, 0.056; p = 0.002). Cord C-peptide levels were inversely associated with Matsuda index (β = -0.746; 95% CI -1.188, -0.304; p < 0.001 for cord C-peptide higher by 1 SD) in the primary model.. This study demonstrates that higher birthweight and SSF are associated with greater childhood insulin sensitivity and lower glucose levels following a glucose load, associations that were further strengthened after adjustment for maternal glucose levels during pregnancy. Graphical abstract.

Topics: Adiposity; Adult; Age Factors; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Child; Female; Fetal Blood; Follow-Up Studies; Humans; Hyperglycemia; Infant, Newborn; Insulin Resistance; Male; Pregnancy; Prenatal Exposure Delayed Effects; Prospective Studies; Risk Assessment; Risk Factors; Skinfold Thickness; Young Adult

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

Neonates at the highest and lowest percentiles of birth weight present an increased risk of developing metabolic diseases in adult life. While environmental events in utero may play an important role in this association, some genetic variants are associated both with birth weight and type 2 diabetes mellitus (T2DM), suggesting a genetic link between intrauterine growth and metabolism in adult life. Variants rs11708067 in ADCY5 and rs7754840 in CDKAL1 are associated with low birth weight, risk of T2DM, and lower insulin secretion in adults. We aimed to investigate whether, besides birth weight, these polymorphisms were related to insulin secretion at birth.. A cohort of 218 healthy term newborns from uncomplicated pregnancies were evaluated for anthropometric and biochemical variables. Cord blood insulin and C-peptide were analyzed by ELISA. Genotyping of rs11708067 in ADCY5 and rs7754840 in CDKAL1 was performed.. Newborns carrying the A allele of ADCY5 rs11708067 had lower cord blood insulin and C-peptide, even after adjusting by maternal glycemia, HbA1c, and pregestational BMI. Lower birth weight was found for AA-AG genotypes compared to GG, but no differences were seen in adjusted birth weight or z-score. Variant rs7754840 in CDKAL1 was not associated with birth weight, neonatal insulin, or C-peptide for any genotype or genetic model.. The variant rs11708067 in ADCY5 is associated with lower neonatal insulin and C-peptide concentrations. Our results suggest that the genetic influence on insulin secretion may be evident from birth, even in healthy newborns, independently of maternal glycemia and BMI.

Topics: Adenylyl Cyclases; Adult; Birth Weight; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Infant, Newborn; Insulin; Pregnancy; tRNA Methyltransferases

Newborn adiposity is associated with childhood obesity. Cord blood metabolomics is one approach that can be used to understand early-life contributors to adiposity and insulin resistance.. To determine the association of cord blood metabolites with newborn adiposity and hyperinsulinemia in a multiethnic cohort of newborns.. Cross-sectional, observational study.. Hyperglycemia and Adverse Pregnancy Outcome study.. One thousand six hundred multiethnic mother-newborn pairs.. Cord blood C-peptide, birthweight, and newborn sum of skinfolds.. Meta-analyses across four ancestry groups (Afro-Caribbean, Northern European, Thai, and Mexican American) demonstrated significant associations of cord blood metabolites with cord blood C-peptide, birthweight, and newborn sum of skinfolds. Several metabolites, including branched-chain amino acids (BCAAs), medium- and long-chain acylcarnitines, nonesterified fatty acids, and triglycerides were negatively associated with cord C-peptide but positively associated with birthweight and/or sum of skinfolds. 1,5-Anhydroglucitol, an inverse marker of recent maternal glycemia, was significantly inversely associated with birthweight and sum of skinfolds. Network analyses revealed groups of interrelated amino acid, acylcarnitine, and fatty acid metabolites associated with all three newborn outcomes.. Cord blood metabolites are associated with newborn size and cord blood C-peptide levels after adjustment for maternal body mass index and glucose during pregnancy. Negative associations of metabolites with C-peptide at birth were observed. 1,5-Anhydroglucitol appears to be a marker of adiposity in newborns. BCAAs were individually associated with birthweight and demonstrated possible associations with newborn adiposity in network analyses.

Topics: Adiposity; Adult; Anthropometry; Biomarkers; Birth Weight; C-Peptide; Cross-Sectional Studies; Ethnicity; Female; Fetal Blood; Glucose Tolerance Test; Humans; Hyperglycemia; Hyperinsulinism; Infant, Newborn; Male; Metabolomics; Native Hawaiian or Other Pacific Islander; Obesity; Pregnancy; Pregnancy Outcome; Severity of Illness Index

We aimed to determine the association of maternal metabolites with newborn adiposity and hyperinsulinaemia in a multi-ethnic cohort of mother-newborn dyads.. Targeted and non-targeted metabolomics assays were performed on fasting and 1 h serum samples from a total of 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, underwent an OGTT at ~28 weeks gestation and whose newborns had anthropometric measurements at birth.. In this observational study, meta-analyses demonstrated significant associations of maternal fasting and 1 h metabolites with birthweight, cord C-peptide and/or sum of skinfolds across ancestry groups. In particular, maternal fasting triacylglycerols were associated with newborn sum of skinfolds. At 1 h, several amino acids, fatty acids and lipid metabolites were associated with one or more newborn outcomes. Network analyses revealed clusters of fasting acylcarnitines, amino acids, lipids and fatty acid metabolites associated with cord C-peptide and sum of skinfolds, with the addition of branched-chain and aromatic amino acids at 1 h.. The maternal metabolome during pregnancy is associated with newborn outcomes. Maternal levels of amino acids, acylcarnitines, lipids and fatty acids and their metabolites during pregnancy relate to fetal growth, adiposity and cord C-peptide, independent of maternal BMI and blood glucose levels.

Topics: Adult; Birth Weight; C-Peptide; Female; Glucose Tolerance Test; Humans; Hyperinsulinism; Infant, Newborn; Male; Metabolome; Metabolomics; Pregnancy; Pregnancy Outcome; Triglycerides

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

Maternal genetic risk of type 2 diabetes (T2D) can influence offspring birthweight through shared offspring genetic risk and by altering intrauterine glycemic status. The aim of this study was to estimate the independent effects of maternal and offspring genetic risk scores (GRSs) of T2D on offspring birthweight and the extent to which intrauterine glycemic traits mediate the effect of maternal GRSs on offspring birthweight.. The study involved 949 mother-offspring pairs of African ancestry from the Hyperglycemia Adverse Pregnancy Outcome study. GRSs of T2D were calculated separately for mothers and offspring as the weighted sum of 91 T2D risk alleles identified in a genome-wide association study meta-analysis in African Americans. Linear regression models were fit to estimate changes in birthweight by quartiles of GRSs. Mediation analysis was implemented to estimate the direct and indirect effects of maternal GRS on offspring birthweight through cord blood C-peptide and maternal fasting and postchallenge glucose levels.. Maternal and offspring GRSs were independently and differentially associated with offspring birthweight. Changes (95% CI) in birthweight across increasing quartiles of maternal GRSs were 0 g (reference), 83.1 g (6.5, 159.6), 103.1 g (26.0, 180.2), and 92.7 g (12.6, 172.8) (P trend = 0.041) and those of offspring GRSs were 0 (reference), -92.0 g (-169.2, -14.9), -64.9 g (-142.4, 12.6), and 2.0 g (-77.8, 81.7) (P trend = 0.032). Cord blood C-peptide mediated the effect of maternal GRS on offspring birthweight, whereas maternal postchallenge glucose levels showed additive effects with maternal GRS on birthweight.. Maternal and offspring GRSs of T2D were independently and differentially associated with offspring birthweight.

Topics: Adult; Birth Weight; Black or African American; Black People; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Female; Fetal Blood; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Infant, Newborn; Linear Models; Maternal Health; Meta-Analysis as Topic; Pregnancy; Risk Assessment; Risk Factors

The aim of this prospective, observational study was to investigate the impact of gestational weight gain (GWG) among euglycaemic obese pregnant women on maternal and foetal metabolic parameters and neonatal outcome. Total GWG was recorded for 101 obese, non-diabetic women with a singleton pregnancy. At 28 weeks of gestation, fasting maternal blood samples were analysed for glucose, insulin, c-peptide and lipids. Cord bloods were collected at delivery for analysis of glucose, c-peptide and lipids. GWG (mean ± SD =10.9 ± 5.5 kg) was greatest among those of younger age and lower body mass index and 58% of women exceeded the Institute of Medicine GWG recommendations of 5-9 kg for obese pregnancy. GWG was significantly positively associated with increased risk of birthweight >4 kg, cord c-peptide levels and inversely associated with cord total cholesterol. This study identified that higher GWG in obese pregnancy may increase the risk of macrosomia and neonatal hyperinsulinaemia, within a euglycaemic maternal cohort. Impact statement Excess gestational weight gain (GWG) and maternal obesity frequently co-occur with adverse consequences for maternal and neonatal health; however, little is known of the underlying biological pathways which may be affected to contribute to adverse outcomes. Greater understanding of the biological mechanisms involved may help guide future studies to develop targeted interventions for more effective clinical outcomes. This study identified that higher GWG among obese pregnant women resulted in foetal hyperinsulinaemia even in the absence of maternal hyperglycaemia, potentially representing a biological pathway for larger birthweight babies. These results may highlight the need for more intensive dietary and lifestyle interventions among obese women who would not normally receive additional counselling beyond standard antenatal care if not diagnosed with glucose intolerance in pregnancy.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Fasting; Female; Fetal Blood; Humans; Insulin; Lipids; Obesity; Pregnancy; Pregnancy Complications; Prospective Studies; Weight Gain

Maternal glycemia is a key determinant of birth weight, but recent large-scale genome-wide association studies demonstrated an important contribution of fetal genetics. It is not known whether fetal genotype modifies the impact of maternal glycemia or whether it acts through insulin-mediated growth. We tested the effects of maternal fasting plasma glucose (FPG) and a fetal genetic score for birth weight on birth weight and fetal insulin in 2,051 European mother-child pairs from the Exeter Family Study of Childhood Health (EFSOCH) and the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study. The fetal genetic score influenced birth weight independently of maternal FPG and impacted growth at all levels of maternal glycemia. For mothers with FPG in the top tertile, the frequency of large for gestational age (birth weight ≥90th centile) was 31.1% for offspring with the highest tertile genetic score and only 14.0% for those with the lowest tertile genetic score. Unlike maternal glucose, the fetal genetic score was not associated with cord insulin or C-peptide. Similar results were seen for HAPO participants of non-European ancestry (

Topics: Adult; Birth Weight; Black People; Blood Glucose; C-Peptide; Caribbean Region; Diabetes, Gestational; Female; Fetal Blood; Fetal Development; Fetal Macrosomia; Genome-Wide Association Study; Genotype; Humans; Infant, Newborn; Insulin; Male; Mexican Americans; Pregnancy; White People

Topics: Birth Weight; Body Mass Index; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Humans; Incidence; Infant, Newborn; Metabolic Syndrome; Overweight; Pregnancy; Pregnancy Complications; Weight Gain

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

To study gender differences in insulin and C-peptide concentrations at birth using cord blood collection.. This study was conducted in a maternity hospital, in Jammu province of Jammu and Kashmir, India. All women with pregnancy who were hospitalized for delivery were followed. All pregnant ladies who had no medical condition affecting insulin levels, as per history and routine antenatal blood testing, were included in the study. The test for cord plasma insulin and C-peptide was done in 60 (30 males) full-term (≥ 37 completed weeks) normal delivery babies within 4 hours of the collection of samples using the electro-chemiluminescence immunoassay (ECLIA) on Roche elecsys module immunoassay analyzer. Weight of the babies was taken immediately after birth using digital scales.. Cord plasma insulin and C-peptide measured in EDTA were compared between boys and girls and also related to birth weight. Girls were lighter (2,830 ± 37 vs. 3,236 ± 46 g; p = < 0.001) but had higher cord insulin (16.48 ± 4.88 vs. 10.53 ± 4.04 µU/mL; p = < 0.001), and C-peptide (2.47 ± 0.66 vs. 0.834 ± 0.26 ng/mL; p = < 0.001) concentrations than newborn boys.. Female newborn babies have higher cord plasma insulin and C-peptide concentrations than male newborns, despite being smaller, suggesting intrinsic insulin resistance in girls.

Topics: Birth Weight; C-Peptide; Female; Fetal Blood; Gestational Age; Humans; India; Infant, Newborn; Insulin; Insulin Resistance; Male; Pregnancy; Sex Characteristics; Sex Factors

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

We investigated whether obese pregnant women negative for gestational diabetes (GDM) still experience dysglycemia, as indicated by high glycated hemoglobin (Hb A1c) at delivery, and whether this impacts offspring and long-term maternal outcomes.. Data of 462 mother-child pairs of our prospective Programming of Enhanced Adiposity Risk in Childhood - Early Screening (PEACHES) cohort study were analyzed. Of 885 obese and normal-weight pregnancies prospectively enrolled after GDM testing according to the International Association of Diabetes and Pregnancy Study Groups criteria, 462 GDM-negative mothers and their offspring were investigated. We assessed associations of maternal Hb A1c at delivery with large-for-gestational-age (LGA) birth weights, cord-blood C-peptide, and biomarkers of glucose metabolism and inflammation in obese mothers followed for 2.9 years (median) postpartum (n = 42).. Cumulative distribution analysis in GDM-negative normal-weight women (n = 155) revealed that 12% had Hb A1c ≥5.7% at delivery (high Hb A1c). Among obese GDM-negative women (n = 307), 31.9% (95% CI, 26.7%-37.4%) equaled or exceeded this cutoff. In obese GDM-negative women with Hb A1c ≥5.7% (n = 98) vs <5.7% (n = 209) at delivery, newborns were more likely to be born LGA [adjusted odds ratio 3.56 (95% CI, 1.64-8.02)], and mean cordblood serum C-peptide was increased by 0.09 ng/mL (95% CI, 0.01-0.17 ng/mL). In the mothers at follow-up, mean postpartum Hb A1c, fasting glucose, high-sensitivity C-reactive protein, and fibrinogen concentrations were higher by 0.3% (95% CI, 0.1%-0.5%), 6.0 mg/dL (95% CI, 2.4-9.5 mg/dL), 6.8 mg/L (95% CI, 1.4-12.3 mg/L), and 74.9 mg/dL (95% CI, 13.6-136.2 mg/dL), respectively.. Increased Hb A1c in obese GDM-negative women at delivery indicates gestational dysglycemia, potentially conferring offspring and long-term maternal health risks. These findings should raise awareness as to careful monitoring of obese pregnancies. Measurement of Hb A1c at delivery could help select women who may need closer postpartum health checks.

Topics: Birth Weight; Blood Glucose; C-Peptide; Child, Preschool; Delivery, Obstetric; Diabetes, Gestational; Female; Fetal Blood; Glycated Hemoglobin; Humans; Infant; Infant, Newborn; Male; Obesity; Postpartum Period; Pregnancy; Pregnancy Complications; Prospective Studies

The study was undertaken to assess the selected carbohydrate parameters in children exposed to gestational diabetes in utero.. 50 children exposed to gestational diabetes were compared with 46 control subjects. Anthropometric parameters of a newborn were obtained from the medical records. In all participants height, body mass, waist and hip circumferences were measured; BMI, WHR and WHtR were calculated. Values of fasting glucose, insulin, C-peptide and HbA1c were measured and HOMA2-IR, HOMA2-S, HOMA2-B were calculated. In obese children (BMI ≥95th percentile) OGTT was performed.. The prevalence of overweight/obesity in the study group was 38%, in the control group 41% (p=0.19). Higher fasting glucose level (p=0.02) and HbA1c (p=0.00004) were found in the study group comparing to the control. In children exposed to GDM in utero a positive correlation of fasting insulin and WHR (Rs=0.31, p=0.028) as well as significantly lower HOMA2-B (p=0.03) were observed. In the study group higher HOMA2-IR (p=0.0002) and HOMA2-B (p=0.0000039) and also lower HOMA2-S (p=0.0002) were observed among participants with overweight/obesity comparing to children with normal body weight. In the study group a correlation of HOMA2-IR and SD of the birth weight was found (Rs=0.28, p=0.049).. Children exposed to gestational diabetes in utero, in spite of similar prevalence of overweight/obesity comparing to their non-exposed peers, could have higher risk of glucose intolerance and diabetes mellitus in future. Towards observed decreased insulin sensitivity and compensatory increase in insulin secretion, prevention of overweight and obesity in this group seems to be essential.

Topics: Adolescent; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Case-Control Studies; Child; Diabetes, Gestational; Female; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Male; Obesity; Overweight; Pregnancy; Prenatal Exposure Delayed Effects; Prevalence; Waist-Height Ratio; Waist-Hip Ratio

It is important to identify the possible risk factors for the occurrence of large for gestational age (LGA) in newborns and to determine the effect of birth weight and metabolic parameters on subsequent growth. We aimed to determine the effects of maternal weight, weight gain during pregnancy, maternal hemoglobin A1c (HbA1c), C-peptide and insulin as well as cord C-peptide and insulin levels on birth weight and postnatal growth during the first two years of life.. Healthy, non-diabetic mothers and term singleton newborns were included in this prospective case-control cohort study. Fasting maternal glucose, HbA1c, C-peptide and insulin levels were studied. Cord blood was analyzed for C-peptide and insulin. At birth, newborns were divided into two groups according to birth size: LGA and appropriate for GA (AGA). Infants were followed at six-month intervals for two years and their length and weight were recorded.. Forty LGA and 43 AGA infants were included in the study. Birth weight standard deviation score (SDS) was positively correlated with maternal body mass index (BMI) before delivery (r=0.2, p=0.04) and with weight gain during pregnancy (r=0.2, p=0.04). In multivariate analyses, the strongest association with macrosomia was a maternal C-peptide level >3.85 ng/mL (OR=20). Although the LGA group showed decreased growth by the 6-month of follow-up, the differences between the LGA and AGA groups in weight and length SDS persisted over the 2 years of follow-up.. The control of maternal BMI and prevention of overt weight gain during pregnancy may prevent excessive birth weight. The effect of the in utero metabolic environment on the weight and length SDS of infants born LGA persists until at least two years of age.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Case-Control Studies; Child Development; Female; Gestational Age; Glycated Hemoglobin; Homeostasis; Humans; Infant; Infant, Newborn; Insulin; Logistic Models; Placental Circulation; Pregnancy; Prospective Studies

Gestational diabetes mellitus (GDM) occurs in 3-5% of all pregnancies. GDM increases both maternal and fetal risks, causes fetal macrosomia, and hence increases the rates of caesarean sections and delivery complications such as shoulder dystocia. An early predictive marker and consequent early treatment could be beneficial, so amniotic fluid insulin and C-peptide have been examined in several studies. Increased amniotic fluid insulin in early amniocentesis between the 14th and 20th gestational week predicted a later GDM. A potential direct association with fetal macrosomia remains to be determined.. This retrospective study investigated amniotic fluid insulin/C-peptide from amniocenteses between 14 and 20 weeks of gestation in correlation with fetal birth weight, type of delivery, and complications. To focus on effects of fetal hyperinsulinism apart from therapeutic confounders, we included patients who did not participate in GDM screening. Insulin and C-peptide were measured in 144 samples of frozen amniotic fluid. Birth weight, type of delivery, complications, and birth injuries were noted.. Birth weights ranged from 760 g to 4410 g with a mean weight of 3424 g at an average of 40 weeks gestation. The mean amniotic fluid insulin was 4.36 U/ml and the mean C-peptide concentration was 0.076 ng/ml. There was no correlation between amniotic fluid insulin or C peptide and birth weight, type of delivery, complications, and birth injuries.. Amniotic fluid insulin and C-peptide are unsuitable as predictive marker for fetal macrosomia, type of delivery, complications, or birth injuries.

Topics: Amniocentesis; Amniotic Fluid; Biomarkers; Birth Injuries; Birth Weight; C-Peptide; Diabetes Complications; Diabetes, Gestational; Female; Fetal Macrosomia; Humans; Insulin; Iodine Radioisotopes; Obstetric Labor Complications; Pregnancy; Retrospective Studies

To use multilevel functional principal component analysis to exploit the information inherent in the shape of longitudinally sampled glucose curves during pregnancy, and to analyse the impact of glucose curve characteristics on neonatal birth weight, percentage fat and cord blood C-peptide.. A cohort study of healthy, pregnant women (n = 884). They underwent two oral glucose tolerance tests (gestational weeks 14-16 and 30-32), which gave two glucose curves per woman.. Glucose values were higher, and peaked later in third trimester than in early pregnancy. The curve characteristic "general glucose level" accounted for 91% of the variation across visits, and 72% within visits. The curve characteristics "timing of postprandial peak", and "oscillating glucose levels" accounted for a larger part of the variation within visits (15% and 8%), than across visits (7% and <2%). A late postprandial peak during pregnancy, and high general glucose levels in third trimester had significant, positive effects on birth weight (p<0.05). Generally high glucose levels during pregnancy had a significant, positive impact on neonatal percentage fat (p = 0.04). High general glucose level in third trimester had a significant, positive impact on cord blood C-peptide (p = 0.004).. Shape information in entire OGTT curves provides significant physiological information of importance for several outcomes, and may contribute to the understanding of the metabolic changes during pregnancy.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Regression Analysis; Risk Factors; Young Adult

To examine the associations between gestational weight gain (GWG) exceeding Institute of Medicine (IOM) guidelines and neonatal adiposity in the five North American field centers of the Hyperglycemia and Adverse Pregnancy Outcome study.. GWG was categorized as less than, within, or greater than 2009 IOM guidelines. Birthweight, body fat percentage, cord serum C-peptide, and sum of neonatal flank, subscapular, and triceps skin fold thicknesses were dichotomized as >90th percentile or ≤90th percentile obtained by quantile regression. Logistic regression analysis was used.. Of the 5297 participants, 11.6% gained less, 31.9% gained within, and 56.5% gained more than the recommendation. With adjustment for glucose tolerance levels, normal and overweight women who gained more than the recommendation had increased odds of delivering infants with sum of skin folds >90th percentile (OR = 1.75 and 4.77, respectively) and percentage body fat >90th percentile (OR = 2.41 and 2.59, respectively), and normal weight and obese women who gained more than the recommendation had increased odds of delivering infants with birthweight >90th percentile (OR = 2.80 and 1.93, respectively) compared to women who gained within the recommendation.. This analysis showed independent associations between exceeding IOM GWG recommendations and neonatal adiposity in normal and overweight women, controlling for glucose tolerance levels.

Topics: Adiposity; Adult; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Female; Gestational Age; Glucose Tolerance Test; Humans; Hyperglycemia; Infant, Newborn; Male; North America; Obesity; Overweight; Pregnancy; Pregnancy Complications; Pregnancy Outcome; United States; Weight Gain

Large-for-gestational age (LGA) newborns can increase the risk of metabolic syndrome. Previous studies have shown that the levels of maternal blood lipids, connecting peptide (C-peptide), insulin and glycosylated hemoglobin (HbA1c) were significantly different between LGA and appropriate-for-gestational age (AGA) newborns. This study aimed to determine the effect of the levels of maternal lipids, C-peptide, insulin, and HbA1c during late pregnancy on LGA newborns.. This study comprised 2790 non-diabetic women in late pregnancy. Among their newborns, 2236 (80.1%) newborns were AGA, and 554 (19.9%) newborns were LGA. Maternal and neonatal characteristics were obtained from questionnaires and their case records. The levels of maternal fasting serum apolipoprotein A1 (ApoA1), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), C-peptide, insulin and blood HbA1c were measured. The chi-square and Mann-Whitney U test were used to analyze categorical variables and continuous variables between the AGA and LGA groups, respectively. Binary logistic regression analysis was made to determine the independent risk factors for LGA newborns.. Maternal TG, C-peptide, insulin and HbA1c levels were significantly higher in the LGA group than in the AGA group (P<0.05). The LGA group had significantly lower levels of maternal TC, HDL-C and LDL-C than the AGA group (P<0.05). After adjustment for confounding variables, including maternal age, pre-pregnancy body mass index, education, smoking, annual household income, amniotic fluid volume, gestational hypertension, newborn gender and gestational age at blood collection, high maternal TG levels remained significantly associated with LGA newborns (P<0.05).. High maternal TG level during late pregnancy is significantly associated with LGA newborns.

Topics: Adult; Birth Weight; Body Mass Index; C-Peptide; Female; Fetal Macrosomia; Gestational Age; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Lipids; Male; Pregnancy; Risk Factors

The intrauterine environment affects the development of insulin resistance in adulthood. To determine the influence of foetal growth restriction on glucose metabolism, we assessed indices of insulin sensitivity soon after birth in very premature infants. Blood samples were collected at birth from 52 premature infants with a gestational age of ≤31 weeks, who were divided into a group whose birth weight was small for their gestational age (SGA group, n=19) and a group whose birth weight was appropriate for their gestational age (AGA group, n=33). Blood glucose, serum insulin and C-peptide immunoreactivity (CPR) levels were measured in both groups. Furthermore, the quantitative insulin check index (QUICKI) was also calculated. Correlations between these indices and glucose metabolism and the standard deviation (SD) score for birth weight were also determined. The levels of insulin and CPR were significantly (p<0.05) lower in the SGA group than in the AGA group. The QUICKI was significantly (p<0.05) higher in the SGA group compared with the AGA group. The SD score for birth weight was correlated with the QUICKI (p<0.01), the serum insulin level (p<0.05) and the CPR level (p<0.05) in all 52 infants.. In very premature infants, poor foetal growth may impair foetal insulin secretion and affect the QUICKI at birth.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Female; Gestational Age; Humans; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Insulin; Male; Middle Aged

Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment.. Among 77,885 twins in the Danish Twin Registry, 155 of the most BW-discordant MZ twin pairs (median BW difference 0.5 kg) were assessed using a 2 h oral glucose tolerance test with sampling of plasma (p-)glucose, insulin, C-peptide, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. HOMA for beta cell function (HOMA-β) and insulin resistance (HOMA-IR), and also insulin sensitivity index (BIGTT-SI) and acute insulin response (BIGTT-AIR), were calculated. Subgroup analyses were performed in those with: (1) double verification of BW difference; (2) difference in BW >0.5 kg; and (3) no overt metabolic disease (type 2 diabetes, hyperlipidaemia or thyroid disease).. No intra-pair differences in p-glucose, insulin, C-peptide, incretin hormones, HOMA-β, HOMA-IR or BIGTT-SI were identified. p-Glucose at 120 min was higher in the twins with the highest BW without metabolic disease, and BIGTT-AIR was higher in those with the highest BW although not in pairs with a BW difference of >0.5 kg.. BW-discordant MZ twins provide no evidence for a detrimental effect of low BW on glucose metabolism in adulthood once genetic factors and rearing environment are controlled for.

Topics: Adult; Aged; Analysis of Variance; Birth Weight; Blood Glucose; C-Peptide; Denmark; Diabetes Mellitus, Type 2; Disease Susceptibility; Female; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin Resistance; Logistic Models; Male; Middle Aged; Risk Factors; Surveys and Questionnaires; Twins, Monozygotic

To understand the relationships between maternal glycemia during pregnancy and prenatal and early postnatal growth by evaluating cord C-peptide and IGF-I as mediating biomarkers in boys and girls separately.. We evaluated 342 neonates within the EDEN mother-child cohort study born to mothers without diabetes diagnosis before pregnancy. We measured maternal glycemia at 24-28 weeks of gestation and neonates' cord blood C-peptide (used as a proxy for fetal insulin) and IGF-I at birth. Reported maternal prepregnancy BMI and all measured infant weights and lengths in the 1st year were recorded. Growth modeling was used to obtain an individual growth curve for each infant in the 1st year. Path models, a type of structural equation modeling, were used for statistical analysis. Path analysis is a multivariate method associated with a graphical display that allows evaluation of mediating factors and distinguishes direct, indirect, and total effects.. Cord C-peptide at birth was positively correlated with maternal prepregnancy BMI and maternal glycemia and was higher in girls. In a path model that represented prenatal growth, there was no significant direct effect of maternal glycemia on birth weight, but the effect of maternal glycemia on birth weight was mediated by fetal insulin and IGF-I in both girls and boys. However, in girls only, higher concentrations of cord C-peptide (but not cord IGF-I or maternal glucose) were associated with slower weight growth in the first 3 months of life.. Our study underlines the role of the fetal insulin-IGF-I axis in the relationship between maternal glycemia during pregnancy and birth weight. We also show for the first time that high insulin concentration in female fetuses is associated with slower early postnatal growth. This slow, early growth pattern may be programmed by fetal hyperinsulinemia, and girls may be more susceptible than boys to its consequences.

Topics: Birth Weight; Blood Glucose; Body Height; C-Peptide; Child Development; Cohort Studies; Diabetes, Gestational; Female; Fetal Blood; Growth; Humans; Infant; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Male; Mothers; Pregnancy; Pregnancy Complications; Sex Factors

Infants of diabetic mothers (IDM) are considered as a risk group for atherosclerosis. Increased aortic intima-media thickness has been reported in IDM. The purpose of this study was to assess carotid artery intima-media thickness (CA-IMT), left ventricular mass index (LVMI) and atherosclerotic risk factors in IDM.. Thirty IDM and 25 healthy controls were included in the study. Of these infants, 14 were appropriate-for-gestational age (AGA) and 16 were large-for-gestational age (LGA). CA-IMT and LVMI were obtained by M-mode echocardiographic examination. The relationship between parameters of atherosclerosis and echocardiographic measurements was assessed by Pearson's correlation analysis.. LVMI was higher in LGA IDM when compared to AGA IDM and controls. CA-IMT was not significantly different between the groups and was also not related to atherosclerotic risk factors. Serum lipid and insulin levels were higher in LGA IDM when compared with AGA IDM and controls. There were no correlations between CA-IMT, LVMI and atherosclerotic risk factors.. In contrast to previous reports indicating an increase in CA-IMT in IDM, no differences were found between IDM and controls in this study. Our results indicate that macrosomic IDM are prone to hypertrophic cardiomyopathy but not to atherosclerotic changes in the blood vessels.

Topics: Atherosclerosis; Birth Weight; Blood Glucose; C-Peptide; Carotid Intima-Media Thickness; Case-Control Studies; Cholesterol; Female; Fetal Blood; Heart; Heart Ventricles; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy Complications, Cardiovascular; Pregnancy in Diabetics; Prospective Studies; Statistics, Nonparametric; Triglycerides; Ultrasonography, Doppler

The high incidence of insulin resistance, type 2 diabetes, and metabolic syndrome in Western societies and their impact on quality of life emphasize the importance of identifying underlying susceptibility loci for metabolic diseases. The polycystic ovary syndrome (PCOS) susceptibility locus D19S884 allele 8 (A8) is associated with measures of insulin resistance, beta-cell dysfunction, and other metabolic phenotypes in PCOS families. We now investigate the role of D19S884 A8 in pregnancy.. Using the multiethnic Hyperglycemia and Adverse Pregnancy Outcome cohort, we assessed the associations of D19S884 A8 with measures of maternal glycemia and fetal size.. We tested for association of maternal D19S884 A8 with maternal outcomes (fasting, 1-h, and 2-h plasma glucose, and fasting and 1-h C-peptide from an oral glucose tolerance test) and fetal and maternal D19S884 A8 with fetal outcomes (birth weight, length, head circumference, sum of skin folds, fat mass, cord C-peptide, and 2-h neonatal plasma glucose).. We analyzed 4424 Caucasian mothers and 3347 offspring of northern European ancestry, 1957 Thai mothers and 2089 offspring from Bangkok, 1208 Afro-Caribbean mothers and 1209 offspring from Barbados, and 774 Hispanic mothers and 762 offspring from Bellflower, California.. After adjusting for confounding variables and multiple testing, neither maternal nor fetal D19S884 A8 showed significant evidence for association with any of the outcomes tested.. The PCOS susceptibility locus, D19S884 A8, is not a major factor contributing to glycemia during pregnancy or fetal size in a general obstetric population.

Topics: Alleles; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Development; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; Insulin Resistance; Polycystic Ovary Syndrome; Pregnancy; Pregnancy Outcome

Inflammatory mediators are associated with type 2 and gestational diabetes. It is unknown whether there are associations with glucose in pregnant women with lesser degrees of hyperglycemia.. The objective of the study was to examine associations of inflammatory mediators with maternal glucose levels and neonatal size in a subset of participants in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.. Eligible pregnant women underwent a 75-g oral glucose tolerance test between 24 and 32 wk gestation, and levels of C-peptide, adiponectin, plasminogen activator inhibitor type 1 (PAI-1), C-reactive protein (CRP), and resistin were measured in fasting serum samples. Associations of inflammatory mediators with maternal glucose and with birth size were assessed using multiple linear regression analyses, adjusting for maternal body mass index (BMI), fasting C-peptide, and other potential confounders.. Mean levels of adiponectin declined, and PAI-1 and CRP increased across increasing levels of maternal glucose, BMI, and C-peptide. For example, for fasting plasma glucose less than 75 mg/dl and fasting plasma glucose of 90 mg/dl or greater, adiponectin was 22.5 and 17.4 μg/ml and PAI-1 was 30.9 and 34.2 ng/ml, respectively. Associations with 1- and 2-h plasma glucose remained significant for adiponectin (P<0.001), PAI-1 (P<0.05), and CRP (P<0.01) after adjustment for BMI and C-peptide. Adiponectin and CRP were inversely associated with birth weight, sum of skinfolds and percent body fat, and PAI-1 with sum of skinfolds (all P<0.05) after adjustment for confounders. Resistin was not associated with 1- or 2-h glucose or birth size.. Levels of inflammatory mediators are associated with levels of maternal glucose in pregnant women without overt diabetes.

Topics: Adiponectin; Birth Weight; Blood Glucose; Body Mass Index; Body Size; C-Peptide; C-Reactive Protein; Female; Gestational Age; Humans; Infant, Newborn; Inflammation; Male; Plasminogen Activator Inhibitor 1; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Resistin

Topics: Biomarkers; Birth Weight; C-Peptide; Diabetes, Gestational; Female; Glucose Tolerance Test; Humans; Infant, Newborn; Length of Stay; Pregnancy; Pregnancy Outcome

Neonatal diabetes is a heterogeneous group of disorders with diabetes manifestation in the first 6 months of life. The most common etiology in permanent neonatal diabetes is mutations of the ATP-sensitive K(+) channel subunits; in transient neonatal diabetes, chromosome 6q24 abnormalities are the most common cause.. We report a sporadic case of diabetes without ketoacidosis diagnosed on the fourth day of life.. Analysis of the KCNJ11 gene found a novel R365H mutation in the proband and her unaffected father. The functional analysis did not support pathogenicity of this variant. When the patient's diabetes remitted in the seventh month of life, the 6q24 region was analyzed and a paternally inherited duplication was identified.. Our case reports a coincidental novel KCNJ11 variant in a patient with transient neonatal diabetes due to a 6q24 duplication, illustrating the difficulty in testing neonates before the clinical course of neonatal diabetes is known.

Topics: Birth Weight; C-Peptide; Chromosomes, Human, Pair 6; Diabetes Mellitus; Female; Gene Duplication; Genetic Variation; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin; Male; Mutation, Missense; Potassium Channels, Inwardly Rectifying

Mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF) 1beta cause various phenotypes including maturity-onset diabetes of the young type 5 (MODY5) and kidney disease. We provide molecular and pathophysiologic characterization of a 23-year-old male patient with clinical presentation typical for MODY5 with renal involvement. Clinical studies (including intravenous glucose tolerance test and magnetic resonance imaging) of the patient and 5 family members in comparison with unrelated control subjects and molecular analysis of the HNF-1beta gene (direct sequencing, paternity testing, and restriction fragment length polymorphism analysis for parental mosaicism) were performed. The patient was born with low birth weight (2250 g), whereas his dizygotic twin sister was of normal weight (3500 g) and healthy. He had cystic renal dysplasia with progressive renal failure and pancreas atrophy with beta-cell dysfunction and early-onset diabetes mellitus but no family history of diabetes. Intravenous glucose tolerance test showed a markedly reduced but not absent acute insulin response compared with controls (n = 6). A mutation in the HNF-1beta gene S148L (C443T) in exon 2 within the pseudo-POU domain was identified. All other family members and the control group (n = 255) did not have the mutation, suggesting that we described a de novo mutation in HNF-1beta. Paternity was confirmed, and no signs of mosaicism in DNA analysis of both parents could be detected. Of note, the low birth weight of the patient in contrast to his healthy twin sister provides interesting support for the fetal insulin hypothesis for reduced birth weight.

Topics: Adult; Birth Weight; C-Peptide; Diabetes Mellitus, Type 2; DNA; Exons; Glucose Tolerance Test; Hepatocyte Nuclear Factor 1-beta; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin; Kidney; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Mutation; Paternity; Pedigree; Phenotype; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Reverse Transcriptase Polymerase Chain Reaction

To verify whether a diabetes family history might be a risk factor for the development, in adult age, of metabolic disorders, leptin, anthropometric and endocrine parameters were analysed in 95 babies with grandparents affected by type 2 diabetes (DF) and in 95 matched babies without diabetes family history (NDF). A sexual dimorphism for leptin was present in the NDF group (males: 6.7+/-4.1 ng/ml; females: 12.3+/-6.5; p < 0.0001) but not in the DF group (males: 9.0+/-5.5; females: 10.8+/-6.4), due to the significant increase in DF male leptin level, compared to that of NDF males (p < 0.05). In DF males only, leptin was positively correlated with body length, PI, C-peptide, IGF-1 and IGF1BP3. These results suggest that the increase in DF male leptin could be a compensatory mechanism for reduced insulin sensitivity in a pre-clinical alteration of glucose metabolism.

Topics: Birth Weight; Body Height; C-Peptide; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Fetal Blood; Genetic Predisposition to Disease; Humans; Infant, Newborn; Insulin; Insulin Resistance; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Italy; Leptin; Male; Sex Characteristics

Low birth weight is associated with insulin resistance and type 2 diabetes in adults. The fetal programming hypothesis has shown that insulin resistance and its associated metabolic disturbances result from a poor gestational environment, for which low birth weight is a surrogate. An at-home questionnaire survey was performed on 660 middle school students (12-15 years) in Seoul, Korea, and 152 cases were randomly selected based on their birth weight. Subjects were divided into three groups according to birth weight. We recorded their birth weight and measured their current anthropometric data, blood pressure, lipid profile, HOMA-IR, and HOMA-beta, and compared these parameters among the groups. The relation of birth weight to physiological characteristics in adolescence was examined. Systolic blood pressure, lipid profiles, and fasting plasma glucose, HOMA-beta were not significantly different among the groups, but diastolic blood pressure was lower in the third tertile. Insulin, C-peptide, and HOMA-IR were higher in the lower birth weight tertile. After adjustment for confounding factors, birth weight was inversely related to diastolic blood pressure, insulin, C-peptide, and HOMA-IR. We conclude that low birth weight may predict the risk of the insulin resistance and its progression over age, and that adequate gestational nutrition is therefore necessary to prevent low birth weight.

Topics: Adolescent; Birth Weight; Blood Pressure; C-Peptide; Child; Female; Humans; Hyperinsulinism; Insulin; Insulin Resistance; Insulin-Secreting Cells; Korea; Male

Low birth weight has long-term effects on glucose-insulin homeostasis. Factors that could mediate intra-uterine "programing" of glucose homeostasis include endogenous and exogenous glucocorticoids, adipose tissue-secreted factors such as adiponectin, and in utero hypoxia. Here, we studied 123 fetuses with gestational age (GA) between 25 and 37 wk and birth weight sd score (BW SDS) between -2.79 and 2.42. We measured proinsulin, C-peptide, insulin, and adiponectin in umbilical vein (UV) plasma and calculated the proinsulin to insulin ratio as a measure of beta-cell secretory function. These indices were related to GA, BW SDS, time since the last maternal betamethasone administration, and blood gas data. Insulin and C-peptide were correlated with BW SDS but not GA, whereas the proinsulin to insulin ratio was inversely correlated with BW SDS. The proinsulin to insulin ratio was raised (P = 0.002) in fetuses with UV PO(2) less than or equal to 21.3 mm Hg (i.e. the 50th percentile) compared with those with PO(2) more than 21.3 mm Hg, inferring that in utero hypoxia engenders beta-cell secretory dysfunction. Proinsulin, insulin, and C-peptide were markedly but transiently (<24 h) elevated after maternal betamethasone administration, returning thereafter to concentrations measured in noncorticosteroid-treated fetuses. However, there was considerable variability within the less than 24-h betamethasone group: the indices of insulin secretion were related to UV PO(2), suggesting that hypoxia attenuates the responsiveness of fetal beta-cells to corticosteroids. Adiponectin was not related to any of the insulin indices. In conclusion, we have identified two environmental signals that modulate fetal insulin output: maternal corticosteroids produce a transient surge in fetal insulin synthesis and secretion, whereas in utero hypoxia disturbs the insulin secretory process.

Topics: Adiponectin; Adrenal Cortex Hormones; Betamethasone; Birth Weight; Blood Glucose; C-Peptide; Female; Gestational Age; Humans; Infant, Newborn; Insulin; Intercellular Signaling Peptides and Proteins; Islets of Langerhans; Male; Pregnancy; Proinsulin; Umbilical Veins

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

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

To investigate different factors related to fetal growth restriction (FGR) and to find out the possible causes of FGR with unclear etiologies.. Sixty-three women who were suspected of FGR during pregnancy between March 2002 and March 2003 were included in this study. Their age, body mass index (BMI) before pregnancy, and gestational weeks were recorded at the time when they were first diagnosed. Haemoglobin levels, haematocrit (HCT), TORCH, anticardiolipin antibody (ACA), 50 gram glucose challenge test (50g GCT), 75 gram oral glucose tolerance test (75g OGTT), leptin levels, systolic/diastolic (S/D) ratio by color doppler monitor and chlamydia trachomatis (CT) were detected and urine culture was done in these groups during the same period. The gestational week, birth weight, body length and the gender were recorded at the delivery period. The FGR group was then divided into two subgroups according to the birth weights: study A group whose birth weights were lower than 10th% of the birth weights at the given gestational weeks (29 cases) and study B group whose birth weights were beyond 10th% (34 cases). The chromosome, leptin, C-peptide, insulin and TORCH of umbilical blood were measured at delivery. The other 25 normal pregnant women were included as control and the same tests were performed accordingly.. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test of study A were (3.8 +/- 0.6) mmol/L and (4.5 +/- 1.1) mmol/L. The fetal leptin, C-peptide, and insulin were (7.3 +/- 5.2) ng/ml, (0.5 +/- 0.3) nmol/L and (2.3 +/- 1.3) mU/L. The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of asymptomatic bacteriuria were 3.06, 20.7%, 24.1%, 44.8% and 62.1% respectively. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test of study B were (4.4 +/- 0.7) mmol/L and (4.6 +/- 1.1) mmol/L. The fetal leptin, C-peptide, and insulin were (13.2 +/- 11.3) ng/ml, (0.7 +/- 0.4) nmol/L and (4.3 +/- 3.3) mU/L. The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of asymptomatic bacteriuria were 2.63, 2.9%, 0%, 5.9% and 44.1% respectively. The fasting glucose and the third hour's glucose of 75 gram oral glucose tolerance test in control were (4.3 +/- 0.7) mmol/L and (5.3 +/- 1.2) mmol/L. The fetal leptin, C-peptide, and insulin were (20.5 +/- 12.0) ng/ml, (1.0 +/- 0.4) nmol/L and (6.3 +/- 4.0) mU/L. The S/D ratio of umbilical artery, maternal and fetal infection rate of CMV, positive rate of ACA-IgM and the rate of the asymptomatic bacteriuria were 2.80, 0, 0, 0 and 24.0% respectively. All these items were significantly higher in study A than those in the control (P < 0.05). There was no significant difference between the study B and the control in all the items.. Many factors may play a role in the pathogenesis of FGR, including the maternal blood glucose level, the ability for fetus to use the glucose, the infection of some microorganisms, insufficiency of the blood supply and the autoimmunity of the mother. Finding out the possible causes of FGR and managing them accordingly may improve the outcomes of the fetus.

Topics: Adult; Birth Weight; C-Peptide; Cytomegalovirus Infections; Female; Fetal Growth Retardation; Glucose Metabolism Disorders; Glucose Tolerance Test; Humans; Insulin; Leptin; Pregnancy; Pregnancy Outcome; Risk Factors

Our purpose was to evaluate which factors regulate insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in preterm fetuses.. We studied 76 singleton births between 25 and 36 weeks of gestation. Forty-nine pregnancies were complicated by hypertensive disease; 24 pregnancies were complicated by preterm labor or preterm rupture of membranes; and antenatal glucocorticoids were given in 49 pregnancies. Pathology reports showed infarct(s) or hematoma(s) in 31 of 69 placentas. We recorded blood gas values in umbilical artery and vein and measured glucose, C-peptide, and insulin-like growth factor-I and insulin-like growth factor binding protein-1 concentrations in umbilical vein.. Birth weight correlated with umbilical vein insulin-like growth factor-I (r = 0.68, P <.0001) and inversely with insulin-like growth factor binding protein-1 (r = -0.26, P =.02). Babies with birth weight of 25th percentile. Two-factor analysis of variance showed that umbilical vein insulin-like growth factor-I was determined by gestational age (P =.0004) and birth weight percentile (P <.0001), whereas insulin-like growth factor binding protein-1 was not affected by gestational age. Umbilical vein C-peptide was highly correlated with insulin-like growth factor binding protein-1 (r = -0.55, P <.0001), but not insulin-like growth factor-I, levels. Blood gas values in umbilical artery and vein, particularly umbilical artery PO (2), were correlated with umbilical vein insulin-like growth factor-I and insulin-like growth factor binding protein-1 (r = 0.51 and -0.48, respectively; P <.0001); changes in insulin-like growth factor-I and insulin-like growth factor binding protein-1 occurred at umbilical artery PO (2) <14.8 mm Hg. Multiple regression analysis showed that umbilical vein insulin-like growth factor-I was predicted by umbilical artery PO (2), gestational age, and the presence of placental infarcts/hematomas (R (2) of model = 0.58, P <.0001), and umbilical vein insulin-like growth factor binding protein-1 by umbilical vein C-peptide, umbilical artery PO (2), and placental infarcts/hematomas (R (2) = 0.49, P <.0001).. In the preterm fetus, circulating insulin-like growth factor-I is related to gestational age and the in utero growth potential, whereas insulin-like growth factor binding protein-1 is related only to the in utero growth potential. The PO (2) is a robust determinant of both insulin-like growth factor-I and insulin-like growth factor binding protein-1 levels; hypoxia may restrain fetal growth through its effects on the insulin-like growth factor/insulin-like growth factor binding protein axis. Insulin is a powerful determinant of insulin-like growth factor binding protein-1, but not insulin-like growth factor-I, concentrations in the preterm fetus.

Topics: Betamethasone; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Gestational Age; Glucocorticoids; Humans; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Osmolar Concentration; Oxygen; Partial Pressure; Pregnancy; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Umbilical Arteries; Umbilical Veins

The purpose of this study was to examine the relationships between maternal and cord leptin concentrations, maternal and neonatal outcomes, and measures of glycemic control in diabetic and nondiabetic pregnancy.. This was a prospective study of 60 type 1 diabetic and 50 nondiabetic pregnancies in a university teaching hospital. Serum leptin and hemoglobin A(1c) were measured serially throughout pregnancy; leptin, insulin, insulin-like growth factor-1, and C-peptide in venous cord blood were measured at delivery. Leptin was measured with the use of enzyme-linked immunosorbent assay. Data were analyzed with specific computer software.. Maternal leptin levels correlated with cord leptin levels in the nondiabetic group only. Cord leptin levels correlated with cord C-peptide, cord insulin-like growth factor-1, birth weight, birth weight corrected for gestational age, and neonatal anthropometry in both groups and with hemoglobin A(1c) in the diabetic group only. Cord leptin levels increased significantly with increasing birth weight corrected for gestational age but remained significantly higher at all birth weights in the diabetic group.. There are strong associations between cord leptin levels and other measures of fetal growth in both groups and with glycemic control in the diabetic group.

Topics: Adult; Birth Weight; C-Peptide; Case-Control Studies; Female; Fetal Blood; Gestational Age; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Leptin; Osmolar Concentration; Pregnancy; Pregnancy in Diabetics

We studied the contribution of the tumor necrosis factor system and leptin to insulin resistance during the course of normal pregnancy.. Forty-five healthy pregnant women (15 in the 1st, 15 in the 2nd2 and 15 in the 3rd3 trimester) and 25 age-matched healthy nonpregnant women as controls. Twenty-three newborns delivered by women followed in the 2nd and 3rd trimesters were also investigated. Fasting serum immunoreactive tumor necrosis factor-alpha, soluble tumor necrosis factor receptor-1, soluble tumor necrosis factor receptor-2, leptin (by enzyme-linked immunoassay) and C-peptide (by radioimmunoassay) concentrations in the patients and controls were measured. Body weight, length and head circumference of the newborns were analyzed in connection with the measured maternal parameters.. Significantly elevated tumor necrosis factor-alpha, tumor necrosis factor receptor-1 and -2, leptin, and C-peptide levels were found in the 3rd3 trimester as compared with the 1st1 and 2nd2 trimesters and with the nonpregnant controls. Tumor necrosis factor-alpha, tumor necrosis factor receptor-2, C-peptide, leptin concentrations and body mass index were found to be in a significant positive linear correlation with each other. Significant negative linear correlations were calculated among maternal serum C-peptide, tumor necrosis factor-alpha and leptin concentrations and the head circumference of the newborns.. In conclusion, increased tumor necrosis factor-alpha and leptin levels may contribute to insulin resistance in late pregnancy. Tumor necrosis factor-alpha and leptin may be regulators of intrauterine bone development of newborns.

Topics: Adult; Anthropometry; Antigens, CD; Birth Weight; Body Height; Body Mass Index; C-Peptide; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant, Newborn; Insulin Resistance; Leptin; Pregnancy; Pregnancy Trimesters; Radioimmunoassay; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type II; Tumor Necrosis Factor-alpha

Despite their low socioeconomic status, infants of North African immigrants have been reported to have high birth weights in Belgium. The aim of the study was to further explore potential mechanisms explaining this high birth weight.. Venous umbilical cord blood samples and perinatal characteristics of live-born infants from mothers of North African and Belgian nationality were collected in 1997 through 1998 at the University Hospital La Citadelle, Liège, Belgium.. The median connecting peptide (C-peptide) concentration was significantly higher among North African than Belgian neonates (0.125 vs 0.110 pmol/mL, P=.04). However, the median insulin-like growth factor-I concentrations among North African and Belgian newborn infants were, respectively, 74.0 and 69.6 ng/mL (P=.45). Nationality remained significantly associated with C-peptide after adjusting for age and parity. C-peptide, insulin-like growth factor-I correlated positively with birth weight and remained significant factors for birth weight after adjusting for confounders in multiple regression.. These results suggest a link between higher C-peptide levels and birth weights among North African neonates in Belgium.

Topics: Adult; Africa, Northern; Belgium; Birth Weight; Black People; C-Peptide; Emigration and Immigration; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Insulin-Like Growth Factor I; Organ Size; Placenta; Pregnancy; Risk Assessment; Sampling Studies; Social Class; White People

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

Several studies have linked low birth weight (LBW) and type 2 diabetes. We investigated hepatic and peripheral insulin action including intracellular glucose metabolism in 40 19-year-old men (20 LBW, 20 matched control subjects), using the hyperinsulinemic-euglycemic clamp technique at two physiological insulin levels (10 and 40 mU/m(2) per min), indirect calorimetry, and [3-(3)H]glucose. Insulin secretion was examined during an oral and intravenous glucose tolerance test. Fasting p-glucose was higher in the LBW group (5.6 +/- 0.1 vs. 5.4 +/- 0.1; P < 0.05). Basal plasma glycerol concentrations were significantly lower in the LBW group. Insulin-stimulated glycolytic flux was significantly reduced, and suppression of endogenous glucose production was enhanced in the LBW group. Nevertheless, basal and insulin-stimulated rates of whole-body peripheral glucose disposal, glucose oxidation, lipid oxidation, exogenous glucose storage, and nonoxidative glucose metabolism were similar in the two groups. Insulin secretion was reduced by 30% in the LBW group, when expressed relative to insulin sensitivity (disposition index = insulin secretion x insulin action). We propose that reduced insulin-stimulated glycolysis precedes overt insulin resistance in LBW men. A lower insulin secretion may contribute to impaired glucose tolerance and ultimately lead to diabetes.

Topics: 3-Hydroxybutyric Acid; Alanine; Birth Weight; Blood Glucose; C-Peptide; Denmark; Fatty Acids, Nonesterified; Glucagon; Glucose; Glucose Clamp Technique; Glucose Tolerance Test; Glycerol; Humans; Hyperinsulinism; Infant, Low Birth Weight; Infant, Newborn; Insulin; Insulin Secretion; Lactates; Male; Reference Values; Registries; White People

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

To investigate the frequency of macrosomia in an homogeneous cohort of type 1 diabetic mothers and to analyze the influence of maternal factors and glycemic control on the incidence of fetal macrosomia.. Fifty-five consecutive type 1 diabetic first-pregnancies were prospectively studied. Macrosomia was defined by a ponderal index above the 90(th) percentile. Venous cord blood levels of insulin, C peptide and leptin were measured at delivery. The influence of HbA1c levels and other maternal variables on the occurrence of macrosomia and on the ponderal index was assessed using a stepwise regression logistic model.. The mean (+/- SD) birth weight was 3482 (+/- 497) g at 37.4 +/- 1.0 weeks gestation. Macrosomia occurred in 29 cases (53.7%). Fetal insulin, C peptide and leptin levels were significantly higher in macrosomic than in non macrosomic infants. Maternal age, duration of diabetes, pregravid body mass index, parity, weight gain during pregnancy, presence of a microangiopathy, nephropathy, smoking habits, gestational hypertension or preeclampsia, and HbA1c levels throughout pregnancy did not differed between mothers of macrosomic and non macrosomic infants. In the stepwise analysis none of these covariates was explanatory of the ponderal index.. The frequency of macrosomia remains very high in infants of type 1 diabetic mothers despite a reasonable degree of glycemic control. The variability of the fetal growth response to mild hyperglycemia prompts for the identification of other factors involved in the modulation of fetal growth.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Embryonic and Fetal Development; Female; Fetal Macrosomia; Gestational Age; Glycated Hemoglobin; Humans; Hypoglycemia; Infant, Newborn; Insulin; Leptin; Maternal Age; Placenta; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Reference Values

Insulin-like growth factor-binding protein-1 (IGFBP-1) is believed to be an inhibitory factor for fetal growth. The regulation of IGFBP-1 secretion in the fetus is uncertain, although insulin and oxygen tension (PO2) and saturation are thought to play a role. We studied IGFBP-1 levels in umbilical cord artery (UA) and vein (UV) of 98 singleton fetuses at term with clinical signs of distress during labor, i.e. meconium-stained liquor or/and an abnormal fetal heart rate tracing. Blood gas values and serum C-peptide and IGFBP-1 concentrations were measured in both UA and UV. Twenty-five fetuses had an UA pH<7.20. The concentrations of IGFBP-1 were similar in UA and UV and were highly correlated (r=0.98). IGFBP-1 levels were inversely correlated with birth weight, with increased concentrations in small-for-gestational age fetuses (< or =10th weight percentile). IGFBP-1 levels were negatively correlated with C-peptide concentrations, and remained so after correction for birth weight (r=-0.37 for both UA and UV; P<0.001); more specifically, IGFBP-1 levels were increased in the lowest C-peptide quartile (<0.23 nmol/l) compared with the other quartiles. In addition, IGFBP-1 levels were inversely correlated with PO(2) values (r=-0.39 in UA and r=-0.34 in UV; P<0.001); quartiles of UA and UV PO2 showed a gradual increase in IGFBP-1 concentrations with lower PO2 values. A regression model with C-peptide and PO2 values as independent variables predicted IGFBP-1 concentrations (R2 of model was 0.25 and 0.22 for UA and UV respectively; P<0.001). Other blood gas values (pH, PCO2, HCO3- and base deficit) did not correlate with IGFBP-1 levels. The data of this study indicate that serum IGFBP-1 levels in term fetuses are determined by both insulin and PO2 levels, and suggest that acute hypoxemia stimulates IGFBP-1 secretion in the fetus.

Topics: Analysis of Variance; Birth Weight; C-Peptide; Female; Fetal Distress; Humans; Insulin-Like Growth Factor Binding Protein 1; Obstetric Labor Complications; Oxygen; Partial Pressure; Pregnancy; Umbilical Arteries; Umbilical Veins

To determine the relationships between serum leptin levels and maternal weights in late pregnancy and cord blood leptin levels to birth-weights, C-peptide, insulin and insulin like growth factor (IGF-II).. Fifty normal pregnant women at 37-38 weeks and their newborns were studied, and 29 non-pregnant women were set as control. Venous blood was taken from women and from the cord at delivery. Blood leptin and cord blood C-peptide, insulin, and IGF-II were measured by radio-immunoassay.. The average leptin level in maternal sera was (13.62 +/- 3.68) micrograms/L, significantly higher than that in the control (6.60 +/- 3.04) micrograms/L and that in cord blood (8.05 +/- 4.61) micrograms/L. Maternal leptin levels were significantly correlated with maternal weights and body mass index (BMI. r = 0.33, 0.35, P < 0.05), but not with infant birth-weights (r = 0.10, P > 0.05). Cord blood leptin levels were significantly correlated with birth-weights and BMI (r = 0.54, 0.49, P < 0.001) but have no correlation with maternal leptin levels (r = 0.19, P > 0.05). Significant difference of the cord leptin levels was not seen between the males and females. The cord blood C-peptide was (0.86 +/- 0.35) microgram/L, insulin (8.49 +/- 4.76) mU/L and IGF-II (0.218 +/- 0.076) microgram/T. Cord leptin levels were correlated with C-peptide levels (r = 0.37, P < 0.05), but not with insulin and IGF-II levels (r = 0.19, -0.14, P > 0.05).. Maternal leptin levels in late pregnancy were significantly higher than those in normal non-pregnant women and positively correlated with maternal weights and BMI. Cord blood leptin levels were positively correlated with birth-weights and BMI of the newborns. The leptin levels of cord blood were correlated with those of C-peptide but not insulin and IGF-II.

Topics: Adult; Birth Weight; Body Weight; C-Peptide; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor II; Leptin; Pregnancy

Previous data suggested that small for gestational age newborns have increased levels of IGF binding protein 1 (IGFBPI) in amniotic fluid (AF) at 15-16 wk of pregnancy. In this study, we developed an RIA for IGFBP1 and measured IGFBP1 concentrations in 209 AF samples with normal fetal karyotype between 14 and 20 wk; we measured IGF-I, IGF-II, and C-peptide in the same samples. Concentrations of these growth-modulating factors were all positively correlated with gestational age at sampling (p < 0.0001). After correcting for gestational age, AF IGFBP1 remained strongly correlated with IGF-I and IGF-II (both p < 0.0001); their concentrations were many times higher in AF than in cord serum during the third trimester. None of the growth-modulating factors in AF correlated with birth weight, after correction for gestational age; birth weight percentile distribution was comparable in two groups of newborns who had AF values of IGF-I, IGF-II, IGFBP1, or C-peptide that were either less than or equal to the 50th percentile or more than the 50th percentile at sampling. However, placenta weight and the placenta weight to birth weight percentage were negatively correlated with AF IGF-I, IGF-II, and IGFBP1; placenta weight to birth weight percentage was lower in pregnancies with IGFBP1 values more than the 50th percentile compared with those less than or equal to the 50th percentile at sampling. In conclusion, AF concentrations of IGFBP 1 increase gradually between 14 and 20 wk gestational age and correlate with IGF-I and IGF-II levels; high IGFBP1 levels do not predict small for gestational age newborns, but are associated with lower placenta weight.

Topics: Adult; Amniocentesis; Amniotic Fluid; Analysis of Variance; Birth Weight; Body Constitution; C-Peptide; Female; Fetal Blood; Gestational Age; Humans; Infant, Newborn; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Karyotyping; Middle Aged; Placenta; Predictive Value of Tests; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Radioimmunoassay

To examine the relation between maternal body fat and fetal metabolism.. In this observational study, cord blood samples were collected from 60 infants of healthy women for the measurement of insulin and C peptide concentrations. Maternal weight, height, body mass index (BMI) and body composition (skinfold thickness measurements and bioelectrical impedance) were assessed at 13-15 weeks of gestation. Twenty five of the volunteers agreed to have a 75 g oral glucose tolerance test at 28-31 weeks of gestation.. Positive correlations were observed with both cord insulin or C peptide concentrations and maternal early pregnancy BMI (r=0.44, p=0.002 and r=0.33, p=0.008, respectively). There was no significant correlation between cord insulin or C peptide concentrations and birthweight or birth weight centiles.. Maternal BMI could be a predictor of fetal cord insulin concentration.

Topics: Anthropometry; Birth Weight; Blood Glucose; Body Mass Index; C-Peptide; Female; Fetal Blood; Follow-Up Studies; Humans; Infant, Newborn; Insulin; Male; Pregnancy

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

The risks of pregnancy caused by maternal diabetes are well known. Patients with unrecognized gestational diabetes mellitus (GDM) represent a special problem. The aim of our study was to find out, whether the determination of insulin and C-peptide in cord blood serum offers a valuable tool for retrospective analysis.. In 600 paired serum samples from maternal venous blood and neonatal cord blood insulin and C-peptide were determined radioimmunologically. A reference group consisting of 338 mothers and their newborns was established by exclusion of all patients with known pregnancy complications.. Positive correlations could be identified between fetal insulin and fetal C-peptide, as well as correlations of these parameters with birth weight and body length, with maternal values of insulin, C-peptide, body-mass index, weight, and weight gain during pregnancy respectively. Increased levels of cord serum insulin were found in complicated pregnancies as well as in patients with previous pregnancy losses, preterm deliveries or stillbirths.. Cord serum insulin and C-peptide were found to be useful parameters for immediate postnatal identification of impaired glucose tolerance during the course of pregnancy.

Topics: Adolescent; Adult; Birth Weight; Body Height; Body Mass Index; C-Peptide; Female; Fetal Blood; Humans; Insulin; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Pregnancy, Multiple; Radioimmunoassay; Reference Values; Retrospective Studies; Risk Factors

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

Topics: Birth Weight; C-Peptide; Fetal Blood; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin

Free insulin cannot cross the placenta but insulin complexed to anti-insulin antibodies has been demonstrated in cord blood. We studied whether antibody-bound insulin in diabetic patients can evoke fetal macrosomia independently of maternal metabolic control. In 457 non insulin-treated controls and 173 insulin-treated diabetic patients we measured 1187 anti-insulin antibody levels and maternal blood glucose, maternal fructosamine, cord blood insulin, cord blood C-peptide, cord blood fructosamine and amniotic fluid insulin. Mean anti-insulin antibody levels in maternal blood and cord blood were significantly higher in insulin treated diabetic patients (4.6 and 5.4 U/ml) than in controls (1.8 and 1.7 U/ml) with maxima of 89.2 in maternal and 120.0 U/ml in cord blood, respectively. In insulin treated diabetic patients 16.6% (maternal blood) and 22% (cord blood) anti-insulin antibody levels were above the 97th percentile. There was a high significant correlation between maternal and cord blood anti-insulin antibodies (R = 0.987, P = < 0.0001), but no correlation of anti-insulin antibodies with maternal (glucose, fructosamine) or fetal (insulin, C-peptide, and fructosamine in cord blood, amniotic fluid insulin) metabolic parameters. While maternal and fetal metabolic parameters correlated with birth weight neither maternal nor cord blood anti-insulin antibody levels correlated with birth weight. These findings do not support the hypothesis that maternal anti-insulin antibodies independently influence fetal weight.

Topics: Amniotic Fluid; Autoantibodies; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Diabetes, Gestational; Female; Fetal Blood; Fructosamine; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics

The aetiology of the metabolic syndrome remains unknown. This study investigated whether two components of this syndrome, higher blood pressure and higher plasma insulin concentrations, are related at birth. Neonates in the study were from 23 European, 25 Maori, 22 South Asian, and 25 Pacific Islands women having normal singleton pregnancies as well as 6 Maori, 5 Indian, and 19 Pacific Islands women with gestational diabetes (diagnosed by a 3 h 100 g oral glucose tolerance test at 28-32 weeks). Additional fasting glucose and fructosamine concentrations were measured at 36-38 weeks. Umbilical cord blood was taken for insulin, C-peptide, fructosamine and insulin-like growth factor I. Neonatal anthropometry and blood pressure were measured 24 h after delivery. Compared with those with a lower systolic blood pressure (SBP), neonates with a higher SBP had higher umbilical cord insulin (45.6 (39.6-52.8) vs 63.0 (54.6-72.6) pM, p < 0.01), C-peptide (0.22 (0.20-0.25) vs 0.28 (0.26-0.30) nmol l-1, p < 0.001) and fructosamine concentrations, higher maternal fructosamine concentrations and heavier placentas. These data suggest that neonatal hyperinsulinaemia, possibly driven by minor elevations in maternal glycaemia, may be linked to a higher neonatal SBP.

Topics: Asia; Birth Weight; Blood Glucose; Blood Pressure; Body Constitution; C-Peptide; Diabetes, Gestational; Diastole; Female; Fetal Blood; Fructosamine; Glucose Tolerance Test; Humans; India; Infant, Newborn; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Labor, Obstetric; Maternal Age; New Zealand; Pacific Islands; Parity; Prediabetic State; Pregnancy; Reference Values; Regression Analysis; Systole; White People

Previous studies have demonstrated an association between low weight at birth and risk of later development of non-insulin-dependent diabetes mellitus (NIDDM). It is not known whether this association is due to an impact of intrauterine malnutrition per se, or whether it is due to a coincidence between the putative "NIDDM susceptibility genotype" and a genetically determined low weight at birth. It is also unclear whether differences in gestational age, maternal height, birth order and/or sex could explain the association. Twins are born of the same mother and have similar gestational ages. Furthermore, monozygotic (MZ) twins have identical genotypes. Original midwife birth weight record determinations were traced in MZ and dizygotic (DZ) twins discordant for NIDDM. Birth weights were lower in the NIDDM twins (n = 2 x 14) compared with both their identical (MZ; n = 14) and non-identical (DZ; n = 14) non-diabetic co-twins, respectively (MZ: mean +/- SEM 2634 +/- 135 vs 2829 +/- 131 g, p < 0.02; DZ: 2509 +/- 135 vs 2854 +/- 168 g, p < 0.02). Using a similar approach in 39 MZ and DZ twin pairs discordant for impaired glucose tolerance (IGT), no significantly lower birth weights were detected in the IGT twins compared with their normal glucose tolerant co-twins. However, when a larger group of twins with different glucose tolerance were considered, birth weights were lower in the twins with abnormal glucose tolerance (NIDDM + IGT; n = 106; 2622 +/- 45 g) and IGT (n = 62: 2613 +/- 55 g) compared with twins with normal glucose tolerance (n = 112: 2800 +/- 51 g; p = 0.01 and p = 0.03, respectively). Furthermore, the twins with the lowest birth weights among the two co-twins had the highest plasma glucose concentrations 120 min after the 75-g oral glucose load (n = 86 pairs: 9.6 +/- 0.6 vs 8.0 +/- 0.4 mmol/l, p = 0.03). In conclusion, the association between low birth weight and NIDDM in twins is at least partly independent of genotype and may be due to intrauterine malnutrition. IGT was also associated with low birth weight in twins. However, the possibility cannot be excluded that the association between low birth weight and IGT could be due to a coincidence with a certain genotype causing both low birth weight and IGT in some subjects.

Topics: Aged; Birth Order; Birth Weight; Blood Glucose; Body Height; C-Peptide; Cholesterol; Diabetes Mellitus, Type 2; Disease Susceptibility; Diseases in Twins; Female; Genomic Imprinting; Genotype; Glucose Tolerance Test; Humans; Infant, Low Birth Weight; Infant, Newborn; Insulin; Male; Middle Aged; Proinsulin; Sex Characteristics; Triglycerides; Twins, Dizygotic; Twins, Monozygotic

To examine the impact of gestational diabetes mellitus(GDM) on perinatal outcome in a setting where influences of maternal age and obesity would be minimal.. A case-control study was done to compare the outcome of pregnancy in 65 women with GDM and 153 women with normal carbohydrate metabolism matched for age, height, and prepregnancy weight.. The frequencies of preeclampsia and primary cesarean sections were higher and delivery was earlier in pregnancies complicated by GDM. Birth weight, symmetry index, and chest circumference were greater, and macrosomia and need for phototherapy were more common in offspring of mothers with GDM. Cord-serum C-peptide and insulin concentrations were higher in the infants of mothers with GDM and were strongly correlated with birth weight and symmetry index. However, maternal age, prepregnancy weight, and prepregnancy BMI were not correlated with birth weight. Postprandial glucose levels during the first 2 weeks after diagnosis of GDM had associations with the infants' birth weight, symmetry index, and cord insulin concentration in the diet-treated patients with GDM.. Antepartum maternal glucose metabolism was significantly associated with fetal hyperinsulinemia and excessive fetal growth in relatively nonobese Korean women. These findings support a direct role for metabolic factors in the adverse outcomes in pregnancies complicated by GDM.

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Case-Control Studies; Cesarean Section; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Infant, Newborn; Jaundice, Neonatal; Korea; Maternal Age; Morbidity; Obesity; Parity; Phototherapy; Pregnancy; Pregnancy Complications; Pregnancy in Diabetics; Regression Analysis

Recently, a missense mutation replacing tryptophan with arginine at codon 64 of the beta 3-adrenergic receptor gene was shown to be associated with insulin resistance in nondiabetic subjects and to an earlier onset of NIDDM in Pima Indians. We studied whether the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor gene in a cohort of young healthy Danes was associated with high birth weight, accelerated weight gain during childhood and adolescence, present obesity, or impaired insulin sensitivity. The protocol included 380 unrelated white subjects in whom insulin sensitivity and secretion were measured during a combined intravenous glucose and tolbutamide tolerance test. A number of biochemical and anthropometric characteristics were determined for each subject. The subjects were genotyped for the codon 64 polymorphism by applying polymerase chain reaction restriction fragment-length polymorphism screening with the use of endonuclease BstN1. The allelic frequency of the mutated allele was 7% (95% CI: 5-10%), and it was similar in obese and nonobese subjects. The beta 3-adrenergic receptor gene variant was not related to birth weight or weight gain during childhood or adolescence. In its heterozygous form, the gene variant was not associated with an altered insulin sensitivity index (SI) or other features of the insulin resistance syndrome (BMI, blood pressure, fasting serum lipid levels, or fasting serum fibrinolytic variables). Three homozygous carriers of the polymorphism were identified, and each had a significantly higher BMI (27.4 +/- 1.3 vs. 23.5 +/- 3.7 kg/m2 [mean +/- SD]; P = 0.032), lower SI [4.9 +/- 2.9 vs. 15.4 +/- 9.0 10(-5) x (min x pmol/l)-1; P = 0.013], and higher fasting serum C-peptide (730 +/- 155 vs. 471 +/- 158 pmol/l; P = 0.016) than the wild-type carriers. The homozygous carriers also had significantly higher levels of fasting serum triglyceride (P = 0.042) and serum LDL cholesterol (P = 0.013). When adjustments were made for age, sex, BMI, and VO2max in a multiple regression analysis, a significantly negative association was found between homozygosity for the codon 64 variant and the SI (P = 0.009). We conclude that in young healthy Danes, the homozygous form but not the heterozygous form of the codon 64 amino acid polymorphism of the beta 3-adrenergic receptor may be associated with obesity and, independent of BMI, with a low SI. Since only three homozygous carriers were identified among 380 subjects, the results mu

Topics: Adult; Birth Weight; Body Weight; C-Peptide; Denmark; Female; Gene Frequency; Glucose; Heterozygote; Homozygote; Humans; Insulin; Insulin Resistance; Male; Obesity; Point Mutation; Polymorphism, Genetic; Receptors, Adrenergic, beta

To evaluate if an increased proinsulin-to-insulin ratio (PI/I) in former gestational diabetes mellitus (GDM) subjects could be a marker for later impairment of glucose tolerance.. This study is a prospective follow-up. In a previous follow-up study of former GDM subjects 3-4 years after an index pregnancy, an increased PI/I was found also in normoglycemic nonobese former GDM subjects compared with control subjects. A 75-g oral glucose tolerance test (OGTT) was performed 3 years after the first follow-up, i.e., 6-7 years after the index pregnancy in 97 of the former GDM subjects and in 23 control subjects. A 75-g OGTT according to the World Health Organization was performed. Glucose, insulin, proinsulin, and C-peptide were determined at 0, 30, 60, 90, 120, 150, and 180 min after the glucose intake.. Since the first follow-up, an additional 3 in 97 (3.1%) and 15 in 97 (15.5%) of the former GDM subjects had NIDDM or impaired glucose tolerance (IGT), respectively. All control subjects still had a normal OGTT. The fasting PI/I at follow-ups 1 and 2 was significantly correlated in the former GDM subjects (r = 0.41, P < 0.001) and in the control group (r = 0.46, P < 0.05). There was no significant correlation between the PI/I in follow-up 1 and the fasting or 2-h glucose values at follow-up 2. If GDM subjects with a PI/I in the upper quartile in the first follow-up were compared with those with a lower PI/I, there were no significant differences in outcome of OGTT in the second follow-up.. The hypothesis that an increased fasting PI/I is a marker for later development of NIDDM or IGT in former GDM subjects could not be supported.

Topics: Adult; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Middle Aged; Predictive Value of Tests; Pregnancy; Proinsulin; Reference Values; Statistics, Nonparametric; Time Factors

Small and disproportionate size at birth are associated with type 2 diabetes and coronary heart disease in adult life. Insulin has an important role in controlling growth in utero and we hypothesised that reduced fetal insulin secretion could be one factor underlying these associations. We therefore measured cord plasma concentrations of proinsulin, 32-33 split proinsulin, insulin and C-peptide in 391 babies born at term and related them to the weight of the placenta and to the babies' size and proportions at birth. Babies with a small placental weight and a lower birth weight had lower cord plasma concentrations of split proinsulin and insulin. Babies who were disproportionate, either having a high ratio of head to abdominal circumference or being thin, had lower concentrations of split proinsulin, split proinsulin and insulin. The relations with split proinsulin were especially strong, the geometric mean concentration (pmol/l) falling from 14.2 in babies with a head to abdominal circumference ratio of 101.6% or less to 7.2 in those with a ratio above 107.3% (P < 0.0001), and from 17.4 in babies with a ponderal index above 28.5 kg/m3 to 7.4 in those with a ponderal index of 25.5 kg/m3 or less (P < 0.0001). These findings support the hypothesis that reduced fetal insulin secretion may be one factor underlying the associations between reduced growth in utero and type 2 diabetes and coronary heart disease in adult life.

Topics: Anthropometry; Birth Weight; Body Constitution; C-Peptide; Cephalometry; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Labor, Obstetric; Placentation; Pregnancy; Proinsulin; Protein Precursors; Regression Analysis

As insulin is a major fetal growth hormone, we have related the mother's nutrient intakes (assessed by a food frequency questionnaire) and other influences associated with fetal growth to the baby's concentrations of insulin and its propeptides in umbilical cord plasma. Among 391 term babies studied, those whose mothers had high energy intakes in early pregnancy and low protein intakes in late pregnancy had lower cord plasma concentrations of 32-33 split proinsulin, insulin, and C-peptide. Concentrations of split proinsulin fell by 0.66 (95% Cl 0.29 to 1.03, p = 0.0006) log pmol l-1 for each log kcal increase in the mother's energy intake in early pregnancy and by 0.005 (95% Cl 0.000 to 0.010, p = 0.04) log pmol l-1 for each g decrease in protein intake in late pregnancy. Insulin and propeptide concentrations were however unrelated to the mother's height and body mass index, and to smoking during pregnancy. These observations parallel recent studies relating the same pattern of dietary intakes to impaired fetal and placental growth. Although dietary intakes assessed by food frequency questionnaires allow only cautious conclusions, our findings could have implications for the offspring's risk of Type 2 diabetes mellitus in adult life.

Topics: Adolescent; Adult; Birth Weight; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Diet; Energy Intake; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Nutritional Physiological Phenomena; Pregnancy; Proinsulin; Protein Precursors; Risk Factors; Social Class

Insulin concentration correlates negatively with sex hormone-binding globulin (SHBG) in adults, although the age at which this relationship develops is unknown. The present study assesses this relationship in a cohort of European, Maori, South Asian, and Pacific Islands neonates from 125 normal and 35 pregnancies complicated by diabetes. Maternal glycemia was assessed with a 3-h 100-g oral glucose tolerance test with fasting glucose and fructosamine concentrations determined at 36-38 weeks. Umbilical cord blood was taken for insulin, C peptide, fructosamine, SHBG, sex hormone, and insulin-like growth factor I (IGF-I) measurements, and neonatal anthropometry was measured 24 h after delivery. Babies from pregnancies complicated by diabetes were heavier, fatter, hyperinsulinemic (90.4 vs. 130.6 pmol/L, respectively; P < 0.01), with similar SHBG (44.0 +/- 6.5 vs. 44.2 +/- 12.0) and sex hormone levels and higher IGF-I concentrations (57.1 +/- 24.2 vs. 70.1 +/- 37.1; P < 0.05). There were no ethnic differences in cord SHBG, sex hormones, or IGF-I. SHBG correlated negatively with cord insulin concentrations [males, -0.31 (P < 0.01); females, -0.35 (P < 0.001)], birth weight [males, -0.25 (P < 0.05); females, -0.36 (P < 0.001)] and other measures of neonatal size. In both normal pregnancies and those complicated by diabetes, cord IGF-I correlated with cord C peptide levels [0.32 (0.32 (P < 0.001) and 0.42 (P < 0.05), respectively] and neonatal size, but only in normal babies was there a correlation between IGF-I and insulin [0.43 (P < 0.001) and 0.10] or SHBG [-0.28 (P < 0.01) and -0.01]. These data confirm that relationships between insulin concentration and SHBG are present at birth and are likely to be physiological.

Topics: Adult; Birth Weight; Body Composition; C-Peptide; Cohort Studies; Dehydroepiandrosterone; Dehydroepiandrosterone Sulfate; Estradiol; Female; Fetal Blood; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Male; Pregnancy; Pregnancy in Diabetics; Radioimmunoassay; Reference Values; Regression Analysis; Sex Hormone-Binding Globulin; Testosterone

C-peptide concentrations in the cord blood of 29 macrosomic neonates born of nondiabetic mothers were higher than in 23 control infants whose birth weight was appropriate for gestational age, and there was a significant direct correlation between birth weight and C-peptide concentration. Six of the macrosomic infants studied (20%) had hypoglycemia in the first 24 hours of life, compared with none of the infants born with appropriate weight. We conclude that chronic fetal hyperinsulinemia may be one of the causes of macrosomia and neonatal hypoglycemia in infants of nondiabetic mothers.

Topics: Birth Weight; C-Peptide; Diabetes, Gestational; Female; Fetal Blood; Fetal Macrosomia; Gestational Age; Humans; Hypoglycemia; Infant, Newborn; Pregnancy; Radioimmunoassay

To examine endocrine states of mothers with normal 75-g oral glucose tolerance tests (GTTs) who gave birth to large for gestational age (LGA) neonates (group I) and to examine those neonates.. We examined plasma glucose levels and serum immunoreactive insulin responses after the 75-g oral GTT was given to group I mothers (N = 34), mothers with an abnormal oral GTT who gave birth to LGA neonates (group II, N = 21), and those with normal oral GTTs having appropriate for gestational age neonates (group III, N = 173). We also examined the infants, checking neonatal birth weight, levels of immunoreactive insulin and C-peptide immunoreactivity in cord sera at birth and the lowest blood sugar level after birth to see if a correlation existed between them.. Group I and II mothers showed higher titers in plasma glucose levels and remarkably enhanced ratios of 60- to 30-minute immunoreactive insulin values (immunoreactive insulin up-ratio) after load compared with those of group III mothers. Cord serum immunoreactive insulin and C-peptide immunoreactivity were significantly higher and the lowest blood sugar level was significantly reduced in group I and II neonates compared with those in group III. We observed a positive correlation between cord serum immunoreactive insulin, C-peptide immunoreactivity, and birth weight, but a negative correlation between cord serum immunoreactive insulin, birth weight, and the lowest blood sugar level in group I and II neonates (strongest tendency in group II), but not in group III neonates.. All of the abnormal carbohydrate metabolic responses in group I mothers and neonates may result in the promotion of growth in LGA fetuses similar to group II, but to a lesser extent. Identification of group I mothers by the immunoreactive insulin up-ratio after oral GTT will help predict the occurrence of LGA neonates and their possible hypoglycemia.

Topics: Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Glucose Intolerance; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy Complications

To compare the correlation between fetal insulin production (as estimated by amniotic fluid [AF] C-peptide concentration) and neonatal body fat (as estimated by both anthropometrics and total body electrical conductivity) with that between fetal insulin production and birth weight or fat-free mass.. Amniotic fluid C-peptide concentration measured within 1 week of delivery was correlated with birth weight and neonatal body composition, estimated by both anthropometric measures and total body electrical conductivity within 24 hours of birth. Eighteen term neonates were studied: 13 from pregnancies complicated by diabetes and five from mothers with normal glucose tolerance.. Six infants were large for gestational age and 12 were appropriate for gestational age. There was a significant correlation between AF C-peptide level and neonatal fat mass, estimated by either anthropometric measures (r = 0.72, P = .0008) or total body electrical conductivity (r = 0.61, P = .008) methodology. The correlation was weaker between AF C-peptide level and either ponderal index (r = 0.44, P = .064) or total weight (r = 0.39, P = .11). The correlation with fat-free mass estimated by either method was not statistically significant.. Our results suggest that fetal insulin production, as estimated by AF C-peptide concentration, influences fetal growth primarily through increasing fetal fat deposition rather than lean body mass.

Topics: Amniocentesis; Amniotic Fluid; Anthropometry; Birth Weight; Body Composition; Body Mass Index; C-Peptide; Electric Conductivity; Electric Impedance; Female; Fetal Macrosomia; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Linear Models; Male; Pregnancy; Pregnancy in Diabetics

Our purpose was to determine the correlation between birth weight and hormones or growth factors believed to be involved in fetal growth: insulin, insulin-like growth factors I and II, and insulin-like growth factor binding protein-1.. Five hundred thirty-eight cord serum samples were analyzed for insulin-like growth factor-I, insulin-like growth factor-II, C-peptide, and insulin-like growth factor binding protein-1 by immunoassay. Samples included all gestational ages in the third trimester and a large range of birth weights.. Cord serum insulin-like growth factor-I concentrations increased until 39 weeks (+84% from 28 to 29 weeks), followed by a 21% decline at 41 weeks. Insulin-like growth factor-I levels were decreased by 40% in small-for-gestational-age (< 10th percentile) newborns and were increased by 28% in large-for-gestational-age (> 90th percentile) newborns in the absence of diabetes. Insulin-like growth factor-I levels were best correlated with birth weight (R = 0.48, p < 0.001). Cord serum insulin-like growth factor-II concentrations were sixfold to tenfold higher than those of insulin-like growth factor-I and were 8% to 10% (p < 0.001) higher in large-for-gestational-age than in average-weight and small-for-gestational-age newborns. Cord serum C-peptide concentrations were 28% and 34% higher in large-for-gestational-age than in average-for-gestational-age and small-for-gestational-age newborns, respectively. Insulin-like growth factor binding protein-1 levels were increased in preterm average-for-gestational-age and in term small-for-gestational-age newborns compared with term average-for-gestational-age newborns and showed a negative correlation with birth weight (R = -0.43, n = 131, p < 0.001). Insulin-like growth factor binding protein-1 was not correlated with C-peptide concentrations.. Insulin-like growth factors I and II and insulin are all related to fetal growth and weight gain, and insulin-like growth factor-I correlates best with birth weight. Insulin is mainly related to fetal overgrowth (macrosomia). Insulin-like growth factor binding protein-1 may be a growth inhibitor in the fetus.

Topics: Adult; Birth Weight; C-Peptide; Carrier Proteins; Female; Fetal Blood; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Male

We have previously demonstrated that women who had given birth to large infants had a six-fold increased risk of developing Type 2 (non-insulin-dependent) diabetes mellitus compared with a control group matched for age and parity. However, the patients were extremely obese which explained, in part, the increased risk. In the present investigation we studied whether the delivery of large infants correlated with risk factors for atherosclerotic vascular disease other than obesity and diabetes, and therefore could serve as early markers for syndrome X. The study consisted of 73 women who 20-27 years earlier had given birth to large infants weighing 4,500 g or more. Another group of 73 women matched for age, parity and BMI who had delivered infants weighing less than 4,500 g within a 3-month period served as a control group. Of these 73 patient/control pairs, 48 (66%) were able to participate in the investigation. Mean age was 52.2 years (range 40-66 years). No differences were noted for family history of diabetes and medication prescribed for vascular disease between the groups. An oral glucose tolerance test was performed and glucose, insulin and C-peptide at 0 and 2 h were estimated. Triglycerides, cholesterol, LDL and HDL cholesterol were analysed at baseline. We found no tendency towards hyperinsulinaemia and hyperglycaemia in the patients and both groups had the same relative increase in levels of insulin and C-peptide. No difference between the groups regarding manifest symptoms of vascular disease, either in blood pressure or in proteinuria were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Arteriosclerosis; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Cholesterol, HDL; Cholesterol, LDL; Female; Glucose Tolerance Test; Humans; Incidence; Insulin; Middle Aged; Predictive Value of Tests; Risk Factors; Triglycerides

to investigate whether differences in the glucose-insulin axis are present at birth in neonates from ethnic groups at high risk of diabetes.. fructosamine samples were taken from Maori, European and Pacific Island expectant mothers at their 28 week appointment at the public outpatients clinic at National Women's Hospital, Auckland. Umbilical cord samples for insulin, C-peptide and fructosamine assay were taken at delivery and babies had their subscapular skinfold fat thickness measured by callipers.. the mean maternal 28 week fructosamine was similar in the three populations in spite of a higher prevalence of gestational diabetes among Pacific Islanders. Of the 1066 deliveries, cord samples were available for 207 Europeans, 81 Maoris and 113 Pacific Islanders. Both Pacific Island and Maori babies had higher cord fructosamine concentrations than European babies. However, Pacific Island babies were also heavier, and had higher cord insulin concentrations and subscapular skinfold thickness than European babies.. the elevated cord fructosamine concentrations suggest that Maori and Pacific Island babies, who share a high risk of noninsulin dependent diabetes mellitus later in life, are hyperglycaemic at birth. The paradoxical insulin results and the cause for the relative neonatal hyperglycemia warrant further investigation.

Topics: Adult; Anthropometry; Birth Weight; Body Height; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Ethnicity; Europe; Female; Fetal Blood; Fructosamine; Head; Hexosamines; Hospitals, Maternity; Hospitals, Public; Humans; Hyperinsulinism; Infant, Newborn; Insulin; New Zealand; Parity; Polynesia; Pregnancy; Prevalence; Risk Factors; Skinfold Thickness

To assess the distribution of cord blood insulin in an unselected population, and examine its relation to birthweight centiles.. District General Hospital in Nottinghamshire.. 209 unselected singleton births.. Cord blood insulin; cord blood C-peptide; birthweight centiles.. Hyperinsulinaemic babies (greater than 97th centile for cord insulin) were found at all birthweight centiles. 15% of high birthweight babies were hyperinsulinaemic. For low birthweight babies, the distribution of cord insulin/C-peptide was skewed indicating a high number of low values. Hypoinsulinaemic babies were present up to the 50th centile for birthweight.. Abnormalities of fetal insulinisation may be found in babies of all birthweights.

Topics: Birth Weight; C-Peptide; Fetal Blood; Humans; Infant, Newborn; Insulin; Neonatal Screening; Radioimmunoassay

Gestational diabetes mellitus (GDM) is a strong predictor of glucose intolerance later in life. Former GDM (n = 145) and control (n = 41) subjects were studied 3-4 yr after the index pregnancy. They were subjected to a 75-g oral glucose tolerance test (OGTT) with measurements of insulin, C-peptide, and proinsulin in the basal state and every 30 min for 180 min. In the former GDM group, 5 subjects (3.4%) had developed non-insulin-dependent diabetes mellitus (NIDDM), and 32 (22%) had developed impaired glucose tolerance (IGT; by World Health Organization criteria). In the control group, 2 (4%) had IGT. In the GDM group, IGT or NIDDM was significantly associated with obesity (body mass index [BMI] greater than or equal to 25 kg/m2) and earlier diagnosis of GDM during pregnancy (P less than 0.001). Nonobese (BMI less than 25 kg/m2) GDM subjects with normal glucose tolerance at follow-up had significantly higher mean glucose (P less than 0.01), insulin (P less than 0.05), and proinsulin (P less than 0.001) values during the OGTT than control subjects, whereas there was no significant difference in C-peptide values. A comparison between control subjects with normal OGTT and BMI less than 25 kg/m2 (n = 39) and GDM subjects (n = 39) selected to have a comparable area under the glucose curve, BMI, and age demonstrated no group differences in glucose, C-peptide, or insulin levels, whereas the proinsulin levels were significantly higher (P less than 0.001) during the glucose load. The molar ratio between proinsulin and insulin was also significantly higher among the former GDM subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Birth Weight; Blood Glucose; Body Mass Index; Body Weight; C-Peptide; Diabetes Mellitus, Type 2; Diabetes, Gestational; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Infant, Newborn; Insulin; Pregnancy; Proinsulin

Serum growth hormone (GH), insulin-like growth factor (IGF-I), insulin and C-peptide were measured by RIA in fetal blood collected in utero by umbilical cord puncture performed for a variety of indications. Eighty-four fetuses were aged 19-25 weeks and 14 were 26-37 weeks. IGF-I values were lower than the sensitivity of the method. The range for GH was 3-197 micrograms/l (GH-micrograms/l x 2 = mU/l), for insulin 14.3-117 pmol/l, for C-peptide 66.2-827.5 pmol/l. GH significantly increased from week 19 to 25; insulin and C-peptide levels increased from week 19 to 37. GH levels at 19-25 weeks were significantly higher in fetuses with femoral length less than the 5th compared with those with femoral length greater than the 95th centile for that age. GH and insulin levels did not correlate with weight at birth or with maternal hormone levels. These data provide evidence for a presence in living fetuses, from the 19th week, of high levels of GH and of insulin levels not very different from those in adults but these hormones do not seem to be directly responsible for fetal growth.

Topics: Birth Weight; C-Peptide; Embryonic and Fetal Development; Female; Fetal Blood; Gestational Age; Growth Hormone; Humans; Infant, Newborn; Insulin; Insulin-Like Growth Factor I; Pregnancy

In the present study the antepartum relationship between maternal diabetic glucose control and fetal hypoxaemia was examined in 44 Type 1 (insulin-dependent) diabetic and 23 non-diabetic control pregnancies. Maternal HbA1C was used to assess maternal integrated blood glucose control while fetal metabolic control was evaluated by antepartum glucose, insulin, and C-peptide determinations in amniotic fluid at elective caesarean delivery. Fetal hypoxaemia was assessed indirectly by fetal umbilical vein plasma erythropoietin level at delivery. A prospectively developed statistical pathway model was used to examine the relationship of these variables. In applying forced stepwise multiple regression with this model, we observed in the diabetic subjects that mean maternal HbA1C during the last month of pregnancy correlated significantly with fetal umbilical venous erythropoietin at delivery (r = 0.57, p less than 0.001). Additional significant contributions to umbilical venous erythropoietin were found for amniotic fluid glucose and amniotic fluid insulin when these two independent variables were added in stepwise fashion (p less than 0.01). We conclude that in diabetic pregnancy, antepartum control of maternal hyperglycaemia is a significant factor associated with fetal hypoxaemia. We speculate that this effect is mediated through perturbations which accelerate fetal metabolism and which is expressed by amniotic fluid levels of glucose and insulin.

Topics: Amniotic Fluid; Biomarkers; Birth Weight; Blood Glucose; C-Peptide; Cesarean Section; Diabetes Mellitus, Type 1; Erythropoietin; Female; Fetal Blood; Glucose; Glycated Hemoglobin; Humans; Infant, Newborn; Insulin; Models, Biological; Pregnancy; Pregnancy in Diabetics; Prospective Studies; Reference Values; Regression Analysis; Umbilical Veins

Gestational diabetes is a predictor of glucose intolerance in subsequent pregnancies and in the nongravid state. Many pregnant women are not tested for gestational diabetes, although they or their offspring may show signs suggestive of antecedent hyperglycemia. We examined the diagnostic utility of a postpartum (within 48 hours), 100 gm, oral glucose tolerance test and cord plasma glucose, cord plasma C-peptide, and 2-hour neonatal plasma glucose tests to detect antecedent gestational diabetes in women with documented gestational diabetes (n = 37) or with normal glucose tolerance test results late in the third trimester (n = 28). The 1-hour, 2-hour, and incremental 1-hour + 2-hour [( 1-hour - fasting] + [2-hour - fasting]) [2-hour - fasting]) glucose values of the postpartum glucose tolerance test showed significant differences between study participants with and without gestational diabetes (164 +/- 30 versus 115 +/- 22, 145 +/- 31 versus 101 +/- 21, and 153 +/- 51 versus 67 +/- 33 mg/dl, respectively, p less than 0.025). Maternal fasting and 3-hour postpartum glucose tolerance test glucose, cord plasma glucose, cord plasma C-peptide, and 2-hour neonatal plasma glucose values showed no significant between-group differences. Receiver operating characteristic curve analyses for these tests indicated that the incremental 1-hour + 2-hour postpartum glucose tolerance test glucose values best sustain test specificity at the low test threshold values necessary for high test sensitivity. A threshold of 110 mg/dl for this test yielded a predicted specificity of 90% and sensitivity of 80% with regard to antecedent gestational diabetes.

Topics: Birth Weight; Blood Glucose; C-Peptide; Capillaries; Female; Fetal Blood; Glucose Tolerance Test; Humans; Infant, Newborn; Postpartum Period; Pregnancy; Pregnancy in Diabetics; Reference Values; Statistics as Topic

In 18 women with gestational diabetes the variables of an oral glucose tolerance test (fasting and 2-hour blood glucose values and area under the blood glucose curve) performed in the last trimester of pregnancy correlated significantly with the urinary C-peptide excretion during the first 12 hours of the life (r = 0.47, 0.71, and 0.60, respectively). In a combined group with 28 type II pregnant diabetic women there was also a significant correlation between the urinary C-peptide excretion of the infants and their skinfold. Assay of the urinary C-peptide excretion of the neonate, reflecting its insulin production, seems to be a sensitive parameter to study the influence of the maternal carbohydrate metabolism in the offspring.

Topics: Birth Weight; Blood Glucose; Body Height; C-Peptide; Female; Glucose Tolerance Test; Humans; Infant, Newborn; Pregnancy; Pregnancy in Diabetics; Retrospective Studies; Skinfold Thickness

A population of 40 mother-newborn pairs with a wide range of birth weight has been studied. Seventeen of the mothers were diabetic, while the other 23 were normal pregnant women. The chronic blood glucose levels were assessed in the mothers through the percentage of glycosylated hemoglobin (HbA1) at delivery. The functional activity of the pancreatic beta-cells in the newborns was estimated through the concentration of insulin and C-peptide in the cord blood. Maternal HbA1 was not quantitatively related to the birth weight ratio. In contrast, both insulin and C-peptide correlated significantly with it. Is is concluded that in populations with a good metabolic control, blood glucose levels, as measured by HbA1, are not the major determinant of fetal growth.

Topics: Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Fetal Macrosomia; Fetus; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans; Pregnancy; Pregnancy in Diabetics

This study of 74 diabetic pregnant women shows that tight maternal blood glucose control before the 32nd week of gestation significantly reduces the incidence of fetal macrosomia (11%) when compared with that of patients with fair to poor control before the 32nd week of gestation (44%, P less than .05) or with those whose good diabetic control was not achieved until after the 32nd week of gestation (34%, P less than .05). The macrosomic infant produced by a diabetic mother is associated frequently with an elevated amniotic fluid C-peptide level, which shows the evidence of intrauterine fetal hyperinsulinism. The use of tight diabetic control early in pregnancy to reduce the risk of fetal macrosomia and/or neonatal complications is of clinical importance in the management of diabetes in pregnancy.

Topics: Amniotic Fluid; Birth Weight; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 1; Female; Follow-Up Studies; Gestational Age; Humans; Hypoglycemia; Infant, Newborn; Infant, Small for Gestational Age; Jaundice, Neonatal; Longitudinal Studies; Pregnancy; Pregnancy in Diabetics; Time Factors

The interrelationship between amniotic fluid (AF) concentration and content (AF X conc) of C-peptide and cortisol was studied in four groups of women comprising 10 gestational and 16 type-I diabetics, 11 women with intrauterine growth retarded fetuses (IUGR), and 17 healthy control women. Mean AF volume was significantly greater (P less than 0.05) in the type-I diabetic group than in the control group. Both concentration and content of AF C-peptide was significantly higher in the type-I diabetic group than in the control group (P less than 0.05 and P less than 0.01, respectively). The corresponding values were significantly lower in mothers with IUGR fetuses compared to controls (P less than 0.05). AF cortisol content was significantly higher (P less than 0.05) in the gestational diabetic group compared to the control group; there were no other significant differences between the groups regarding the cortisol concentration or content. Both cortisol and C-peptide contents were significantly interrelated in both control women (r = 0.68, P less than 0.01) and women with gestational (r = 0.68, P less than 0.05) and type-I diabetes (r = 0.63, P less than 0.01). The C-peptide/cortisol ratio was lowest in the IUGR group and highest in the type-I diabetic group. The same ratio was intermediate and almost equal in the control and gestational diabetic group. Both C-peptide and cortisol concentrations were unrelated to AF volume as well as infant birthweight. C-peptide content was significantly correlated to birthweight percentile in type-I diabetic women (r = 0.61, P less than 0.05). No such correlation was found in the three other groups.

Topics: Amniotic Fluid; Birth Weight; C-Peptide; Diabetes Mellitus, Type 1; Female; Fetal Growth Retardation; Fetus; Gestational Age; Humans; Hydrocortisone; Infant, Newborn; Pregnancy; Pregnancy in Diabetics

Birth weight ratios (BWRs) and cord blood C-peptide values were significantly higher in neonates born to mothers with well-controlled gestational diabetes (GD) than in those born to mothers with well-controlled established diabetes (ED) or mothers with normal results on glucose tolerance testing. The neonates born to the ED mothers had the highest cord blood acetylated fetal haemoglobin (Hb F1) values, and these values correlated with cord C-peptide values. The cord C-peptide values in the GD group correlated with BWRs, but not with Hb F1 values. These results suggest differential tissue utilization of glucose in neonates born to mothers with different types of diabetes.

Topics: Birth Weight; C-Peptide; Female; Fetal Blood; Fetal Hemoglobin; Humans; Infant, Newborn; Pregnancy; Pregnancy in Diabetics

We have examined gravida with gestational diabetes mellitus (GDM), as defined by the National Diabetes Data Group (Diabetes 1979; 28:1039), for phenotypic and genotypic heterogeneity. Fasting plasma glucose (FPG) at diagnosis was used for further stratification of GDM according to putative metabolic severity into class A1 (FPG less than 105 mg/dl [N = 129]), class A2 (FPG 105-129 mg/dl [N = 47]), and class B1 (FPG greater than or equal to 130 mg/dl [N = 23]). All GDM classes tended to be older and heavier than consecutive gravida with documented normal glucose tolerance (controls, N = 148). Subdivision into "lean" and "obese" indicated that plasma immunoreactive insulin (IRI) was greater after overnight fast in the obese of all groups except B1. However, absolute increases in IRI above fasting levels in response to glucose during OGTT were significantly enhanced by obesity only in class A2 gravida. Adjustment for the effects of age and weight by covariate analysis indicated that the IRI response to glycemic stimulation is usually attenuated in all forms of GDM. Mean values for increases in IRI above fasting values during the first 15 min and IRI increments relative to the increases in plasma glucose throughout the 180-min OGTT were below control values in all GDM groups and progressively so, i.e., A1 less than A2 less than B1. The absolute insulinopenia was not invariable; a small number of gravida from all GDM groups displayed well-preserved IRI responses to oral glucose. Genotypic evaluation of the GDM population disclosed an increased occurrence of "markers" known to be associated with type I diabetes mellitus.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Autoantibodies; Birth Weight; Blood Glucose; Body Weight; C-Peptide; Fasting; Female; Fetal Blood; Glucose Tolerance Test; Histocompatibility Antigens Class II; HLA-DR3 Antigen; HLA-DR4 Antigen; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Maternal Age; Pregnancy; Pregnancy in Diabetics

Nonhuman primate models of gestational diabetes have produced fetopathies most similar to those of the human infant of the mother with gestational diabetes (IGDM). Fetal hyperglycemia, hyperinsulinemia, macrosomia, selective organomegaly, intrauterine death, and placental hyperplasia are hallmarks of the fetopathy of the IGDM. The chronic infusion of insulin into the fetus of a normal pregnant rhesus monkey results in fetal hyperinsulinemia with normal to low plasma metabolic substrate concentrations. Under these conditions, fetal hyperinsulinemia is sufficient to cause fetal growth and hormone changes observed in the human IGDM. Our studies provide evidence that the soft tissue hyperplasia in the fetal macrosomia syndromes in humans and nonhuman primates in which fetal hyperinsulinemia is observed is the direct result of that chronic in utero hyperinsulinemia.

Topics: Adipose Tissue; Amino Acids; Animals; Birth Weight; Blood Glucose; C-Peptide; Disease Models, Animal; Erythropoietin; Female; Fetal Blood; Fetal Hypoxia; Fetus; Glucagon; Hydrocortisone; Insulin; Macaca mulatta; Pregnancy; Pregnancy in Diabetics

Twenty women with abnormal glucose tolerance, detected from a routine program of antenatal screening for gestational diabetes mellitus (GDM) at 28 wk, were admitted for 24-h metabolic profiles. They were then alternately allocated to either insulin and dietary restriction or dietary restriction alone and then retested 4 wk later while on therapy. Ten normal controls were assessed twice at similar gestations to the study group. Before treatment, the 20 gestational diabetic subjects had higher mean concentrations of plasma glucose and 3-hydroxybutyrate than the controls for most of the profile, but mean insulin values were similar. Insulin therapy was associated with a reduction in mean glucose concentrations so that the profile was similar to the controls, while in the diet-alone group the reduction was less. The 3-hydroxybutyrate concentrations rose between profiles in the normal group and also rose in those treated by diet alone, but still remained within the upper range of normal even at night. Insulin therapy resulted in a similar 3-hydroxybutyrate profile to the controls. The C-peptide response to breakfast was reduced in both groups to levels below that of the controls. Neonatal outcome indices were similar in the two treatment groups, despite the differences in maternal metabolites, but because of the size of this study, conclusions about the neonate must be tentative.

Topics: 3-Hydroxybutyric Acid; Adult; Birth Weight; Blood Glucose; Body Weight; C-Peptide; Circadian Rhythm; Female; Gestational Age; Humans; Hydroxybutyrates; Insulin; Pregnancy; Pregnancy in Diabetics

Increased cord blood C-peptide levels in neonates born to mothers with gestational diabetes (GD) were directly correlated with the increased relative birth weight ratio (BWR) of these neonates. In addition, the percentage oxygen saturation of the cord blood was inversely correlated with cord blood C-peptide levels and with the relative BWR. These correlations were absent in neonates delivered to normal mothers. The results indicate the presence of both hyperinsulinaemia and mild hypoxaemia in neonates of mothers with GD. In poorly controlled diabetic pregnancy this hypoxaemia may constitute an important fetal risk factor.

Topics: Birth Weight; C-Peptide; Female; Fetal Blood; Humans; Hyperinsulinism; Hypoxia; Infant, Newborn; Oxygen; Partial Pressure; Pregnancy; Pregnancy in Diabetics

A single measurement of total maternal glycosylated haemoglobin (Hb A1) in the late third trimester of a diabetic pregnancy is of limited value in assessing diabetic control. There was no significant correlation between maternal Hb A1 values and neonatal C-peptide values or birth-weight ratios. An isolated Hb A1 measurement is not sufficiently sensitive to monitor the control of diabetes during pregnancy nor is it useful in predicting perinatal outcome.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Glycated Hemoglobin; Humans; Pregnancy; Pregnancy in Diabetics; Pregnancy Trimester, Third

The concentrations of the somatomedins (SMs) insulin-like growth factors I and II (SM-C/IGF-I and IGF-II) were measured by RIA in six normal and seven insulin-dependent diabetic pregnant women and their infants at delivery. SM-C/IGF-I and IGF-II levels in the two groups of women were similar. Maternal IGF-II concentrations correlated with maternal hemoglobin AIc levels (r = 0.68) and infant birth weight ratios (actual birth weight/expected 50th percentile sex-corrected birth weight for gestation age; r = 0.54). SMC/IGF-I and IGF-II levels in umbilical plasma in infants of diabetic mothers did not differ from those in control infants, but were lower than the corresponding maternal values. In contrast, umbilical plasma levels of C-peptide immunoreactivity were significantly elevated in the infants of diabetic mothers (2.25 +/- 1.85 (+/-SD) vs. 0.34 +/- 0.15 pmol/ml; P less than 0.01). The infant birth weight ratio was logarithmically correlated with the umbilical plasma C-peptide immunoreactivity (r = 0.78). SM levels were also measured by radioreceptor assay in five normal and five hyperinsulinemic rhesus monkey fetuses. When chronic hyperinsulinemia was produced by continuous SC infusion of insulin in the fetal rhesus monkey, the fetal birth weight ratio was also found to be logarithmically correlated with the fetal plasma insulin concentration (r = 0.81). The fetal SM peptide content was elevated only in the fetuses with plasma insulin levels greater than 3000 microU/ml. The fetal weight gains in response to hyperinsulinemia in the human and rhesus are similar. Since fetal SM levels in the humans and monkeys were not significantly different in the two groups, our data suggest that insulin plays the predominant role in stimulating human and subhuman primate excess fetal weight gain of the infant of the diabetic mother during the latter part of gestation.

Topics: Adult; Animals; Birth Weight; C-Peptide; Female; Fetal Blood; Glycated Hemoglobin; Humans; Insulin; Macaca mulatta; Peptides; Pregnancy; Pregnancy in Diabetics; Somatomedins

The concentrations of C-peptide and phosphatidylglycerol in the amniotic fluid were determined in 36 pregnant diabetic women. Twenty-one patients who were being treated with insulin for gestational diabetes as well as 15 patients who were insulin dependent were studied. All patients were subjected to a program of strict metabolic control, and amniocentesis was performed at gestational week 36-37. Phosphatidyl glycerol was present in the amniotic fluid in 15 cases and absent in 21. The mean concentration of C-peptide did not differ whether phosphatidyl glycerol was present or absent. (C-peptide: 0.56 +/- 0.06 and 0.43 +/- 0.05 nmol/l respectively). Although the mean value for amniotic fluid C-peptide in both groups was close to that in diabetic pregnancies with an uneventful neonatal outcome, it was significantly higher than that in non-diabetic pregnancies, indicating minor fetal hyperinsulinemia. The level of C-peptide in the amniotic fluid showed a correlation to the subsequent birthweight of the infant (r = 0.50; p less than 0.01). It is concluded that with rigorous metabolic control of the pregnant diabetic patient, the presence or absence of phosphatidyl glycerol, as an index of fetal lung maturity, is apparently not related to the level of C-peptide in the amniotic fluid.

Topics: Amniocentesis; Amniotic Fluid; Birth Weight; C-Peptide; Female; Humans; Infant, Newborn; Phosphatidylglycerols; Pregnancy; Pregnancy in Diabetics; Pregnancy Trimester, Third

Fatty acid composition in lecithin and C-peptide was analysed in amniotic fluid samples obtained from 28 normal and 24 insulin-treated diabetic women in the 34th to 39th week of pregnancy. The pattern of changes of fatty acid composition of amniotic fluid (AF) lecithin was essentially the same in pregnancies complicated by diabetes as in non-diabetic controls. However, at 36/37 weeks, the mean values for palmitoleic acid (16:1) were statistically higher in diabetic women (P less than 0.02), and the mean values for stearic acid (18:0) were higher for normals (P less than 0.02). The mean C-peptide value was more than twice as high (0.71 nmol/l) in the diabetic group than in the control group (P less than 0.01). The lecithin/sphingomyelin (L/S) and palmitic/stearic acid (P/S) ratios were equal in both groups. Neither in five diabetic patients with fetuses indicating marked hyperinsulinism (C-peptide greater than 1.0 nmol/l) nor in the remaining group of patients was there any relationship between C-peptide levels and the lecithin fatty acid composition.

Topics: Adult; Amniotic Fluid; Birth Weight; C-Peptide; Fatty Acids; Female; Gestational Age; Humans; Infant, Newborn; Phosphatidylcholines; Pregnancy; Pregnancy in Diabetics; Pregnancy Trimester, Third

Fructosamine, an indicator of glycosylated serum protein, was measured in 79 non-diabetic pregnant women and 20 women with gestational diabetes. The test provided a clear discrimination between groups; it detected 17 (85%) of the women with gestational diabetes and gave only 4 (5%) false-positive results. 19 women with established diabetes before pregnancy had very high levels. Maternal fructosamine at 29 weeks' gestation correlated significantly with both fasting blood glucose levels at the time and birthweight ratio. Levels of fructosamine in cord blood were significantly higher in gestational diabetic than in normal pregnancies, suggesting a possible additional role for fructosamine in retrospectively detecting the hyperglycaemic fetus. Fructosamine estimation is fully automated and may provide a simple, inexpensive means to screen for diabetes in pregnancy.

Topics: Adult; Birth Weight; Blood Glucose; C-Peptide; Female; Fetal Blood; Fructosamine; Gestational Age; Glucose Tolerance Test; Glycated Hemoglobin; Hexosamines; Humans; Infant, Newborn; Insulin; Pregnancy; Pregnancy in Diabetics

Antibodies to insulin were found in 92% of the 138 insulin-treated pregnant diabetic patients studied. No effect of pregnancy was shown on insulin antibody levels. Higher insulin antibody levels were significantly associated with the previous use of conventional insulins. Change from conventional to highly purified porcine insulin during pregnancy produced a significant reduction in insulin antibody levels. The combination of protamine zinc and soluble insulin used before pregnancy was found to be the most immunogenic. Insulin antibodies were freely transferred to the fetus but not detectable after the first 8 months of life. No insulin antibodies were found in the cord blood or during the next few weeks in the infants of mothers who had no antibodies to their injected insulin. There was a tendency for higher insulin antibody levels to be associated with indices of neonatal morbidity but not with percentile birth weights and C-peptide levels in cord sera.

Topics: Animals; Antibodies; Birth Weight; C-Peptide; Cattle; Diabetes Mellitus; Epitopes; Female; Fetal Blood; Fetal Death; Humans; Insulin; Maternal-Fetal Exchange; Postpartum Period; Pregnancy; Pregnancy in Diabetics; Swine

Topics: Amniotic Fluid; Birth Weight; C-Peptide; Female; Humans; Infant, Low Birth Weight; Infant, Newborn; Peptides; Pregnancy; Pregnancy Trimester, Second

Amniotic fluid (AF) volumes were determined by sodium p-aminohippurate (PAH) dilution in a consecutive series of 24 diabetic women at 34-35 weeks gestation. AF and maternal venous blood samples were analysed for C-peptide immunoreactivity (CPR). When the patients were subgrouped according to the presence (n = 17) or absence (n = 8) of neonatal morbidity, AF volumes (1340 +/- 236 ml vs 807 4/- 130 ml; mean +/- SEM), AF concentrations of CPR (1.38 +/- 0.54 nmol/l vs 0.61 +/- 0.14 nmol/l) and maternal blood glucose levels (5.3 +/- 0.2 nmol/l vs 4.8 +/- 0.3 nmol/l) during the last trimester of pregnancy were not different. The total content of CPR was significantly (P less than 0.05) greater in pregnancies with neonatal complications (1.25 +/- 0.31 nmol/ compared with that in pregnancies without neonatal complications (0.54 +/- 0.18 nmol). AF volumes were significantly (P less than 0.02) larger in pregnancies where feeding problems occurred (1546 +/- 307 ml, n = 9) compared with that in pregnancies without such problems (957 +/- 188 ml, n = 16). These findings indicate an impact of fetal hyperinsulinism on the functional maturation of the fetus. When the patients were subgrouped according to the presence or absence of detectable maternal plasma CPR, i.e. greater than 0.05 nmol/l, and to insulin dependent and gestational diabetes no differences of AF volumes, AF concentrations of CPR or total AF contents of CPR were found.

Topics: Amniotic Fluid; Birth Weight; Blood Glucose; Body Weight; C-Peptide; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Peptides; Pregnancy; Pregnancy in Diabetics

Amniotic fluid C-peptide (AFCP) was monitored as an indicator of the amount of insulin secreted by the fetus in utero. Levels of amniotic fluid and cord blood C-peptide, insulin, and glucose were measured in 103 nondiabetic infants at greater than or equal to 36 weeks's gestation. Infants were grouped according to birth weight and gestational age at delivery, as follows: small gestational age (SGA, less than or equal to 10%, n = 11), average for gestational age (AGA, 10% to 90%, n = 75), large for gestational age (LGA, greater than 90%, n = 17). AFCP correlated best with infant weight-gestational age percentile classification: low AFCP in SGA infants and high AFCP in LGA infants. The data from this study suggest that a persistently low production of insulin by SGA fetuses and a high production of insulin by LGA fetuses may lead to the different intrauterine growth rates observed.

Topics: Amniotic Fluid; Birth Weight; C-Peptide; Female; Fetal Blood; Fetus; Gestational Age; Glucose; Growth; Humans; Infant, Newborn; Infant, Small for Gestational Age; Insulin; Peptides; Pregnancy; Prospective Studies

In a previous study we determined the glucose disappearance rate (kt) in 129 newborn large-for-dates infants (LFD) born to mothers without known diabetes. Twenty-six infants (i.e. 20.6%) had elevated kt values similar to those in offspring of diabetic mothers. A follow-up study of 123 of these mothers was performed 7 years after delivery and included determination of early insulin and C-peptide response to intravenous glucose, plasma concentrations of 3-hydroxybutyrate, cholesterol, triglycerides, lipoproteins and HLA-typing. Two subjects had developed diabetes and altogether 14% had a kt below 1.0. Measures of the early insulin and C-peptide response to glucose were equally well correlated to maternal kt values (r = 0.40, P less than 0.001). Measures of the early insulin and C-peptide responses were significantly correlated (r = 0.64, P less than 0.001). The frequency distribution of HLA antigens were not different from normal and there was no association between HLA-B8 or B15 and impaired insulin response or glucose tolerance. Multiple regression and discriminate analysis of clinical and biochemical variables could not accurately identify women with high or low kt values. Multiple regression analysis using infant kt value as the dependent variable disclosed only a weak, but significant, inverse association to maternal insulin response to glucose at follow-up.

Topics: Adult; Birth Weight; Blood Glucose; Body Weight; C-Peptide; Female; Follow-Up Studies; Glucose Tolerance Test; HLA Antigens; Humans; Infant, Newborn; Insulin; Lipids; Peptides; Pregnancy

Amniotic fluid C-peptide (AFCP), insulin, and glucose levels were measured in 33 diabetic and 126 nondiabetic pregnant women at greater than or equal to 36 weeks' gestation. Levels of AFCP distinguished diabetic from nondiabetic patients more reliably than amniotic fluid (AF) insulin or glucose. Levels of AFCP in diabetic patients correlated well with infant birth weight adjusted for gestational age (large for gestational age greater than adequate for gestational age), degree of diabetic control (fair to poor control greater than good control), or diabetogenic infant morbidity, but did not correlate with classes of diabetes within the limits of the population studied. We conclude that AFCP is a useful prognostic index for predicting fetal outcome in diabetic pregnancies. A level of AFCP of greater than or equal to 1.0 pmoles/ml is associated with an increased risk of macrosomia in infants of diabetic mothers.

Topics: Adult; Amniotic Fluid; Birth Weight; C-Peptide; Female; Fetal Blood; Fetal Monitoring; Glucose; Humans; Infant, Newborn; Insulin; Peptides; Pregnancy; Pregnancy in Diabetics; Prognosis

C peptide is secreted by pancreatic beta cells in amounts equimolar with insulin, and its levels provide a direct indication of endogenous fetal levels of insulin despite the presence of maternal insulin antibodies. To determine the presence of hyperinsulinemia and its relation to the development of complications in infants of diabetic mothers, we measured cord serum levels of C peptide in 79 infants of diabetic mothers and 62 infants of nondiabetic mothers. Infants of diabetic mothers had higher cord levels of C peptide, which were significantly associated with neonatal hypoglycemia and macrosomia (P less than 0.001) but not with hyaline-membrane disease. Cord levels of C peptide in infants of diabetic mothers were elevated at the earliest gestational age studied (less than 34 weeks) and were directly related to the severity of maternal diabetes, as assessed by the White classification. We conclude that hyperinsulinemia is present in infants of diabetic mothers and that it is related to some major complications in such infants.

Topics: Birth Weight; C-Peptide; Female; Fetal Blood; Gestational Age; Humans; Hyaline Membrane Disease; Hypoglycemia; Infant, Newborn; Infant, Newborn, Diseases; Insulin; Peptides; Pregnancy; Pregnancy in Diabetics