Cord Insulin Concentrations Research Articles

Associations of cord leptin and cord insulin with adiposity and blood pressure in White British and Pakistani children aged 4/5 years

Background: Cord leptin and cord insulin concentrations may be important biomarkers of child adiposity and cardiovascular health, especially in populations with an increased long-term risk of type 2 diabetes and cardiovascular diseases. We aimed to determine whether cord leptin and insulin are associated with adiposity and early cardiovascular health at age 4/5, and whether any associations differ between White British and Pakistani children. Methods: Using bi-ethnic cohort data from 6060 mother-offspring pairs (2717 (44.8%) White British, 3343 (55.2%) Pakistani), we examined associations of cord leptin and insulin with adiposity (BMI, skinfold thickness) and systolic and diastolic blood pressure at age 4/5. Results: Cord leptin and insulin were higher in Pakistani compared to White British children (7.4 ng/ml versus 6.7 ng/ml and 4.1 mU/L versus 3.63 mU/L , respectively). Associations with adiposity measurements were similar in both groups and close to the null value. For example, each 10 ng/ml higher cord leptin was associated with a difference in mean childhood BMI of 0.10 kg/m 2 (95% CI 0.01, 0.19) in White British, 0.01 kg/m 2 (95% CI -0.08, 0.10) in Pakistani and 0.04 kg/m 2 (95% CI -0.02, 0.11) in both groups combined. Associations with systolic and diastolic blood pressure were also close to the null and consistent in both groups. Conclusions: We found no evidence that cord leptin or insulin were likely to be valuable biomarkers for predicting later adiposity and blood pressure in White British or Pakistani children. For now, other factors such as family history and social-economic status may be more useful markers of risk.

Associations of cord leptin and cord insulin with adiposity and blood pressure in White British and Pakistani children aged 4/5 years.

Background: Cord leptin and cord insulin concentrations may be important biomarkers of child adiposity and cardiovascular health, especially in populations with an increased long-term risk of type 2 diabetes and cardiovascular diseases. We aimed to determine whether cord leptin and insulin are associated with adiposity and early cardiovascular health at age 4/5, and whether any associations differ between White British and Pakistani children. Methods: Using bi-ethnic cohort data from 6060 mother-offspring pairs (2717 (44.8%) White British, 3343 (55.2%) Pakistani), we examined associations of cord leptin and insulin with adiposity (BMI, skinfold thickness) and systolic and diastolic blood pressure at age 4/5. Results: Cord leptin and insulin were higher in Pakistani compared to White British children (7.4 ng/ml versus 6.7 ng/ml and 4.1 mU/L versus 3.63 mU/L , respectively). Associations with adiposity measurements were similar in both groups and close to the null value. For example, each 10ng/ml higher cord leptin was associated with a difference in mean childhood BMI of 0.10kg/m 2 (95% CI 0.01, 0.19) in White British, 0.01kg/m 2 (95% CI -0.08, 0.10) in Pakistani and 0.04kg/m 2 (95% CI -0.02, 0.11) in both groups combined. Associations with systolic and diastolic blood pressure were also close to the null and consistent in both groups. Conclusions: We found no evidence that cord leptin or insulin were likely to be valuable biomarkers for predicting later adiposity and blood pressure in White British or Pakistani children. For now, other factors such as family history and social-economic status may be more useful markers of risk.

Maternal and fetal insulin levels at birth in women with polycystic ovary syndrome: data from a randomized controlled study on metformin

Metformin is suggested to reduce pregnancy complications in women with polycystic ovary syndrome (PCOS). Metformin crosses the placenta and therapeutic concentrations are measured in the fetal circulation. Whether metformin treatment in pregnant PCOS women affects maternal and fetal insulin concentrations at birth is not clarified. To investigate the possible effect of metformin on insulin concentrations in umbilical cord blood and the possible association between maternal and fetal insulin concentrations. Post-hoc analysis of a subgroup of PCOS women participating in a double-blind randomized controlled trial. University hospital setting. Women with PCOS (n=118), aged 19-39 years. Maternal and umbilical cord insulin concentrations immediately after birth. At delivery women randomized to metformin had lower insulin concentrations than those randomized to placebo (259±209 vs 361±261 pmol/l; P=0.020). No difference was found in insulin concentrations in umbilical venous (P=0.95) and arterial (P=0.39) blood between the metformin and placebo groups. The arteriovenous difference was also equal between the groups (P=0.38). Insulin concentrations were higher in the umbilical vein than in the umbilical artery independent of randomization (70±51 vs 45±48 pmol/l; P<0.0005). In PCOS, metformin treatment during pregnancy resulted in lower maternal insulin concentrations at delivery. Metformin treatment did not affect fetal insulin concentrations. Higher insulin concentrations in the umbilical vein indicate that the placenta somehow secretes insulin to the fetus. The possibility of placental insulin secretion to the fetus deserves further investigations.

Increased cord blood angiotensin II concentration is associated with decreased insulin sensitivity in the offspring of mothers with gestational diabetes mellitus

To determine cord blood angiotensin II (Ang II) concentration and assess its relationship to fetal insulin sensitivity in the offspring of mothers with gestational diabetes mellitus (GDM) at birth. Thirty women with GDM and 30 healthy women were evaluated at elective cesarean delivery. Cord blood was obtained for measurement of Ang II, glucose and insulin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate fetal insulin sensitivity. The offspring of mothers with GDM had higher ponderal index (PI), HOMA-IR and cord Ang II and insulin concentrations than the offspring of healthy mothers. Cord insulin concentration and HOMA-IR were positively associated with PI in all the offspring. Cord Ang II concentration was positively associated with HOMA-IR in the offspring of mothers with GDM. Increased cord Ang II concentration is associated with decreased insulin sensitivity in the offspring of mothers with GDM.

Relationship of fetal total bile acid and the change of fetal pancreas endocrine secretion and its impact on fetal growth and development in intrahepatic cholestasis of pregnancy

To investigate the relationship of fetal total bile acid (TBA) concentration with the change of fetal pancreas endocrine secretion and its impact on fetal growth and development in intrahepatic cholestasis of pregnancy (ICP). The concentrations of TBA, insulin, glucagon and glucose in the cord blood were measured in 30 fetuses with maternal ICP (case group) and 30 fetuses of normogravidas (control group) after elective cesarean section during the same period in the Department of Obstetrics of Xiangya Second Hospital of Central South University from March 2007 to February 2008. The cord blood TBA concentration was investigated by enzyme method and the concentrations of insulin and glucagon were investigated by radioimmunoassay. The glucose was measured by oxidase-superoxide method. The neonatal weight, length and the ponderal index (PI) were measured after parturition. (1) The cord blood insulin concentration (9.0 +/- 3.3) mU/L and the ratio of insulin over glucagon 0.048 +/- 0.028 in the case group was significantly lower than that of controls (10.1 +/- 3.7) mU/L, 0.050 +/- 0.020 (P < 0.05). The concentrations of TBA (10.3 +/- 3.8) miromol/L and glucagon (235 +/- 57) ng/L in case group were obviously higher than that in controls (4.1 +/- 1.3) micromol/L, (205 +/-34) ng/L (P < 0.05). But no difference was shown in the glucose concentration in cord blood between the case and control groups [(3.4 +/- 1.1) mmol/L vs. (3.6 +/- 1.2) mmol/L, P > 0.05]. (2) The neonatal weight and length in case group were significantly lower than that of control [(3163 +/- 478) g vs. (3498 +/- 393) g, (46.5 +/- 2.3) cm vs. (49.3 +/- 1.9) cm, P < 0.01]; while the Ponderal index in case group was significantly higher than that of control group (3.13 +/- 0.23 vs. 2.92 +/- 0.29, P < 0.01). (3) The cord blood TBA concentration respectively showed a linear relationship with the cord blood insulin concentration, the cord blood glucagon concentration and the ratio of insulin over glucagon in the case group. With the increase in cord blood TBA concentration, the cord insulin concentration and the ratio of insulin over glucagon decreased; meanwhile the cord blood glucagon concentration rose (P < 0.01). The cord blood insulin concentration and the ratio of insulin over glucagon in case group were respectively positively correlated with the neonatal weight and length, and were negatively correlated with the PI (P < 0.01); while the cord glucagon concentration was respectively negatively correlated with the neonatal weight and length, and positively correlated with the PI (P < 0.01). In ICP fetus pancreas, there are hypoinsulinism, glucagon oversecretion, and decrease of the ratio of insulin over glucagon, which is closely correlated with fetal TBA concentration. The endocrine function of fetal pancreas affects the fetal growth and development.

Milk Intake and Feeding Behavior in the First Week of Life and Its Relationship to Cord Blood Ghrelin, Leptin, and Insulin Concentrations

Milk Intake and Feeding Behavior in the First Week of Life and Its Relationship to Cord Blood Ghrelin, Leptin, and Insulin Concentrations

Mutations in the Glucokinase Gene of the Fetus Result in Reduced Placental Weight

In human pregnancy, placental weight is strongly associated with birth weight. It is uncertain whether there is regulation of the placenta by the fetus or vice versa. We aimed to test the hypothesis that placental growth is mediated, either directly or indirectly, by fetal insulin. Birth weight and placental weight were measured in 43 offspring of 21 parents with mutations in the glucokinase (GCK) gene (25 had inherited the mutation and 18 had not), which results in reduced fetal insulin secretion. Birth weight, placental weight, umbilical cord insulin, and maternal glucose and insulin concentrations were measured in 573 nondiabetic, healthy, term pregnancies. GCK mutation carriers were lighter and also had smaller placentas (610 vs. 720 g, P = 0.042). This difference was also seen in 17 discordant sibling pairs (600 vs. 720 g, P = 0.003). GCK mRNA was not detected in the placenta by RT-PCR. In the normal pregnancies, placental weight was strongly correlated with birth weight (r = 0.61, P < 0.001). Cord insulin concentrations were directly related to placental weight (r = 0.28) and birth weight (r = 0.36) (P < 0.001 for both). These results suggest that insulin, directly or indirectly, plays a role in placental growth, especially as a mutation in the GCK gene, which is known to only alter fetal insulin secretion, results in altered placental weight. This finding is consistent with the preferential localization of the insulin receptors in the fetal endothelium of the placenta in the last trimester of pregnancy.

Impact of fetal growth restriction on body composition and hormonal status at birth in infants of small and appropriate weight for gestational age

Fetal growth restriction (FGR) has been related to several health risks, which have been generally identified in small-for-gestational age (SGA) individuals. To evaluate the impact of FGR on body composition and hormonal status in infants born either small- or appropriate-for-gestational age (AGA). Fetal growth was assessed by ultrasound every 4 weeks from mid-gestation to birth in 248 high-risk pregnancies for SGA. Fetal growth velocity was calculated as change in the estimated fetal weight percentiles and FGR defined as its reduction by more than 20 percentiles from 22 gestational weeks to birth. Impact of FGR on body composition, cord insulin, IGF-I, IGF binding protein-3 (IGFBP-3), and cortisol concentrations was assessed in SGA and AGA newborns. Growth-retarded AGA infants showed significantly reduced birth weight, ponderal index, percentage of fat mass, and bone mineral density when compared with AGA newborns with stable intrauterine growth. Cord IGF-I and IGFBP-3 concentrations were significantly decreased in growth-retarded infants in both SGA and AGA groups. Cord insulin concentration was significantly lower and cord cortisol significantly higher in AGA infants with FGR versus AGA newborns with stable intrauterine growth. After adjustment for gestational age and gender, birth weight was directly related to fetal growth velocity and cord IGF-I concentration. The variation in infant's adiposity was best explained by fetal growth velocity and cord insulin concentration. FGR affects body composition and hormonal parameters in newborns with birth weight within the normal range, suggesting these individuals could be at similar metabolic risks as SGA. .

Measurement of Cord Insulin and Insulin-Related Peptides Suggests That Girls Are More Insulin Resistant Than Boys at Birth

We aimed to examine sex differences in insulin and insulin propeptide concentrations at birth using validated cord blood collection. We tested the impact on insulin and insulin propeptides of taking 13 cord blood samples in heparin and EDTA and then centrifuging and separating plasma after 1, 2, 24, or 48 h at room temperature (heparin) or 4 degrees C (EDTA). Cord plasma insulin and insulin propeptides concentrations were measured in 440 babies and correlated with offspring anthropometry measured at birth. Cord insulin concentrations significantly decreased (74% those at baseline by 24 h; P = 0.01) in the samples taken in heparin and stored at room temperature, but those taken on EDTA and refrigerated remained stable for up to 48 h. Insulin propeptides were stable in both. Cord plasma insulin and insulin propeptides measured in EDTA were related to all measures of birth size and maternal glycemia and BMI (r > 0.11; P < 0.03 for all) and were higher in those delivered via caesarean section. Girls were lighter (3,497 vs. 3,608 g; P = 0.01) but had higher cord insulin (46.7 vs. 41.2 pmol/l; P = 0.031), total proinsulin (34.1 vs. 25.8 pmol/l; P < 0.001), and intact proinsulin (9.5 vs. 8.3 pmol/l; P = 0.004) concentrations than boys; this was further confirmed when cord insulin concentrations of boys and girls were compared after pair matching for birth weight (insulin 49.7 vs. 42.1 pmol/l; P = 0.004). When using appropriate sample collection methods, female newborns have higher insulin concentrations than male newborns, despite being smaller, suggesting intrinsic insulin resistance in girls.

Paternal insulin resistance and its association with umbilical cord insulin concentrations

Fetal growth is influenced by genetic factors as well as the intra-uterine environment. We hypothesised that some genetic factors may alter fetal insulin secretion and insulin action. To assess this, we analysed plasma insulin concentration in umbilical cord blood from 644 normal, term, UK Caucasian deliveries from the Exeter Family Study of Childhood Health. We tested for associations between cord insulin and each of parental anthropometry, fasting glucose, insulin and lipids. As expected, cord insulin concentrations correlated with all measures of birth size (weight, length, head and arm circumferences, sum of skinfold thicknesses, ponderal index: r=0.16-0.4, p<0.01 for all) and maternal BMI (r=0.11, p=0.005), maternal glucose (r=0.25, p<0.001) and maternal insulin resistance (r=0.23, p<0.001). Paternal fasting insulin and insulin resistance were correlated with cord insulin (r=0.15, p=0.006; r=0.13, p=0.001, respectively), and this was independent of paternal BMI. Multiple linear regression analysis revealed paternal insulin resistance to be a predictor of cord insulin concentrations, independently of maternal factors. Our results show an independent relationship between paternal insulin resistance and cord insulin concentrations. This is consistent with heritability of insulin resistance from father to offspring and a compensatory increase in fetal insulin secretion, the latter occurring pre-natally before the homeostatic feedback loop between glucose and insulin is established.

Type 1 diabetes-related antibodies in the fetal circulation: prevalence and influence on cord insulin and birth weight in offspring of mothers with type 1 diabetes.

During pregnancy, maternal type 1 diabetes-associated autoantibodies may cross the placenta. It is proposed that insulin antibodies (IA) allow transfer of insulin across the placenta, contributing to fetal hyperinsulinemia and macrosomia. We assessed the prevalence of IA, the tyrosine phosphatase IA-2, and glutamic acid decarboxylase (GADA) in cord blood from offspring of mothers with type 1 diabetes (ODM, n = 138) and control mothers (control, n = 47) and further assessed cross-sectional relationships of antibody titers to birth weight and fetal insulin. In ODM, antibodies were frequently present in cord blood; 124 ODM (95%) were positive for IA, 82 (59%) were positive for GADA antibodies, and 61 (44%) were positive for IA-2 antibodies. In controls, GADA and IA-2 antibodies were absent, whereas seven controls (15%) were positive for IA at low titers (P < 0.0001 ODM vs. controls for all).ODM with IA (IA positive) or without IA (IA negative) had similar birth weights (mean +/- sd: IA positive, 3.8 +/- 0.7 kg; IA negative, 4.0 +/- 0.6 kg; P = 0.31) and cord insulin concentrations (IA positive: median, 112 pmol/liter; interquartile range, 62-219 pmol/liter; IA negative: median, 114 pmol/liter; interquartile range, 59-194 pmol/liter; P = 0.96). Similarly, the presence of GADA and/or IA-2 autoantibodies (n = 103) was not associated with differences in birth weight or insulin concentrations. Antibody titers were not associated with birth weight or insulin as continuous variables in either controls or ODM. Islet autoantibodies and IA are a common finding in cord blood of ODM, but we found no evidence that they influence offspring insulin concentrations or weight at birth.

Antenatal obesity is associated with raised umbilical cord insulin concentrations in normal polynesians

Antenatal obesity is associated with raised umbilical cord insulin concentrations in normal polynesians

Observational study of maternal anthropometry and fetal insulin

AIMSTo examine the relation between maternal body fat and fetal metabolism.METHODSIn this observational study, cord blood samples were collected from 60 infants of healthy women for the measurement of insulin...

Increased macrosomia and perinatal morbidity independent of maternal obesity and advanced age in Korean women with GDM.

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.

Association between neonatal blood pressure and umbilical cord insulin concentration.

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.

Association between neonatal blood pressure and umbilical cord insulin concentration.

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.

Differences in umbilical cord insulin and birth weight in non-diabetic pregnancies of women from different ethnic groups in New Zealand

Many ethnic groups at high risk of non-insulin-dependent diabetes mellitus are hyperinsulinaemic by early adult life. This study assessed whether such hyperinsulinaemia is present at birth. Cross sectional comparisons of maternal biochemistry, umbilical cord biochemistry and neonatal anthropometry were made between one 'low risk' and three 'high risk' ethnic groups, without diabetes in pregnancy in Auckland, New Zealand. The study comprised 123 European, Polynesian (Maori and Pacific Islands) and Indian normal pregnancies. Indian mothers were the smallest, with the highest insulin and non-esterified fatty acid concentrations. Polynesian mothers were the most obese with a higher fructosamine concentration. From these pregnancies, Indian neonates were smaller, slimmer, with the highest cord triglyceride (0.6 mmol/l vs 0.4 mmol/l, p < 0.01), and lowest cord insulin concentrations (7.1 mU/l vs 8.6 mU/l (European), 9.2 mU/l (Polynesian), p < 0.05). Polynesian babies had a high cord insulin: C-peptide ratio (52.5 mU/nmol vs 44.4 mU/nmol (European), 44.1 mU/nmol (Indian), p = 0.05). Although reduced intrauterine growth may contribute to the excess of diabetes and heart disease in Indians, it cannot explain the excess of diabetes in Polynesians. Exposure to minor relative maternal hyperglycaemia in the mother and abnormal neonatal insulin handling (as demonstrated by the higher insulin: C-peptide ratio) may be of long-term significance in Polynesians.

Cord plasma glucose and insulin concentrations and maternal-fetal relations.

The concentration of glucose and insulin was estimated in 854 samples of umbilical cord blood plasma and 503 concurrently collected maternal blood samples. The mean cord insulin concentration, excluding all infants born to known diabetic mothers, was 7 muU./ml., but the distribution was skewed with 10 per cent of infants having a value of 12 muU./ml. or more. The giving of intravenous sugar-coating fluids to the mother during labor tended to exaggerate the skewness rather than move the whole distribution to the right. Babies born by vaginal route, whatever the presentation of method of delivery, had slightly lower mean insulin values than those born by Caesarean section. It thus seems unlikely that "stress" is a factor causing high cord insulin values at birth. Other data concerning maternal-fetal glucose and insulin relations are discussed.