Cord Blood C-peptide Research Articles

Hormonal enteroinsular axis in newborn infants of insulin-treated diabetic mothers.

To study whether the increased glucose levels in the amniotic fluid during diabetic pregnancies induce an early maturation of the hormonal enteroinsular axis, we measured blood glucose levels and plasma concentrations of C-peptide, pancreatic glucagon, enteroglucagon, and gastric inhibitory polypeptide (GIP) in cord blood from 18 newborn infants of insulin-treated diabetic mothers (IDM) and 18 infants of nondiabetic mothers. In addition, we studied the same parameters in 20 IDM and 12 control infants before and after their first feed comprising human milk (5 mL/kg), given by nasogastric tube at the age of 2 h. The IDM had significantly higher blood glucose levels and plasma C-peptide concentrations in their cord blood than the control infants, which was followed postnatally by a substantial fall in these levels, whereas a more modest decrease could be seen in the control infants. Circulating enteroglucagon and GIP concentrations at the age of 2 h were significantly higher than those observed in cord blood in both the IDM and the control infants, but the IDM had significantly lower blood glucose levels, higher plasma C-peptide, and lower enteroglucagon concentrations before the first feed. There was a significant increase in blood glucose levels after the feed in both the IDM and the control infants, and the concentrations 2 h after feeding were of the same magnitude in the two groups. No significant C-peptide response could be observed in either group, but the IDM continuously had higher C-peptide concentrations. A significant enteroglucagon and GIP response could be seen in the IDM, whereas the controls exhibited only a GIP response. However, no significant differences were found between the two groups in the absolute postprandial plasma concentrations of these hormones. Our results show rapid, substantial postnatal changes in circulating concentrations of enteroinsular hormones in both IDM and control infants. Enteral feeding with human milk corrects early postnatal hypoglycemia within 2 h in most IDM without causing any exacerbation of their hyperinsulinemia. The absence of any C-peptide response to the first feed and of any observed differences between IDM and normal infants in absolute concentrations of enteroglucagon and GIP after the first feed suggests that the enteroinsular axis matures postnatally in both groups of infants.

Cord insulin and C-peptide--distribution in an unselected population.

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.

Asymmetric Septal Hypertrophy in Infants of Diabetic Mothers

Maternal hyperglycemia may result in fetal hyperinsulinemia and asymmetric septal hypertrophy, macrosomia, and hypoglycemia in infants of diabetic mothers. We monitored glycosylated hemoglobin levels in 61 pregnant diabetic women each trimester as an index of maternal glycemic control and did serial fetal echocardiograms starting at 18 weeks of gestation. At delivery, cord blood C-peptide levels were obtained as an index of fetal hyperinsulinemia. Infants were assessed for hypoglycemia, macrosomia and septal thickening by echocardiography. Nineteen of the 61 infants (31%) had septal hypertrophy, were heavier, and had higher cord blood C-peptide levels and lower serum glucose levels than unaffected infants. Maternal glycosylated hemoglobin levels were higher during the third trimester in mothers of affected infants. Our data support a possible relationship between third-trimester maternal hyperglycemia and neonatal asymmetric septal hypertrophy, macrosomia, and hypoglycemia.

SERUM LEVELS OF SOMATOMEDINS AND SOMATOMEDIN BINDING PROTEIN IN PREGNANT WOMEN AND THEIR INFANTS

Serum levels of IGF-I, IGF-II and the low molecular form of somatomedin binding protein (SMBP) were determined in pregnant women and their infants. Longitudinal studies during pregnancy were performed in healthy women, women with GH deficiency (n=3) and women with diabetes or gestational diabetes (n=44). IGF-I, IGF-II and SMBP were determined by radioimmunoassays using polyclonal antibodies. The serum levels of IGF-I and SMBP, but not IGF-II, increased during pregnancy in both healthy women and women with diabetes. In GH deficient women the levels rose to normal pregnant levels. The birth weight percentile of the infants increased with the maternal IGF-I levels and decreased with the maternal SMBP levels. The ratio between maternal IGF-I and SMBP levels improved the correlation to the birth weight percentile. No correlation was found between the birth weight and the isolated values of IGF-I, IGF-II, SMBP and C-peptide in cord blood. The IGF-II levels in cord blood from infants of diabetic women were 50% higher than those of nondiabetic women. The correlation between maternal levels of the birth weight of the infants indicates that maternal IGF-I levels may play a role in the transfer of nutrients to the fetus. The elevated IGF-II levels in cord blood of infants of diabetic women suggest that IGF-II could participate in the glucose homeostasis of the fetus.

Spiral artery lesions in relation to metabolic control in diabetes mellitus.

Decidual and intramyometrial spiral arteries from 18 insulin-dependent diabetic and 18 non-diabetic women were compared histologically. All women were normotensive and none had signs of pre-eclampsia. None of the infants in either group had intra-uterine growth retardation. Metabolic control in the diabetic women was assessed by pregnancy glucose level from the last trimester of pregnancy and by C-peptide in amniotic fluid and cord blood as a measure of the fetal beta-cell function. The intramyometrial and decidual parts of the spiral artery were normal in the non-diabetic group. None of the diabetic patients showed pathological changes in the intramyometrial part of the spiral artery. Two of the 18 diabetic patients had pathological changes (intramural fibrosis) in the decidual portion of the spiral artery. These two women had signs of diabetic angiopathy (White's class D and F) and in one of them, the background diabetic retinopathy progressed markedly during pregnancy. The pregnancy glucose level was above normal (greater than 6.2 mM/l) in 3 of 18 diabetics. The C-peptide values in amniotic fluid and cord blood were above normal in 11 of 17 and in 5 of 17, respectively. Both patients with spiral artery lesions had pregnancy glucose levels in the upper range, 5.86 and 5.98 mM/l, respectively and the highest value of C-peptide in the amniotic fluid and cord blood, suggesting exaggerated fetal beta-cell function.

Investigation on serum C-peptide concentrations in pregnant diabetic women and in newborns of diabetic mothers.

Serum C-peptide concentrations at delivery and neonatal complications were investigated in a group of diabetic mothers and in their infants (IDM, n = 29). Furthermore, the changes in B-cell function and in daily insulin demand was followed up in 12 pregnant diabetics (of them 8 with long-term and 4 with short-term and "mild" diabetes) during pregnancy. All these diabetic mothers were under an intensive metabolic control with the aim to achieve normoglycaemia mainly in the second part of pregnancy. Mean cord blood C-peptide level of 29 IDM was 0,58 +/- 0,43 nmol/l, being not significantly higher than either the average C-peptide concentration of our adult control group (0,50 +/- 0,15 nmol/l, n = 24) or that of seven infants born to healthy mothers (0,58 +/- 0,37 nmol/l). Early hypoglycaemia was observed in five, macrosomia in three and IRDS in one neonate, resp. mothers coming to our intensive care after the 13th week of gestation gave birth with a higher incidence of neonatal complications than those controlled already in the first trimester or even preconceptionally. In 20 of 25 mothers studied venous C-peptide concentrations at delivery were undetectably low, in spite of their infants having cord blood C-peptide levels in the measurable range. In 8 of the 12 diabetic mothers with long-term diabetes C-peptide levels remained under the detection limit of the assay throughout pregnancy. In the 4 other cases with "mild" diabetes (and, hence, with a late start of intensive control) C-peptide values increased in the course of pregnancy; however, 3 of the four mothers gave birth with neonatal complications. These results indicate that (1) early--preferably preconceptional--intensive metabolic control of pregnant diabetics may reduce the incidence of neonatal complications; (2) fetal C-peptide can neither during pregnancy nor at birth pass through the placental barrier, and (3) mothers with "mild" diabetes require the same early and strict metabolic control as the more severe cases to avoid neonatal complications.

Cord blood C-peptide:glucose ratio - a good indicator of B cell function in infants of diabetic mothers.

Cord blood C-peptide:glucose ratio - a good indicator of B cell function in infants of diabetic mothers.

Monocyte insulin receptors in infants of strictly controlled diabetic mothers.

Infants of diabetic mothers have hyperinsulinism at birth, presumably resulting from maternal hyperglycemia or some other derangement of maternal metabolism, and are extremely sensitive to insulin. Such infants have significantly greater numbers of insulin receptors on cord blood monocytes compared to normal infants. To assess the role of maternal diabetic control, nine infants of insulin-dependent diabetic mothers, who were intensively treated during pregnancy, were studied. Maternal blood glucose values were measured during weekly out-patient visits throughout pregnancy, and insulin therapy was given to maintain fasting blood glucose values below 100mg/dl. When necessary, the patients were hospitalized early in pregnancy in order to achieve glucose control, and all patients were hospitalized for up to 2 weeks before delivery for strict glucose control. The mean birth weight (+/- SD) of these infants (3.23 +/- 0.23 kg) was lower than that of nine infants of mothers with gestational diabetes not receiving insulin or intensive efforts at maintenance of normoglycemia (3.99 +/- 0.12; P less than 0.01) and was not significantly different from that of normal infants (3.51 +/- 0.37 kg). Mean cord blood C-peptide levels (+/- SD), determined by RIA, were 1.6 +/- 0.78 ng/ml for infants of these strictly controlled diabetic mothers and 1.4 0.1 ng/ml for normal infants. Scatchard analysis of [125]insulin binding to cord blood monocytes yielded mean receptor numbers for infants of diabetic mothers of 22,500 vs. 105,000 sites/cell for infants of diabetic mothers (P less than 0.001) and 26,600 sites/cell for normal infants. We conclude that the strict control of maternal diabetes during the last trimester of pregnancy prevents fetal hyperinsulinemia and is associated with the development of normal numbers of insulin receptors on the infants' monocytes.

Amniotic fluid C-peptide as an index for intrauterine fetal growth

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 ≥36 weeks' gestation. Infants were grouped according to birth weight and gestational age at delivery, as follows: small for gestational age (SGA, ≤10%, n = 11), average for gestational age (AGA, 10% to 90%, n = 75), large for gestational age (LGA, >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.

Cord blood C-peptide: Glucose ratio in the newborn of diabetic mothers

SummaryCord blood C-peptide and glucose have been measured in 32 babies of non-diabetic mothers and 40 babies of diabetic mothers. A significant correlation was found between cord blood C-peptide and glucose in babies of poorly controlled diabetic mothers. A positive correlation was also found between the cord blood C-peptide: glucose ratio and the birth weight ratio in the same group of newborn. The cord blood C-peptide and C-peptide: glucose ratio was raised in nearly half of the babies of poorly controlled diabetic mothers and was frequently associated with neonatal hypoglycaemia