METABOLIC EVENTS IN INFANTS OF DIABETIC MOTHERS DURING FIRST 24 HOURS AFTER BIRTH I.

ABSTRACT. Changes in plasma glucose, nonantibody-bound insulin and glucagon concentrations were studied in 32 newborn infants of diabetic mothers (IDM) during the first 24 hours after birth. Ten infants were born to White class A mothers and 22 to class B-F mothers. The infants were kept fasting during the investigative period and blood was sampled from an umbilical artery catheter. At birth, plasma glucose and glucagon levels were similar in the class A and B-F infants, whereas nonantibody-bound insulin levels were approximately 15-fold higher in the class B-F infants than in the class A infants (p<0.001). After birth, plasma glucose fell in all infants, the nadir being reached at two hours (p<0.01). Plasma glucose fell by approximately 35 % in the class A infants and 63 % in the class B-F infants (p<0.01). Eight IDM had asymptomatic hypoglycemia (plasma glucose <1.9 mmol/l) and four of these infants had glucose levels below 1.7 mmol/l and were withdrawn from further study. In the remaining four hypoglycemic IDM, plasma glucose was about 1.6-fold higher (p<0.01) and insulin about 11-fold higher (p<0.001) at birth compared to the 24 normoglycemic IDM. The hypoglycemia was attended by unchanged insulin levels in the class A infants, whereas insulin fell in the class B-F infant (p<0.01). However, during the whole investigative period, plasma insulin of the class B-F infants was higher than that of the class A infants (p<0.01). After birth, plasma glucagon increased slowly in all IDM and peak values were reached after 12 hours in the class A infants (p<0.05) and 24 hours in the class B-F infants (p<0.01). Only those infants who became hypoglycemic after birth exhibited a significant increment in plasma glucagon from 0-2 hours (p<0.05). These results suggest that neonatal hypoglycemia of IDM results from high plasma levels of nonantibody-bound insulin together with a very retarded increment in plasma glucagon levels. The degree of neonatal hypoglycemia and hyperinsulinemia of an individual IDM seems to be positively correlated to the severity of the diabetes of the mother.     

Effect of glucagon on blood glucose homeostasis in infants of diabetic mothers.

Thirty infants of diabetic mothers (IDM) were randomly selected and divided into 3 groups of 10 babies each. Group A were used as controls. Group B received glucagon 300 mug/kg i.m. and Group C received glucagon 300 mug/kg i.v. at birth. Hypoglycemia developed in 6 infants in Group A and 4 infants in Group B. None of the infants in Group C had hypoglycemia. Mean blood glucose was higher in Group C in the first 3 hours than Group A, and higher in Group B in the first (/2-1 hour. I.v. glucshon, 300 mug/kg when given in the first 15 minutes after birth prevented hypoglycemia in IDM in the first hours of life.     

EFFECT OF GLUCAGON ON BLOOD GLUCOSE HOMEOSTASIS IN INFANTS OF DIABETIC MOTHERS

ABSTRACT: Wu, P. Y. K., Modanlou, H. and Karelitz, M. (Department of Pediatrics, University of Southern California School of Medicine, Los Angeles County-University of Southern California Medical Center, Los Angeles, USA). Effect of glucagon on blood glucose homeostasis in infants of diabetic mothers. Acta Paediatr Scand, 64:441, 1975.–Thirty infants of diabetic mothers (IDM) were randomly selected and divided into 3 groups of 10 babies each. Group A were used as controls. Group B received glucagon 300Uµg/kg i.m. and Group C received glucagon 300µg/kg i.v. at birth. Hypoglycemia developed in 6 infants in Group A and 4 infants in Group B. None of the infants in Group C had hypoglycemia. Mean blood glucose was higher in Group C in the first 3 hours than Group A, and higher in Group B in the first 1/2-1 hour. I.v. glucagon, 300µg/kg when given in the first IS minutes after birth prevented hypoglycemia in IDM in the first hours of life.     

Plasma noradrenaline and adrenaline in newborn infants of diabetic mothers: relation to plasma lipids

No significant differences in plasma noradrenaline and adrenaline concentrations were found between 14 infants of diabetic mothers (IDMs) and 7 infants of non-diabetic mothers at birth or at 2 hours of age, although the mean values were higher in the IDMs. The mean blood glucose concentration declined from birth to 2 hours of age and it was lower at 2 hours of age in the IDMs although only one IDM became hypoglycaemic. Plasma non-antibody bound insulin concentrations were approximately 12 fold higher at birth and at 2 hours of age in the IDMs than in the control infants. Similar increases in plasma free fatty acids and free glycerol concentrations from birth to 2 hours of age were observed in the 2 groups. At 2 hours of age positive correlations were found between plasma noradrenaline and free fatty acids (r = 0.85, p less than 0.01) and free glycerol (r = 0.65, p less than 0.05) and between plasma adrenaline and free glycerol (r = 0.71, p less than 0.05) and the rise in free glycerol from birth to 2 hours of age (r = 0.65, p less than 0.05) in the IDMs. At birth positive correlations between plasma free fatty acids and plasma noradrenaline (r = 0.69, p less than 0.02) and plasma adrenaline (r = 0.88, p less than 0.01) were found in the IDMs. No correlations were found in the control infants. These findings indicate that the catecholamines counteracts the inhibitory effect of insulin on lipolysis in IDMs.     

Plasma Noradrenaline and Adrenaline in Newborn Infants of Diabetic Mothers: Relation to Plasma Lipids

ABSTRACT. No significant differences in plasma noradrenaline and adrenaline concentrations were found between 14 infants of diabetic mothers (IDMs) and 7 infants of non-diabetic mothers at birth or at 2 hours of age, although the mean values were higher in the IDMs. The mean blood glucose concentration declined from birth to 2 hours of age and it was lower at 2 hours of age in the IDMs although only one IDM became hypoglycaemic. Plasma non-antibody bound insulin concentrations were approximately 12 fold higher at birth and at 2 hours of age in the IDMs than in the control infants. Similar increases in plasma free fatty acids and free glycerol concentrations from birth to 2 hours of age were observed in the 2 groups. At 2 hours of age positive correlations were found between plasma noradrenaline and free fatty acids ( r =0.85, p < 0.01) and free glycerol ( r =0.65, p < 0.05) and between plasma adrenaline and free glycerol ( r =0.71, p < 0.05) and the rise in free glycerol from birth to 2 hours of age ( r =0.65, p < 0.05) in the IDMs. At birth positive correlations between plasma free fatty acids and plasma noradrenaline ( r =0.69, p < 0.02) and plasma adrenaline ( r =0.88, p < 0.01) were found in the IDMs. No correlations were found in the control infants. These findings indicate that the catecholamines counteracts the inhibitory effect of insulin on lipolysis in IDMs.     

Influence of the maternal plasma glucose concentration at delivery on the risk of hypoglycaemia in infants of insulin-dependent diabetic mothers

Plasma glucose concentrations at birth and at two hours of age were measured in 53 infants of insulin-dependent mothers (IDMs). The plasma glucose concentrations at delivery were measured in the mothers of 17 IDMs and in the remaining 36 mothers, glucose was estimated by interpolation from concentrations achieved just before and after delivery. Clinical and laboratory data from the two groups were otherwise similar, so the groups were combined for further analyses. The maternal plasma glucose at delivery correlated positively with the glucose concentration of the IDMs at birth (rho = 0.82, p less than 0.001) and negatively with the glucose concentration at two hours of age (rho = -0.46, p less than 0.001). Maternal plasma glucose concentration was higher in mothers delivered by caesarean section than in vaginally delivered mothers (p less than 0.05). Eleven IDMs became hypoglycaemic at two hours of life (plasma glucose less than or equal to 1.7 mmol/l). These infants had higher cord plasma glucose concentrations at birth than those who remained normoglycaemic; the maternal glucose concentration was also higher. None of the IDMs became hypoglycaemic if the maternal glucose concentration at delivery was less than 7.1 mmol/l. In 28 IDMs the simultaneous plasma concentrations of non-antibody bound immunoreactive insulin (IRI) were recorded. Cord plasma IRI correlated with glucose and IRI at two hours of age (rho = -0.73, p less than 0.001 and rho = 0.77, p less than 0.001, respectively). Cord plasma IRI was higher in IDMs who became hypoglycaemic than in the remaining infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma glucagon levels in the term human infant and effect of hypoxia

The mean plasma pancreatic glucagon level at birth in 44 normal infants delivered vaginally was 140 pg/ml. The simultaneous maternal level was 122 pg/ml which was not quite significantly different at the P [unk]0.05 level. 2 hours after birth 30 of these infants had a mean rise in plasma glucagon of 51 pg/ml (P [unk] 0.01), and their mothers had a fall of 38 pg/ml (P [unk] 0.05). The mean plasma pancreatic glucagon level at birth in 12 normal infants delivered by caesarean section was 130 pg/ml which did not differ significantly from the group delivered vaginally. The glucagon level at birth in 20 infants with fetal distress (fetal scalp pH [unk] 7.2 or umbilical artery pH [unk] 7.15) was 244 pg/ml, and this was significantly higher than for normal infants at birth (P [unk] 0.01). Whereas the rise in neonatal glucagon 2 hours after birth might have been caused by a mean fall in blood glucose of 23 mg/100 ml, the infants with fetal distress had normal glucose levels, so that another mechanism must be responsible for their raised glucagon.     

The effect of early feeding on plasma glucose levels in SGA infants

Plasma glucose levels were measured during the first day of life in 24 small-for-gestational-age (SGA) infants who began formula feedings within two hours of birth. In contrast to the high incidence of low blood sugar seen previously in fasted SGA infants, no infant had a plasma glucose below 30 mg/dl; after the first feeding, no values below 40 mg/dl occurred. Mean plasma glucose levels were lower in infants born to mothers with preeclampsia (57.2 +/- 2 vs 69.7 +/- 2.3 mg/dl, p less than .005). The results indicate that hypoglycemia (plasma glucose less than 40 mg/dl) can be easily avoided in SGA infants simply by providing adequate calories without delay after delivery.     

PLASMA NORADRENALINE AND ADRENALINE IN INFANTS OF DIABETIC MOTHERS AT BIRTH AND AT TWO HOURS OF AGE

ABSTRACT. Plasma noradrenaline and adrenaline in the umbllical artery were very high in many infants of both diabetic mothers (IDM) and non-diabetic mothers (controls) compared to values obtained in adults. Blood pH was slightly but significantly lower in IDM than in controls at delivery. There was a significant negative correlation between plasma noradrenaline and blood pH in IDM at birth, but no correlation between plasma noradrenaline and blood glucose, birth weight and Apgar scores. Plasma noradrenaline decreased significantly from birth to two hours of age both in IDM and controls. At two hours of age plasma noradrenaline and adrenaline were significantly greater in IDM compared to controls whereas blood glucose concentration was lower in the former group. There was a close inverse correlation between plasma noradrenaline and adrenaline, respectively, and blood glucose in IDM at two hours of age but not in controls. The elevated plasma noradrenaline at delivery in IDM may be explained by clinically undetectable acidosis whereas elevated plasma catecholamines at two hours are probably due to hypoglycaemia.     

Perinatal outcome of infants born to diabetic mothers.

Two hundred and sixty three pregnant diabetic mothers' perinatal outcome was evaluated. Two hundred and twenty five infants were born to gestational diabetic mothers (IGDM) and 38 infants to mothers with established diabetes mellitus (IDM). In IGDM group, 34 babies (15%) were preterm and 45 (20%) were low birth weight (less than 2500 g). Thirty eight babies (17%) were large-for-dates (LFD) and 14 (6.2%) were small-for-dates (SFD). Among IDM group, 8 (21%) babies were preterm and 8 (21%) were low birth weight (less than 2500 g). Fifteen babies (39.5%) were LFD and 3 (8%) were SFD. Out of all babies, hypoglycemia occurred in 43 (16%), birth asphyxia in 24 (9%) and respiratory distress in 21 (8%). Nearly half of respiratory distress were due to hyaline membrane disease. Perinatal mortality rate was significantly higher (p less than 0.001) in IDM (237/1000 live birth) as compared to IGDM (40/1000 live birth).     

Influence of the Maternal Plasma Glucose Concentration at Delivery on the Risk of Hypoglycaemia in Infants of Insulin-Dependent Diabetic Mothers

Plasma glucose concentrations at birth and at two hours of age were measured in 53 infants of insulin-dependent mothers (IDMs). The plasma glucose concentrations at delivery were measured in the mothers of 17 IDMs and in the remaining 36 mothers, glucose was estimated by interpolation from concentrations achieved just before and after delivery. Clinical and laboratory data from the two groups were otherwise similar, so the groups were combined for further analyses. The maternal plasma glucose at delivery correlated positively with the glucose concentration of the IDMs at birth (Q=0.82, p <0.001) and negatively with the glucose concentration at two hours of age (Q= -0.46, p <0.001). Maternal plasma glucose concentration was higher in mothers delivered by caesarean section than in vaginally delivered mothers ( p <0.05). Eleven IDMs became hypoglycaemic at two hours of life (plasma glucose ≥1.7 mmol/1). These infants had higher cord plasma glucose concentrations at birth than those who remained normoglycaemic; the maternal glucose concentration was also higher. None of the IDMs became hypoglycaemic if the maternal glucose concentration at delivery was less than 7.1 mmol/l. In 28 IDMs the simultaneous plasma concentrations of non-antibodybound immunoreactive insulin (IRI) were recorded. Cord plasma IRI correlated with glucose and IRI at two hours of age (Q=-0.73, p <0.001 and Q=0.77, p <0.001, respectively). Cord plasma IRI was higher in IDMs who became hypoglycaemic than in the remaining infants. The results suggest that among the factors which may be responsible for neonatal hypoglycaemia in IDMs a major factor may be the maternal plasma glucose concentration at the time of delivery.     

METABOLIC EVENTS IN INFANTS OF DIABETIC MOTHERS DURING FIRST 24 HOURS AFTER BIRTH II.

ABSTRACT. Changes in plasma glycerol (FG), free fatty acids (FFA) and triglyceride (TG) were studied in 24 normo- and 8 hypoglycemic infants of diabetic mothers (IDM). In both groups a normal rise in plasma FG 2 hours after birth was found indicating unimpaired lipolysis. The rise in plasma FFA, however, was only about 50% of normal in normoglycemic IDM and about 25% of normal in hypoglycemic IDM. The rise in plasma TG was normal in normoglycemic and about 70% of normal in hypoglycemic IDM. The 2 hour rise in plasma FFA correlated with the 2 hour concentration of insulin and glucose, whereas the rise in plasma FG and TG did not. Maternal plasma FFA correlated with fetal FFA retention (unbilical vein minus artery (V-A) FFA concentrations). No correlations were found between maternal plasma FFA values and birth-weights nor between umbilical V-A FFA concentrations and birth-weights.     

An immunohistochemical study of islet cells with macronuclei in infancy

The presence of hypertrophic islet cells in infancy as evidenced by nuclear enlargement (2 to 6 times normal size) has been mentioned as a morphological accompaniment of hyperinsulinemic hypoglycemia of infancy. We report an immunohistochemical and semiquantitative study of hypertrophic islet cells in 14 infants with neonatal hypoglycemia (10 with documented persistent neonatal hypoglycemia and 4 with probable persistent neonatal hypoglycemia) and 6 infants born to diabetic mothers (IDM), using an indirect immunoperoxidase methods for the demonstration of insulin, somatostatin, and glucagon. Quantitation of immunoreactivity was performed in each case on 20 hypertrophic cells. Polyploid cells were positive for insulin and somatostatin but negative for glucagon; insulin-positive cells outnumbered somatostatin-positive cells in both groups. As nuclear hypertrophy is considered to be a sign of hyperfunction, our findings are in accordance with the concept that IDM involves reactive beta-cell hypertrophy and similar findings in the pancreases of infants with persistent neonatal hypoglycemia (PNH) suggest a primary dysfunction of their beta cells, too.     

METABOLIC EVENTS IN INFANTS OF DIABETIC MOTHERS DURING FIRST 24 HOURS AFTER BIRTH III.

ABSTRACT. Plasma amino acid concentrations (AAC) were studied in 31 diabetic mothers (10 of White class A, 10 of B-C and 11 of D-F) and their 32 infants during the first 24 hours after birth. Only minor differences between the 3 groups were found at birth and 2 hours, and none at 12 and 24 hours after birth. The individual AAC in umbilical vein plasma did not correlate with birthweight. All AAC except aspartic acid, aspargine, cystine and glutamic acid were higher in umbilical venous plasma than in maternal plasma. Umbilical venousarterial differences of amino acids did not correlate with maternal or umbilical vein insulin concentrations except for threonine and valine. In general essential amino acids decreased after birth. In 8 infants with hypoglycemia and hyperinsulinism at 2 hours of age several plasma amino acids were lower than in the normoglycemic infants.     

Glucose tolerance and insulin secretion in very small babies.

Nineteen exchange transfusions were performed via the umbilical artery using blood preserved with acid-citrate and dextrose in 8 infants of 34-40 weeks gestation (larger infants) and 9 very small infants of 26-33 weeks gestational age. The plasma glucose rise which was similar in both groups stimulated insulin secretion from the larger infants but not the very small infants. No significant differences occurred between the groups in the fall in mean free fatty acid levels or increase in growth hormone secretion. Following transfusion there was a sharp rise in mean plasma insulin concentration in the larger infants and a smaller rise in the very small infants. A highly significant positive correlation was found between the maximum posttransfusion plasma insulin and the birth weight of the infants. Plasma glucose levels of less than 30 mg/100 ml occurred in 2 larger and 5 very small infants during the first 3 hours after transfusion. One infant of birth weight 0.98 kg received four transfusions; in 2 where he received ACD blood via the umbilical artery or vein, insulin secretion was not stimulated but in the other 2 in which glucagon or arginine was added to the ACD donor blood, insulin secretion was stimulated. Feeding practice should take account of the fact that although very small infants secret less insulin than larger infants during exchange transfusion they are more likely to become hypoglycaemic in the immediate posttransfusion period.     

EFFECT OF INTRAVENOUS HYDROCORTISONE ADMINISTRATION ON GLUCOSE HOMEOSTASIS IN SMALL FOR GESTATIONAL AGE INFANTS

Abstract. The effects of I.V. hydrocortisone (H) (10 mg/kg) on glucose homeostasis were evaluated at 25 to 85 hours of age in 14 infants who were small for gestational age (SGA) in comparison to 17 control SGA infants. Three hours after H administration, higher levels of plasma glucose than in controls were detected (mean ±S.E.M.): 4.78±0.2 vs. 2.88±0.2 mmol/1 ( p <0.01), while lower levels were found for blood pyruvate (38±7 vs. 89±12 μmol/l— p <0.01), plasma insulin (6.4±0.5 vs. 12±0.8 μIU/ml— p <0.05) and plasma glucagon (62.25±6.6 vs. 81.6±6.6 pmol/l— p <0.05). Three hours after H administration, I.V. injection of l -alanine (150 mg/kg) produced a significant rise over baseline of plasma glucose concentration from 4.78±0.2 to 5.94±0.2 mmol/l at 50 min ( p <0.05), whereas no significant change was observed in controls. There was no significant change in plasma glucagon and insulin concentrations after l -alanine injection in either group. These results show that in SGA infants primed with H, the rise of plasma glucose concentration after l -alanine administration is observed with low plasma insulin levels and without stimulation of glucagon secretion. They suggest that H induced a reduced peripheral utilization of glucose by lowering the plasma levels of insulin and a production of glucose from alanine through gluconeogenesis.     

Hyperammonemia in hypoglycemic preterm neonates

Plasma glucose, blood urea nitrogen, and ammonia were measured simultaneously in 44 newborns a few hours after birth. When the concentration of plasma glucose was below 30 mg/dl, plasma ammonia concentration was significantly higher (129 +/- 67 mumol/l) than in normoglycemic infants (74 +/- 33 mumol/l; p less than 0.01). Blood urea nitrogen was slightly lower in hypoglycemic infants (3.65 +/- 0.7 mmol/l) than in the control group (4.5 +/- 1 mmol/l) but the difference was not significant. These data show that hyperammonemia can be associated to hypoglycemia in low birth weight infants. Therefore, further investigations are required to determine the link between urea and glucose production rates in hypoglycemic newborns and whether hyperammonemia participates in the deleterious effects of hypoglycemia on the neonatal brain.     

Leptin, insulin, and glucose serum levels in large-for-gestational-age infants of diabetic and non-diabetic mothers

BACKGROUND: It has been suggested that hyperleptinemia could be caused by hyperinsulinemia in infants of diabetic mothers (IDMs). AIM: To compare leptin, insulin, and glucose levels in large-for-gestational-age (LGA) and appropriate-for-gestational-age (AGA) infants. Methods: A cross-sectional study was conducted in IDMs, infants of non-diabetic mothers (INDM) and AGA infants. RESULTS: Seventy-seven newborns were studied (11 IDM, 16 INDM, and 50 AGA infants). Leptin levels were significantly higher in LGA infants than in the AGA group and a trend for higher levels in IDM than NIDM was observed. Insulin levels and insulin resistance were significantly higher in IDMs. Glucose levels were lower in both groups of LGA infants. CONCLUSIONS: We found insulin resistance, hyperinsulinism and hyperleptinemia in IDMs, and the trend of higher leptin levels in IDMs than INDMs shows that leptin could be related to insulin resistance in these infants.     

Follow-up of children of insulin-dependent and gestational diabetic mothers. Neuropsychological outcome

Ninety-four infants of 28 weeks gestation or more were born to 85 women, 64 type I and 21 gestational diabetics, between 1969-1972 at Sabbatsberg's Hospital, Stockholm. Perinatal mortality rate was 6.3%. The follow-up study was conducted when the children were approximately 5 years of age and included a physical and a neurological evaluation, IQ determination of mother and child, and an interview of mother by a psychologist. Fifty-three infants of insulin-dependent (IDM) and 20 infants of gestational diabetic mothers (IGDM) (83%) participated, 3 families could not be traced and 12 were unwilling. The group lost to follow-up (13 IDM, 2 IGDM) had more perinatal complications including congenital malformations than the follow-up group. All children had normal physical and neurological development. IQ was normal, the majority were above 100, the average in IDM was 115 (range 98-144) and 112 in IGDM (range 95-133). No obvious relationship was found between maternal acetonuria during pregnancy, infant birthweight, blood glucose during first hours after birth or neonatal complications and IQ of the children. A correlation (r = 0.364, p less than 0.01) was found between maternal and child IQ. Mothers exhibiting emotional disorders (anxiety, depression) had significantly higher life stress scores based on 29 stress variables and reported more frequently about conduct and behavioural disorders in their children than mothers without emotional disturbances.     

Blood sugar,free fatty acids and triglycerides in infants of diabetic mothers

Blood sugar (BS), free fatty acids (FFA) and triglycerides (TG) were estimated in eighteen neonates of diabetic mothers (IDM) and 36 appropriate for gestational age (AGA) term newborns of non-diabetic mothers, delivered normally and having normal blood sugar levels (30 mg/dl and above) were taken as controls. Even though blood sugar levels in the cord blood were higher in IDM group, mean levels were much lower than controls in first few hours of birth and nearly 45 per cent them developed hypoglycemia. A rise in FFA from cord levels in first few hours of birth was seen in all the cases, but levels were lower in IDM as compared to controls. TG levels showed a steady and mild rise from birth onwards. Changes in BS and FFA in IDM can be explained on the basis of hyperinsulinemic state in them in utero and in immediate postnatal period.