Insulin and Leptin Levels in Appropriate-for-Gestational-Age Infants of Diabetic Mother

Objective

Intensified management of gestational diabetes mellitus can normalize birth weight. However, it is still unknown whether intrauterine exposure to maternal diabetes is a risk factor for changing hormone levels involved in the development of insulin resistance in these infants. We compared insulin and leptin levels in appropriate for gestational age (AGA) infants of diabetic and non diabetic mothers.

Methods

We performed a cross-sectional study in the department of Neonatology of the Hospital of Gynecology-Pediatrics, in Leon, Mexico. We evaluated 182 full term AGA newborns (86 infants of diabetic and 96 of non-diabetic mothers). A venous blood sample was taken from cord blood immediately after the separation of the placenta and glucose, insulin and leptin levels were measured. In all diabetic mothers HbA1c was also evaluated immediately post-partum.

Findings

Leptin, insulin and insulin resistance index were significantly higher in infants of diabetic mothers. Leptin levels were positive correlated with insulin, parents‘ body mass index and age in the entire group. In infants of diabetic mothers only insulin levels showed a significantly correlation, whereas in those of non-diabetic mothers only mothers‘ age was significantly correlated with leptin levels.

Conclusion

AGA infants of diabetic mothers showed higher leptin, insulin levels and insulin resistance index than those of non-diabetic mothers.     

Neonatal Jaundice in Infants of Diabetic Mothers

Jährig, D., Jährig, K., Stiete, S., Beyersdorff, E., Poser, H. and Hopp, H. (Department of Paediatrics, the Data Centre of the Ernst Moritz Arndt University of Greifswald, Greifswald, and the'Gerhard Katsch'Central Research Institute for Diabetes, Karlsburg, G.D.R.). Neonatal jaundice in infants of diabetic mothers. Acta Paediatr Scand Suppl 360: 101, 1989.
357 IDMs and 20 healthy newborns of non-diabetic mothers were examined at term for body measurements, red blood cell count, serum bilirubin, cord blood insulin and blood glucose during the first postnatal week. The stage of maternal diabetes did not influence the course of neonatal bilirubin levels, but the IDMs had prolonged and higher bilirubinaemia compared with the controls. Hyperbilirubinaemia was found to be most prominent in newborns with an increased birthweightllength ratio and was not simply related to macrosomia (LGA). These infants had significantly lower blood glucose concentrations immediately after birth, whereas cord blood insulin was found to be identical between the IDM sub-groups. Bilirubinaemia in heavy for length infants was slightly correlated to haematocrit. For the pathogenesis of hyperbilirubinaemia in IDMs induction of heme oxygenase (due to a lack of energy provision following a phosphory lation disorder) is discussed. Nutritional support (early feeding, glucose infusions) does not affect the course of bilirubinaemia.     

Neonatal hypoglycaemia in infants of diabetic mothers

OBJECTIVE: To determine whether umbilical cord blood glucose correlates with subsequent hypoglycaemia after birth in infants of well-controlled diabetic mothers. METHODOLOGY: Thirty-eight term infants of well-controlled diabetic mothers were enrolled. Five mothers had pre-existing diabetes. Of the 33 gestational diabetic mothers, 16 were managed on insulin and 17 on diet. Maternal blood glucose was maintained between 4 and 8 mmol/L during labour and delivery. Infants' plasma glucose levels were measured from venous cord blood and serially, at less than 30 min, 1 h and 2 h of life by glucose hexokinase method. Blood glucose levels were further monitored by bedside Dextrostix for 24 h. RESULTS: Eighteen (47%) infants developed hypoglycaemia (blood glucose level less than 2 mmol/L) during the first 2 h of life. There was no difference in the cord blood glucose levels between infants with or without hypoglycaemia (3.7 +/- 1.1 vs 4.5 +/- 1.1 mmol/L, respectively). Infants of mothers with diabetes diagnosed prior to 28 weeks gestation were at a higher risk of developing hypoglycaemia (8 of 10 vs 10 of 28, OR 7.2, 95%CI 1.3-40.7). Hypoglycaemic infants were of significantly higher birthweight, and were more likely to be born to Caucasian mothers and by Caesarean section. Raised maternal fructosamine blood level, the need for insulin treatment or the infant's haematocrit were not different between infants with or without hypoglycaemia. CONCLUSIONS: In well-controlled diabetic mothers, the incidence of early hypoglycaemia in infants is still high, particularly in those mothers who had a longer duration of diabetes. Cord blood glucose level did not identify the infants with hypoglycaemia.     

Gastrointestinal enhanced insulin release in response to glucose in newborn infants

The purpose of this investigation was to determine whether or not gastrointestinal (GI) enhanced insulin response occurs in newborn infants soon after birth. Glucose infusion by intravenous or orogastric routes was given to infants during the first 4 days of life, aiming at achieving similar plasma glucose concentrations. Their plasma insulin responses were then compared. Thirty term, newborn infants (10 appropriate for gestational age, 8 small for gestational age, 6 large for gestational age, and 6 infants of diabetic mothers) were studied. With intravenous glucose infusions of 8 mg/kg/min or orogastric infusion of 16 mg/kg/min, the plasma glucose concentrations achieved were similar and approximated 110 mg/dl. Plasma insulin responses were greater in infants receiving glucose via the GI route. The finding was in contrast to our previous data, in which no GI enhancement of insulin response was demonstrated. The present data suggest that in the term newborn infant, GI enhanced insulin release occurs only when a threshold of plasma glucose concentration has been exceeded. It appears that the enteroinsular axis is functional in newborns soon after birth.     

Glucose disappearance in infants of diabetic mothers I. Relationship to maternal glucose tolerance and insulin production

Glucose disappearance and insulin response were determined in mother--infant pairs of normal, gestational diabetic and diabetic pregnancies following an intravenous glucose load. Mothers were studied in the third trimester of pregnancy and at least 6 wk postpartum. Significant differences were present in glucose disappearance and insulin response in both gestational diabetic and diabetic mothers during pregnancy compared with the control group. Infants were studied within 4 h of birth while fasting, and glucose and insulin levels followed through the first 3 days of life. Neonatal hypoglycemia did not occur and glucose disappearance (KT) was not different among the three groups. There was no correlation between maternal glucose tolerance or insulin production and that of their infants. The only distinguishing factor among the infants was higher insulin production in infants of diabetic mothers during the 60-min intravenous glucose tolerance test which persisted up to 4 h following the infusion. It is concluded that factors other than the degree of maternal glucose tolerance are responsible for the development of neonatal hypoglycemia in infants of diabetic mothers, most notably control of maternal diabetes, the amount of glucose infused immediately before delivery and neonatal glucose production.     

Effect of Glucose on Plasma Glucagon,Growth Hormone,and Insulin in Exchange Transfusion

Exchange transfusions were performed on term normal-for-dates, and term small-for-dates infants using blood preserved with acid citrate and glucose or acid citrate alone. The plasma concentrations of glucose, free fatty acids, glycerol, insulin, glucagon, and growth hormone were measured in the donor blood and in blood from the infant at different times during the transfusion. The total amounts of the metabolites and hormones infused and removed from the infant were calculated. The infusion of glucose in blood preserved with acid citrate and glucose caused a rise in plasma glucose, insulin, and growth hormone levels and a fall in plasma free fatty acid levels. The plasma glycerol levels did not change significantly during transfusions with blood preserved with acid citrate and glucose, or acid citrate alone. In both types of exchange transfusion there was a similar gradual fall in plasma glucagon concentration and net loss of free fatty acid, glycerol, and glucagon. A net loss of growth hormone occurred which was greater in transfusions performed with blood preserved with acid citrate and glucose than in transfusions performed with blood preserved with acid citrate. In transfusions performed with blood preserved with acid citrate and glucose there was a net accumulation of glucose by the infant and a net loss of insulin.     

Blood glucose and plasma amino acid concentrations in infants of diabetic mothers.

Postnatal blood glucose and individual plasma free amino acid levels were measured in 14 newborn infants of diabetic mothers. All infants had a significantly lower blood glucose concentration than normal controls but no significant correlation was observed between the blood glucose values and any of the amino acids determined. As regards the quantitative and qualitative changes of the plasma aminogram, the total concentration of amino acids and the level of a few individual amino acids (glycine, alanine, taurine, and valine) were significantly elevated in full-term babies. However, no significant difference was found in the total plasma concentration of amino acids between premature infants of diabetic mothers and premature control infants, but the plasma alanine level was higher in the former. It is of interest that total plasma amino acid, alanine, and glycine levels were elevated in the asphyxiated babies. This suggests that the postnatal hyperaminoacidemia observed in infants of diabetic mothers was due to birth asphyxia rather than to impaired gluconeogenesis. The possible role of a defective gluconeogenesis in the etiology of postnatal hypoglycemia in infants of diabetic mothers is not supported by these data.     

Fatty Acid Composition of Subcutaneous Adipose Tissue in Mother-Infant Pairs

ABSTRACT. The fatty acid composition of microsamples from 10 AGA term, 8 SGA term, 7 AGA preterm and 4 SGA preterm, 2–4 day old infants and their mothers were analyzed. In AGA preterm newborns the mean percent of palmitic and stearic acid was lower and the mean percent of linoleic acid was higher than in AGA term infants indicating that there is an increase in fatty acids derived by synthesis from glucose throughout gestation. SGA infants had relative amounts of palmitic and stearic acid similar to what was found in AGA term infants. This indicates that the enzymes involved in synthesis of fatty acids from glucose are intact in intrauterine growth retardation (IUGR). The absolute amount of adipose tissue and fatty acids, however, is smaller in SGA infants due to a reduced availability of glucose in IUGR gestation. No differences were found in the fatty acid composition of subcutaneous adipose tissue from the mothers in the 4 groups. All mothers had a lower mean percent of palmitic and stearic acid and a higher mean percent of oleic and linoleic acid than their infants, ensuring a transplacental gradient to the fetus of this latter essential fatty acid. The fatty acid composition of plasma free fatty acids generally reflected the composition of the subcutaneous adipose tissue in the infants.     

Monitoring of early postnatal glucose homeostasis and cerebral function in newborn infants of diabetic mothers. A pilot study

The aims of this pilot study were to evaluate a new technique in the monitoring of postnatal glucose homeostasis (microdialysis) and also to study possible associations between early postnatal hypoglycaemia and influences on cerebral function monitoring (CFM) in 12 newborn infants of diabetic mothers.In order to study the postnatal glucose homeostasis, frequent dialysate samples were obtained from a subcutaneous microdialysis catheter for measurements of glucose. In addition, we also received samples of dialysate lactate and glycerol. Dialysate glucose concentrations were correlated to capillary blood glucose levels, measured by a glucose oxidase method. The cerebral function monitor was applied postnatally and a registration was obtained continuously.Capillary blood glucose decreased initially, and seven newborns received intravenous glucose infusions due to glucose concentrations less than 2.2 mmol/l. Dialysate glucose concentrations were, on average, 0.4 mmol/l higher than corresponding concentrations in capillary blood. The correlation coefficient between the two measurements was 0.63 and the coefficient of variation was 19.2%. Dialysate lactate and glycerol levels increased significantly, with peak values 3-4 h postnatally. No significant overall influence of hypoglycaemia was detectable in the CFM tracing.We conclude that a relatively poor correlation was observed between glucose measurements in capillary samples and microdialysis. However, using the microdialysis technique saw indication of marked lipolysis and increased lactate production, which may be of importance for cerebral postnatal adaptation. The mild postnatal hypoglycaemia in infants of diabetic mothers does not seem to give visually detectable influences on CFM.     

Fatty acid composition of subcutaneous adipose tissue in mother-infant pairs

The fatty acid composition of microsamples from 10 AGA term, 8 SGA term, 7 AGA preterm and 4 SGA preterm, 2-4 day old infants and their mothers were analyzed. In AGA preterm newborns the mean percent of palmitic and stearic acid was lower and the mean percent of linoleic acid was higher than in AGA term infants indicating that there is an increase in fatty acids derived by synthesis from glucose throughout gestation. SGA infants had relative amounts of palmitic and stearic acid similar to what was found in AGA term infants. This indicates that the enzymes involved in synthesis of fatty acids from glucose are intact in intrauterine growth retardation (IUGR). The absolute amount of adipose tissue and fatty acids, however, is smaller in SGA infants due to a reduced availability of glucose in IUGR gestation. No differences were found in the fatty acid composition of subcutaneous adipose tissue from the mothers in the 4 groups. All mothers had a lower mean percent of palmitic and stearic acid and a higher mean percent of oleic and linoleic acid than their infants, ensuring a transplacental gradient to the fetus of this latter essential fatty acid. The fatty acid composition of plasma free fatty acids generally reflected the composition of the subcutaneous adipose tissue in the infants.     

Total parenteral nutrition in infants. Blood levels of glucose, lactate, pyruvate, free fatty acids, glycerol, d-beta-hydroxybutyrate, triglycerides, free amino acids and insulin.

Two regimens (A and B) for TPN were designed to meet the requirements of newborn infants for calories, amino acids, fatty acids, electrolytes, trace elements and vitamins. Both "A" and "B" included fat emulsion (Intralipid). "A" contained fructose and glucose, "B" glucose only. "A" provided amino acids (Vamin) in proportions similar to those of whole egg, "B" similar to those of human milk. All nutrients were given simultaneously into peripheral veins by constant infusion. Nineteen patients (11 newborns, 8 infants) were studied for 1-28 days. Twelve infants recovered, 7 died. In none could TPN be regarded as the cause of death. Treatment was complicated by sepsis in 5 infants. During the course of treatment, blood levels of substrates and insulin were measured before, during and 30 min after discontinuation of TPN. Highly raised concentrations of circulating substrates seen in 3 infants seemed to be related to a poor clinical condition rather than to the regimen used. Infants in good condition tolerated TPN well. Low levels of branch-chained amino acids and tendency to ketonemia, when infusion was stopped, suggested that minimal rather than optimal supply of energy and of amino acids in relation to energy was provided with both regimens. Low insulin levels associated with elevated blood levels of substrates suggested that insulin administration to selected cases might be indicated. Fructose (0.30 g/kg X hour-1) given with regimen A increased blood lactate concentrations. Homocystinaemia appeared in 2 cases; disappearance after excess vitamin B6 administration indicated increased B6 requirement.     

Glucagon,Insulin, and Growth Hormone Response to Exchange Transfusion in Premature and Term Infants

Exchange transfusions were performed on premature or term infants using blood preserved with acid citrate and glucose. The plasma concentrations of glucose, free fatty acids, insulin, glucagon, and growth hormone were measured in the donor blood and in blood from the infant at different times during the transfusion. The total amounts of metabolite and hormone infused and removed from the infant were calculated. The exchange transfusion caused a larger rise in plasma glucose of premature infants than of term infants, due in part to a higher plasma glucose in the donor blood used for premature infants. Despite the higher plasma glucose levels, the premature infants secreted less insulin in response to the glucose challenge, as judged by the rise in plasma insulin and the insulin balance. The transfusions were associated with increased growth hormone secretion in both groups. Premature infants secreted more growth hormone per kg bodyweight than term infants. Plasma glucagon levels in term and premature infants before transfusion were higher than those found in normal infants under comparable conditions. The transfusion caused a similar fall in plasma concentration and a similar negative balance of free fatty acids and glucagon in each group.     

Metabolic and hormonal consequences of exchange transfusion via the umbilical artery or vein.

Twenty exchange transfusions for hyperbilirubinaemia were performed via the umbilical vein or artery in 17 term and pre-term infants. Blood preserved with acid citrate and dextrose was used and the effect of the route of transfusion on plasma glucose, free fatty acid, insulin and growth hormone (GH) concentrations was measured during the transfusion and for 3 h afterwards. Infants transfused via the umbilical vein secreted more insulin than those transfused via the artery although both groups had similar rises in plasma glucose. After transfusion, glucose disappearance was faster and minimum plasma glucose levels were lower in infants transfused via the vein. This group had a smaller fall in plasma free fatty acids during transfusion, but otherwise plasma free fatty acid levels were similar in both groups. More GH was secreted by infants transfused via the artery resulting in higher plasma levels during and after transfusion.     

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.     

TOTAL PARENTERAL NUTRITION IN INFANTS Blood Levels of Glucose, Lactate, Pyruvate, Free Fatty Acids, Glycerol, D-β-Hydroxybutyrate, Triglycerides, Free Amino Acids and Insulin

Abstract. Two regimens (A and B) for TPN were designed to meet the requirements of newborn infants for calories, amino acids, fatty acids, electrolytes, trace elements and vitamins. Both "A" and "B" included fat emulsion (Intralipid®). "A" contained fructose and glucose, "B" glucose only. "A" provided amino acids (Vamin®) in proportions similar to those of whole egg, "B" similar to those of human milk. All nutrients were given simultaneously into peripheral veins by constant infusion. Nineteen patients (11 newborns, 8 infants) were studied for 1–28 days. Twelve infants recovered, 7 died. In none could TPN be regarded as the cause of death. Treatment was complicated by sepsis in 5 infants. During the course of treatment, blood levels of substrates and insulin were measured before, during and 30 min after discontinuation of TPN. Highly raised concentrations of circulating substrates seen in 3 infants seemed to be related to a poor clinical condition rather than to the regimen used. Infants in good condition tolerated TPN well. Low levels of branch-chained amino acids and tendency to ketonemia, when infusion was stopped, suggested that minimal rather than optimal supply of energy and of amino acids in relation to energy was provided with both regimens. Low insulin levels associated with elevated blood levels of substrates suggested that insulin administration to selected cases might be indicated. Fructose (0.30 g/kg × hour^-1) given with regimen A increased blood lactate concentrations. Homocystinaemia appeared in 2 cases; disappearance after excess vitamin B₆ administration indicated increased B₆ requirement.     

Leptin and metabolic hormones in infants of diabetic mothers

AIMS: To investigate the effect of maternal diabetes on leptin in term newborns and to determine whether leptin correlates with insulin and its associated biochemical parameters in support of the hypothesis that a functional "adipoinsular axis" might exist at this stage of development. METHODS: A total of 116 term newborns were prospectively enrolled and categorised into three groups: 44 were infants of non-diabetic mothers (control group C); 41 were infants born to mothers with gestational diabetes on dietary treatment (group D); and 31 were infants born to mothers with gestational or pregestational diabetes on insulin treatment (group I). RESULTS: No significant difference in serum leptin was observed between the three groups; the results of the study population were therefore pooled and analysed. Serum leptin correlated significantly with serum insulin, insulin:glucose ratio, birth weight, body length, body mass index, placenta weight, and maternal HbA(1c). Female infants had significantly higher serum leptin than male infants. All parameters except placenta weight and body length remained significantly associated with serum leptin when multivariate stepwise regression analysis was applied. Subgroup analysis revealed a significant correlation between serum leptin and cortisol in group D. CONCLUSIONS: There was no significant difference in serum leptin between infants born to diabetic and non-diabetic mothers, though infants born to mothers requiring insulin treatment had the highest median serum leptin concentrations. The significant association between serum leptin and insulin or insulin:glucose ratio supports the hypothesis that a functional adipoinsular axis might exist in term newborns. Furthermore, the significant correlation between maternal HbA(1c) and circulating leptin of the studied infants suggests that the clinical control of maternal diabetes could affect the regulation of serum leptin in these infants.     

Antepartum glucocorticoid treatment: the effect of prednisolone on umbilical blood glucose, plasma free fatty acids and individual free amino acid levels.

Blood glucose, plasma free fatty acid and individual free amino acid levels were measured in the cord blood of preterm newborns whose mothers had received prednisolone treatment to prevent RDS. No significant differences were found in either of the metabolites between the prednisolone treated and the control group of comparable gestational age and birth weight. The results suggest that corticosteroid treatment has no gross adverse effect on fuel homeostasis.     

The usefulness of measuring fructosamine in the cord blood of the newborn infants of diabetic mothers

The aim of our study was to evaluate the usefulness of fructosamine measurement (Fram) in cord blood as an index of glucose metabolism in the last week of pregnancy in infants of diabetic mothers. In newborns and their respective mothers Fram values were surprisingly greater in N than in IDM and IGDM and neonatal and maternal values appeared to be strictly related. While intrauterine growth was associated with metabolic control indexes of 2nd and 3rd trimester gestation. Fram value appeared positively correlated to cord insulin. In conclusion Fram level appears as a good index of glucose metabolic control of the last week of pregnancy and it is associated to cord insulin level and to neonatal hypoglycemia.     

The Effect of Prenatal Glucose and Insulin Infusion on Carbohydrate Metabolism in the Newborn

10 women in labor received a drip infusion of 500 ml of 10% glucose with 16 units of crystalline insulin and further 10 received glucose infusion without insulin, about 30 min. before giving birth. In the newborn infants of these mothers was a continuous fall in the high initial blood glucose values in capillary blood, with significant decrease in ballast excess lactate, without increase in oxygen consumption. It would appear that prenatal infusion of glucose with insulin decreased partially anaerobic metabolism, without increasing the oxidative component. Such an effect might lower the tendency of the newborn to go into metabolic acidosis after birth, and assist the establishment of normal respiration.     

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.