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.     

Metabolic events in infants of diabetic mothers during first 24 hours after birth. I. Changes in plasma glucose, insulin and glucagon

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 less than 0.001). After birth, plasma glucose fell in all infants, the nadir being reached at two hours (p less than 0.01). Plasma glucose fell by approximately 35% in the class A infants and 63% in the class B-F infants (p less than 0.01). Eight IDM had asymptomatic hypoglycemia (plasma glucose less than 1.9 mmol/l) and four of these infants had glucose levels below 1.7 mmol/l and were withdrawn from further study.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 less than 0.01) and insulin about 11-fold higher (p less than 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 infants (p less than 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 less than 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 less than 0.05) and 24 hours in the class B-F infants (p less than 0.01). Only those infants who became hypoglycemic after birth exhibited a significant increment in plasma glucagon from 0.2 hours (p less than 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.     

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.     

Glycerol metabolism and triglyceride-fatty acid cycling in the human newborn: effect of maternal diabetes and intrauterine growth retardation.

Kinetics of glycerol metabolism and triglyceride/fatty acid cycling were quantified in 12 healthy, normal, appropriate-for-gestational-age (AGA) infants, eight small-for-gestational-age (SGA) infants, and five infants of insulin-dependent diabetic mothers (IDM) at less than 48 h of age. Stable isotope-labeled [2-13C]glycerol and [6,6-2H2]glucose in combination with indirect respiratory calorimetry were used. The tracers were used as constant rate infusion and steady state isotopic enrichment of glucose, glycerol, and bicarbonate was measured by mass spectrometric methods. After a 7- to 9-h fast, the plasma glucose, glycerol, and FFA concentrations were similar in the AGA and IDM groups. In the SGA group, the plasma glucose concentration was significantly lower than that in the AGA group throughout the study, but plasma FFA and glycerol concentrations were not different from those in the AGA infants. Plasma betahydroxybutyrate concentration was significantly elevated in the AGA group compared with IDM and SGA infants (AGA 0.59 +/- 0.39, SGA 0.35 +/- 0.09, IDM 0.33 +/- 0.21 mmol/L; mean +/- SD). The rate of appearance of glycerol was significantly elevated (p less than 0.05) in SGA infants (AGA 9.47 +/- 2.11, IDM 9.55 +/- 2.14, SGA 12.15 +/- 3.87 mumol/kg.min). Between 80 and 90% of glycerol turnover was converted to glucose, accounting for 20% of glucose turnover with no significant difference in the three groups. Approximately 35% of glycerol carbon was recovered in the bicarbonate (CO2) pool. Less than 5% of CO2 carbon was derived from glycerol. Estimation of triglyceride-fatty acid cycle revealed that the triglyceride energy mobilized was increased in SGA infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ketonuria does not exclude hyperinsulinemic hypoglycemia

We examined the relationship between serum beta-hydroxybutyrate (BOHB) and plasma glucose concentrations and between serum free fatty acid (FFA) and glucose concentrations in 34 normal children who fasted for up to 24 hours. The BOHB concentration correlated inversely with the glucose concentration, as did the FFA concentration. We compared these results with those in six patients with hypoglycemia due to hyperinsulinism. In the hyperinsulinemic children, hypoglycemia was invariably associated with relative hypoketonemia (glucose concentration, less than 40 mg/dL; BOHB concentration, less than 2mM; greater than 2 SDs below the mean). The FFA concentrations were also unduly low (greater than 2 SDs). However, despite being significantly hypoketonemic when hypoglycemic, four of the six hyperinsulinemic patients had ketonuria. Since it does not exclude hyperinsulinism, ketonuria may be a potentially misleading finding in a hypoglycemic child.     

Fasting adaptation in idiopathic ketotic hypoglycemia: a mismatch between glucose production and demand

In order to study the pathophysiology of hypoglycemia in idiopathic ketotic hypoglycemia (KH), glucose kinetics during fasting in patients with KH were determined. A fasting test was performed in 12 children with previously documented KH. Besides determination of glucoregulatory hormones, plasma ketones, FFA and alanine, the rates of endogenous glucose production (EGP), glucose uptake, gluconeogenesis (GNG) and glycogenolysis (GGL) were quantified using the [6,6-(2)H(2)] glucose isotope dilution method and the deuterated water method. The five youngest subjects (age 2.5-3.9 years) became hypoglycemic (glucose <3.0 mmol/l) during the test. Mean differences in glucose kinetics between overnight fasting and the end of the test in the hypoglycemic vs. the normoglycemic subjects were: EGP: -31.9% vs. -17.9% (p = 0.007), GGL: -66.2% vs. -50.8% (p = 0.465) and GNG 6.8% vs. 19.5% (p = 0.465). Plasma alanine levels were significantly lower (p = 0.028) at the end of the test in the hypoglycemic subjects. Plasma ketones and FFA levels were in the normal range for fasting duration in all subjects. We conclude that hypoglycemia in KH is caused by the inability to sustain an adequate EGP during fasting in view of the higher glucose requirement in young children. The decrease in GGL is not accompanied by a significant increase in GNG, possibly because of a limitation in the supply of alanine. Our results support the hypothesis that KH represents the lower tail of the Gaussian distribution of fasting tolerance in children.     

INFLUENCE OF ENVIRONMENTAL TEMPERATURE AND ACIDOSIS ON LIPID MOBILIZATION IN THE HUMAN INFANT DURING THE FIRST TWO HOURS AFTER BIRTH

Arterial concentrations of glycerol, FFA, glucose, lactate and β-hydroxybutyrate were serially measured during the first two hours after birth in normal fullterm infants in a thermo-controlled environment. Blood gas tensions, acid-base balance, pulmonary gas exchange, motor activity and heart rate were also determined: a detailed report of these data will be published separately. In 22 infants the glycerol concentrations showed a rapid immediate increase after birth wheras the rises in FFA concentrations were delayed until between 30 and 120 minutes, indicating a prompt increase in lipolysis and a suppression of lipid mobilization during the first half hour after birth. This suppression might be explained by a high rate of reesterification or oxidation of FFA within adipose tissue. The influence of environmental temperature (2 8.7-3 4.8 ^oC) and degree of acidosis on the pattern of changes in FFA and glycerol were only marginal. No inhibition of lipolysis and lipid mobilization was shown in an infant who developed postnatal asphyxia.
At 120 min after birth, when acidosis had been eliminated, an inverse correlation was found between the rise in FFA from birth to 120 min and the respiratory exchange ratio (co₂/o₂).
The glucose concentrations were related neither to the FFA nor to the glycerol concentrations. The rate of elimination of lactate and β-hydroxybutyrate was not influenced by environmental temperature or acidosis. Minute amounts of administered heparin caused an increased rise in FFA and glycerol concentrations which were associated with the appearance of lipoprotein lipase activity.     

THE EFFECT OF FEEDING ON OXYGEN CONSUMPTION, RQ AND PLASMA LEVELS OF GLUCOSE, FFA, AND D-β-HYDROXYBUTYRATE IN NEWBORN INFANTS OF DIABETIC MOTHERS AND SMALL FOR GESTATIONAL AGE INFANTS

Abstract. Eight infants of strictly controlled diabetic mothers (IDM), 8 infants of gestational diabetic mothers (IGDM) and 6 small for gestational age infants (SGA) were studied before the first feeding and during an early feeding regimen. In IDMs and IGDMs continuous monitoring from 2 hours up to 7 1/2 hours after birth before feeding revealed no consistent changes of Vo₂ and RQ. The groups of infants were studied on 4 different occasions: (I) 2 to 16 hours, (II) 1 to 2 days, (III) 3 to 4 days, and (IV) 7 to 11 days. Prefeeding Vo₂-values were not significantly different between each of the groups, but mean RQ was higher in IGDMs than in IDMs. Age of the infant and prefeeding RQ were inversely correlated (r=-0.537, p<0.02). With increasing age and milk intake Vo₂ increased significantly in all groups. RQ decreased during the first 24 to 48 hours in all groups and rose thereafter with highest values at 7 to 11 days. Plasma levels of glucose, FFA, and D-β-hydroxybutyrate were not significantly different between each of the groups. The highest values for D-β-hydroxybutyrate were found at 1–2 days when the lowest RQ values were also recorded. D-β-hydroxybutyrate concentrations and RQ values (r= -0.648, p<0.001) were inversely correlated suggesting increasing oxidation of fat. Feeding resulted in a marked rise in RQ to values around unity, which preceded a distinct increase in Vo₂ that reached a maximum at 1 to 1 1/2 hours after the feed, then slowly returned to pretest values. The rise in Vo₂ was accompanied by an increase in rectal temperature (0.4 to 1.5°C). Vo₂, RQ, and plasma levels of glucose, FFA, and D-β-hydroxybutyrate, were almost identical for each of the groups. We suggest: 1) That differences in feeding practice is the most likely explanation for the discrepancy between reported values for Vo₂, RQ, and circulating substrates in normal and low birth weight newborns. 2) That the rise in Vo₂ during the neonatal period, caused by feeding, reflects the cost of growth.     

Ketogenesis in hypoglycemic neonates. Carnitine and dicarboxylic acids in neonatal hypoglycemia

Since hypoglycemic neonates do not exhibit compensative ketosis, we investigated the possible involvement of carnitine deficiency or omega-oxidation in neonatal hypoglycemia. In a first group of 49 neonates, serum free fatty acid, acetoacetate and beta-hydroxybutyrate concentrations were similar in hypoglycemic and normoglycemic neonates. Serum free carnitine concentrations did not show any difference in the hypoglycemic small-for-date infants (median 40 mumol/l, range 16-92 mumol/l) compared to the normoglycemic small-for-date infants (median 30 mumol/l, range 8-64 mumol/l). In a second group of 45 neonates, urinary excretion of dicarboxylic acids (adipic, suberic, sebaric and succinic acids) was similar in hypoglycemic infants compared to normoglycemic neonates. Despite the limitations of interpretation of free carnitine determination, these data do not suggest an impaired beta-oxidation by carnitine depletion or an enzymatic defect in hypoglycemic neonates.     

Plasma metabolites after a lipid load in infants with congenital heart disease

Growth retardation is common in infants with congenital heart defects. The aim of this study was to investigate whether growth retardation or type of heart defect in infants with congenital heart defects is related to disturbances in lipid metabolism. Sixteen infants with ventricular septal defects and six infants with transposition of the great arteries were given an intravenous load of lipid emulsion (Intralipid^® 20 mg/ml) corresponding to 0.5 g fat/kg body weight for 5 min after fasting for 8 h. Blood samples were drawn immediately before the infusion and 3, 20, 60, 120 and 240 min after the infusion was completed. Plasma concentrations of triglycerides (TG), free fatty acids (FFA), ketones, lactate, pyruvate, alanine, glycerol and glucose were determined. The fatty acid patterns in the TG and FFA fractions were measured using gas chromatography. Severe growth retardation in infants with defects of these kinds was correlated to higher fasting and maximum levels of linoleic acid in plasma FFA. The maximum levels of linoleic acid in the TG fraction were positively correlated to weight SD score, and maximum glycerol levels were higher in the most growth-retarded infants, indicating faster intravascular lipolysis. Linoleic acid in the TG fraction was still elevated at 120 and 240 min after the lipid load. Some differences between the cyanotic and VSD groups could be noted. These indicate decreased metabolic capacity to utilize released FFA in the cyanotic group. Infants with cyanotic heart defects also had higher lactate and alanine levels compared to infants with VSD. Our results support the hypothesis that lipid metabolism is disturbed in infants with congenital heart defects.     

Zinc tolerance test patterns in normal children and in moderate and severe zinc deficiency states

Twenty-six normal, 38 moderately and 14 severely zinc-deficient children, aged 2–12 years, were examined by clinical and laboratory approaches. After fasting-blood sampling, 120 mg zinc sulphate (25 mg elemental zinc) were administerd orally to each group of children, to obtain zinc tolerance curve patterns. Sampling proceeded to the 2nd and 4th hours of the loadingtest period. Plasma zinc was assessed on an atomic absorption spectrophotmeter. In normal children, at the 2nd hour of loading, a significant (p < .001) elevation (1.764 ± 0.133 mg/l) in the mean (± SEM) plasma zinc level was noted; also at the 4th hour a significant (p < .001) decrease (1.506 + 0.123 mg/l) in the mean plasma zinc level was shown. The mean plasma zinc level at the 4th hour was found higher than the mean fasting plasma zinc level (1.054 +- 0.061 mg/l), but lower than the mean level found at the 2nd hour. In moderately zinc-deficient children, the rise in the 2nd hour and the fall in the 4th hour in the plasma zinc level were highly significant (p < .001 and p < .001, respectively) in relation to fasting blood level However, in severely zinc-deficient children, the intensity of the increase (0.746 + 0.147 mg/l) in plasma zinc level at the 2nd hour was of lesser significance (p < .006) and the fall (0.424 + 0.061) mg/l) at the 4th hour was not significant. Therefore, in children with normal plasma zinc levels, an increase of more than 0.50 mg/l was seen at the 2nd hour of loading. This rise was seen to persist at the 4th hour. However, in children with moderate zinc deficiency, although again an increase of 0.50 mg/l was seen at the 2nd hour this increase did not persist at the 4th hour; and the 4th-hour value showed a significant decrease in relation to the 2nd hour value. Whereas, in children with severe zinc deficiency the rise of plasma level at the 2nd hour was less than 0.5 mg/l and the fall at the 4th hour was to such a level which was not significant in relation to fasting zinc level. This could be due to enhanced uptake bf zinc off the circulation by the depleted tissues in severe zinc deficiency.     

Parathormone and perinatal calcium homeostasis.

Plasma parathormone (PTH) and calcium concentrations were measured in 309 specimens collected from 190 newborns during the first 7 days of life. The patient material consisted of 51 preterm, 130 term, and 9 postterm infants, including 22 infants of diabetic mothers (IDM), 38 infants with hypocalcemia, and 25 asphyxiated infants. PTH was detectable, although in low concentrations, in cord blood samples despite the presence of elevated calcium concentrations. Postpartum, PTH concentrations in term, appropriate for gestational age (AGA) infants remained low during the first 2 days of life; a significant (P less than 0.05) and sustained increase in plasma hormone levels was noted starting on day 3. PTH concentrations in IDM and preterm infants remained low for 3 days and a significant hormone increase did not occur until day 4. Hypocalcemia was common in IDM and asphyxiated infants; these infants accounted for two-thirds of all hypocalcemic infants. The profile of plasma calcium in IDM during the first week of life was different than that of any other group of infants. Plasma calcium concentrations remained depressed over this period of time and exhibited a temporary drop on day 4 accompanied by an increase in plasma PTH levels. Asphyxiated infants exhibited low plasma calcium concentrations, despite PTH levels that were significantly (P less than 0.007) higher than those of age-matched term AGA newborns.     

Brain excitatory amino acid concentrations are lower in the neonatal pig: a buffer against excitotoxicity?

Hypoglycemic brain damage has been associated with high levels of the excitatory amino acids (EAA) aspartate and glutamate in the newborn and adult. We hypothesized that newborn piglet EAA would be different from those of older pigs when stressed with severe insulin-induced hypoglycemia (<30 mg/dl). Brain EAA were measured in piglets and adolescent pigs via microdialysis. Eleven of 12 newborn normoglycemic piglets had no detectable baseline levels (<0.5 microM) of EAA, while pigs had aspartate and glutamate concentrations of 1.78 +/- 0.44 and 3.43 +/- 1.14 microM (mean +/- SEM), respectively. Piglet aspartate and glutamate concentrations reached but did not significantly exceed normoglycemic pig levels after 2 h with plasma glucose values < or =20 mg/ml. Elevations in EAA were only detected in piglets whose EEG activity ceased. Aspartate and glutamate concentrations did not increase in insulin-treated pigs nor in control animals. We speculate that newborns with blood glucose less than clinically acceptable values (35 mg/dl) may be protected from EAA-associated neuronal damage during acute hypoglycemia. Lower normoglycemic and hypoglycemic levels of EAA in newborns when compared to older pigs provide this protection.     

Postnatal surge in serum calcitonin concentrations: no contribution to neonatal hypocalcemia in infants of diabetic mothers

It has been suggested that hypercalcitoninemia may contribute to neonatal hypocalcemia in infants of diabetic mothers (IDM). Because the role of calcitonin (CT) in Ca metabolism in humans is questionable, we hypothesized that serum CT peaks similarly after birth in IDM and controls and that serum Ca concentrations do not correlate with serum CT. Forty-seven term IDM (White classes B-RT) were compared with 31 controls. Controls were born after normal pregnancies, labors, and deliveries. Blood samples (cord and 24 h) were analyzed for Ca, Mg, parathyroid hormone (PTH), and CT. Repeated measures analysis showed increasing serum Mg, PTH, and CT, and decreasing Ca over time. The incidence of hypocalcemia was significantly higher in the diabetic group (p less than 0.01) and the incidence of hypomagnesemia was borderline significantly higher (p less than 0.06). There were no differences in cord or 24-h serum concentrations of CT between groups. In multiple regression analysis, serum Ca and PTH were correlated (p less than 0.02, R2 = 0.33), but not serum Ca and CT; the increase in serum PTH in relation to serum Ca at the nadir (24 h) correlated directly with serum Mg concentrations (R2 = 0.31, p less than 0.05). Thus, serum CT increases after birth irrespective of the rate of decrease of serum Ca in both IDM and controls; high CT concentrations observed after birth (as compared with adult norms) do not seem to play a role in the pathogenesis of neonatal hypocalcemia in IDM; and responsiveness of parathyroid gland at birth is adversely affected by hypomagnesemia, which supports the theory of functional hypoparathyroidism in Mg deficiency.     

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.     

METABOLIC OBSERVATIONS IN INFANTS OF STRICTLY CONTROLLED DIABETIC MOTHERS Plasma Levels of Glucose, FFA, Glycerol and D-β-hydroxybutyrate during the First Two Hours after Brith

Arterial concentrations of FFA, glycerol, glucose and D-β-hydroxybutyrate were serially measured during the first 2 hours after birth in IDMs, IGDMs and in control infants. All diabetic mothers were subjected to a well defined program of control during pregnancy. IDMs had only a slight increase in mean plasma FFA concentrations and the values were significantly lower than those of the IGDM and control groups at all times. In contrast the rise in mean plasma glycerol values was significant and similar in all groups, suggesting a comparable increase in lipolysis. Following birth IDMs showed a more pronounced decrease in mean plasma glucose values than the other groups. Mean plasma values of D-β-hydroxybutyrate showed a significant drop during the first 60 minutes and thereafter the values remained low and were not significantly different between the groups. The pattern of changes in FFA, glycerol and glucose was not influenced by type of delivery, duration of diabetes and/or presence of retinopathy in the mothers, nor was there any apparent relationship to the degree of maternal metabolic control during pregEancy. It is suggested that the low mean FFA levels despite of increasing mean glycerol concentrations in IDMs are explained by an increased rate of re-esterification of FFA withi!i adipose tissue. Thcse findings can only partly be explained by postnatal functional hyper-insulinism. The recent demonstration af higher than normal glycogen concentrations within adipose tissue in IDMs cffers a more plausible explanation for the increased rate of re-esterification during the first hours after birth. The p;esent data do not allow of conclusions as to thc relative importance of increased glycogen stores as compared with that of hyperinsulin-ism during the first 2 hours after birth in IDMs.     

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.     

Postheparin lipolytic activity and Intralipid clearance in very low-birth-weight infants

The effect of heparin (10 U/kg) on serum lipolytic activity, triglyceride and FFA levels, during four hours infusion of 0.5 gm/kg Intralipid was measured in 18 AGA infants, 25 to 32 weeks' gestational age. PHLA, TG, and FFA were measured at 0, 10, 30, 120, and 240 minutes of infusion of Intralipid, before and following a bolus of 10 U/kg heparin iv. Lipolytic activity, measured by hydrolysis of activated tri-3H-oleate and expressed in mumol FFA released per milliliter serum per hour, was not detected in serum before heparin administration. Ten minutes after heparin administration peak PHLA was significantly higher in infants of 27 to 32 weeks' gestation than in infants of 25 to 26 weeks' gestation. There was no significant difference in peak PHLA between infants of 27 to 28 and 29 to 32 weeks' gestation. PHLA returned to baseline (zero) two hours after heparin administration in all infants. Infants of 25 to 26 weeks' gestational age had significantly higher concentrations of serum triglycerides before and during Intralipid infusion than in infants of 27 to 32 weeks' gestational age. Although there was a transient rise in FFA 10 and 30 minutes after heparin administration, the levels of FFA and triglycerides were not different at the end of infusion with or without heparin in either group, suggesting that a single bolus of heparin has only a transient effect on Intralipid clearance.     

EFFECTS OF INJECTED LIPID EMULSION ON OXYGEN CONSUMPTION, RQ, TRIGLYCERIDE, FREE-FATTY-ACID AND β-HYDROXYBUTYRATE LEVELS IN SMALL-FOR-GESTATIONAL-AGE (SGA) INFANTS

ABSTRACT. Ten SGA infants were studied from 4 hours after birth (day 1) and again at 28 hours (day 2) before and for 4 hours after single injections of 0.5 g of Intralipid® fat/kg b. w. (IL-group). Eight other SGA infants were given 9–10 ml/kg of breast milk (BM-group). After lipid injection the elimination of triglycerides (TG) from plasma was markedly delayed. On day 2 lipolysis had improved, but was still slower than in previously studied AGA infants. The initial FFA plasma level was higher on day 1 than on day 2. Oxidation of released fatty acids was confirmed by a significant increase of V_o, and a decrease of RQ on day 1 and 2. In all infants the β-hydroxybutyrate level in plasma increased and was still elevated 4 hours after injection of fat. A negative correlation was found between β-hydroxybutyrate levels and RQ. In the BM-group changes in TG and β-hydroxybutyrate levels were small and insignificant. FFA had decreased 60 min after breast milk on day 1. In conclusion: TG elimination from plasma was impaired on day 1 and had slightly improved on day 2. The fatty acids released by lipolysis were oxidized as seen by increasing V_o, falling RQ and increasing β-hydroxybutyrate plasma levels both on day 1 and day 2.     

Placental function in maternal-fetal fat transport in diabetes

High levels of triglycerides (TG) and free fatty acids (FFA) in maternal plasma, in diabetes, promote fat passage to the fetus. In the streptozotocin-diabetic rat a significant correlation exists between maternal plasma and fetal tissue lipid contents, as shown by the accretion of labeled fatty acids or linoleate used as markers of maternal fat transfer. The passage of lipids through the placenta is not direct--this organ serves as an interim storage barrier with its lipid content increasing in proportion to the maternal TG and FFA level. Very low density lipoprotein (VLDL) TG are taken up with the aid of lipoprotein lipase as evident from TG = glycerol exchange when doubly labeled VLDL-TG are presented to the placenta. Esterification rate of albumin-bound FFA is considerably higher indicating that the rate of TG lipolysis is rate limiting and that the FFA are the main precursor of the placental lipids. The uptake of both FFA and VLDL-TG is associated with the retention of a substantial amount of FFA in the placenta. The size of the FFA pool corresponds to the size of the extracellular fluid space. The FFA cannot be eluted by repeated washing, suggesting that they are membrane bound. Placental slices with prelabeled TG gradually release FFA into the medium upon reincubation with FFA-free albumin, indicating that TG and FFA traverse the placenta in part by a sequential process of esterification and lipolysis and in part by diffusion as FFA. The latter are probably moving from the maternal to the fetal side within the interfacial capillary membrane lipids.