Marvin Cornblath

The incidence of neonatal hypoglycemia—a completed survey

A two year survey of blood glucose values in low-birth-weight infants during their first 5 postnatal days has been carried out. Fourteen (5.7 per cent) of the infants had two or more blood glucose values less than 20 mg. per cent and had clinical manifestations which disappeared following the parenteral administration of glucose.

Hypoglycemia in the Newborn

There is no universal definition for hypoglycemia. Various investigators have empirically recommended different blood lucose levels (BGLs) that should be maintained in neonatal period to prevent injury to the developing brain. The “normal” range of blood glucose is variable and depends upon factors like birth-weight, gestational age, body stores, feeding status, availability of energy sources as well as the presence or absence of disease. Further, there is no concrete evidence to show the causation of adverse long-term outcomes by a particular level or duration of hypoglycemia. Hence, a consensus has been to evolve an “operational threshold”.

Neonatal hypoglycemia: A discussion

The following symposium was prompted by persistent questions from practicing pediatricians and pediatric residents about hypoglycemia in the newborn infant. Several investigators with special interests in this subject have been asked to reply to selected questions considered relevant to an understanding of the pathogenesis, clinical manifestations, and management of this inadequately understood disorder. In some instances when the responses were in agreement all replies are included to indicate the consensus; in other instances only one opinion is presented for the sake of brevity. In those instances in which there are differences of opinion, each participants position is presented.

INTRAVENOUS GLUCOSE TOLERANCE, PLASMA INSULIN, FREE FATTY ACIDS AND β‐HYDROXYBUTYRATE IN UNDERWEIGHT NEWBORN INFANTS

Blood glucose, plasma insulin, FFA and β‐hydroxybutyrate values during intravenous glucose tolerance were reported in 20 small for gestational age (SGA) and 15 appropriate for gestational age (AGA) low birthweight infants. The babies were divided into three groups according to their age when tested; <24 hours, 24–48 hours and >48 hours.

THE INCIDENCE OF NEONATAL HYPOGLYCEMIA IN A NURSERY FOR PREMATURE INFANTS.

Two or more blood glucose determinations were obtained during the first 5 days of life from 128 of 166 infants admitted consecutively to the Premature Nursery, Research and Educational Hospitals. Eight infants (6 per cent) had significant hypoglycemia (less than 20 mg. per 100 ml.) and symptoms. The predictive value of signs, symptoms, and gestational age are discussed.

Enzymatic adaptations in newborn pig liver

Abstract Numerous studies during the neonatal period in the rat have demonstrated that many changes occur in the activities of liver enzymes of carbohydrate metabolism especially those of glycolysis, gluconeogenesis, and glycogen synthesis and degradation. Such information, however, has not been available in the newborn pig. The present study of several regulatory enzymes was undertaken to determine if an enzymatic defect could explain fasting hypoglycemia in the newborn pig. The hepatic liver enzymes, non-specific hexokinase, glucokinase, glucose-6-phosphatase, UDPG: α-glucan glucosyltransferase, phosphorylase, phosphofructokinase, aldolase, fructose diphosphatase, and phosphopyruvate carboxylase have been measured in developing pig liver. The activity of all hepatic enzymes except hexokinase were low in fetal tissue and increased after birth in livers from both fed and fasted pigs. Hexokinase activity was present prior to birth and remained essentially unchanged after birth and was not affected by prolonged starvation. Liver glycogen was rapidly mobilized at birth in both fed and fasted newborn animals. It is concluded that a defect in enzymes measured under the stated assay conditions does not exist and can not be offered as an explanation for the observed fasting hypoglycemia in newborn pigs.

Distribution of phosphopyruvate carboxylase in pig liver

Abstract Phosphopyruvate carboxylase (GTP:oxaloacetate carboxylase (transphorylating), EC 4.1.1.32) activity has been found in pig and lamb liver mitochondria and in the soluble cell fraction in rat, hamster, and mouse livers. In pig liver, the cellular distribution was found to be 60–70% soluble and 15–25% mitochondrial. This cellular distribution was similar in both fed and 72-h fasted pigs. The specific activity increased 2 fold in the mitochondria and 3 fold in the soluble fraction prior to sacrifice. The K m constants for pig phosphopyruvate carboxylase at pH 6.4 obtained from the 100 000 × g cell supernatant were phosphoenolpyruvate, 6.65·10−4 M; Mn2+, 9.33·10−4 M; NaHCO3, 1.47·10−2 M; and IDP, 5.4·10−5 M.

Ketotic hypoglycemia in a Russell dwarf

A Russell dwarf with hypoglycemic seizures is presented. He was found to have ketogenic hypoglycemia. Fasting levels of growth hormone in plasma and the increase following insulin hypoglycemia were normal.

Abnormal Glucose Metabolism in Skin Fibroblasts Cultured from a Patient with a New Syndrome of Ketoacidemia

Extract: Studies of substrate oxidation by cultured skin fibroblasts from an infant (CC) with severe recurrent episodes of ketoacidosis showed normal rates of oxidation of pro-pionate (CC 55. ± 8 versus control 65 ± 13 μμmoles/mg protein/hr), and succinate (73. ± 16 versus 45 ± 8 μμmoles/mg protein/hr).In contrast, both oxidation and uptake of glucose by these cells were decreased in comparison with controls. Essentially neither glucose-6-14C nor glycerol-U-14C was converted to 14CO2 by fibroblasts of the patient, and glucose-1-14C was oxidized at 45–65% of control rates. In the absence of glucose, oxidation of pyruvate-2-14C did not differ from that of normal controls (710 versus 940 μμmoles/mg protein/hr). In the presence of 2.5 mM glucose, however, fibroblasts of the patient did not show the expected decrease in pyruvate-2-14C oxidation whereas control cells showed a fourfold decrease. Studies of glucose uptake demonstrated that with glucose as the only substrate extended incubation periods of 12–18 hr were necessary before the cells of the patient began to utilize measurable quantities of glucose.The results of the metabolic studies in skin fibroblasts, when viewed in conjunction with the clinical manifestations and laboratory studies, have excluded the known causes of infantile ketoacidosis. The data reported indicate a correlation of this form of ketoacidosis with a block in the terminal pathway of glycolysis.Speculation: A defect in glycolysis may produce intracellular hypoglycemia resulting in the activation of unknown mechanisms in peripheral tissue that initiate lipolysis and ketosis. It could also be that a yet undefined block in ketoacid metabolism might result in the observed irregular glucose oxidation. The basic abnormality may be a result of an in-balance in redox cofactors, an absence of a critical intermediate, or a reduction of an end product. These possibilities are currently being investigated.

CHAPTER 3 – Hypoglycemia

Publisher Summary This chapter discusses definition, incidence, clinical manifestations, and pathogenesis of hypoglycemia, followed by a clinical classification of hypoglycemic syndromes, emphasizing their unique characteristics related to the age of onset. At any age, hypoglycemia may or may not be associated with symptoms or clinical manifestations. In an earlier study, adults, organic hyperinsulinism, reactive or functional hyperinsulinism, and hepatic causes of low blood glucose accounted for over 80% of the patients with spontaneous symptomatic hypoglycemia. The neonate with hypoglycemia may have episodes of tremors, apnea, cyanosis, irregular respirations, limpness, twitching, a high pitched or weak cry, refusal to feed, eye rolling, coma, and convulsions. Persistent or chronic hypoglycemia may produce such bizzare manifestations as to be completely misleading. Hypoglycemia is not a disease but represents a defect in the complex physiological mechanisms that maintain normoglycemia.