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The transition from intrauterine to extrauterine life requires prompt adaptations to maintain glucose homeostasis. Increased rates of glucose utilization in infants and children compared to adults heighten dependency on coordinated glycogenolysis, gluconeogenesis, and fatty acid oxidation to prevent hypoglycemia during early life. Consequently, hypoglycemic disorders often present in the neonatal period or in infancy during transitions to longer feeding intervals. Since the brain during this time is particularly susceptible to injury due to glucose deprivation, prompt recognition and treatment of hypoglycemia is paramount.

Glucose is the preferred substrate for cerebral metabolism and accounts for almost all of its energy requirements. Since the brain can neither synthesize nor efficiently store glucose, its function and health depend on a continuous glucose supply. Metabolic demands of the developing brain raise glucose utilization rates during infancy and early childhood, when the brain is a relatively larger contributor to body mass. Thus, to avoid neurological damage, diagnosing and appropriately treating hypoglycemia is particularly critical during infancy and early childhood, when adequate glucose delivery is essential for neural growth and cognitive development. To promote the prompt diagnosis and treatment of hypoglycemia by the primary care physician and endocrinologist, this chapter integrates current molecular and clinical knowledge.


Normal Pathways ofGlucose Production

Regulation of blood glucose levels in the normal state relies on a delicate balance between nutrient intake and energy expenditure. Nutrition comprises the fundamental processes by which essential nutrients are absorbed by the gut and transferred through the bloodstream and across membranes for transport into cells for metabolism. All metabolic pathways which generate adenosine triphosphate (ATP) pass through glucose or key amino acids. Thus, abnormalities in the absorption, transport, storage, and metabolism of glucose provide the mechanisms for diseases resulting in low levels of glucose in blood (hypoglycemia). Clinically, low glucose levels in key body fluids (notably blood and the cerebrospinal fluid) allow initial identification of such diseases. Beyond infancy, these disorders present rarely; thus, the astute clinician recognizes that, while many patients attribute their symptoms and problems to hypoglycemia, actual hypoglycemia is seldom documented adequately and its prevalence often overestimated.1

Adaptation to separation from energy supplied via the placenta to self-sufficiency at birth requires rapid activation of three counter-regulatory mechanisms: glycogenolysis, gluconeogenesis, and lipolysis. Thesemechanisms are immature in the newborn and even more rudimentary in premature, asphyxiated, hypoxic, or small-for-gestational age (SGA) infants. The rate of glucose turnover in newborns is 6 mg/kg/min, approximately three times the adult rate. Although the demand for glucose is high, the activities of several liver enzymes involved in glucose production (eg, glucose-6-phosphatase) and ketogenesis are diminished, particularly in preterm infants. Consequently, before the first feeding, approximately 10% of normal term newborns and approximately 67% of preterm SGA infants display blood glucose levels below 30 mg/dL in the first hours of life. These data highlight ...

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