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Hypoglycemia is a medical emergency that poses serious threats to the child, including seizure and brain damage. Hypoglycemia can also cause developmental delay. Hypoglycemic disorders are generally classified as either fasting hypoglycemia or reactive or postprandial hypoglycemia. The risk of hypoglycemia varies depending upon the underlying disorder. With the exception of late dumping syndrome, a form of reactive hypoglycemia associated with Nissen fundoplication or a gastric tube, childhood hypoglycemia is uniformly a disorder of fasting adaptation. Specific endocrine disorders and associated risk factors for hypoglycemia are discussed in this chapter. Defects in the metabolic systems are discussed in Chapter 134.

Normal fasting adaptation involves 5 major systems: 4 metabolic systems (hepatic gluconeogenesis, hepatic glycogenolysis, adipose tissue lipolysis, and oxidation of fatty acids for hepatic ketogenesis), as well as the hormonal system that regulates these metabolic systems. Within 2 to 3 hours of a meal, when intestinal absorption of glucose ceases, hepatic glycogenolysis and gluconeogenesis produce glucose to meet the requirement for brain glucose oxidation and to prevent a decline in blood glucose concentrations. Prolonged fasting of 8 to 12 hours or more depletes glucose and glycogen stores, and adipose tissue lipolysis is activated to provide fatty acids used by muscle and for ketogenesis by the liver. In young children fatty acids become the main fuel source for most of the body after 12 to 24 hours of fasting. Glucose is spared for use by the brain. Ketones become a major fuel for the brain to further spare glucose utilization. The changing serum levels of these fuels obtained during fasting reflect these metabolic processes as shown in Figure 545-1.

Figure 545-1.

Normal changes in metabolic fuels during fasting. Levels of these fuels obtained during the fast and at the time of hypoglycemia reflect the operation of the metabolic systems. Within 2 to 3 hours of a meal, hepatic gluconeogenesis and glycogenolysis are activated to maintain blood glucose. As hepatic glycogen stores are depleted and gluconeogenesis is activated, blood glucose and lactate levels decline. With more prolonged fasting, adipose tissue lipolysis is activated and plasma free fatty acid concentrations increase, followed by a dramatic increase in β-hydroxybutyrate as the fatty acids are oxidized to ketones in the liver. The high levels of ketones can be used by the brain to spare glucose utilization.

The metabolic systems for fasting adaptation are subject to strict hormonal regulation. Insulin negatively regulates all 4 fasting metabolic systems. As blood glucose concentrations decline during the initial phase of fasting, insulin levels fall. This allows increased rates of glucose release from hepatic glycogenolysis and gluconeogenesis. As fasting progresses, the further fall in blood glucose and further suppression of insulin release permit activation of lipolysis and fatty acid oxidation.

The inhibitory effects of insulin is counterbalanced by actions of glucagon, epinephrine, cortisol, and growth hormone. These hormones activate the metabolic systems ...

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