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
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