Endocrinology and Metabolism Clinics of North America
HYPOGLYCEMIA IN INFANTS AND CHILDREN
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GLUCOSE HOMEOSTASIS IN INFANTS AND CHILDREN
The exact regulation of glucose homeostasis in newborns and young infants is not well-established. Most conclusions are drawn from studies performed in experimental animals. Although children and adults may have similar substrate and hormonal control of glucose metabolism, glucose homeostasis in newborns has some different features.
When the pregnant woman receives adequate nutrition, gluconeogenesis and ketogenesis in the fetus are virtually absent.45 The precise timing of the induction of the
DEFINITION OF HYPOGLYCEMIA
Cornblath and Schwartz defined hypoglycemia in the 1960s as a blood glucose level of 20 mg/dL in preterm infants, 30 mg/dL in term infants during the first 3 days of life, and 40 mg/dL in older infants.31 When these studies were carried out, early feeding was commonly discouraged. More recent studies have shown that, except during the first postnatal hours, a blood glucose level lower than 40 mg/dL is uncommon in both premature and full-term infants fed immediately after birth.110, 128 Some
SIGNS AND SYMPTOMS
Signs and symptoms of hypoglycemia are nonspecific in the neonate. Clinical manifestations include lethargy, hypotonia, irritability, feeding difficulties, cyanosis, tachypnea, apnea, hypothermia, seizures, and coma. A similar presentation may be seen in several other disorders, including septicemia, brain injury, severe respiratory distress, and congenital heart disease. Infants who are at a higher risk for hypoglycemia need to be closely monitored because serious sequelae may develop when
ADVERSE SIDE EFFECTS
Glucose is an essential substrate for neuronal metabolism. In animal models, severe and sustained hypoglycemia leads to major structural damage, including neural necrosis with loss of dendrites. Neural damage is most likely caused by the activation of receptors for excitatory amino acids, mainly the N-methyl- D-aspartate (NMDA) receptor.7 Prolonged excitation of NMDA receptors causes cell depolarization with subsequent cell swelling and activation of lipases and proteases. A subtle decrease in
DIAGNOSTIC APPROACH
A methodical approach is required when the diagnosis of hypoglycemia is suspected. A careful medical history and a thorough physical examination give important clues to the diagnosis. Hypoglycemia that is triggered by certain components of the diet may be indicative of an inborn error of metabolism such as galactosemia, maple syrup urine disease, and fructose intolerance. Marked obesity at birth suggests some forms of hyperinsulinism. Cholestasis and micropenis occur in the setting of
TREATMENT
The goal of treatment is to normalize blood glucose concentrations by providing adequate glucose enterally or parenterally. In patients with hyperinsulinemia, subcutaneous glucagon (0.03 mg/kg) can reverse the hypoglycemia. Prevention of hypoglycemia is dependent on its cause. If hypoglycemia develops with increased fasting, uncooked cornstarch is often useful (see section on glycogen storage disease).
HYPOGLYCEMIC DISORDERS
Several classifications of hypoglycemic disorders have been proposed depending on the age and clinical characteristics103 of the patient or based on the pathophysiology of hypoglycemia (increased glucose use or decreased glucose production).55 For the purpose of this review, hypoglycemic disorders are listed without any specific reference to glucose metabolism (Table 1).
CONCLUSION
Childhood hypoglycemia remains a challenging but fascinating subject. Conditions that cause hypoglycemia should be promptly recognized and treated. Delaying therapy may lead to neuronal damage, especially in premature and young infants.
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Address reprint requests to W. F. Schwenk, MD, Division of Pediatric Endocrinology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905
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Section of Pediatric Endocrinology, Mayo Medical School, Rochester, Minnesota