IV. HYPOGLYCEMIA
Hypoglycemia is characterized by 1) central nervous system (CNS) symptoms, including confusion, aberrant behavior, or coma; 2) a simultaneous blood glucose level ≤50 mg/dl; and 3) symptoms being resolved within minutes following glucose administration (Fig. 23.13). Hypoglycemia is a medical emergency because the CNS has an absolute requirement for a continuous supply of bloodborne glucose to serve as a metabolic fuel. Transient hypoglycemia can cause cerebral dysfunction, whereas severe, prolonged hypoglycemia causes brain damage. Therefore, it is not surprising that the body has multiple overlapping mechanisms to prevent or correct hypoglycemia. The most important hormone changes in combating hypoglycemia are increased secretion of glucagon and the catecholamines, combined with decreased insulin secretion.
A. Symptoms
The symptoms of hypoglycemia can be divided into two categories. Adrenergic (neurogenic, autonomic) symptoms, such as anxiety, palpitation, tremor, and sweating, are mediated by catecholamine release (primarily epinephrine) regulated by the hypothalamus in response to hypoglycemia. Adrenergic symptoms typically occur when blood glucose levels fall abruptly. The second category of hypoglycemic symptoms is neuroglycopenic. The impaired delivery of glucose to the brain (neuroglycopenia) results in impairment of brain function, causing headache, confusion, slurred speech, seizures, coma, and death. Neuroglycopenic symptoms often result from a gradual decline in blood glucose, often to levels <50 mg/dl. The slow decline in glucose deprives the CNS of fuel but fails to trigger an adequate adrenergic response.
B. Glucoregulatory systems
Humans have two overlapping glucose-regulating systems that are activated by hypoglycemia: 1) the pancreatic α cells, which release glucagon, and 2) receptors in the hypothalamus, which respond to abnormally low concentrations of blood glucose. The hypothalamic glucoreceptors can trigger both the secretion of catecholamines (mediated by the sympathetic division of the autonomic nervous system) and release of adrenocorticotropic hormone (ACTH) and growth hormone by the anterior pituitary (see Fig. 23.13). [Note: ACTH increases cortisol synthesis and secretion in the adrenal cortex (see p. 239).] Glucagon, the catecholamines, cortisol, and growth hormone are sometimes called the counterregulatory hormones because each opposes the action of insulin on glucose use.
1.
Glucagon and epinephrine: Secretion of these counterregulatory hormones is most important in the acute, short-term regulation of blood glucose levels. Glucagon stimulates hepatic glycogenolysis and gluconeogenesis. Epinephrine promotes glycogenolysis and lipolysis. It inhibits insulin secretion, thereby preventing GLUT-4–mediated uptake of glucose by muscle and adipose tissues. Epinephrine assumes a critical role in hypoglycemia when glucagon secretion is deficient, for example, in the late stages of type 1 diabetes mellitus (see p. 340). The prevention or correction of hypoglycemia fails when the secretion of both glucagon and epinephrine is deficient.
2.
Cortisol and growth hormone: These counterregulatory hormones are less important in the short-term maintenance of blood glucose concentrations. They do, however, play a role in the long-term (transcriptional) management of glucose metabolism.
C. Types