What are the physiological defenses against pediatric hypoglycemia?

Updated: Feb 19, 2018
  • Author: Robert P Hoffman, MD; Chief Editor: Sasigarn A Bowden, MD  more...
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Answer

The body normally defends against hypoglycemia by decreasing insulin secretion and increasing glucagon, epinephrine, growth hormone, and cortisol secretion. These hormonal changes combine to increase hepatic glucose output, increase alternative fuel availability, and decrease glucose use (see the diagram below).

Normal hypoglycemic counterregulation. Normal hypoglycemic counterregulation.

The increase in hepatic glucose production is initially caused by the breakdown of liver glycogen stores resulting from lower insulin levels and increased glucagon levels. When glycogen stores become depleted and protein breakdown increases because of increased cortisol levels, hepatic gluconeogenesis replaces glycogenolysis as the primary source of glucose production. The breakdown of protein is reflected by increased plasma levels of the gluconeogenic amino acids alanine and glutamine. Decreased use of peripheral glucose occurs initially because of a fall in insulin levels and later because of increases in epinephrine, cortisol, and growth hormone levels.

All 3 events increase lipolysis and plasma free fatty acid levels, which are available as an alternative fuel and competitively inhibit glucose use. Increased plasma and urinary ketone levels indicate the use of fat as an energy source. Plasma free fatty acids also stimulate glucose production. Hypoglycemia occurs when 1 or more of these counterregulatory mechanisms fail because of the overuse of glucose (as in hyperinsulinism), the underproduction of glucose (as in the glycogen-storage diseases), or both (as in growth hormone or cortisol deficiency). (See Etiology.)


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