What is the role of hyperinsulinemia in the etiology of pediatric hypoglycemia?

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

Hyperinsulinemia is characterized by an excessive use of glucose. Possible causes of hyperinsulinism in children include maternal diabetes in pregnancy, persistent hyperinsulinemic hypoglycemia of infancy, insulin-producing tumors, and child abuse. Hyperinsulinism causes excess glucose use primarily by stimulating skeletal muscle to take up glucose. This is aggravated by insulin-induced suppression of hepatic glycogenolysis and gluconeogenesis. [2]

In infants, hyperinsulinemia may be due to various genetic defects that cause a loss of glucose regulation of insulin secretion. This disorder is known as endogenous-persistent hyperinsulinemic hypoglycemia of infancy (previously termed nesidioblastosis). The most common of these disorders is associated with an inactive or only partially active potassium channel. This channel is composed of 2 parts: the sulfonylurea receptor (SUR1) and the potassium pore (Kir6.2). The former is encoded by the ABCC8 gene, and the latter by the KCNJ11 gene. [3]

No genetic defect is identified in 50% of patients with hyperinsulinism, although unusual single nucleotide polymorphisms defects have been found that may be responsible in some infants. [4]

Infants of mothers with diabetes also have high insulin levels after birth due to the high glucose exposure in utero; the poorer the glucose control during pregnancy, the greater the likelihood of hyperinsulinism in the infant. In older children, hyperinsulinemia is rare, but an insulin-producing tumor is the most common cause. Exogenous administration of insulin or oral hypoglycemic agents, either accidental or due to abuse, must be considered.

Hyperinsulinemia can also result from in utero or perinatal stress (eg, maternal hypertension, prematurity, small for gestational age, hypoxia, Caesarian delivery). [5] These infants have no genetic mutations. Hypoglycemia is temporary and resolves in 1-14 months. The mechanism is unclear.


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