• Deficiency in counterregulatory hormones (glucagon, epinephrine, cortisol, growth hormone) or excessive insulin response
  • Serum glucose <70 mg/dL

Risk Factors

  • Strict glycemic control with insulin
  • Prior hypoglycemia episodes
  • Hypoglycemia unawareness
  • Decreased counterregulation
  • <5 yr of age or elderly
  • Comorbid conditions:
    • Renal disease
    • Malnutrition
    • Coronary artery disease
    • Liver disease

  • Congenital metabolic and endocrine disorders that decrease gluconeogenic ability (e.g., hereditary fructose intolerance)
  • Congenital hyperinsulinism
  • Neonatal diabetes mellitus (often a mutation effecting an ATP-dependent potassium channel)


  • Increased insulin levels:
    • Overdose of oral hypoglycemic agent or insulin
    • Oral antihyperglycemics (i.e., α-glucosidase inhibitors, biguanides, and thiazolidinediones) do not cause hypoglycemia alone, but may enhance the risk when used with insulin or sulfonylureas
    • Sepsis
    • Insulinoma
    • Autoimmune hypoglycemia
    • Alimentary hyperinsulinism
    • Renal failure (partially responsible for insulin metabolism)
    • Liver cirrhosis (responsible for significant insulin metabolism)
  • Underproduction of glucose:
    • Alcohol (inhibitory effect on glycogen storage and gluconeogenesis)
    • Drugs
    • Salicylates
    • β-blockers (including eye drops)
    • SSRIs
    • Some antibiotics (e.g., sulfonylureas, pentamidine)
    • Adrenal insufficiency
    • Malnutrition
    • Dehydration
  • Cerebral edema
  • Extremes of age
  • Congestive heart failure
  • Counterregulatory hormone deficiency
  • Hypothyroidism or hyperthyroidism

Pregnancy Considerations
  • Third-trimester pregnant patients risk relative substrate deficiency–induced hypoglycemia
  • The fetus is less likely to become hypoglycemic during mother's hypoglycemic episode secondary to active glucose transport across placenta:
    • Oral hypoglycemic use in pregnancy may lead to profound and prolonged neonatal hypoglycemia

Pediatric Considerations
Most common cause of hypoglycemia in the first 3 mo of life is persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in mothers with diabetes

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