Hyperinsulinemic Hypoglycemia

Hyperinsulinemic Hypoglycemia

 

Hypoglycemia may constitute a medical emergency because it may result in permanent neurologic defects.

Epidemiology

  • Incidence of hypoglycemia
    • Newborns – 1-3/1,000 live births
    • Familial forms – 1/50,000 in sporadic populations (high in Ashkenazi Jews)
    • Diabetic patients
      • Type 1 – 10-30%/yr
      • Type 2 – 1-2%/yr

Risk Factors

  • Infants or Newborns
    • Newborn hyperinsulinemic hypoglycemia
    • Genetic
      • Defects in genes ABCC8 or KCNJ11
      • Gain-of-function mutations in glucokinase and glutamate dehydrogenase
      • Loss-of-function mutations in short-chain acyl-CoA dehydrogenase
      • Beckwith-Wiedemann syndrome
    • Intrauterine growth retardation
    • Maternal diabetes mellitus
  • Children
    • Diabetes mellitus
      • Higher risk in patients receiving insulin
    • Medication abuse
      • Insulin
      • Oral hypoglycemic agents
  • Adults
    • Diabetes mellitus
      • Higher risk in patients receiving insulin
    • Medication abuse
      • Insulin
      • Oral hypoglycemic agents
    • Insulinoma
    • Insulin autoantibodies
    • Autoimmune diseases
    • Post bariatric surgery patients (gastric bypass procedures)

Pathophysiology

  • Dysregulated insulin secretion with defects in glucose counter-regulatory hormones
  • Insulin drives glucose into sensitive tissues (liver, adipose, skeletal muscle) which can cause profound hypoglycemia
  • Nesidioblastosis (abnormally enlarged islets, hypertrophic beta cells and periductal cells in the pancreas) is likely explanation for pathology in gastric bypass patients

Clinical Presentation

  • Adults and children
    • Lethargy, confusion, anxiety, sweating
    • Nausea
    • Focal neurologic defects
    • Seizures
    • Post gastric bypass patients may experience symptoms 1-2 years after procedure and 1-3 hours postprandially
  • Infants and newborns
    • Lethargy, confusion, sweating
    • Poor feeding
    • Recurrent hypoglycemia can cause neurologic damage
    • Beckwith-Wiedemann syndrome – omphalocele, gigantism, macroglossia, microcephaly, visceromegaly
      • 50% of infants have hyperinsulinemic hypoglycemia  
    • Hypoglycemias associated with all but genetic defects tend to be transient and resolve spontaneously after several months

Diagnosis

  • Indications for testing – suspicious history
  • Laboratory testing
    • Glucose – decreased
      • May need to do a fasting level to see blood glucose drop
    • Insulin – increased
    • Based on clinical scenario, other tests to consider include:
      • C-peptide – elevated (decreased with exogenous insulin use)
        • Elevated insulin and C-peptide may also be seen with insulinoma and surreptitious use of sulfonylureas  
      • Beta hydroxybutyrate – low
      • Free fatty acids – low (if high, consider fatty acid oxidation disorders)
      • Rule out sulfonylurea hypoglycemics surreptitious use of oral hypoglycemic agents
      • Insulin antibodies
      • Proinsulin

Treatment

  • Prevent hypoglycemia when possible
  • Treat hypoglycemia with intravenous glucose

See Also