Hypoglycemia, Nondiabetic

Hypoglycemia, Nondiabetic is a topic covered in the 5-Minute Clinical Consult.

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  • Hypoglycemia defined by the Whipple triad
    • Low plasma glucose level (≤60 mg/dL) with hypoglycemic symptoms that are relieved when glucose is corrected
    • Occurs commonly in patients with diabetes receiving sulfonylurea or insulins; less commonly in patients without diabetes
  • Reactive hypoglycemia occurs in response to a meal, drugs, herbal substances, or nutrients and may occur 2 to 3 hours postprandially or later (1).
    • Symptoms are generally observed with serum glucose ≤60 mg/dL, lower in patients with hypoglycemic unawareness.
    • Also seen after GI surgery (in association with dumping syndrome in some patients)
  • Spontaneous (fasting) hypoglycemia may be associated with primary conditions including hypopituitarism, Addison disease, myxedema, or disorders related to hepatic dysfunction or renal failure (1,2).
    • If hypoglycemia presents as a primary disorder, consider hyperinsulinism and extrapancreatic tumors.


  • True incidence is unknown.
  • 0.5–8.6% of hospitalized patients ≥65 years (3,4,5)
    • Asymptomatic in 25% of cases


True prevalence is unknown:

  • Predominant age: older adult
  • Predominant sex: female > male

Etiology and Pathophysiology

  • Reactive, postprandial
    • Alimentary hyperinsulinism
    • Meals high in refined carbohydrate
    • Certain nutrients, including fructose, galactose, leucine
    • Glucose intolerance (prediabetes)
    • GI surgery, especially gastric bypass
    • Idiopathic (unknown cause)
  • Spontaneous
    • Fasting
    • Alcohol or prescription medication–associated (6) (insulin, sulfonylureas, thiazolidinediones, incretin mimetics, DPP-IV inhibitors, β-blockers, salicylates, quinine, hydroxychloroquine, fluoroquinolones, doxycycline, sertraline, disopyramide, pentamidine, gabapentin, tramadol)
    • Nonprescription over-the-counter (OTC) agents, including performance-enhancing agents. Adulterated versions of phosphodiesterase inhibitors and performance-enhancing agents are routinely imported and may contain sulfonylureas and other hypoglycemic agents.
    • Consider medication errors as a source of unexplained hypoglycemia even in patients without diabetes.
    • Surreptitious drug use (self-injection of insulin or ingestion of oral hypoglycemic medications in patients with diabetes)
    • Natural medicines or herbs (bitter melon, caffeine, cassia cinnamon, chromium, fenugreek, ginseng, guarana, mate, stevia, vanadium)
    • Postsurgical (e.g., bariatric surgery, gastrectomy, Roux-en-Y) hypoglycemia/dumping syndrome
    • Islet cell hyperplasia or tumor (insulinoma)
    • Extrapancreatic insulin-secreting tumor
    • Autoimmune hypoglycemia (Hirata disease)
    • Hepatic disease
    • Glucagon deficiency
    • Adrenal insufficiency
    • Catecholamine deficiency
    • Hypopituitarism
    • Hypothyroidism
    • Eating disorders
    • Exercise
    • Fever
    • Pregnancy
    • Renal glycosuria
    • Large tumors
    • Ketotic hypoglycemia of childhood
    • Enzyme deficiencies or defects
    • Severe malnutrition
    • Sepsis
    • Total parenteral nutrition therapy
    • Hemodialysis

Some aspects may involve genetics (e.g., hereditary fructose intolerance).

Risk Factors

Refer to “Etiology and Pathophysiology.”

General Prevention

  • Follow dietary and exercise guidelines.
  • Patient recognition of early symptoms and knowledge of corrective action
Pediatric Considerations
  • Usually divided into two syndromes
    • Transient neonatal hypoglycemia
    • Hypoglycemia of infancy and childhood
  • Screening infants for hypoglycemia is appropriate when pregnancy was complicated by maternal diabetes.
  • Cases of hypoglycemia observed in children taking propranolol for infantile hemangioma
  • Associated with indomethacin when treating patent ductus arteriosus
Geriatric Considerations
  • More likely to have underlying disorders or be caused by medications
  • Iatrogenic hypoglycemia is common in the hospitalized elderly with renal insufficiency.

Commonly Associated Conditions

  • Severe liver disease; alcoholism
  • Addison disease; adrenocortical insufficiency
  • Myxedema
  • Malnutrition (patients with renal failure)
  • GI surgery
  • Panhypopituitarism
  • Insulinoma

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