Hypoglycemia, Nondiabetic

Description

• 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.

Epidemiology

• 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

Genetics
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

Commonly Associated Conditions

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