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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)
- 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
- Eating disorders
- Renal glycosuria
- Large tumors
- Ketotic hypoglycemia of childhood
- Enzyme deficiencies or defects
- Severe malnutrition
- Total parenteral nutrition therapy
Some aspects may involve genetics (e.g., hereditary fructose intolerance).
Refer to “Etiology and Pathophysiology.”
- Follow dietary and exercise guidelines.
- Patient recognition of early symptoms and knowledge of corrective action
- 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
- 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
- Malnutrition (patients with renal failure)
- GI surgery