Hypoglycemia, Nondiabetic
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Basics
Description
- Hypoglycemia is 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 insulin secretagogues (sulfonylureas, meglitinides) or insulins; is less common in patients without diabetes
- Postprandial or reactive hypoglycemia occurs in response to a meal, drugs, herbal substances, or nutrients and may occur 2 to 3 hours postprandially or later. This is noncongenital, beta-islet dysregulation with or without hyperplasia and insulin secretion.
- Autonomic symptoms are generally observed with a serum glucose ≤60 mg/dL, and neuroglycopenic symptoms at a serum glucose of ≤50 mg/dL, or lower in patients with hypoglycemic unawareness.
- Hypoglycemia is also seen after GI or bariatric surgery (in association with dumping syndrome in some).
- Spontaneous (fasting) hypoglycemia may be associated with primary conditions including hypopituitarism, Addison disease, myxedema, or disorders related to critical illness, heart failure, hepatic or renal failure.
- If hypoglycemia presents as a primary disorder, consider hyperinsulinism and extrapancreatic tumors.
Epidemiology
Incidence
Prevalence
True prevalence is unknown:
- Predominant age: older adult
- Predominant sex: female > male
Etiology and Pathophysiology
- Reactive, postprandial
- Alimentary hyperinsulinism
- Meals including refined or processed carbohydrates, liquid forms of fructose, sucrose, or glucose
- Certain nutrients, including galactose, leucine
- Glucose intolerance (prediabetes)
- GI surgery, especially bariatric surgery (i.e., Roux-en-Y gastric bypass)
- Idiopathic (unknown causes)
- Spontaneous
- Fasting
- Situations or housing with restricted food access (i.e., unhoused persons, those in hospitals, prisons)
- Alcohol or prescription medication–associated (insulin, sulfonylureas, meglitinides, thiazolidinediones, incretin mimetics, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, DPP-IV inhibitors, angiotensin-converting enzyme inhibitors, β-blockers, salicylates, quinine, hydroxychloroquine, fluoroquinolones, doxycycline and tetracycline derivatives, linezolid, sertraline, disopyramide, pentamidine, gabapentin, tramadol) (3)
- 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 administration errors as a source of unexplained hypoglycemia in persons without diabetes, especially those with polypharmacy (6 or more medications).
- This includes accidental, surreptitious, or malicious use of insulin or oral hypoglycemics.
- Natural medicines or herbs (bitter melon, caffeine, cassia cinnamon, chromium, fenugreek, ginseng, guarana, mate, stevia, vanadium)
- Postsurgical (e.g., Roux-en-Y bariatric surgery, gastrectomy) hypoglycemia/dumping syndrome
- Islet cell hyperplasia or tumor (insulinomas)
- Extrapancreatic insulin-secreting tumors and other large tumors secreting insulin-like growth factor 2 (IGF-2)
- Autoimmune hypoglycemia (Hirata disease) and insulin receptor mutations
- Heart failure with or without SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin)
- Hepatic disease or failure; renal disease or failure
- Renal glycosuria
- Glucagon deficiency
- Adrenal insufficiency
- Catecholamine deficiency
- Hypopituitarism
- Hypothyroidism
- Eating disorders
- Exercise or physical activity (i.e., manual labor)
- Fever
- Pregnancy
- Ketotic hypoglycemia of childhood
- Severe nutrient deficiencies (i.e., selenium)
- Congenital disorders
- Sepsis, cachexia, anorexia
Genetics
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
- Heart failure; severe, chronic hepatic and renal disease; alcoholism
- Addison disease; adrenocortical insufficiency
- Myxedema
- Malnutrition (patients with renal failure)
- GI and bariatric surgery
- Panhypopituitarism
- Insulinoma
-- To view the remaining sections of this topic, please log in or purchase a subscription --
Basics
Description
- Hypoglycemia is 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 insulin secretagogues (sulfonylureas, meglitinides) or insulins; is less common in patients without diabetes
- Postprandial or reactive hypoglycemia occurs in response to a meal, drugs, herbal substances, or nutrients and may occur 2 to 3 hours postprandially or later. This is noncongenital, beta-islet dysregulation with or without hyperplasia and insulin secretion.
- Autonomic symptoms are generally observed with a serum glucose ≤60 mg/dL, and neuroglycopenic symptoms at a serum glucose of ≤50 mg/dL, or lower in patients with hypoglycemic unawareness.
- Hypoglycemia is also seen after GI or bariatric surgery (in association with dumping syndrome in some).
- Spontaneous (fasting) hypoglycemia may be associated with primary conditions including hypopituitarism, Addison disease, myxedema, or disorders related to critical illness, heart failure, hepatic or renal failure.
- If hypoglycemia presents as a primary disorder, consider hyperinsulinism and extrapancreatic tumors.
Epidemiology
Incidence
Prevalence
True prevalence is unknown:
- Predominant age: older adult
- Predominant sex: female > male
Etiology and Pathophysiology
- Reactive, postprandial
- Alimentary hyperinsulinism
- Meals including refined or processed carbohydrates, liquid forms of fructose, sucrose, or glucose
- Certain nutrients, including galactose, leucine
- Glucose intolerance (prediabetes)
- GI surgery, especially bariatric surgery (i.e., Roux-en-Y gastric bypass)
- Idiopathic (unknown causes)
- Spontaneous
- Fasting
- Situations or housing with restricted food access (i.e., unhoused persons, those in hospitals, prisons)
- Alcohol or prescription medication–associated (insulin, sulfonylureas, meglitinides, thiazolidinediones, incretin mimetics, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, DPP-IV inhibitors, angiotensin-converting enzyme inhibitors, β-blockers, salicylates, quinine, hydroxychloroquine, fluoroquinolones, doxycycline and tetracycline derivatives, linezolid, sertraline, disopyramide, pentamidine, gabapentin, tramadol) (3)
- 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 administration errors as a source of unexplained hypoglycemia in persons without diabetes, especially those with polypharmacy (6 or more medications).
- This includes accidental, surreptitious, or malicious use of insulin or oral hypoglycemics.
- Natural medicines or herbs (bitter melon, caffeine, cassia cinnamon, chromium, fenugreek, ginseng, guarana, mate, stevia, vanadium)
- Postsurgical (e.g., Roux-en-Y bariatric surgery, gastrectomy) hypoglycemia/dumping syndrome
- Islet cell hyperplasia or tumor (insulinomas)
- Extrapancreatic insulin-secreting tumors and other large tumors secreting insulin-like growth factor 2 (IGF-2)
- Autoimmune hypoglycemia (Hirata disease) and insulin receptor mutations
- Heart failure with or without SGLT-2 inhibitors (empagliflozin, dapagliflozin, canagliflozin)
- Hepatic disease or failure; renal disease or failure
- Renal glycosuria
- Glucagon deficiency
- Adrenal insufficiency
- Catecholamine deficiency
- Hypopituitarism
- Hypothyroidism
- Eating disorders
- Exercise or physical activity (i.e., manual labor)
- Fever
- Pregnancy
- Ketotic hypoglycemia of childhood
- Severe nutrient deficiencies (i.e., selenium)
- Congenital disorders
- Sepsis, cachexia, anorexia
Genetics
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
- Heart failure; severe, chronic hepatic and renal disease; alcoholism
- Addison disease; adrenocortical insufficiency
- Myxedema
- Malnutrition (patients with renal failure)
- GI and bariatric surgery
- Panhypopituitarism
- Insulinoma
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