What are the causes and management of hypoglycemia (low blood sugar) in non-diabetic individuals?

Causes and Management of Hypoglycemia in Non-Diabetic Individuals

Hypoglycemia in non-diabetic individuals is primarily caused by medications, endocrine disorders, critical illness, and nutritional factors, with management focused on addressing the underlying cause while preventing recurrent episodes.

Common Causes of Non-Diabetic Hypoglycemia

Medication-Related Causes

• Inadvertent use of insulin or sulfonylureas is the most common cause of non-diabetic hypoglycemia 1
• Other medications that can cause hypoglycemia include:
  • Quinine, quinolones, pentamidine, and certain antibiotics 1
  • Beta-blockers (can mask hypoglycemic symptoms) 1

Endocrine Disorders

• Adrenal insufficiency with cortisol deficiency impairs counterregulatory responses to hypoglycemia 2
• Insulinoma and other islet cell tumors causing endogenous hyperinsulinism 3
• Hypopituitarism affecting counterregulatory hormones 3

Kidney Disease

• End-stage renal disease significantly increases hypoglycemia risk due to 4:
  • Decreased renal gluconeogenesis
  • Impaired insulin clearance
  • Poor nutritional status
  • Accumulation of uremic toxins affecting glucose metabolism

Critical Illness and Hospital-Related Causes

• Sepsis with dysregulated glucose metabolism 1
• Malnutrition or interrupted nutritional intake 5
• Liver failure with impaired gluconeogenesis 3
• Low albumin levels affecting drug pharmacokinetics 1

Rare Causes

• Autoimmune hypoglycemia (insulin antibodies or insulin receptor antibodies) 3
• Non-islet cell tumor hypoglycemia (NICTH) due to IGF-2 secretion 3
• Post-bariatric surgery hypoglycemia 6
• Inborn errors of metabolism presenting in adulthood 3

Risk Factors for Non-Diabetic Hypoglycemia

Patient-Specific Risk Factors

• Advanced age (≥75 years) with reduced counterregulatory hormone responses 1
• Cognitive impairment or dementia limiting ability to recognize symptoms 1
• Malnutrition or poor nutritional status 5
• Cardiovascular disease 1

Social and Nutritional Factors

• Food insecurity with irregular access to adequate nutrition 1
• Alcohol consumption (inhibits gluconeogenesis) 1
• Fasting for religious or cultural reasons 1

Diagnostic Approach

Confirming True Hypoglycemia

• Apply Whipple's triad to confirm hypoglycemia 6:
  1. Low plasma glucose level (<70 mg/dL)
  2. Symptoms consistent with hypoglycemia
  3. Resolution of symptoms when glucose is corrected

Initial Evaluation

• Detailed medication history to identify potential culprits 5
• Laboratory evaluation during symptomatic episode should include 6:
  • Glucose, insulin, C-peptide, and proinsulin levels
  • Beta-hydroxybutyrate and free fatty acids
  • Cortisol and growth hormone levels

Specialized Testing

• 72-hour supervised fast for suspected insulinoma 6
• Mixed-meal test for suspected reactive hypoglycemia 6
• Adrenal function testing if adrenal insufficiency is suspected 3

Management Strategies

Acute Management

• Oral glucose (15g) for conscious patients with mild-moderate hypoglycemia 5
• IV glucose or glucagon for severe hypoglycemia or unconscious patients 5

Addressing Underlying Causes

• Discontinue or adjust medications that may be causing hypoglycemia 5
• Treat underlying endocrine disorders (adrenal insufficiency, insulinoma) 2
• Adjust nutrition in malnourished patients or those with interrupted intake 5
• Special considerations for renal patients: adjust medication dosing and improve nutritional status 4

Prevention of Recurrent Episodes

• Implement a hypoglycemia prevention protocol in hospitalized patients 5
• Monitor blood glucose in high-risk patients, especially those with kidney disease 4
• Educate patients and caregivers about recognition and treatment of hypoglycemia 5

Special Considerations

Hospital Setting

• Implement a standardized hypoglycemia management protocol 5
• Document all hypoglycemic episodes for quality improvement 5
• Review treatment regimens when blood glucose <70 mg/dL is documented 5
• Be vigilant about nutrition-insulin mismatches in hospitalized patients 5

Elderly Patients

• Elderly patients often have blunted symptoms of hypoglycemia 5
• They may experience failure of regulatory mechanisms, especially in stress situations 5
• Reduced release of glucagon and epinephrine in response to hypoglycemia is common 5

Clinical Pitfalls to Avoid

• Failing to consider non-diabetic causes of hypoglycemia in patients with recurrent episodes 6
• Overlooking medication-related causes, including inadvertent use of hypoglycemic agents 5
• Neglecting to adjust medication dosing in patients with kidney disease 4
• Continuing the same treatment regimen after a hypoglycemic episode without investigating the cause 5