Causes of Hypoglycemia
The primary causes of hypoglycemia include medication-related factors (especially insulin and insulin secretagogues), endocrine disorders, critical illness, and nutritional factors. 1
Medication-Related Causes
- Insulin therapy is the most common cause of hypoglycemia, particularly with intensive insulin regimens using multiple daily injections or insulin pumps 1, 2
- Sulfonylureas and meglitinides stimulate insulin release and are the second most common medication cause of hypoglycemia 1, 3
- Other medications that can cause hypoglycemia include NSAIDs, analgesics, antibacterials, antimalarials, antiarrhythmics, and antidepressants 4
- Excess insulin administration or changes in insulin regimen can precipitate hypoglycemia 2
Clinical and Biological Risk Factors
- Recent history of severe hypoglycemia (within past 3-6 months) significantly increases risk of future episodes 5, 1
- Impaired hypoglycemia awareness (reduced ability to perceive warning symptoms) is a major risk factor 5
- End-stage kidney disease increases risk due to decreased renal gluconeogenesis and impaired insulin clearance 5, 6
- Cognitive impairment or dementia limits ability to recognize or respond to hypoglycemic symptoms 5, 1
- Advanced age (≥75 years) is associated with reduced counterregulatory hormone responses 5, 1
- Female sex has been identified as a risk factor in multiple studies 5
- High glycemic variability contributes to unpredictable glucose levels 5
- Chronic kidney disease (eGFR <60 mL/min/1.73 m²) reduces renal glucose production 5, 6
- Cardiovascular disease is associated with increased hypoglycemia risk 5
- Diabetic complications including neuropathy and retinopathy increase risk 5
Social, Cultural, and Economic Risk Factors
- Food insecurity with irregular access to adequate nutrition increases risk 5, 1
- Low-income status limits resources for proper diabetes management 5, 1
- Housing insecurity affects medication adherence and meal timing 5, 1
- Fasting for religious or cultural reasons can precipitate hypoglycemia 5, 1
- Alcohol consumption inhibits gluconeogenesis and can cause hypoglycemia, especially when combined with diabetes medications 5, 1
Hospital-Specific Risk Factors
- Interruptions in nutritional intake (NPO status, delayed meals) are common causes in hospitalized patients 1
- Changes in medication regimens during hospitalization can disrupt glucose control 1
- Critical illness alters metabolism and increases insulin resistance 1
- Sepsis causes dysregulated glucose metabolism 1
- Low albumin levels alter drug binding and pharmacokinetics 1
Physiologic Mechanisms
- Hypoglycemia occurs when blood glucose falls below 70 mg/dL (<3.9 mmol/L), with neuroglycopenic symptoms typically beginning at levels below 54 mg/dL (<3.0 mmol/L) 5
- In healthy individuals, falling glucose levels trigger decreased insulin secretion and increased counterregulatory hormones (glucagon, epinephrine) 7
- In diabetes, this counterregulatory response is often impaired, especially after recurrent hypoglycemic episodes 5, 7
- Hypoglycemia unawareness develops when autonomic warning symptoms fail to occur, creating a dangerous cycle where hypoglycemia begets more hypoglycemia 5
Clinical Pitfalls to Avoid
- Failing to adjust insulin doses in patients with declining kidney function 6
- Continuing the same insulin regimen when nutrition is interrupted in hospitalized patients 1
- Overlooking the potential for drug interactions that increase hypoglycemia risk 2, 3
- Not recognizing that several weeks of strict hypoglycemia avoidance can help restore hypoglycemia awareness in affected patients 5
- Underestimating the risk of hypoglycemia in elderly patients or those with multiple comorbidities 5, 1