What are the causes of pseudohypoglycemia?

Causes of Pseudohypoglycemia

Pseudohypoglycemia is caused by laboratory measurement errors that falsely report low glucose levels when true blood glucose is normal, primarily due to interfering substances, hematologic abnormalities, or impaired peripheral circulation affecting capillary blood sampling.

Laboratory Interference Causes

Metabolic and Chemical Interferences

• High triglycerides, uric acid (>20 mg/dL), or bilirubin cause falsely low glucose readings on point-of-care meters 1
• High acetaminophen levels (>8 mg/dL) paradoxically cause falsely high readings, which can mask true hypoglycemia 1
• Ascorbic acid interferes with electrochemical glucose sensors 1

Hematologic Factors

• Low hematocrit (<35%) results in falsely elevated glucose readings on glucose oxidase (GO)-based meters, which can mask true hypoglycemia 1
• Conversely, high hematocrit may cause falsely low readings 2

Oxygen-Related Interference

• Hypoxia (PaO2 <45 mmHg) causes falsely high glucose readings on GO-based meters 1
• Oxygen therapy (PaO2 >150 mmHg) causes falsely low glucose readings on GO-based meters 1

Medication and Dialysis-Related Causes

Glucose Meter Enzyme Interference

• GDH-PQQ-based meters cannot distinguish glucose from other sugars and show falsely elevated readings with:
  • Icodextrin (peritoneal dialysis solutions) 1
  • Maltose, galactose, or xylose in parenteral solutions 1
  • Certain immunoglobulins and abatacept 1

Critical pitfall: GDH-PQQ and GO-based meters should never be used in patients with end-stage kidney disease on dialysis or those receiving interfering medications, as this can lead to dangerous mismanagement of true hypoglycemia 1

Circulatory Causes

Impaired Peripheral Perfusion

• Raynaud phenomenon causes discordant capillary versus venous glucose due to increased tissue glucose extraction from prolonged capillary transit time 3
• Peripheral vascular disease similarly causes falsely low capillary readings 3
• Shock states with poor peripheral perfusion lead to increased glucose extraction before blood reaches the sampling site 3
• Hypothermia reduces peripheral blood flow and causes pseudohypoglycemia 4

Key diagnostic approach: When pseudohypoglycemia from circulatory causes is suspected, warming the extremity before sampling or comparing capillary to venous blood glucose confirms the diagnosis—venous samples will show normal glucose while capillary samples remain falsely low 3

Clinical Recognition

When to Suspect Pseudohypoglycemia

• Asymptomatic "hypoglycemia" on finger-stick testing 5, 3
• Discrepancy between capillary and venous glucose measurements 4, 3
• Known conditions predisposing to measurement error (ESKD on dialysis, Raynaud phenomenon, critical illness) 1, 3
• Cold extremities or poor peripheral perfusion during sampling 4, 3

Confirmation Strategy

• Obtain simultaneous venous plasma glucose when capillary readings seem inconsistent with clinical presentation 4, 3
• For circulatory causes: warm the extremity and recheck capillary glucose—values should normalize 3
• For dialysis patients: use hexokinase (HK), GDH-NAD, or GDH-FAD methods instead of GDH-PQQ or GO-based meters 1
• Verify the glucose meter methodology being used and check for known interfering substances 1

Important Distinctions

This differs from true hypoglycemia, which has entirely different causes including insulin/sulfonylurea therapy, end-stage kidney disease with impaired insulin clearance, adrenal insufficiency, critical illness, and nutritional factors 6, 7. Pseudohypoglycemia represents a measurement artifact rather than an actual metabolic derangement, making recognition essential to avoid unnecessary and potentially harmful interventions 5, 3.