Can erythropoietin (EPO) increase glucose levels?

Erythropoietin's Effect on Blood Glucose Levels

Erythropoietin (EPO) can decrease blood glucose levels based on recent evidence from multiple studies, making glucose monitoring important for patients receiving EPO therapy, especially those with diabetes. 1, 2, 3

Mechanism and Evidence

Erythropoietin has demonstrated glucose-lowering effects through several mechanisms:

• A 2021 study showed that patients with hematologic disorders (MDS or multiple myeloma) had significantly lower blood glucose levels while on EPO therapy (105.64 ± 5.11 mg/dL) compared to when they were not receiving EPO (116.38 ± 5.21 mg/dL) 1
• This glucose-lowering effect was observed in both diabetic and non-diabetic patients 1
• EPO appears to:
  • Increase glucose uptake via activation of the Akt pathway 3
  • Enhance glucose transporter 4 (GLUT4) translocation to the plasma membrane 3
  • Reduce hepatic PEPCK expression (an enzyme involved in gluconeogenesis) 2
  • Increase insulin sensitivity 2

Clinical Implications

For Patients with Diabetes

Patients with diabetes who receive EPO therapy (commonly those with chronic kidney disease or anemia related to chemotherapy) require special consideration:

• Glucose monitoring is advised due to potential hypoglycemic effects 1
• Diabetic patients showed approximately 19 mg/dL reduction in glucose levels when receiving EPO therapy 1
• In patients with diabetes and end-stage renal disease, EPO therapy can affect HbA1c measurements, potentially leading to falsely decreased values 4

For Monitoring Glycemic Control in Patients on EPO

The KDOQI guidelines note that in patients receiving EPO:

• HbA1c remains the best clinical marker of long-term glycemic control but should be interpreted with caution 4
• Consider alternative glycemic markers such as:
  • Glycated albumin (reflects glycemic control over 2 weeks) 4
  • Continuous glucose monitoring for more accurate daily management 4

Potential Benefits Beyond Anemia Correction

The glucose-lowering effect of EPO may provide additional benefits:

• Animal studies show EPO can attenuate body weight gain and reduce hemoglobin A1c in obesity models 5
• EPO demonstrates protective effects against high glucose-induced oxidative stress in renal tubular cells 6
• EPO inhibits high glucose-induced renal tubular cell apoptosis through anti-oxidative stress effects 6

Precautions and Monitoring

While EPO's glucose-lowering effect may be beneficial in some contexts, it requires careful monitoring:

• Patients with diabetes receiving EPO should be monitored for potential hypoglycemia 1
• EPO therapy carries other risks including thrombotic events, hypertension, and seizures that need to be balanced against potential metabolic benefits 7
• The target hemoglobin level should not exceed 12 g/dL due to increased risks observed at higher levels 7

Conclusion

The evidence clearly demonstrates that EPO therapy can lower blood glucose levels through multiple mechanisms. This effect should be considered when managing patients receiving EPO, particularly those with diabetes, as it may necessitate adjustments to antidiabetic medications to prevent hypoglycemia.