A direct effect of the hematocrit on blood glucose: Evidence from hypoxia- and erythropoietin-treated mice.

Summary

Hypoxia lowers glucose in obese mice by stimulating erythropoiesis; the resulting hematocrit rise directly reduces glycemia independent of weight. Transfusion rapidly lowers glucose, and EPO acts via hematopoietic cells rather than nonhematopoietic tissues to improve glycemia.

Key Findings

• Hypoxia-induced erythropoiesis lowers blood glucose and improves insulin sensitivity without weight loss.
• Red cell mass directly lowers glycemia; transfusion promptly reduces glucose.
• EPO reduces glycemia via receptors on hematopoietic cells, not by direct action on nonhematopoietic tissues.

Clinical Implications

Anti-anemic therapies (EPO, transfusions) and conditions elevating hematocrit (polycythemia, high altitude, smoking) may influence glycemia; glycemic monitoring and dose tailoring may be warranted.

Limitations

• Predominantly preclinical murine data; human confirmation is needed
• Potential confounders (e.g., stress responses to hypoxia) require further dissection

Future Directions

Quantify hematocrit–glucose coupling in humans under EPO therapy and high-altitude exposure; define erythrocyte glucose handling and its pharmacologic modulation.