Influence of erythropoietin on cognitive performance during experimental hypoglycemia in patients with type 1 diabetes mellitus: a randomized cross-over trial

PLoS One. 2013;8(4):e59672. doi: 10.1371/journal.pone.0059672. Epub 2013 Apr 5.


Introduction: The incidence of severe hypoglycemia in type 1 diabetes has not decreased over the past decades. New treatment modalities minimizing the risk of hypoglycemic episodes and attenuating hypoglycemic cognitive dysfunction are needed. We studied if treatment with the neuroprotective hormone erythropoietin (EPO) enhances cognitive function during hypoglycemia.

Materials and methods: Eleven patients with type 1 diabetes, hypoglycemia unawareness and recurrent severe hypoglycemia completed the study. In a double-blind, randomized, balanced, cross-over study using clamped hypoglycemia they were treated with 40,000 IU of EPO or placebo administered intravenously six days before the two experiments. Cognitive function (primary endpoint), hypoglycemic symptoms, and counter-regulatory hormonal response were recorded.

Results: Compared with placebo, EPO treatment was associated with a significant reduction in errors in the most complex reaction time task (-4.7 (-8.1 to -1.3), p = 0.01) and a less reaction time prolongation (-66 (-117 to -16) msec, p = 0.02). EPO treatment did not change performance in other measures of cognition. Hypoglycemic symptoms, EEG-changes, and counter-regulatory hormone concentrations did not differ between EPO and placebo treatment.

Conclusion: In patients with type 1 diabetes and hypoglycemia unawareness, treatment with EPO is associated with a beneficial effect on cognitive function in a complex reaction time task assessing sustained attention/working memory. Hypoglycemic symptoms and hormonal responses were not changed by EPO treatment.

Trial registration: NCT00615368.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / metabolism
  • Cognition / drug effects*
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / metabolism
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Electroencephalography
  • Electrophysiological Phenomena / drug effects
  • Erythropoietin / pharmacology*
  • Female
  • Glucose Clamp Technique*
  • Hematologic Tests
  • Hormones / metabolism
  • Humans
  • Male
  • Middle Aged
  • Monitoring, Physiologic


  • Blood Glucose
  • Hormones
  • Erythropoietin

Associated data


Grant support

The study was funded by grants from the Tvergaard Foundation, Foundation of Harald Jensen and Wife, Foundation of Hans Christensen, Foundation of King Christian 10th, Research Foundation of Hillerød Hospital, Brødrene Hartmann Foundation, and Olga Bryde Nielsen Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.