title: Influence of erythropoietin on cognitive performance during experimental hypoglycemia in patients with type 1 diabetes mellitus: a randomized cross-over trial.
abstract: BACKGROUND
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00615368.
authors.affiliation: Endocrinology Section, Department of Cardiology, Nephrology and Endocrinology, Hillerød Hospital, Hillerød, Denmark. pelk@hih.regionh.dk
authors.forename: Peter Lommer
authors.initials: PL
authors.lastname: Kristensen
authors.forename: Ulrik
authors.initials: U
authors.lastname: Pedersen-Bjergaard
authors.forename: Troels Wesenberg
authors.initials: TW
authors.lastname: Kjær
authors.forename: Niels Vidiendal
authors.initials: NV
authors.lastname: Olsen
authors.forename: Flemming
authors.initials: F
authors.lastname: Dela
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Jens
authors.initials: J
authors.lastname: Faber
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Birger
authors.initials: B
authors.lastname: Thorsteinsson
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000378:metabolism / Q000503:physiopathology*; D004569:Electroencephalography; D055724:Electrophysiological Phenomena / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D005260:Female; D015309:Glucose Clamp Technique; D006403:Hematologic Tests; D006728:Hormones / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic
chemical_list: D001786:Blood Glucose; D006728:Hormones; D004921:Erythropoietin