title: Erythropoietin and vascular endothelial growth factor as risk markers for severe hypoglycaemia in type 1 diabetes.
abstract: OBJECTIVE
  Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes.
  
  
  METHODS
  Prospective observational follow-up study.
  
  
  METHODS
  Totally 219 patients with type 1 diabetes (41% females, age 46+/-13 years (mean+/-s.d.), duration of diabetes 21+/-12 years, and HbAlc 8.5+/-1.1%) were followed in a 1-year observational study. Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h.
  
  
  RESULTS
  Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported by 82 patients (37%). At baseline, plasma EPO was 8.6 (3.1-34.3) U/l (median (range)), and serum VEGF was 52.2 (6.6-337) pg/ml. The levels of EPO and VEGF were not associated with frequency of severe and mild hypoglycaemia. The levels of EPO were not associated with age, sex, duration of diabetes, body mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex.
  
  
  CONCLUSIONS
  Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes.
authors.affiliation: Endocrinology Section, Department of Cardiology and Endocrinology, Hillerød Hospital, Dyrehavevej 29, DK-3400 Hillerød, Denmark. pelk@hih.regionh.dk
authors.forename: P L
authors.initials: PL
authors.lastname: Kristensen
authors.forename: U
authors.initials: U
authors.lastname: Pedersen-Bjergaard
authors.forename: C
authors.initials: C
authors.lastname: Schalkwijk
authors.forename: N V
authors.initials: NV
authors.lastname: Olsen
authors.forename: B
authors.initials: B
authors.lastname: Thorsteinsson
mesh_terms: D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D004921:Erythropoietin / Q000009:adverse effects / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000150:complications / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors; D042461:Vascular Endothelial Growth Factor A / Q000009:adverse effects / Q000097:blood*
chemical_list: D015415:Biomarkers; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin