title: Circulating endothelial progenitor cells, endothelial function, carotid intima-media thickness and circulating markers of endothelial dysfunction in people with type 1 diabetes without macrovascular disease or microalbuminuria.
abstract: OBJECTIVE
  Type 1 diabetes is associated with premature arterial disease. Bone-marrow derived, circulating endothelial progenitor cells (EPCs) are believed to contribute to endothelial repair. The hypothesis tested was that circulating EPCs are reduced in young people with type 1 diabetes without vascular injury and that this is associated with impaired endothelial function and increased carotid intima-media thickness (CIMT).
  
  
  METHODS
  We compared 74 people with type 1 diabetes with 80 healthy controls. CD34, CD133, vascular endothelial (VE) growth factor receptor-2 (VEGFR-2) and VE-cadherin antibodies were used to quantify EPCs and progenitor cell subtypes using flow-cytometry. Ultrasound assessment of endothelial function by brachial artery flow-mediated dilatation (FMD) and CIMT was made. Circulating endothelial markers, inflammatory markers and plasma plasminogen activator inhibitor-1 (PAI-1) levels were measured.
  
  
  RESULTS
  CD34+VE-cadherin+, CD133+VE-cadherin+ and CD133+VEGFR-2+ EPC counts were significantly lower in people with diabetes (46-69%; p = 0.004-0.043). In people with type 1 diabetes, FMD was reduced by 45% (p < 0.001) and CIMT increased by 25% (p < 0.001), these being correlated (r = -0.25, p = 0.033). There was a significant relationship between FMD and CD34+VE-cadherin+ (r = 0.39, p = 0.001), CD133+VEGFR-2+ (r = 0.25, p = 0.037) and CD34+ (r = 0.34, p = 0.003) counts. Circulating high-sensitivity C-reactive protein, PAI-1, interleukin-6 and E-selectin were significantly higher in the diabetes group (p < 0.001 to p = 0.049), the last two of these correlating with FMD (r = -0.27, p = 0.028 and r = -0.24, p = 0.048, respectively).
  
  
  CONCLUSIONS
  These findings suggest that abnormalities of endothelial function in addition to pro-inflammatory and pro-thrombotic states are already common in people with type 1 diabetes before development of clinically evident arterial damage. Low EPC counts confirm risk of macrovascular complications and may account for impaired endothelial function and predict future cardiovascular events.
authors.affiliation: ICM-Diabetes, Newcastle University, Framlington Place, Newcastle upon Tyne NE2 4HH, UK. latikasibal@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Sibal
authors.forename: A
authors.initials: A
authors.lastname: Aldibbiat
authors.forename: S C
authors.initials: SC
authors.lastname: Agarwal
authors.forename: G
authors.initials: G
authors.lastname: Mitchell
authors.forename: C
authors.initials: C
authors.lastname: Oates
authors.forename: S
authors.initials: S
authors.lastname: Razvi
authors.forename: J U
authors.initials: JU
authors.lastname: Weaver
authors.forename: J A
authors.initials: JA
authors.lastname: Shaw
authors.forename: P D
authors.initials: PD
authors.lastname: Home
mesh_terms: D000293:Adolescent; D000328:Adult; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002096:C-Peptide / Q000097:blood; D002339:Carotid Arteries / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012016:Reference Values; D017539:Tunica Intima / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D017540:Tunica Media / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology / Q000502:physiology; D014664:Vasodilation; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D017395:Plasminogen Activator Inhibitor 1; D040301:Vascular Endothelial Growth Factor Receptor-2