title: Reduced levels of circulating endothelial progenitor cells in acute myocardial infarction patients with diabetes or pre-diabetes: accompanying the glycemic continuum.
abstract: BACKGROUND
  Diabetic patients have a significantly worse prognosis after an acute myocardial infarction (AMI) than their counterparts. Previous studies have shown that the number of circulating endothelial progenitor cells (EPCs) significantly increase early after an AMI in normoglycemic patients. However, it is well known that type 2 diabetes mellitus (DM) is associated with impaired function and reduced circulating EPCs levels. Nonetheless, few studies have analyzed EPCs response of diabetics to an AMI and the EPC response of pre-diabetic patients has not been reported yet. Therefore, we hypothesized that in the acute phase of an AMI, diabetic and pre-diabetics have lower circulating EPCs levels than patients with normal glucose metabolism. We also evaluated the possible capacity of chronic antidiabetic treatment in the recovery of EPCs response to an AMI in diabetics.
  
  
  METHODS
  One-hundred AMI patients were prospectively enrolled in the study. Using the high-performance flow cytometer FACSCanto II, circulating EPCs (CD45dimCD34+KDR+ and CD45dimCD133+KDR+ cells) were quantified, within the first 24 hours of admission. In addition, as an indirect functional parameter, we also analyzed the fraction of EPCs coexpressing the homing marker CXCR4.
  
  
  RESULTS
  We found that in the acute phase of an AMI, diabetic patients presented significantly lower levels of circulating CD45dimCD34+KDR+ and CD45dimCD133+KDR+ EPCs by comparison with nondiabetics, with a parallel decrease in the subpopulations CXCR4+ (p < 0.001). Indeed, this study suggests that the impaired response of EPCs to an AMI is an early event in the natural history of DM, being present even in pre-diabetes. Our results, also demonstrated that numbers of all EPCs populations were inversely correlated with HbA1c (r = -0.432, p < 0.001 for CD45dimCD34+KDR+ cells). Finally, this study suggests that previous chronic insulin therapy (but not oral antidiabetic drugs) attenuate the deficient response of diabetic EPCs to an AMI.
  
  
  CONCLUSIONS
  This study indicates that there is a progressive decrease in EPCs levels, from pre-diabetes to DM, in AMI patients. Moreover, glycemic control seems to be determinant for circulating EPCs levels presented in the acute phase of an AMI and chronic insulin therapy may probably attenuate the deficit in EPCs pool seen in diabetics.
authors.affiliation: Laboratory of Pharmacology and Experimental Therapeutics, Institute for Biomedical Imaging and Life Sciences, Faculty of Medicine, University of Coimbra, Coimbra, Portugal. natalia.antonio@gmail.com.
authors.forename: Natália
authors.initials: N
authors.lastname: António
authors.forename: Rosa
authors.initials: R
authors.lastname: Fernandes
authors.forename: Ana
authors.initials: A
authors.lastname: Soares
authors.forename: Francisco
authors.initials: F
authors.lastname: Soares
authors.forename: Ana
authors.initials: A
authors.lastname: Lopes
authors.forename: Tiago
authors.initials: T
authors.lastname: Carvalheiro
authors.forename: Artur
authors.initials: A
authors.lastname: Paiva
authors.forename: Guilherme Mariano
authors.initials: GM
authors.lastname: Pêgo
authors.forename: Luís A
authors.initials: LA
authors.lastname: Providência
authors.forename: Lino
authors.initials: L
authors.lastname: Gonçalves
authors.forename: Carlos Fontes
authors.initials: CF
authors.lastname: Ribeiro
mesh_terms: D000368:Aged; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D038321:Glycemic Index / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011236:Prediabetic State / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D011446:Prospective Studies; D013234:Stem Cells / Q000378:metabolism*