title: Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels of circulating angiogenic factors.
abstract: Tuberculosis-diabetes co-morbidity (TB-DM) is characterized by increased inflammation with elevated circulating levels of inflammatory cytokines and other factors. Circulating angiogenic factors are intricately involved in the angiogenesis-inflammation nexus.
  
  
  
  To study the association of angiogenic factors with TB-DM, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3 in individuals with either TB-DM (n = 44) or TB alone (n = 44).
  
  
  
  Circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly higher in TB-DM compared to TB individuals. Moreover, the levels of VEGF-A, C, R2 and/or R3 were significantly higher in TB-DM with bilateral or cavitary disease or with hemoptysis, suggesting an association with both disease severity and adverse clinical presentation. The levels of these factors also exhibited a significant positive relationship with bacterial burdens and HbA1c levels. In addition, VEGF-A, C and R2 levels were significantly higher (at 2 months of treatment) in culture positive compared to culture negative TB-DM individuals. Finally, the circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly reduced following successful chemotherapy at 6 months.
  
  
  
  Our data demonstrate that TB-DM is associated with heightened levels of circulating angiogenic factors, possibly reflecting both dysregulated angiogenesis and exaggerated inflammation.
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Nathella Pavan
authors.initials: NP
authors.lastname: Kumar
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Kadar
authors.initials: K
authors.lastname: Moideen
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Shanmugam
authors.initials: S
authors.lastname: Sivakumar
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
authors.forename: Pradeep A
authors.initials: PA
authors.lastname: Menon
authors.affiliation: Prof. M. Viswanathan Diabetes Research Center, Chennai, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Viswanathan
authors.affiliation: University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: Hardy
authors.initials: H
authors.lastname: Kornfeld
authors.affiliation: National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India; LPD, NIAID, NIH, MD, USA. Electronic address: sbabu@mail.nih.gov.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000097:blood* / Q000302:isolation & purification; D058491:Bacterial Load; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D016207:Cytokines / Q000097:blood; D048909:Diabetes Complications / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood* / Q000382:microbiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D014376:Tuberculosis / Q000097:blood* / Q000150:complications* / Q000382:microbiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000302:isolation & purification; D042582:Vascular Endothelial Growth Factor C / Q000097:blood / Q000302:isolation & purification; D042643:Vascular Endothelial Growth Factor D / Q000097:blood / Q000302:isolation & purification
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D016207:Cytokines; C467484:VEGFA protein, human; C579459:VEGFD protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D
keywords: Angiogenesis; Biomarkers; Diabetes; Tuberculosis