title: Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.
abstract: BACKGROUND
  Lipopolysaccharide (LPS)/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM) and its complications. Endotoxin core antibodies (EndoCAb), LPS binding protein (LBP) and soluble CD14 (sCD14) act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC) and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF).
  
  
  METHODS
  A total of 197 subjects (64 normal glucose tolerance (NGT) subjects, 97 T1DM subjects without MVC and 36 with MVC) were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays.
  
  
  RESULTS
  Compared to NGT, T1DM subjects (both with and without MVC) had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p<0.05). No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC.
  
  
  CONCLUSIONS
  Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications.
authors.affiliation: AU-KBC Research Centre, MIT Campus of Anna University, Chennai, India; Dept of Genetics, Dr ALM PG IBMS, University of Madras, Taramani, Chennai, 600113, India.
authors.forename: Vivekanandhan
authors.initials: V
authors.lastname: Aravindhan
authors.affiliation: Madras Diabetes Research Foundation & Dr. Mohan's Diabetes Specialties Centre, WHO Collaborating Centre for Non-Communicable Diseases Prevention and NGT, International Diabetes Federation (IDF) Centre for Education, Chennai, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.affiliation: Biostatistics & Programming, Algorithm Inc, Bengaluru, India.
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Arunkumar
authors.affiliation: AU-KBC Research Centre, MIT Campus of Anna University, Chennai, India.
authors.forename: Sreedharan
authors.initials: S
authors.lastname: Sandhya
authors.affiliation: National Institutes of Health-International Center for Excellence in Research, National Institute for Research in Tuberculosis, Chennai, India.
authors.forename: Subash
authors.initials: S
authors.lastname: Babu
mesh_terms: D000209:Acute-Phase Proteins; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002352:Carrier Proteins / Q000097:blood; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications*; D019446:Endotoxemia / Q000097:blood / Q000150:complications*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000097:blood; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; D002352:Carrier Proteins; D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D014409:Tumor Necrosis Factor-alpha; D000099231:Lipopolysaccharide-Binding Protein