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Observational Study
. 2015 Sep 14;10(9):e0137618.
doi: 10.1371/journal.pone.0137618. eCollection 2015.

Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications

Vivekanandhan Aravindhan  1 , Viswanathan Mohan  2 , Namasivayam Arunkumar  3 , Sreedharan Sandhya  4 , Subash Babu  5
Affiliations
Observational Study

Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications

Vivekanandhan Aravindhan et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. T1DM is characterized by systemic endotoxemia with significantly decreased levels of LBP and EndoCAb.
Serum levels of LPS (a), LBP (b), sCD14 (c) and EndoCAb (d) were determined in NGT (n = 64), T1DM without MVC (n = 97) and T1DM subjects with MVC (n = 36) by immune-assays. Each dot represents individual values with the horizontal line representing the geo mean. 36 T1DM subjects without MVC and 26 with MVC had undetectable levels of EndoCAb. Significance was calculated by non-parametric Mann–Whitney U test and p<0.05 was considered significant. The indicated p values are for pair-wise comparisons.
Fig 2
Fig 2. T1DM is characterized by systemic inflammation with high levels of serum pro-inflammatory cytokines.
Serum levels of IL-1β (a), IL-6 (b), TNF-α (c), and GM-CSF (d) were determined in NGT (n = 64), T1DM without MVC (n = 97) and T1DM subjects with MVC (n = 36) by ELISA. Each dot represents individual values with the horizontal line representing the geo mean. Significance was calculated by non-parametric Mann–Whitney U test and p<0.05 was considered significant. The indicated p values are for pair-wise comparisons.
See this image and copyright information in PMC

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