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Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes

Abstract

Emerging data indicate that gut-derived endotoxin (metabolic endotoxemia) may contribute to low-grade systemic inflammation in insulin-resistant states. Specific gut bacteria seem to serve as lipopolysaccharide (LPS) sources and several reports claim a role for increased intestinal permeability in the genesis of metabolic disorders. Therefore, we investigated the serum levels of LPS and zonulin (ZO-1, a marker of gut permeability) along with systemic levels of tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) in patients with type 2 diabetes mellitus (T2DM) compared to control subjects. Study subjects were recruited from the Chennai Urban Rural Epidemiology Study [CURES], Chennai, India. Study group (n = 45 each) comprised of a) subjects with normal glucose tolerance (NGT) and (b) patients with T2DM. LPS, ZO-1, TNF-α, and IL-6 levels were measured by ELISA. Serum levels of LPS [p < 0.05], LPS activity [p < 0.001], ZO-1 [p < 0.001], TNFα [p < 0.001], and IL-6 [p < 0.001] were significantly increased in patients with T2DM compared to control subjects. Pearson correlation analysis revealed that LPS activity was significantly and positively correlated with ZO-1, fasting plasma glucose, 2 h post glucose, HbA1c, serum triglycerides, TNF-α, IL-6, and negatively correlated with HDL cholesterol. Regression analysis showed that increased LPS levels were significantly associated with type 2 diabetes [odds ratio (OR) 13.43, 95 % CI 1.998–18.9; p = 0.003]. In Asian Indians who are considered highly insulin resistant, the circulatory LPS levels, LPS activity, and ZO-1 were significantly increased in patients with type 2 diabetes and showed positive correlation with inflammatory markers and poor glycemic/lipid control.

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Abbreviations

T2DM:

Type 2 diabetes mellitus

NGT:

Normal glucose tolerance

ZO-1:

Zonulin-1

LPS:

Lipopolysaccharide

TNF-α:

Tumor necrosis factor-α

IL-6:

Interleukin-6

CURES:

Chennai Urban Rural Epidemiology Study

OR:

Odds ratio

OGTT:

Oral glucose tolerance test

BMI:

Body mass index

HbA1c:

Glycated hemoglobin

LAL:

Limulus amebocyte lysate

ELISA:

Enzyme linked immunosorbent assay

TLR4:

Toll-like receptor-4

HDL:

High density lipoprotein

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Acknowledgments

Authors acknowledge the financial support from the Department of Biotechnology (DBT), Government of India. Authors also acknowledge and thank the scientific inputs on clinical immunology aspects by Dr. R. B. Naryananan, Centre for Biotechnology, Anna University.

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Correspondence to M. Balasubramanyam.

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Jayashree, B., Bibin, Y.S., Prabhu, D. et al. Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. Mol Cell Biochem 388, 203–210 (2014). https://doi.org/10.1007/s11010-013-1911-4

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  • DOI: https://doi.org/10.1007/s11010-013-1911-4

Keywords

  • LPS
  • Zonulin
  • Gut permeability
  • Proinflammation
  • Type 2 diabetes