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Molecular and Cellular Biochemistry

, Volume 388, Issue 1–2, pp 203–210 | Cite as

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

  • B. Jayashree
  • Y. S. Bibin
  • D. Prabhu
  • C. S. Shanthirani
  • K. Gokulakrishnan
  • B. S. Lakshmi
  • V. Mohan
  • M. Balasubramanyam
Article

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.

Keywords

LPS Zonulin Gut permeability Proinflammation Type 2 diabetes 

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

Notes

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.

Conflict of interest

None.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • B. Jayashree
    • 2
  • Y. S. Bibin
    • 1
  • D. Prabhu
    • 1
  • C. S. Shanthirani
    • 1
  • K. Gokulakrishnan
    • 1
  • B. S. Lakshmi
    • 2
  • V. Mohan
    • 1
  • M. Balasubramanyam
    • 1
  1. 1.Department of Cell and Molecular BiologyMadras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre [WHO Collaborating Centre for Non-Communicable Diseases Prevention and Control & IDF Centre of Education]ChennaiIndia
  2. 2.Centre for BiotechnologyAnna UniversityChennaiIndia

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