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. BalasubramanyamEmail author


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.


LPS Zonulin Gut permeability Proinflammation Type 2 diabetes 



Type 2 diabetes mellitus


Normal glucose tolerance






Tumor necrosis factor-α




Chennai Urban Rural Epidemiology Study


Odds ratio


Oral glucose tolerance test


Body mass index


Glycated hemoglobin


Limulus amebocyte lysate


Enzyme linked immunosorbent assay


Toll-like receptor-4


High density lipoprotein



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



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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
    Email author
  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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