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

Mol Cell Biochem. 2014 Mar;388(1-2):203-10. doi: 10.1007/s11010-013-1911-4. Epub 2013 Dec 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood*
  • Blood Glucose
  • Cholesterol, HDL / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Endotoxemia / blood
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Inflammation / blood*
  • Insulin Resistance
  • Interleukin-6 / blood
  • Lipopolysaccharides / blood*
  • Male
  • Middle Aged
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / blood
  • Zonula Occludens-1 Protein / blood*

Substances

  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • Glycated Hemoglobin A
  • IL6 protein, human
  • Interleukin-6
  • Lipopolysaccharides
  • TJP1 protein, human
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • Zonula Occludens-1 Protein
  • hemoglobin A1c protein, human