title: 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.
authors.affiliation: Centre for Biotechnology, Anna University, Chennai, 600025, India.
authors.forename: B
authors.initials: B
authors.lastname: Jayashree
authors.forename: Y S
authors.initials: YS
authors.lastname: Bibin
authors.forename: D
authors.initials: D
authors.lastname: Prabhu
authors.forename: C S
authors.initials: CS
authors.lastname: Shanthirani
authors.forename: K
authors.initials: K
authors.lastname: Gokulakrishnan
authors.forename: B S
authors.initials: BS
authors.lastname: Lakshmi
authors.forename: V
authors.initials: V
authors.lastname: Mohan
authors.forename: M
authors.initials: M
authors.lastname: Balasubramanyam
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001786:Blood Glucose; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D019446:Endotoxemia / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D062826:Zonula Occludens-1 Protein / Q000097:blood*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; C508600:IL6 protein, human; C569042:TJP1 protein, human; C517652:hemoglobin A1c protein, human