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

• Published in: Molecular and cellular biochemistry Vol. 388; no. 1-2; pp. 203 - 210
• Main Authors: Jayashree, B., Bibin, Y. S., Prabhu, D., Shanthirani, C. S., Gokulakrishnan, K., Lakshmi, B. S., Mohan, V., Balasubramanyam, M.
• Format: Journal Article
• Language: English
• Published: Boston Springer US 01.03.2014; Springer; Springer Nature B.V
• Subjects: Biochemistry; Biomarkers; Biomarkers - blood; Biomedical and Life Sciences; Blood cholesterol; Blood Glucose; Cardiology; Cholesterol, HDL - blood; Circulatory system; Comparative analysis; Correlation analysis; Dextrose; Diabetes; Diabetes Mellitus, Type 2 - blood; Diabetes therapy; Endotoxemia - blood; Endotoxins; Enzyme-linked immunosorbent assay; Epidemiology; Female; Glucose; Glucose metabolism; Glycated Hemoglobin A - metabolism; Humans; Inflammation; Inflammation - blood; Insulin Resistance; Interleukin-6 - blood; Life Sciences; Lipopolysaccharides - blood; Male; Medical Biochemistry; Metabolic disorders; Middle Aged; Mitogens; Oncology; Patients; Permeability; Regression analysis; Triglycerides - blood; Tumor necrosis factor; Tumor Necrosis Factor-alpha - blood; Type 2 diabetes; Zonula Occludens-1 Protein - blood; Gut permeability; Type 2 diabetes; Zonulin; Proinflammation; LPS
• ISSN: 0300-8177; 1573-4919; 1573-4919
• DOI: 10.1007/s11010-013-1911-4

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.