PMID- 24347174 OWN - NLM STAT- MEDLINE DCOM- 20141021 LR - 20221207 IS - 1573-4919 (Electronic) IS - 0300-8177 (Linking) VI - 388 IP - 1-2 DP - 2014 Mar TI - Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes. PG - 203-10 LID - 10.1007/s11010-013-1911-4 [doi] AB - 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-alpha (TNF-alpha) 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-alpha, 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], TNFalpha [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-alpha, 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. FAU - Jayashree, B AU - Jayashree B AD - Centre for Biotechnology, Anna University, Chennai, 600025, India. FAU - Bibin, Y S AU - Bibin YS FAU - Prabhu, D AU - Prabhu D FAU - Shanthirani, C S AU - Shanthirani CS FAU - Gokulakrishnan, K AU - Gokulakrishnan K FAU - Lakshmi, B S AU - Lakshmi BS FAU - Mohan, V AU - Mohan V FAU - Balasubramanyam, M AU - Balasubramanyam M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131218 PL - Netherlands TA - Mol Cell Biochem JT - Molecular and cellular biochemistry JID - 0364456 RN - 0 (Biomarkers) RN - 0 (Blood Glucose) RN - 0 (Cholesterol, HDL) RN - 0 (Glycated Hemoglobin A) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (TJP1 protein, human) RN - 0 (Triglycerides) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Zonula Occludens-1 Protein) RN - 0 (hemoglobin A1c protein, human) SB - IM MH - Biomarkers/*blood MH - Blood Glucose MH - Cholesterol, HDL/blood MH - Diabetes Mellitus, Type 2/*blood MH - Endotoxemia/blood MH - Female MH - Glycated Hemoglobin/metabolism MH - Humans MH - Inflammation/*blood MH - Insulin Resistance MH - Interleukin-6/blood MH - Lipopolysaccharides/*blood MH - Male MH - Middle Aged MH - Triglycerides/blood MH - Tumor Necrosis Factor-alpha/blood MH - Zonula Occludens-1 Protein/*blood EDAT- 2013/12/19 06:00 MHDA- 2014/10/22 06:00 CRDT- 2013/12/19 06:00 PHST- 2013/09/18 00:00 [received] PHST- 2013/11/15 00:00 [accepted] PHST- 2013/12/19 06:00 [entrez] PHST- 2013/12/19 06:00 [pubmed] PHST- 2014/10/22 06:00 [medline] AID - 10.1007/s11010-013-1911-4 [doi] PST - ppublish SO - Mol Cell Biochem. 2014 Mar;388(1-2):203-10. doi: 10.1007/s11010-013-1911-4. Epub 2013 Dec 18.