Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes
Increased circulatory levels of lipopolysaccharide (LPS) and zonulin signify novel biomarkers of proinflammation in patients with type 2 diabetes
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DOI：
10.1007/s11010-013-1911-4
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发表时间：
2014-03-01
影响因子：
4.3
通讯作者：
Balasubramanyam, M.
中科院分区：
文献类型：
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作者：
Jayashree, B.;Bibin, Y. S.;Balasubramanyam, M.
新出现的数据表明，肠源性内毒素（代谢性内毒素血症）可能导致胰岛素抵抗状态下的低度全身性炎症。特定的肠道细菌似乎是脂多糖（LPS）的来源，一些报告声称肠道通透性增加在代谢紊乱的发生中起作用。因此，我们研究了与对照受试者相比，2型糖尿病（T2 DM）患者的LPS和zonulin（ZO-1，肠道通透性的标志物）的血清水平沿着全身肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平。研究受试者招募自Chennai Urban Rural Epidemiology Study [CURES]，Chennai，India。研究组（每组n = 45）包括a）正常葡萄糖耐量（NGT）受试者和（B）T2 DM患者。通过ELISA测量LPS、ZO-1、TNF-α和IL-6水平。与对照受试者相比，T2 DM患者的LPS [p < 0.05]、LPS活性[p <0.001]、ZO-1 [p <0.001]、TNF α [p < 0.001]和IL-6 [p < 0.001]的血清水平显著升高。Pearson相关分析显示，LPS活性与ZO-1、空腹血糖、餐后2 h血糖、HbA 1c、血清甘油三酯、TNF-α、IL-6呈显著正相关，与HDL胆固醇呈显著负相关。回归分析显示，增加的LPS水平与2型糖尿病显著相关[比值比（OR）13.43，95%CI 1.998-18.9; p = 0.003]。在被认为高度胰岛素抵抗的亚洲印度人中，2型糖尿病患者的循环LPS水平、LPS活性和ZO-1显著升高，并与炎症标志物和血糖/血脂控制不良呈正相关。
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], TNF alpha [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.