Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.
Chronic Endotoxemia in Subjects with Type-1 Diabetes Is Seen Much before the Onset of Microvascular Complications.
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DOI：
10.1371/journal.pone.0137618
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Babu S
中科院分区：
文献类型：
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作者：
Aravindhan V;Mohan V;Arunkumar N;Sandhya S;Babu S
据推测，脂多糖 (LPS)/内毒素在与 1 型糖尿病 (T1DM) 及其并发症相关的慢性炎症中发挥重要作用。内毒素核心抗体 (EndoCAb)、LPS 结合蛋白 (LBP) 和可溶性 CD14 (sCD14) 充当 LPS 诱导的体内先天免疫系统激活的调节剂。在本研究中，我们评估了有或没有微血管并发症 (MVC) 的 T1DM 受试者的 LPS 及其易位标记物的水平，并将其与 T1DM 的临床参数和血清炎症细胞因子水平（TNF-α、IL-6、IL-1β 和 GM-CSF）相关联。本研究共纳入 197 名受试者（64 名正常糖耐量（NGT）受试者、97 名无 MVC 的 T1DM 受试者和 36 名有 MVC 的 T1DM 受试者），并通过免疫测定法测量血清 LPS、其易位标记物和细胞因子的水平。与 NGT 相比，T1DM 受试者（无论是否接受 MVC）LPS 水平显着升高，LBP 和 EndoCAb 水平降低，同时 IL-1β、IL-6、TNF-α 和 GM-CSF 水平显着升高（p<0.05）。在患有和不患有 MVC 的 T1DM 受试者之间，这些生物标志物的水平没有发现显着变化。 EndoCAb 和 LBP 水平降低表明 T1DM 受试者甚至在微血管并发症发生之前就存在持续的内毒素活性。
Lipopolysaccharide (LPS)/Endotoxin is hypothesized to play an important role in chronic inflammation associated with Type-1 diabetes (T1DM) and its complications. Endotoxin core antibodies (EndoCAb), LPS binding protein (LBP) and soluble CD14 (sCD14) act as modulators of LPS induced activation of innate immune system in vivo. For the present study we estimated the levels of LPS and its translocation markers in T1DM subjects with and without microvascular complications (MVC) and correlate them with clinical parameters of T1DM and serum inflammatory cytokine levels (TNF-α, IL-6, IL-1β and GM-CSF). A total of 197 subjects (64 normal glucose tolerance (NGT) subjects, 97 T1DM subjects without MVC and 36 with MVC) were included in this study and the levels of serum LPS, its translocation markers and cytokines measured by immunoassays. Compared to NGT, T1DM subjects (both with and without MVC) had significantly higher levels of LPS, reduced levels of LBP and EndoCAb along with significant increase in the levels of IL-1β, IL-6, TNF-α and GM-CSF (p<0.05). No significant change was seen in the levels of these biomarkers between T1DM subjects with and without MVC. Decreased levels of EndoCAb and LBP suggest sustained endotoxin activity in T1DM subjects even before the onset of microvascular complications.