sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy.
sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy.
复制标题
DOI：
10.1186/cc10420
复制
发表时间：
2011-08-26
期刊：
影响因子：
--
通讯作者：
Bouchama A
中科院分区：
文献类型：
--
作者：
Arabi YM;Dehbi M;Rishu AH;Baturcam E;Kahoul SH;Brits RJ;Naidu B;Bouchama A
高血压是非糖尿病重症患者的独立预后因素，但在糖尿病患者中并非如此。在这种情况下，有一个正在进行的辩论的好处，强化胰岛素治疗，特别是在糖尿病患者。我们验证了这样一种假设，即晚期糖基化终产物受体（receptor for advanced glycation end-products，RECEPTOR）的表达可能是这种差异的基础，RECEPTOR是一种重要的信号转导受体，可增强核因子κ B（NF-κB）的持久激活。β-内酰胺酶的表达受多种配体调节，包括高迁移率族蛋白-1（HMGB-1），并通过其释放的可溶性形式（β-内酰胺酶）反映。对76例年龄≥18岁、血糖> 6.1 mmol/L的高血糖重症患者（33例2型糖尿病，43例非糖尿病）前瞻性采集的样本进行预先设计的分析，这些患者入组了一项比较强化胰岛素治疗与常规胰岛素治疗的随机对照试验。在第1、3、5和7天，在ICU中评价sCRP及其配体HMGB-1以及IL-6和可溶性血栓调节蛋白（分别作为炎症和内皮细胞损伤的标志物）。来自18名健康受试者的血浆样品用作对照。糖尿病和非糖尿病高血糖患者在入住ICU时均表现出血浆sIgA、HMGB-1和可溶性血栓调节蛋白水平升高。血浆IL-6浓度仅在非糖尿病患者中升高。与非糖尿病患者相比，糖尿病患者的血浆胰岛素水平较高。在糖尿病患者中，强化胰岛素治疗导致第7天的sweep和血栓调节蛋白显著降低，但非糖尿病患者则无此结果。循环血肌酐水平与IL-6和可溶性血栓调节蛋白水平呈正相关，与HMGB-1呈负相关。多因素回归分析显示，糖尿病患者血清胰岛素水平与HMGB-1仍独立相关。无论是皮肤炎还是任何炎症标志物都与死亡率无关。这些发现支持了这样的假设：高血糖糖尿病和非糖尿病重症患者之间的sRAGE释放、时程和对强化胰岛素治疗的反应不同。这种差异是否是这两种情况下高血糖症临床结局不同的基础，需要进一步研究。
Hyperglycemia represents an independent prognostic factor in critically ill non-diabetic patients but not in those with diabetes. In this context, there is an ongoing debate on the benefit of an intensive insulin therapy, particularly in diabetic patients. We tested the hypothesis that expression of the receptor for advanced glycation end-products (RAGE), an important signal transduction receptor that elicits long-lasting nuclear factor kappa B (NF-κB) activation, may underlie this difference. RAGE expression is regulated by multiple ligands, including high mobility group box-1 (HMGB-1), and is reflected by its released soluble form (sRAGE). A predesigned analysis was conducted of prospectively collected samples from 76 hyperglycemic critically ill patients (33 type-2 diabetes, 43 non-diabetes) aged ≥18 years with blood glucose of > 6.1 mmol/L enrolled in a randomized controlled trial comparing intensive insulin therapy with conventional insulin therapy. sRAGE and its ligand HMGB-1 together with IL-6, and soluble thrombomodulin (as markers of inflammation and endothelial cell injury, respectively) were evaluated in ICU, at Days 1, 3, 5 and 7. Plasma samples from 18 healthy subjects were used as controls. Both diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble thrombomodulin levels at the time of admission to ICU. Plasma IL-6 concentration was only increased in non-diabetic patients. Plasma levels of sRAGE were higher in diabetic compared with non-diabetic patients. Intensive insulin therapy resulted in a significant decrease of sRAGE and thrombomodulin at Day 7, in diabetic but not in non-diabetic patients. Circulating sRAGE levels correlated positively with IL-6 and soluble thrombomodulin levels and inversely with HMGB-1. Multivariate regression analysis demonstrated that sRAGE remains independently correlated with HMGB-1 only in diabetic patients. Neither sRAGE nor any inflammatory markers are associated with mortality. These findings support the hypothesis that sRAGE release, time-course and response to intensive insulin therapy differ between hyperglycemic diabetic and non-diabetic critically ill patients. Whether this difference underlies the dissimilarity in clinical outcome of hyperglycemia in these two conditions warrants further studies.
登录
查看更多内容
影响因子：
9.6
作者：
Briot R;Frank JA;Uchida T;Lee JW;Calfee CS;Matthay MA
通讯作者：
Matthay MA
影响因子：
3.1
作者：
Nakamura, K;Yamagishi, S;Imaizumi, T
通讯作者：
Imaizumi, T
影响因子：
8.8
作者：
Egi, Moritoki;Bellomo, Rinaldo;Bailey, Michael
通讯作者：
Bailey, Michael
影响因子：
2.2
作者：
Bopp, Christian;Hofer, Stefan;Weigand, Markus A.
通讯作者：
Weigand, Markus A.
影响因子：
10
作者：
Calfee, C. S.;Ware, L. B.;Matthay, M. A.
通讯作者：
Matthay, M. A.