srage in diabetic and non-diabetic critically ill patients effects of intensive insulin therapysrage在糖尿病和非糖尿病危重患者强化胰岛素治疗的影响.pdf

Arabi et al. Critical Care 2011, 15:R203 /content/15/4/R203 RESEARCH Open Access sRAGE in diabetic and non-diabetic critically ill patients: effects of intensive insulin therapy 1,2* 3 2 3 2 2 Yaseen M Arabi , Mohammed Dehbi , Asgar H Rishu , Engin Baturcam , Salim H Kahoul , Riette J Brits , Brintha Naidu2 and Abderrezak Bouchama2,4 Abstract Introduction: 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-B) 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). Methods: 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. Results: Both diabetic and non-diabetic hyperglycemic patients showed increased plasma sRAGE, HMGB-1 and soluble throm