sRAGE in diabetic and non-diabetic critically ill patients effects of intensive insulin therapy 英文参考文献.docVIP

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sRAGE in diabetic and non-diabetic critically ill patients effects of intensive insulin therapy 英文参考文献.doc

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sRAGE in diabetic and non-diabetic critically ill patients effects of intensive insulin therapy 英文参考文献

Arabietal.CriticalCare2011,15:R203 /content/15/4/R203 RESEARCH OpenAccess sRAGEindiabeticandnon-diabeticcriticallyill patients:effectsofintensiveinsulintherapy YaseenMArabi1,2*,MohammedDehbi3,AsgarHRishu2,EnginBaturcam3,SalimHKahoul2,RietteJBrits2, BrinthaNaidu2andAbderrezakBouchama2,4 Abstract Introduction:Hyperglycemiarepresentsanindependentprognosticfactorincriticallyillnon-diabeticpatientsbut notinthosewithdiabetes.Inthiscontext,thereisanongoingdebateonthebenefitofanintensiveinsulin therapy,particularlyindiabeticpatients.Wetestedthehypothesisthatexpressionofthereceptorforadvanced glycationend-products(RAGE),animportantsignaltransductionreceptorthatelicitslong-lastingnuclearfactor kappaB(NF-B)activation,mayunderliethisdifference.RAGEexpressionisregulatedbymultipleligands, includinghighmobilitygroupbox-1(HMGB-1),andisreflectedbyitsreleasedsolubleform(sRAGE). Methods:Apredesignedanalysiswasconductedofprospectivelycollectedsamplesfrom76hyperglycemic criticallyillpatients(33type-2diabetes,43non-diabetes)aged≥18yearswithbloodglucoseof6.1mmol/L enrolledinarandomizedcontrolledtrialcomparingintensiveinsulintherapywithconventionalinsulintherapy. sRAGEanditsligandHMGB-1togetherwithIL-6,andsolublethrombomodulin(asmarkersofinflammationand endothelialcellinjury,respectively)wereevaluatedinICU,atDays1,3,5and7.Plasmasamplesfrom18healthy subjectswereusedascontrols. Results:Bothdiabeticandnon-diabetichyperglycemicpatientsshowedincreasedplasmasRAGE,HMGB-1and solublethrombomodulinlevelsatthetimeofadmissiontoICU.PlasmaIL-6concentrationwasonlyincreasedin non-diabeticpatients.PlasmalevelsofsRAGEwerehigherindiabeticcomparedwithnon-diabeticpatients. IntensiveinsulintherapyresultedinasignificantdecreaseofsRAGEandthrombomodulinatDay7,indiabeticbut notinnon-diabeticpatients.CirculatingsRAGElevelscorrelatedpositivelywithIL-6andsolublethrombomodulin levelsandinverselywithHMGB-1.MultivariateregressionanalysisdemonstratedthatsRAGEremainsindependently correlatedwithHMGB-1onlyindiabeticpatien