AustralianDiabetesSociety GuidelinesforRoutineGlucoseControlinHospital 2012

Contents
Introduction Section1MethodologyandProcess Page3 Page5

Section2Whatglucosetargetshouldbeaimedforinacutemyocardialinfarction? Page6 Section3Whatglucosetargetshouldbeaimedforinacutestroke? Section4Whatareappropriateglucosetargetsforpatientsingeneralhospital wards? Section5Whatspecialmeasuresneedtobeundertakenforpeopleonenteralor parenteralnutrition? Section6Howissteroidinducedhyperglycaemiabestmanaged? Section7Whatistheoptimalmeansofachievingandmaintainingglycaemic controlinhospitalisedpatientswhoarenotcriticallyill?? Section8Howshouldpatientsoninsulinpumptherapybemanagedinhospital? Section9Whatisappropriateglucosecontrolinendoflifesituations? Section10Atwhatlevelishyperglycaemiainhospitalpredictiveofdiabetesand howshouldpatientswithnewlydiscoveredhyperglycaemiabefollowed up? Section11Whatistheroleofaspecialistdiabetesinpatientteam? Section12Whatroutinemeasuresshouldbeundertakenforpeoplewith diabetesadmittedtohospital? Appendices Contributors Glossary References Page8 Page9

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Introduction
Diabetesisestimatedtoaffect7.4%oftheAustralianpopulation1,andisincreasingannuallyby0.8%2.People withdiabeteshaveahigherutilisationofbothprimaryandtertiaryhealthservices.In200405,9%ofall hospitaladmissionswererecordedashavingdiabetes3.Thisislikelytobeanunderestimateasclinicalaudits fromAustraliaandoverseashavefoundhospitalratesofdiabetesof1125%49andfurthermore,manycases areundiagnosedatthetime10.Australiandataindicatethattheproportionofpeoplewithdiabetesasa diagnosisinhospitalhasbeenincreasing,witha35%increaseinnumbersbetween200001and2004053. Theyalsohavelongerlengthsofhospitalstay,beingabout2dayslongerthanpeoplewithoutdiabetes3,9.The AustralianInstituteofHealthandWelfarehasestimatedthecostofdiabetestohospitalservicesin200405 was$371M3. Diabetesandhyperglycaemiahasbeenshowninanumberofobservationalstudiestobeassociatedwith pooreroutcomesandaremarkersofmorbidityandmortality.Reasonsfortheincreasedmorbidityand mortalitymayberelatedtopoorimmuneresponse,delayedhealing,inflammationandthrombosisassociated withhyperglycaemiaaswellasahigherrateofcomorbidconditionsinthispatientgroup11. Independentofdiabetes,hyperglycaemiaperseisalsoassociatedwithworsehospitaloutcomes.Thisisthe casewhetherthepersonhasdiabetesornot,buttherelationshipisstrongerforpeoplewhodonothave diabetes.Therelationshipbetweenhyperglycaemiaandadversehospitaloutcomes,inparticularmortality, hasbeenclearlydemonstratedinmanydifferenthospitalsettings,includingmyocardialinfarction,stroke, generalmedicalandsurgicalwards,trauma,cardiothoracicsurgery,TPN,intensivecare,andemergency admissions.Forhyperglycaemicpeoplewhoarenotknowntohavediabetes,itisunclearifthehigher mortalityisduetothehyperglycaemia,orifthehyperglycaemiaisbutamarkerofunderlyingcriticalillness. Mostofthehighqualitystudiesdemonstratingbenefitoftightglycaemiccontrolhavecomefromcriticalcare situations,andeventhesehaveproducedconflictingresults. Forpatientswithhyperglycaemiathatisnewlydiscoveredinhospital,thereisahighprobabilityof undiagnoseddiabetes,orfuturediabetes.However,atpresentfollowupisoftenhaphazard,andthe opportunityforearlydiagnosisandtreatmentofdiabetesandtherebypreventionofacuteandlongterm complicationsmaybemissed. Theaimofthisdocumentistoprovideguidanceforthemanagementofhyperglycaemiainarangeofhospital situations.TheADShasfocusedonthemanagementofhyperglycaemiainpatientswithmyocardialinfarction andstroke,ongeneralhospitalwards,receivingenteralandparenteralnutrition,withsteroidinducedor exacerbatedhyperglycaemia,andinendoflifesituations.Theoptimalmeansofachievingtightcontrol,the roleofthespecialistinpatientdiabetesteam,inpatientmanagementofinsulinpumptherapy,andgeneral measuresfordiabetesmanagementhavealsobeenexamined.Wealsoprovideguidanceforthefollowupof patientswithnewlydiscoveredhyperglycaemia.Therecommendationswerebasedonevidenceobtained fromsystematicreviewswheretrialshadbeenperformed;otherwisetheyweremadebyconsensus.
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Itisnottheintentionoftheseguidelinestodealwithscreeningfordiabetes,themanagementofdiabetic emergenciessuchasdiabeticketoacidosis,hyperglycaemichyperosmolarstate,andhypoglycaemia,nordo theycoverpaediatrics,obstetricsorintensivecare.Otherwisetheyshouldprovideguidanceforthe managementofpatientswithhyperglycaemiainthemajorityofhospitalwards,andarecomplementarytothe AustralianDiabetesSocietyPerioperativeDiabetesManagementGuidelines. Wesoughttoachieveconcordanceinourrecommendationtoasingletargetglucoselevelforthemajorityof clinicalsituations,althoughtherearesomedifferencesinthelimiteddatafordifferentscenarios.Theoverall recommendationisthatformosthospitalpatientswithhyperglycaemia,treatmentshouldbeinstitutedto achieveandmaintainbloodglucose(BG)levelsbelow10mmol/L,butbecauseofthepotentialdangersof hypoglycaemia,treatmentshouldnotaimtolowerglucoselevelsbelow5mmol/L.

Section1: MethodologyandProcess
Systematicreviewswereconductedtoprovidethebestpossibleevidencebasefortherecommendations. PICOsearchesoftheCochraneDatabaseforSystematicReviews,andPubmedClinicalQuerieswere undertaken.Systematicreviews,metaanalysesandexistingguidelinesrelatingtoourquestionswere reviewedbyamemberoftheWritingGroup,andsummarised(Appendix1).Keycitedarticleswerealso reviewed.Wheresystematicreviewswerenotavailable,generalsearchesoftheliteraturewereundertaken. TheevidencewasdiscussedinanADSworkshopcomprisinganexpertpanelofEndocrinologistsandDiabetes Educators,heldinJuly2011.Atthisworkshop,recommendationsforeachsectionoftheguidelines,and overallrecommendationswereagreedupon.Wheretherewaslittleornoevidence,thenthecommittee reliedonexperience,judgmentandconsensustomaketheirrecommendations.Issuesarisingfromthe discussion,forwhichthereisnoevidencebase,areincludedaspracticepoints.TheWritingGroupdraftedthis document,whichwascirculatedforfurtherfeedbackfromtheparticipantsoftheWorkshop,andotherswho wereunabletoattend.

Section2: WhatGlucoseTargetShouldbeAimedforinAcuteMyocardialInfarction?
HyperglycaemiaandCardiacMortality Hyperglycaemiaiscommonwithmyocardialinfarction.Datafromnumerousobservationalstudiesshowa clearandconsistentassociationbetweentheinitialadmissionglucoselevelandinfarctoutcomes,inparticular mortality.AmetaanalysisbyCapesetal12showedthatamongstpatientswithoutdiabetes,thosewithan admissionbloodglucoselevel(BGL)6.18.0mmol/Lhada3.9fold(95%CI2.95.4)higherriskofdeaththan thosewithlowerBGL.Forpatientswithdiabetes,thosewithaBGL1011.0mmol/Lhada1.7fold(95%CI1.2 2.4)increasedriskofdeath.Themajorityofstudiesinthispublicationwereperformedintheprethrombolytic era,butnewerpublicationsshowsimilarresults(Appendix2,Table2.1).Virtuallyallhaveshownadose relationshipandaglucosethresholdforincreasedmortalityofaround68mmol/L.Inaddition,thereare observationaldatademonstratingarelationshipbetweenglucoselevelsinthefirst24hoursaftermyocardial infarctionandmortality(Appendix2,table2.2).Theseindicatethatpersistenthyperglycaemia,evenifmild,is alsoassociatedwithincreasedmortalityfollowingmyocardialinfarction. Hypoglycaemia Moststudieshaveconcentratedontherelationshipbetweenhyperglycaemiaandincreasedmortality.There arealsosomedatathathypoglycaemiaisassociatedwithadverseoutcomes,withaUshapedrelationship beingdescribedinseveralobservationalstudies15,23,25.Theincreasedriskwasseeninpatientswithadmission BGLsrangingfrom<3.3to<7mmol/L.IntheDIGAMIStudywheretherewasactiveloweringofglucose,there wasnoincreaseinmortalityorothermajoroutcomesamongstsubjectswhodevelopedhypoglycaemia<3 mmol/L,afteradjustmentforconfoundingvariables31. ClinicalTrialDataandExistingRecommendations Fivesystematicreviewswithspecificanalysis(insomecasessubanalysis)ofwhethertightglucosecontrolin myocardialinfarctionimprovessurvivalwereidentified3236.Oneoldersystematicreviewwhichpredateda numberofthemorerecenttrialswithnegativeresults,foundareductioninmortalitywithtightglucose control32.Amorerecentreviewsuggestedthattightglycaemiccontrolcanreducemortalitybutdidnotmake thisconclusiononthebasisofametaanalysis35,whilstanotheronedecidedthattheevidenceis inconclusive34.Tworecenthighqualitysystematicreviewsconcludedthattightglycaemiccontroldidnot reducemortality33,36,butoneincludedcardiacconditionsotherthanmyocardialinfarction. Fouroftherandomisedcontrolledstudiesidentifiedinthesystematicreviewshadsetspecificglucosetargets fortheirintervention(Appendix2,Table2.4)28,31,44,48.Therewasimprovementinsurvivalintheintensive treatmentarmonlyintheoldestofthesestudies,wheretheglucosetargetwas710mmol/L31.Ithasbeen postulatedthatthefailuretodemonstrateaneffectinthemorerecentstudiesmaybeduetoi)failureto
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achievealargeenoughdifferentialinglucoselevelsbetweenthearmsofthestudy,ii)glucoselevelsinthe controlarmbeingonlyminimallyelevated,iii)theadventofmoderntreatmentsforAMI(PTCA,thrombolysis, antiplatelettherapy,betablockade,statintherapy),overwhelminganybenefitofglucosecontrol53. Existingguidelinescoveringglucosecontrolinmyocardialinfarctionhavegivendiverserecommendations (Appendix2,Table2.5)5457.Twoofthe4guidelinesdidnothavespecificrecommendationsformyocardial infarction,butencompassedmyocardialinfarctionwithinbroaderguidelinesforhospitalglucosecontrol55,57. TwooftheguidelinesrecommendedtargetBGs<10mmol/L55,56,onerecommendednormallevels54,and onerecommendedagainsttightcontrol57. Conclusions Observationaldataindicateaclearassociationbetweenhyperglycaemiaandmortalityinmyocardial infarction.However,onlyoneRCTofpatientswithmyocardialinfarctionhasshownabenefitofglycaemic control,withaglucosetargetof710mmol/L.Intheotherstudies,nomortalitybenefitoftightcontrolwas seen.Despitethis,mostprofessionalorganizationshaverecommendedaglucosetargetof<10mmol/L, providedthatthiscanbeachievedsafely. RecommendationsandPracticePoints 1. Patientsadmittedtohospitalwithmyocardialinfarctionwhohavehyperglycaemia,shouldbetreated toachieveandmaintainglucoselevelslessthan10mmol/L. 2. Hypoglycaemiamustbeavoided.Itwouldbeprudenttoavoidtreatmentwhichlowerstheglucose below5mmol/L. 3. Insulininfusiontherapymayallowfortightertargetsbutthisrequiresfrequentmonitoringandhigh levelstafftraining.

Section3: WhatGlucoseTargetShouldbeAimedforinAcuteStroke
HyperglycaemiaandStrokeMortality Datafromnumerousobservationalstudiesshowanassociationbetweeninitialglucoselevelsandoutcomesof stroke,inparticularmortality.AnothermetaanalysisbyCapesetalshowedthatamongstpatientswithout diabetes,thosewithanadmissionBGL6.18.0mmol/Lhada3.07fold(95%CI2.503.79)higherriskofdeath thanthosewithlowerBGL58.Therewasnoincreaseinriskamongstpatientswithdiabetesattheselevels(RR 1.3,95%CI0.493.43)increasedriskofdeath.Mortalityfromhaemorrhagicstrokemortalitywasnot associatedwithadmissionhyperglycaemia.Morerecentpublicationsshowsimilarresults(Appendix3,Table 3.1).Observationaldataalsoindicatethatthereisarelationshipbetweenglucoselevelsduringthefirst24 hoursafterstrokeandmortalityorinfarctsize(Appendix3,Table3.2). ClinicalTrialDataandExistingRecommendations The3systematicreviewsexaminingstudiesoftightglucosecontrolinstrokecametodivergentconclusions (Appendix3,Table3.3)36,75,76.Althoughnoneofthestudiesrevieweddemonstratedabenefitofglucose control,onereviewrecommendedinsulintherapyifglucoselevelsexceed10mmol/L75.Therewere7 randomisedcontrolledtrialsoftightglycaemiccontrolforstroke.Onehadalargesamplesizebutwas discontinuedearlyduetoslowrecruitmentandfailedtodemonstrateabenefitofglucosecontrol78.Mostof theothertrialsweremoreofapilotnature(Appendix3,Table3.4).AnadditionalrecentAustralianstudy wheretherewasaglucosecontroltargetof48demonstrateda16%reductioninmortalitywiththe interventionarm85.Howeverglucosecontrolwasonlyoneof3factorsintheinterventionpackage(theothers beingmanagementofswallowingandfever),anditisdifficulttodeterminethecontributionofglucosecontrol totheoutcome.Thisstudyhadnotbeenincludedinanyoftheabovesystematicreviews. Twosetsofstrokeguidelineswhichprovidedsomerecommendationsregardingglucosecontrolwere identified(Appendix3,Table3.4).BothsuggestedaimingtokeepBGsbelowalevelaround10mmol/L,but admitthattheevidenceforthisisweak. Conclusions Observationaldataindicateaclearassociationbetweenhyperglycaemiaandmortalityinacutethrombotic stroke.Thereisalackofclinicaltrialevidenceregardingappropriateglucosetargetsinstroke,andthe recommendationismadeonthebasisofextrapolationfromotherclinicalsituations,andconsensus. RecommendationsandPracticePoints 1. Patientsadmittedtohospitalwithacutethromboticstrokewhohavehyperglycaemia,shouldbe treatedtoachieveandmaintainglucoselevelslessthan10mmol/L. 2. Hypoglycaemiamustbeavoided,andthereforeitwouldbeprudenttoavoidtreatmentwhichlowers theglucosebelow5mmol/L.

Section4: WhatareAppropriateGlucoseTargetsforPatientsinGeneralHospitalWards?
HyperglycaemiaandComplicationsinGeneralHospitalWards Anumberofobservationalstudieshavedemonstratedanassociationbetweenglucoselevelsandadverse outcomesinpatientsingeneralhospitalwards.Thesehaveshownahigherriskofadverseoutcomesabovea randomglucoselevelof812.2mmol/L(Appendix4,Table4.1).Theadverseoutcomesincludeinfection, mortality,andlongerlengthofstay.Thereisalsoadoserelationshipbetweenglucoselevelsandmortality9193. Therelationshipbetweenhyperglycaemiaandmortalityinthegeneralwardsismuchstrongeramongthose withnewlydiscoveredhyperglycaemiathanamongthosewithknowndiabetes. SystematicReviewsandExistingGuidelines Threesystematicreviewshaveexaminedclinicaltrialsoftightglycaemiccontroloutsideoftheintensivecare situation,andnotspecificallyfocusingonmyocardialinfarctionorstroke(Appendix4,Table4.2).Moststudies includedinthesereviewswereintheperioperativecontext,orincludedsubjectswithmyocardialinfarction. Thefindingshavebeenmixed,withonereviewfindingareductioninmortalitywithtightglycaemiccontrol withcardiacsurgery94,onefindingnobenefitinthenonICUorperioperativesettings36,andathirdfindinga reductionininfectionrateonly95.Thereisarecentstudyingeneralsurgicalpatientswhichfoundthattreating toapremealglucosetargetof<7.8mmol/Lwithbasal,bolusandsupplementalinsulinresultedinbetter glycaemiccontrolandfewerwoundinfectionsandtotalcomplicationsthanusingslidingscaleinsulinwiththe sametarget104.Howeverthisstudywasdesignedtocomparethe2insulinregimes,ratherthantheeffectof treatingtotheirtarget.Notrialshaveastheirprimaryobjective,examinedtheeffectoftreatingtospecific glucosetargetsingeneralmedicalwards. Threeexistingguidelinesforglucosecontrolinnoncriticallyillhospitalpatientshaverecommendedglucose levelsbelow10mmol/L(Appendix4,Table4.3)55,105,107.Afourthguidelinemaintainsthatthereisnoevidence forstrictcontrolinnonICUpatients106.TheAmericanAssociationofClinicalEndocrinologists/American DiabetesAssociationandEndocrineSocietyofAmericaguidelinesalsorecommendpremealglucoselevelsof 3.97.8mmol/L,withoutgivingtherationalefordifferentpremealandrandomglucosetargets55,107.The caveatthattheseshouldonlybethetargetsiftheycanbesafelyachievedhasalsobeenstated. Conclusions Astheevidenceislimited,ourrecommendationsarebasedonexistingguidelinesandextrapolationsfrom otherclinicalsituations.Havingthesameglucosetargetsasformyocardialinfarctionandstrokewas consideredimportantforuniformityacrossthehospital,andtoavoidconfusion.Althoughonewouldnot regardglucoselevelsasbeinginthehypoglycaemicrangeuntiltheyarebelow4mmol/L,activeintervention
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shouldnotaimtoreducetheglucoselevelsbelow5mmol/L,whichallowsforanaddedmarginofsafety.If aimingfortightglycaemiccontrol,frequentglucosetestingisrequired. RecommendationsandPracticePoints 1. Mostpatientsingeneralhospitalwardswithhyperglycaemiashouldbetreatedtoachieveand maintainglucoselevelslessthan10mmol/L. 2. Hypoglycaemiamustbeavoided.Itwouldbeprudenttoavoidtreatmentwhichlowerstheglucose below5mmol/L. 3. Toachievetightglucosecontrolsafely,frequentglucosemonitoringisrecommended

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Section5: WhatSpecialMeasuresNeedtobeUndertakenforPeopleonEnteralor ParenteralNutrition?

HyperglycaemiaandEnteralandParenteralFeeding Hyperglycaemiaisacommonoccurrenceinpatientsreceivingnutritionalsupporteitherintheformofenteral orparenteralnutrition.Thespecificeffectofhyperglycaemiaonclinicaloutcomesinpatientsreceiving nutritionsupporthasonlybeenreportedbyoneobservationalstudy.Aretrospectivestudyof111patients receivingtotalparenteralnutrition(TPN)foundthatincreasedbloodglucoselevelswereassociatedwithan increasedriskofcardiaccomplications,infection,sepsis,acuterenalfailureanddeath91.ThosereceivingTPN withmeanglucoselevels>9.1mmol/lhada10foldgreaterriskofmortalitythanthosewithmeanglucose levels6.9mmol/l.Thisassociationwasindependentofage,sexandpresenceofpreexistingdiabetes.This addsfurtherweighttotheoverwhelmingevidenceofaclearrelationshipbetweenhighbloodglucoselevels andadverseoutcomesincriticallyillorhospitalisedpatients,asreviewedintheearliersectionsofthis guideline. Amajorgoalinthemanagementofpatientswithdiabetesreceivingnutritionalsupportistheachievementof goodglycaemiccontrol,avoidingbothhyperglycaemiaandhypoglycaemia,withtheirassociatedrisksoffluid imbalanceanddehydration,ketoacidosisandhyperosmolarcoma,infectionandneurologicalevents. However,howbesttoachievegoodglycaemiccontrolinthesepatientsremainsunclear.Acriticalfactorfor considerationiswherethepatientwillbecaredfor:intheICUorgeneralward.Otherimportant considerationsincludethemethodofnutritionaltherapy(enteralvsparenteral)andcompositionofthefeeds particularlycarbohydrate/dextrosecontent.Ingeneral,diabeticenteralformulas(lowcarbohydratehigh monounsaturatedfattyacidformulas)arepreferabletostandardhighcarbohydrateformulasinpatientswith diabetes107.ClosemonitoringofBGLsandreviewofdiabetesmanagementisessentialwhen enteral/parenteralfeedsceaseandoralintakeresumes. ClinicalTrials Nostudiesinvestigatingtheeffectsoforalglucoseloweringagentsonbloodglucoselevelsandoutcomesin patientsreceivingenteralorparenteralnutritionwereidentified.Thereare2studies,bothofpoorqualityand athighriskofbias,whichhaveinvestigatedtheeffectsofdifferentinsulinregimensinpatientsreceiving enteralnutrition(Appendix5,Table5.1),butnoneinthesituationofparenteralnutrition.Onecomparedthe effectsofslidingscaleinsulintoslidingscaleinsulinandregularsubcutaneousglargineinsulin,showingno differencesinbloodglucoselevels,adverseoutcomesorlengthofstay108.However,asignificantproportionof thepatientsintheslidingscalealonegroupalsoreceivedNPHinsulinduringfollowup.Thissuggeststhata basalinsulinontopofacorrectionalinsulinregimen,hasaroleinachievingadequateglycaemiccontrolin patientsreceivingenteralnutrition.Asecond(nonrandomized)pilotstudywitharetrospectivecontrolgroup foundthatabasalbolusinsulinprotocolachievedlowermeanglucoselevelsthanavariabledosepreprandial
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insulinregime,attheexpenseofasmallincreaseinhypoglycaemia109.Thenurseledinsulinprotocolwas implementedintheICUsettingwhichlimitsitsgeneralisability. Conclusions Onthebalanceofthelimitedevidence,insulintherapyislikelytobethemosteffectiveagentforimmediate controlofbloodglucoselevelsinpatientsreceivingenteralandparenteralnutritionalsupport.The recommendationsmadearebasedonexperienceandconsensus. RecommendationsandPracticePoints 1. Individualisednutritionalplansshouldbeprovidedasinsulintherapywilldependonthenatureofthe feedingcycle. 2. Slidingscaleinsulinshouldnotbeusedalonetooptimizeglucosecontrolinpatientsreceivingenteral orparenteralnutrition. 3. Insulintherapyshouldincluderegularbasalinsulin(intermediateorlongactinginsulin)withprandial andcorrectionalinsulinifrequired. 4. PerformBGtesting46hourly.WithbolusenteralorparenteralnutritionperformBGtestingbefore eachbolusisgiven. 6. Patientswithunstablemetaboliccontrolorvariableparenteralfeedingmaybenefitfroman intravenousinsulininfusiontherapy. 7. Closeliaisonwiththedietitianorteammanagingtheenteralorparenteralnutritioniscritical particularlyifcalorieintakeischanging,asinsulindoseswillneedtobeadjusted.

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Section6: HowisSteroidInducedHyperglycaemiaBestManaged?
Prevalenceandriskfactors Hyperglycaemia is common amongst inpatients who are receiving glucocorticoids (GC), with reported incidences of 6471%110,111. Risk factors for development of hyperglycaemia amongst inpatients include a pre existing diagnosis of diabetes110,112, higher HbA1c113, increasing age111, steroid dose114, and family history of diabetes115,116. There is little data on temporal BG profile of individuals receiving GC. An open prospective observational trial performed on acute hospital wards examined the interstitial glucose profiles of pts admitted with COPD treated with at least prednisone 20mg/day as compared to pts with COPD, not known to have diabetes, admitted for another indication who did not receive GC117. Patients receiving GC in the morning had higher BGLs in the afternoon and evening, as compared to those not receiving GCs (with the greatest elevation seen in those with known diabetes). A rise in fasting glucose is also seen when extremely high dose GC (e.g. methylprednisone 2501000mg/day) are administered113. Based on ambulatory data, the effect of GC on BG profile is rapid, with a change seen within 23 hours of administration of GC118,119. This is also rapidly reversible,inthatlowerglucoselevelsareseenonGCfreedaysinpatientswhoreceivealternatedayGC120. ScreeningfordevelopmentofhyperglycaemiaandmonitoringinthosewithDM Prior to or upon the initiation of GC, it is prudent to exclude the presence of undiagnosed diabetes through measurement of serum glucose (see section 11). Screening for development of steroidinduced hyperglycaemia by afternoon fingerprick BG assessment is likely to detect the development of most cases of hyperglycaemia112, and twice daily GC induced hyperglycaemia should still be detected. Reliance on fasting glucose is inadequate. If hyperglycaemia is detected, BG monitoring should occur as per the general diabetes protocol. Managementofglucocorticoidinducedhyperglycaemia There are no prospective trials on the use of any antidiabetic medication for the management of GC related hyperglycaemia. The limited observational data are outlined in Appendix 6, Table 6.2. Sulphonylureas have a limited role in the treatment of steroidinduced hyperglycaemia in hospital. There are reports of thiazolidinedione use in the setting of organ transplantation, but these agents are also unsuitable for most patients in hospital. The management of new onset diabetes after transplantation has been addressed in otherguidelines140andwillnotbefurtherdiscussedinthisdocument. Although therearenotrials of itsuse insteroidinduced hyperglycaemia, insulin is considered to be the agent of choice for the management of steroidinduced hyperglycaemia in hospital. Benefits provided by insulin include greater dose flexibility, more rapid onset of action and titration and that there is usually no dose ceiling as compared to other glucose lowering agents. Insulin dose requirements will always need to be individualised,andrequirepreemptivetitrationastheGCdoseisadjusted,usuallyonadailybasis.Theinsulin
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regimen should predominantly target postprandial control, and with morning GC administration, the afternoon hyperglycaemia. The use of isophane insulin for management of steroidinduced hyperglycaemia hasbeenadvocated,withtheinitialdosedeterminedaccordingtoGCdoseandpatientweight124,139.Isophane typeinsulincan be supplementedwith ultraquickinsulin analoguewithmeals139.With twice,thrice or 4times a day GC regimens, isophane insulin twice daily with prandial rapid acting analogue can be initiated. A regime that controlled glycaemia on previous occasions can be reinitiated, e.g. when cyclical GCs are required, as longastherehasbeennomajorintervalchangeinweightorrenalfunction.Forthosewithpreexistinginsulin requiring diabetes, a preemptive increase in insulin will be required, and further adjustment based on blood glucoseresponse. RecommendationsandPracticePoints 1. In patients receiving glucocorticoids, undiagnosed diabetes should beexcluded. Those free ofdiabetes should be screened for the development of hyperglycaemia by random blood glucose monitoring performedintheafternoonfollowingmorningadministrationofGC. 2. Hyperglycaemia is best managed with insulin: basal insulin as isophane type insulin, and rapid acting analoguewithmealsasrequired. 3. In individuals already on insulin the likely need for increased insulin should be recognised. Dose requirementsneedtobeindividualisedandrequiredailyreview.

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Section7: WhatistheOptimalMeansofAchievingandMaintainingGlycaemicControlin HospitalisedPatientswhoarenotCriticallyIll?

Thissectionexaminestheoptimalmethodsforachievingandmaintaininggoodroutineglycaemiccontrolin hospital.Itdoesnotdiscusstheuseofinsulininfusiontherapy,orperioperativemanagement.Forthelatter, wereferthereadertotheAustralianDiabetesSocietyPerioperativeDiabetesManagementGuidelines141. Thereisapaucityofdatainthenoncriticallyillpatientgroupastothebestmethodofmaintainingglycaemic control.Thisgroupofpatientsdiffersgreatlyfromthosecriticallyillastheyareofteneating.Intensiveinsulin therapyhasbeenshowntobebeneficialinacriticallyillpatientpopulation,buttherehavebeennostudies evaluatingoutcomesingeneralmedicalwards.Themainadverseeventwithintensivesubcutaneousinsulin therapyishypoglycaemiawhichcanbequitesevere. Intensiveinsulintherapyrequiresfrequentmonitoringandshouldnotjustbereactivetochangesinglucose loads,e.g.food.Itsapplicationrequiresaspecificskillsetforstafftomaintain.Traditionallyslidingscaleshave beenusedtomaintainbloodglucoselevelsinnoncriticalhospitalizedpatients.Thismethodofinjectingaset doseofinsulinatsettimesisoftenreactivetohighlevelsofbloodglucose.BGsoftenfluctuatefromhighto low,whichcanpotentiallybedetrimental.Slidingscaleadministrationofinsulinisnotrecommended,and Americanguidelinesrecommendthataninsulinregimenwithbasal,nutritionalandsupplemental(correction) componentsbeutilizedforhospitalisedpatientswithdiabetesorstresshyperglycaemia142. Therearefewstudiesthathaveexamineddifferentsubcutaneousinsulinregimensinnoncriticalhospitalised patients(Appendix7).Moststudieshavemoderatetohighriskofbiasandoutcomemeasureshavebeen inconsistentbetweenthedifferentstudies.Basalbolusregimenshavebeenshowntobesuperiortosliding scaleregimensforglucosecontrol102,104,andslidingscaleinsulinalonehasbeennomoreeffectivethan continuationofthepatientsusualdiabetesmedication101.Effectiveuseofbasalbolusinsulinrequires frequentandregularbloodglucosemonitoring(atleast4andpreferably68timesdaily).Basedonclinical expertise,currentpracticesandthelimitedliterature,thefollowingconsensusrecommendationsweremade. RecommendationsandPracticePoints 1. Slidingscaleinsulinshouldnotbeusedtooptimiseglucosecontrolintheinpatientgeneralmedicalor surgicalsetting. 2. Oralhypoglycaemicagentsorpremixedinsulincanbeusedincertainstablehospitalisedpatientswho areeatingregularly.Supplementalinsulinshouldbewrittenupinaddition. 3. Insulintherapyinhospitalisedpatientsshouldotherwiseconsistofabasalinsulin,prandialand supplementalinsulin.

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Section8: HowShouldPatientsonInsulinPumpTherapybeManagedinHospital?
ContinuousSubcutaneousInsulinInfusionTherapyinHospital Continuoussubcutaneousinsulininfusion(CSII)orinsulinpumptherapyisusedinthemanagementofgrowing numbers of patients with Type 1 diabetes in Australia. Anecdotal reports suggest that patients established on CSII usually prefer to continue on their pumps during hospital admissions. Hospital health care providers will increasinglybefacedwiththeissueofhowtomanagesuchinpatients.Anumberofpublicationshavedetailed guidelines regarding inpatient management of patients previously established on CSII144147. Whilst there are no data from randomised trials available, observational reports indicate that patients admitted to hospital continued on CSII who are managed with bestpractice consensus protocols fare at least as well as those changedover to subcutaneous insulin injections andmanaged bytheendocrinology team. Thedataregarding hypoglycaemia is conflicting with one study indicating a lower incidence in those inpatients continued on CSII which was not confirmed with a subsequent study148,149. A caveat is that these reports have stemmed from tertiary academic medical centres in the United States and their applicability to a spectrum of hospitals (including community hospitals) in Australia is yet to be determined. The recommendations below are based uponaconsensusopinion. ManagementofCSIIinHospital General recommendations for CSII therapy in hospital are outlined in Appendix 8, Table 8.1. In appropriate circumstances, CSII may be the preferred method of insulin delivery. However, device operating menus and programs vary not only according to the manufacturer but also from model to model. It is highly unlikely that nonspecialised medical and nursing staff will be familiar with the operation of all available devices. We therefore recommend that CSII therapy is be continued in hospital only in those situations where the patient (or guardian) has the ability to safely selfmanage their insulin dosing and the pump. The competency requirements are outlined inAppendix 8,Table 8.2. If these criteriaare not met CSII must be substituted with eitherasubcutaneousinsulinregimenoranintravenousinsulininfusion.ContraindicationstoCSIItherapyare listedinAppendix8,Table8.3.AllaspectsofCSIImanagementshouldbedocumented(Appendix8,Table8.4) anditisrecommendedthattheEndocrineteambeinvolved. CSIIandSurgery Surgery itself is not an absolute contraindication to continuation of CSII. If CSII is to be continued intra operatively this decision must be made in conjunction with the anaesthetist, surgeon/proceduralist, and endocrinology team with the documented consent of the patient or their guardian. CSII and an intravenous insulin infusion should not be used simultaneously for any extended period150. The situations appropriate for intraoperativeCSIIorforitssubstitutionwithanintravenousinsulininfusionareoutlinedinAppendix8,Table 8.5. When CSII is being used intraoperatively, it is important for there is a protocol for its management (Appendix 8, Table 8.6.). Appropriate overlap and timing is important when switching a patient from CSII to insulininfusionormultiplesubcutaneousinsulininjections,andviceversa(Table8.6.).
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 RecommendationsandPracticePoints 1. Ingeneral,CSIIshouldbecontinuedinhospitalwherethepatientcancompetentlyandsafelyself managethepumpandselfdosing. 2. Detailsofpumptherapyshouldbedocumented,andsupportedbytheendocrineteam 3. CSIImaybecontinuedforshortoperativeproceduresifthoseresponsibleforthepatients intraoperativecarearecomfortablewithitsuse.

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Section9: WhatisAppropriateGlucoseControlinEndofLifeSituations?
DiabetesandEndofLife For patients with diabetes and advanced disease limiting their life expectancy there is no body of evidence availableregardingtheimpactoftightglycaemiccontrolonoutcomes.Lifelimitingdiseaseincludes,butisnot limited to, cancer and includes any disease process such as advanced dementia, end stage cardiac and respiratory failure, which is incurable and significantly shortens the patients life expectancy. As the patient with diabetes approaches the end of their life the guidelines regarding glucose monitoring and glycaemic targets detailed earlier in this document may no longer be appropriate with a potential for discomfort, inconvenience and significant morbidity relating to hypoglycaemia. Tight glycaemic control is questionable benefit and the avoidance of longterm complications is no longer relevant. Conversely it is important to maintain a level of glycaemia to prevent hyperglycaemia associated thirst, dehydration, polyuria associated urinary frequency, altered conscious state and symptomatic hypoglycaemia. Treatment regimens need to be individualisedaccordingtothepatientscircumstances. Palliativecareisdefinedasmedicalorcomfortcarethatreducestheseverityofadiseaseorslowsitsprogress rather than providing a cure. Currow et al151 have described 4 phases in the end of life pathway: Stable, unstable, deteriorating, and terminal (see Appendix 9, Table 9.1 for details). Palliative patients may be admitted to hospital for management of an acute illness, either intercurrent or related to their primary underlying disorder or for terminal care. There is an absence of level I data though there are a number of valuableconsensusbasedguidelinesaddressingtheglobalmanagementofpalliativepatientswithdiabetes151 153 . The following represents a consensus of opinion in the absence of a suitable evidence base, and is in part based on the 2010 Guidelines for Managing Diabetes at the End of Life152. This consensus document focuses on the inpatient management of hyperglycaemia in those patients with diabetes deemed as requiring palliative care. As management should be individualised to each patients needs this document provides general principles for the inpatient management of palliative care patients with diabetes and detailed protocolscannotbeprovided. GlucoseManagementinEndofLifeSituations Glucose management during inpatient admissions will depend on the type of diabetes and the phase of the end of life pathway (see Appendix 9, Table 9.2 for details). In general, in the earlier stages of end of life, the persons usual diabetes medication would be continued, with adjustments based on the many situational factors which would affect glycaemic stability (Appendix 9, Table 9.3). The decision to simplify and rationalise treatment regimes and targets would need to be made on an individual basis. As the person progresses through the phases of end of life, the emphasis shifts towards maintenance of comfort, with corresponding reductionsinmedicationandglucosetesting,andsomeliberalisationoffoodrestriction.Thisdoesnotimplya nihilisticapproachinthemetabolicmanagementofpalliativepatients.Avoidanceofmarkedhyperglycaemiais still relevant, particularly in hospital, to avoid symptoms of hyperglycaemia, and improve wound healing and
18

resistance to infection. Hypoglycaemia must also be avoided. With type 1 diabetes, ketoacidosis is likely to precipitatedeath, so itshould be preventeduntil a decision is made to withdrawall treatmentin the terminal phase. Therefore until then, some glucose testing and insulin administration may remain necessary. It is reasonabletocontinueoninsulinpumptherapyinthosepatientsestablishedonthesedevices. The views of the patient and their family need to be determined. They may require advice and counseling regarding the management of the patients glucose levels as many years may have been spent where glucose levels have been diligently maintained in a target range. The realisation that longterm survival is no longer a viable proposition and that maintenance of tight glycaemic control is of dubious value and could even adversely impact quality of life can be confronting. Ultimately the decision of the patient and their family will take precedence. The status of the patient may be evolving continuously requiring the ongoing reassessment ofglycaemicmanagementstrategiesbythemedicalteam. RecommendationsandPracticePoints 1. Palliative care patients may still benefit from a level of glucose control in hospital so diabetes treatmentremainsrelevant. 2. The level of intervention would generally be less intensive than for other hospital patients, and needs tobeindividualised,dependingonthephaseofendoflife,andothersituationalfactors.

19

Section10: At What Level is Hyperglycaemia in Hospital Predictive of Diabetes and How ShouldPatientswithNewlyDiscoveredHyperglycaemiabeFollowedup?
StressHyperglycaemia Patientswithaknownhistoryofdiabetescommonlyhavehyperglycaemiainhospital,butpatientswithouta historyofdiabetesmayalsobefoundtohaveelevatedbloodglucoselevels.Hyperglycaemiainpatientsnot knowntohavediabetesmaybesecondarytostressortoundiagnoseddiabetes.Itisoftendifficultto distinguishthecauseofhyperglycaemiainashorthospitalstay. Stresshyperglycaemiamostcommonlyoccursinpatientswithacuteorcriticalillnessandismorelikelyto occurinamorecriticallyillpatient.Hyperglycaemiaispostulatedtobemediatedthroughcytokines,the sympatheticnervoussystemandthehypothalamicpituitaryadrenalaxis155.Itisnotclearwhetherpatients whomanifeststresshyperglycaemiahaveanunderlyingimpairmentintheirglucosemetabolism,butinthe longterm,inpatienthyperglycaemiamayheraldundiagnoseddiabetesorthedevelopmentofdiabetesinthe future.Theprevalenceofundiagnoseddiabetesvariesindifferentinpatientsettingsandcanbeupto60% (Appendix10,table10.1).Itisimportanttodiagnosepatientswithdiabetesearlytoensureappropriate management,bothlifestyleandmedicationtopreventthedevelopmentoflongtermcomplications. Thereislimitedliteraturetoguidethelevelofhyperglycaemiapredictiveofdiabetesortosuggestan appropriatealgorithmfordetectionofdiabetesintheacutehospitalsetting.TheAmericanAssociationof ClinicalEndocrinologists/AmericanDiabetesAssociationconsensusrecommendationsdefinesaBSL >7.8mmol/LasinpatienthyperglycaemiaandsuggestanHbA1cmayassistindiagnosisofdiabetes.HbA1c >6.5%(48mmol/mol)isstronglysuggestiveofunderlyingdiabetes55,160.However,thereisconsiderable heterogeneityamongststudieslookingatpredictorsofdiabetesininpatientpopulations(Appendix10,table 10.1).Differentglucosevalueshavebeenusedtodefinehyperglycaemia.HbA1clevelsusedtodefinea diagnosisofdiabetesandthepopulationsstudiedhavealsobeenquitevariable.WhilstHbA1chasnotbeen ratifiedforthegeneraldiagnosisofdiabetesinAustralia,thereisnodoubtthatforapatientwith hyperglycaemia,itisastrongindicatorofunderlyingdiabetes. Whilstinhospital,patientswithnewlydiagnoseddiabetesshouldbereferredtotheSpecialistDiabetes InpatientTeam(section12)ortheEndocrineTeamformanagement.Irrespectiveofwhetherdiabetesis definitivelydiagnosedinhospital,patientswithinpatienthyperglycaemiashouldreceivefollowuptoensure thatthediagnosisisclarified,andappropriatecounselingandmanagementinstituted.Notificationofthe generalpractitionerisvitaltothisprocess. Asuggestedalgorithmfortheapproachforthediagnosisandfollowupofaninpatientwithnewlydiscovered hyperglycaemiaisgiveninAppendix11,Figure11.1.
20

RecommendationsandPracticePoints 1. Allinpatientswithnewlydiscoveredhyperglycaemia(randomplasmaglucose>7.8mmol/L)should haveanHbA1cperformed. 2. Allinpatientswhoarenewlydiagnosedwithdiabetesshouldbemanagedappropriatelyfordiabetes.If thereisdiabetesexpertiseavailable,anearlyreferralshouldbemade. 3. Allpatientswithabnormalglucosemetabolismdetectedinhospitalshouldhaveadequatefollowup arranged,andthefindingsshouldbecommunicatedtotheusualcarepractitioner.

21

Section11: WhatistheRoleofaSpecialistInpatientDiabetesTeam?
Improvingglycaemiccontrolhasbeenshowntoreducetheriskofadverseoutcomesassociatedwith hyperglycaemia,buttheevidencefortheseclinicalbenefitshavebeenobtainedinandlimitedtospecific individualclinicalunits.Translatingtheseimprovedoutcomestoawholehospitalismorechallengingand requiresadifferentapproach.Ratherthanfocusingonimprovedclinicaloutcomes,oronspecificblood glucosetargets,hospitalwideapproacheshavefocusedonreducingthedifferenceinlengthofstayforpeople withdiabetesbyimprovingoveralldiabetesmanagement.Thedriversforthisapproacharenotsomuchan improvementinqualityofcareorclinicaloutcomes,butratherreductionsinassociatedcostsandimproved bedutilisation.Thefactorscontributingtoincreasedlengthofstayandpooreroutcomesassociatedwith diabetesthatarepotentiallymodifiableincludebloodglucosecontrol,inappropriatediabetesmanagement anddelayedinvolvementofspecialistdiabetesservices. Differentapproachestothisproblemhavebeenutilised,withvaryinglevelsofevidencetosupportthe intervention.Thesevaryfromthetraditionalconsultativeservice,tosystematichospitalwidediabetes programmes,tothenewerconceptoftheSpecialistDiabetesInpatientManagementTeam(Appendix11, table11.1).Therehasnowbeenonerandomisedcontrolledtrial164andanumberofcomparativestudies whichhavedemonstratedimprovedoutcomeswiththelatterapproach(Appendix11,Table11.2). TheseteamsusuallycomprisededicatedDiabetesInpatientSpecialistNurses(DISN),usuallyledbya consultantindiabetes.Theroleofsuchteamshasincludedimprovingdiabetesmanagementexpertise throughoutthehospital,thedevelopmentandimplementationofdiabetesmanagementprotocols,direct managementofdiabeteswithspecificreferralcriteria,wardliaison,troubleshooting,managementadvice,and dischargeplanning(Appendix11,Table11.3).DISNsarecurrentlyinvolvedin3050%ofUKhospitals171,with DiabetesUKrecommendingaratioofoneDiabetesDISNforevery300beds172.TheNHS(UK)hasadoptedthis approachtoimprovediabetesinpatientmanagementthroughthewholehealthsystem,resultingin reductionsinadverseoutcomesandlengthofhospitalstay9.InAustralia,theintroductionofSpecialist DiabetesInpatientManagementTeamswillrequireadditionalresources,butthelongtermeconomic argumentiscompelling.Theliteraturesuggeststhathospitalswhichhaveintroducedtheseteamshave realisedshorterlengthsofstayandsignificantcostsavings165,166,167,170.Healthadministratorsneedtoinvestin suchteamswhichshouldresultinbetterinpatientdiabetescare,shorterlengthsofhospitalstay,andcost savingstothehealthsystem.Forwardplanningisalsoneededforthetrainingofthespecialisedworkforce requiredforDiabetesInpatientManagementTeams. Recommendation 1. HospitalsshouldconsidertheintroductionofSpecialistDiabetesInpatientManagementTeams

22

Section12: What Routine Measures Should be Undertaken for People with Diabetes AdmittedtoHospital?
Effectiveinpatientdiabetesmanagementshouldbeprovidedearlyandcontinuouslythroughoutthehospital admission.Tosupportoptimalglycaemiccontrolinhospitalanddiabetesmanagementafterdischarge,itis importanttohaveestablishedroutineprocessesandprotocolsforthecareofpeoplewithdiabetesinhospital. Theserecommendationsaregenerallybasedongoodgeneralhospitalpractice,experience,andcommon sense.Generalrecommendationsinclude:clearidentificationofdiabetesinthemedicalrecord,bloodglucose monitoring,ahypoglycaemiamanagementprotocol,HbA1ctesting,amultidisciplinaryteamapproach, dieteticassessment,diabetesselfmanagementeducationwhenappropriate,anddischargeplanning142. Insulinisacommonsourceofmedicationerror171,172,andmustbeminimisedbymechanismssuchasstaff education,pharmacistoversight,anddedicatedinsulinprescriptioncharts173. BloodGlucoseMonitoring Wheretightglycaemiccontrolisdesired,andparticularlyforpatientsoninsulin,itisimportantforblood glucosemonitoringtooccurbeforeandaftermeals.Thisiscriticaltofacilitateappropriateadjustmentstothe patientsinsulindosage,andmonitorforhypoglycaemia.Additionaltestingatbedtimeandovernightisoften alsohelpful.Forstablepatients,orthosewheretightglucosecontrolisnotanaim,testingcanbereduced accordingly. DischargePlanningandDiabetesEducation Whilstthisdocumentfocusesonthemanagementinhospital,itisimportanttotaketheopportunityto improvethepostdischargemanagementofdiabetesaswell.Liaisonwiththegeneralpractitionerisan importantcomponentofthis.Notonlymightthisimprovepatientoutcomes,butitmayreducetheneedfor readmissiontohospital.Thevariousteammembersparticipatingininpatientmanagementalsohavearolein promotingandfacilitatingbetterdiabetescarepostdischarge(Appendix12,Table12.1).Appropriatediabetes educationisacriticalcomponentofinpatientpatientcareanddischargeplanning.Afocusonthecontinuityof carewhere thepatientisthecentralmemberinthemanagementofdiabetesisimportant,andtheirfamily membersmayneedtobebroughtintothediscussion. RecommendationsandPracticePoints 1. Ensureclearprocessesandprotocolsareimplementedinthehospitalforroutinediabetescare. 2. Ensuredischargeplanningwhichfacilitatesoptimallongtermdiabetesmanagement.

23

Appendices
Appendix1:SearchMethodologyofSystematicReviews Table1.1.PICOsearchquestionsandsearchtermsusedforeachofthechapters.
Question Whatglucosetargetshouldbeaimedforinacute myocardialinfarction? Whatglucosetargetshouldbeaimedforinacute stroke? Whatareappropriateglucosetargetsforpatientsin generalhospitalwards? Whatspecialmeasuresneedtobeundertakenfor peopleonenteral+parenteralnutrition? Howissteroidinducedhyperglycaemiabest managed? Whatistheoptimalmeansofachievingroutine glucosecontrolinhospital? Howshouldpatientsoninsulinpumptherapybe managedinhospital? Whatisappropriateglucosecontrolinendoflife situations Howshouldpatientswithnewlydiscovered hyperglycaemiabefollowedup? Whatistheroleofaspecialistdiabetesinpatient team? Whatroutinemeasuresshouldbeundertakenfor peoplewithdiabetesadmittedtohospital? SearchTerms hyperglyc(a)emia,diabetes,intensiveglucosecontrol,tightglucosecontrol,intensiveglyc(a)emic control,tightglyc(a)emiccontrol,myocardialinfarction,acutecoronarysyndrome,withthe outcomesofmortalityordeath. hyperglyc(a)emia,diabetes,intensiveglucosecontrol,tightglucosecontrol,intensiveglyc(a)emic control,tightglyc(a)emiccontrol,myocardialinfarction,stroke,cerebrovascularaccident,withthe outcomesofmortalityordeath. intensiveglucosecontrol,tightglucosecontrol,intensiveglyc(a)emiccontrol,tightglyc(a)emic control,hospital,surgery,medicine Diabetesand(enteralnutritionorparenteralnutrition) (Metformin or sulphonylurea or incretins or DipeptidylPeptidase IV Inhibitors or thiazolidinediones orinsulin)and(glucocorticoidsorprednisone)and(hyperglycaemiaordiabetes) hyperglyc(a)emia,diabetes,intensiveglucosecontrol,bloodglucose/sugarcontrol,intensive glyc(a)emiccontrol,tightglyc(a)emiccontrol,hospital,inpatient diabetes,guidelines,hyperglyc(a)emia,hypoglyc(a)emia,hospitaladmission,acutecare,inpatient care,perioperativemanagement,CSII,insulinpump,insulinpumptherapy,IPT diabetes,guidelines,hyperglyc(a)emia,hypoglyc(a)emia,hospitaladmission,inpatientcare,endof life,palliativecare,terminalillness,advancedcancer,hospice,insulin,oralhypoglyc(a)emicagents, slidingscale,bloodglucose,therapy,andmanagement hyperglyc(a)emia,diabetes,intensiveglucosecontrol,bloodglucose/sugarcontrol,intensive glyc(a)emiccontrol,tightglyc(a)emiccontrol,hospital,inpatient Diabetes,hospital,inpatient Consensusonly

24

Appendix2:LiteraturereviewedforWhatGlucoseTargetShouldbeAimedforinAcuteMyocardialInfarction? Table2.1.Recentstudiesexaminingtherelationshipbetweenadmissionglucoselevelsandmortalityfollowingmyocardialinfarction
Study Subjects Characteristics Elevatedadmission Thresholdlevel glucosepredictive foreffect? ofmortality? STEMI Yes 8mmol/L Comments Methodology

Wong2004

13

158

Stranders 14 2004 Timmer 15 2004 Kosiborod 16 2005

846

AnyAMI

Yes

Similarrelationshipforbothinpatientand6 monthmortality RelationshipbetweenBGanddeathpresent withandwithoutreperfusiontherapy 11.1mmol/Lfor Above11.1mmol/L,nondiabeticshad nondiabetics sameriskasthosewithdiabetes. 7.8mmol/L Alsoassociationwithlargerinfarctsizeand reducedLVfunction

Clinicalcohort study

356

141680

STEMIwith PTCAor reperfusion Age>65

Yes

Yes

Straumann 17 2005 18 Meier2005

978 227

AllhadPTCA AllAMI

Yes Yes

Goyal2006

19

1469

Bhadriraju 20 2006 Naber2009

21

9020

5866

Sinnaeve

13526

Subanalysisof CARDINAL Trial Subanalysisof OPUSTIMI trial Nondiabetic STEMI(ACOS Registry) Globalregistry

Yes(onlyfornon diabetics) Yes

Yes

6.1mmol/Lfor Similarresultsfor30dayandoneyear mortality nondiabetes 13.3mmol/Lfor diabetes 7.8mmol/L Similarresultsfor30dayandlongerterm mortality 7.4mmol/Lfor Survival>3.5yearswasassessed nondiabetics, 7.9mmol/Lfor diabetes Lowermortalityamongstnondiabetics wheretherewasagreaterdropinBGover 24hrs 5.6mmol/L Relationshipstrongerfornondiabetics. Resultsalsovalidatedinsubanalysisof TACTICSTIMItrial 8.3mmol/L Inpatientand1yearmortality

Retrospective clinicalcohort study Posthoc subanalysisofa clinicaltrialcohort Analysisof database

Analysisof database Clinicalcohort study

Posthoc subanalysisofa clinicaltrialcohort Posthoc subanalysisofa clinicaltrialcohort Cohortstudy

Yes

6.9mmol/L 25

RandomBGLassociatedwithinpatient

Analysisof

2009

22

Ishihara 23 2009 Dziewiercz 24 2009 Goyal2009

25

3750 763

30536

DeMulder 26 2010 Timmer 27 2011

1185

4176

Within48hrs ofAMI NonSTEMI treated conservatively CREATEECLA andOASIS6 cohorts Both preinvasive andPTCAeras Nondiabetic STEMI

Yes Yes

(random) 5.6mmol/L (fasting) 7mmol/L 5mmol/L

mortalityonly,fastingBGLassociatedwith bothinpatientand6monthmortality. Ushapedcurveforpatientswithdiabetes, increasedmortalityifBGL<7or>11mmol/L Relationshipstrongerfornondiabetic subjects Hypoglycaemia<3.3alsopredicted mortality

database

Cohortstudy Analysisof database Posthocanalysisof clinicaltrialcohorts

Yes

7.8mmol/L

Yes

11mmol/L

Yes

8.2mmol/L

Eachmmol/Lincreasecorrespondedtoa7% Cohortstudy increasedmortality(adjustedHR1.07,95% CI1.041.10) Cohortstudy 30dayand1yearmortalityassessed.U shapedcurveformortalitywithincreased mortalityforthosewithBGL6.9mmol/L

26

Table2.2.Observationaldataofarelationshipbetweenaverageglucoselevelsorglucoselevelsachievedinthefirst24hoursaftermyocardial infarctionandmortality.
Study Subjects Characteristics Glucose parameter Elevated glucose predictiveof mortality? Yes Threshold levelfor effect? 8mmol/L Comments Methodology

Cheung 28 2006 , 29 2008

240

Kosiborod 30 2008

7820

Myocardial 12hourly infarct with capillaryBGs known diabetes or admission BG 7.8mmol/L AllAMI Meanglucose Yes measurements

Posthocsubanalysis ofaclinicaltrial cohort

6.1mmol/L

Mortalitylowerininsulin treatedpatients

Analysisofdatabase

27

Table2.3.Systematicreviewsofrandomizedcontrolledtrialsoftightglucosecontrolinmyocardialinfarction,wheretheprimaryoutcomewas death.
Review Pittas 200432 SearchMethod Medline, Cochrane Controlled ClinicalTrials Register Medline, CENTRAL, EMBASE Medlineand Embase SelectionQuestion StudiesofInsulinincritically illhospitalizedadult patients.Subanalysis:those aimingforglucosecontrol Studies AMIsubanalysis:8studies. Davies199137,Malmberg 199531,Scott199938,Lazar 200039,Szabo200140,van denBerghe200141,Groban 200242,Smith200243 AMIsubanalyis:3studies. 31 Malmberg1995 , 44 Malmberg2005 ,Cheung 28 2006 31 Malmberg1995 ,Diaz 45 1998 ,Ceremuzynski 46 44 1999 ,Malmberg2005 , 47 CREATEECLA2005 , 28 Cheung2006 Subjects Subanalysis: 2772 Result/Conclusion Subanalysis:29% reductionin mortality(RR0.71, 95%CI0.540.93) Comment Subanalysisincluded studiesofcoronary surgeryandICU patients

Zhao 201033

RCTsofGIKorinsulin glucose.Subanalysis:insulin glucoseonly RandomisedtrialsofACS withhyperglycaemia comparinginsulininfusion orGIKwithactivecontrols whichassessedmortality andmorbidity Trialswithinsulininpatients withunstableanginaorAMI. Subanalysis:thoseaiming forglucosenormalization

Subanalysis: 2113

Subanalysis:No reductionin mortality(RR1.07, 95%CI0.851.36)

Devine 201034

Currentevidence Metaanalysisnot thatinsulintherapy done reducesmortality andmorbidityinACS isinconclusive Intensiveglucose loweringinsulin therapycanreduce mortality NonICU:9studies, noreductionin shorttermmortality (RR1.0,95%CI0.94 1.07) AMI:Nomortality reduction Metaanalysisnot done

AMIsubanalysis:3studies. 31 Malmberg1995 , 44 Malmberg2005 ,Cheung 28 2006 Kansagara MEDLINE, RCTsusinginsulintoachieve AMIsubanalysis:6studies 36 31 2011 Cochrane strictglycaemiccontrol. Malmberg1995 ,Vander 48 Databaseof Subanalysis:AMI. Horst2003 ,Malmberg 44 28 Systematic 2005 ,Cheung2006 , 49 Reviews, Rasoul2007 ,Oksanen ClinicalTrials.gov 50 2007 , Lipton 201135 Bold=studieswithspecifiedobjectiveofintensiveglucosecontrolinAMI

Pubmed

Subanalysis: 4007

6foldriskofhypos (BGL<2.2mmol/L)in allsettingsRR6.0, 95%CI4.068.87, p<0.001). 50 Oksanen =studyof subjectsfollowingVF

Table2.4.Randomisedcontrolledtrialsofmyocardialinfarctionwithaspecificglucosetarget.
28

Trial DIGAMI, Malmberg 31 1995 , 51 1997

Subjects EntryCriteria 620 Myocardialinfarct andadmissionBG >11.0mmol/L.

InsulinRegimen Variablerate glucoseinsulin solutionforat least24hrs.

Glucose Target 710 mmol/L

Primary Outcome Reducedone yearmortalityin insulininfusion group(18.6%vs 26.1%, p=0.027).

Secondary Findings Greatestbenefit topatientswith lowpremorbid cardiovascular riskprofile.

Comments Amongstfirst327subjects,blood glucoseat24hourslowerininsulin thanincontrolsubjects(9.22.9vs 124.4mmol/L).Insulingroup receivedregularsubcutaneousinsulin afterdischarge,whichmayhave contributedtobetteroutcomes. MedianBGat16hours7.7mmol/Lfor GIKgroupand8.1mmol/Lforcontrols (NS).

GIPS,van derHorst 48 2003

940

Within24hrsofST segmentelevation infarct(allhad PTCA).

DIGAMI2, Malmberg 44 2005

1253

HI5, Cheung 28 2006

240

20%glucose potassium solutionat 3mls/kg/hrwith insulinat variablerate. Myocardialinfarct Variablerate andeitherknown glucoseinsulin type2diabetesor solutionforat admissionBG>11.0 least24hrs. mmol/L. Myocardialinfarct Variablerate withknown insulinwith5% diabetesor dextrose80 admissionBG7.8 mls/hr. mmol/L.

711 Nosignificant mmol/L. reductionin30 daymortality (4.8%vs5.8%).

710 mmol/L

Noreductionin mortalitywith insulininfusion.

410 mmol/L

Noreductionin mortalitywith insulininfusion.

BGat24hoursininsulintreated groupsonly0.9mmol/Llowerthanfor conventionaltreatmentgroup (9.13.0and9.12.8vs103.6 mmol/L,p=0.0001) Mortalityhigher Mean24hourBGininsulintreated insubjectswith grouponly0.7mmol/Llowerthanfor conventionaltreatmentgroup mean24hour (8.32.2vs9.02.8mmol/L,NS) bloodglucose level>8.0 mmol/L.

Other trials of insulin glucose therapy where there were no glucose targets were excluded from consideration: ECLA (1998)45, POLGIK (1999)46, CREATEECLA(2005)47,GIPSII(2006)52 Table2.5.Guidelinesregardingglucosecontrolinmyocardialinfarction
Guideline ESCandEASDguidelinesondiabetes, prediabetesandcardiovasculardisease, Population Peoplewith diabetesandAMI Recommendation

Thereisreasonableevidencetoinitiateglucosecontrolbymeansofinsulin infusionindiabeticpatientswhoareadmittedforAMIswithsignificantlyelevated
29

2007 AACE/ADAconsensusstatementon 55 inpatientglycemiccontrol,2009 Allhospitalized patients

54

bloodglucoselevelsinordertoreachnormoglycaemiaassoonaspossible(Class IIa,LevelB)
Insulininfusionshouldbeusedtocontrolhyperglycaemiainthemajorityofcriticallyill patientsintheICUsetting,withastartingthresholdofnohigherthan10mmoml/L.Target 7.810mmol/L,andgreaterbenefitmayberealizedatthelowerendofthisrange. Formajorityofnoncriticallyillpatients,premeal<7.8mmol/L,random<10mmol/L.as longasthiscanbesafelyachieved. ReasonabletouseinsulinbasedregimentoachieveandmaintainBG<10mmol/Lwhilst avoidinghypoglycaemia DonotuseintensiveinsulintherapytostrictlycontrolglucoseinnonICUpatientswithor withoutdiabetesmellitus

ACC/AHAguidelinesforthemanagement ofpatientswithSTelevationmyocardial 56 infarction,2009 ACPguidelinesforintensiveinsulin therapyforthemanagementofglycemic 57 controlinhospitalizedpatients,2011

STelevationAMI

Allhospitalized patients

30

Appendix3:LiteraturereviewedforWhatGlucoseTargetShouldbeAimedforinAcuteStroke? Table3.1.Recentstudiesexaminingtherelationshipbetweenadmissionglucoselevelandstrokeoutcomes.
Study
59

Subjects Characteristics

Baird2003 Allport2004 AlvarezSabin 61 2004 Farrokhnia 62 2005

60

25 31 138

Ischaemicstroke Acuteischaemic stroke MCAterritory treatedwithtPA Acutestroke

Relationbetween admissionglucose andmortality? N/A N/A N/A

Relationbetween admissionglucoseand otheroutcome? Yes,infarctsize,NIHSS andmRS Yes,insularcortical ischaemia YeswithNIHSSandmRS

Thresholdlevelfor effect? 7mmol/L N/A N/A

Comment

Detrimentalassociation greatestwithearlyreperfusion therapy. Thresholddeterminedfrom ROC

447

Yes(onlyfornon diabetic)

N/A

Stollberger 63 2005 64 Gentile2006 65 Yong2008

66

992 960 748

Allacutestroke Ischaemicstroke ReceivedtPAfor acutehemispheric stroke Acuteischaemic stroke Acuteischaemic stroke

Yes Yes Yes

N/A N/A Yes,withBI,mRS,7day neurological improvement YeswithmRS Yeswithstrokeseverity andfunctional impairment Yes,withsymptomatic intracerebral haemorrhageandmRS Yes,withNIHSSand mRS Yes,withNIHSSand mRS 31

Diabetes:10.3 mmol/L,non diabetics:6.3 mmol/L 9.2mmol/Lfor nondiabetics 7.2mmol/L 7.8mmol/L

Effectnotseenamongsubjects withknowndiabetes Thresholddeterminedfrom ROC Relationshipstrongerfor patientswithoutdiabetes

Fuentes2009 Stead2009
68 67

476 447

Yes Yes

8.6mmol/L 7.2mmol/L

Poppe2009
69

1098

Ntaios2010 Ahmed2010
70

1446 16049

Acuteischaemic Yes stroketreatedwith tPA Ischaemicstroke N/A Ischaemicstroke treatedwith thrombolysis Yes

N/A

<3.7and>7.2 mmol/L 6.7mmol/L

similarthresholdfordiabetes andnondiabetics

Dziedzic2010 72 Saposnik2011 Kimura2011

74 73

71

302 8223 97

Hu2012

774

Ischaemicstroke Acuteischaemic strokeinregistry ReceivedtPA within3hoursof strokeonset Acutestroke

Yes Yes N/A

N/A N/A Infarctvolumelarger andworsemRS Yes,withNIHSS,BIand mRS

N/A 7.5mmol/L 7.2mmol/L

Relationshipnotpresent amongstthosewithsuccessful earlyrecanalisation.

Notreported

Diabetes:8.9 mmol/L,non diabetics:6.8 mmol/L

NIHSS=NationalInstitutesofHealthStrokeScale,BI=BarthelIndex,mRS=modifiedRankinScore

32

Table3.2.Studiesexaminingtherelationshipbetweenmeanglucoselevelsandstrokeoutcomes:
Study Subjects Characteristics Glucose parameter Elevatedglucose predictiveof mortality? N/A Relationbetween Thresholdlevelforeffect? admissionglucoseand otheroutcome? Yes,infarctsize,NIHSS 7mmol/L andmRS N/A 10.3mmol/Lfordiabetes,6.3mmol/L fornondiabetics(basedonROC) 7.8mmol/L

Baird 59 2003

25

Ischaemicstroke

Meancapillary andmeanCGMS Meancapillary

Farrokhnia, 447 62 2005 Yong 65 2008 748

Acutestroke

Yes

ReceivedtPAfor acutehemispheric stroke Ischaemicstroke

Glucoseat24hrs

Yes

Yes,BI.mRS,7day neurologicalrecovery.

Fuentes 66 2009

476

Maximum capillaryglucose

Yes

Yes,mRS

8.6mmol/L

NIHSS=NationalInstitutesofHealthStrokeScale,BI=BarthelIndex,mRS=modifiedRankinScore

33

Table3.3.Systematicreviewsofrandomizedcontrolledtrialsoftightglucosecontrolinstroke,wheretheprimaryoutcomewasdeathorameasure ofdisability.
Review SearchMethod SelectionQuestion RCTsusinginsulinto achievestrictglycaemic control.Subanalysis: strokeandacutebrain injury Studies Walters2006 ,Gray 2007 ,Azevedo 2007 ,Bruno2008 , Yang2009
81 79 80 78 77

Subjects Result/Conclusion NonICUsetting:9studies,no reductioninshortterm mortality(RR1.0,95%CI0.94 1.07) Strokeandacutebraininjury: Noreductioninmortality BG>10mmol/Lshouldtrigger insulinadministration.

Comment Increasedriskof hypoglycaemiainall settings.

Kansagara MEDLINE,Cochrane 36 Databaseof 2011 SystematicReviews, ClinicalTrials.gov

Kruyt 75 2010

Notstated

Studiesinvestigatingthe Walters200677,Gray 78 80 feasibilityandefficacy 2007 ,Bruno2008 oftightglycaemic controlinpatientswith ischaemicstroke

RCTscomparing intensivelymonitored insulintherapyversus usualcareinadultpatients withacuteischaemic stroke.

Reviewnotrestricted toRCTs

Bellolio 76 2011

CochraneStroke GroupTrials Register,CENTRAL, MEDLINE,EMBASE, CINAHL,Science CitationIndex,Web ofScience,Scopus

Vinychuk2005 , Walters2006 ,Gray 2007 ,Staszewski 2007*,Bruno2008 , Kreisel2009 , Johnston2009

84 83 80 78 77

82

1296

Nodifferenceindeathor disabilityanddependence(OR 1.00,95%CI0.78to1.28)or nalneurologicaldecit(SMD 0.12,95%CI0.23to0.00).

Increased hypoglycaemiawith intervention.Some studiesinthisreview werenotdesignedto assessneuro outcomes.

Bold=studiesofstrokeonly,*Unpublished

Table3.4.Randomisedcontrolledtrialsofstrokewithaspecificglucosetarget.
34

Trial Vinychuk 82 2005

Subjects 128

EntryCriteria Within24 hoursof ischaemic strokeonset, admissionBG 716mmol/L Within24 hoursof ischaemic strokeonset, admissionBG 820mmol/L Within24 hoursof strokeonset, admissionBG 617mmol/L Within12 hoursof cerebral infarctandBG 8.3mmol/L Within24 hoursof ischaemic strokeonset Within12 hoursof cerebral infarctandBG 6.1mmol/L

Insulin Regimen Glucose potassiu minsulin infusion

Glucose Target <7 mmol/L

Walters 77 2006

25

Variable rate insulin infusion

5 8 mmol/L

Glucose Achieved Diabetes:7 vs11.2 mmol/Lat 1224hrs Nodiabetes: 5.8vs8.1 mmol/L Intarget 87%ofthe timevs71% ofthetime (p<0.001) GKIgroup 0.57mmol/L lower (p<0.001)

Primary Secondary Outcome Findings Improvemen tinNHISS comparedto

Comments 4armstostudy

Hypos Notreported

1deathinsulin Apilotstudy group,0in controlgroup

1ininsulin group,0in controls

GISTUK, Gray 78 2007

933

Glucose potassiu minsulin infusion

4 7 mmol/L

Noreduction indeathat 90dayswith GKI

Bruno 80 2008

46

Kreisel 83 2009

40

Johnston 84 2009

74

Variable rate insulin infusion for72hrs Variable rate insulin infusion Variable rate insulin infusion

<7.2 mmol/L

7.4vs10.5 mmol/L

Diffin glucose achieved

Trialdiscontinued earlyduetoslow recruitment.BG dropped spontaneouslyin controlgroup. 2deathinsulin Apilotstudy group,0in controlgroup

Noreduction inresidual disabilityor functional recovery

41.2%GKI patientshadBG <4mmol/Land 15.7%required rescueiv glucose 35%vs13%had hypos<3.3

4.46.1 mmol/L

6.5vs8.0 mmol/L, p<0.0005 6.2vs8.4 mmol/L

Diffin glucose achieved Diffin glucose achieved

3.96.1 mmol/L

Nodifference indeathor functional outcome Nodifference indeathor functional outcome

Notpoweredtodetect 25vs2hypo events(p<0.05) differenceindeath anddisability 3armstostudy 30%vs4%had Notpoweredtodetect atleastone hypo differenceindeath anddisability

35

Middleton 1126 85 2011

Within48 hoursof acutestroke

Variable rate insulin infusionif BG>=11 mmol/Lif diabetes, >=16for non diabetics, upto72 hours

4 8 mmol/L orlocal guidelin esonce insulin infusion comme nced

7.0vs6.8 mmol/L, p=0.02 (Notesmall difference only)

Differencein mortalityor dependency 42%vs58% (p=0.002)

Nodifference inBarthel index,but higherSF36 PhysicalHealth Scorein intervention

Interventionwas Notreported. packageofglucose, fever,andswallowing management.Not possibletodetermine contributionofglucose control.

Table3.4.Guidelinesregardingglucosecontrolinstroke
Guideline AHA/ASAguidelinesfortheearly Population Ischaemicstroke Recommendation

managementofadultswith ischemicstroke,200786
EuropeanStrokeGuidelines,2008
87

Serumglucoseconcentrations(possibly>7.8to10.3mmol/L)probably shouldtriggeradministrationofinsulin(ClassIIa,LevelofEvidenceC). Treatmentofserumglucoselevels>10mol/Lwithinsulintitrationis recommended(ClassIVevidence). Severehypoglycaemia[<2.8mmol/Lshouldbetreatedwith intravenousdextroseorinfusionof1020%glucose(ClassIVevidence)

Ischaemicstroke

36

Appendix4:LiteratureReviewedforQuestionWhatareAppropriateGlucoseTargetsforPatientsinGeneralHospitalWards? Table4.1.Observationalstudiesexaminingtherelationshipbetweenhyperglycaemiaandoutcomesinhospitaloutsideofthesituationsof intensivecare,myocardialinfarctionandstroke.

Study Pomposelli 1999Study88 Golden 199989 Umpierrez, 200290 Cheung 200591 Baker200892 Subjects 97patientsundergoing generalsurgery 411CABGpatients 2030admissionstoa communityteaching hospital 122subjectsonTPN Finding SingleBGL>12.2mmol/Lpredictiveofnosocomialinfection Comment

MeancapillaryBGL11.5mmol/Lassociatedwith increasedinfection 2xFastingBGL7.0mmol/LorrBGL11.1mmol/L associatedwithincreasedmortality,needforICUand longerLOS MeanBGL7.9mmol/Lassociatedwithincreasedinfection MeanBGL9.1mmol/Lassociatedwithincreasedmortality AdmissionBGL5.6mmol/Lassociatedwithincreased mortality

Riskhigherfornewhyperglycaemiathan diabetes

903patientsingeneral medicalward

NoassociationbetweenBGlevelsand mortalityamongstpeoplewithknown diabetes.HbA1calsopredictiveof mortalityinnondiabetics. Riskhigherfornewhyperglycaemiathan diabetes

Cheung, 200893

6187admissionstoa teachinghospital

AdmissionBGL>8.0mmol/Lpredictiveofmortalityand longerLOS

Table4.2.Systematicreviewsofstudiesexaminingtrialsoftightglycaemiccontroloutsideoftheintensivecaresetting,andnotspecifically focusingonmyocardialinfarctionorstroke
37

Review Haga 201194

SelectionQuestion

Studies

Effectsoftightversus 3studies:Groban200242,Lazar normalglycaemiccontrol,peri 200496,Ingels200697 andpostoperatively,inpatients undergoingcardiacsurgery.

Total subjects 686

Result/Conclusion 48%reductioninmortality(OR 0.52,95%CI0.30.91,p=0.02). Maybesomebenefittotight glycaemiccontrolduringandafter cardiacsurgery. NonICUsetting:noreductionin shorttermmortality(RR1.0, 95%CI0.941.07). Perioperative:noreductionin shorttermmortality.

Comment

Kansagara RCTsusinginsulintoachieve strictglycaemiccontrol. 201136 Subanalysis:NonICUstudies Subanalysis:Perioperative

9nonICUstudies:Malmberg NonICU: 199531,VanderHorst200341, 2677 Butterworth2005,Li2006, Cheung200628,Oksanen200750, Azevedo200779,Yang200981, 5perioperativestudies:Smith 200243,Lazar200439,Butterworth 200598,Li200699,Barcellos2007100 Variedfor 19studies:RCTsMalmberg 199531,Dickerson2003101,vander different Horst200348,Malmberg200531, analyses 28 77 Cheung2006 ,Walters2006 , Umpierrez2007102,Umpierrez 2009103,Umpierrez2011104

Murad 201295

Observationalorrandomized studiesthatcomparedthe effectofintensiveglycaemic controltoacontrolgroup seekinglessaggressive normalization ofglycaemiclevels.Intensive caresettingexcluded.

Noassociationbetweenintensive glucosecontrolandriskofdeath, myocardialinfarctionorstroke. Associationwithreducedriskof infection(RR0.41,95%CI0.21 0.77).Trendtoincreased hypoglycaemia.

Notrialsin generalmedical wards Perioperative studiesmostly poorquality RRhypoglycaemia 6.0,95%CI4.06 8.87,p<0.001). Inclusionof observational studiesis questionable.

38

Table4.3.Existingguidelinesforglucosetargetsinnoncriticallyillpatientsinhospital.
Guideline AACE/ADA,200955 Population Allhospitalized patients Recommendation Insulininfusionshouldbeusedtocontrolhyperglycaemiainthemajorityofcriticallyill patientsintheICUsetting,withastartingthresholdofnohigherthan10mmol/L.Target7.8 10mmol/L,andgreaterbenefitmayberealizedatthelowerendofthisrange. Formajorityofnoncriticallyillpatients,premeal<7.8mmol/L,random<10mmol/L,aslong asthiscanbesafelyachieved. SocietyforAmbulatory Anesthesia,2010105 Preandintra operative Insufficientdatatorecommendthelevelofpreoperativefastingbloodglucoseabovewhich electiveambulatorysurgeryshouldbepostponed.Noevidencethatanyparticularblood glucoseleveliseitherbeneficialorharmfulforpatientsundergoingambulatorysurgical procedures.Suggestthatinpatientswithwellcontrolleddiabetes,intraoperativeblood glucoselevelsbemaintained<10mmol/L. DonotuseintensiveinsulintherapytostrictlycontrolglucoseinnonICUpatientswithor withoutdiabetesmellitus. Recommendpremealtarget<7.8mmol/L,randomtarget<10mmol/L,butmodifyaccordingto clinicalstatus.ReassesstherapyifBGvaluesfallbelow5.6mmol/L.ModifytherapywhenBG valuesare<3.9mmol/L.

ACP,2011106

Allhospitalized patients

EndocrineSociety,2012107

39

Appendix5:LiteratureReviewedforQuestionWhatisthebestmethodtomaintainglycaemiccontrolinahospitalizedpatientwhoisreceiving parenteralorenteralnutrition?
Table5.1.Clinicaltrialsofglucosecontrolamongpatientsreceivingenteralorparenteralfeeding. Paper Koryt kowski 2009108 Design Slidingscaleinsulin(46hourlyifBGL >7.1mmol/l)vsslidingscaleinsulin andglargine. Targetglucoserange(5.610mmol/l). Noncriticallyillhospitalizedpatients with2BGLsover7.2mmol/l(withor withoutpriordiagnosisofdiabetes) Receivingenteralnutritiontherapy formulaanddeliveryatdiscretionof nutritionteamwithmajorityreceiving 50%carbohydrate. Quality Levelof Statisticalprecision evidence Nodifferencebetween thetreatmentgroupsin meanstudyglucose levelsp=NS. Sizeanddirection Relevance ofeffect Noeffect.Both regimens effectivein loweringmean glucoselevels. Similarratesof hypoglycaemia onBGmeasures, totaladverse eventsandLOS. Similartotaldaily insulindoses. Inpatient population receiving enteral nutrition therapy.

Grainger 2007109

Variabledosepreprandialinsulin (standardofcare)vsnurseledinsulin protocol(variabledoselispro,regular +correctionaldose)andfixeddose glargine(weightdependent). Criticallyillhospitalisedpatientswith knowntype2diabetesorFBG>11.1. Receivingbolusenteralnutrition (TwoCalHNorNeprorenalfailure)q4 hourstoprovide6feeds/day.

Selectionbias,randomization II processnotdescribed. Informationbias,openlabel study.FinancedbySanofi Aventis;clearlydisclosedand statedthatsponsordidnot influencestudydesign conduct.Inclusion/exclusion criteriadescribed. Baselinecharacteristicssimilar betweengroups.Large percentage(55%)ofpatients inSSIarmalsoreceivedNPH insulin. Selectionbias,high. III3 Informationbias,high. Inclusion/exclusioncriteria described. Usedhistoricalcontrolsfrom beforeprotocol implementation. ExcludedNIRDMpatients. Baselinecharacteristics,few reportedbutsimilar.

Lowermeanglucosein interventioncfcontrol groupp<0.001.Greater proportionin interventiongroup achievedgoalglucose rangep<0.01,+shorter timetoachieveglucose control21vs60hrs,p notreported.Increased hypoglycaemiap=0.02.

Insulinprotocol increased proportionof patients achievingtarget bloodglucose range. Modestincrease in hypoglycaemia.

ICU inpatient population receiving enteral nutrition therapy.

40

Appendix6:LiteraturereviewedfortheQuestionHowissteroidinducedhyperglycaemiabestmanaged? Table6.1.Incidenceofsteroidinducedhyperglycaemia.
Author Fajans1954115 StudyDesign Steroid CRHorcortisone Incidenceofsteroidinduced hyperglycaemia N/A Riskfactorsforsteroidinduced hyperglycaemia Firstdegreerelativewith diabetes Steroiddose(oddsratiorose from1.77for39mg/day hydrocortisoneequivalent,rising to10.34for120mg/dayormore HigherHbA1c Preexistingdiabetes Comment Hyperglycaemia basedonprescription oforalantidiabetic agent 21%patientsnot screened UsedCGMS

steroidgiven priortoaGTT Gurwitz1994114 Casecontrol study

Anyoralglucocorticoids N/A

FeldmanBillard Retrospective audit 2005113 Donihi2006110 Retrospective audit Fong2011111 Burt,2011112 Prospective audit Prospective study

Pulse methylprednisolone Atleastprednisone40 mg/dayorequivalent for2days Atleastprednisone25 mg/dayfor2days Atleastprednisone20 mg/dayfor2days

64%hadatleastoneBG14 mmol/L Overall64%hadatleastone BG11.1mmol/L. 56%amongstnondiabetics. 71%hadatleastoneBG 10mmol/L 53%hadatleastoneBG 10mmol/L

Age Preexistingdiabetes

41

Table6.2.Evidenceregardingtheeffectivenessofantidiabeticmedicationinthemanagementofsteroidinducedhyperglycaemia.
Medication Class Metformin Sulphonyl ureas(SU) InterventionStudies Notrialsidentified Noprospectivetrials.Studiesinambulatorysettingonly. A retrospective review of 40 ambulatory pts with diabetes at baseline who had received prednisone (dose range 540mg/day for management of nonendocrine conditions such as COPD and SLE)described5patientswhohadreceivedrepaglinide.However insulin was also required to achieve glycaemic control in 4 of the 5121. Kasayama reported 3 adult ambulatory patients with immunological conditions, initially requiring prednisone 20 40mg/day, and maintained on 510mg/day, who developed hyperglycaemia after 12 yrs of maintenance GC therapy122. All 3 were able to be controlled with glimepiride monotherapy (1 3mg),achievingHba1c<7%. Publishedreportsofuseforsteroidinducedhyperglycaemiain settingoforgantransplantationonly.Pioglitazoneimproved glycaemiccontrolasanadjuncttoinsulin(meanHbA1cfallingby 1.28%)inaseriesofrenaltransplantrecipientsmanagedwith prednisone(420mg/day)andsirolimusormycophenolate,6of the10patientshaddiabetespredatingtheirtransplant127. Efficacyofotherthiazolidinedionesforposttransplantdiabetes orGCrelatedDMhasalsobeendescribed128130. No completed trials identified. A trial of vildagliptin in the managementofposttransplantdiabetesisinprogress131. Notrialsofinsulinregimensinmanagementofsteroidinduced hyperglycaemiainhospitalotherthanintravenousinsulin133. Observationalreportsuggeststhatuseofmorningisophane insulinversuslongactinginsulin(eitherinsulinwithrapidacting insulinatmealtime)achievedglycaemiccontrolmorequickly134. Preliminaryreportsuggeststhatearlyuseofbasalinsulininthe 42 OtherLiteratureandComments Limitationstoitsuseintheinpatientsettingmayincludethepresence ofriskfactorsforlacticacidosis,orvariableoralintake AlthoughpredominanteffectofGCsisareductionininsulinsensitivity, individualswhodevelophyperglycaemiawithGCadministration,havea reducedinsulinsecretorycapacity123.Henceinsulinsecretogoguesare notanidealchoice.RiskofhypoglycaemiaasGCtaperediflongacting agentsareused124,wherethereismealomission125orifrenalfunctionis reduced126.SUusehasbeensuggestedtobelimitedtothosewith milderdegreesofGCinducedhyperglycaemia,wherefastingBG <7mmol/L126.SinceinpatientsusuallyreceivehighGCdosesandmay havevariableoralintakeorrenalfunction,SUshavealimitedrole.

Thiazolidine diones

Delayedonsetofactionmakesthisgroupgenerallyunsuitableforacute inpatientmanagementofhyperglycaemia.

Incretins

PotentialrolehasbeenexploredbyvanRaalte132.

Insulin

Wheremarkedfastinghyperglycaemia(>10mmol/L)ispresent,insulinis thought to provide better management than oral agents126,137. Insulin providesgreaterdoseflexibility,morerapidonsetofactionandtitration and there is usually no dose ceiling. Insulin dose requirements need to be individualised, due to variations in insulin sensitivity, insulin secretory capacity, GC regimen and dosing, oral intake, renal function

settingofrenaltransplantation,preventsthedevelopmentof subsequentnewonsetdiabetes135. Inresponsetoprednisone60mg/dayaseriesof10patientswith T1DMmanagedwithsubcutaneousinsulinpumprequiredan increaseofbetween30100%136.

and prior control. Preemptive increases and decreases in insulin required as GC dose is adjusted. This usually requires daily adjustment. Generally the insulin regimen or adjustments to a preexisting regimen should predominantly target postprandial control, and with morning GC administration, the afternoon hyperglycaemia. Clore has advocated the use of isophane insulin for management of steroid hyperglycaemia124,theinitialdosedeterminedaccordingtoGCdoseand patient weight (e.g. prednisone 10mg daily requires 0.1unit/kg/day as isophane insulin; prednisone 40mg daily requires 0.4 unit/kg/day), and titratedaccordingtoresponse.Forapatientalreadyoninsulin,thismay be added to the existing regimen. This titration schedule is easier to continue upon discharge than more complex regimens, and more likely to be successful if patients have a consistent routine and carbohydrate consumption from day to day138. Isophane insulin can be supplemented with ultraquick insulin analogue with meals139. Basal plus prandial insulin is likely to be required in patients receiving high dose GC (eg >50mg prednisone/day) where prior glycaemic control was poor, GCs had been initiated without preemptive consideration of glycaemia or GC are given as split dose. With multiple daily dose GC regimens, isophane insulin twice daily with prandial rapid acting analogue can be initiated. A regime that controlled glycaemia on previous occasions can bereinitiatedwhencyclicalGCsarerequired,aslongastherehasbeen nomajorintervalchangeinweightorrenalfunction.

43

Appendix7:LiteratureReviewedforQuestionWhatisthebestmethodtomaintainglycaemiccontrolinahospitalizedpatientwhoisnot criticallyill? Table7.1.Randomisedcontrolledtrialscomparinginsulinregimesforglucosecontrolinhospital.

Author Studydesign QualityandriskofBias Levelof evidence Statistical precisionand significance Statistical calculations includedin studydesign. Hyperglycaemic and hypoglycaemic events. Sizeanddirectionofeffect Relevance

Dickerson 2003101

Yeldandi 2006143

153subjects. Randomisedtrial comparingglycaemic controlinmedical patientswithtype2 diabetesreceiving slidingscaleinsulin versusroutine diabetes medications. 94patients. Randomisedtrial comparingonce dailyglargineinsulin withtwicedaily NPH/regularinsulin forcontrolof hyperglycaemiain inpatientspost cardiovascular surgery.

Mediumhighriskofbias.Bias III1 thatpopulationchosenfrom conveniencesample. Randomisationprocedure clearlydescribed.Openlabel. Clearexclusioncriteria. Baselinecharacteristicsmostly similar.Mayhavebeen treatmentchangesduring study. Mediumriskofbias. III1 Randomisationprocedurenot described.Openlabel. Noexclusioncriteria.Baseline characteristicssimilar.

Primaryoutcomewas frequencyofhyperglycaemia (>16.7)andhypoglycaemia (<2.8).Nodifferencebetween thetwogroups. Nodifferenceinsecondary outcomewhichwasLOS.

Generalmedical patients,similarto Australiangeneral medicalwards

Nocalculations weredoneto showpower. MeanBG 124mg/dLv 131mg/dL p=0.065 Hypoglycaemia lesswith glargine p=0.036.

Umpierrez 2007 (RABBIT2 Trial)102

130patients. Randomisedtrialof basalbolusinsulin therapycomparedto slidingscaleinsulin intheinpatient

Mediumriskofbias. III1 Notclearlydefinedwhatthe randomizationprocesswas. Openlabel. Inclusionandexclusioncriteria detailed.Baseline 44

Unclearifstudy appropriately powered. FBGp<0.001, meanrandom bloodglucose

Minimaleffect.Calculated% ofBGswithintargetrange. SimilarBGsachievedwith bothregimensinwhole cohort.Subgroupwith diabetes:bdNPHhadlower meanBGthanglargine. Subgroupwithoutdiabetes: nodifferenceinmeanBGs.% ofBGswithintargetrange similarbetweenthegroups. Hypoglycaemialesscommon withglarginep=0.036. Largeeffect.Significant differenceinfavourofBBIin regardsglycaemiccontrol, p<0.001,lowermeandaily glucose,meanrandomBGand FPG.Nodifferencein

Restrictedtopost operativecardiac surgery. Patientscouldhave diagnoseddiabetes orhyperglycaemia. Caloricintakevery diminished thereforepatients notrequiringa prandialinsulin component. Tertiaryhospital. Similarpatient populationand treatingteams. Differenceis ceasingalloral

managementof generalmedical patientswithtype2 diabetes.

characteristicssame. Unrestrictededucational eventfromSanofiAventis

Umpierrez 2009103

Umpierrez 2011 (RABBIT2 Surgery)104

130subjects. Randomisedtrial comparingregimens withdetemirand aspartversusneutral protaminehagedorn andregularin medicalpatients withtype2diabetes. 211subjects. Randomisedtrialof basalbolusinsulin therapycomparedto slidingscaleinsulin intheinpatient managementof patientswithtype2 diabetesundergoing generalsurgery

Mediumriskofbias.Selection III bias,randomisationprocess unclear.Informationbias, openlabelstudy.Inclusion andexclusioncriteriadetailed. Baselinecharacteristicsthe same.FinancedbyNovo Nordisk(disclosedandhadno influenceonstudydesign). II Mediumriskofbias. Computergenerated randomisation.Openlabel. Inclusionandexclusioncriteria detailed.Baseline characteristicsthesame. Unrestrictededucational eventfromSanofiAventis

hypoglycaemic agentson admission. Slidingscalenot appropriate comparator. Noeffect.Bothregimens Nodifference Tertiaryhospital. betweenthe equallyaseffectivein Similarpatient loweringmeanBGsandlead treatment populationand groups,p=NS tosimilarratesof treatingteams. hypoglycaemia. Differenceis BG<140mg/dLwasachieved ceasingalloral in45%ofBBIgroupand48% hypoglycaemic insplitmixedgroup. agentson admission. Largeeffect.BBIbetterthan Appropriately Tertiaryhospital. SSIintreatinghyperglycaemia. Similarpatient powered. FBGp=0.037, Significantdifferencebetween populationand groupsinregardsglycaemic meanBG treatingteams. control,p<0.001,lowermean Differenceis p<0.001,BG dailyBGandFPG.More <140mg/dL ceasingalloral p<0.001. hypoglycaemiainBBIgroup. hypoglycaemic Differenceinsecondary Secondary agentson endpointsfavourBBI,with outcomes admission. p=0.003,wound reducedwoundinfectionsand Slidingscalenot ICUstay.NodifferenceinLOS appropriate infection ormortality.Significant p=0.05. comparator. differenceinunitsofinsulin used.

p<0.001,mean glucose throughout hospitalstay p<0.001.

hypoglycaemia.Nodifference insecondaryendpoints(LOS andmortality).Significant differenceintheunitsof insulinused.

45

Appendix8:HowShouldPatientsonInsulinPumpTherapybeManagedinHospital? Table8.1.Generalrecommendationsfordiabeticpatientswhocontinuecontinuoussubcutaneousinsulininfusiontherapyinhospital.
CSII therapy is to be continued in hospital only in those situations where the patient or their guardian have the ability to selfmanage their insulin dosingandthepump(buttonpushingandsetchanges)safely. CSIIshouldneversubstituteforanintravenousinsulininfusiontotreatpatientswithdiabeticketoacidosis. Inametabolicallystablepatient,whoisabletoeat,CSIImaybemoreappropriatethananintravenousinsulininfusionorabasal+topupinjection regimen. RegardlessastowhetherCSIIistobecontinuedorceasedduringthepatientshospitalizationitisstronglyrecommendedthatanendocrineservice consultation (if available) is obtained for all patients at the time of admission. The endocrinologist usually responsible for the care of the patient shouldbenotifiedatthetimeofadmission. The patient will be responsible (in consultation with the endocrine team) for setting basal rates, determining bolus doses administered with meals ortocorrectelevatedglucoselevelsandforsetchanges. ComprehensivedocumentationallaspectsofCSIImanagementisrequired. CSIItherapymustbesubstitutedwitheitherasubcutaneousinsulinregimenoranintravenousinsulininfusionif: 1/Thepatientorguardianisnotabletodemonstratethattheyareabletosafelyandreliablymanagetheinsulinpump. 2/Asevereacuteillnessispresent. 3/AprocedureorinvestigationisplannedpotentiallyrenderingCSIItherapyineffectiveortheanaestheticstaffarenotconfident regardingthemanagementofthepump. 4/Thereareconcernsregardingamalfunctioninthepump. Shouldtherebeconcernsregardingthetechnicalfunctioningofthepumpmanufacturershelplineshouldbecontacted. CSII therapy should never be discontinued without first ensuring the provision of insulin via an alternative route (IV infusion or subcutaneous injection) ThepatientsadmissiontohospitalshouldbeusedasanopportunitytoreviewallaspectsofCSIImanagementbytheEndocrinologyteam.

46

Table8.2.MinimumpatientcompetencyrequirementsforcontinuedinpatientCSIItherapy.
Abilitytooperatethemanagementmenuofthedevicetoalterbasalrates. Ability to operate the management menu of the device to modify parameters of and operate the bolus calculator (including a basic level of proficiencyincarbohydratecounting) Abilitytoperformasetchangeandmanagelineocclusionsorleaksandhaverelevantsuppliestoimplementasetchange.

Table8.3.ContraindicationstocontinuedinpatientCSIItherapy.
Patientisunabletodemonstrateabasiclevelofcompetencyintheoperationoftheirinsulinpump. Impairedorfluctuatingconsciousstate. Majorpsychiatricdisorder(psychosis) Severeacuteillness(includingdiabeticketoacidosis)requiringaninsulininfusion Lackofsupplies(infusionsets,batteriesandotherequipmentrequiredtocontinuethepatientonCSIItherapy) Extensiveskininfectionsorinflammation. Concernsregardingtechnicalmalfunctionofthepump. Numerous radiological procedures (CT and MRI). The pump should be suspended and disconnected prior to the patient entering a CT or MRI scanner. Patientundergoinglengthyorcomplicatedsurgery,orseriousmedicalillnesslikelytobeaccompaniedbysignificantmetabolicdisturbance.

47

Table8.4.HospitaldocumentationrecommendedforinpatientscontinuingCSII.
ThemodelofthepumpanddurationofCSII. Datecurrentpumppurchased. Detailsofinsulindeliveryline. Thenameoftheinsulininfusedwithanindicationthatitisbeingdeliveredviaapump. Insulindeliveryparametersincludingbasalrates,insulintocarbohydrateratios,correctionfactors,durationofinsulinactionandglucosetargets. Any changes to the pump insulin delivery settings should be clearly documented at the time they are implemented. It should also be documented thatthesechangeshavebeenclearlyconveyedtoandconfirmedbythepatientortheirguardian. Thedateandtimeofsetchanges.Afollowupfingerprickglucoseshouldbeperformed2hrslateranddocumented. Fingerprick glucose readings. At least 4 (premeal and bedtime) and preferably 7 (premeal, 2 hour post meal and bedtime) fingerprick glucose readingsarerecommended.Theseshouldbedocumentedontheglucosemonitoringchart. Ketonereadings.Bloodketonesarepreferabletourinaryketonemeasurements. A signed agreement with the patient that clearly documents the patients responsibilities with regard to inpatient CSII management is recommended.

Table8.5.IntraoperativeconditionsappropriateforCSIIorswitchtotemporaryinsulininfusion
SituationsappropriateforintraoperativeCSII Procedureofshortduration(e.g.D&C). Medicalandanaestheticstaffthatarefamiliarwithpumps. Patientawakeandalertintraoperatively. Patientmetabolicallystable. Patient alert and to resume eating shortly after completion of the procedure. Indicationsforintraoperativeintravenousinsulininfusion Prolonged and complicated procedure (eg coronary bypass surgery). MedicalandanaestheticstaffunfamiliarwithCSII. Patientcriticallyunwellandmetabolicallyunstable. Prolongedpostoperativerecoveryperiod.

48

Table8.6.RecommendationsforperioperativemanagementofCSII.
Situation Preoperative Recommendations Intraoperative Performasetchangeonthemorningorafternoonofthedaypriortotheprocedure.Ensurethattheinsertionsiteiswellawayfrom theoperativefield. Infastingpatientsconsiderinfusinginsulinatareducedtemporarybasalrateeg70%. IVdextrose(eg5%at80ml/hr)shouldbeinfusedtopreventketosis. Nobolusesarenecessaryunlesstheyareusedtocorrectelevatedglucoselevels. Monitorglucoselevelsandketoneswithincreasedfrequencyasperthehospitalsestablishedprotocols. IfCSIIistobecontinuedintraoperativelyconsentmustbeobtainedfromthepatientortheirguardian. IfCSIIistobecontinuedintraoperativelyalabelwhichisclearlyvisiblemustbeattachedtothepatientstatingthattheyhaveType1 diabetesandareusinganinsulinpump. EnsurethattheanaesthetistisawarethatCSIIistobecontinuedduringsurgeryandisabletodisconnectthepumpifnecessary. Ensurethatthepumpisaccessibletotheanaesthetistintraoperatively. Glucoselevelsshouldbemonitoredfrequently(atleasthourly)andketonesasdeterminedbytheanaesthetist. IntheeventofanunexplainedelevationinglucoselevelsorfrankketosisanIVinsulininfusionshouldbecommencedandtheinsulin pumpsuspendedanddisconnected. Intheeventofintraoperativehypoglycaemia,thepumpshouldbesuspendedimmediatelyandabolusofIVdextroseadministered. Oncehypoglycaemiahasbeenabolishedtheinsulinpumpcanberecommencedatareducedbasalrate.AlternativelytheIVdextrose canbeinfusedatagreaterrate.Inthefaceofunstableglucoselevels,andananaesthetistwithlimitedCSIIexperience,CSIIshouldbe ceasedandaformalIVinsulininfusioncommenced. Bipolardiathermyiscontraindicated.Unipolardiathermycanbeused. WhencommencingpatientsmanagedwithCSIIonasubcutaneousinsulinregimenthefirstinjection(s)shouldbegivenatthetime CSIIisceasedandshouldincludealongactinginsulinanalogue. Anintravenousinsulininfusionshouldbecommencedwithin2hoursofcessationofCSII. InhospitalizedpatientswhereCSIIhasbeenceasedwiththepatientmanagedonaninsulininfusionormultipledailyinjections,when recommencingCSIIispreferablethatCSIIberecommencedinthemorningandwiththeinsertionofanewline. Inthosemanagedwithmultipledailyinjectionswhileaninpatient,iftheyareonalongactinganalogueadministeredintheevening, halfthedoseshouldbegivenonthenightwithCSIIcommencedthenextmorning. CSIIshouldberecommencedimmediatelypriortocessationofaninsulininfusion.

Ceasingand Recommencing CSII

49

Appendix9:AppropriateGlucoseControlinEndofLifeSituations Table9.1.Phasesofendoflifepathway Phase

Stable Unstable Deteriorating Terminal Table9.2.Suggestedinpatientmanagementoftype1andtype2diabetesinthephasesoftheendoflifepathway Phase Stable Type1diabetes Inpatientmanagementofglycaemiaasperstandardcare.Insulin shouldnotbeceased.Hospitalisationmayprovideanopportunity toreviewtheappropriatenessofthepatientscurrentinsulin regimen,glycaemiatargets,needforanynondiabetes medicationsexacerbatingglycaemiaandgeneraldiabetes education.StablePhasepalliativepatientsareusuallydischarged homefromhospital.Postdischargefollowupshouldbeorganized. AsforStablePhase.Ifthepatientistobedischargedhome considersimplifyingtheirinsulinregimenifappropriate. Liberalisationofthepatientsdietshouldbeconsidered. Type2diabetes Inpatientmanagementofglycaemiaasperstandardcare. Hospitalisationmayprovideanopportunitytoreviewthe appropriatenessofthepatientscurrentdiabetesregimen,glycaemia targets,needforanynondiabetesmedicationsexacerbating glycaemiaandgeneraldiabeteseducation.StablePhasepalliative patientsareusuallydischargedhomefromhospital.Postdischarge followupshouldbeorganised. As for Stable Phase. If the patient is to be discharged home from hospital, a review of the current medication regimen should be undertaken aiming for simplicity, minimisation of the risk for hypoglycaemia and other adverse effects associated with some oral agents.Liberalisationofthepatientsdietshouldbeconsidered. Ifthepatientisonoralhypoglycaemicagentsatthetimeof hospitalisationadecisionisrequiredastowhetherthesearestill appropriateandtheneedforeachreviewed.Ifhyperglycaemiais presentandresponsibleforsymptomsconsidercommencinga simpleinsulinregimene.g.asingledoseofbasalinsulintopromote comfort.Ifthepatientisalreadyoninsulin,simplificationofthe

Description
Thepersonssymptomsareadequatelycontrolledontheirestablishedmanagementplanbutinterventionstomaintainsymptom controlandqualityoflifehavebeenplanned.Thisphasemaylastforseveralyears. Thepersondevelopsanewunexpectedproblemorarapidincreaseintheseverityofexistingproblems. Thepersonsexistingsymptomsgraduallyworsenortheydevelopnewbutunexpectedproblems. Deathislikelyinamatterofdaysandnoacuteinterventionisplannedorrequired.

Unstable

Deteriorating

Adjustments to usual insulin regimen are likely to be required at the time of hospitalisation particularly if nutritional intake is reduced with cachexia, renal and hepatic impairment, delirium or altered conscious state, increasing pain, mucositis, nausea and vomiting.Insulinshouldnotbewithdrawncompletelyunlessitisat the request the patient or their family. Consider simplification of 50

Terminal

the insulin regimen e.g. single basal insulin injection with topups of short actinginsulin analogueto maintaincomfort.Less frequent BGmonitoring(12 perday)andketone checks arerecommended. Aim for BGs between 5.015.0 mmol/L. Remove food restrictions. Review the need for any nondiabetes medications exacerbating hyperglycaemia or hypoglycaemia. If patient is to be discharged home from hospital, consider modifying insulin regimen aiming for simplicity and minimisation of the risk for hypoglycaemia. Ensure followupandsupportofthepatientpostdischarge. The patients preferences or those of their carer take precedence. The primary objectiveis to maintain patient comfort. Asingledaily injection of basal insulin administration may be required to maintain comfort by addressing severe hyperglycaemia and to preventfrankketoacidosis.Considerminimising/ceasingallglucose and ketone monitoring after the appropriate discussion with the patientortheircarer.

currentinsulinregimenshouldbeimplementedifpossiblewithless frequentBGmonitoring(12perday).AimforBGsbetween5.015.0 mmol/L.Removefoodrestrictions.Reviewtheneedforanynon diabetesmedicationsexacerbatinghyperglycaemiaor hypoglycaemia.Ensurefollowupandsupportofthepatientpost discharge.

Theprimaryobjectiveistomaintaincomfort.Considerceasingall glucosemonitoring.Considerceasingallinsulinandoral hypoglycaemicagents.Ifseverehyperglycaemiaandthepatient symptomaticfromhyperglycaemiaconsidercommencingadaily injectionofbasalinsulin.

Table9.3.Factorspotentiallyinfluencingmanagementofglycaemia.
Anorexiaandweightloss. Confusionandalteredconsciousstate. Thestressresponsetopain,anxiety,infectionandunrelatedintercurrentillness. Disturbanceinglucosemetabolismresultingfromsomemalignanttumours. Useofcorticosteroidsandotherdiabetogenicmedications. Metabolicderangementincludingrenalandhepaticdysfunction.

51

Appendix10:HowShouldPatientswithNewlyDiscoveredHyperglycaemiabeFollowedUp? Table10.1.IncidenceofnewlydiagnoseddiabetesatvariousglucoseandHbA1cscreeningthresholds
Study Aim Glucose thresholdand diabetes prevalence 22%prevalence ofundiagnosed diabetesat randomplasma glucose7.8 mmol/l. 60%prevalence ofundiagnosed diabetesat randomplasma glucose6.9 mmol/l. Subjects above Threshold 88 Subjects not described Quality Levelof evidence Riskof Measuresofaccuracyfor Relevance Bias HbA1c

Krebs 2000156

Prevalence study. Retrospect ivetrial.

Greci 2003157

Studyof diagnostic yield.

Nodeclarationof conflictof interest. Inclusion/ exclusioncriteria unclear. 35 Nodeclarationof conflictof Subjects interest. were Smallnumberof described patients. Inclusion/ exclusioncriteria detailed.

IV

Mode rate

IV

High

Gray 2004158

George 2005159

Studyof diagnostic yield,but also prevalence study. Prevalence study.

21%prevalence ofundiagnosed diabetesat randomplasma glucose6.1 mmol/l. 33%prevalence ofundiagnosed diabetesat randomplasma glucose7.0

62 Subjects were described

Declarationsof conflictof interest. Inclusion/ exclusioncriteria detailed previously. Nodeclarations 36 ofconflictof Subjects interest. not Inclusion/ described exclusioncriteria

IV

Mode rate

Atplasmaglucoseof 7.8mmol/LandHbA1c 6.0%. Sensitivity47%. Specificityunableto calculatefromthedata. Sensitivityandspecificity atrandomBG6.9 mmol/landHbA1c>6.0% were57%and100% respectively. Sensitivityandspecificity atrandomBG6.9 mmol/landHbA1c5.2% were100%and50% respectively. PPVat>6%100%,NPVat <5.2%100%. WithrandomBGof6.1 mmol/landHbA1c6.2% Sensitivity=86%, specificity=94% PPV80%,NPV96%

NewZealandhospital. Diabetesdiagnosedby variousmethods.

Similarpatient population. Diabetesdiagnosedon basisoffastingBGx2or GTT. BetterHbA1cassay available(notHPLC)

IV

Mode rate

HbA1cnotdone.

Patientgroupconfined tothosewithacute stroke.UKsetting. Diabetesdiagnosedon basisofGTT. Hba1c6.2%,HbA1c assayHPLC UKhospitalemergency department. Diabetesdiagnosedon basisoffastingplasma glucosex2

52

Wong 2010155

mmol/l. Prevalence 8%prevalence substudyof ofundiagnosed RCToftight diabetesat glucose randomplasma controlfor glucose7.8 myocardial mmol/l. infarction. 11%prevalence ofundiagnosed diabetesat randomplasma glucose5.5 mmol/l.

Valentine Studyof 2011160 diagnostic yield,but also prevalence study.

detailed. 55 Declarationthat therewereno Subjects conflictsof interest. were described Inclusion/ exclusioncriteria detailed previously. 2672 Declarationof conflictof Subjects interestfrom were authors. described Noinclusion/ exclusioncriteria

IV

Mode rate

HbA1cnotreported.

Australianpopulation. Patientgroupconfined tohyperglycaemic patientswith myocardialinfarction. Diabetesdiagnosed mainlyonbasisofGTT.

IV

Mode rate

De Mulder 2011161

Studyof diagnostic yield,but also prevalence study.

25%prevalence ofundiagnosed diabetesat randomplasma glucose7.8 mmol/l.

109 Subjects were described

Declarationthat therewereno conflictsof interest. Inclusion/ exclusioncriteria detailed.

IV

Mode rate

Nomeasuresofaccuracy. Similarpatient population,general medicalpatientsin Australiansetting. Diabetesdiagnosedon basisofHbA1c6.5% (HPLC)only.Poor uptakeofoGTTpost discharge. Dutchhospital.Patient AtrandomBGof groupconfinedto 7.8mmol/LandHbA1c hyperglycaemicpatients 6.5%. Sensitivity29%,specificity withacutecoronary 100%,PPV100%,NPV syndrome. Diabetesdiagnosedby 71% GTT.

Figure11.1.Suggestedapproachtodiagnosisofdiabetesandfollowupofinpatientwithnewlydiscoveredhyperglycaemia.

53

Elevatedrandomblood glucose>7.8mmol/L

DetermineHbA1c

6.5%* (48mmol/mol)

<6.5% (48mmol/mol)

Manageasdiabetes Earlyreferralto inpatient specialistdiabetes teamifavailable Appropriate outpatientfollow up

oralGTTasan outpatientorrepeat HbA1c

EnsureappropriatecommunicationtotheGP

*Internationalexpertcommittee

54

Appendix11:TheSpecialistDiabetesInpatientManagementTeam. Table11.1.Hospitalapproachestodiabetesmanagement Approach

Consultant Service. Systematic Hospitalwide Diabetes Programme Specialist Diabetes Inpatient Management Team

Description
Thetraditionalhospitalmodelofcare,wherebyspecialiseddiabetes servicesareinvited,atthediscretionoftheadmittingteam,toassistwith specificpatientsdiabetesmanagement. Theseprogrammesaimtoimprovetheidentificationofpatientswith diabetesandtoenhancethediabetesmanagementskillsofallstaff,by educationandimplementationofdiabetesmanagementandprescription guidelines.Theresponsibilityofmanagingthepatientsdiabetesremains withtheadmittingteam. Thisinvolvesamultidisciplinaryteamapproach,withtheroleofthe InpatientDiabetesManagementTeamvaryingfromanadvisoryfunction toactivemanagementofthepatientsdiabetes,forallpatientswith diabetesandusuallycommencesatthetimeofthepatientsadmission.

Evidence
Thereisnoevidencethatimprovingthismodelhasresulted inanysubstantialbenefits.Anecdotalevidencesuggeststhat thisisakintoshuttingthegateoncethehorsehasbolted. Theevidencesupportingsuchaninstitutionwideapproach inimprovingdiabetesrelatedoutcomesislimitedtoone comparativestudy162whichdemonstratedareductionin lengthofstayof1.8daysforpatientswithprimarydiabetes followingtheintervention. Severalcomparativetrials(49)haveshownreductionsin ALOSof0.265.6daysfollowinginterventionbyaninpatient diabetesmanagementteam,primarilyinvolvingaspecialist diabetesnurse(somewithprescribingcapabilities).Seetable 11.2.

Table11.2.StudiesexaminingeffectivenessofSpecialistDiabetesInpatientTeams
Koprosky 1997163 StudyDesign RCTofDiabetes TeamCarevs standardcare Subjects Team 179 Diabetesnurse educatorand Endocrinologist Finding Primarydiagnosisdiabetes:medianLOS5.5days (Team)vs7.5days(control) Secondarydiagnosisdiabetes:medianLOS10days (Team)vs10.5days(control) PostdischargecontrolbetterwithTeamCare:75% goodcontrolvs46%.ReadmissionlowerwithTeam Care:15%vs32%,p=0.01. MedianLOS8days(intervention)vs11days(control), p<0.001. Nodifferencereadmissionrate. Interventiongroupmoresatisfiedwithdiabetescare (p<0.001). Controlgroup436moreexpensiveperpatient. MedianLOSdecreasedfrom11to8days(p<0.001) 55 Comment Failuretoachieve significancedueto smallsamplesize? Setting SingleUS medical centre

Davies 2001164

RCTofDiabetes 300 SpecialistNurseCare vsstandardcare

Diabetes specialistnurse

SingleUK teaching hospital

Cavan

Retrospective

1811

Diabetes

Netsavingof4171

SingleUK

2001165

Sampson 2006166

Newton 2006167

analysisofdiabetic admissionspreand postintervention Retrospective analysisofdiabetic admissionspreand postintervention Randomchartaudit preandpost intervention

specialistnurse 14722 Diabetes inpatient specialistnurse service Diabetesclinical nursespecialist, Diabetesnurse casemanagers, medicaldirector Diabetes SpecialistNurse withprescribing rights 5specialist nurses, consultantand specialty registrar Endocrinologist, diabetesnurse specialist,junior doctor

amongstmedicalpatientsand8to5days(p<0.001)in beddaysoverone surgicalpatients year Meanexcessbeddaysfordiabetesadmissions reducedfrom1.9daysto1.2daysafterintroduction oftheservice Reductioninmeanglucoselevelsfrom9.8mmol/Lto 8.4mmol/L(p<0.0001).ReductioninLOSforpatients withdiabetesfrom6.010.32to5.750.38days (p=0.01). Reductioninmedicationerrorsfrommedian6to4 (p<0.01). ReductioninLOSfrommedianfrom9to7days (p<0.05) LOSfellfrom8.3018to7.70.10(p=0.002).Effect predominantlyinmedicalpatients. Emergencyadmissionsfellfrom9.70.2to9.20.2 (p<0.001). Nochangeinelectiveadmissions. ReductioninaverageLOSforallpatientswithdiabetes from9.39to3.76days. NochangeinaverageLOSforpatientswithprimary diagnosisofdiabetes Estimated700bed dayssavedper 1000inpatients withdiabetes Estimatedsavingof $2.2Mperyearfor thehospital

hospital

SingleUK teaching hospital SingleUS tertiary care hospital 6wards inUK general hospital SingleUK teaching hospital

Not reporte d

Courtney 2007168

Flanagan 2008169

Prospectivestudy comparingdiabetic admissionswith interventionvs historicalcontrols Retrospective analysisofdiabetic admissionspreand postintervention Retrospectiveaudit

452

28,016

Brooks 2011170

1140

Estimatedcost saving132,500 over3months

SingleUK district hospital

Table11.3.TheroleoftheSpecialistDiabetesInpatientTeam
Improvingdiabetesmanagementexpertisethroughoutthehospital, Developmentandimplementationofspecificdiabetesmanagementprotocols, Directmanagementofdiabeteswithspecificreferralcriteria, Wardliaison,troubleshooting,managementadvice, Dischargeplanning,

56

Appendix12:WhatRoutineMeasuresShouldbeUndertakenforPeoplewithDiabetesAdmittedtoHospital? Table12.1:Roleofvariousteammembersinensuringoptimalroutinediabetescareinhospitalandafterdischarge.
Teammember Diabetes Educator Roleinhospitalmanagement Ensureappropriatebloodglucosetesting andqualitycontrolofglucosetestingkits, supporttowardnursingstaff. Provideclinicalleadershipandcontinuing stablecareinanenvironmentoftransitional androtatingmedical,nursingandallied healthworkforce. Reportbacktothediabetesteamifinput shouldbeofferedtothereferringunit. Dietitian Ensureappropriatedietinhospitaland nutritionalneedsaremet. Assessreadinesstochangeeatingbehaviour,anddietarycounselingthatis innovativeandspecifictotherequirementsoftheindividual. Roleindischargeplanning Assessandconsolidateknowledgeandskillsregardingeatingplan,physicalactivity, selfmonitoring,medicationusage,insulinadjustment,sickdaymanagement,foot care. Qualifiedprofessionalsare"ADEACredentialledDiabetesEducators"176.Ifavailable, theservicesofadiabeteseducatorareusefulintheearlystagesandacontinuing liaisoncanbeestablished.

LiaisewithDiabetesTeamregardingchanges Providedieteticinterventionrecommendationsthatincludeconsistencyindayto indietparticularlyinthesituationofenteral daycarbohydrateintake,substitutionofsucrosecontainingfoods,usualprotein intake,cardioprotectivenutritioninterventions,weightmanagementstrategies, andparenteralnutrition. regularphysicalactivity Pharmacist Podiatrist Medicinesreview Podiatricadviceandinitialmanagementof highriskfoot Homemedicinesreviewondischargeforpatientswithcomorbidities. Organisefollowupmanagementofhighriskfoot.NoteMedicareEnhancedPrimary CareitemavailableforGPreferrals. Providingculturallyappropriateandpracticalsupportandcounselingforongoing care,thusimprovingpatientunderstandingandadherencetotreatmentprograms. Withoutensuringotheraspectsofthepatientandhis/herfamilywelfarearecatered for,gooddiabetesmanagementmaybechallengingtoachieve. 57

AboriginalHealth Worker SocialWorker Liaisonwithfamilyandsocialservices

ContributorstotheADSGuidelinesforRoutineGlucoseControlinHospital
WritingParty A/ProfNWahCheung DrDavidChipps MsShirleyCornelius* DrBarbaraDepczynski *RepresentingAustralianDiabetesEducatorsAssociation ExpertConsultativePanelandAdditionalContributors ProfFrankAlford MsJanAlford A/ProfSofianosAndrikopoulos A/ProfMarkBoughey ProfLesleyCampbell DrJenniferConn ProfTimothyDavis A/ProfMichaelDEmden DrShirleyElkassaby DrPGerryFegan A/ProfJeffFlack A/ProfJennyGunton A/ProfSanghamitraGuha DrJaneHolmesWalker A/ProfAliciaJenkins A/ProfMaartenKamp MsJenKinsella DrMargaretLayton AworkshopwiththeExpertConsultativePanelwasheldwithsupportfromtheNationalDiabetesServices SchemeinJuly2012. MsFionaMcIver DrAlisonNankervis MsAnnONeill DrGlynisRoss A/ProfAshimSinha DrStephenNStranks ProfHelenaTeede DrVincentWong MsKristineHeels* DrDavidONeal DrJenniferWong A/ProfSophiaZoungas

58

GLOSSARYOFTERMSUSEDRELATINGTOINSULIN Slidingscaleinsulin Supplementalinsulin Correctionalinsulin Basalinsulin Prandialinsulin Basalbolusinsulin Theprescriptionofinsulingiveninavariabledosedependingon theglucoselevelatthetime.Oftenthisisthesoleinsulin prescribed. Theadministrationofvariabledoseinsulintocorrect hyperglycaemia,giveninconjunctionwithappropriateadjustments tothepatientsscheduledantidiabetictherapy. Thistermisusedinterchangeablywithsupplementalinsulin Intermediateorlongactinginsulinprovidingbackgroundinsulin(eg Protaphane,HumulinNPH,Lantus,Levemir) Rapidactinginsulingivenatmealtimes(egNovorapid, Humalog,Apidra) Insulinregimecomprisingthecombinationofabasalinsulinwith multipledailydosesofprandialinsulin Intermediateactinginsulin(egProtaphane,HumulinNPH)

Ispohaneinsulin

Continuoussubcutaneousinsulin Insulinadministeredbycontinuoussubcutaneousinfusionviaan infusion(CSII) patientselfmanagedinsulinpump

59

REFERENCES
1) 2) DunstanD,ZimmetP,WelbornTetal.Therisingprevalenceofdiabetesandimpairedglucose tolerance:TheAustralianDiabetes,ObesityandLifestyleStudy.DiabetesCare2002;25:82934. BarrE,MalianoD,ZimmetPetalAusDiab2005.TheAustralianDiabetes,ObesityandLifestyleStudy. Trackingtheacceleratingepidemic:itscausesandoutcomes.Report.Melbourne:International DiabetesInstitute,2006. Australian Institute of Health and Welfare 2008. Diabetes: Australian facts 2008. Diabetes series no. 8. Cat.no.CVD40.Canberra:AIHW. AubertR,GeissL,BallardD,CocanougherB,Herma.WeDiabetesrelatedhospitalizationandhospital utilization.DiabetesinAmerica.2ndEd.Bethesday,MD:NationalInstitutesofHealth;533559,1995. LevetanC,PassaroM,JablonskiK,KassM,RatnerR.Unrecogniseddiabetesamonghospitalized patients.DiabetesCare21:2469,1998. Abourizk NN, Vora CK, Verma PK. Inpatient diabetology: The new frontier. J Gen Intern Med 2004; 18: 46671. Rando L, Keith C, Sardjono DA, Robertson MB, Colman PG. Diabetes Ward management Room for Improvement.JPharmPractRes2004;34:9599. Wallymahmed ME, Dawes S, Clarke G, Saunders S, Younis N, MacFarlane IA. Hospital inpatients with diabetes:increasingprevalenceandmanagementproblems.DiabetMed2005;22:1079. NHS Institute for Innovation and Improvement. Focus on: Inpatient care for people with diabetes. Coventry:2008. Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: An independent marker of inhospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002; 87:978982. Clement S, Braithwaite SS, Magee MF et al. Management of diabetes and hyperglycemia in hospitals. DiabetesCare2004;27:553591. Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000: 355: 773778. WongV, Ross DL, Park K, Boyages S, Cheung NW. Hyperglycemia following acute myocardial infarction isapredictorofpoorcardiacoutcomesinthereperfusionera.DiabetesResClinPract2004;64:8591. Stranders I, Diamant M, van Gelder RE et al. Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus. Arch Int Med 2004; 164: 982988. Timmer JR, van der Horst ICC, Ottervanger JP et al. Prognostic value of admission glucose in non diabeticpatientswithmyocardialinfarction.AmHeartJ2004;148:399404. Kosiborod M, Rathore SS, Inzucchi SE et al. Admission glucose and mortality in elderly patients hospitalizedwithacutemyocardialinfarction.Circulation2005;111:307886.
60

3) 4) 5) 6) 7) 8) 9) 10)

11) 12)

13) 14)

15) 16)

17)

StraumannE,KurzDJ,MuntwylerJetal.Admissionglucoseconcentrationsindependentlypredictearly and late mortality in patients with acute myocardial infarction treated by primary or rescue percutaneouscoronaryintervention.AmHeartJ2005;150:10001006. Meier JJ, Launhardt V, Deifuss A et al. Plasma glucose at hospital admission and previous metabolic control determine myocardial infarct size ans survival in patients with and without type 2 diabetes. DiabetesCare2005;28:25512553. Goyal A, Mahaffey KW, Garg J et al. Prognostic significance of the change in glucose level in the first 24h after acute myocardial infarction: results from the CARDINAL study. Eur Heart J 2006; 27: 1289 1297. BhadrirajuS, RayKK, DeFrancoACet al. Associationbetween bloodglucoseand longtermmortalityin patientswithacutecoronarysyndromesintheOPUSTIMI16trial.AmJCardiol2006;97:15731577. Naber CK, Mehta RH, Junger C et al. Impact of admission blood glucose on outcomes of nondiabetic patients with acute STelevation myocardial infarction (from the German Acute Coronary Syndromes [ACOS]Registry).AmJCardiol2009;103:58387. Sinnaeve PR, Steg GS, Fox KAA et al. Association of elevated fasting glucose with increased shortterm and 6month mortality in STsegment elevation and nonSTsegment elevation acute coronary syndromes.ArchIntMed2009;169:40209. Ishihara M, Kojima S, Sakamoto T et al. Comparison of blood glucose values on admission for acute myocardialinfarctioninpatientswithversuswithoutdiabetesmellitus.AmJCardiol2009;104:76974. Dziewierz A,Giszterowicz D,SiudakZetal. Impact of admissionglucose level and presenceofdiabetes mellitus on mortality in patients with nonSTsegment elevation acute coronary syndrome treated conservatively.AmJCardiol2009;103:95458. Goyal A, Mehta SR, Diaz R et al. Differential clinical outcomes associated with hypoglycemia and hyperglycemiainacutemyocardialinfarction.Circulation2009;120:242937. DeMulder,CornelJH,vanderPloegT,BoersmaE,UmansVA.Elevatedadmissionglucoseisassociated with increased longterm mortality in myocardial infarct patients, irrespective of the initially applied reperfusionstrategy.AmHeartJ2010;160:41219. Timmer JR, Hoekstra M, Nijsten MWN et al. Prognostic value of admission glycosylated haemoglobin and glucose in nondiabetic patients with STsegment elevation myocardial infarction treated with percutaneouscoronaryintervention.Circulation2011;124:70411. Cheung NW, Wong V, McLean M. The Hyperglycemia: Intensive Insulin Infusion In Infarction (HI5) Study A randomised controlled trial of insulin infusion therapy for myocardial infarction. Diabetes Care2006;29:76570. Cheung NW, Wong VW, McLean M. What glucose target should we aim for in myocardial infarction? DiabetesResClinPract2008;80:41115. Kosiborod M, Inzucchi SE, Krumholz HM et al. Glucose normalization and outcomes in patients with acutemyocardialinfarction.ArchintMed2009;169(5):43846.

18)

19)

20) 21)

22)

23) 24)

25) 26)

27)

28)

29) 30)

61

31)

Malmberg K, Ryden L, Efendic S et al. Randomised trial of insulinglucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI Study): effectsonmortalityat1year.JAmCollCardiol1995;26:5765. Pittas AG, Siegel RD, Lau J. Insulin therapy for critically ill hospitalized patients. Arch Intern Med 2004; 164:200511. Zhao YT, Weng CL, Chen ML et al. Comparison of glucoseinsulinpotassium and insulinglucose as adjunctive therapy in acute myocardial infarction: a contemporary metaanalysis or randomized controlledtrials.Heart2010;96:162226. Devine MJ, Chandrasekara WM, Hardy KJ. Review: Management of hyperglycaemia in acute coronary syndrome.BrJDiabetesVascDis2010;10:5965. Lipton JA, Can A, Akoudad S, Simoons ML. The role of glucose normalization and insulin therapy in patientswithacutecoronarysyndrome.NethHeartJ2011;19:7984. Kansagara D, Fu R, Freeman M, Wolf F, Helfand M. Intensive insulin therapy in hospitalized patients. A systematicreview.AnnInternMed2011;154:26882. Davies RR, Newton RW, McNeill GP, Fisher BM, Kesson CM, Pearson D. Metabolic control in diabetic subjectsfollowingmyocardialinfarction.ScottMedJ1991;36:7476. Scott JF, Robinson GM, French JM, OConnell JE, Alberti KG, Gray CS. Glucose potassium insulin infusions inthetreatment of acute stroke patients with mildtomoderate hyperglycemia.Stroke 1999; 30:793799. Lazar HL, Chipkin S, Philippides G, Bao Y, Apstein C. Glucoseinsulinpotassium solutions improve outcomesindiabeticswhohavecoronaryarteryoperations.AnnThoracSurg2000;70:145150. Szabo Z, Arnqvist H, Hakanson E, Jorfeldt L, Svedjeholm R. Effects of highdose glucoseinsulin potassium on myocardial metabolism after coronary surgery in patients with type II diabetes. Clin Sci (Lond)2001;101:3743. VandenBergheG,WoutersP,WeekersF,etal.Intensiveinsulintherapyincriticallyillpatients.NEngJ Med2001;345:13591367. Groban L, Butterworth J, Legault C, Rogers AT, Kon ND, Hammon JW. Intraoperative insulin therapy does not reduce the need for inotropic or antiarrhythmic therapy after cardiopulmonary bypass. J CardiothoracVascAnesth2002;16:405412. Smith A, Grattan A, Harper M, Royston D, Riedel BJ. Coronary revascularization: a procedure in transitionfromonpumptooffpump?JCardiothoracVascAnesth2002;16:413420. Malmberg K, Ryden L, Wedel H et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2); effects on mortality and morbidity. Eur HeartJ2005;26:650661. Diaz R, Paolasso EC, Piegas LS et al. Metabolic modulation of acute myocardial infarction: the ECLA glucoseinsulinpotassiumpilottrial.Circulation1998;98:22272234. Ceremuzynski L, Budaj A, Czepiel A et al. Lowdose glucoseinsulinpotassium is ineffective in acute myocardial infarction: results of a randomized multicenter PolGIK trial. Cardiovasc Drugs Ther 1999; 13:191200.
62

32) 33)

34) 35) 36) 37) 38)

39) 40)

41) 42)

43) 44)

45) 46)

47) 48) 49) 50) 51) 52)

TheCREATEECLATrialGroupInvestigators.Effectofglucoseinsulinpotassiuminfusiononmortalityin patientswithacuteSTsegmentelevationmyocardialinfarction.JAMA2005;293:437446. VanderHorstICC,ZijlstraF,vantHofAWJetal.Glucoseinsulinpotassiuminfusioninpatientstreated withprimaryangioplastyforacutemyocardialinfarction.J.Am.Coll.Cardiol.(2003)42:784791. Rasoul S, Ottervanger JP, Timmer JR et al. One year outcomes after glucoseinsulinpotassium in ST elevationmyocardialinfarction.TheGlucoseinsulinpotassiumstudyII.IntJCardiol2007;122:5255. Oksanen T, Skrifvars MB, Varpula T et al. Strict versus moderate glucose control after resuscitation fromventricularfibrillation.IntensiveCareMed2007;33:2093100. Malmberg K. Prospective randomized study of intensive insulin treatment on long term survival after acutemyocardialinfarctioninpatientswithdiabetesmellitus.Br.Med.J.(1997)314:151215. Timmer JR, Svilaas T, Ottervanger JP et al. Glucoseinsulinpotassium infusion in patients with acute myocardial infarction without signs of myocardial infarction: The GlucoseInsulinPotassium Study (GIPS)II.JAmCollCardiol2006;47:173031. CheungNW.Glucosecontrolduringacutemyocardialinfarction.InternMedJ2008;38:34548. Ryden L, Standl E, Bartnik M, et al. Guidelines on diabetes, prediabetes, and cardiovascular diseases: executivesummary.EurHeartJ2007;28:88136. Moghissi ES, Korytkowski MT, DiNardo M et al. American Association of Clinical Endocrinologists and American Diabetes Association Consensus Statement on inpatient glycemic control. Diabetes Care 2009;32:11191131. 2009 focused updates: ACC/AHA guidelines for the management of patients with STelevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guideline on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update).CathcardiovcascIntervent2009;74:E2568. Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: A clinical practice guideline from the AmericanCollegeofPhysicians.AnnInternMed2011;154:26067. CapesSE,HuntD,Malmberg,K,PathakP,GersteinHC.Stresshyperglycaemiaandprognosisofstroke innondiabeticanddiabeticpatients:asystematicoverview.Stroke2001;32:24262432. Baird TA, Parsons MW, Phanh T et al. Persistent poststroke hyperglycemia is independently associated withinfarctexpansionandworseclinicaloutcomes.Stroke2003;34:220814. Allport LE, Burcher KS, Baird TA et al. Insular cortex ischemia is independently associated with acute stresshyperglycemia.Stroke2004;35:188691. AlvarezSabin J, Molina CA, Ribo M et al. Impact of admission hyperglycemia on stroke outcome after thrombolysis:Riskstratificationinrelationtotimetoreperfusion.Stroke2004;35:249398. FarrokhniaN,BjorkE, Lindback J,TerentA. Blood glucosein acute stroke,differenttherapeutic targets fordiabeticandnondiabeticpatients?ActaNeuroScand2005;112:8187. StollbergerC,ExnerI,FinstererJ,Slany J, Steger C.Strokein diabeticand nondiabetic patients: course andprognosticvalueofserumglucose.AnnalsMed2005;37:35764.
63

53) 54) 55)

56)

57)

58) 59) 60) 61) 62) 63)

64) 65) 66) 67) 68)

Gentile NT, Seftchick MW, Huynh T, Kruus LK, Gaughan J. Decreased mortality by normalizing blood glucoseafterischemicstroke.AcadEmergMed2006;13:17480. Yong M, Kaste M. Dynamic of hyperglycemia as a predictor of stroke outcome in the ECASSII Trial. Stroke2008;39:274955. Fuentes B, Castillo J, San Jose B et al. The prognostic value of capillary glucose levels in acute stroke: TheGlycemiainAcuteStroke(GLIAS)Study.Stroke2009;40:56268. Stead L, Gilmore R, Bellolio M et al. Hyperglycemia as an independent predictor of worse outcome in nondiabeticpatientspresentingwithacuteischemicstroke.NeurocritCare2009;10:181868. Poppe AY, Majumdar SR, Jeerakathil T, Ghali W, Buchan AM, Hill MD. Admission hyperglycaemia predicts a worse outcome in stroke patients treated with intravenous thrombolysis. Diabetes Care 2009;32:61722. Ntaios G, Egli M, Faouzi M, Michel P. Jshaped association between serum glucose and functional outcomeinacuteischemicstroke.Stroke2010;41:236670. Ahmed N, Davalos A, Eriksson E et al. Association of admission blood glucose and outcome in patients treatedwithintravenousthrombolysis.ArchNeurol2010;67:112330. Dziedzic T, Pera J, TrabkaJanik E, Szczudlik A, Slowik A. Impact of postadmission glycemia on stroke outcome:glucosenormalizationisassociatedwithbettersurvival.Atherosclerosis2010;211:58488. SaposnikG,KapralMK,LiuYetal.IScore:Ariskscoretopredictdeathearlyafterhospitalizationforan acuteischemicstroke.Circulation2011;123:73949. Kimura K, Sakamoto Y, Iguchi Y et al. Admission hyperglycemia and serial infarct volume after tPA therapyinpatientswithandwithoutearlyrecanalization.JNeurolSci2011;307:5559. HuGC,HsiehSF,ChenYM,HuYN,KangYN,ChienKL.Theprognosticrolesofinitialglucoseleveland functionaloutcomesinpatientswithischemicstroke:differencebetweendiabeticandnondiabetic patients.DisabilRehab2012;34:3439. Kruyt ND, Biessels GJ, DeVries JH, Roos YB. Hyperglycemia in acute ischemic stroke: pathophysiology andclinicalmanagement.NatRevNeurol2010;6:14555. Bellolio MF, Gilmore RM, Stead LG. Insulin for glycaemic control in acute ischaemic stroke. Cochrane DatabaseofSystematic Reviews2011,Issue9. Walters MR, Weir CJ, Lees KR. A randomized controlled pilot study to investigate the potential benefit of intervention with insulin in hyperglycaemic acute ischemic stroke patients. Cerebrovasc Dis 2006; 22:11622. Gray CS, Hildreth AJ, Sandercock PA et al. Glucosepotassiuminsulin infusions in the management of poststrokehyperglycaemia:theUKGlucoseInsulininStrokeTrial(GISTUK).Lancet2007;6:397406. AzevedoJR,LimaER,CossettiRJ,AzevedoRP.Intensiveinsulintherapyversusconventionalglycemic controlinpatientswithacuteneurologicalinjury:aprospectivecontrolledtrial.ArqNeuropsiquiatr 2007;65:7338. Bruno A, Kent TA, Coull BM et al. Treatment of hyperglycemia in ischemic stroke (THIS): A randomized pilottrial.Stroke2008;39:38489.
64

69) 70) 71) 72) 73) 74)

75) 76) 77)

78) 79)

80)

81)

YangM,GuoQ,ZhangXetal.Intensiveinsulintherapyoninfectionrate,daysinNICU,inhospital mortalityandneurologicaloutcomeinseveretraumaticbraininjurypatients:arandomizedcontrolled trial.IntJNursStud2009;46:7538. VinychukSM,MalnykVS,MargitichVM.Hyperglycemiaafteracuteischemicstroke:prediction, significanceandimmediatecontrolwithinsulinpotassiumsalinemagnesiuminfusions.HeartDrug 2005;5:197204. KreiselSH,BerschinUM,HammesHPetal.Pragmaticmanagementofhyperglycaemiainacute ischaemicstroke:safetyandfeasibilityofintensiveintravenousinsulintreatment.Cerebrovasc Diseases2009;27:16775. JohnstonKC,HallCE,KisselaBM,BleckTP,ConawayMR,GRASPInvestigators.GlucoseRegulationin AcuteStrokePatients(GRASP)trial:arandomizedpilottrial.Stroke2009;40:38049. MiddletonS,McElduffP,WardJetal.Implementationofevidencebasedtreatmentprotocolsto managefever,hyperglycaemiaandswallowingdysfunctioninacutestrokeimproves90dayoutcomes: QASC,aclusterrandomisedcontrolledtrial.Lancet2011;378(9804):16991706. AHA/ASA Guideline. Guidelines for the early management of adults with ischemic stroke. Circulation 2007;115:e478e534. European Stroke Organisation (ESO) Executive Committee and the ESO Writing Committee. Guidelines for management if ischaemic stroke and transient ischaemic attack 2008. Cerebrovasc Dis 2008; 25: 457507. PomposelliJ,BaxterJ,BabineauTetal.Earlypostoperativeglucosecontrolpredictsnosocomial infectionrateindiabeticpatients:JParenterEnterNutr22:7781,1998. GoldenSH,KaoWHL,PeartVigilanceC,BrancatiFL.Perioperativeglycemiccontrolandtheriskof infectiouscomplicationsinacohortofadultswithdiabetes.DiabetesCare1999;22:14081414. UmpierrezGE,IsaacsSD,BazarganN,YouX,ThalerLM,KitabchiAE.Hyperglycemia:Anindependent markerofinhospitalmortalityinpatientswithundiagnoseddiabetes.JClinEndocrinolMetab.2002; 87:978982. CheungNW,NapierB,ZaccariaC,FletcherJP.Hyperglycemiaisassociatedwithadverseoutcomesin patientsreceivingtotalparenteralnutrition.DiabetesCare2005;28:236771. BakerST,ChianCY,ZajacJD,BachA,JerumsG,MacIsaacRJ.Outcomesforgeneralmedicalpatients withdiabetesmellitusandnewhyperglycaemia.MedJAust2008;188:34043. CheungNW,MaG,LiS,CramptonR.Therelationshipbetweenadmissionbloodglucoselevelsand hospitalmortality.Diabetologia2008;51:9525. HagaKK,McClymontKL,ClarkeSetal.Theeffectoftightglycaemiccontrol,duringandaftercardiac surgery,onpatientmortalityandmorbidity:Asystematicreviewandmetaanalysis.JCardiothorSurg 2011;6:3. MuradMH,CoburnJA,CotoYglesiasFetal.Glycemiccontrolinnoncriticallyillhospitalizedpatients: Asystematicreviewandmeaanalysis.JClinEndocrinolMetab2012;97:4958.

82)

83)

84) 85)

86) 87)

88) 89) 90)

91) 92) 93) 94)

95)

65

96)

LazarHL,ChipkinSR,FitzgeraldCA,BaoY,CabralH,ApsteinCS.Tightglycemiccontrolindiabetic coronaryarterybypassgraftpatientsimprovesperioperativeoutcomesanddecreasesrecurrent ischemicevents.Circulation2004;109:1497502. IngelsC,DebaveyeY,MilantsIetal.Strictbloodglucosecontrolwithinsulinduringintensivecareafter cardiacsurgery:impacton4yearssurvival,dependencyonmedicalcare,andqualityoflife.EurHeartJ 2006,27:27162724. ButterworthJ,WagenknechtLE,LegaultCetal.Attemptedcontrolofhyperglycemiaduring cardiopulmonarybypassfailstoimproveneurologicorneurobehavioraloutcomesinpatientswithout diabetesmellitusundergoingcoronaryarterybypassgrafting.JThoracCardiovascSurg2005;130: 1319. LiJY,SunS,WuSJ.Continuousinsulininfusionimprovespostoperativeglucosecontrolinpatientswith diabetesmellitusundergoingcoronaryarterybypasssurgery.TexHeartInstJ2006;33:44551. BarcellosCdaS,WenderOC,AzambujaPC.Clinicalandhemodynamicoutcomefollowingcoronary arterybypasssurgeryindiabeticpatientsusingglucoseinsulinpotassium(GIK)solution:arandomized clinicaltrial.RevBrasCirCardiovasc2007;22:27584. DickersonLM,YeX,SackJL,HuestonWJ.Glycemiccontrolinmedicalinpatientswithtype2diabetes mellitusreceivingslidingscaleinsulinregimensversusroutinediabetesmedications:Amulticenter randomizedcontrolledtrial.AnnFamMed2003;1:2935. UmpierrezGE,SmileyD,ZismanAetal.Randomizedstudyofbasalbolusinsulintherapyinthe inpatientmanagementofpatientswithtype2diabetes(RABBIT2trial).DiabetesCare2007;30:2181 2186. UmpierrezGE,HorT,SmileyDetal.Comparisonofinpatientinsulinregimenswithdetemirplusaspart versusneutralprotamineHagedornplusregularinmedicalpatientswithtype2diabetes.JClin EndocrinolMetab2009;94:564569 UmpierrezGE,SmileyD,JacobsSetal.Randomizedstudyofbasalbolusinsulintherapyintheinpatient managementofpatientswithtype2diabetesundergoinggeneralsurgery(RABBIT2Surgery).Diabetes Care2011;34:256261. JoshiGP,ChungF,VannMAetal.SocietyforAmbulatoryAnesthesiaconsensusstatementon perioperativebloodglucosemanagementindiabeticpatientsundergoingambulatorysurgery.Anesth Analg2010;111:137887. QaseemA,HumphreyLL,ChouR,SnowV,ShekelleP.Useofintensiveinsulintherapyforthe managementofglycemiccontrolinhospitalizedpatients:Aclinicalpracticeguidelinefromthe AmericanCollegeofPhysicians.AnnInternMed2011;154:26067. KreymanKG,BergerMM,DeutzNEPetal.ESPENGuidelinesonEnteralNutrition:intensivecare.Clin Nutr2006;25:21023. KorytkowskiMT,SalataRJ,KoerbelGLetal.Insulintherapyandglycemiccontrolinhospitalized patientswithdiabetesduringenteralnutritiontherapy:arandomizedcontrolledclinicaltrial.Diabetes Care2009;32:5946.

97)

98)

99) 100)

101)

102)

103)

104)

105)

106)

107) 108)

66

109)

GraingerA,EidenK,KemperJ,ReedsD.Apilotstudytoevaluatetheeffectivenessofglargineand multipleinjectionsoflisproinpatientswithtype2diabetesreceivingtubefeedingsinacardiovascular intensivecareunit.NutrClinPract2007;22:54552. DonihiAC,RavalD,SaulM,KorytkowskiMT,DeVitaMA.Prevalenceandpredictorsofcorticosteroid relatedhyperglycemiainhospitalizedpatients.EndocrPract.2006;12:358362. Fong AC, Cheung NW. The high incidence of steroid induced hyperglycaemia in hospital. Abstract, AustralianDiabetesSocietyAnnualScientificMeeting2011. Burt MG, Roberts GW, AguilarLoza NR, Frith P, Stranks SN. Continuous monitoring of circadian glycemic patterns in patients receiving prednisolone for COPD. J Clin Endocrin Metab 2011; 96: 1789 1996. FeldmanBillard S, Lissak B, Kassaei R, Hron E. Shortterm tolerance of pulse methylprednisolone therapyinpatientswithdiabetesmellitus.Ophthalmology2005;112:511515. GurwitzJH,BohnRL,GlynnRJ,MonaneM,MogunH,AvornJ.Glucocorticoidsandtheriskforinitiation ofhypoglycemictherapy.ArchInternMed1994;154:97101. FajansSS,ConnJW.Anapproachtopredictionofdiabetesmellitusbymodificationoftheglucose tolerancetestwithcortisone.Diabetes1954;3:296304. HenriksenJE,AlfordF,WardGM,BeckNielsenH.Riskandmechanismofdexamethasoneinduced deteriorationofglucosetoleranceinnondiabeticfirstdegreerelativesofNIDDMpatients. Diabetologia,1997;40:14391448. FeldmanBillardS,LissakB,BenrabahR,KassaeiR,HronE.Intravenouspulsemethylprednisolone therapyineyediseaseeffectonglucosetolerance.Ophthalmology2003;110:23692371 SchneiterP,TappyL.Kineticsofdexamethasoneinducedalterationsofglucosemetabolisminhealthy humans.AmJPhysiol1998;275(5Pt1):E80613. PellacaniA,FornengoP,BrunoAetal.Acutemethylprednisoloneadministrationinducesatransient alterationofglucosetoleranceandpyruvatedehydrogenaseinhumans.EurJClinInvest1999;29:861 7. GreenstoneMA,ShawAB.Alternatedaycorticosteroidcausesalternatedayhyperglycaemia.Postgrad MedJ1987;63:761764. Braithwaite SS, Kaufman C, Wittrock JR. Repaglinide monotherapy for diabetes mellitus during glucocorticoidtherapy.TheEndocrinol2003;13:163168. KasayamaS,TanakaT,HashimotoK,KogaM,KawaseI.Efficacyofglimepirideforthetreatmentof diabetesoccurringduringglucocorticoidstherapy.DiabetesCare2002;25:23592360. HenriksenJE,AlfordF,WardGM,BeckNielsenH.Riskandmechanismofdexamethasoneinduced deteriorationofglucosetoleranceinnondiabeticfirstdegreerelativesofNIDDMpatients. Diabetologia1997;40:14391448. CloreJN,ThurbyHayL.Glucocorticoidinducedhyperglycemia.EndocrPract2009;15:469474. OyerDS,ShahA,BettenhausenS.Howtomanagesteroiddiabetesinthepatientwithcancer.JSupport Oncol2006;4:479483.
67

110) 111) 112)

113) 114) 115) 116)

117) 118) 119)

120) 121) 122) 123)

124) 125)

126) 127) 128) 129) 130) 131)

Hoogwerf B, Danese RD. Drug Selection and the management of corticosteroidrelated diabetes mellitus.RheumDiseasClNAmer.1999;25:489505. Luther P, Baldwin D. Pioglitazone in the management of diabetes mellitus after transplantation. Am J Transplant2004;4:21352138. Fujibayashi K, Nagasaka S, Itabashi N et al. Troglitazone efficacy in a subject with glucocorticoid induceddiabetes.DiabetesCare1999;22:20882089. WilliSM,KennedyA,BrantBP,WallaceP,RogersNL,GarveyWT.effectiveuseofthiazolidinedionesfor thetreatmentofglucocorticoidinduceddiabetes.DiabetesResClinPract2002;58:8796. Villanueva G, Baldwin D. Rosiglitazone therapy of posttransplant diabetes mellitus. Transplantation. 2005;80:14021405. Haidinger M, Werzowa J, Voigt HC et al. A randomized, placebocontrolled, doubleblind, prospective trial to evaluate the effect of vildagliptin in newonset diabetes mellitus after kidney transplantation. Trials2010;11:9197. VanRaalteDH,GenugtenRE,LinssenMML,OuwensDM,DiamantM.Glucagonlikepeptide1receptor agonist treatment prevents glucocorticoidinduced glucose intolerance and isletcell dysfunction in humans.DiabCare2011;34:412417. COIITSS Study Investgators. Corticosteroid treatment and intensive insulin therapy for septic shock in adultsarandomisedcontrolledtrial.JAMA2010;303:341348. Scalzo PL, Banks IM, Harris NA, Basu A, Shah P. Glucocorticoid induced hyperglycemia in the inpatient. Abstract,AmericanDiabetesAssociation2010;678P. Hecking M, Werzowa J, Haidinger M, Dller D, Pacini G, Semann M. Early basal insulin therapy prevents newonset diabetes after transplantation by improving endogenous insulin secretion. Abstract,AmericanDiabetesAssociation2011;72OR. Bevier WC, Zisser HC, Jovanovic L et al. Use of continuous glucose monitoring to estimate insulin requirements in patients with type 1 diabetes mellitus during a short course of prednisone. J Diabetes SciTechnol2008;2:578583. HirschIB,PaauwDS.Diabetesmanagementinspecialsituations.EndocrinMetCl1997;26:631645. Mooradian AD, Berbaum M, Albert SG. Narrative review: a rational approach to starting insulin therapy.AnnInternMed2006;145:125134. LeahyJ.Insulinmanagementofdiabeticpatientsongeneralmedicalsurgicalfloors.EndocrPract2006; 12(Suppl3):8690. Wilkinson A, Davidson J, Dotta F et al. Guidelines for the treatment and management of new onset diabetesaftertransplantation.ClinTransplant2005;19:291298. Australian Diabetes Society. Perioperative diabetes management guidelines. ADS 2012. Available at http://www.diabetessociety.com.au/downloads/ADS%20Diabetes%20and%20Surgery%20Guidelines% 20DRAFT%20May%202011.pdf. American Diabetes Association. Standards of care in diabetes 2011. Diabetes Care 2011; 34(suppl 1): S11S61.
68

132)

133) 134) 135)

136)

137) 138) 139) 140) 141)

142)

143)

YeldandiRR,LurieA,BaldwinD.ComparisonofoncedailyglargineinsulinwithtwicedailyNPH/regular insulin for control of hyperglycemia in inpatients after cardiovascular surgery. Diabetes Technol Ther. 2006;8:60916. Cook CB, Boyle ME, Cisar NS et al Use of Subcutaneous Insulin Infusion (Insulin Pump) Therapy in the HospitalSetting;ProposedGuidelinesandOutcomeMeasures.DiabetesEducator2005;31:849857. Inpatient Guidelines: Insulin Infusion Pump Management. Centre for Healthcare Improvement. QueenslandGovernment.July2010. Noschese M, Di Nardo MM, Donihi AC et al. Patient outcomes after implementation of a protocol for inpatientinsulinpumptherapy.EndocrinPract2009.15:415424. Bailon RM, Partlow BJ, MillerCage VM et al. Continuous subcutaneous insulin infusion (insulin pump) therapycanbesafelyusedinthehospitalinselectpatients.EndocrinPract2009;15:2429. LeeSW, ImR,MagbualR.Current perspectiveson the useof continuous subcutaneous insulin infusion intheacutecaresettingandoverviewoftherapy.CritCareNursingQ2004.172184. Nassar AA, Partlow BJ, Boyle ME et al. Outpatienttoinpatient transition of insulin pump therapy: successesandcontinuingchallenges.JDiabetesSciandTechnol2010;4:863872. CookCB.AreTwoInsulinPumpsBetterThanOne?WebM&M.http://webmm.ahrq.gov.CaseID192. CurrowDC,EagarK,AounS,FildesD,YatesPandKristjansonLJ.Isitfeasibletocollectvoluntarily qualityandoutcomedatanationallyinpalliativeoncologycare?JClinOncol200826:385359. DunningT.SavageS,DugganN.MartinP.Guidelinesformanagingdiabetesattheendoflife.Centreof NursingandAlliedHealthResearch,2010Geelong,ISBN9780646536101. Kilvert A, Sinclair A, Rowles S. Association of British clinical diabetologists position statement: Diabetes andendoflifecare.Version630.11.10.PracticalDiabetesInternat2011;28:2627. AngeloM,RuchalskiC,SprogeJB.Anapproachtodiabetesmellitusinhospiceandpalliativemedicine.J PallMed2011;14:8387. WongKYC,WongVW,HoJT,TorpyDJ,McLeanM,CheungNW.Highcortisollevelsinhyperglycemic myocardialinfarctpatientssignifystresshyperglycemiaandpredictsubsequentnormalizationof glucosetolerance.ClinEndocrinol2010;72:18995. KrebsJD,RobinsonGM,SmithRB,ToomathRJ.Followuptestingofhyperglycaemiaduringhospital admission:combineduseoffastingplasmaglucoseandHbA1cNZMedJ2000;113:37981. Greci LS Kailasam M, Malkani S et al. Utility of HbA1c levels for diabetes case finding in hospitalized patientswithhyperglycaemia.DiabetesCare2003;26:10648. GrayCS,ScottJF,FrenchJM,AlbertiKG,O'ConnellJE.Prevalenceandpredictionofunrecognized diabetesmellitusandimpairedglucosetolerancefollowingacutestroke.AgeAgeing2004;33:71. GeorgePM,ValabhjitJ,DawoodM,HenryJA.Screeningfortype2diabetesintheaccidentand emergencydepartment.DiabeticMed2005;22:176669. ValentineNA,AlhawassiTM,RobertsGW,VoraPP,StranksSN,DoogueMP.Detectingundiagnosed diabetesusingglycatedhaemoglobin:anautomatedscreeningtestinhospitalizedpatients.MedJAust 2011;194:160164.
69

144) 145) 146) 147) 148) 149) 150) 151) 152) 153) 154) 155)

156) 157) 158) 159) 160)

161)

DeMulderM,OemrawsinghRM,StamF,BoersmaE,UmansVA.Comparisonofdiagnosticcriteriato detectundiagnoseddiabetesinhyperglycaemicpatientswithacutecoronarysyndrome.Heart2012; 98:3741. OlsonL,MuchmoreJ,LawrenceCB.Thebenefitsofinpatientdiabetescare:improvingqualityofcare andthebottomline.EndocrinPract2006;12(Suppl3):3542. KoproskyJ,PrettoZ,PoretskyL.Effectsofaninterventionbyadiabetesteaminhospitalizedpatients withdiabetes.DiabetesCare1997;20:155355. DaviesM,DixonS,CurrieCJ,DavisRE,PetersJR.Evaluationofahospitaldiabetesspecialistnursing service:arandomizedcontrolledtrial.DiabetMed2001;18:3017. CavanDA,HamiltonP,EverettJ,KerrD.Reducinghospitalstayforpatientswithdiabetes.DiabetMed 2001;18:1624. SampsonMJ,CrowleT,DhatariyaKetal.Trendsinbedoccupancyforinpatientswithdiabetesbefore andaftertheintroductionofadiabetesinpatientspecialistnurseservice.DiabetMed2006;23:1008 15. NewtonCA,YoungS.Financialimplicationsofglycemiccontrol:resultsofaninpatientdiabetes managementprogram.EndocrinPract2006;12(Suppl3):4348. CourtneyM,CareyN,JamesJ,HillsM,RolandJ.Anevaluationofaspecialistnurseprescriberon diabetesinpatientservicedelivery.PracticalDiabetesInt2007;24:6974. FlanaganD,MooreE,BakerS,WrightD,LynchP.Diabetescareinhospitaltheimpactofadedicated inpatientcareteam.DiabetMed2008;25:14751. BrooksAP,VoonL,ChongJSWetal.Theworkofadedicatedinpatientdiabetescareteaminadistrict generalhospital.PracticalDiabetesInt2011;28:702. NHS.NationalDiabetesInpatientAudit2010.Prontaprint2010.Availablefrom http://www.diabetes.nhs.uk/information_and_data/diabetes_audits/national_diabetes_inpatient_aud it/. DiabetesUKTaskandFinishGroup.Commissioningspecialistdiabetesservicesforadultswithdiabetes. DiabetesUK2010.Availablefromhttp://www.diabetes.org.uk/Professionals/Publicationsreportsand resources/Reportsstatisticsandcasestudies/Reports/CommissioningSpecialistDiabetesServicesfor AdultswithDiabetesDefiningASpecialistDiabetesUKTaskandFinishGroupReportOctober 2010/ Editorial.Highalertmedicationsandpatientsafety.IntJQualHealthCare2001;13:33940. ClinicalExcellenceCommission(CEC)andNSWDepartmentofHealth2010.Clinicalincident managementintheNSWpublichealthsystem2009.JanuaryJune.Sydney. CheungNW,CinnadaioN,ONeillAetal.Implementationofadedicatedsubcutaneousinsulin prescriptionchart:Effectonglycaemiccontrol.DiabetesResClinPract2011;92:33741. TheCredentialledDiabetesEducatorinAustralia:Roleandscopeofpractice.AustralianDiabetes EducatorsAssociation,2007.Holder,ACT.ISBN9780975079041.
70

162) 163) 164) 165) 166)

167) 168) 169) 170) 171)

172)

173) 174) 175)

176)