AustralianDiabetesSociety

GuidelinesforRoutineGlucoseControlinHospital



2012

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 Contents
Introduction Page3

Section1MethodologyandProcess Page5

Section2Whatglucosetargetshouldbeaimedforinacutemyocardialinfarction? Page6

Section3Whatglucosetargetshouldbeaimedforinacutestroke? Page8

Section4Whatareappropriateglucosetargetsforpatientsingeneralhospital Page9
wards?

Section5Whatspecialmeasuresneedtobeundertakenforpeopleonenteralor Page11
parenteralnutrition?

Section6Howissteroidinducedhyperglycaemiabestmanaged? Page13

Section7Whatistheoptimalmeansofachievingandmaintainingglycaemic Page15
controlinhospitalisedpatientswhoarenotcriticallyill??

Section8Howshouldpatientsoninsulinpumptherapybemanagedinhospital? Page16

Section9Whatisappropriateglucosecontrolinendoflifesituations? Page18

Section10Atwhatlevelishyperglycaemiainhospitalpredictiveofdiabetesand Page20
howshouldpatientswithnewlydiscoveredhyperglycaemiabefollowed
up?

Section11Whatistheroleofaspecialistdiabetesinpatientteam? Page22

Section12Whatroutinemeasuresshouldbeundertakenforpeoplewith Page23
diabetesadmittedtohospital?

Appendices Page24

Contributors Page59

Glossary Page60

References Page61

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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.

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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.

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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.

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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.

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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
incidencesof6471%110,111.Riskfactorsfordevelopmentofhyperglycaemiaamongstinpatientsincludeapre
existing diagnosisof diabetes110,112, higher HbA1c113, increasingage111, steroid dose114, and family history of
diabetes115,116.

ThereislittledataontemporalBGprofileofindividualsreceivingGC.Anopenprospectiveobservationaltrial
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,
admittedforanotherindicationwhodidnot receive GC117. Patients receiving GCinthemorning hadhigher
BGLsintheafternoonandevening,ascomparedtothosenotreceivingGCs(withthegreatestelevationseen
in those with known diabetes). A rise in fasting glucose is also seen when extremely high dose GC (e.g.
methylprednisone2501000mg/day)areadministered113.Basedonambulatorydata,theeffectofGConBG
profile is rapid, with a change seen within 23 hours of administration of GC118,119. This is also rapidly
reversible,inthatlowerglucoselevelsareseenonGCfreedaysinpatientswhoreceivealternatedayGC120.

ScreeningfordevelopmentofhyperglycaemiaandmonitoringinthosewithDM

PriortoorupontheinitiationofGC,itisprudenttoexcludethepresenceofundiagnoseddiabetesthrough
measurement of serum glucose (see section 11). Screening for development of steroidinduced
hyperglycaemiabyafternoonfingerprickBGassessmentislikelytodetectthedevelopmentofmostcasesof
hyperglycaemia112, and twice daily GC induced hyperglycaemia should still be detected. Reliance on fasting
glucoseisinadequate.Ifhyperglycaemiaisdetected,BGmonitoringshouldoccurasperthegeneraldiabetes
protocol.

Managementofglucocorticoidinducedhyperglycaemia

TherearenoprospectivetrialsontheuseofanyantidiabeticmedicationforthemanagementofGCrelated
hyperglycaemia.ThelimitedobservationaldataareoutlinedinAppendix6,Table6.2.Sulphonylureashavea
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.

Althoughtherearenotrialsofitsuseinsteroidinducedhyperglycaemia,insulinisconsideredtobetheagent
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
typeinsulincanbesupplementedwithultraquickinsulinanaloguewithmeals139.Withtwice,thriceor4times
adayGCregimens,isophaneinsulintwicedailywithprandialrapidactinganaloguecanbeinitiated.Aregime
that controlled glycaemia on previous occasions can be reinitiated, e.g. when cyclical GCs are required, as
longastherehasbeennomajorintervalchangeinweightorrenalfunction.Forthosewithpreexistinginsulin
requiringdiabetes,apreemptiveincreaseininsulinwillberequired,andfurtheradjustmentbasedonblood
glucoseresponse.

RecommendationsandPracticePoints

1. Inpatientsreceivingglucocorticoids,undiagnoseddiabetesshouldbeexcluded.Thosefreeofdiabetes
should be screened for the development of hyperglycaemia by random blood glucose monitoring
performedintheafternoonfollowingmorningadministrationofGC.

2. Hyperglycaemiaisbestmanagedwithinsulin:basalinsulinasisophanetypeinsulin,andrapidacting
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
numbersofpatientswithType1diabetesinAustralia.Anecdotalreportssuggestthatpatientsestablishedon
CSIIusuallyprefertocontinueontheirpumpsduringhospitaladmissions.Hospitalhealthcareproviderswill
increasinglybefacedwiththeissueofhowtomanagesuchinpatients.Anumberofpublicationshavedetailed
guidelinesregardinginpatientmanagementofpatientspreviouslyestablishedonCSII144147. Whilstthereare
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
changedovertosubcutaneousinsulininjectionsandmanagedbytheendocrinologyteam.Thedataregarding
hypoglycaemiaisconflictingwithonestudyindicatingalowerincidenceinthoseinpatientscontinuedonCSII
whichwasnot confirmedwitha subsequentstudy148,149. Acaveatis that thesereportshavestemmedfrom
tertiary academic medical centres in the United States and their applicability to a spectrum of hospitals
(includingcommunityhospitals)inAustraliaisyettobedetermined.Therecommendationsbelowarebased
uponaconsensusopinion.

ManagementofCSIIinHospital

General recommendations for CSII therapy in hospital are outlined in Appendix 8, Table 8.1. In appropriate
circumstances, CSII maybethe preferredmethodofinsulindelivery.However,device operatingmenusand
programsvarynotonlyaccordingtothemanufacturerbutalsofrommodeltomodel.Itishighlyunlikelythat
nonspecialised medical and nursing staff will be familiar with the operation of all available devices. We
thereforerecommendthatCSIItherapyisbecontinuedinhospitalonlyinthosesituationswherethepatient
(or guardian) has the ability to safely selfmanage their insulin dosing and the pump. The competency
requirementsareoutlinedinAppendix8,Table8.2.IfthesecriteriaarenotmetCSIImustbesubstitutedwith
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
endocrinologyteamwith thedocumentedconsent ofthepatientortheirguardian.CSIIandan intravenous
insulininfusionshouldnotbeusedsimultaneouslyforanyextendedperiod150.Thesituationsappropriatefor
intraoperativeCSIIorforitssubstitutionwithanintravenousinsulininfusionareoutlinedinAppendix8,Table
8.5. When CSII is being used intraoperatively, it is important for there is a protocol for its management
(Appendix8,Table8.6.).AppropriateoverlapandtimingisimportantwhenswitchingapatientfromCSIIto
insulininfusionormultiplesubcutaneousinsulininjections,andviceversa(Table8.6.).

16


RecommendationsandPracticePoints

1. Ingeneral,CSIIshouldbecontinuedinhospitalwherethepatientcancompetentlyandsafelyself
managethepumpandselfdosing.

2. Detailsofpumptherapyshouldbedocumented,andsupportedbytheendocrineteam

3. CSIImaybecontinuedforshortoperativeproceduresifthoseresponsibleforthepatients
intraoperativecarearecomfortablewithitsuse.

17
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
urinaryfrequency,alteredconsciousstateandsymptomatichypoglycaemia.Treatmentregimensneedtobe
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
.Thefollowingrepresentsaconsensusofopinionintheabsenceofasuitableevidencebase,andisinpart
basedonthe2010GuidelinesforManagingDiabetesattheEndofLife152.Thisconsensusdocumentfocuses
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

Glucosemanagementduringinpatientadmissionswilldependonthetypeofdiabetesandthephaseofthe
endoflifepathway(seeAppendix9,Table9.2fordetails).Ingeneral,intheearlierstagesofendoflife,the
persons usual diabetes medication would be continued, with adjustments based on the many situational
factorswhichwouldaffectglycaemicstability(Appendix9,Table9.3).Thedecisiontosimplifyandrationalise
treatment regimes and targets would need to be made on an individual basis. As the person progresses
throughthephasesofendoflife,theemphasisshiftstowardsmaintenanceofcomfort,withcorresponding
reductionsinmedicationandglucosetesting,andsomeliberalisationoffoodrestriction.Thisdoesnotimplya
nihilisticapproachinthemetabolicmanagementofpalliativepatients.Avoidanceofmarkedhyperglycaemiais
stillrelevant,particularlyinhospital,toavoidsymptomsofhyperglycaemia,andimprovewoundhealingand
18
resistance to infection. Hypoglycaemia must also be avoided. With type 1 diabetes, ketoacidosis is likely to
precipitatedeath,soitshouldbepreventeduntiladecisionismadetowithdrawalltreatmentintheterminal
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
regardingthemanagementofthepatientsglucoselevelsasmanyyearsmayhavebeenspentwhereglucose
levelshavebeendiligentlymaintainedinatargetrange.Therealisationthatlongtermsurvivalisnolongera
viable proposition and that maintenance of tight glycaemic control is of dubious value and could even
adverselyimpactqualityoflifecanbeconfronting.Ultimatelythedecisionofthepatientandtheirfamilywill
takeprecedence.Thestatusofthepatientmaybeevolvingcontinuouslyrequiringtheongoingreassessment
ofglycaemicmanagementstrategiesbythemedicalteam.

RecommendationsandPracticePoints

1. Palliative care patients may still benefit from a level of glucose control in hospital so diabetes
treatmentremainsrelevant.

2. Thelevelofinterventionwouldgenerallybelessintensivethanforotherhospitalpatients,andneeds
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

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?
Appendices
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)
(MetforminorsulphonylureaorincretinsorDipeptidylPeptidaseIVInhibitorsorthiazolidinediones
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 Comments Methodology

glucosepredictive foreffect?
ofmortality?
13
Wong2004 158 STEMI Yes 8mmol/L Similarrelationshipforbothinpatientand6 Clinicalcohort
monthmortality study
RelationshipbetweenBGanddeathpresent
withandwithoutreperfusiontherapy
Stranders 846 AnyAMI Yes 11.1mmol/Lfor Above11.1mmol/L,nondiabeticshad Retrospective
14
2004 nondiabetics sameriskasthosewithdiabetes. clinicalcohort
study
Timmer 356 STEMIwith Yes 7.8mmol/L Alsoassociationwithlargerinfarctsizeand Posthoc
15
2004 PTCAor reducedLVfunction subanalysisofa
reperfusion clinicaltrialcohort
Kosiborod 141680 Age>65 Yes 6.1mmol/Lfor Similarresultsfor30dayandoneyear Analysisof
16
2005 nondiabetes mortality database
13.3mmol/Lfor
diabetes
Straumann 978 AllhadPTCA Yes 7.8mmol/L Similarresultsfor30dayandlongerterm Analysisof
17
2005 mortality database
18
Meier2005 227 AllAMI Yes 7.4mmol/Lfor Survival>3.5yearswasassessed Clinicalcohort
nondiabetics, study
7.9mmol/Lfor
diabetes
19
Goyal2006 1469 Subanalysisof Yes(onlyfornon Lowermortalityamongstnondiabetics Posthoc
CARDINAL diabetics) wheretherewasagreaterdropinBGover subanalysisofa
Trial 24hrs clinicaltrialcohort
Bhadriraju 9020 Subanalysisof Yes 5.6mmol/L Relationshipstrongerfornondiabetics. Posthoc
20
2006 OPUSTIMI Resultsalsovalidatedinsubanalysisof subanalysisofa
trial TACTICSTIMItrial clinicaltrialcohort
21
Naber2009 5866 Nondiabetic Yes 8.3mmol/L Inpatientand1yearmortality Cohortstudy
STEMI(ACOS
Registry)
Sinnaeve 13526 Globalregistry Yes 6.9mmol/L RandomBGLassociatedwithinpatient Analysisof

25
 22
2009 (random) mortalityonly,fastingBGLassociatedwith database
5.6mmol/L bothinpatientand6monthmortality.
(fasting)
Ishihara 3750 Within48hrs Yes 7mmol/L Ushapedcurveforpatientswithdiabetes, Cohortstudy
23
2009 ofAMI increasedmortalityifBGL<7or>11mmol/L
Dziewiercz 763 NonSTEMI Yes 5mmol/L Relationshipstrongerfornondiabetic Analysisof
24
2009 treated subjects database
conservatively
25
Goyal2009 30536 CREATEECLA Yes 7.8mmol/L Hypoglycaemia<3.3alsopredicted Posthocanalysisof
andOASIS6 mortality clinicaltrialcohorts
cohorts
DeMulder 1185 Both Yes 11mmol/L Eachmmol/Lincreasecorrespondedtoa7% Cohortstudy
26
2010 preinvasive increasedmortality(adjustedHR1.07,95%
andPTCAeras CI1.041.10)
Timmer 4176 Nondiabetic Yes 8.2mmol/L 30dayand1yearmortalityassessed.U Cohortstudy
27
2011 STEMI shapedcurveformortalitywithincreased
mortalityforthosewithBGL6.9mmol/L

26
Table2.2.Observationaldataofarelationshipbetweenaverageglucoselevelsorglucoselevelsachievedinthefirst24hoursaftermyocardial
infarctionandmortality.

Study Subjects Characteristics Glucose Elevated Threshold Comments Methodology

parameter glucose levelfor
predictiveof effect?
mortality?
Cheung 240 Myocardial 12hourly Yes 8mmol/L Posthocsubanalysis
28
2006 , infarct with capillaryBGs ofaclinicaltrial
29 known diabetes cohort
2008
oradmissionBG
7.8mmol/L
Kosiborod 7820 AllAMI Meanglucose Yes 6.1mmol/L Mortalitylowerininsulin Analysisofdatabase
30
2008 measurements treatedpatients

27
Table2.3.Systematicreviewsofrandomizedcontrolledtrialsoftightglucosecontrolinmyocardialinfarction,wheretheprimaryoutcomewas
death.

Review SearchMethod SelectionQuestion Studies Subjects Result/Conclusion Comment

Pittas Medline, StudiesofInsulinincritically AMIsubanalysis:8studies. Subanalysis: Subanalysis:29% Subanalysisincluded
200432 Cochrane illhospitalizedadult Davies199137,Malmberg 2772 reductionin studiesofcoronary
Controlled patients.Subanalysis:those 199531,Scott199938,Lazar mortality(RR0.71, surgeryandICU
ClinicalTrials aimingforglucosecontrol 200039,Szabo200140,van 95%CI0.540.93) patients
Register denBerghe200141,Groban
200242,Smith200243
Zhao Medline, RCTsofGIKorinsulin AMIsubanalyis:3studies. Subanalysis: Subanalysis:No
31
201033 CENTRAL, glucose.Subanalysis:insulin Malmberg1995 , 2113 reductionin
EMBASE glucoseonly 44 mortality(RR1.07,
Malmberg2005 ,Cheung
28
2006 95%CI0.851.36)
31
Devine Medlineand RandomisedtrialsofACS Malmberg1995 ,Diaz Currentevidence Metaanalysisnot
201034 Embase withhyperglycaemia 45
1998 ,Ceremuzynski thatinsulintherapy done
comparinginsulininfusion 46
1999 ,Malmberg2005 ,
44 reducesmortality
orGIKwithactivecontrols CREATEECLA2005 ,
47 andmorbidityinACS
whichassessedmortality 28 isinconclusive
Cheung2006
andmorbidity
Lipton Pubmed Trialswithinsulininpatients
AMIsubanalysis:3studies. Intensiveglucose Metaanalysisnot
31
201135 withunstableanginaorAMI. Malmberg1995 , loweringinsulin done
Subanalysis:thoseaiming 44 therapycanreduce
Malmberg2005 ,Cheung
forglucosenormalization 28
2006 mortality
Kansagara MEDLINE, RCTsusinginsulintoachieve AMIsubanalysis:6studies Subanalysis: NonICU:9studies, 6foldriskofhypos
36 31
2011 Cochrane strictglycaemiccontrol. Malmberg1995 ,Vander 4007 noreductionin (BGL<2.2mmol/L)in
Databaseof Subanalysis:AMI. 48 shorttermmortality allsettingsRR6.0,
Horst2003 ,Malmberg
Systematic 44
2005 ,Cheung2006 ,
28 (RR1.0,95%CI0.94 95%CI4.068.87,
Reviews, 49
Rasoul2007 ,Oksanen 1.07) p<0.001).
50
ClinicalTrials.gov 50 AMI:Nomortality Oksanen =studyof
2007 ,
reduction subjectsfollowingVF
Bold=studieswithspecifiedobjectiveofintensiveglucosecontrolinAMI

Table2.4.Randomisedcontrolledtrialsofmyocardialinfarctionwithaspecificglucosetarget.
28
Trial Subjects EntryCriteria InsulinRegimen Glucose Primary Secondary Comments
Target Outcome Findings
DIGAMI, 620 Myocardialinfarct Variablerate 710 Reducedone Greatestbenefit Amongstfirst327subjects,blood
Malmberg andadmissionBG glucoseinsulin mmol/L yearmortalityin topatientswith glucoseat24hourslowerininsulin
31
1995 , >11.0mmol/L. solutionforat insulininfusion lowpremorbid thanincontrolsubjects(9.22.9vs
51 least24hrs. group(18.6%vs cardiovascular 124.4mmol/L).Insulingroup
1997
26.1%, riskprofile. receivedregularsubcutaneousinsulin
p=0.027). afterdischarge,whichmayhave
contributedtobetteroutcomes.
GIPS,van 940 Within24hrsofST20%glucose 711 Nosignificant MedianBGat16hours7.7mmol/Lfor
derHorst segmentelevation potassium mmol/L. reductionin30 GIKgroupand8.1mmol/Lforcontrols
48
2003 infarct(allhad solutionat daymortality (NS).
PTCA). 3mls/kg/hrwith (4.8%vs5.8%).
insulinat
variablerate.
DIGAMI2, 1253 Myocardialinfarct Variablerate 710 Noreductionin BGat24hoursininsulintreated
Malmberg andeitherknown glucoseinsulin mmol/L mortalitywith groupsonly0.9mmol/Llowerthanfor
44
2005 type2diabetesor solutionforat insulininfusion. conventionaltreatmentgroup
admissionBG>11.0 least24hrs. (9.13.0and9.12.8vs103.6
mmol/L. mmol/L,p=0.0001)
HI5, 240 Myocardialinfarct Variablerate 410 Noreductionin Mortalityhigher Mean24hourBGininsulintreated
Cheung withknown insulinwith5% mmol/L mortalitywith insubjectswith grouponly0.7mmol/Llowerthanfor
28
2006 diabetesor dextrose80 insulininfusion. mean24hour conventionaltreatmentgroup
admissionBG7.8 mls/hr. bloodglucose (8.32.2vs9.02.8mmol/L,NS)
mmol/L. level>8.0
mmol/L.
Othertrialsofinsulinglucosetherapywheretherewerenoglucosetargetswereexcludedfromconsideration:ECLA(1998)45,POLGIK(1999)46,
CREATEECLA(2005)47,GIPSII(2006)52

Table2.5.Guidelinesregardingglucosecontrolinmyocardialinfarction

Guideline Population Recommendation

ESCandEASDguidelinesondiabetes, Peoplewith Thereisreasonableevidencetoinitiateglucosecontrolbymeansofinsulin
prediabetesandcardiovasculardisease, diabetesandAMI infusionindiabeticpatientswhoareadmittedforAMIswithsignificantlyelevated
29
 54
2007
AACE/ADAconsensusstatementon
55
inpatientglycemiccontrol,2009
ACC/AHAguidelinesforthemanagement
ofpatientswithSTelevationmyocardial
56
infarction,2009
ACPguidelinesforintensiveinsulin
therapyforthemanagementofglycemic
controlinhospitalizedpatients,2011
bloodglucoselevelsinordertoreachnormoglycaemiaassoonaspossible(Class
IIa,LevelB)
Allhospitalized Insulininfusionshouldbeusedtocontrolhyperglycaemiainthemajorityofcriticallyill
patients patientsintheICUsetting,withastartingthresholdofnohigherthan10mmoml/L.Target
7.810mmol/L,andgreaterbenefitmayberealizedatthelowerendofthisrange.
Formajorityofnoncriticallyillpatients,premeal<7.8mmol/L,random<10mmol/L.as
longasthiscanbesafelyachieved.
STelevationAMI ReasonabletouseinsulinbasedregimentoachieveandmaintainBG<10mmol/Lwhilst
avoidinghypoglycaemia
Allhospitalized DonotuseintensiveinsulintherapytostrictlycontrolglucoseinnonICUpatientswithor
patients withoutdiabetesmellitus
57
30
Appendix3:LiteraturereviewedforWhatGlucoseTargetShouldbeAimedforinAcuteStroke?

Table3.1.Recentstudiesexaminingtherelationshipbetweenadmissionglucoselevelandstrokeoutcomes.

Study Subjects Characteristics Relationbetween Relationbetween Thresholdlevelfor Comment

admissionglucose admissionglucoseand effect?
andmortality? otheroutcome?
59
Baird2003 25 Ischaemicstroke N/A Yes,infarctsize,NIHSS 7mmol/L
andmRS
60
Allport2004 31 Acuteischaemic N/A Yes,insularcortical N/A
stroke ischaemia
AlvarezSabin 138 MCAterritory N/A YeswithNIHSSandmRS N/A Detrimentalassociation
61
2004 treatedwithtPA greatestwithearlyreperfusion
therapy.
Farrokhnia 447 Acutestroke Yes(onlyfornon N/A Diabetes:10.3 Thresholddeterminedfrom
62
2005 diabetic) mmol/L,non ROC
diabetics:6.3
mmol/L
Stollberger 992 Allacutestroke Yes N/A 9.2mmol/Lfor
63
2005 nondiabetics
64
Gentile2006 960 Ischaemicstroke Yes N/A 7.2mmol/L
65
Yong2008 748 ReceivedtPAfor Yes Yes,withBI,mRS,7day 7.8mmol/L Effectnotseenamongsubjects
acutehemispheric neurological withknowndiabetes
stroke improvement
66
Fuentes2009 476 Acuteischaemic Yes YeswithmRS 8.6mmol/L Thresholddeterminedfrom
stroke ROC
67
Stead2009 447 Acuteischaemic Yes Yeswithstrokeseverity 7.2mmol/L Relationshipstrongerfor
stroke andfunctional patientswithoutdiabetes
impairment
68
Poppe2009 1098 Acuteischaemic Yes Yes,withsymptomatic N/A
stroketreatedwith intracerebral
tPA haemorrhageandmRS
69
Ntaios2010 1446 Ischaemicstroke N/A Yes,withNIHSSand <3.7and>7.2
mRS mmol/L
70
Ahmed2010 16049 Ischaemicstroke Yes Yes,withNIHSSand 6.7mmol/L similarthresholdfordiabetes
treatedwith mRS andnondiabetics
thrombolysis
31
 71
Dziedzic2010 302 Ischaemicstroke Yes N/A N/A
72
Saposnik2011 8223 Acuteischaemic Yes N/A 7.5mmol/L
strokeinregistry
73
Kimura2011 97 ReceivedtPA N/A Infarctvolumelarger 7.2mmol/L Relationshipnotpresent
within3hoursof andworsemRS amongstthosewithsuccessful
strokeonset earlyrecanalisation.
74
Hu2012 774 Acutestroke Notreported Yes,withNIHSS,BIand Diabetes:8.9
mRS mmol/L,non
diabetics:6.8
mmol/L
NIHSS=NationalInstitutesofHealthStrokeScale,BI=BarthelIndex,mRS=modifiedRankinScore

32
Table3.2.Studiesexaminingtherelationshipbetweenmeanglucoselevelsandstrokeoutcomes:

Study Subjects Characteristics Glucose Elevatedglucose Relationbetween Thresholdlevelforeffect?

parameter predictiveof admissionglucoseand
mortality? otheroutcome?

Baird 25 Ischaemicstroke Meancapillary N/A Yes,infarctsize,NIHSS 7mmol/L

59
2003 andmeanCGMS andmRS

Farrokhnia, 447 Acutestroke Meancapillary Yes N/A 10.3mmol/Lfordiabetes,6.3mmol/L

62
2005 fornondiabetics(basedonROC)

Yong 748 ReceivedtPAfor Glucoseat24hrs Yes Yes,BI.mRS,7day 7.8mmol/L

65
2008 acutehemispheric neurologicalrecovery.
stroke

Fuentes 476 Ischaemicstroke Maximum Yes Yes,mRS 8.6mmol/L

66
2009 capillaryglucose

NIHSS=NationalInstitutesofHealthStrokeScale,BI=BarthelIndex,mRS=modifiedRankinScore

33
Table3.3.Systematicreviewsofrandomizedcontrolledtrialsoftightglucosecontrolinstroke,wheretheprimaryoutcomewasdeathorameasure
ofdisability.

Review SearchMethod SelectionQuestion Studies Subjects Result/Conclusion Comment

77
Kansagara MEDLINE,Cochrane RCTsusinginsulinto Walters2006 ,Gray NonICUsetting:9studies,no Increasedriskof
36 78
2011 Databaseof achievestrictglycaemic 2007 ,Azevedo reductioninshortterm hypoglycaemiainall
SystematicReviews, control.Subanalysis: 79
2007 ,Bruno2008 ,
80 mortality(RR1.0,95%CI0.94 settings.
ClinicalTrials.gov strokeandacutebrain Yang2009
81 1.07)
injury Strokeandacutebraininjury:
Noreductioninmortality
Kruyt Notstated Studiesinvestigatingthe Walters200677,Gray BG>10mmol/Lshouldtrigger Reviewnotrestricted
75 78 80
2010 feasibilityandefficacy 2007 ,Bruno2008 insulinadministration. toRCTs
oftightglycaemic
controlinpatientswith
ischaemicstroke

RCTscomparing 82
Bellolio CochraneStroke Vinychuk2005 , 1296 Nodifferenceindeathor Increased
76 GroupTrials intensivelymonitored 77 disabilityanddependence(OR hypoglycaemiawith
2011 Walters2006 ,Gray
Register,CENTRAL, insulintherapyversus 1.00,95%CI0.78to1.28)or
usualcareinadultpatients
78
2007 ,Staszewski intervention.Some
MEDLINE,EMBASE, finalneurologicaldeficit(SMD
withacuteischaemic 2007*,Bruno2008 ,
80 studiesinthisreview
CINAHL,Science 0.12,95%CI0.23to0.00).
stroke. 83 werenotdesignedto
CitationIndex,Web Kreisel2009 ,
assessneuro
ofScience,Scopus Johnston2009
84
outcomes.

Bold=studiesofstrokeonly,*Unpublished

Table3.4.Randomisedcontrolledtrialsofstrokewithaspecificglucosetarget.
34
Trial Subjects EntryCriteria Insulin Glucose Glucose Primary Secondary Comments Hypos
Regimen Target Achieved Outcome Findings
Vinychuk 128 Within24 Glucose <7 Diabetes:7 Improvemen 4armstostudy Notreported
82
2005 hoursof potassiu mmol/L vs11.2 tinNHISS
ischaemic minsulin mmol/Lat comparedto
strokeonset, infusion 1224hrs
admissionBG Nodiabetes:
716mmol/L 5.8vs8.1
mmol/L
Walters 25 Within24 Variable 58 Intarget 1deathinsulin Apilotstudy 1ininsulin
77
2006 hoursof rate mmol/L 87%ofthe group,0in group,0in
ischaemic insulin timevs71% controlgroup controls
strokeonset, infusion ofthetime
admissionBG (p<0.001)
820mmol/L
GISTUK, 933 Within24 Glucose 47 GKIgroup Noreduction Noreduction Trialdiscontinued 41.2%GKI
Gray hoursof potassiu mmol/L 0.57mmol/L indeathat inresidual earlyduetoslow patientshadBG
78
2007 strokeonset, minsulin lower 90dayswith disabilityor recruitment.BG <4mmol/Land
admissionBG infusion (p<0.001) GKI functional dropped 15.7%required
617mmol/L recovery spontaneouslyin rescueiv
controlgroup. glucose
Bruno 46 Within12 Variable <7.2 7.4vs10.5 Diffin 2deathinsulin Apilotstudy 35%vs13%had
80
2008 hoursof rate mmol/L mmol/L glucose group,0in hypos<3.3
cerebral insulin achieved controlgroup
infarctandBG infusion
8.3mmol/L for72hrs
Kreisel 40 Within24 Variable 4.46.1 6.5vs8.0 Diffin Nodifference Notpoweredtodetect 25vs2hypo
83
2009 hoursof rate mmol/L mmol/L, glucose indeathor differenceindeath events(p<0.05)
ischaemic insulin p<0.0005 achieved functional anddisability
strokeonset infusion outcome
Johnston 74 Within12 Variable 3.96.1 6.2vs8.4 Diffin Nodifference 3armstostudy 30%vs4%had
84
2009 hoursof rate mmol/L mmol/L glucose indeathor Notpoweredtodetect atleastone
cerebral insulin achieved functional differenceindeath hypo
infarctandBG infusion outcome anddisability
6.1mmol/L

35
Middleton 1126 Within48 Variable 48 7.0vs6.8 Differencein Nodifference Interventionwas Notreported.
85
2011 hoursof rate mmol/L mmol/L, mortalityor inBarthel packageofglucose,
acutestroke insulin orlocal p=0.02 dependency index,but fever,andswallowing
infusionif guidelin (Notesmall 42%vs58% higherSF36 management.Not
BG>=11 esonce difference (p=0.002) PhysicalHealth possibletodetermine
mmol/Lif insulin only) Scorein contributionofglucose
diabetes, infusion intervention control.
>=16for comme
non nced
diabetics,
upto72
hours

Table3.4.Guidelinesregardingglucosecontrolinstroke

Guideline Population Recommendation

AHA/ASAguidelinesfortheearly Ischaemicstroke Serumglucoseconcentrations(possibly>7.8to10.3mmol/L)probably

managementofadultswith
ischemicstroke,200786
87
EuropeanStrokeGuidelines,2008
shouldtriggeradministrationofinsulin(ClassIIa,LevelofEvidenceC).
Ischaemicstroke Treatmentofserumglucoselevels>10mol/Lwithinsulintitrationis
recommended(ClassIVevidence).
Severehypoglycaemia[<2.8mmol/Lshouldbetreatedwith
intravenousdextroseorinfusionof1020%glucose(ClassIVevidence)

36
Appendix4:LiteratureReviewedforQuestionWhatareAppropriateGlucoseTargetsforPatientsinGeneralHospitalWards?

Table4.1.Observationalstudiesexaminingtherelationshipbetweenhyperglycaemiaandoutcomesinhospitaloutsideofthesituationsof
intensivecare,myocardialinfarctionandstroke.

Study Subjects Finding Comment

Pomposelli 97patientsundergoing SingleBGL>12.2mmol/Lpredictiveofnosocomialinfection

1999Study88 generalsurgery

Golden 411CABGpatients MeancapillaryBGL11.5mmol/Lassociatedwith

199989 increasedinfection

Umpierrez, 2030admissionstoa 2xFastingBGL7.0mmol/LorrBGL11.1mmol/L Riskhigherfornewhyperglycaemiathan

200290 communityteaching associatedwithincreasedmortality,needforICUand diabetes
hospital longerLOS
Cheung 122subjectsonTPN MeanBGL7.9mmol/Lassociatedwithincreasedinfection
200591 MeanBGL9.1mmol/Lassociatedwithincreasedmortality

Baker200892 903patientsingeneral AdmissionBGL5.6mmol/Lassociatedwithincreased NoassociationbetweenBGlevelsand

medicalward mortality mortalityamongstpeoplewithknown
diabetes.HbA1calsopredictiveof
mortalityinnondiabetics.

Cheung, 6187admissionstoa AdmissionBGL>8.0mmol/Lpredictiveofmortalityand Riskhigherfornewhyperglycaemiathan

200893 teachinghospital longerLOS diabetes

Table4.2.Systematicreviewsofstudiesexaminingtrialsoftightglycaemiccontroloutsideoftheintensivecaresetting,andnotspecifically
focusingonmyocardialinfarctionorstroke

37
Review SelectionQuestion Studies Total Result/Conclusion Comment
subjects
Haga Effectsoftightversus 3studies:Groban200242,Lazar 686 48%reductioninmortality(OR
201194 normalglycaemiccontrol,peri 200496,Ingels200697 0.52,95%CI0.30.91,p=0.02).
andpostoperatively,inpatients Maybesomebenefittotight
undergoingcardiacsurgery. glycaemiccontrolduringandafter
cardiacsurgery.
Kansagara RCTsusinginsulintoachieve 9nonICUstudies:Malmberg NonICU: NonICUsetting:noreductionin Notrialsin
201136 strictglycaemiccontrol. 199531,VanderHorst200341, 2677 shorttermmortality(RR1.0, generalmedical
Subanalysis:NonICUstudies Butterworth2005,Li2006, 95%CI0.941.07). wards
Subanalysis:Perioperative Cheung200628,Oksanen200750, Perioperative:noreductionin Perioperative
Azevedo200779,Yang200981, shorttermmortality. studiesmostly
5perioperativestudies:Smith poorquality
200243,Lazar200439,Butterworth RRhypoglycaemia
200598,Li200699,Barcellos2007100 6.0,95%CI4.06
8.87,p<0.001).
Murad Observationalorrandomized 19studies:RCTsMalmberg Variedfor Noassociationbetweenintensive Inclusionof
201295 studiesthatcomparedthe 199531,Dickerson2003101,vander different glucosecontrolandriskofdeath, observational
effectofintensiveglycaemic Horst200348,Malmberg200531, analyses myocardialinfarctionorstroke. studiesis
28 77
controltoacontrolgroup Cheung2006 ,Walters2006 , Associationwithreducedriskof questionable.
seekinglessaggressive Umpierrez2007102,Umpierrez infection(RR0.41,95%CI0.21
normalization 2009103,Umpierrez2011104 0.77).Trendtoincreased
ofglycaemiclevels.Intensive hypoglycaemia.
caresettingexcluded.

38
Table4.3.Existingguidelinesforglucosetargetsinnoncriticallyillpatientsinhospital.

Guideline Population Recommendation

AACE/ADA,200955 Allhospitalized Insulininfusionshouldbeusedtocontrolhyperglycaemiainthemajorityofcriticallyill

patients patientsintheICUsetting,withastartingthresholdofnohigherthan10mmol/L.Target7.8
10mmol/L,andgreaterbenefitmayberealizedatthelowerendofthisrange.

Formajorityofnoncriticallyillpatients,premeal<7.8mmol/L,random<10mmol/L,aslong
asthiscanbesafelyachieved.

SocietyforAmbulatory Preandintra Insufficientdatatorecommendthelevelofpreoperativefastingbloodglucoseabovewhich

Anesthesia,2010105 operative electiveambulatorysurgeryshouldbepostponed.Noevidencethatanyparticularblood
glucoseleveliseitherbeneficialorharmfulforpatientsundergoingambulatorysurgical
procedures.Suggestthatinpatientswithwellcontrolleddiabetes,intraoperativeblood
glucoselevelsbemaintained<10mmol/L.

ACP,2011106 Allhospitalized DonotuseintensiveinsulintherapytostrictlycontrolglucoseinnonICUpatientswithor

patients withoutdiabetesmellitus.

EndocrineSociety,2012107 Recommendpremealtarget<7.8mmol/L,randomtarget<10mmol/L,butmodifyaccordingto
clinicalstatus.ReassesstherapyifBGvaluesfallbelow5.6mmol/L.ModifytherapywhenBG
valuesare<3.9mmol/L.

39
Appendix5:LiteratureReviewedforQuestionWhatisthebestmethodtomaintainglycaemiccontrolinahospitalizedpatientwhoisreceiving
parenteralorenteralnutrition?

Table5.1.Clinicaltrialsofglucosecontrolamongpatientsreceivingenteralorparenteralfeeding.

Paper Design Quality Levelof Statisticalprecision Sizeanddirection Relevance

evidence ofeffect
Koryt Slidingscaleinsulin(46hourlyifBGL Selectionbias,randomization II Nodifferencebetween Noeffect.Both Inpatient
kowski >7.1mmol/l)vsslidingscaleinsulin processnotdescribed. thetreatmentgroupsin regimens population
2009108 andglargine. Informationbias,openlabel meanstudyglucose effectivein receiving
Targetglucoserange(5.610mmol/l). study.FinancedbySanofi levelsp=NS. loweringmean enteral
Noncriticallyillhospitalizedpatients Aventis;clearlydisclosedand glucoselevels. nutrition
with2BGLsover7.2mmol/l(withor statedthatsponsordidnot Similarratesof therapy.
withoutpriordiagnosisofdiabetes) influencestudydesign hypoglycaemia
Receivingenteralnutritiontherapy conduct.Inclusion/exclusion onBGmeasures,
formulaanddeliveryatdiscretionof criteriadescribed. totaladverse
nutritionteamwithmajorityreceiving Baselinecharacteristicssimilar eventsandLOS.
50%carbohydrate. betweengroups.Large Similartotaldaily
percentage(55%)ofpatients insulindoses.
inSSIarmalsoreceivedNPH
insulin.
Grainger Variabledosepreprandialinsulin Selectionbias,high. III3 Lowermeanglucosein Insulinprotocol ICU
2007109 (standardofcare)vsnurseledinsulin Informationbias,high. interventioncfcontrol increased inpatient
protocol(variabledoselispro,regular Inclusion/exclusioncriteria groupp<0.001.Greater proportionof population
+correctionaldose)andfixeddose described. proportionin patients receiving
glargine(weightdependent). Usedhistoricalcontrolsfrom interventiongroup achievingtarget enteral
Criticallyillhospitalisedpatientswith beforeprotocol achievedgoalglucose bloodglucose nutrition
knowntype2diabetesorFBG>11.1. implementation. rangep<0.01,+shorter range. therapy.
Receivingbolusenteralnutrition ExcludedNIRDMpatients. timetoachieveglucose Modestincrease
(TwoCalHNorNeprorenalfailure)q4 Baselinecharacteristics,few control21vs60hrs,p in
hourstoprovide6feeds/day. reportedbutsimilar. notreported.Increased hypoglycaemia.
hypoglycaemiap=0.02.

40
Appendix6:LiteraturereviewedfortheQuestionHowissteroidinducedhyperglycaemiabestmanaged?

Table6.1.Incidenceofsteroidinducedhyperglycaemia.

Author StudyDesign Steroid Incidenceofsteroidinduced Riskfactorsforsteroidinduced Comment

hyperglycaemia hyperglycaemia
Fajans1954115 steroidgiven CRHorcortisone N/A Firstdegreerelativewith
priortoaGTT diabetes
Gurwitz1994114 Casecontrol Anyoralglucocorticoids N/A Steroiddose(oddsratiorose Hyperglycaemia
study from1.77for39mg/day basedonprescription
hydrocortisoneequivalent,rising oforalantidiabetic
to10.34for120mg/dayormore agent
FeldmanBillard Retrospective Pulse 64%hadatleastoneBG14 HigherHbA1c
2005113 audit methylprednisolone mmol/L
Donihi2006110 Retrospective Atleastprednisone40 Overall64%hadatleastone Preexistingdiabetes 21%patientsnot
audit mg/dayorequivalent BG11.1mmol/L. screened
for2days 56%amongstnondiabetics.
Fong2011111 Prospective Atleastprednisone25 71%hadatleastoneBG Age
audit mg/dayfor2days 10mmol/L
Burt,2011112 Prospective Atleastprednisone20 53%hadatleastoneBG Preexistingdiabetes UsedCGMS
study mg/dayfor2days 10mmol/L

41
Table6.2.Evidenceregardingtheeffectivenessofantidiabeticmedicationinthemanagementofsteroidinducedhyperglycaemia.
Medication InterventionStudies
Class
Metformin Notrialsidentified
Sulphonyl Noprospectivetrials.Studiesinambulatorysettingonly.
ureas(SU) A retrospective review of 40 ambulatory pts with diabetes at
baseline who had received prednisone (dose range 540mg/day
formanagementofnonendocrineconditionssuchasCOPDand
SLE)described5patientswhohadreceivedrepaglinide.However
insulinwasalsorequiredtoachieveglycaemiccontrolin4ofthe
5121.
Kasayama reported 3 adult ambulatory patients with
immunological conditions, initially requiring prednisone 20
40mg/day, and maintained on 510mg/day, who developed
hyperglycaemiaafter12yrsofmaintenanceGCtherapy122.All3
were able to be controlled with glimepiride monotherapy (1
3mg),achievingHba1c<7%.
Thiazolidine Publishedreportsofuseforsteroidinducedhyperglycaemiain
diones settingoforgantransplantationonly.Pioglitazoneimproved
glycaemiccontrolasanadjuncttoinsulin(meanHbA1cfallingby
1.28%)inaseriesofrenaltransplantrecipientsmanagedwith
prednisone(420mg/day)andsirolimusormycophenolate,6of
the10patientshaddiabetespredatingtheirtransplant127.
Efficacyofotherthiazolidinedionesforposttransplantdiabetes
orGCrelatedDMhasalsobeendescribed128130.
Incretins No completed trials identified. A trial of vildagliptin in the
managementofposttransplantdiabetesisinprogress131.
Insulin Notrialsofinsulinregimensinmanagementofsteroidinduced
hyperglycaemiainhospitalotherthanintravenousinsulin133.
Observationalreportsuggeststhatuseofmorningisophane
insulinversuslongactinginsulin(eitherinsulinwithrapidacting
insulinatmealtime)achievedglycaemiccontrolmorequickly134.
Preliminaryreportsuggeststhatearlyuseofbasalinsulininthe
OtherLiteratureandComments
Limitationstoitsuseintheinpatientsettingmayincludethepresence
ofriskfactorsforlacticacidosis,orvariableoralintake
AlthoughpredominanteffectofGCsisareductionininsulinsensitivity,
individualswhodevelophyperglycaemiawithGCadministration,havea
reducedinsulinsecretorycapacity123.Henceinsulinsecretogoguesare
notanidealchoice.RiskofhypoglycaemiaasGCtaperediflongacting
agentsareused124,wherethereismealomission125orifrenalfunctionis
reduced126.SUusehasbeensuggestedtobelimitedtothosewith
milderdegreesofGCinducedhyperglycaemia,wherefastingBG
<7mmol/L126.SinceinpatientsusuallyreceivehighGCdosesandmay
havevariableoralintakeorrenalfunction,SUshavealimitedrole.
Delayedonsetofactionmakesthisgroupgenerallyunsuitableforacute
inpatientmanagementofhyperglycaemia.
PotentialrolehasbeenexploredbyvanRaalte132.
Wheremarkedfastinghyperglycaemia(>10mmol/L)ispresent,insulinis
thought to provide better management than oral agents126,137. Insulin
providesgreaterdoseflexibility,morerapidonsetofactionandtitration
andthereisusuallynodoseceiling.Insulindoserequirementsneedto
be individualised, due to variations in insulin sensitivity, insulin
secretory capacity, GC regimen and dosing, oral intake, renal function
42
 settingofrenaltransplantation,preventsthedevelopmentof
subsequentnewonsetdiabetes135.
Inresponsetoprednisone60mg/dayaseriesof10patientswith
T1DMmanagedwithsubcutaneousinsulinpumprequiredan
increaseofbetween30100%136.
and prior control. Preemptive increases and decreases in insulin
requiredasGCdoseisadjusted.Thisusuallyrequiresdailyadjustment.
Generallytheinsulinregimenoradjustmentstoapreexistingregimen
should predominantly target postprandial control, and with morning
GCadministration,theafternoonhyperglycaemia.Clorehasadvocated
the use of isophane insulin for management of steroid
hyperglycaemia124,theinitialdosedeterminedaccordingtoGCdoseand
patient weight (e.g. prednisone 10mg daily requires 0.1unit/kg/day as
isophaneinsulin;prednisone40mgdailyrequires0.4unit/kg/day),and
titratedaccordingtoresponse.Forapatientalreadyoninsulin,thismay
be added to the existing regimen. This titration schedule is easier to
continueupondischargethanmorecomplexregimens,andmorelikely
tobesuccessfulifpatientshaveaconsistentroutineandcarbohydrate
consumptionfromdaytoday138.Isophaneinsulincanbesupplemented
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,
isophaneinsulintwicedailywithprandialrapidactinganaloguecanbe
initiated.Aregimethatcontrolledglycaemiaonpreviousoccasionscan
bereinitiatedwhencyclicalGCsarerequired,aslongastherehasbeen
nomajorintervalchangeinweightorrenalfunction.
43
Appendix7:LiteratureReviewedforQuestionWhatisthebestmethodtomaintainglycaemiccontrolinahospitalizedpatientwhoisnot
criticallyill?

Table7.1.Randomisedcontrolledtrialscomparinginsulinregimesforglucosecontrolinhospital.

Author Studydesign QualityandriskofBias Levelof Statistical Sizeanddirectionofeffect Relevance

evidence precisionand
significance
Dickerson 153subjects. Mediumhighriskofbias.Bias III1 Statistical Primaryoutcomewas Generalmedical
2003101 Randomisedtrial thatpopulationchosenfrom calculations frequencyofhyperglycaemia patients,similarto
comparingglycaemic conveniencesample. includedin (>16.7)andhypoglycaemia Australiangeneral
controlinmedical Randomisationprocedure studydesign. (<2.8).Nodifferencebetween medicalwards
patientswithtype2 clearlydescribed.Openlabel. Hyperglycaemic thetwogroups.
diabetesreceiving Clearexclusioncriteria. and Nodifferenceinsecondary
slidingscaleinsulin Baselinecharacteristicsmostly hypoglycaemic outcomewhichwasLOS.
versusroutine similar.Mayhavebeen events.
diabetes treatmentchangesduring
medications. study.
Yeldandi 94patients. Mediumriskofbias. III1 Nocalculations Minimaleffect.Calculated% Restrictedtopost
2006143 Randomisedtrial Randomisationprocedurenot weredoneto ofBGswithintargetrange. operativecardiac
comparingonce described.Openlabel. showpower. SimilarBGsachievedwith surgery.
dailyglargineinsulin Noexclusioncriteria.Baseline MeanBG bothregimensinwhole Patientscouldhave
withtwicedaily characteristicssimilar. 124mg/dLv cohort.Subgroupwith diagnoseddiabetes
NPH/regularinsulin 131mg/dL diabetes:bdNPHhadlower orhyperglycaemia.
forcontrolof p=0.065 meanBGthanglargine. Caloricintakevery
hyperglycaemiain Hypoglycaemia Subgroupwithoutdiabetes: diminished
inpatientspost lesswith nodifferenceinmeanBGs.% thereforepatients
cardiovascular glargine ofBGswithintargetrange notrequiringa
surgery. p=0.036. similarbetweenthegroups. prandialinsulin
Hypoglycaemialesscommon component.
withglarginep=0.036.
Umpierrez 130patients. Mediumriskofbias. III1 Unclearifstudy Largeeffect.Significant Tertiaryhospital.
2007 Randomisedtrialof Notclearlydefinedwhatthe appropriately differenceinfavourofBBIin Similarpatient
(RABBIT2 basalbolusinsulin randomizationprocesswas. powered. regardsglycaemiccontrol, populationand
Trial)102 therapycomparedto Openlabel. FBGp<0.001, p<0.001,lowermeandaily treatingteams.
slidingscaleinsulin Inclusionandexclusioncriteria meanrandom glucose,meanrandomBGand Differenceis
intheinpatient detailed.Baseline bloodglucose FPG.Nodifferencein ceasingalloral

44
 managementof characteristicssame. p<0.001,mean hypoglycaemia.Nodifference hypoglycaemic
generalmedical Unrestrictededucational glucose insecondaryendpoints(LOS agentson
patientswithtype2 eventfromSanofiAventis throughout andmortality).Significant admission.
diabetes. hospitalstay differenceintheunitsof Slidingscalenot
p<0.001. insulinused. appropriate
comparator.
Umpierrez 130subjects. Mediumriskofbias.Selection III Nodifference Noeffect.Bothregimens Tertiaryhospital.
2009103 Randomisedtrial bias,randomisationprocess betweenthe equallyaseffectivein Similarpatient
comparingregimens unclear.Informationbias, treatment loweringmeanBGsandlead populationand
withdetemirand openlabelstudy.Inclusion groups,p=NS tosimilarratesof treatingteams.
aspartversusneutral andexclusioncriteriadetailed. hypoglycaemia. Differenceis
protaminehagedorn Baselinecharacteristicsthe BG<140mg/dLwasachieved ceasingalloral
andregularin same.FinancedbyNovo in45%ofBBIgroupand48% hypoglycaemic
medicalpatients Nordisk(disclosedandhadno insplitmixedgroup. agentson
withtype2diabetes. influenceonstudydesign). admission.
Umpierrez 211subjects. Mediumriskofbias. II Appropriately Largeeffect.BBIbetterthan Tertiaryhospital.
2011 Randomisedtrialof Computergenerated powered. SSIintreatinghyperglycaemia. Similarpatient
(RABBIT2 basalbolusinsulin randomisation.Openlabel. FBGp=0.037, Significantdifferencebetween populationand
Surgery)104 therapycomparedto Inclusionandexclusioncriteria meanBG groupsinregardsglycaemic treatingteams.
slidingscaleinsulin detailed.Baseline p<0.001,BG control,p<0.001,lowermean Differenceis
intheinpatient characteristicsthesame. <140mg/dL dailyBGandFPG.More ceasingalloral
managementof Unrestrictededucational p<0.001. hypoglycaemiainBBIgroup. hypoglycaemic
patientswithtype2 eventfromSanofiAventis Secondary Differenceinsecondary agentson
diabetesundergoing outcomes endpointsfavourBBI,with admission.
generalsurgery p=0.003,wound reducedwoundinfectionsand Slidingscalenot
infection ICUstay.NodifferenceinLOS appropriate
p=0.05. ormortality.Significant comparator.
differenceinunitsofinsulin
used.

45
Appendix8:HowShouldPatientsonInsulinPumpTherapybeManagedinHospital?

Table8.1.Generalrecommendationsfordiabeticpatientswhocontinuecontinuoussubcutaneousinsulininfusiontherapyinhospital.

CSIItherapyistobecontinuedinhospitalonlyinthosesituationswherethepatientortheirguardianhavetheabilitytoselfmanagetheirinsulin
dosingandthepump(buttonpushingandsetchanges)safely.
CSIIshouldneversubstituteforanintravenousinsulininfusiontotreatpatientswithdiabeticketoacidosis.
Inametabolicallystablepatient,whoisabletoeat,CSIImaybemoreappropriatethananintravenousinsulininfusionorabasal+topupinjection
regimen.
RegardlessastowhetherCSIIistobecontinuedorceasedduringthepatientshospitalizationitisstronglyrecommendedthatanendocrineservice
consultation(ifavailable)isobtainedforallpatientsatthetimeofadmission.Theendocrinologistusuallyresponsibleforthecareofthepatient
shouldbenotifiedatthetimeofadmission.
Thepatientwillberesponsible(inconsultationwiththeendocrineteam)forsettingbasalrates,determiningbolusdosesadministeredwithmeals
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.
Anychangestothepumpinsulindeliverysettingsshouldbeclearlydocumentedatthetimetheyareimplemented.Itshouldalsobedocumented
thatthesechangeshavebeenclearlyconveyedtoandconfirmedbythepatientortheirguardian.
Thedateandtimeofsetchanges.Afollowupfingerprickglucoseshouldbeperformed2hrslateranddocumented.
Fingerprickglucosereadings.Atleast4(premealandbedtime)andpreferably7(premeal,2hourpostmealandbedtime)fingerprickglucose
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 Indicationsforintraoperativeintravenousinsulininfusion
Procedureofshortduration(e.g.D&C). Prolonged and complicated procedure (eg coronary bypass
Medicalandanaestheticstaffthatarefamiliarwithpumps. surgery).
Patientawakeandalertintraoperatively. MedicalandanaestheticstaffunfamiliarwithCSII.
Patientmetabolicallystable. Patientcriticallyunwellandmetabolicallyunstable.
Patient alert and to resume eating shortly after completion of the Prolongedpostoperativerecoveryperiod.
procedure.

48
Table8.6.RecommendationsforperioperativemanagementofCSII.

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

49
Appendix9:AppropriateGlucoseControlinEndofLifeSituations

Table9.1.Phasesofendoflifepathway

Phase Description
Stable Thepersonssymptomsareadequatelycontrolledontheirestablishedmanagementplanbutinterventionstomaintainsymptom
controlandqualityoflifehavebeenplanned.Thisphasemaylastforseveralyears.
Unstable Thepersondevelopsanewunexpectedproblemorarapidincreaseintheseverityofexistingproblems.
Deteriorating Thepersonsexistingsymptomsgraduallyworsenortheydevelopnewbutunexpectedproblems.
Terminal Deathislikelyinamatterofdaysandnoacuteinterventionisplannedorrequired.

Table9.2.Suggestedinpatientmanagementoftype1andtype2diabetesinthephasesoftheendoflifepathway

Phase Type1diabetes Type2diabetes

Stable Inpatientmanagementofglycaemiaasperstandardcare.Insulin
shouldnotbeceased.Hospitalisationmayprovideanopportunity
toreviewtheappropriatenessofthepatientscurrentinsulin
regimen,glycaemiatargets,needforanynondiabetes
medicationsexacerbatingglycaemiaandgeneraldiabetes
education.StablePhasepalliativepatientsareusuallydischarged
homefromhospital.Postdischargefollowupshouldbeorganized.
Unstable AsforStablePhase.Ifthepatientistobedischargedhome AsforStablePhase.Ifthepatientistobedischargedhomefrom
considersimplifyingtheirinsulinregimenifappropriate.
Liberalisationofthepatientsdietshouldbeconsidered.
Deteriorating Adjustments to usual insulin regimen are likely to be required at
the time of hospitalisation particularly if nutritional intake is
reducedwithcachexia,renalandhepaticimpairment,deliriumor
altered conscious state, increasing pain, mucositis, nausea and
vomiting.Insulinshouldnotbewithdrawncompletelyunlessitisat
the request the patient or their family. Consider simplification of
Inpatientmanagementofglycaemiaasperstandardcare.
Hospitalisationmayprovideanopportunitytoreviewthe
appropriatenessofthepatientscurrentdiabetesregimen,glycaemia
targets,needforanynondiabetesmedicationsexacerbating
glycaemiaandgeneraldiabeteseducation.StablePhasepalliative
patientsareusuallydischargedhomefromhospital.Postdischarge
followupshouldbeorganised.
hospital, a review of the current medication regimen should be
undertaken aiming for simplicity, minimisation of the risk for
hypoglycaemiaandotheradverseeffectsassociatedwithsomeoral
agents.Liberalisationofthepatientsdietshouldbeconsidered.
Ifthepatientisonoralhypoglycaemicagentsatthetimeof
hospitalisationadecisionisrequiredastowhetherthesearestill
appropriateandtheneedforeachreviewed.Ifhyperglycaemiais
presentandresponsibleforsymptomsconsidercommencinga
simpleinsulinregimene.g.asingledoseofbasalinsulintopromote
comfort.Ifthepatientisalreadyoninsulin,simplificationofthe

50
 theinsulinregimene.g.singlebasal insulin injectionwithtopups
ofshortactinginsulinanaloguetomaintaincomfort.Lessfrequent
BGmonitoring(12perday)andketonechecksarerecommended.
AimforBGs between5.015.0mmol/L. Removefoodrestrictions.
Review the need for any nondiabetes medications exacerbating
hyperglycaemia or hypoglycaemia. If patient is to be discharged
homefromhospital,considermodifyinginsulinregimenaimingfor
simplicity and minimisation of the risk for hypoglycaemia. Ensure
followupandsupportofthepatientpostdischarge.
Terminal Thepatientspreferencesorthoseoftheircarertakeprecedence.
Theprimaryobjectiveistomaintainpatientcomfort.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 Subjects Quality Levelof Riskof Measuresofaccuracyfor Relevance

thresholdand above evidence Bias HbA1c
diabetes Threshold
prevalence
Krebs Prevalence 22%prevalence 88 Nodeclarationof IV Mode Atplasmaglucoseof NewZealandhospital.
2000156 study. ofundiagnosed conflictof rate 7.8mmol/LandHbA1c Diabetesdiagnosedby
Retrospect diabetesat Subjects interest. 6.0%. variousmethods.
ivetrial. randomplasma not Inclusion/ Sensitivity47%.
glucose7.8 described exclusioncriteria Specificityunableto
mmol/l. unclear. calculatefromthedata.
Greci Studyof 60%prevalence 35 Nodeclarationof IV High Sensitivityandspecificity Similarpatient
2003157 diagnostic ofundiagnosed conflictof atrandomBG6.9 population.
yield. diabetesat Subjects interest. mmol/landHbA1c>6.0% Diabetesdiagnosedon
randomplasma were Smallnumberof were57%and100% basisoffastingBGx2or
glucose6.9 described patients. respectively. GTT.
mmol/l. Inclusion/ Sensitivityandspecificity BetterHbA1cassay
exclusioncriteria atrandomBG6.9 available(notHPLC)
detailed. mmol/landHbA1c5.2%
were100%and50%
respectively.
PPVat>6%100%,NPVat
<5.2%100%.
Gray Studyof 21%prevalence 62 Declarationsof IV Mode WithrandomBGof6.1 Patientgroupconfined
2004158 diagnostic ofundiagnosed Subjects conflictof rate mmol/landHbA1c6.2% tothosewithacute
yield,but diabetesat were interest. Sensitivity=86%, stroke.UKsetting.
also randomplasma described Inclusion/ specificity=94% Diabetesdiagnosedon
prevalence glucose6.1 exclusioncriteria PPV80%,NPV96% basisofGTT.
study. mmol/l. detailed Hba1c6.2%,HbA1c
previously. assayHPLC
George Prevalence 33%prevalence 36 Nodeclarations IV Mode HbA1cnotdone. UKhospitalemergency
2005159 study. ofundiagnosed ofconflictof rate department.
diabetesat Subjects interest. Diabetesdiagnosedon
randomplasma not Inclusion/ basisoffastingplasma
glucose7.0 described exclusioncriteria glucosex2
52
 mmol/l. detailed.

Wong Prevalence 8%prevalence 55 Declarationthat IV Mode HbA1cnotreported. Australianpopulation.
2010155 substudyof ofundiagnosed therewereno rate Patientgroupconfined
RCToftight diabetesat Subjects conflictsof tohyperglycaemic
glucose randomplasma were interest. patientswith
controlfor glucose7.8 described Inclusion/ myocardialinfarction.
myocardial mmol/l. exclusioncriteria Diabetesdiagnosed
infarction. detailed mainlyonbasisofGTT.
previously.
Valentine Studyof 11%prevalence 2672 Declarationof IV Mode Nomeasuresofaccuracy. Similarpatient
2011160 diagnostic ofundiagnosed conflictof rate population,general
yield,but diabetesat Subjects interestfrom medicalpatientsin
also randomplasma were authors. Australiansetting.
prevalence glucose5.5 described Noinclusion/ Diabetesdiagnosedon
study. mmol/l. exclusioncriteria basisofHbA1c6.5%
(HPLC)only.Poor
uptakeofoGTTpost
discharge.
De Studyof 25%prevalence 109 Declarationthat IV Mode AtrandomBGof Dutchhospital.Patient
Mulder diagnostic ofundiagnosed therewereno rate 7.8mmol/LandHbA1c groupconfinedto
2011161 yield,but diabetesat Subjects conflictsof 6.5%. hyperglycaemicpatients
also randomplasma were interest. Sensitivity29%,specificity withacutecoronary
prevalence glucose7.8 described Inclusion/ 100%,PPV100%,NPV syndrome.
study. mmol/l. exclusioncriteria 71% Diabetesdiagnosedby
detailed. GTT.

Figure11.1.Suggestedapproachtodiagnosisofdiabetesandfollowupofinpatientwithnewlydiscoveredhyperglycaemia.

53
 Elevatedrandomblood
glucose>7.8mmol/L

DetermineHbA1c

6.5%* <6.5%
(48mmol/mol) (48mmol/mol)

#
Manageasdiabetes oralGTTasan
outpatientorrepeat
Earlyreferralto HbA1c
inpatient
specialistdiabetes
teamifavailable #
EnsureappropriatecommunicationtotheGP
Appropriate
outpatientfollow
*Internationalexpertcommittee
up

54
Appendix11:TheSpecialistDiabetesInpatientManagementTeam.

Table11.1.Hospitalapproachestodiabetesmanagement

Approach Description Evidence

Consultant Thetraditionalhospitalmodelofcare,wherebyspecialiseddiabetes Thereisnoevidencethatimprovingthismodelhasresulted
Service. servicesareinvited,atthediscretionoftheadmittingteam,toassistwith inanysubstantialbenefits.Anecdotalevidencesuggeststhat
specificpatientsdiabetesmanagement. thisisakintoshuttingthegateoncethehorsehasbolted.
Systematic Theseprogrammesaimtoimprovetheidentificationofpatientswith Theevidencesupportingsuchaninstitutionwideapproach
Hospitalwide diabetesandtoenhancethediabetesmanagementskillsofallstaff,by inimprovingdiabetesrelatedoutcomesislimitedtoone
Diabetes educationandimplementationofdiabetesmanagementandprescription comparativestudy162whichdemonstratedareductionin
Programme guidelines.Theresponsibilityofmanagingthepatientsdiabetesremains lengthofstayof1.8daysforpatientswithprimarydiabetes
withtheadmittingteam. followingtheintervention.
Specialist Thisinvolvesamultidisciplinaryteamapproach,withtheroleofthe Severalcomparativetrials(49)haveshownreductionsin
Diabetes InpatientDiabetesManagementTeamvaryingfromanadvisoryfunction ALOSof0.265.6daysfollowinginterventionbyaninpatient
Inpatient toactivemanagementofthepatientsdiabetes,forallpatientswith diabetesmanagementteam,primarilyinvolvingaspecialist
Management diabetesandusuallycommencesatthetimeofthepatientsadmission. diabetesnurse(somewithprescribingcapabilities).Seetable
Team 11.2.

Table11.2.StudiesexaminingeffectivenessofSpecialistDiabetesInpatientTeams

StudyDesign Subjects Team Finding Comment Setting

Koprosky RCTofDiabetes 179 Diabetesnurse Primarydiagnosisdiabetes:medianLOS5.5days Failuretoachieve SingleUS
1997163 TeamCarevs educatorand (Team)vs7.5days(control) significancedueto medical
standardcare Endocrinologist Secondarydiagnosisdiabetes:medianLOS10days smallsamplesize? centre
(Team)vs10.5days(control)
PostdischargecontrolbetterwithTeamCare:75%
goodcontrolvs46%.ReadmissionlowerwithTeam
Care:15%vs32%,p=0.01.
Davies RCTofDiabetes 300 Diabetes MedianLOS8days(intervention)vs11days(control), SingleUK
2001164 SpecialistNurseCare specialistnurse p<0.001. teaching
vsstandardcare Nodifferencereadmissionrate. hospital
Interventiongroupmoresatisfiedwithdiabetescare
(p<0.001).
Controlgroup436moreexpensiveperpatient.
Cavan Retrospective 1811 Diabetes MedianLOSdecreasedfrom11to8days(p<0.001) Netsavingof4171 SingleUK

55
2001165 analysisofdiabetic specialistnurse amongstmedicalpatientsand8to5days(p<0.001)in beddaysoverone hospital
admissionspreand surgicalpatients year
postintervention
Sampson Retrospective 14722 Diabetes Meanexcessbeddaysfordiabetesadmissions Estimated700bed SingleUK
2006166 analysisofdiabetic inpatient reducedfrom1.9daysto1.2daysafterintroduction dayssavedper teaching
admissionspreand specialistnurse oftheservice 1000inpatients hospital
postintervention service withdiabetes
Newton Randomchartaudit Not Diabetesclinical Reductioninmeanglucoselevelsfrom9.8mmol/Lto Estimatedsavingof SingleUS
2006167 preandpost reporte nursespecialist, 8.4mmol/L(p<0.0001).ReductioninLOSforpatients $2.2Mperyearfor tertiary
intervention d Diabetesnurse withdiabetesfrom6.010.32to5.750.38days thehospital care
casemanagers, (p=0.01). hospital
medicaldirector
Courtney Prospectivestudy 452 Diabetes Reductioninmedicationerrorsfrommedian6to4 6wards
2007168 comparingdiabetic SpecialistNurse (p<0.01). inUK
admissionswith withprescribing ReductioninLOSfrommedianfrom9to7days general
interventionvs rights (p<0.05) hospital
historicalcontrols
Flanagan Retrospective 28,016 5specialist LOSfellfrom8.3018to7.70.10(p=0.002).Effect SingleUK
2008169 analysisofdiabetic nurses, predominantlyinmedicalpatients. teaching
admissionspreand consultantand Emergencyadmissionsfellfrom9.70.2to9.20.2 hospital
postintervention specialty (p<0.001).
registrar Nochangeinelectiveadmissions.
Brooks Retrospectiveaudit 1140 Endocrinologist, ReductioninaverageLOSforallpatientswithdiabetes Estimatedcost SingleUK
2011170 diabetesnurse from9.39to3.76days. saving132,500 district
specialist,junior NochangeinaverageLOSforpatientswithprimary over3months hospital
doctor diagnosisofdiabetes

Table11.3.TheroleoftheSpecialistDiabetesInpatientTeam

Improvingdiabetesmanagementexpertisethroughoutthehospital,
Developmentandimplementationofspecificdiabetesmanagementprotocols,
Directmanagementofdiabeteswithspecificreferralcriteria,
Wardliaison,troubleshooting,managementadvice,
Dischargeplanning,

56
Appendix12:WhatRoutineMeasuresShouldbeUndertakenforPeoplewithDiabetesAdmittedtoHospital?

Table12.1:Roleofvariousteammembersinensuringoptimalroutinediabetescareinhospitalandafterdischarge.

Teammember Roleinhospitalmanagement Roleindischargeplanning

Diabetes Ensureappropriatebloodglucosetesting Assessandconsolidateknowledgeandskillsregardingeatingplan,physicalactivity,

Educator andqualitycontrolofglucosetestingkits, selfmonitoring,medicationusage,insulinadjustment,sickdaymanagement,foot
supporttowardnursingstaff. care.

Provideclinicalleadershipandcontinuing Qualifiedprofessionalsare"ADEACredentialledDiabetesEducators"176.Ifavailable,
stablecareinanenvironmentoftransitional theservicesofadiabeteseducatorareusefulintheearlystagesandacontinuing
androtatingmedical,nursingandallied liaisoncanbeestablished.
healthworkforce.

Reportbacktothediabetesteamifinput
shouldbeofferedtothereferringunit.

Dietitian Ensureappropriatedietinhospitaland Assessreadinesstochangeeatingbehaviour,anddietarycounselingthatis

nutritionalneedsaremet. innovativeandspecifictotherequirementsoftheindividual.

LiaisewithDiabetesTeamregardingchanges Providedieteticinterventionrecommendationsthatincludeconsistencyindayto
indietparticularlyinthesituationofenteral daycarbohydrateintake,substitutionofsucrosecontainingfoods,usualprotein
andparenteralnutrition. intake,cardioprotectivenutritioninterventions,weightmanagementstrategies,
regularphysicalactivity

Pharmacist Medicinesreview Homemedicinesreviewondischargeforpatientswithcomorbidities.

Podiatrist Podiatricadviceandinitialmanagementof Organisefollowupmanagementofhighriskfoot.NoteMedicareEnhancedPrimary

highriskfoot CareitemavailableforGPreferrals.

AboriginalHealth Providingculturallyappropriateandpracticalsupportandcounselingforongoing
Worker care,thusimprovingpatientunderstandingandadherencetotreatmentprograms.

SocialWorker Liaisonwithfamilyandsocialservices Withoutensuringotheraspectsofthepatientandhis/herfamilywelfarearecatered

for,gooddiabetesmanagementmaybechallengingtoachieve.

57
ContributorstotheADSGuidelinesforRoutineGlucoseControlinHospital

WritingParty

A/ProfNWahCheung MsKristineHeels*

DrDavidChipps DrDavidONeal

MsShirleyCornelius* DrJenniferWong

DrBarbaraDepczynski A/ProfSophiaZoungas

*RepresentingAustralianDiabetesEducatorsAssociation

ExpertConsultativePanelandAdditionalContributors

ProfFrankAlford DrPGerryFegan MsFionaMcIver

MsJanAlford A/ProfJeffFlack DrAlisonNankervis

A/ProfSofianosAndrikopoulos A/ProfJennyGunton MsAnnONeill

A/ProfMarkBoughey A/ProfSanghamitraGuha DrGlynisRoss

ProfLesleyCampbell DrJaneHolmesWalker A/ProfAshimSinha

DrJenniferConn A/ProfAliciaJenkins DrStephenNStranks

ProfTimothyDavis A/ProfMaartenKamp ProfHelenaTeede

A/ProfMichaelDEmden MsJenKinsella DrVincentWong

DrShirleyElkassaby DrMargaretLayton

AworkshopwiththeExpertConsultativePanelwasheldwithsupportfromtheNationalDiabetesServices
SchemeinJuly2012.

58
GLOSSARYOFTERMSUSEDRELATINGTOINSULIN

Slidingscaleinsulin Theprescriptionofinsulingiveninavariabledosedependingon
theglucoselevelatthetime.Oftenthisisthesoleinsulin
prescribed.

Supplementalinsulin Theadministrationofvariabledoseinsulintocorrect
hyperglycaemia,giveninconjunctionwithappropriateadjustments
tothepatientsscheduledantidiabetictherapy.

Correctionalinsulin Thistermisusedinterchangeablywithsupplementalinsulin

Basalinsulin Intermediateorlongactinginsulinprovidingbackgroundinsulin(eg
Protaphane,HumulinNPH,Lantus,Levemir)

Prandialinsulin Rapidactinginsulingivenatmealtimes(egNovorapid,
Humalog,Apidra)

Basalbolusinsulin Insulinregimecomprisingthecombinationofabasalinsulinwith
multipledailydosesofprandialinsulin

Ispohaneinsulin Intermediateactinginsulin(egProtaphane,HumulinNPH)

Continuoussubcutaneousinsulin Insulinadministeredbycontinuoussubcutaneousinfusionviaan
infusion(CSII) patientselfmanagedinsulinpump

59


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