Variability of insulin sensitivity during the first 4 days of critical illness: implications for tight glycemic control

Pretty, Le, Chase J, Shaw, Preiser Jean-Charles, Penning Sophie, Desaive, Desaive Thomas

Description

Effective tight glycemic control (TGC) can improve outcomes in critical care patients, but it is difficult to achieve consistently. Insulin sensitivity defines the metabolic balance between insulin concentration and insulin-mediated glucose disposal. Hence, variability of insulin sensitivity can cause variable glycemia. This study quantifies and compares the daily evolution of insulin sensitivity level and variability for critical care patients receiving TGC. Methods This is a retrospective analysis of data from the SPRINT TGC study involving patients admitted to a mixed medical-surgical ICU between August 2005 and May 2007. Only patients who commenced TGC within 12 hours of ICU admission and spent at least 24 hours on the SPRINT protocol were included (N = 164). Model-based insulin sensitivity ( SI ) was identified each hour. Absolute level and hour-to-hour percent changes in SI were assessed on cohort and per-patient bases. Levels and variability of SI were compared over time on 24-hour and 6-hour timescales for the first 4 days of ICU stay. Results Cohort and per-patient median SI levels increased by 34% and 33% ( p < 0.001) between days 1 and 2 of ICU stay. Concomitantly, cohort and per-patient SI variability decreased by 32% and 36% ( p < 0.001). For 72% of the cohort, median SI on day 2 was higher than on day 1. The day 1–2 results are the only clear, statistically significant trends across both analyses. Analysis of the first 24 hours using 6-hour blocks of SI data showed that most of the improvement in insulin sensitivity level and variability seen between days 1 and 2 occurred during the first 12–18 hours of day 1. Conclusions Critically ill patients have significantly lower and more variable insulin sensitivity on day 1 than later in their ICU stay and particularly during the first 12 hours. This rapid improvement is likely due to the decline of counter-regulatory hormones as the acute phase of critical illness progresses. Clinically, these results suggest that while using TGC protocols with patients during their first few days of ICU stay, extra care should be afforded. Increased measurement frequency, higher target glycemic bands, conservative insulin dosing, and modulation of carbohydrate nutrition should be considered to minimize safely the outcome glycemic variability and reduce the risk of hypoglycemia.

Sujets

• Critical care
• Hyperglycemia
• Insulin resistance
• Mathematical model
• Algorithm

Informations

• Publié par: biomed
• Publié le: 01 janvier 2012
• Nombre de lectures: 8
• Langue: English
• Poids de l'ouvrage: 2 Mo

Extrait

Pretty
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2012,
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http://www.annalsofintensivecare.com/content/2/1/17

RESEARCH

OpenAccess

Variabilityofinsulinsensitivityduringthefirst
4daysofcriticalillness:implicationsfortight
glycemiccontrol
ChristopherGPretty
1
,AaronJLeCompte
1
,JGeoffreyChase
1*
,GeoffreyMShaw
2
,Jean-CharlesPreiser
3
,
SophiePenning
4
andThomasDesaive
4*

Abstract
Background:
Effectivetightglycemiccontrol(TGC)canimproveoutcomesincriticalcarepatients,butitisdifficultto
achieveconsistently.Insulinsensitivitydefinesthemetabolicbalancebetweeninsulinconcentrationandinsulin-mediated
glucosedisposal.Hence,variabilityofinsulinsensitivitycancausevariableglycemia.Thisstudyquantifiesandcompares
thedailyevolutionofinsulinsensitivitylevelandvariabilityforcriticalcarepatientsreceivingTGC.
Methods:
ThisisaretrospectiveanalysisofdatafromtheSPRINTTGCstudyinvolvingpatientsadmittedtoamixed
medical-surgicalICUbetweenAugust2005andMay2007.OnlypatientswhocommencedTGCwithin12hoursofICU
admissionandspentatleast24hoursontheSPRINTprotocolwereincluded(N=164).Model-basedinsulinsensitivity(
SI
)
wasidentifiedeachhour.Absolutelevelandhour-to-hourpercentchangesin
SI
wereassessedoncohortandper-patient
bases.Levelsandvariabilityof
SI
werecomparedovertimeon24-hourand6-hourtimescalesforthefirst4daysofICU
sat.yResults:
Cohortandper-patientmedian
SI
levelsincreasedby34%and33%(
p
<
0.001)betweendays1and2ofICU
stay.Concomitantly,cohortandper-patient
SI
variabilitydecreasedby32%and36%(
p
<
0.001).For72%ofthecohort,
median
SI
onday2washigherthanonday1.Theday1
–
2resultsaretheonlyclear,statisticallysignificanttrendsacross
bothanalyses.Analysisofthefirst24hoursusing6-hourblocksof
SI
datashowedthatmostoftheimprovementin
insulinsensitivitylevelandvariabilityseenbetweendays1and2occurredduringthefirst12
–
18hoursofday1.
Conclusions:
Criticallyillpatientshavesignificantlylowerandmorevariableinsulinsensitivityonday1thanlaterin
theirICUstayandparticularlyduringthefirst12hours.Thisrapidimprovementislikelyduetothedeclineof
counter-regulatoryhormonesastheacutephaseofcriticalillnessprogresses.Clinically,theseresultssuggestthatwhile
usingTGCprotocolswithpatientsduringtheirfirstfewdaysofICUstay,extracareshouldbeafforded.Increased
measurementfrequency,highertargetglycemicbands,conservativeinsulindosing,andmodulationofcarbohydrate
nutritionshouldbeconsideredtominimizesafelytheoutcomeglycemicvariabilityandreducetheriskof
hypoglycemia.
Keywords:
Criticalcare,Hyperglycemia,Insulinresistance,Mathematicalmodel,Algorithms

*Correspondence:[e-mail];[e-mail]
1
DepartmentofMechanicalEng,CentreforBio-Engineering,
UniversityofCanterbury,PrivateBag4800,Christchurch8054,NewZealand
4
CardiovascularResearchUniversityofLiege,Liege,Belgium
Fulllistofauthorinformationisavailableattheendofthearticle

©2012Prettyetal.;licenseeSpringer.ThisisanOpenAccessarticledistributedunderthetermsoftheCreativeCommons
AttributionLicense(http://creativecommons.org/licenses/by/2.0),whichpermitsunrestricteduse,distribution,andreproduction
inanymedium,providedtheoriginalworkisproperlycited.

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Background
Table1Summarydetailsofthestudysubjects
Safe,effectivetightglycemiccontrol(TGC)ofcriticallyill
N164
patientscanimproveoutcomes[1-4],butitisdifficultto
Age(yr)65[56
–
74]
achieveconsistently[5-7].Glycemiclevelandvariabilityin
Gender(M/F)102/62
TGCareafunctionofvariabilityininsulinsensitivity,
APACHEIIscore19[16
–
25]
potentiallyresultingfromthelevelandevolutionofthe
stressresponse[8],andareindependentlyassociatedwith
APACHEIIROD(%)32[17
–
52]
mortality[9-12].
Operative/nonoperative66/98
Insulinsensitivitydefinesthemetabolicbalancebe-
Hospitalmortality25%
tweeninsulinconcentrationandglucosedisposal.
ICUmortality18%
Insulin-mediatedglucosedisposalisadominantpathway
ICUlengthofstay(hr)142[70
–
308]
toreduceandcontrolglycemiaincriticallyillpatients.
Diabetichistory:typeI/typeII10/22
Forafixedinsulinconcentration,agivenpercentage
changeofinsulinsensitivityresultsinaproportional
Dataarepresentedasmedian[interquartilerange]whereappropriate.
changetoglucosedisposalandthusglycemiclevel,all
elseequal.fromamodel-basedcontrollerthatmodulatesbothinsu-
Understandingthevariabilityofinsulinsensitivity,overlinandnutritionalinputs.Theprotocoltitratesinsulin
hoursanddays,isimportantforsafelyandeffectivelydosesandnutritionratestoestimatedpatient-specific
managingglycemiclevelswithexogenousinsulin.Severalinsulinsensitivityfortightglycemiccontrolintherange
patient-andtreatment-relatedfactorsinfluenceinsulin4.0
–
6.1mmol/LBGrange[1,13,14].SPRINThasbeenthe
sensitivity.SomeoftheinfluentialandpredictablefactorsstandardofcareintheChristchurchICUsinceAugust
(drugtherapiesandexistingpatientconditions)aretaken2005.Therequirementforthepatientsinthisstudytobe
intoaccountwhendevelopingtherapeuticalgorithmsforontheSPRINTprotocolensuredthattheyhadregular
insulintreatment.andaccuraterecordsofbloodglucoselevels,insulinadmi-
Theobjectiveofthisstudywastoexaminetheevolutionnistered,andnutritiongiven.
ofinsulinsensitivitylevelandvariabilityoverthefirstTheentrycriterionfortheSPRINTprotocolwastwo
4daysofintensivecareunit(ICU)stayusingdatafromBGmeasurements
>
8mmol/Lduringnormalpatient
theSPRINTTGCstudy[1].Analyseswereperformedonmonitoring,oratthediscretionoftheclinician.Once
twoseparatetimescales,using24-hourand6-hourblocksontheprotocol,BGwasmeasured1-to2-hourly,witha
ofdata.Theimpactofthisinsulinsensitivityevolutiononmedianmeasurementintervalforthiscohortof1.5
glycemiainthecontextofTGCprotocolsisconsidered.hours.BGmeasurementsweretakenbynursingstaff
usingtheArkraySuper-GlucocardIIglucometer(Arkray
Methods
Inc.,Japan).Bloodsamplestestedweretypicallyarterial,
Patients
althoughwhenanarteriallinewasnotpresent,capillary
Thisstudyisaretrospectiveanalysisofpatientdatabloodwasused.AdditionalFile1containsamore
(N=164patients,12,067hours)fromtheSPRINTclin-detaileddescriptionofSPRINTandspecific,uniquedif-
icalpractisechangeintheChristchurchHospitalICUferencestootherprotocols.
[1].AllpatientsadmittedbetweenAugust2005andMay
2007wereincludedwheretheSPRINTTGCprotocol
Model-basedinsulinsensitivity
wascommencedwithin12hoursofICUadmissionandModel-basedmethodsprovideameansofdetermining
continuedforatleast24hours.Allpatientsweretreatedphysiologicalparametersthateithercannotbemeasured
perprotocol,withnospecificexclusions.Table1pre-directlyorareimpracticaltomeasurewiththerequired
sentsasummaryofcohortdetails.frequency.Inthisstudy,model-basedinsulinsensitivity
TheChristchurchHospitalICUisa15-bed,closed,(
SI
)wasidentifiedusinganintegralmethod[15]witha
mixedmedical-surgicalunitledbyintensivecarespecialistsvalidatedglucose-insulinsystemmodeldevelopedfor
inatertiaryaffiliatedteachinghospital.Glycemiccontrolcriticalcarepatients[16,17].Theglucose-insulinsystem
datawerecollectedfromhandwrittendailyICUchartsandmodelisillustratedschematicallyinFigure1andpre-
enteredintoaspreadsheetdatabase.TheUpperSouthsentedingreaterdetailinAdditionalFile2.
RegionalEthicsCommittee,NewZealand,grantedapprovalThe
SI
parameterrepresents
“
whole-body
”
insulinsensi-
fortheaudit,analysis,andpublicationofthisdata.tivity.Theparameterdefinestheglycemicresponseto
exogenousinsulinandnutrition,capturingtherelativenet
TheSPRINTprotocol
effectofalteredendogenousglucoseproduction,periph-
TheSPRINTprotocol(SPecialisedRelativeInsulineralandhepaticinsulinmediatedglucoseuptake,and
NutritionTables)isasimple,lookup-tablesystemderivedendogenousinsulinsecretion.However,thistime-varying

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Gp
G
.
G
(
t
)
SI
.
G
(
t
)
Q
(
t
)
P
(
t
)
EGPCNS
1
G
Q
(
t
)
V
G
Qt()Qn
I
(
I
(
t
)
Q
(
t
))
n
C
1
G
Q
(
t
)
In
K
I
(
t
)
n
L
I
(
t
)
n
I
(
I
(
t
)
Q
(
t
))
u
ex
(
t
)(1
x
L
)
u
en
(
G
)
1
I
I
(
t
)
V
I
V
I
Figure1
Schematicillustrationoftheglucose-insulinsystemmodelusedinthisanalysis.

Page3of10

insulinsensitivityparameterhasbeenshowntocorrelateevolutionof
SI
overthefirst4daysofICUstayisana-
verywell(r
>
0.9)withthe
“
goldstandard
”
euglycemiclyzedin24-hourblocks.Bagshaw[12]reportedanasso-
clamp[17]andhasbeenusedtoguidemodel-basedTGCciationbetweenhypoglycemiaandvariabilityduringthe
inseveralstudies[18-20].first24hoursofICUstayandmortality.Wetherefore
Avalueof
SI
wasidentifiedeveryhour[15]foreachpa-