Glucose(Blood,serum,plasma)

Nameanddescriptionofanalyte

1.1

Nameofanalyte
Glucose(plasma;alsoblood,serum)

Alternativenames
None,thoughwhenusedtherapeutically,glucoseisoftenreferredtoas
dextrose.

NMLCcode

Descriptionofanalyte
Glucoseisamonosaccharidehexosesugar.

Functionofanalyte
Glucoseisanobligatemetabolicfuelforsometissues(e.g.erythrocytes)
andpreferredfuel(particularlyintheshortterm)formanyothers(e.g.
centralnervoussystem).Inthebody,therearethreesources:dietary
carbohydrate;gluconeogenesis(e.g.fromlactate)andhepatic
glycogenolysis.Glycogenisaglucosepolymerandtheprincipalstorage
form.Glycogenisalsostoredinskeletalmusclebuttheglucosederived
fromitisnotreleasedintothecirculation.
Glucoseconcentrationsinthebloodaremaintainedwithinanarrow
rangebytheactionofvarioushormones,theprincipalofwhichare
insulin(whichhashypoglycaemicactions)andglucagon
(hyperglycaemic).

1.2

1.3
1.4
1.5

2 Samplerequirementsandprecautions

2.1 Mediuminwhichmeasured
1.Glucosecanbemeasuredinblood,serumorplasma:thisarticlerefers
onlytomeasurementsinthesefluidsmadeinlaboratories.Pointofcare
testing(usingcapillaryblood)iswellestablished.Interstitialfluid
[glucose]measurementandnoninvasive(extracorporeal)measurements
arenotconsideredhere.
2.Glucosecanalsobemeasuredincerebrospinalfluidasanadjuncttothe
diagnosisofmeningitis.Itwasformerlyproposedthatitsmeasurementin
e.g.pleuralfluidcouldcontributetodistinguishingbetweenanaspirate
andanexudate,butitisofnovalueinthiscontext.
3.Measurementofglucoseinurineisthesubjectofaseparateentry.

2.2 Precautionsresampling,handlingetc.
Glucoseistheobligatesourceofenergyforerythrocytes;becauseofthis,
[glucose]fallsinwholebloodinvitro(atarateof0.4mmol/L/hatroom
temperature,lowerifunrefrigerated)unlessaninhibitorofglycolysisis
present.Forthisreason,bloodforglucosemeasurementisusually
collectedintotubescontainingfluoride(asaninhibitorofglycolysis)and
citrate,EDTAoroxalate(asanticoagulants).[Glucose]isstableinplasma
orserumonlyafterthefluidhasbeenseparatedandremovedfromthe
cellularelements,althoughforpracticalpurposesissuitableforuse
providedthatnomorethan90minuteshaselapsedbeforeseparationand
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3.1

thereisnobacterialcontaminationorleucocytosis.Notethatblood
[glucose]tendstobeupto1015%lowerthanserumorplasma[glucose]
becauseofitslowerintracellularconcentration,althoughtheexact
percentagedependsonhaematocritandtherateofanychangein
[glucose].
Notethatbecauseofthehighriskofartefact,thereshouldbealow
thresholdforrepeatingmeasurementsof[glucose]whenanunexpectedly
abnormalresultisfound.
Summaryofclinicalusesandlimitationsofmeasurements

Uses
1.Diagnosisandmonitoringofthetreatmentofdiabetesmellitusand
otherhyperglycaemicconditionsandmonitorpatientsatriskof
developingtheseconditions.
2.Diagnosisandmonitoringthetreatmentofhypoglycaemiaand
monitoringpatientsatriskofdevelopinghypoglycaemia

3.Monitoringpatientsreceivingglucosecontainingintravenousfluids.

3.2 Limitations
Measurementsofglucosecannotprovideinformationastothe
causeofeitherhyperorhypoglycaemia.
Notethatdiagnosticvaluesfor[glucose]inthisarticlereferto
measurementsinvenousplasmaunlesswherestatedotherwise.

4 Analyticalconsiderations

4.1 Analyticalmethods

Glucoseismeasuredusingenzymaticmethods.Formerlyusednon

enzymiccolorimeticmethodsareobsolete.Anyofthreeenzymesmaybe

used:hexokinase,glucosedehydrogenaseandglucoseoxidasein

reactionseithercoupledtoachromophoreorinvolvingthegenerationof

anelectriccurrent.Theassaysthatgenerateelectriccurrentare

particularlysuitableforuseinpointofcareinstruments.
1. Hexokinase(E.C.2.7.1.1)coupledwithglucose6phosphate
dehydrogenase(Dglucose6phosphate:NAD(P)+1oxidoreductase,
EC1.1.1.49)(GD).Thereactionsare:

Glucose+MgATP(HK)glucose6phosphate(G6P)+MgADP
G6P+NAD(P)+(GD)6phosphogluconolactone+NAD(P)H+H+

TheformationofNAD(P)Hismeasuredspectrophotometricallyat340
nm.Thismethod,usingaspecimenblank,isthemostwidelyused.
Hexokinasemethodscanalsobeusedinmethodswithchromogensto
produceacolouredproduct.
2. Glucosedehydrogenase(Dglucose:NAD(P)+1oxidoreductaseEC
1.1.1.47).Thereactionis:

Glucose+NAD+(G6Pdehydrogenase)6phosphogluconolactone
+NADH

TheformationofNADHismeasuredspectrophotometricallyat340
nm.
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3Glucoseoxidase(Dglucose:oxygen1oxidoreductase,EC1.1.3.4)
3.1Withgenerationofacolourchromogenusingperoxidase(Mn(II)
hydrogenperoxideoxidoreductase,EC1.11.1.7)

Glucose+O2(glucoseoxidase)gluconolactone+H2O2
H2O2+chromogenicoxygenacceptor(e.g.odiansidine)
(peroxidase)colourchromogen+H2O

3.2Usingpolarography
Inthisvariant,theconsumptionofoxygenismeasureddirectly.
GlucoseoxidaseisspecificforDglucose,whereasinsolution,
glucoseisapproximately2/3intheformand1/3inthe.Kits
incorporatemutarotasetoconverttheformtothe.

Themajorroutinemethodsarebasedonhexokinaseorglucoseoxidase.
Theglucoseoxidasemethodissuitableforuseindryslidetechniques.

Referencemethod
Aversionofthehexokinaseenzymaticmethod(see4.1)inwhichserum
orplasmaisfirstdeproteinated.

4.2

4.3
Referencematerial

Dglucose(StandardReferenceMaterial(SRM)917,NationalBureauof

Standards,WashingtonDC,USA).

4.4Interferingsubstances
1.Hexokinasemethod:haemolysis(Hb>0.5g/dL)causesnegative,and
bilirubinandtriglycerides(>55mmol/L),positive,interference.
2.Glucoseoxidasemethod:peroxidaseisinhibitedbyvarioussubstances
includingbilirubinandhaemoglobin,leadingtolowresults.

4.5Sourcesoferror
Theglucoseoxidasepolarographymethodisnotsuitableforwholeblood
becauseredcellsconsumeoxygen.

5
Referenceintervalsandvariance

5.1.1 Referenceintervals
Blood[glucose]variesinrelationtofoodintake.Cutoffvaluesfor
diagnosisofconditionsofimpairedglucosetolerancearediscussedin
section9.
Lowerreferencelimitsaredefinedforfastingspecimens:thevalueat
whichsymptomsofhypoglycaemiabecomeapparentishighlyvariable
betweenindividuals.Avalueof<2.8mmol/L(venousplasma)is
commonlyused,butdecreasedendogenousinsulinsecretionmaybe
detectableat<4.0mmol/L.
Upperreferencelimitsaredefinedforfastingandpoststandardised
glucoseintakespecimens.Twovaluesarerecommendedfortheupper
referencelimit(fasting):5.6mmol/L(AmericanDiabeticAssociation,
ADA)and6.1mmol/L(WorldHealthOrganisation,WHO).
Fornonfastingvalues,see(6.1).

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5.1.2 Thesamereferencelimitsapplyacrosstheentireagerange,anddonot
differ
betweenmalesandfemales.
5.1.3 Extentofvariation
5.1.3.1 InterindividualCV:12.5%
5.1.3.2 IntraindividualCV:8.3%
5.1.3.3 Indexofindividuality:0.66
5.1.3.4 CVofmethod:typically<2%
5.1.3.5 Criticaldifference:24%
5.1.4 Thevariationin[glucose]isduetothetimesince(andthenatureof)the
lastmealandfactorsthattheremovalofglucosefromtheblood,
particularlythehormonalmilieuandrequirementsforenergy
consumption.

6
Clinicalusesofmeasurementsandinterpretationofresults

6.1 Usesandinterpretation
1.Diagnosisofdiabetesmellitus
Diabetesmaybesuspectedonclinicalgroundsorscreenedforin
individualsatrisk,e.gpatientswithpancreaticinsufficiency,
endocrinopathiesknowntocausehyperglycaemiaetc.
Diabetesmellitusisdiagnosedifvenousplasmaglucoseis7.0mmol/L
(fasting)or11.1mmol/L(2hafteringestionof50ganhydrousglucoseor
equivalent(i.e.theoralglucosetolerancetest)inasymptomaticpatient;
inanasymptomaticpatient,asecondsuchvaluemustbedemonstrated
onadifferentday.
2.Diagnosisofimpairedglucosetoleranceandimpairedfastingglycaemia
Impairedglucosetoleranceisdiagnosediffastingglucoseis<7.0mmol/L
and2hpostglucoseingestionglucoseis7.8mmol/Lbut<11.1mmol/L;
ImpairedfastingglycaemiaisdiagnosedonWHOcriteriaiffastingglucose
is6.1mmol/Land<7.0mmol/L.
3.Monitoringtreatmentofestablisheddiabetes
Bloodglucosemeasurements,oftenbypatients,canprovideimportant
informationtoguidetreatment,especiallywhenintensiveinsulin
regimensareused.Measurementsofglycatedhaemoglobin(HbA1c)are
preferredforassessmentoftheadequacyoftreatmentoverthelonger
term.Measurementsofglucosearealsorequiredtoconfirmaclinical
diagnosisofhypoglycaemia(see(7)).
4.Monitoringtreatmentofhyperglycaemia
Glucosemeasurementsareessentialtoinformthemanagementof
diabeticketoacidosisandhyperosmolarnonketotichyperglycaemia.
5.Monitoringtreatmentofdiabetesduringsurgeryetc.
Trauma,surgery,intercurrentillnessetc,allincreaseinsulin
requirementsandhavethepotentialtocauseadeteriorationinglycaemic
control:regularmonitoringof[glucose]isessentialundersuch
circumstances.
6.Monitoringtreatmentinvolvingintravenousglucoseinfusion
Regularmeasurementsofglucoseareessentialtothepreventionof
hyperglycaemiaduringintravenousglucoseinfusion,e.g.aspartof
parenteralnutrition.
7.Diagnosisandmonitoringthetreatmentofhypoglycaemia.
Alaboratoryglucosemeasurementisessentialforthediagnosisof
hypoglycaemiaofanycause(althoughtreatmentshouldnotbedelayed
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pendingthereceiptofaresultwhentheconditionhasbeendiagnosed
clinically)andinthemonitoringoftreatment,bothtoensureitsadequacy
andtoavoidhyperglycaemia.

6.2

Confoundingfactors
None.

Causesofabnormalresults

7.1 Highconcentrations(assumingpatientisnotreceivingglucoseorallyor

parenterally).
7.1.1 Causes:
diabetesmellitus(type1,type2orsecondary)
impairedglucosetolerance
impairedfastingglycaemia.
7.1.2 Investigation
See6.1.Formalglucosetolerancetestingisonlyindicatedinindividualsin
whomadiagnosisofdiabetesisbeingconsideredandinwhomfastingor
postprandialglucoseconcentrationsaloneis/arenotdiagnostic.Note
thateveninapatientwithclinicalfeaturessuggestiveofdiabetes,the
diagnosisisunlikelyifrandomglucoseis<5.5mmol/L.

7.2
Lowconcentrations
7.2.1 Causesofhypoglycaemiainclude:
treatmentwithinsulinorsomeoralhypoglycaemicdrugs
hyperinsulinism(e.ginsulinoma)
othertumours
alcoholandotherdrugs
endocrinopathies,e,g,adrenalorpituitaryfailure
chronicliverorkidneydisease
sepsis
gastricsurgeryleadingtorapidtransit
inheritedmetabolicdiseases
etc.
7.2.2 Investigation
Oncehypoglycaemiahasbeenconfirmedbylaboratorymeasurementand
clinicalfeaturesshowntoresolveonrestorationofnormoglycaemia,the
followingshouldbemeasuredwhenthepatientishypoglycaemic:insulin,
Cpeptide,(proinsulin).
high[insulin]and[Cpeptide]:endogenoushyperinsulinism
high[insulin],low[Cpeptide]:exogenoushyperinsulinism
low[insulin],low[cpeptide]:endocrinopathies;liver,kidneydisease;
inheritedmetabolicdiseases.
Measurementofserum3OHbutyratemayalsobeinformative.Insulin
suppressestheproductionofthismetabolite.Aconcentration>600
mol/Linapatientwithsuppressedinsulinsecretionsuggestsan
endocrinecauseforthehypoglycaemia.

7.3

Notes
1.Severe,symptomatichyperglycaemiaandhyperglycaemiaofany
degreewithketosisaremedicalemergencies.Patientsarelikelyto
requirehospitaladmissionandmanagementaccordingtostandard
protocols,includingintravenousfluidsandinsulin.

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2.Symptomatichypoglycaemiaisamedicalemergency.Patientsrequire
theimmediateadministrationofglucose(orallyorparenterally)or
intramuscularglucagontoraisetheirbloodglucoseconcentration;
glucoseadministrationmayneedtobecontinuedorrepeateduntilthe
underlyingcauseisdiagnosedandtreated.
3.Becauseoftheprofoundclinicalconsequencesofhypoand
hyperglycaemiaifuntreated,laboratoriesshouldestablishanddocument
telephonealertvaluesandhaveadocumentedpolicyforinformingan
appropriatemedicalofficershouldsucharesultbefound.
4.Formalglucosetolerancetestingisonlyrequiredinsuspecteddiabetes
ifpreliminaryresultsareequivocal.
5.Pointofcareinstrumentsaresatisfactoryformonitoring[glucose]but
shouldnotbeusedtodiagnosediabetes.Insuspectedhypoglycaemia,a
pointofcareresultmustbeconfirmedbyalaboratorymeasurement,
thoughthisshouldnothinderinitiationoftreatment.

Performance

8.1

Sensitivity,specificityetc.forindividualconditions
1.Diabetesmellitusandotherhyperglycaemicstatesarediagnosedonthe
basisofglucosemeasurements(See9.2.1).Sensitivityandspecificityare
thus100%.
2.Hypoglycaemiaisdiagnosedonthebasisofmeasurementsofglucose,
characteristicclinicalfeatures(ofincreasedsympatheticactivityand
neuroglycopaenia)andtheresolutionofthesefeatureswheneuglycaemia
isrestored.Thereis,however,variationwithinandbetweenindividuals
astothe[glucose]atwhichclinicalfeaturesbecomeapparent.
Physiologicaldisturbancescantypicallybedetectedathigher[glucose]
thancausesymptoms.

9 Systematicreviewsandguidelines

9.1 Systematicreviews
Numerousreviewshavebeenpublished.Theyfallintotwocategories:
thoseexaminingtheevidencethathyperglycaemiaisariskfactore.g.for
cardiovasculardisease,andthoseexaminingtheevidenceofbenefitfrom
monitoringbloodglucose.Forexample:
1.KellyTN,BazzanoLA,FonsecaVAetal.Systematicreview:glucose
controlandcardiovasculardiseaseintype2diabetes.AnnIntMed2009;
191:394403.Theauthorsconcludethatintensiveglucosecontroldecreases
theriskofnonfatalmyocardialinfarctionbutnotcardiovasculardeathor
allcausemortality,andisassociatedwithasignificantincreaseintherisk
ofhypoglycaemia.
2.CosterS,GullifordMC,SeedPTetal.Monitoringbloodglucosecontrol
indiabetesmellitus:asystematicreview.HealthTechnologyAssessment
2000;4(12).Theauthorsconcludedthatdespitethewideusageofglucose
selfmonitoring,itsoptimalusehadnotbeendetermined..
3.PolsupN,SuksomboonN,JiamsathitW.Systematicreviewofthe
benefitsofselfmonitoringofbloodglucoseonglycemiccontrolintype2
diabetespatients.DiabetesTechnologyand
Therapeutics2008;10(Supplement1):S51S66.Theauthorsconcluded
thatselfmonitoringofbloodglucoseusedtoadjusttreatmentregimensled
toimprovedglycaemiccontrolinpatientswithtype2diabetesnottreated
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withinsulin.Seealso:
http://www2.cochrane.org/reviews/en/ab005060.html(accessed
26.iv.2012)

9.2 Guidelines
1.NICEandDiabetes:asummaryofrelevantguidelines.
www2.cochrane.org/reviews/en/ab005060.html(accessed26.iv.2012)
Thissummaryreferstobothdiagnosisandmanagement.Diagnosticcutoffs
forvenousplasmaglucoseare:
normal:<6.1mmol/L(fasting)
impairedfastingglycaemia6.1mmol/L,<7.0mmol/L(fasting)
impairedglucosetolerance<7.0mmol/L(fasting)and7.8mmol/L,
<11.1mmol/L(2hpostglucose).
Diabetes7.0*mmol/L(fasting)or>11.1*mmol/L(2hpostglucose).(2
hpostglucose=2hfollowingingestionof75ganhydrousglucose.)
*Inasymptomaticindividuals,tworesultsonseparatedaysinthediabetic
rangearerequiredfordiagnosis.

2.Type1diabetes:diagnosisandmanagementoftype1diabetesin

children,youngpeopleandadults.NICEClinicalGuideline15,July2004

updatedMarch2010withadditionalchangesApril2010.

3.Type2diabetes:nationalclinicalguidelineformanagementin

primaryandsecondarycare.NationalCollaboratingCentreforChronic

conditions.NICEClinicalGuideline66May2009(updateCG87,June2009

referstoneweragentsfortreatment).

9.2Recommendations
http://www.patient.co.uk/doctor/SelfMonitoringBloodGlucose
(SMBG)inDiabetesMellitus.htm(accessed26.iv.2012)Detailed
recommendationsontheroleandfrequency
ofselfmonitoringofbloodglucoseindiabetesbasedonSIGNandNICE
guidelinesandothersources.

10

Links

10.1Relatedanalytes

None

10.2Relatedtests
1.Semiquantitativedetectionofurineglucosewasformerlywidelyused
tomonitorpatientswithdiabetes,butisnowonlyappropriatefor
patientsnottreatedwithinsulinwhoareunableorunwillingtoperform
bloodglucosemeasurements.Detectionofurineglucosehasnoroleinthe
diagnosisofdiabetes.
2.Glycatedhaemoglobin(HbA1c)isrecommendedformonitoring
establisheddiabetes;considerationiscurrentlybeinggiventoallowing
diabetestobediagnosedonthebasisofHbA1cvalues.
3.Adipsticktestforurinaryketonesissufficienttoindicateketosisin
suspecteddiabeticketoacidosisorpatientsatrisktherof.Measurementof
bloodketonesisavailablebutseldomrequired.
4.Measurementofalbumin:creatinineratioisusedtodetectincipient
diabeticnephropathy.

Author:WilliamMarshall
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