Table Of ContentBLUK103-Allgrove August1,2007 16:47
Evidence-based
Paediatric and
Adolescent Diabetes
Edited by
Jeremy Allgrove
BartsandtheLondonNHSTrust
RoyalLondonHospital
London,UK
Peter G.F. Swift
LeicesterRoyalInfirmary
Children’sHospital
Leicester,UK
Stephen Greene
UniversityofDundee
DepartmentofMaternalandChildHealthSciences
NinewellsHospital
Dundee,UK
BLUK103-Allgrove August1,2007 16:47
(cid:2)C 2007byBlackwellPublishing
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1 2007
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Evidence-basedpaediatricandadolescentdiabetes/editedbyJeremyAllgrove,PeterG.F.
Swift,StephenGreene.
p.;cm.
“BMJbooks.”
Includesbibliographicalreferences.
ISBN978-1-4051-5292-1(hardback)
1.Diabetesinchildren. 2.Diabetesinadolescence. 3.Evidence-basedmedicine.
I.Allgrove,Jeremy. II.Swift,PeterG.F. III.Greene,StephenA.
[DNLM:1.DiabetesMellitus. 2.Adolescent. 3.Child. 4.Evidence-BasedMedicine.
WK810E932007]
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BLUK103-Allgrove August2,2007 14:50
Contents
Listofcontributors,v
Foreword,ix
Preface,xi
1 Methodologyofevidence-basedmedicine,1
JeremyAllgrove
2 Definition,epidemiologyandclassificationofdiabetesandstructure
ofthediabetesteam,9
MariaCraig,SarahJ.Glastras&KimDonaghue
3 Aetiologyoftype1diabetesmellitus–genetics,autoimmunity
andtriggerfactors,26
LoredanaMarcovecchio,DavidB.Dunger,
MarkPeakman&KeithW.Taylor
4 Type1diabetesmellitus–management,42
JoanneJ.Spinks,JulieA.Edge,KrystynaMatyka&ShitalMalik
5 Type1diabetesmellitusintheveryyoungchild,63
StuartBrink
6 Adolescenceanddiabetes:clinicalandsocialscienceperspectives,76
AlexandraGreene&StephenGreene
7 Managementofspecialsituationsindiabetes,93
FergusJ.Cameron&JeremyAllgrove
8 Dietarymanagement:optimisingdiabetesoutcomes,104
SheridanWaldron
9 Educationinchildhooddiabetes,123
PeterG.F.Swift
10 Psychologicalinterventionsinchildhooddiabetes,141
JohnW.Gregory&SueChannon
11 Screeningforassociatedconditionsandpreventionofcomplications,157
CatherinePeters&JeremyAllgrove
12 Type2diabetesmellitus–genetics,diagnosisandmanagement.
Polycysticovariansyndrome,175
JohnPorter&TimothyG.Barrett
iii
BLUK103-Allgrove August2,2007 14:50
Contents
13 Rareformsofdiabetes,197
JulianShield,MaciejT.Malecki,NicolaA.Bridges&JeremyAllgrove
14 Diabetesandinformationtechnology,221
KennethJ.Robertson
Abbreviations,228
Index,232
iv
BLUK103-Allgrove August2,2007 14:50
Contributors
JeremyAllgroveMBBChir,MA, Children’sCentre
MD,FRCP,FRCPCH StDavid’sHospitalCanton
ConsultantinPaediatricEndocrinologyand Cardiff,UK
Diabetes
BartsandtheLondonNHSTrust MariaCraig,MBBS,PhD,FRACP,
RoyalLondonHospital MMed(ClinEpid)
London,UK
PaediatricEndocrinologist
InstituteofEndocrinologyandDiabetes
TimothyG.BarrettPhD,MBBS,
Children’sHospitalWestmead
MRCP,MRCPCH,DCH
Westmead,Australia
ProfessorofPaediatrics
InstituteofChildHealth
KimDonaghue,MBBS,PhD,
Birmingham,UK
FRACP
AssociateProfessor
NicolaA.Bridges,DM,MRCP,
HeadofDiabetesServices
FRCPCH
TheChildren’sHospitalatWestmead
ConsultantPaediatricEndocrinologist UniversityofSydney
ChelseaandWestminsterHospital Westmead,Australia
London,UK
DavidB.Dunger,MD,FRCPCH
StuartBrink,MD
ProfessorofPaediatrics
SeniorEndocrinologist
DepartmentofPaediatrics
New England Diabetes and Endocrinology
Addenbrooke’sNHSTrust
Center(NEDEC)
Cambridge,UK
AssociateClinicalProfessorofPediatrics
TuftsUniversitySchoolofMedicine
Waltham,USA JulieA.Edge,MD,FRCPCH
ConsultantinPaediatricDiabetes
FergusJ.Cameron andEndocrinology
AssociateProfessor DepartmentofPaediatrics
HeadDiabetesServices JohnRadcliffeHospital
DeputyDirector Oxford,UK
DepartmentofEndocrinologyandDiabetes
RoyalChildren’sHospital SarahJ.Glastras,MBBS(Hons),
Parkville,Australia BScPsychol(Hons)
JuniorMedicalOfficer
SueChannon,BScDClinPsych
InstituteofEndocrinologyandDiabetes
ConsultantClinicalPsychologist TheChildren’sHospitalatWestmead
ChildPsychologyDepartment Westmead,Australia
v
BLUK103-Allgrove August2,2007 14:50
Contributors
AlexandraGreene MarkPeakman,BSc,MSc,PhD,
SeniorResearchFellow MBBS,FRCPath
HealthServicesResearchCentre ProfessorofClinicalImmunology
UniversityofAberdeen DepartmentofImmunology
Scotland,UK King’sCollegeLondon
SchoolofMedicineatGuy’s
StephenGreene,MBBS,FRCP, King’sCollegeandStThomas’Hospital
FRCPCH Guy’sHospital
London,UK
ReaderinChildandAdolescentHealth
MaternalandChildHealthSciences
UniversityofDundee CatherinePeters,MD,MRCPCH
NinewellsHospital SpRPaediatricEndocrinology
Dundee,UK RoyalLondonHospital
London,UK
JohnW.Gregory,MBChB,DCH,
MD,FRCP,FRCPCH
JohnPorter,BA(Hons),MBBS
ProfessorofPaediatricEndocrinology
SpecialistRegistrar
DepartmentofChildHealth
DepartmentofEndocrinology
WalesCollegeofMedicine
BirminghamChildren’sHospital
CardiffUniversity
Birmingham,UK
Cardiff,UK
MaciejT.Malecki,MD,PhD KennethJ.Robertson,MBChB,
FRCP,FRCPCH
SeniorLecturer
DepartmentofMetabolicDiseases ConsultantPaediatrician
JagiellonianUniversity RoyalHospitalforSickChildren
MedicalCollege Glasgow,UK
Krakow,Poland
J.P.H.Shield,MD,MRCP,FRCPCH
ShitalMalik,MRCPCH,MD,DCH,
ReaderinDiabetesandMetabolic
DNB
Endocrinology
PaediatricSpecialistRegistrar UniversityofBristol
UniversityHospitalCoventryand BristolRoyalHospitalforChildren
WarwickshireNHSTrust Bristol,UK
Coventry,UK
JoanneJ.Spinks,BSc(Hons),BM,
LoredanaMarcovecchio MRCPCH
ResearchFellow SpecialistRegistrarPaediatricDiabetesand
UniversityofCambridge Endocrinology
DepartmentofPaediatrics JohnRadcliffeHospital
Addenbrooke’sHospital Oxford,UK
Cambridge,UK
PeterG.F.Swift,MA,FRCPCH,
KrystynaMatyka,MRCP,MD DCH
SeniorLecturerinPaediatrics ConsultantPaediatrician
ClinicalSciencesResearchInstitute LeicesterRoyalInfirmary
UniversityofWarwick Children’sHospital
Coventry,UK Leicester,UK
vi
BLUK103-Allgrove August2,2007 14:50
Contributors
KeithW.Taylor,MB,PhD,FRCP SheridanWaldron,PhD
EmeritusProfessor DieteticManager
BartsandtheLondon LeicestershireNutritionandDietetic
QueenMary’sSchoolofMedicineand Service
Dentistry LeicesterRoyalInfirmary
London,UK Leicester,UK
vii
BLUK103-Allgrove August2,2007 14:50
Foreword
There appear to be a number of irrefutable facts about diabetes in childhood: some to
dowithaetiologyandothersrelatedtothemanagementofthisgroupofdisorders[1].
First, type 1 diabetes mellitus (T1DM) accounts for the vast majority of children and
youths with diabetes. T1DM is increasing in incidence worldwide at the rate of 2–5%
peryear,withimmigrantpopulationsrelativelyquicklyassumingthehigherincidencein
their new countries. Second, there has been a staggering increase in childhood obesity
worldwide,bringingwithitasignificantincreaseinearlieronsetofT2DM,probablynot
yetoftheepidemicproportionsintheyouththatmanyhavethreatened.Third,molec-
ulargenetictechnologieshavehelpedunravelthemysteriesofanincreasingnumberof
monogenictypesofdiabetes,bothneonatalandchildhood/youngadultonset.Finally,the
dataderivedfromtwosentinelrandomisedcontroltrials,namelytheDiabetesControl
and Complications Trial (DCCT) andits extension observation study Epidemiology of
DiabetesInterventionsandComplications(EDIC)inT1DM,andtheUnitedKingdom
ProspectiveDiabetesStudy(UKPDS)inT2DMinformthecurrentapproachtothecontrol
ofhyperglycaemiainordertopreventtheonsetorslowtheprogressionofdiabetes-related
complications.
Whilecertain‘facts’mayseemirrefutable,whatislessrobustarethedataneededtofill
inthedetailsaboutthewhy’s,when’s,what’sandhow-to’saboutthecause,courseand
complicationsofalltypesofdiabetes.Thisiswhereacarefuldistillationoftheavailable
informationisrequiredanddecisionsaremadebasedonthemostconvincingevidence.
Thedisciplineofevidence-basedmedicinehasarisenandrapidlyevolvedasameansof
accomplishingthisasaccuratelyandreproduciblyaspossibleinordertoprovidethestate-
of-the-artrecommendationsfordiagnosis,treatmentandprognosisoftheconditionunder
review.Thereareseveralcaveatsthatwarrantattentionhere.First,therecommendations
can only be as strong as the data that underpin them. Second, there is in the field of
diabetesinchildrenandtheyouthapaucityofdataonwhichtomakethehighestgrade
recommendations.Thisisafactoflifeinmostareasofpaediatricmedicine.Finally,the
evidencechanges,anditmaydosoquiterapidlywiththeemergenceofnewtherapeutic
agents(e.g.insulinanaloguesandoralhypoglycaemicagents).Hopefully,thismeansthat
assteadilyastheevidenceaccumulatesandimproves,sodoesthetreatmentandoutcome
ofthecondition.
A couple of sobering thoughts are in order here. First, a study from the Centers for
DiseaseControlinAtlanta,USA[2],in2003reportedalossofalmost20lifeyearsfor10-
year-oldchildrendiagnosedwithdiabetesintheyear2000.AndGalefromBristol[3]has
pointedoutthatthemajorityofchildrenwithdiabetesworldwidewillnotachievelevels
ofcontrolcommensuratewithreasonableprotectionfrommicrovascularcomplications.
Furthermore,‘theindividualandcommunallegacyofpoorglucosecontrolwillremainwith
usforthenextthirtyyears,evenifaneffectivemeansofpreventingnewcasesofthedisease
ix
BLUK103-Allgrove August2,2007 14:50
Foreword
weretobeintroducedtomorrow.’Galeconcludedthat‘thegreatestneedisformoreeffective
implementationofwhatisalreadyknown’[3].
In this book, editor Jeremy Allgrove has marshalled the energies and expertise of a
highlyqualifiedandaccomplishedinternationalgroupofchildhooddiabetesspecialists
tosiftcarefullythroughtheevidence(‘whatisalreadyknown’)andmakethebestpossible
recommendationsforthecareofchildrenandtheyouthwithdiabetes.Theresultisan
outstandingadditiontotheliteratureinthisfield.Thishasbeenagargantuan,buthighly
worthwhile,taskatanumberoflevels.First,ithelpsthereaderunderstandjusthowstrong
(ornot)theevidenceisforrecommendingoneapproachoveranother.Then,ithighlights
theareaswheretheevidenceisnotbasedonthetypeofstudiesneededtoprovidehigh-
grade recommendations, but in which there is general consensus as to a most sensible
approach.Inmanyoftheseinstances,thegold-standardstudy,arandomisedcontrolled
trial,isunlikelytobeperformed.Finally,itlaysbaretheissuesthatremaininadequately
addressedsuchthatnodefinitiverecommendationscanbemade.
Undoubtedly,boththeeditorandthechapterauthorsaswellasthereadershopethat
therecommendationswillsoonbeoutofdatewiththeemergenceof‘newerandbetter’
approachestodiabetespredictionandpreventioninbothT1DMandT2DM,management
thatfacilitatesachievementandmaintenanceofnormoglycaemiawithouttheever-present
threatofhypoglycaemiaandpreventionorreversalofcomplications.Untilsuchtimeas
theseadvancesbecomereality,thisvolumewillstandasawonderfulnavigatorforhealth-
careprofessionalsinvolvedinthecareofchildrenwithalltypesofdiabetes.Myheartiest
congratulationstoDrAllgroveandhiscontributorsfortheirsuperbefforts.
DenisDaneman
PastPresident,ISPAD
References
1 DanemanD.Type1diabetes.Lancet2006;367:847–58.
2 NarayanKM,BoyleJP,ThompsonTJetal.LifetimeriskfordiabetesmellitusintheUnitedStates.JAMA
2003;290:1884–90.
3 GaleEA.Type1diabetesintheyoung:theharvestofsorrowgoeson.Diabetologia2005;48:1435–8.
x
BLUK103-Allgrove August2,2007 14:50
Preface
Thisbookisintendedtobepartofaseriesofevidencebasedpublicationsonavariety
oftopics.Itisparticularlyintendedasacompanionvolumeto‘Evidence-BasedDiabetes’
whichwilldealinasimilarmannerwiththefieldofadultdiabetes.Itisnotintendedto
beyetanotherguidelinetothetreatmentofdiabetesasseveralofthesehavealreadybeen
published,butrathertoconcentrateontheevidencethatisavailableinthepaediatricfield
tosupportthedevelopmentofthoseguidelines.Whilstwehavetriedtobeascompre-
hensiveaspossible,therearecertaintopicsthathavenotyethadasignificantimpacton
paediatricpracticeandarethereforenotcovered.Theseincludeinhaledinsulins,thearti-
ficialpancreasandpancreaticcelltransplantation.Nevertheless,therearetopicscovered,
notleastthechapteronType2Diabetes,whichareunlikelytohavebeenincludedina
similarpublicationevenfiveyearsagobutwhichareofincreasingimportancetoday.
Ithasbeenanenormousprivilegetohavebeenaskedtoeditthiseditionof‘Evidence-
BasedPaediatricandAdolescentDiabetes’andagreatpleasuretobeabletoworkwith
myco-authors,PeterSwiftandStephenGreene,bothofthemlong-standingcolleagues
andgoodfriends.Iwishtothankthemandallofourco-authorsfortheirhardworkand
effortinseeingthisbookthroughtoitsfinalstages.Ialsowishtothankthepublishers,
Blackwell’s,fortheirunstintingsupportandencouragementinmakingitpossible.
Manythanksalsotoalloftheauthorswhohavecontributedtothebookandfortheir
efforts in getting manuscripts in on time so that publication can go ahead within the
timeframeoriginallyenvisaged.FinallyIwishtothankmywife,Natalie,forherpatience
andunderstandingintoleratingmyslavingoverahotcomputerwhenotherattractions
beckoned.
Whenoneisresponsibleforeditingabookthatisdependentuponevidence,itis,of
course, necessary to ensure that the evidence presented is as was originally published,
eveniftheconclusionsreachedinthosepapersweredubious.MartinRouth(1755–1854),
BritishacademicandPresidentofMagdalenCollege,Oxfordfrom1791untilhisdeath
in1854,wasonceaskedbyanadmiringstudent,towardstheendofhislife,tosupplya
precept which mightserveasa guidingprinciplein ayoungman’slife. ‘I think, sir,’ he
replied,afteramoment’sthought,‘sinceyoucomefortheadviceofanoldman,youwill
finditaverygoodpracticealwaystoverifyyourreferences!’Ihopethatallofthereferences
quotedherehavebeenverified.
JeremyAllgrove,
Editor-in-Chief
xi
