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Chapter34 General Approach to the Treatment of Diabetes MellitusRamachandiran Coopp an Sinceth elasteditionoft histextbook,major scien tificadvan ceshaveincreasedouru nder stan din gofth e pat hophysiologyun derlyingbothty pe1andtyp e2diabe tesan dhavefue led newap proachest oth erapy. Newinsightsintoth eme chan ismofinsu linaction andinsu linr esist an ce,gre ater unde rstandingofthe mechanismsofcon trollinginsulinsecre tion, an dadvancesingen eticsan din immu nologyh ave contribut edtothisexplosionofknowle dge.Fur ther more,anu mber ofrandomizedpr ospe ctiv estudies demon stratingth ebene fit softightg lyce miccon trolandth eavailabilit yofn ewor alther apiesan din sulin formu lation sp rov ideacompellin grationaleforimprovingth eoverallle velofdiabe tescar e. The r esultsoftheDiabete sControlandC omplicationsTrial(1),the Kumamot oTrial(2), andt heUn it ed KingdomProspectiveDiabete sSt udy(3)hav eprovid edcon clusiveeviden cethattight g lyce miccon trol willpreve ntth eonset, aswellasdelayt heprogre ssion,ofth elong-t ermmicrovascu larcomplications of type 1an dtype 2diabet es.Amore recen tfollow-u pofth eKumamotost udy(4)not edth atth eoptimal degr eeofglyce miccon trolt opre vent orde laycomplication sisaglycosylate dhemog lobin (HbA 1 c )lev el oflesst han 6.5%,afastin gglucos ele veloflessth an110mg/dL, and a2-h ou rpostpran dialb lood glucoseleveloflessth an 180mg/d L.

DIABETES AS A WORLDWIDE HEALTHCARE PROBLEMDiabetesmellitu shasbe comean in tern ationalhe althcarecrisisthatrequ ire snewapproache sto pre vent ionan dtre atment .Du ringth elast20years,th eprev alence ofdiabet eshasin creased dramatic allyinman ypart softh ewor ld. Alth ou ghgen eticfactorsplayaroleinth eet iology,e speciallyof type 2diabe tes,th egrowin gproble mofobe sit ythatparallelsimproved e con omicst atu sin some deve lopingcount rie sisamajoren vir on men talfact orint hisepid emicofd iabetes. Onth eot herh an d,in manyp artsofthe developin gworld,lowb irt hweightandmate rnalmalnu tritiondu ringpre gnan cymaybe amajorfactorun derlyingth einsulinresistancesyn drome andt husinanincreasedriskofdiabetesin late rlife. Atleast 120millionpeople throug houtth ewor ldsu fferfromty pe2diabe tes,anditisproject edth atth e nu mbe rwillin crease to220million bythe year2010.Thisdise aseisnowaworldwidepu bliche althissue th atn otonlycostsmanyn ation smillion sofdollarsfor h ealth care butalsorobsmanydev eloping economiesofthe irmostpreciou sresource ,th eir worke rs.Dataalmostade cade oldgave ane stimat ed pre valence oftyp e2diabe tesinth eUnite dSt ate sof14millionpersonst hat cause dane stimat ed 300, 000deathsandre sultedinhe althcareex penditu resof$100billion (5). Someofthe world'smosthighlyindebt edan dpoorest nat ionsdonothavesufficientr esou rcestopay bac ktheirde btan dtoalsoprovidecar eforpatient swith diabete s,adding t oth eproblem. Inth ese ar eas, alackofadequ ate in sulin supplie sisamajorproblemforyoung c hildre nwithtyp e1diabe tes, an dmanydonotsur viv emoret han 1yearaft eronsetofdisease .Solutionstothisproblemmust b e forthcomin g,becausetr eat men tfor patien tswith type1diabet esexistsan dshouldbewidelydist rib uted (6).

CHANGING DIAGNOSTIC CRITERIA FOR DIABETESIn1997, t heAmerican Diabet esAssociat ion(ADA) ch an gedth ediagnosticcriteriafordiabet esme llitus an drecommen dedth at th euseofRomannu me ralsfor t hetwomajorformsofdiabe tesmellitusbe discontinu edandth atArabic nu me rals1and2be usedinst ead. Th eearlier chan geinth eclassificat ionfromins ulin -depen dent diabet esme llitus(IDDM)an dnon-insulin-depe nden tdiabet esme llitus(NIDDM)tot ype1orty pe2was an att empt tomoveawayfromat reat men t-basedclassificationt oonebasedonun derlying pat hophysiology.Thisne wsystemremov edthe con fusion t hat eme rgedwh enpatientsclassifiedas havingNIDDMu nde rthe oldnome nclatu rewere treatedwithinsu linbe cause ofdisease progression . Wouldthe sepatien tsnowbeclassifie dashavingIDDMorwe rethe yme relypat ien tswithNIDDMwh o nowrequ ir edin sulinthe rapy ?The path oph ysiolog icapproachallowsforth espectr umofchange sin t he un derlyingdiseas eprocessthatdeve lopwithtime and prov ide sarat ionale fortr eatmen tchangesbased onth isprogre ssion. Inmaking t hese chan ges,t heADAalsorev ised thediag nost iccr ite riafor d iabetesandintr odu cedan ew cat egory,impair edfast in gglu cose ( IFG).The oldcriteriare quiredafastingplasmaglucoseleve lof140 mg/dLor higherorag lu coseleve lof200mg/dLor higher 2hoursaftera75-gglu cose challenge to establish adiagn osisofdiabe tes.Th eseolde rcriteriaalsowere inlinewitht here comme ndat ionsofthe World He althOrg anization. Th ene wcrit eriawere developedtoallowearlierdiag nosisofdiabete sthat would,in tur n,leadtoe arlytre atment and, it ishoped, toaredu ction ind iabetes-r elatedcomplicat ions P. 588

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(7). StudiesinEg yptan dthe UnitedSt atesde monstr ate dacorrelationbet we ent hedev elopment of ret in opathy andafastingglucoselevelofmoreth an108to116mg/d L(8,9).Notallgr ou psare en thu siasticaboutth esech ange sin thediagnosticcr ite ria.Some areconce rnedt hat undoemphasison th efastinggluc oseconce ntration swillr educe t heu seoft heoralglucosetole ran cetestt hat maybe ne cessar ytoiden tifyin dividu alswith impairedg lu coset olerance(IGT),whichisassociate dwith greater rateofp rogr ession t oclinicaldiabetesandisariskfact orforcardiovasculardisease(10,11). Furth ermor e,th ereisconcern thatthe newcrite riamayin creasethe prevale nceofdiabete sin many par tsoft heworld andst rainalre adylimitedh ealthcarere sou rces(12,13), although ,ofcour se,th ene w criteriad onotincre aset heactualpre valen ceofdiabe tesbu ton lyt hat ofdiagn ose ddiabetes. Advancesinmolecu larbiologyandge neticshaveh elp edtoelu cid atet hemechanismofin sulin actionan d toide ntifyspecificg enemut ation s[e.g. ,glucokin ase g eneinmat urity-onset diabetesofthe you ng-2 (MODY2)]t hat canleadtod iabetes. Inadd ition,outcomedat aclearlysup port thebe nefitsofstrict glycemiccontr olin retardingbotht hede velopment andp rogr essionofthe long-t ermmicrovascu lar complication sin bot htype 1an dtype2diabete sme llit us.Th esestu die son g lu cosecont rolhavebee n complement edbystu die son macr ovasculardiseaseth atde monstr atet hemajor bene fitsde riv edfrom agg ressivetre atmen tofh yperch oleste rolemiaan delevat edbloodpressu reinpatie ntswithdiab etes. The incr ease in t hen umberoforalmedicat ionsfortreatingtyp e2diabe teshasnowmadeitpossiblefor providersn otonlytochoose ther apiesbase don theu nde rly in gpath oph ysiology ofdiabet esbut alsoto use drugst hat worksyn ergisticallybyaddr essin gdiffe ren tpath oph ysiolog icabnormalities.Th eben efit s oft hisapproach ,whichoften allowsthe useofsubmaximaldosesofdiffe ren tage nts,areimpr ove d glycemiccontr olan dared uction ofth eadv ersee ffe ctsoft hemedicationsuse d.Thech alle ngeinty pe2 diabet esist ostarttr eat men tearly andtouse combinat ionth erapie st hat addre ssbot hthe in sulin resistanceandinsu linsecr etorydefe ctsofth edisease .Theint rodu ction ofrapid- actingh umaninsu lin, aswe llasth ene wlong-actin gin sulin an alogu es,h asmadeitpossibletoapp rox imate normalinsu lin secre tion through the u seofbasalan dpremeal(bolus)in sulinregimens. The cure fordiabe tesstillelud esus.Howeve r,th eprogressmadeint hedev elopment ofne w app roachest ogrowingan dtransplan tin g-cellsandinimmun osu ppressiveth erapyle ndshopet oth e possibilit ythattransplant ed-cells,even thosen otr ender edimmunone utr al,willsurviveforth elong ter mandren derpatients with type1diabete sins ulin -in depen dent ( 14). The approach toachronicdisease su chasdiabetes r equirest reat me ntgoalsthatincludebotht he mainten an ceoft hewell-beingoft heaffectedindividualandth eprev entionoft helon g-ter m complication sassociatedwitht hedisease.The relationshipofg lu cosecont roltothe microv ascular complication shasb eenv alidated;th echallen geistomake pract icalu seofth is informationbyimpr oving th edeliv eryofappropriate care .Thisrequ ire sclosecollaborationamongallmembe rsoft hehe althcare teaminv olvedinth ecar eofpatientswith d iabetes. Desp ite thedr amaticresu lt softh eDiabe tesCont rol an dComplicationsTrial(DCC T),for mostpat ien ts,t here hasbe enn omajor shiftin the careoftype1 diabet esthatwillprovid ethe bene fitsn ote din the int ensivet herapytrials.It isgratifyin gthatthose pat ie ntswhowere in theint ensivetr eatmen tarmofDCC Tandarenowpar tofth eEpidemiolog yof DiabetesIn terv entionsan dComplication s(EDIC)trialhavecontinu edtobene fit fr ompart icipat ioninth e inten siv etre atment armforaslongas4yearsaft erth etrial'se nd.U nfortun ate ly, thisgrouphas expe rienced s omedete rioration inover allglycemiccon troloutsideth een vir on men tofarigorously controlle dclinicaltrial(15).The cost-e ffe ctivene ssofinte nsivetre atment alsoh asbee nexamine dand foundt obeworth while compare dwith the costoftreatingth ecomplication swhen they occur .Toachieve agg ressivegoalsofglycemiccont rol,se lf-mon it oringofbloodglucose(SMBG)mu stbeastan dardforall pat ie nts. Moreover, patien tsshouldhaveacce sstot heappropriatemon it oring e quipme nt, in depen dent oft hety peofdiabetes, andwith thefre quen cyoft estingdet ermin edbyth emedicalp rofe ssionalsand th epat ien t. Many variat ionsofpract icegu id eline sfordiab etesarenowavailable;h owe ver, adhe rence tot hese guidelinesh asnotbee noptimalinmany in stan ces(16).The rear emanyre asonsforthis,andth esemust beassessedcarefu llyifpr ogr essist obemade in thisare a.C urre nttr eatmen tguidelinesarebase don outcome sdataderivedfromc ont rolledclin icalt rialsandex tensiveph ysicianexp erience. Amech an ismis nownee dedtotranslate these guidelin esintoaformatthatwillbebothpr acticalan drealisticin clinical practice.The careofpat ien tswithach ronicdise asesu chasdiab etes, wh ilebe nefitingfromt hemode rn rev olutionininfor mationt echn olog y,stillhasasitsbasisth ecaring ,compassionat e,andun derst anding relat ionsh ipsbe tween the p atient and membersofthe health care team.U nfortun ate ly, curr ent reimburse men tsyste msdonotsupportt heest ablish me ntormainten an ceofth eser elation shipsand t hus workagain steffortstoprovid eopt imalcare topatient swith diabete s. The majorclin icalissueinpatient swith type2diabete s,in addition tothatofachievingsymptomatic controlofhy perglycemia,isthe e normousr iskofcard iovascu lardisease andt heproblemsarisin gfrom microvascularcomplications.Anappreciat ionofthe in terre lations hipsofth evar iousriskfact orst hat leadt ocoron ary heartdisease andt hebe nefitsoft reat in gthe sevigorouslyisgrowin grapidly.Multiple stu die son ch olest erollowe rin g[Scan din avian SimvastatinSurv ivalStu dy(4S)andC holest eroland Rec urre ntEv entst rial(C ARE)](17, 18);bloodpr essure con trol[U nitedKingdomProspectiveDiabet es Stud y(UKPDS)an dHypert ensionOptimalTre atmen t(HOT) st udy](19, 20);andth euse ofaspirin(21),


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inhibitorsofangiote nsin-conve rtingen zyme [Hear tOutcome sPre vent ionEv aluat iontr ial(HOPE)](22), an d-blocke rsreve alsign ifican tben efit sin p atient swith diabete s.Whilethe seran domizedcontr olle d clin icaltr ialsh aveb eencondu ctedpr imarilyin subjects withoutdiabe tes, t hesu bgroupswithdiabe tesalsohad sign ifican tredu ctionsinmajorcard iovascu lar eve ntsanddeath. There centdatafr omthe At herosclerosisR iskinC ommu nities(ARIC)Stu dyshowed th atth eriskfor diabetes inpatient swith hype rten sionisin creasedbytwoan dahalf. Th estu dyalso noted t hat ther iskofdeve lopme ntofdiabete swasnotincre asedby t hiazidediure ticsb utwasincr ease d by-bloc kers.Howeve r,th ebene fits ofth euseof-blocke rsfollowingmyocardialin farctionhavebe en validat edin the literatur e,sothe risk ofdeve lopingdiabet esshouldbeconsidere dofsecond ary importanceinth isgr ou pofpatients(23). The t reatme ntplan forpatientswith d iabetesalsowillbeaffe ctedbyth epre valence ofth edisease in t he population.The prevale nceoftype2diabete sish igh erincer tainet hnicgroups, suchasNative Ame ricans(e speciallyt hePimaIn dians)(24),Hispan icAmerican s,AfricanAmerican s,an dAsian Ame ricans(25, 26, 27).Forman yoft hesegr ou ps,acce sstogoodme dicalcareisaffecte dbyfactorssu ch associoeconomicstatus, in surancecover age, culturalbackgroun d,langu age barrier s,in div idu aland grouph ealth b eliefs, education allev el, and p eerbe havior.The sefactorspre sent specialprob lemsth at willhavetobeadd ressedifthe sepat ien tsar etoachieve opt imalou tcomes. Diabetesinth eolde rpop ulation alsoisaspe cialissueb ecau seoft heincre aseinth eprev alence of diabet eswit haging ,the mu ltipleother con ditionsbeingt reat edinthe elderlypopulation ,an dthe ris ks associate dwith polyph armacy. Th ere isanurge ntn eedtoapp roachth etre atment ofdiabet esinthe se pat ie ntswithe nthu siasmandtosetappropriate goalsforthe rapy .Treatme ntmustbe in dividu alize d,an d th erelationshipofrisk stobe nefitsmustalwaysbecar efully e valuated, butage,per se,isnotare ason toaltert hetarget goalsforglycemiccontr ol.Although mostelderlypat ie ntswithdiabe tesh avety pe2 disease ,manyofthe mh avet ype1(insu lin-d epen dentdiabetes)diseasen ot onlybe cause type1 diabet escan presen tforthe firstt imeinth eelderlybut alsobecause man ypat ie ntswithty pe1diabe tes ar elivinglon genoug htobeincludedinth eelderlygroup .Theelder lydonotalway spresen twithth e classicalsymp tomsan dsign sofh yperglycemia,sothe physicianmustconsider t hisdiagnosis, especially inth osewith n eur opathy ,nonhe alin gulcers, andr ecurr entinfe ctions(28). Although t hischap terwillfocu son the gene ralapproach tothet reat men tofthepatientwith diabetesin th eou tpat ie ntset tin g,th eprinciplesalsoapplytoinp atient s.Themat erialpresen tedh ereisinten dedas age ner alove rvie wofth etre atment ofdiabet es;other chapt ersinth iste xtar edevotedt ospecific issues. P. 589

AN INITIAL APPROACHOnce thediagnosisofdiabete shasbe enes tablish ed, t hequ estion ofinitiatingt herapymustbe add ressed. Thos epatien tswhoprese ntwithdiabe tick etoacidosisorwhoaremar kedlyhype rglycemic an dsymptomat icsh ou ldbe admitt edtothe h osp italforur gent treatme nt. Th ene edfor hos pitalizationat diagn osisappliesprimarilytopat ie ntswithty pe1diabe tes, e specially childre n. Atth isinitialstage ,th ephysicianorhe althcareprofession alwhoisse ein gthe patien tshouldobt aina det ailed h is tor yandp erformacomple teex amin ation with appr opriat elaboratoryt esting.Th efutu re progressionoft hepatient'scare willb eaffect edbyan umberoffactors,includingt heph ysician 's tre atment philosophy,t hepatient'shealthcarebeliefsand c ompeten ceat self- care, and t heavailability ofateamconsistingofadietitian, diabete seducator,exe rcise physiologist ,an d,whe nne eded, social workersandpsych ologist s.Un fortu nately,notallcomponen tsoft histeammaybeavailablein the gen eraloffice p ractice;h owev er,most commu nitiesdoh ave these resource s,an dpatien tsshouldbe refe rredt oth em, asapprop riate, toachieveoptimalglucosecont rol. The approach mu stcon side rthe whole personwithdiabe tes,n ot ju stthe le velsofglycemiccontr olto beachievedorth eth erapy tobe usedt oaccomplisht his(i.e .,insu linororalan tidiab eticther apies).To th isen d,as trong,inte grat edteamapproachisth eon emostlikelytosu cceed. Alth ou gh, asnoted above, the comple tete ammay notexistinmostcases,th ephy sician andt hepatientcanmake considerable p rogr esstogeth er,withoth ercompone ntsofthet eam,espe ciallyth ediabet eseducatoran d dietitian, comin gfromth ecommunity.

The Patient HistoryAdetailedh ist ory isth efou ndationofgooddiabe tescare.Kn owledge aboutth eage ofth epat ie ntan d th eclinicalpre sentation ofte nhe lpth eph ysician deter mine wh eth erth epat ien thastype1or type2 diabet es.Thisisnotalaborat ory -validateddiagnosisbu taclin icalassessment toassist in ch oosingth e initialt reatme nt.Th eclinician b asesth eclassification onaspectsofthe patien t'sh istorysu chasage, bodyweight, familyhistory,du rat ionofsympt oms,an dthe resu ltsofthe blood glu coseandth e HbA 1 c dete rmination s.Considerable het erogene ity exists,espe ciallyintype 2diabe tes,inth eclin ical pre sentation aswellasin the u nde rly in gpath oph ysiology .Somepatie ntsactuallymayhaveaslowly progressiveformofautoimmu ne d iabetes. Theset endtobeyoun geradultsan dgen erallyrequ ire in sulin th erap yrelativelysoon .These patien tscan bediagnosedby measuringce rtainautoimmun emarkersin


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th eblood,such asantibod iest oinsu linandglutamicaciddecarboxylase(GAD).Th ein creasin g pre valence oftyp e2diabe tesinadolescen tsmakesitne cessary todiffere ntiate type1fromtype 2 diabet esinthisgroupofpatien ts.An oth erproblemisth edifficultyinassign in gade fin ite date forth e onsetofdiabet es,particularlyfortype2diabete s,whichcanbeasympt omaticformanyye ars,a det ermin ation thathasimplicationsconce rningth eriskfordiabete scomplicat ions. At theJoslin Clin ic, bothpatientswith n ew-onset d iabetesandth ose seekingconsu lt ation fore xist in gdise asearemaile da det ailed met abolicque stionn aireabou tsymptoms,cu rren tthe rapy ,familyhistory, e xercisepatter ns,and other medicalproblemsandt herapie s.Particular atte ntion mu stbepaidtohistoriesofcoronaryart ery disease ,periph eralvasculardisease,hy perte nsion ,an drenald iseaseinth epat ien tan dthe family. Patient salsoareask edtokeeparecordon adietaryasse ssme ntsh eetorinafoodd iaryfor 2or3days, includingth etime softh eirmealsandth etyp esan dquan titie soffoodse ate n.Thisinformation h elpsthe dietitiande sign an appropriate mealplanbase don thepatient 'sfoodpre feren cesan dlifesty le. Wit hne w information -techn ologysystems,patientscanaccessthe seque stionn airese lect ron ic allyanden tert he information fr omhome .Thiswillavoidmailde lays,he lpge tthe in format ioninat imelymann er,and en han ceth epat ien t'sv isitwithth ephys ician .

Physical ExaminationThe p hysicalexaminat ionisafu ndamen talpart ofth einitiale valuation. Specialatte ntion shouldbepaid tothe heightandweigh t,bodymassin dex(BMI),bloodpre ssure (lyingdownandstandingu p),an d vascularstatus. Ac arefu le xamin ation ofpe rip heralpu lse sand auscu lt ation ofcarot idandfemor al vesse lsforbru itsisext remelyimpor tan tin obt ainingab aselin eforthe fu tur e.The neu rologic examination mus tin clu deacarefu lsearchforeviden ceofn eur opathy .Notonlyar emu scle stren gthand reflexe steste d,vibrat ion, p osition sense, an dappre ciation ofapplication ofa10-gmon ofilamentt oth efeet mu stalsobe assesse d.Whilethe seclin icalmeth ods lackth eprecision ofadetailedlaborat oryn eur olog icev aluat ion,t heyst illp ermitt heclin ician toobtain a bas eline pict ureandtoob tainfur the rin vestigat ionsinappropriatepatients. Inastudy of189patients with diabetes and88contr olsubjects, Thivolete tal.(29)use dagraduated tu ningforktomeasure these nsitivit yofth efeet tovibratorysens ation sand not edth at51%ofpatients withclin icalsy mptomsofne uropat hyinth eextr emities,70%oft hosewit habse ntte ndonre flexe s,an d 75%ofth osewith abnormalner ve-conduct ionve locitie shadlimitedvibration sensation. Onth eot her hand, t hest udybyDycketal. (30)revealedthe prob lemspres entinassessingth eepidemiologicdat aon diabet icn europathy. Par tofth eproblemisth evar iet yofclin ic alt ypesofneu rop ath yand t he charact erizationofneu rologicdysfu nction.With multipleclinicalen titie sandv ariablepre sent ation ,th e best thecliniciancan doistolook foranddocument thepr esen ceofn europathy. I nare cent st udy, Pe rkinset al. (31)reported ont heu sefulnessoffou rsimplete sts:10-gSemmes-We in stein mon ofilame ntex amination ,supe rficialpain sensation, vib rationtest in gbythe on -offmethod,and vibrat ionte stingbyth etime dmet hod.They foun dexce llent sensitivityan dspecificityforeachoft he test sfromthe reporte doper atingch aracteristics.The timed-v ibration met hodtooklon gertoper form th ant heothe rs,but each ofth eother teststookle ssthan10secondsan dshouldth ereforebe p artof th ean nuale xamin ationfor neu ropathy .Ifthe histor yand p hysicalexaminationareatypicalfordiabe tes, an addition alwork upshouldbeu nder take nan dare ferraltoan eurologistconsidere d. The p hysicianalsoshouldpayspe cialatten tion toth epatie nt'sfeet, carefu llypalpatingth edor salis pedisan dpos terior tibial,poplit eal,andfemor alp ulses.Skelet aldefor mitiessuch ashallux v algus, bun ions, callouse s,an dhammertoesmustbe carefu llydocument ed.The combin at ionofvascu lardise ase an dneu ropath yist hemajor cause offootinfe ctionandn on trau maticamputationinpatient swith diabet es. Fin ally, acar efulfun duscopice xamin ationisdone ,alth ou ghth issh ou ldn otsu bstitute foranev aluat ion byanop hth almologistwit hexpe rienceindiab eticeyedisease.Somen ewme thodologiesusing nonmydriat icdigitalretinalimagingser veasanexce llen tscree ningtech nique t opr ioritiz ethe need for formalopht halmologicevalu ation. P. 590

Laboratory StudiesThe ch oiceoflabor atoryte stsperformedisin partde terminedbyt heclin icalp resen tationofthepatient . Ifthe patien tisinastat eofdiabe ticketoacidosisorissy mptomaticfrommarke dhype rgly cemia, the degr eeofhyper glyce mia, theacid -basestatu s,electrolytes, andth epre sence oface ton ear eurg ently asse ssed.Forthe n on acu tesituation ,att hepatie nt'sfir stvisit, theminimumtest srequ ire dare a complete urinalysisan ddete rmination sofbloodglucosean dHbA 1 c . Itisn owu sualtoaddt oth esea che mistrypanelth atinclude smeasure men tsoflipid s,liver andk idn eyfun ction ,an dele ctroly tesan da complete blood c oun t.Ifpossible ,the lipidmeasure men tsshouldbedone on thepatientint hefastin g statetoobt ainan accu rate deter minationofthe trigly ceridelevel.Itmaybe nece ssaryforth epatien tto makeasepar ate v isittothe officeorlabor atoryforthe setest s.Inmost c ases, lipids als oar eevalu ate d onth efirst visit. Totalch oleste rol,tr iglycer ide s,high-de nsitycholester ol,an dlow-den sit ychole sterol ar edete rmine d.Lipidst udiesar ean impor tan taspec tofdiabe tesasse ssme ntbec ause ofth ehighriskof


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macrovascu lardisease ,especiallyin the patien twit htype 2diabet es(32). Atest formicr oalbu minu riaalsoisrecommen ded, since the p resen ceofmicropr ote in uriah eraldsth e fut urede velopmen tofre naldisease (33,34)an disanindepe nden triskfactorforcardiovascu lardisease . Many differ entmeth ods areavailablefor d eterminingth eprese nceanddeg reeofalbumin excre tion, includinganalbumin-to-creatinineratioinaspotu rin e,t imedur in ecollection ,an d24-houru rin e collection.The latter testalsoallowsth edete rmination ofcreatinineclearan ce.The testforalbumin-tocreatinineratioisnowwide lyavailablean dcan e asily b eperformedinthe office,witht hecaveat that moder ate tointe nseph ysicalactivitymayresu lt in afalseincre aseinalbu minex cretion.Itisusu allyn ot ne cessar yin clinicalpractice tomeasureisletcellant ibodies,insulinau toant ibodies,oran ti-GAD an tibodiesinpatientsatthe clinicalonsetofthe dise ase. Th epre senceofan ti-GADant ibodiesmay ident ifyasubgroupofpat ien tswithad ult-on setdiabe teswhoact uallyhaveaslowlyev olvingfor mof au toimmu net ypediabet es[laten tau toimmu nediabe tesofadults(LADA)].Thes etests, tog ethe rwit hth e intraven ou sglu cose t olerancet est,areu sedin researchse ttingstodet ermin ewhichpat ie ntsareat high riskfor developin gdiabete s(35,36).The r ou tin emeasu rement ofinsulinlevelsor C-pept ide isnot recommen dedasaroutine testinclin icalpr actice. In selected inst anc es,th esemeasu rement smay indicate themoreappr opr iateselectionoft herapy.In the olderpatientorinpatie ntswithh igh blood pre ssureorafamilyhistoryofcardiacdisease ,abaselin eelectrocar diogramsh ou ldbe p erforme d.If add itionalcar diovas cularriskfact orsarepre sent orifthe patien tisplan ningtobeginanexe rcise program,consider ation shouldbegiven t ope rformingacardiacstr esstest .Theph ysiciancan orde ra che stx-rayfilmandothe rstudiesasnee ded.Patien tswit htype 1diabet esshouldalsoh ave a th yrotropin lev elmeasure don t hefirstvisitbecauseofthefr eque ntcoexisten ceofimmun e-mediated th yroiddisease.

EDUCATIONFort hepatie ntwithachronicdisease ,edu cation isalifelon gprocessan danopportu nitytoimproveselfcar etech niquesandtorecognize t heonse tofcomplications.Accesst oprint ededu cation almaterialsand tothe servicesofskilleddiabet esnur seedu catorswillhelpfacilit atet hisproce ss.Accesstodiabet es edu cationalmater ialsonth eInt erne tisincr easing, andp rovidingadvice aboutt hemostr eliable site sfor information canbe animp ort ant p artofthe education alproce ss.Caremustbe take nnottoov erwhe lm th epat ien twit hasu rfeitofinformation.The on setofdiabetes ,either type1ort ype2,isadifficulttime emot ionallyforthe p atient ,an dthe physicianmustbe asourceofencour agemen taswellasaprovider oft reatme nt.Th efamilysh ou ldparticipateinth eedu cationalprocessas much aspossib le. Inadu lt swith diabet es,involvin gthe spou sein the education alproce sscanbe veryr ewarding ;howe ver, thepatient mustbee ncouragedtoaccep tresponsibilityu nlessthe rear emitigat in gcon dit ions.Th ein it ialgoalsof edu cationar etoh elpthe familyun derstandth ebasicpathophysiologyofd iabetesandth edifferen ces bet we ent heinsu lin-de pende ntandnon-insu lin-de pende ntforms. Patient swith type1diabete sandt heirfamilieslear nbasicskillsne cessary forth epatie nt'ssurvival. Such nece ssaryskillsinclude (a)insulinadministrat ion;(b)SMBGandte stingforurineg lu coseand ket on es;(c)adjust in gin sulin dosagean dfoodintakeforexer cise;and(d)sick-daycare andpr even tion ofk etoacidosisan dtre atment ofhy poglycemia. Patient swith type2diabete saret augh tsimilarskills,alt hought heemphasisisver ymu chonth e nu trition alprog ramand we igh tcontrol.Itisimpor tan tfor p atient stor ealiz ethatth elossofe ven small amount sofweight(10t o20lb)canbe verybe neficialforoverallglucosecontrol.Theabilitytoselfmon itor bloodglucosealsoisimportantinth esepatients. Exer cise helpsob esepatie ntslose weig ht,andifthe y req uestmorethanasimple exer cisepr escription ,itisappropriateforth ephy sician tore ferth emt oan exe rcis ephysiologis t.Caresh ouldbet aken in prescribingvigorou sexer cise progr amstoolderpatie nts, espe ciallyth osewith diabeticcomplication ss uchasneu ropath yorr etinopath y.The reisalsoth eissueof coron ary d iseaseandsilen tischemia.Ifaqu estionarisesabou tth eprese nceofcoronaryartery disease an dwhet here xercisecanbeu ndert aken wit hsafe ty,th epat ie ntshouldber eferre dtoacard iologistfor app ropr iatete stin g.Astu dyin 1999byJan and-Delenn eetal. (37)of203p atient swith type1or t ype2 diabet esnotedt hat 20. 9%ofmalepatie ntswitht ype2d iabetesh adsile ntmyocardialisch emiawith significantlesion son cardiaccathe terizat ion. Th eau thorsth usre comme ndedrout in escree ningforme n withtyp e2diabe tesofmoreth an10ye ars'duration ore venlessforthosewithmor ethanone car diovas cularriskfact or. Onceth epatie ntiscle are dforanexe rcise program,he orsh eshouldexe rcise th reetofourtime saweek foratle ast30min ute sforth eprogramtobeofany benefit. Thosepatie ntswh owillbere ceiv in goralh ypoglyce micthe rapy must becomek nowledge ableab ou tthe act ionofthe seme dication sandt heiradv erseeffe cts.The yalsomustu nde rstan dthatmanypatient swill failtore spon dtothese agen tswithtime and willn eedinsu linth erapy.Wh enmedication ispr escribed, it isessen tialn ot onlytoinstru ctpat ien tsonhowtotake thepillsbu talsot ocoun selt hemon when to stoptak in gthe mtoavoidpote ntiallyseriou sadve rsesideeffect s.Thisisve ryimportant, becau sethe nu mbe rofn ewme dication sfordiabe teshasin creasedrapidlyand,formanyofthe m, we don ot k now th elong-t ermeffects. P. 591


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Atth ein it ialvisitit alsoisappr opriatetodiscu ssbrieflyther ation aleforglu cose con trolandth e poten tialforcomplication s.Atth istime,th ephy sician 'sinte rpret ation and u nde rstan dingoft hecu rren t lite rat ureonth erelationsh ipbe tween the con trolofdiabete sandcomp licationsan dfamiliaritywithth e standardsofcareset b ythe ADAwillb eextr eme lyimport ant .Ifthe physicianisvagu ean dnoncommittal inprese ntingt hisissu e,th epat ien tmayassume thattightcont rolisn ot nece ssary. Byin dividu alizing th erap yand b uildingonasolidfoun dationofb asicskillsacquire dbythe patient ,th ephysicianisina un iqu eposit iontoguideth epatie nttowar dimprovedcontrol.

CLINICAL GOALSItiseviden tfromthe ear lierdiscussionth atth etype ofdiabet esinflu enc esthe formofth erapychosen . Int hepatie ntwithn ew-onsetdiab eteswh oh asacu telydecompe nsatedtype 1diabe tesorin the p atient withpre viousdiag noseddiabete swhoisinpoor con trol,t hegoalswillin clu de(a)e limination ofket osis; (b)eliminationofsymptomsofh yperg lyce miasu chaspolydip sia,polyu ria,vagin it is, fatigue, and v isu al blurring ;(c)restorat ionofnormalbloodch emistr yvalues; (d )regaining oflostwe igh t;an d(e) rest oration ofsen seofwe ll-being. Atthistime ,the emph asisfor patien tswith previouslydiagnosed diabet esisonr estorin gthosebe hav iorsth atwillimprovediab etescontr olan dthatwillallowthe mto onceagainfullypart icipat ein the ircare. Glucosecontrolatth ist imeisd ire ctedtowar dgettingpatient s tomonitorthe ir b loodgluc ose, toimprov eadh eren cetoprescr ibed medicat ions, tobe comemore confidentatad ministeringinsu lin, and t ogathe rdataon the patte rnsofglu cose testing. Thisin formation becomesveryimport ant when on eisworkingwitht hepatie nttoplan t hech ang esin in sulin dosagean d timingt hat wille nsur ethatth egly cemicgoalssetwillbeachieved. Once theinitialgoalshave been met ,on ecan proceedtoworkon the planne cessar yforlong-ter m succe ss.Theg ener alaimisthe maint enanceofhealt han dwell-be in gthroug hcon trolofth edise ase. It isimpor tan tnottofoste ralife stylethatiscompletelydominatedbydiab etes. Pat ien tsshouldcontrol th eir diabete sandfollowtheirde sire dlifestyleasmu chaspossible .Thisisn ot alwayseasyto accomplish, especially in patien tswith very u nstableor brittletype 1disease .Aminorityofpatien ts ar esever elyin capacitated, and caremustbe take ntosetre alist icgoalsan dpromotebeh aviorthatis notself-depr ecat in g.Forman ypatien tsan dpare ntsofyou ngch ildren ,wor kin gwit hacoun selor, psych olog ist, orpsy chiatristcanhe lpalleviat efeelingsofg uiltanddep ression . AsdiscussedinC hapt er42,foryoung ch ildre nth egoalsareth emainten an ceofn or malgrowthand deve lopment. Again,t helife styleshouldbeasc losetonormalasposs ible,without diabete sbecoming th efocalpointofthe family'sex iste nce. Ideally,children shouldbecomfortableatschool,particip atein sports,andsocialize with theirpe erswit houtbe in gmadetofeeldiffer ent . Marry in gand h avingafamilyisimpor tan tfor you ngad ultswit hdiabet es.Helpingwomen whowisht o havech ildren achieve asucce ssfulpregn ancy isav eryimportantaspectofdiabet escare .Un less t he phy sician hasconsider ableexpe rie nceinth isarea,itispr eferable forth epatie nttobere ferred toa multidisciplinaryte amskilledinmanagin gthe sehigh-riskpre gnancies.However, allph ysiciansshould edu cate you ngwomen wit hdiabet eson appropriat ebir thcontr olme thodsan dthe impor tan ceofgood glycemiccontr olbeforeconcept ion. Un derlyingallthe segoalsisth edesiretocontrolt hediabe tesoptimallysothatlong-t ermmicrovascu lar an dmacrovascu larcomplication scanbe minimized. Sin cethe recur rent lyisnowaytopre dict wh owill deve loplon g-termcomplication s,itseemsprude nttoset agoalofoptimalglycemiccont rol,withinth e limit sofsafe ty,forallpatien ts. Beforeprocee din gwith the rapy, it isuse fulfort heph ysician tod iscu sswith patien tsthe differ ent leve ls ofsu ccessth atmaybe achiev edin the treatme ntofdiabete s.Inge neral, the g oalsofther apycanbe refe rredt oas minimal, average, andint ensive. Th egoalsasdefine dbythe ADA(38)follow. Minimal goals 1. HbA 1 c ,11%to13%;ortot algly cosylat edhemoglobin(HbA 1 ),13. 0%to15. 0% 2. Many SMBGvalues ofhighe rthan300mg/dL 3. Testsforur in aryglucosealmost alwaysposit ive 4. Int ermitt ent ,spon tan eousket on uria Average goals 1. HbA 1 c ,8%to9. 0%;or Hb A 1 ,10%t o11.0% 2. Pr eme alSMBGof160to200mg/d L 3. Testsforur in aryglucoseinte rmitte ntlyposit ive m 4. Rareket on uria Intensive g oals


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1. HBA 1 c ,6. 0%to7.0%;orHbA 1 ,7%t o9%

2. Pr eme alSMBGof70to120mg/dLandpostme alSMBGoflessth an180mg/d L 3. Testsforur in aryglucoseesse ntiallyneve rpositive 4. Nok etonur ia Int hemost r ecen tstan dard sofglycemiccontr ol(38a), t heADAr ecommendsanHbA 1 c oflessth an 7%, apr eprandialplasmaglu cose lev elof90to130mg /dL,an dapostprandialplasmaglucosele velofless th an180mg/dL . Assessment ofth ele velofdiabe tescontrolisbe staccomplishedby measuringbiochemicalparamet ers. Clinicalin dexessu chasbodyweigh t,frequ enc yofpoly uria,polydipsia,nu mbe r P. 592 ofh ypogly cemicreaction s,fat igu e,andsen seofwell-beingareimportantclin icalparamet ersbut canbe mislead in gaboutth eoverallle velofcontr ol.Itistru ethatpat ie ntswithve rypoorcont roloft encanbe ident ifiedeasilybyth eirsymptoms;howeve r,patie ntswh osefastingglucosele velsare 140to180 mg/dLan dpost pran dialglucoselevelsar e180to240mg/dLcanfeelquitewe llan dpresen tafalse clin icalpictu reofsatisfactorydiabe tescontr ol.Int hepast,dailyur in aryglucosemeasu rement sand randomoffice g lu coset estswere relie don .Howe ver, t heaccuracyofu rin ete stin gcan sufferinth e pre senceofah igh renalt hre shold, r enaldisease,orbladder neu ropath y,an dthe selimitation saren ot eliminat edbyth euse ofadoub le-v oidedu rin especimen.Te stin gfor t hepr esence ofke ton esisstillbest accomplishe dwith aur in esample. Du ringth elasttwodecades,ge neralavailabilityoftwoinn ov ation shasr evolu tionize dou rapproach to th erap y.Thefirstofthe sewasSMBG(39), andt hesecond wasthe developmen tofr eliable assaysfor glycosy latedh emoglobin.

Self-Monitoring of Blood GlucoseSinceitsdeve lopment, SMBGhasdevelop edin toasophisticated monitor in gsystem.Avarie tyofglucosemon itoringde vice saren owavailablethatgiveadigitalreadou tofthebloodglucoseconcen tration. The devicescont in uetobeimpr ove d,an dthe timere quiredforthe testt obecomple tedisnowasshortas5 seconds. Inadd ition,th esizeoft hebloodsamplesre quiredh asdecre ased, an dmanymeters u sea directactivationsyste m.Some ofth ene westmetersallowblood samp lingbothfr omthe finge ran dfrom th efor earm,th ere byredu cin gtheover useandcallou sin gofth efinger s.These devicesappe araccurate en ou ghforrou tineu sebypatie nts. Forcon ven ie nce, mech anicallanc etdevicesareav ailable for obtainingblood. Someoft hene werglucosemon itorsinclude compute riz edme morytorecordth eblood glucoselevels,andsomecanbeu sedinconjunct ionwithmor eelaborat epersonalcomputer s.Special machine sareavailablefor visu ally impairedpatient s.Oneconce rnabou tSMBGist heaccuracyoft he recordingsascompar edwit hth oseobtain edinth elabor atoriesoflar geclin icsorrese arch settingst hat use moresophisticate din strumen ts.The patien tmayencoun terman yproble mswithSMBGine veryday use ,eve nafte rrece ivingcarefu linstr uction on the t echn iqu ebyadiabetesn urse educator.One such difficu lty in volvesth epatie nt'sabilityt oobtainadropofblood,place it accuratelyonth ereagent strip, an dtimet hemon it orcarefu lly.Newer monitorsthatdonotrequ ire wipingortimingandth atallowthe use ofver ysmallamount sofbloodcan helpminimize thes eerrors.Astu dyper formedbyJovanovicPe tersone tal.(40),inwh ich four met ersyste mswer ecompar ed,de monstr atedt heleastvarian cefrom th econ trolsy stem(aglucoseau toanalyz er)witha no-wipe system.Use ofth issyst em,which eliminat edth enee dforbloodre movalan dtiming, greatly d ecreasedth evar iabilityin test r esults. ForSMBGt obe effective,itsu semu stbeaccompan ie dbyan education alp rogr amthathelpsth epat ien t un derst andt hefac tor saffectinganyparticularbloodglucoselevelan dthatprovidesappr opr iateoption s forcorr ection sor adjustment s.Thisknowledgeispart icu larly neces saryforpat ie ntsinvolv edin in ten sive insulintre atment prog rams. The rehasbeen somediscussion aboutt hevalu eofr ou tin eSMBGinpat ie ntswithty pe2diab eteswh o ar eusingdietororalage ntsforcon trol(41). Alth ou ghth esepatientsr arelywillmaketr eat men t change sont hebasisofin for mat ionfromSMBG,itcan r einfor cedietar yprinciple sandr evealth e ben efitsofex ercisean dme dication .Patie ntswitht ype2d iabeteswh oarerece iv in gin sulin should definitelyuse SMBG.Hypoglycemiaoccu rsbot hinpat ien tsbeingt reat edwithsulfonylure adru gsand th oser eceivinginsulin;inthisset tin gSMBGcan con firmalowglucoseleve landmayhe lpt heh ealthcare provideradju stthe rapy on amoret imelybasis.The freque ncyofmonitorin gcan easilybeadju stedto th ein div idu alpatien t'sn eedsandcircumstances.SMBGisth ereforeanex tremelyvaluable toolfordaily diabet esmanagement. There centint rodu ction ofasu bcut ane ou scon tin uousglucose-sen sin gmonitor th atcanobtaina3-dayprofileofbloodglucoselevels(240r eadings)canbe avery usefultoolin selecte dpatien ts.Such datacan bevery impor tan tin assessing t hedoseofpreprandialinsulin,in ident ifyingu nre cogn ize dhypoglycemia,an din revealing thedawneffect .Rapidadvan cesinne wg lu cose mon itoringsyst emsareex pected over then extfe wy ears.

Glycosylated Hemoglobin Assays


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Int helastde cadeanu mber ofstu die son g lu cosecont rolan ddiabeticcomplication shavebee n complete d,an dallu seHbA 1 c asasu rrogat emarker forrisk.Th estan dar dsofcar eoft heADAwe re rev ised basedonth efast in gbloodglu cose lev elaswellasont heHbA 1 c fromth esest udies.Cu rren tly, laborat oriescanme asu reeithe rthe tot alglyc osylat edhemoglobinorthe A 1 c fraction .Thelat teristhe test usedinth elarge ou tcomestu die s.Howe ver, theassaysh ave n ot been stan dardized, and becau se commerciallaboratoriesuse differ entmeth od s,the refere ncerange svary, makin gitdifficultforthe clin ician tou seth eresu ltsifth eyvar ycon stan tly.Cliniciansshoulduse thesame laboratorytome asur e A 1 c in the s ame patien tov ertime . Inn or mogly cemicsubject s,acarbohydratemoiety isattach edtoasmallpr oportionofh emoglob in A, th uscreatingwhatiscalled g lycosylate dorglycat edhe moglobin(42).Th eglycosylat edhe moglobincan bese paratedintoth reedistinctfraction s,whicharedesignatedA 1 a ,A 1 b ,andA 1 c .Becauseof electr oph ore ticb ehaviorofthese minorhe moglobins,t heyarere ferred toasfast h emoglobin. Th eA 1 c fractionisthe mostreactivesiteofthe N-valine termin aloft heB-chain,whichaccou ntsfor60%ofth e bound g lu cose. Incondition sofsu staine dhyper gly cemia, suchasin diabete smellit us,th eproportion ofhe moglobinth at isglycosylate din creasessubst ant ially(43).Thisglycos ylation isth eresu lt ofposttranslational modification ofhe moglobinAmolecu les;t hebindingofglucoseisanonen zymaticprocessth atoccurs continu ou slydu ringth elifeofthe r edbloodcell. Thus, theamoun tofglycosylated h emoglobin reflects th egly cemiccontrolofap atient duringt he6-to8-weekpe riodbeforet hebloodsamplewasobtain ed, givent heaveragelifespanofared b loodce llof120days(44). Th eamount ofglycosy latedh emoglobin correlat eswellwithfastin gan dpost pran dialbloodglucoselevels.C urre ntly,t heglycosylatedh emoglobin can bemeasu redbyion-exch an gehigh-pe rfor manceliqu id c hromatog raph y(HPLC ),affinity chr omatography, andimmun ologicmeth ods. Inth eDC CTstud y,an ion-e xchan geHPLCme thodwasu sed, an ddat afromth isst udyhavebe enadopt edasth erefe rence stan dardforassessin gglucosecon trol. Arece ntstu dybySchn edletal.(45)n ote dthatthe rearemore than700kn own varian tsofh emoglobin th atmayaffectth ecurr entlyus edassaysforg lycosylate dhemoglobin .The yevaluatedt heeffe ctofth e followingh emoglob in v arian ts:HbGr az, HbSh erwoodForest, HbOPadova, HbD,andHbS.Th eynoted th atth eHPLC bor on ateaffin it yassaylackedth eresolution nece ssaryt oseparat eoutth evar iantsand th atth eimmunoass aysres ultedinfalselylowlevelsofHbGraz.Itisthe reforerecommen dedth at laborat oriesest ablish an dvalidateassaysforth elocalpopulationtomakeallowancesforan y he moglobinvariant s.Theglycosylatedh emoglobin assay ispre sentlyoneofthe mostwidelyapplie d test sin theman age men tofdiab etes. Itisu sefulfor theassessmentofglycemiccontr ol inpat ie ntswithty pe1diabe tesandinpat ien tswithty pe2diabe tes. Glycosylate dhemoglobinvalue smu stbeass essedwithcaution in patien tswit hun stablediabe tes. L evels ofb loodsu garint hese p atient sflu ctuatefromve rylowtovery h ig hon an almostdailybasis,asitu ation th atcanleadtoun want edsymptomsofhyper gly cemiaanddanger ou sepisodesofhypoglycemia(38).A stu dybyBrewe retal.(46)su ggeste dthatusingapie -shape dgrap hofSMBGd atawith definedtarget rangeparamete rscan aidpatien tsan dtheirfamiliesattaint hede sire dHbA 1 c g oals.Th eau thorsset t he targetr ange forSMBGv aluesfordiffe ren ttimesofthe dayandth ende termin edth enu mber ofvalu es th atn eededt obe with in orabov ethatrangetoach ie veth edesiredHbA 1 c .Foryou ngadults17to35 yearsofageu sin gatargetrange of70to150mg/dl, atleast 38%ofthe v aluesn eeded tobe in t he targetr ange andn omor ethan48%aboveth erangetoach ie vean HbA 1 c oflessth an8%. Th eas sayof glycosy latedh emoglobinsh ou ldbe don eeve ry3to4month s,wit hthe goalofadjust in gthe rapyt o obtainth elowest valuet hat doe sn ot placepat ie ntsatund ueriskforhypoglycemicre actions.In p atient s whohavereache dagoalandareve rystable, the testcanbedone e very6mont hs.However ,it is importantth att heinformation obt ainedfromthet estbecommun icatedt oth epat ien ttouset oimpr ove adh ere ncetoth eprescribed t reatme ntplan .Atprese ntt heHbA 1 c ist hebe stsurr ogatemarke rwehave forsettinggoalsoftreatme nt. Effor tsare unde rwaytostandardiz ethe proce dure formeasu ring glycosy latedh emoglobin. Ultimat ely ,thiswouldresultinacertification processforman ufacture rsan d th usen surest andardizat ionofther esultsuse dbythe healt hcar eprofessionalinse ttingglucosecontrol goalsfort heirpat ie nts. P. 593

INITIATION OF THERAPYFormostadu ltpatient s,in it iation oftre atment issafely accomplish edinth eou tpatie ntset ting.Ver y young childre nan dpat ien tswithdiabe tick etoacidosisorsever e,un con trolleddiab etesu suallyrequ ire hospitalization.Although the d ecisiontouseinsu linu suallyismad ebyth ephysician, itisext remely importanttoexplain t heration aletopatien tsan dtoinclude the minth edecisionpr oces s.Manyh ave an un derst andablefear ofinjection san dofte nregardth isth erapyasanindicationoft hepre sence ofa more severe formoft hedisease.Insu lint herapyne edstobepre sente dasanyother treatme ntoption , an dpat ien tsshouldbemade tou nder stan dthaton e,two,orth reeinjectionsper daymaybe n eede d, depe ndingonth eirresponse .Theph ysicianalsosh ou ld r eviewthe issu eofcont rolan dcomplications and deve lopinitialg oalswithth epatie nt. Atth eJoslinClinic,th edecisiontostartinsulinth erap yisfollowedbyar eferralt oad iabetesn urse


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edu cator,wh owillinstru ctth epat ien torafamilymemberonth etech niquest hat willbe requ ire d. Patient swilladminister theirfirstinjectionat t histimeu nder superv ision .Thisalsoprov ide san oppor tun ity t ote achp atient saboutth etype sofinsu linavailable and t heirch aracteristicpeak sand dur ationsofactivit yand t ore vie wstrat egiesfor dealingwit hhy poglycemiaan dhype rglycemia.The pre sentavailabilityofvery-fast-actin ghu manin sulin an alogu es,aswellasanonpeakingbasalh uman insulinan alogu e,h asincre asedt hene edtoemphasize t opatientst heimportance ofcoordinatingth e timingofme alsan din sulin in jec tionaccor din gtot hety peofinsu linu sed.Th etech niquesformixing reg ularwithinte rme diate-actinginsulinsmaybere viewediftheph ysicianbelievesth att heseare app ropr iateinsulinformu lation sforaspecificpatie nt. Premixedinsu lin[70%neu tralprotamine Hage dor n(NPH)an d30%cr ystallin ezincinsulinor75%n eut ralprotamin elispro(NPL)and25%lispro] can beuse din it iallyinpat ien tswhomaynotbeable tomast erth emixingofin sulin s.Thissimplifiesth e tre atment program,espe ciallywhe npat ie ntshavepr oblemsunde rstandingan dperformin gthe mixin g mane uver s.Fu rth ermore ,th esepre mixedinsu linsarenowavailab leinpr efilledsyringe swith asimple dose-dialin gme chan ism.In manycase s,limit ation sin mixinginsu linsaredue topr oblemssuchas cat aracts,deg ener ativejoin tdise ase, previouscere brovascu laraccident s,orsever eneu ropath y. Most n ewpat ie ntswhoreq uireinsulinwillreceiveh umaninsu linofrecomb in ant DNAorigin.Allergyand lipoat roph yar euncommonwithh umaninsu lins. Beefinsulinan dmixedbe ef-porkin sulinshouldbe av oidedu nlessthe rear especificindicat ionsforth eir useorifh uman insu linisnotavailable .Thes e latte rin sulinsare nowbein gphasedoutinth eUn ite dStat es.Patient salsoareinstru ctedonSMBGat th istimean dareaskedtomaintain closecontactwit hth enur seedu cator,wh ointu rnre vie ws adju stme ntsininsu linth erapyan dthepatient 'sprogresswith t heph ysic ian.In mostpat ien ts,t heblood glucoselevelscan beexpe ctedtobebrough tun dercontr olov era4-to6-week period. Th epatie ntoften isseense veralt imeswit hinth isinte rvalsothatthe physiciancanmonitorprogress, modifyther apy, and rev iewanyinte rimproblemsorconcer ns. Most p atient saren ot start edon an in tensiveman agemen tprogramat t histime, asitisn ecessaryto allowth epat ie nttoadjust tot heemotionalandlife stylechangest hat followadiagn osisofdiab etes. Int ensiveth erapywit hmultipledailyinjectionsor con tin uoussu bcutaneousinsu lininfu sionisusedfor women whoplanapr egnancy, patien tswhocann ot c ont rolth eirglu cose lev elsb ycon vent ional th erap ies, orp atient swhos elifesty lesorcomplication s,espe ciallyh ypoglycemicunaware ness, demand th egreaterflexibilityandcontrolthatin ten sive prog ramsoffer (47). Patient swith knowndiabet esinpoorcontr olor with complicationsofdiabet eswillunde rgoasimilar evalu ationan dphysicalexamination .Atte ntion isfocused h ere ont hepatient'sgen eralapp roachtothe disease ,wit haparticular focusonth epatie nt'saccept ance ofth edisease anditstr eatmen t req uirements. TheJoslinC linicoffe rsan out patien tprogramcalledDOIT, in whichpat ie ntsareseen byateamoverape riodofthre ean dahalfdays.Th isprogramallowsacompreh ensive r eviewoft he pat ie nt'sprob lemsan dfor t hese problemstobeadd ressedonanindividu albasis.Th isprogramh as becomenece ssarybe cau se,withth echangingh ealth care-insu ran ceen vir on men t,th eoldinpatient edu cationprogramsar enolonge ravailab leinman yin stitutions.Man ypat ien tshaveanov erwhe lmin g fearofh ypog lyce mia.Some willd eliber atelyavoidusingr apid-acting insu lin orwillomitthe ir e ven in g injection s,whichpr edictablyres ultsin hype rgly cemia. Othe rswillover compen sateandtr eat any symptomsasasignofpote ntialhypoglycemiaand somewillstart tomonitor g lu coseleve lswith exce ssive frequ encyinanefforttodiscove rlowervalu esinth ehopeofavoidingse vere hypogly cemic reaction s.Itisimportan ttoreviewth enu tritionalp rogr ams,exe rcise habits, alcoh olin tak e,an d psych osocialst atu softh esepatients. Even somepatie ntswithdiabetesoflongdu rat iondonot app ropr iatelytime t heirinsulininjection totheiringe stionofcalor ie s.Also,some patien tsmaketh e mistakeofregu larly in je ctin gin sulin ath ypert roph ie dsit es,withre sultan tun predictabilit yofinsu lin abs orpt ion. In gen eral,n oacutech an gesinthe in sulin prog ramare mad eataninitialv isit,bu tth e pat ie ntfre quen tly isaskedtomonitorbloodglucosethr eetofou rtimesadayforth enex tmont h,with th efocu sbeingonth enu tritionalpr ogr am. Change sofinsulinth erap yaremade byteleph on eor at fut urevisits.Patien tswit hmajorpsy chologicalp roblemsare referr edtoapsych ologistorpsych iatrist. Un le ssthese issu esar eaddre ssed,diab etescontr olwillcon tin uet obeaproble m. Somepatientswillre quirehospitalization.Att heh ospital,t hefocusofthet reat men twillbeedu cation an dclosemon it oring t oiden tify p ote ntialproble mssu chasn octu rnalh ypoglyc emiawithr ebound hy perglycemia,hy poglycemicunawaren ess,orinh eren tly unst ablediabet es.Ev enth ou ghth eprese nt economicclimate ismakingitmor edifficulttohospitaliz ethe sepat ien ts,t here isn oway ofsat isfactor ily add ressingsome ofth eseproblemsint heoutpatient se tting. I ft hepatientishospitaliz ed,itisimpor tan t toatt emp ttor eproducet hepatient'snormallifestyleascloselyaspossible, in clu din gthe timingan d conten tofmealsandex ercise.Complicat eddiabet esrequ ir esin div idu aliz edthe rapyt hat isbothcomple x an dtime-c ons uming .Forappropriateindividualizedcaretobeprovidedforpat ien ts,spe cificissu esth at mayinte rferewithoptimalc ont rolmustbe iden tified andaddresse dcare fu llyandsympath etically. Solut ionsth atoffert hepatie ntth egre atest opportu nityforasu ccessfulou tcomesh ou ldbe sou ghtin consultationwith t hepatientandth epatie nt'sfamily.Ver yofte nindivid ualswit hun stab leglucose controlwilln eedtohaveth eirgly cemicgoalschangedtoav oiddan geroush ypoglyce mia,de spit eearlier

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en cou rage men ttomain taint igh tcon trol. Patient swith type2diabete smayrequ ire in sulin wh en t heyarefirstsee n,particularlyifthe yarev ery symptomaticandh avelostweight. Insomeinstance s,in sulin can bediscon tin uedwh encont rolis ach ie vedandadh ere ncetodiethastak eneffe ct(48).Howe ver, man ypat ie ntswillrequ ir ein sulin indefinitely;th isbe comesobviouswh ent heybe comeket on urican dhyper glyc emicwit har educt ionin insulindose. The b asisofth erap yin type2diabete sistopromotelifestylechange swith anu trition alprog ram designe dtor educe caloriesanden cou rage weig htloss. An exer cise progr amisanessen tialpart ofan y efforttoloseweigh t.Glyce miccon trolcanoften beimprovedby c aloricrest rict ionalone, even before significantweigh tlossoc curs.Att hesamet ime,itisalsoimp ort ant topaycloseatten tion tot herisk fact orsformacrovascu lardisease .Thisme anscontr ollin glipidsandh ypert ensionan dcou nselingon smokingce ssationan dthe v alueofglu cose con trol. Pat ien tswithty pe2diabe tesalsoare t au ghtSMBG, an dthe freque ncyoftestingisindivid ualized.SMBGisalway sthepr eferre dme thodofglucose mon itoring, with urinet estingbeing u sedonlyin specialsit uat ions. The d ecisiontouseoralantidiabeticth erap iesisgen erallymadeafterat rialofnu trition alther apyu nless th ein it ialrandomgluc oseleve lishigher than350mg/dL.In gene ral,a4-to12-weektr ialpe riodofdiet an dlifesty le modificat ionisreason able,andift hefastin gglucosecon cent rat ionre mains h ig hert han 140 mg/dLor postp rand ialvalu esar ehigher than200mg/dL,t reat me ntwithoralpharmacologicagen tsis initiated. Mu chhaschangedint hisareasin ceth elastedition ofth ist extbook .Thelast 5yearshave see nthe in troductionnotonlyofn ewsulfon ylu reasbutalsoofn ewnonsu lfonylur eainsu lin secre tagogu es.The latterdr ugsar eoft enmor erapidactin gthanth esulfon ylureasan dmaybever ywell suited in t reatin gpost pran dialh yper glyce mia. Th ebiguanideme tfor min,wh ich hasb eenavailablein manyp artsofthe worldfordecade s,wasint rodu cedintothe United St ate sr elativelyrece ntly.Th eglucosidaseinhibitorsoffer anoth eroptionforcontr ollingbloodglucoseleve ls,e speciallyaftermeals. A totallynewclassofor almedication, thet hiozolidine dione s,alsoisav ailable .Dru gsinthisclassar e novelinsulin-sen sit izingagent sthatwor kthrough specificn uclear recept ors. The p hysiciannowispresen tedwithanumber ofchoicesan dtriesclin icallytomatchth epre sume d un derlyingabnormalityinth eindividualpat ie nttoaparticularph armacologicappr oach.Bec ause type2 diabet esinvolve saduald efect, t hee arlyuseofcombinationt herapymaybeve ryad vant ageous. Cu stomarily,t hepatie ntwillstartwithas ulfony lu reaoranin sulinsensitizer .Itisveryimp ort ant forth e he althcareprovidertobeawareofthe con train dicationst oth euse ofeachdru gaswellthemon it oring req uirementst oavoidseriousadv ersere actions.Failureofcon trolwith asin gledrugwillre sultin the use ofacombin ationregimenth atcantakead van tageofthe diffe rent mech an ismsofaction. Subst itu tion ofdru gsfromoneclasstoan ot herisrarelysuccessfu l;h owe ver,t headdit ionofadru gfrom an ot herclassoften improvesglucosecontr ol. The r ecen tly c omple tedUK PDSd emonst rate dthatmanyofthe oralmonother apieswillfailtocontrolthe bloodglucosele velsforlonger t han 5ye ars(3).Muchofthe failu reisduetoth eprogression ofth ecelld efect, with con tin ued r educt ionininsulinproduct ion. Somepatien tswhofailt oobtaincont rolwit h th emaximaldoseoforalmedicationmayben efitfromth ecombinedu seofinsu linandoralmedication . Usu ally abedtimedoseofinte rme diate-actinginsulinorabasalin sulin analogue (48a)isgive n,witht he oraldrug b ein gcon tinue d(49).Ifthe patien thash ig hbloodglucosele velsfollowingsupp er,amixtu re ofashort-actingan dan int ermediate -actinginsu lincanbegiven beforesupp er.Itisoftenu sefultouse apr emixed in sulin (70/30h umaninsu linmixture or75/25lis promixture )in patien tswhohav edifficulty withmixing oradju stinginsulindose.Sev eralstu die sofcombinationt herapyhavebe encomplete d. Gene rally ,pat ien tswhohaveresiduale ndogen ous insu linse cretionrespond b est,alt houghpatient s' resp on sesvar ygreatly andt reat men tsmustbeindividualized(48). Fore verypatient ,diabete smanage me ntmustinclude acar efulnut rit ionalassessmentandth e implement ation ofarealisticdiet arypr ogr am.Thegoalofn utr itionalth erapy in type2diabete sisth e controlofbloodglucoselevels,normaliz ation oflipidleve ls,andmainte nan ceofide albodywe igh t.For young childre nwithdiabe tes,t hegoalshouldbeth emain ten an ceofn ormalgrowthanddev elopment ,as wellasofareasonablebod yweig ht. Inge ner al,the die tit ianwillprescribeame alplanbase don the in dividualp atient 'stype ofdiabe tesan d modeoftre atment .Patientsr eceivingexogen ou sin sulin mu stpayparticularatte ntion tot hetimin gof mealsan dsnack stopr even tun duefluctu ationoft hebloodglucoselevels.Th eme alplanis individ ualizedwithre specttoweightgoals,pe rson alfoodpre fe ren ces,an dexe rcise habits. Manyobese pat ie ntswithdiabe tesmayre quirespec ialweight -lossprogramsan dbehaviormodificationth erap yto maintain we igh tloss. U nfortu nat ely ,mostpatientsdonotsucc eedinth eir effor tstoloseweightandto maintain we igh tlossforprolonge dperiod s. Diet ther apyoften isre fe rredt oasthecorn erstoneoftre atment ,par ticu larlyin type2diabete s.Fort he pat ie nttoben efit maximallyfromthisasp ectofpatient manage me nt,ateamapproach, whichin cludes th eservicesofaskilledr egistere ddie tit ian,isrecommen ded.Althoug hthe seskillsar enotalways av ailable in p hysician'soffices,th eyareoffe redinlocalcommun it yhospit alsand bysomedietitian sin privat epractice .Adetaileddiscussiononthiscompone ntoftreatme ntisprese nte din C hapter36on


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nu trition alther apy. Exe rciseplaysan importan trole in diabete sman age men t.For patien tswit htype 1diabet es,ex ercise shouldnotbet hought ofast hemajorwayofimprovin gglucosecon trolbu trather aspar toft heoverall app roachtomain taining ahe althylife style.Physicalactivitycanben efit thep atient byloweringt he bloodglucosele velifoverallcontrolisgood .Howe ver,caremustbe take ntoin stru ctthe p atient on the possibilit yofph ysicale xerciseprovokin ghypoglycemicr eactionsorworse ningcontr olwhen unde rtaken inth eprese nceofhigher b loodglu coseleve lsandket on uria. Fur the rmore, patien tswit hthe complication s ofr etinopath yan dneu ropath ycan p lacethe mse lve sin jeopardywit hexce ssive exer cise. Inge ner al,pat ien tswhoare freeofcomplicationscanen gage in anyt ypeofexercise. Cert ainact ivities, such asscu badivin g,h avetobeassessedinlightofthece rtification requiremen tsissuedbyappropriate organ ization s.Patient soften mayben efit fromaconsu ltation with ane xerciseph ysiologist.In patien ts withtyp e2diabe tes,anindividualizedex erciseprogramshouldbepartoftheover alltr eatmen tplan. Exe rcisehelpspromote weigh tloss, optimize glyce miccon trol, an dreduce cardiovascu larrisk.The se pat ie ntsn eedtobescre ened forearlyneu ropath yor peripher alvascu lardise asebe fore they start an exe rcis eprogram.Silen tischemiais morecommon in patien tswit hdiabet esthaninth egen eral population,andap prop riatepatie ntssh ou ldh ave astre sst estbeforest arting thee xerciseprogram. Routine screen in gofmenwith type2diabete soflon gerth an10ye ars'duration orlessifthey have more thanon ecar diovascularriskfact orisrecommen dedbe cause ofth ehighpr evalen ceofmyocardial ischemiawit hsignificantlesion samon gmen wit htype 2diabet es(37).The progr amshouldbedone th reetofourtime saweek tobe effective, with appropriat ewarm-ups, settingt arget exer ciseleve lswith mon itoringofpulseratean dcoolin g-down time. Afu rth erdiscussion ofth isimport ant areaappe arsin th eeditorialby Ne sto(50)inth eissueofDiabe tes Careth atpu blishe dthe abovestu dy[refer ence (37)]. P. 595

FOLLOW-UPAcriticalpartofdiabet esmanag eme ntisregu larfollow-u pofpatie nts. Th isisbase don the g oals establish edwit hth epat ien tinthe in it ialmanagement plan.Ate achv isitth ereafter, thepatient 's progressisrev iewe dand ong oingproblemsareaddresse d.The fr eque ncyofvisitsdep endsonth e individ ualpat ie nt,t ypeofd iabetes, goalsofcon trol, an doth ermedicalcon dit ions.Pat ien tsstarting insulinth erap yneed tobe seenfr eque ntlyin it ially,bu tonceth eircon dit ionh asstabilized,t heycanbe see nthr eetofou rtime sayear.In addition ,patien tsar eencour agedt omaintain telephone con tactwith th eot hert eamme mbe rs.Somepatientswith t ype2diabetesn eedt obese enonlyeve ry6mon ths. Aspar tofth isfollow-upprocess, aninte rimhistoryisobt ained, resu ltsofglucosemonitoringar e rev iewe d,an dnewpr oblemsorilln essesth ataffectdiabe tescontrolareaddresse d. Acompre hen sive physicalexaminationisdoneannu ally .Atin ter imvisits, previou sly abnormalfin din gs ar eree valuat edan dheigh t,weight, an dblood p ressur eare deter mined .Foryoun gerpatie nts, an asse ssme ntofsexualmat urationsh ou ldbe don e.Acomplete ,dilatedey eexaminationby an ophth almologistshouldbepe rfor medann uallyin allpatientsolderth an30ye arsandinpatie nts12to30 yearsoldwh ohaveh addiabet esfor moreth an 5years. Atest forglycosylatedh emoglob in sh ou ld b edon eat leastqu arte rly in p atient swith type1diabete sand semiann uallyin thosewithty pe2diabe tes. Th epat ie ntwithadult-on setdiab etesalsomayben efit from havingeithe rafastin gor postp ran dialglucoselevelche ckedasame ansofjudgingoverallglycemic control.Adete rmination offast in glev elsoftriglycerides, cholest erol, andh igh -den sity lipop rot ein (HDL) cholester olshouldbeper formedannu ally andmor eoft eninpatie ntswithdy slipidemia.Urinalysisdone at leastyearlyisu seful.Afte r5yearsofdiabetes, patien tsshouldbete stedformicroalbuminuriay early. Ifproteinu riaispr esen t,th epat ien t'scr eat in in ean dblood u reanitrogenleve lssh ou ldbe closely mon itored ;inaddition, aggre ssiv ean tih ypert ensiveth erapyan dproteinrest rictionsh ou ldbe con side red. Ateachvisit theover allman agemen tplan, includ in gthen utr itionalprograman dthe exer ciseplan ,is rev iewe dand modifiedasrequ ire d.Inaddit ion, theover allemotionalst atu softh epat ien tisreviewed. Thistype ofcompre hen sive care isex tremelyimportan tfor patien tswit hach ron ic, life-lon gdise ase such asdiabe tes.Th isch apte rhasr eviewedth egen eralprinciplesofman agemen tofdiab etes. Manyof th edetailswillbefoundinothe rchaptersint histextbook.Sinceth elasteditionthe reh avebe enman y importantadvan cesinthe unde rstandingofthepathophy siologyandtr eatmen tofdiabe tes. Ne w diagn osticcriteriah ave been developed,andne wgoalsoftreatmenth ave b eende fin ed.Man ystud ies demon stratingth evalue noton lyofglucosecon trolbu talsoofriskfact orre ductionan dcardiovascu lar disease hav ebeen publish edandincorpor ate din tot herout in eapproac htodiabete sman age men t.In add ition,th erapeut icch oiceshaveincre asedg reat ly, andt herapycan nowbebase don the u nde rly in g pat hophysiologicmech anismsofdisease .The p rimar ygoalintr eat in gpatien tswith diabete sistohe lp th emavoidsh ort -termproble msandlon g-termcomplication s.Arecen tstu dyofadultswit htype 1or type 2diabe tesinvest igatedcognitivere presen tat ionsofillness,se lf-re gulationofd iabetes, quality-oflife, and behavioralfactor s.Theauth orsfoun dthatindividu als'u nder stan din gofdiabe tesandth eir per ception sofcontr olove rthe dise asewer ethe mostimportantpr edict or sofoutcome (51). This


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reinforcest hen eedtocontinue top rovideongoingself-edu cationfor patient sand t opr ovideth emwith th eeviden ce,nowavailable ,thatcontrolofdiabet esisp ossiblean dthatcomplicationscanbe avoide d. Tot hepracticin gphysician, diabete soffer sthech alle ngeofprovid in goptimalpatien tcare atev eryvisit . Itallowst heph ysician the opportu nityan dprivilege top racticen otonlyth escie ncebu talsotheartof medicin e.

REFERENCES1.Thee ffe ctofint ensivetr eatmen tofdiab etesonth edeve lopmentandprogre ssionoflong-t erm complication sin in sulin depen den tdiabete smellitu s.Diabetes C on trolandComplicat ionsTrial Re sear chGr ou p.N En gl J Med1993;329:977986. 2.Ohku boY, K ish ikawaH,ArakE, etal.In tensive insu lint herapypre vent sthepr ogr essionof diabe ticmicrov ascular complicat ionsinJapan esepat ie ntswithn on in sulin depen dent d iabetes mellitus:aran domizedprospective 6-yearstu dy.Diabe tes Re s Clin Pract1995;28:103117. 3.Inte nsivebloodglucosecontrolwith sulfon ylu reasorinsu lincomparedwith conv entionaltre atmen t andth eriskofcomplicationsin pat ien tswithtyp e2diabe tes(UK PDS33):U KProspect ive Diabet es Stu dy(UKPDS)Group.Lancet 1998;352:837853. 4.ShichiriM,Oh kuboY,KishikawaH,etal. Lon gtermresu lt softh eKumamotost udyinoptimal diabe tescontrolin type2diabeticpat ien ts.D iabete s C are 2000; 23[Su ppl2]:B21B29. 5.JavittJC ,Ch iangY.E con omicimpactofdiabete s.In:NationalDiabete sDataGroup,e ds.Diabe tes in America.Bet hesda,MD:Nat ionalIn stitute ofDiabetesandKidne yDiseases,1995:601611;NIH pu blicat ion95-1468. 6.YudkinJS.In sulin for t heworld'spoor estnation s.Lan cet2000;355: 919921. 7.Ame ricanDiabetesAssociation .Re port ofth eExpe rtCommittee ofth eDiag nosisandClassification ofDiabet esMellitus. Diabet es Car e2000;23[Suppl1]:S4S19. 8.McCan ceDR ,Han son RL,Ch arlesMA,et al.Comparison oftes tsforglycatedh emoglobinand fast in gan dtwoh ou rplasmaglucos econ cent rationsasdiag nosticmeth odsfordiabe tes.BMJ 1994;308:13231328. 9.En gelgauMM,ThompsonTJ, He rmanWH,e tal.Comparisonoffastingan d2-h ou rglu cose and HbA 1 c levelsford iagnosin gdiabete s:diagnosticcrit eriaan dperformanc erevisited.D iabete s Care 1997;20:785791. 10.Albert iKGGM. Th eclin icalimp licationsofimpairedglucosetoleran ce.D iabet Med1996;13:927 937. 11.Glucosetoler ance and mortality:comparison ofWHOan dAmer icanDiabetesAssociation diagn ost iccriter ia.TheDecodeStu dygroup.E uropeanDiabe tesE pide miologyGr ou p.Diab etes Ep ide miology:collaborat ive analysisofdiabetescr ite riainEu rope .Lan cet1999;354:617621. 12.Le vit tNS,UnwinNC ,Bradsh awD,etal. Ap plicat ionofthen ewADAcriter iaforth ediagn osisof diabe testopop ulation sstudiesinsu b-Saharan Africa.Diab et Med2000;17:381385. 13.Sh awJE, Zimmet PZ,McCartyD,etal. Type2diab etesworldwide accordingtothe n ew classification andcr ite ria.D iabetes C are 2000;23[Su ppl2]:B5B10. 14.Sh apiroJAM,LakeyJR T, Ryan EA,e tal.Islettransplan tat ioninsev enpatie ntswitht ype1 diabe tesmellitusu sin gaglucocor ticoid-freeimmun osu ppressive r egimen .N En gl J Med 2000;343:230238. 15.E pide miologyofDiabete sInte rven tionsandComplicat ions(E DIC). Design ,impleme ntation ,an d pre liminaryre sultsofalong-t ermfollow-upofthe Diabet esContr olan dComplication sTr ialcohort. Diabetes C are1999;22:99111. P. 596


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16.American Diabet esAssociat ion. St and ardsofmed icalcareforpatien tswit hdiabet esme llitus. Diabetes C are2000;23[Su ppl1]:S32S42. 17.R andomised trialofcholester olloweringin4444patie ntswithcoronaryhe artdisease:th e Scan dinavianSurvivalStu dy(4S). Lance t1994;344:13831389. 18.SacksFM,PfefferMA,Lemue lA.Th eeffectofpravastatinon cor on arye vent safter myocard ial infar ction inpatient swith aver agech oleste rollevels.N En gl J Med1996;335:10011009. 19.Tightbloodpr essure con trolandth eriskofmacrovascularandmicrovascularcomplicationsin typ e2diabe tes(UK PDS35):U KProspect ive Diabe tesStud yGroup .BMJ1998;317:703713. 20.HanssonL,Zanche ttiA,Carrut hersSG,et al.Effect sofinte nsivebloodpressu relowe rin gan d low-doseaspir in inp atient swith hype rten sion:principalre sultsofth eHyper ten sionOptimal Treatment(HOT)randomized trial:HOTStu dyGrou p.Lancet1998;351:17551762. 21.C ollaborativeover vie wofrandomisedtr ialsofant iplat ele tth erapy -1:pre vent ionofdeat h, myocardialin farct ion,andstr oke byprolonge dant iplat ele tthe rapy inv ariou scate gor iesofpat ien ts. Ant iplat ele tTrialists'Collab oration .BMJ1994;308:81106. 22.E ffectsofr amipr ilon cardiovascu laran dmicrovascu larou tcomesinpe oplewithdiabe tesmellitus: re sultsofth eHOPE StudyandMICR -HOPESu bstudy:He artOu tcomesPreve ntionEvalu ationStud y In vestigators. Lance t2000;355:253259. 23.GressTW, NietoFJ,Shahar E,et al.Hypert ensionan dant ih ypert ensiveth erapyasriskfactor sfor typ e2diabe tesmellitus. N E ngl J Me d2000;342:905912. 24.Kn owlerWC ,PettittDJ,SavagePJ,etal. Diabet esincidence inPimaIn dians:cont ribu tion of obesityan dpat ernaldiab etes. Am J Epidemiol1981;113:114156. 25.Die hlAK,Ster nMP.Specialhe althpr oblemsofMexican -Amer icans:obesity,gallbladder dise ase, diabe tesmellitusandcardiovasculardisease.Adv Int ern Med1989;34:1356. 26.FujimotoWF. Backgroun dand recru itmen tdatafor theU SDiabet esPre ven tionProgram.Diab etes Care2000;23[Supp l2]:B11B13. 27.Ke nny SJ ,Auber tRE, GeissLS.Prevale nceandincidenc eofn on -in sulin -depen dent diabetes .In: Har risMI,C owieCC ,Ster nMJ,eds.D iabete s in America,2n ded.Bet hesda,MD:Nat ionalIn stit ute of DiabetesandKidn eyDiseases,1995:4767;NIHpu blicat ion95-1468. 28.Minak erKL. W hat d iabetologistsshouldknowabout elde rlypatien ts.Diab etes C are1990;13[Su ppl 2]:3446. 29.Th ivoletC, elFar khJ,PetiotA,etal. Measuring v ibr ation sensation swith agraduatedtu ning fork:asimpleandre liablemeanstodetect diabeticpat ien tsat risk forn europat hicfootulceration . Diabetes C are1990;13:10771080. 30.DyckPJ,Me lt on LJ3rd, O'BrienPC,e tal.Approach estoimproveep idemiologicalstu diesof diabe ticn eur opathy:insight sformth eRocheste rDiabe ticNe uropath yStud y.Diabe tes1997;46[Suppl 2]:S5S8. 31.PerkinsBA, Olaley eD, Zinman B,etal. Simple screen in gtestsforper iph eraln europat hyinth e diabe tesclin ic. Diabete s Car e2001;24:250256. 32.HaffnerSM,Leh toS, Ronne maaT,et al.Mortalityfr omcoronaryh eart dise aseinsub je ctswit h typ e2diabe tesan dinnon-diabe ticsu bjectswithandwithoutpr iormyocardialin farction.N En gl J Med1998;339:229234. 33.Mogense nCE .Pr edict ionofclinicaldiabet icn ephr opathyinIDDMpat ie nts:alte rnativ esto micr oalbu minu ria?D iabete s1990;39:761767.


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34.Mogense nCE .Microalbuminur iapredictsclin icalpr ote in uriaandearly mortalityinmatu rit y-on set diabe tes.N En gl J Med1984;310:356360. 35.ZieglerAG,ZieglerR,VardiP,e tal.Life-table analysisofprog ression todiabe tesofant i-insu lin autoan tibody-positiv erelat ive sofindivid ualswit htype Idiabete s.Diabe tes1989;38:13201325. 36.Kr isch erJP,SchatzD, Riley W J,etal. I nsulinan disletce llau toantibodie sastime -depen dent covariatesinth edevelopme ntofin sulin depen dent diabetes. J Clin Endocrinol Met ab1993;77:743 479. 37.Janand-Dele nne B,SavinB,Habib G,BoryM,et al.Silen tmy ocardialische miainpatientswith diabe tes:whotoscreen .Diabe tes C are1999;22:13961400. 38.Physician's guide to in sulin -depe nden t (type 1) diabet es: diagnosis and t reat men t.Alexandria, VA:Ame ricanDiabete sAssociation ,1988:18. 38a. Amer icanDiabetesAssociation .Stan dar dsofmedicalcareindiab etes. Diabet es Car e2004; [Supp l1]:S19. 39.American Diabet esAssociat ion. Te stsofglycemiaindiabet es.D iabetes C are 2000;23[Su ppl 1]:560582. 40.Jovan ov ic-Peter son L,Pe tersonC M, Dud ley J D,e tal.Iden tify in gsou rcesoferrorinself mon it oringbloodglucose. D iabete s Car e1988;11:791794. 41.Alle nBT,Delong E R,Feu sserJR. Impactofglucoseselfmon itoringonn oninsu lint reat edpat ie nts withty peIIdiabet esme llit us:randomizedcont rolledtrialcomparin gbloodand u rinete sting. Diabetes C are1990;13:10441050. 42.Bu nnHF,Han eyDN,Gabbay KH,etal. Fu rthe ride ntification ofth enatur ean dlinkageofthe carboh ydrateinhe moglobinA 1 c .Bioch em Biophys R es Comm1975;67:103109. 43.R ahbarS.Anabnormalhemoglobin in redcellsofdiabe tics. Clin Chim Act a1968;22:296298. 44.Koen igR J,Pe tersonC M, J one sRL.C orr elation ofglucosere gulation an dhemoglobin A 1 c in diabe tesmellitus. N E ngl J Me d1976;295:417420. 45.Sch nedlWJ,Kr ause R,Halwach -Bau mannG,et al.Evalu ationofHbA 1 c de termin ationme thodsin patie ntswithh emoglob in opathies.D iabete s Car e2000;23:339344. 46.Bre werW,C hase HP,Owe nS,etal. Slicin gthe pie .Correlatin gHbA 1 c valueswithaverageglucose valu esinapie-ch artform.Diabe tes Care1998;21:209212. 47.American Diabet esAssociat ion. Con tinuoussu bcutane ou sins ulin infu sion. Diabet es Care2000;23 [Supp l1]:S90. 48.Gen uth S. Insulinuse in NIDDM.D iabete s C are 1990;13:12401264. 48a. Riddle MC ,Rosenst ockJ, Ger ich J,on beh alfofth ein sulin glargine2002stu dyinvest igator s. Randomized additionofglargine orh umanNPHinsu lin t ooralth erap yoftyp e2diabe ticpatient s. Diabetes C are2003;26:30803086. 49.R iddleMC.E ven in gin sulin .Diabe tes Care1991;13:676686. 50.Nest oRW. Screen in gforasymptomat iccoronar ydise aseindiabe tes. D iabete s Car e 1999;22:13931395. 51.WatkinsK, Con nellCM,Fitz geraldJT,e tal.Effect ofadults'se lf-re gulationofdiab etesonqu ality of-lifeoutcome s.Diabe tes Care2000;23:15111515.


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Copyright (c)2000-2006OvidTech nologies,Inc. Version:rel10.4.1, Sou rceID1.12596.1. 143

Chapter35 Education in the Treatment of DiabetesRic hard S. Beaser Katie Weinger Lisa M. Bolduc-Bisse ll Thisbuildin ggiv enbyth ou san dsofpatientsandth eirfriendsprovidesanop port unity formanytocon trolt heirdiabe tesbymeth odsofteachinghith ertoavailab let oth e privile gedfew. Ch ise led in st on eon the fron toft heJoslinC linicBuild in g,ere ctedin1955,th eaboveinscr ipt ion reflect edElliottP. Joslin'sconv ictionth atedu cationwasn ot ju stapartofd iabetest reat men t,itwast he tre atment .Dr .Joslin'scon cernabou tedu catingboth patien tswit hdiabet esan dtheirfamiliesbe gan more than100ye arsago, wh ensu chinstr uction wasconsidere dbymanytobealu xury. Overth elast twodecad es,th eimportanceofeducation hasbe comemore widelyre cogn iz ed.Asth eWor ldHealt h Organizationcomment edin1980,Ed ucat ionisacorne rstoneofdiabeticthe rapy andvitaltoth e integ rationoft hediabe ticint osocie ty(1). Thisgrowin grecognition ofth evitalrole ofedu cationin the treatme ntofdiabete sle dtot he deve lopmentandpe riodicupdatin goft heNat ionalStandardsfor Diabet esEdu cation byth eNation al DiabetesAdvisoryBoardin1983(2, 3,4).Thiswasfollowedbyth edeve lopmentofare cogn it ionprogram fordiabete seducation b ythe American Diabe tesAssociation(ADA)(5)andofacertificationprogramfor diabet esedu catorsbyth eAme ricanAssociation ofDiabetesE ducator s(6)nowadministere dbya separat eor ganization, the Nation alCert ificationBoardforDiabe tesEd ucat ors. Pr ogr essin makin gedu cation alprogramsavailable t oev eryonewith diabetesh asbee nslowe dbythe reluct ance ofth ir d-part ypaye rstoreimbu rseforeducation alservicesinth eUn ite dState s(7).Th isis nowchanging. In 2001,th eCen terforMedicareandMedicaidServices(C MS)be ganpayingforMe dicare pat ie ntstoat tendgr ou pdiabete seducation p rogr amsandformedicalnut rit ionth erapyvisits. Many privat ein sure rsfollowed s uit.Howe ver, diabetese ducationpr ogr amsarestillatrisk,withman yclosing th eir doorsbecauseofpoorr eimbur seme nt. Onen ation wide studyfoun dthatmoret han 60%ofpeople withdiabe teshavere ceiv edlitt leorn odiabe tesedu cation(8, 9).U nfortun ate ly ,littlee vide ncesu ggests th atth isischanging. Despitet heobstacles, however, healt hcar eprofession alswh ot reat people with diabet escontinue the ircommitme nttopat ie ntedu cationth rou ghth edev elopmentofne wp rogr amsand rese arch in tomoreeffect ive met hodsofte aching t hepr in ciplesandpractice ofdiabe tesself-car e.

WHY IS SELF-MANAGEMENT EDUCATION IMPORTANT IN THE TREATMENT OF DIABETES?The impor tan ceofimpr ove dgly cemiccontrolin delayingth eon setandprogre ssionofseriou s microvascularcomplicationsis n owclear(10,11).Tre atment ofdiabet esleadingt oimpr ove dcon trolisa 24-hour- a-day activityan dofte nincludesimport ant chan gesinlifest yle ,mostofwhichper son swith diabet esmu stprovidefor themselvesonadailybasis.These effort srequ ire carefu lbalancingofvar ious lifest yle funct ionsandact ivitiesth atareinte gralpart softh edailyroutine. Thus, thegoalofd iabetes self-managemente ducat ionisnotsimplytoin creaseknowledgeabou tdiabete s,but rath ertosupp ort individ ualswit hdiabet esan dthe irfamiliesint heireffortstoin cor poratediab etestr eat men tin totheir lifest yle s.Ofcou rse, themoreth atpeoplewithdiabe tesun derstandh owtomaketh esere quiredch an ges an dwhatthe r ationaleisbehind t hem,th emore successfu lth eywillbeinth eirdiabete sselfmanagement . Diabetesse lf-man agement education prov ide sman yben efit s.Edu cationallowspeoplewithdiabe testo takecontrolofth eircon dit ion,int egratin gthe daily r ou tin esofself-monitor in g an ddisciplineintothe ir lifestylerathe rthanper mittingth isconditiontoove rwhelmtheman dcon trol th eir lives. Education in d iabetesse lf-man agemen ttrain sp eop let otaketh ene cessary action sto improvet heirmetab oliccont rol,wh ich helpsmain tainh ealth andwe ll-beingandre ducesth eriskof diabet iccomp lications.Th ewell-ed ucat edpersonwithd iabetesmayalsodecr easet hecostsrelatedto th econ dit ionbot hth edir ectcostofmedicalcare and t heindirect costsr elatedt olost in comeor product ivity(12). Diabetese ducat ionisbot han art andafle dgin gscie nce. Onlywith in the sepast 20ye arsh asre search begu ntoexamine t herolean deffectiven essofe ducationindiab etesself-management ,an dfutu re rese arch isn eeded tofu rthe revalu ateandclarifyoptimalmeth odsforth isedu cationalprocess(4).In P. 598


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add ition,inth islitig iousage,ast hevalu eofeducation g ainscrede nce, thepr ovision ofproper e ducation topeople with diabete sbyah ealthcareprovidermayh elpredu cethe risk ofmalpract icesu it s. The e volut ionofthe s cien tificcompone ntofdiabete seducation h astr aveledalongandsome what bumpy road. Initialst udiesexaminingdiab etesed ucat ionwer edifficulttodesign, perform, and e valuate,and whe nthe ywerecomple ted,t heirvaliditywasoften t hesu bje ctofcont rov ersyamonghe althcare profession als.One reasonforth isdisagr eement wasthe assumptionbyre search ersstu dyingdiabe tes edu cationth atitwasanintegr alcompon en tofcare.Th us,th eusu alstudy desig ncontrastedinte nsive edu cationwit hless-inten siv eedu cation rat hert han with noeducation oraplaceboformofeducation . Somesmallst udiescomparin gthe setwoformsofe ducationsh owed nod iffere ncesinglycemiccon trol bet we engr ou ps.Fore xample ,atr ialcomp aringmin imalvers usin ten sive education showedsimilar improvemen tin the twogr ou ps(13).Goodcon trolwasrelated toth edu rationofsch ooleducation , abs enceofan xie ty,andqu ality ofcontrolandde gree ofself-con fide nceu pon ent ryin tothest udy. A similarstu dy,withadmitte dsocioe con omic b iasaffectingsomeofth esefactor s,showedth ate ducat ion ledtoimprovement sin k nowledg ean dbehaviorbu tnotinimprovemen tsin me taboliccontrol(14). Howe ver, duringth elasttwodecades,man yran domizedclin icalt rialsandsmalle rstud iesh ave examine dthe e fficacyofdiabe tesedu cat ion(4),an dseveralwe ll-donemeta-analyses(15,16,17, 18,19) th atev aluat edthe qualityofeducation summar ize dthe resultsofresearchindiabe tesedu cat ion.Th ese meta-analyse s,alongwithmore recen ttrials(20,21,22, 23,24),provideconvincinge vide nceth at diabet esedu cation ise ffectiveinsupport in gpatien ts'effortstoimproveand/ormaintain physiologicand quality-of-life out comes. Cu rren tly,rese arch in diabete se ducationh asmove dbeyondth eque stion ofwhe ther itisimportantand isbeginningt ofocusonth escie nceofedu cation ,add ressingqu estion sthatclarifyeducation al outcome s,dete rmine whichgroupsofpatien tsrespondb esttowhichformofeducation ,an devalu ate whichareth emostefficientandcost-effe ctiv eme thodsofpr ovidingedu cation(25,26,27, 28).Diabe tes edu cationalreadyen compasse sthefamilyandsocialsupport;re sear chersaren owbeginn in gtocon side r pub lic-healt hasp ectsofd iabetese ducationatthe commu nityandpossiblyth enationalleve l(29).

Education Improves Well-Being and Quality of LifePe oplewithdiab etesmustmake what someperce iv easbeing over whelming lifestylech ange s,yet t heir failuret oacceptth esech ange smayresu ltininadequ atediab etescontr ol.Emotionsr elatedt oth e psych olog icalbu rden ofdiabet es,su chasanxiety, depre ssion, andpoorself-con fiden ce,h ave been showntobeassociat edwit hpoorcont rol(13,30,31, 32,33).Thu s,apr ope rly designede ducat ionprogram notonlyshouldprese ntfactsbutalsoshouldadd ressth eemotionalresp on sestodiabetes. Edu cationimprovesse lf-carepractices(16,17,22, 34)butamer ein creasein knowle dgeandskillsdoes notgu arantee animprov eme ntinmetabolicparamet ers(14).Sev eralpsych olog icalfactor s,havin gbeen implicatedasbar rie rstoimprovedglycemiccontr ol,playanimportantr oleintranslationofk nowledge an dskillsin tothede sir edme tabolicre sults.The sefactorsinclude e motion -base dcopingst yle s(35, 36), diabet es-relat edemot ionaldistre ss(33) ,an dlackofre adinesst och ange (37).Forindividualstobe willin gan dabletomakeallthe n ecessarylife stylechanges, they must hav eknowle dgean dskillsplusa posit ive emotion alou tlookabout t heirdiabe tes,be lievingt hat t hech ang esthe ymakewillle adtobett er he alth. Aned ucat ionalprogramth atde monst rablyimprovesparamete rsofe motion alwell-beinginadditiont o add ressingself-car epract ice shasbe ensh own t oleadtoimprov edme taboliccontr olthatwassu staine d over6month s(38,39).The aut horsofth esestu diessugge stedth ate motion alwe ll-beingitselfmay contribut etoimprovedself-car e(38).Oth ersconte ndth at,formany patien ts,edu cationabout diabetes an dself-care alon eenh an cesemotionalwell-b ein g(40,41,42), wh ich furt herboostsself-care ability.In th efir stran domizedcontrolle dtrialtode monstr ate anaddit ive effectofpsychologicalin terv entionon glycemiccontr ol,Greyandh ercolleag ues(43,44)de monstr ate dthatadole scent swh or eceivedtr aining incopin gskillsalon gwith me thodsofint ensivediabe testre atmen timprovedglycemiccon trolandselfcar ebeh avior smoreth andidadolescen tswhorece ive don lyinte nsivetr eatmen tin stru ction. Howev er, whe ther emotion alwell-be in gleadstoimprovement in s elf-careorvicevers ahasnotbeen cle arly det ermin ed.Mor erese arch isne ededt oclarifyth eassociation samon geducation ,improvedse lf-care, an dimprovede motion alou tlook.

Education Improves Self-Care ManagementEve naft eroneacceptsth ate motion alwell-beingisacr ucialcompon ent ofth eedu cation alin terv ention, th ecomplexityoft hediabe testr eatmen tregimenitselfoft enleads t oconfu sionandmisun derst and in g th atinte rferes with theabilitytomanageon e'sd iabetes. Diabe tesedu cationcan playan impor tan trole inclarifyingth etreatmentr egimen ,reinforcingth eskillsne cessar ytosu ccessfullymanagediabet es,an d supp ort in geffor tstoint egrateself-managementbe haviorsintoon e's life.Seve ralme ta-analyse sand clin icaltr ialse xamin in gthe e ffectsofdiabete se ducationfoun dthatedu cation le adstoimprovedse lfcar ebeh avior saswellastoimprov edknowledge, andmetabolicand p sychologicalou tcomes (15,16,17, 19,22,34,38, 45).Ru bin andh iscolleague s(45) n ot edadiffere ntialeffectamongse lf-care beh avior s:behaviorsr equiringchange sin lifestylesu chasindietandex ercisewere moredifficu ltt o


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maintain ove rtimet han wereless-deman dingbeh avior ssuchasself-monitorin gofbloodglucose (SMBG).

Education Improves Metabolic ControlThe Diabet esControland C omplication sTr ial(DCCT)andth eUn ite dKin gdomProspe ctiveDiab etesStu dy (UK PDS)e stablishedt heprincipleth atimpr ove men tinglycemiccontr olisbe neficialandth atmaint aining glucoselevelsasn eart onormalaspossibler esultsinred uction in the r iskofdeve lopme ntand progressionofse riou smicrov ascularcomplications. Theimportanceofedu cation tothet rainingof pat ie ntswithdiabe tesabou tthe irt reat me ntan dtosupportingth eirself-manag eme nteffortstoimprove th eir glyce miccontrolb ecameapp aren tearly duringth e9-year cour seoft heDCCT(46,47). Moreover , th eimportan ceofamu lt idisciplinaryte amc ons istingofat leastonehe althcarepractition er/edu cator such asar egistere dnur seor n utr it ionistwasde finitivelydocument ed(46,47,48). Th erole sof other teammembe rs,su chasth epodiatrist,psy chologist,ophth almologist,ph armacist, e xercise phy siologist,amongothe rs,arenowbeingre cogn ize daswell(12, 20,21,22, 38, 39,49,50,51). Although initialstu die satte mpting t ode monstr atet hat education improvesdiabet escon trolpr odu ced variable resu lts, again itwasthrough me ta-analyses t hat examinedt hecumulat ive evidence thatthe conclusion canbe drawn thatdiabete seducation canre sultinamode rat etolargeeffect on improvin g glycemiccontr ol(15,16,17, 18,19).Forglyce miccon trol, themagn it udeofthiseffect waspar ticu larly eviden tinstud iest hat we recomplet edafte rme asur eme ntsofgly cosylat edhe moglobin(HbA 1 c )came intowide spreaduse(15). Tr aditionald iabetese ducat ionalsoresu lt edin improvedkn owledge andse lfcar ebeh avior swith asmalleffe cton psychologicalou tcomes(17). Pad gettandcowork ers(16)fou nd th atdietinst ructionhadthe largesteffe ctsiz ewhile relaxationt rainingh adth eweak est. Oth erstu die salsoh aveu nder score dthe impor tan ceofse lect in gthe r igh tou tcome cr it eriafor measu rement. Ifthewr on gou tcomesaremeasu red,e ducationmayn ot appeartoberesponsibleforthe desired improveme nts, bot hwhen lookedat in r elation tovariou sou tcomesoth erth anmetaboliccon trol (52)an dwhen examinedovere xten dedper iods(34,53).Forexample,th eDiabetesE ducationSt udy rep ort edminimaldiffer ence sb etween the education andcont rolgroupsinmeasu rement softh eir kn owledgebu tfou ndn umerous,significant differ ences int heirskillsan dself-care behaviors. Su ch stu die ssuggest thatadu ltlearningth eoryholdstrue :Individualsten dtolearnwh atisimportanttothe m an dwhatthe ycanr elatet oth eirown lifeexpe rie nce(54). Notsu rprisin gly ,disc repan cie smayexist bet we enwh ath ealthc arepr oviders t each and wh atindividualswithd iabetespe rceiveasimpor tan t. The sestudiesalsopoin tou tthe difficultiesofmeasuringth eeffect sofedu cat ionaft erasingle edu cationalinter vent ionth atfocuse sprimar ilyonfactsabou tdiabet esrather thanon behaviorsandth at doesnotincludeongoingfollow-u p(55)ort hat measure sou tcomesinte rmsofselecte dmet abolic par ameter son ly. Su chlimitedstu die softe nfailtode tectallthe pot entiallon g-termben efit sofan ongoin geducation alexper ien ce(56).Oth ersh avemade the impor tan tpoint thatimprovedglycemic controlmaynotbeap paren tun le ssoth ertr eat men tfactors, suchasthe t reatme ntre gimenand individ ualme tabolism,aretakenint oaccoun t(57). Although t hest udiescit edsugg estth atedu cationdoesimprovemetaboliccon trol, moststu dies d onot examine education inisolation .Inanexte nsivere vie wofth ediabete seducation literatur e,C lemen t(58) emphasize dthatne gativestu diesdid notexaminediabe tesedu cat ionth atwasin tegratedintomedic al tre atment .Ther efor e,onemust conclud ethatedu cationalon edoesnotimpr ove met aboliccon trol. This poin twasn icelydemonstratedinaran domizedcontrolled s tudyofnu rsecase manage me ntth atinclude d a12-h ou redu cation program.After 1year,th ecombine dmedical/edu cat ioncas emanag eme ntapproach ledtoagre ater improvementinglycemiccon trolasmeasure dbyHbA 1 c of1.1%ascompared with the controlgrou prece ivingt heu sualcar e(21).These dataan dthee mph asisthatthe DCC Tplacedon edu cationtohelppat ie ntsre achglycemictarge ts(46,48,59, 60,61)supportt hesug gestion thatthe maximalbe nefitofd iabetese ducationisrealizedwh ene ducat ionisin tegr ated int odiabe tescare. P. 599

Education Enhances the Prevention and Early Detection of ComplicationsEviden ceisnoweme rgin gthatdiabe tesedu cationplaysanimportantrole in thepr even tion ande arly det ection ofdiabe tescomplication s.Infact,th eRev ise dNation alSt and ardsforDiab etesSelfManagement Education hav ein clu dedpre vent ion, detect ion,andtr eat men tofboth acut ean dchronic complication samon gthe t enconte ntareasfordiabe tesedu cation(4). Acase -con trolstu dyof886subjectswith long-te rmdiab eticcomplicationsand1,888contr olsubject s withoutcomp licationsfoundt hat ,in addition tob ein gmale ,olde r,an dhavin gtype1or in sulin -treated type 2diabe tes,patientswh odidnotre ceiv ean ykin dofe ducationalint erven tion we reatin creasedrisk ofd evelop in gcomplications. Fu rthe rmore, self-manage men tofin sulin ,askillth atisusu allyde pend ent onrece iving d iabetese ducat ion, hadaprotectivee ffe cton the risk ofcomplic ation s(62). Inaran domizedcontroltrialof352patient sandfourh ealth care prov ider pract icet eams,Litzelmanand he rcolleagu es(23)fou ndth atpatient swith type2diabete swhowe reassign edtoane duca

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