糖尿病基础知识-英文PPT课件.ppt

DiabetesMellitus,Dr.RashaSalamaPhDPublicHealth,SuezCanalUniversity,EgyptDiabetesMSc,CardiffUniversity,UnitedKingdom,.,Diabetesmellitus(DM)isagroupofdiseasescharacterizedbyhighlevelsofbloodglucoseresultingfromdefectsininsulinproduction,insulinaction,orboth.Thetermdiabetesmellitusdescribesametabolicdisorderofmultipleaetiologycharacterizedbychronichyperglycaemiawithdisturbancesofcarbohydrate,fatandproteinmetabolismresultingfromdefectsininsulinsecretion,insulinaction,orboth.Theeffectsofdiabetesmellitusincludelongtermdamage,dysfunctionandfailureofvariousorgans.,Whatisdiabetes?,Diabetesmellitusmaypresentwithcharacteristicsymptomssuchasthirst,polyuria,blurringofvision,andweightloss.Initsmostsevereforms,ketoacidosisoranonketotichyperosmolarstatemaydevelopandleadtostupor,comaand,inabsenceofeffectivetreatment,death.Oftensymptomsarenotsevere,ormaybeabsent,andconsequentlyhyperglycaemiasufficienttocausepathologicalandfunctionalchangesmaybepresentforalongtimebeforethediagnosisismade.,Diabetes,Thelongtermeffectsofdiabetesmellitusincludeprogressivedevelopmentofthespecificcomplicationsofretinopathywithpotentialblindness,nephropathythatmayleadtorenalfailure,and/orneuropathywithriskoffootulcers,amputation,Charcotjoints,andfeaturesofautonomicdysfunction,includingsexualdysfunction.Peoplewithdiabetesareatincreasedriskofcardiovascular,peripheralvascularandcerebrovasculardisease.,DiabetesLong-termEffects,Thedevelopmentofdiabetesisprojectedtoreachpandemicproportionsoverthenext10-20years.InternationalDiabetesFederation(IDF)dataindicatethatbytheyear2025,thenumberofpeopleaffectedwillreach333million90%ofthesepeoplewillhaveType2diabetes.InmostWesternsocieties,theoverallprevalencehasreached4-6%,andisashighas10-12%among60-70-year-oldpeople.Theannualhealthcostscausedbydiabetesanditscomplicationsaccountforaround6-12%ofallhealth-careexpenditure.,BurdenofDiabetes,Type1DiabetesMellitusType2DiabetesMellitusGestationalDiabetesOthertypes:LADA(MODY(maturity-onsetdiabetesofyouth)SecondaryDiabetesMellitus,TypesofDiabetes,Waspreviouslycalledinsulin-dependentdiabetesmellitus(IDDM)orjuvenile-onsetdiabetes.Type1diabetesdevelopswhenthebodysimmunesystemdestroyspancreaticbetacells,theonlycellsinthebodythatmakethehormoneinsulinthatregulatesbloodglucose.Thisformofdiabetesusuallystrikeschildrenandyoungadults,althoughdiseaseonsetcanoccuratanyage.Type1diabetesmayaccountfor5%to10%ofalldiagnosedcasesofdiabetes.Riskfactorsfortype1diabetesmayincludeautoimmune,genetic,andenvironmentalfactors.,Type1diabetes,Waspreviouslycallednon-insulin-dependentdiabetesmellitus(NIDDM)oradult-onsetdiabetes.Type2diabetesmayaccountforabout90%to95%ofalldiagnosedcasesofdiabetes.Itusuallybeginsasinsulinresistance,adisorderinwhichthecellsdonotuseinsulinproperly.Astheneedforinsulinrises,thepancreasgraduallylosesitsabilitytoproduceinsulin.Type2diabetesisassociatedwitholderage,obesity,familyhistoryofdiabetes,historyofgestationaldiabetes,impairedglucosemetabolism,physicalinactivity,andrace/ethnicity.AfricanAmericans,Hispanic/LatinoAmericans,AmericanIndians,andsomeAsianAmericansandNativeHawaiiansorOtherPacificIslandersareatparticularlyhighriskfortype2diabetes.Type2diabetesisincreasinglybeingdiagnosedinchildrenandadolescents.,Type2diabetes,Aformofglucoseintolerancethatisdiagnosedinsomewomenduringpregnancy.GestationaldiabetesoccursmorefrequentlyamongAfricanAmericans,Hispanic/LatinoAmericans,andAmericanIndians.Itisalsomorecommonamongobesewomenandwomenwithafamilyhistoryofdiabetes.Duringpregnancy,gestationaldiabetesrequirestreatmenttonormalizematernalbloodglucoselevelstoavoidcomplicationsintheinfant.Afterpregnancy,5%to10%ofwomenwithgestationaldiabetesarefoundtohavetype2diabetes.Womenwhohavehadgestationaldiabeteshavea20%to50%chanceofdevelopingdiabetesinthenext5-10years.,Gestationaldiabetes,Otherspecifictypesofdiabetesresultfromspecificgeneticconditions(suchasmaturity-onsetdiabetesofyouth),surgery,drugs,malnutrition,infections,andotherillnesses.Suchtypesofdiabetesmayaccountfor1%to5%ofalldiagnosedcasesofdiabetes.,OthertypesofDM,LatentAutoimmuneDiabetesinAdults(LADA)isaformofautoimmune(type1diabetes)whichisdiagnosedinindividualswhoareolderthantheusualageofonsetoftype1diabetes.AlternatetermsthathavebeenusedforLADAincludeLate-onsetAutoimmuneDiabetesofAdulthood,SlowOnsetType1diabetes,andsometimesalsoType1.5Often,patientswithLADAaremistakenlythoughttohavetype2diabetes,basedontheirageatthetimeofdiagnosis.,LADA,LADA(cont.),About80%ofadultsapparentlywithrecentlydiagnosedType2diabetesbutwithGADauto-antibodies(i.e.LADA)progresstoinsulinrequirementwithin6years.Thepotentialvalueofidentifyingthisgroupathighriskofprogressiontoinsulindependenceincludes:theavoidanceofusingmetformintreatmenttheearlyintroductionofinsulintherapy,LADA(cont.),MODYMaturityOnsetDiabetesoftheYoungMODYisamonogenicformofdiabeteswithanautosomaldominantmodeofinheritance:Mutationsinanyoneofseveraltranscriptionfactorsorintheenzymeglucokinaseleadtoinsufficientinsulinreleasefrompancreatic-cells,causingMODY.DifferentsubtypesofMODYareidentifiedbasedonthemutatedgene.Originally,diagnosisofMODYwasbasedonpresenceofnon-ketotichyperglycemiainadolescentsoryoungadultsinconjunctionwithafamilyhistoryofdiabetes.However,genetictestinghasshownthatMODYcanoccuratanyageandthatafamilyhistoryofdiabetesisnotalwaysobvious.,MODY,MODY(cont.),WithinMODY,thedifferentsubtypescanessentiallybedividedinto2distinctgroups:glucokinaseMODYandtranscriptionfactorMODY,distinguishedbycharacteristicphenotypicfeaturesandpatternonoralglucosetolerancetesting.GlucokinaseMODYrequiresnotreatment,whiletranscriptionfactorMODY(i.e.Hepatocytenuclearfactor-1alpha)requireslow-dosesulfonylureatherapyandPNDM(causedbyKir6.2mutation)requireshigh-dosesulfonylureatherapy.,MODY(cont.),SecondarycausesofDiabetesmellitusinclude:Acromegaly,Cushingsyndrome,Thyrotoxicosis,PheochromocytomaChronicpancreatitis,CancerDruginducedhyperglycemia:AtypicalAntipsychotics-Alterreceptorbindingcharacteristics,leadingtoincreasedinsulinresistance.Beta-blockers-Inhibitinsulinsecretion.CalciumChannelBlockers-Inhibitssecretionofinsulinbyinterferingwithcytosoliccalciumrelease.Corticosteroids-Causeperipheralinsulinresistanceandgluconeogensis.Fluoroquinolones-InhibitsinsulinsecretionbyblockingATPsensitivepotassiumchannels.Naicin-Theycauseincreasedinsulinresistanceduetoincreasedfreefattyacidmobilization.Phenothiazines-Inhibitinsulinsecretion.ProteaseInhibitors-Inhibittheconversionofproinsulintoinsulin.ThiazideDiuretics-Inhibitinsulinsecretionduetohypokalemia.Theyalsocauseincreasedinsulinresistanceduetoincreasedfreefattyacidmobilization.,SecondaryDM,Prediabetesisatermusedtodistinguishpeoplewhoareatincreasedriskofdevelopingdiabetes.Peoplewithprediabeteshaveimpairedfastingglucose(IFG)orimpairedglucosetolerance(IGT).SomepeoplemayhavebothIFGandIGT.IFGisaconditioninwhichthefastingbloodsugarleveliselevated(100to125milligramsperdecilitreormg/dL)afteranovernightfastbutisnothighenoughtobeclassifiedasdiabetes.IGTisaconditioninwhichthebloodsugarleveliselevated(140to199mg/dLaftera2-houroralglucosetolerancetest),butisnothighenoughtobeclassifiedasdiabetes.,Prediabetes:Impairedglucosetoleranceandimpairedfastingglucose,Progressiontodiabetesamongthosewithprediabetesisnotinevitable.Studiessuggestthatweightlossandincreasedphysicalactivityamongpeoplewithprediabetespreventordelaydiabetesandmayreturnbloodglucoselevelstonormal.Peoplewithprediabetesarealreadyatincreasedriskforotheradversehealthoutcomessuchasheartdiseaseandstroke.,Prediabetes:Impairedglucosetoleranceandimpairedfastingglucose(cont.),DiagnosisofDiabetesMellitus,ValuesofDiagnosisofDiabetesMellitus,Researchstudieshavefoundthatlifestylechangescanpreventordelaytheonsetoftype2diabetesamonghigh-riskadults.ThesestudiesincludedpeoplewithIGTandotherhigh-riskcharacteristicsfordevelopingdiabetes.Lifestyleinterventionsincludeddietandmoderate-intensityphysicalactivity(suchaswalkingfor21/2hourseachweek).IntheDiabetesPreventionProgram,alargepreventionstudyofpeopleathighriskfordiabetes,thedevelopmentofdiabeteswasreduced58%over3years.,Preventionordelayofdiabetes:Lifestylemodification,Studieshaveshownthatmedicationshavebeensuccessfulinpreventingdiabetesinsomepopulationgroups.IntheDiabetesPreventionProgram,peopletreatedwiththedrugmetforminreducedtheirriskofdevelopingdiabetesby31%over3years.Treatmentwithmetforminwasmosteffectiveamongyounger,heavierpeople(those25-40yearsofagewhowere50to80poundsoverweight)andlesseffectiveamongolderpeopleandpeoplewhowerenotasoverweight.Similarly,intheSTOP-NIDDMTrial,treatmentofpeoplewithIGTwiththedrugacarbosereducedtheriskofdevelopingdiabetesby25%over3years.Othermedicationstudiesareongoing.InadditiontopreventingprogressionfromIGTtodiabetes,bothlifestylechangesandmedicationhavealsobeenshowntoincreasetheprobabilityofrevertingfromIGTtonormalglucosetolerance.,Preventionordelayofdiabetes:Medications,ManagementofDiabetesMellitus,Themajorcomponentsofthetreatmentofdiabetesare:,ManagementofDM,Dietisabasicpartofmanagementineverycase.Treatmentcannotbeeffectiveunlessadequateattentionisgiventoensuringappropriatenutrition.Dietarytreatmentshouldaimat:ensuringweightcontrolprovidingnutritionalrequirementsallowinggoodglycaemiccontrolwithbloodglucoselevelsasclosetonormalaspossiblecorrectinganyassociatedbloodlipidabnormalities,A.Diet,Thefollowingprinciplesarerecommendedasdietaryguidelinesforpeoplewithdiabetes:Dietaryfatshouldprovide25-35%oftotalintakeofcaloriesbutsaturatedfatintakeshouldnotexceed10%oftotalenergy.Cholesterolconsumptionshouldberestrictedandlimitedto300mgorlessdaily.Proteinintakecanrangebetween10-15%totalenergy(0.8-1g/kgofdesirablebodyweight).Requirementsincreaseforchildrenandduringpregnancy.Proteinshouldbederivedfrombothanimalandvegetablesources.Carbohydratesprovide50-60%oftotalcaloriccontentofthediet.Carbohydratesshouldbecomplexandhighinfibre.Excessivesaltintakeistobeavoided.Itshouldbeparticularlyrestrictedinpeoplewithhypertensionandthosewithnephropathy.,A.Diet(cont.),Physicalactivitypromotesweightreductionandimprovesinsulinsensitivity,thusloweringbloodglucoselevels.Togetherwithdietarytreatment,aprogrammeofregularphysicalactivityandexerciseshouldbeconsideredforeachperson.Suchaprogrammemustbetailoredtotheindividualshealthstatusandfitness.Peopleshould,however,beeducatedaboutthepotentialriskofhypoglycaemiaandhowtoavoidit.,Exercise,Therearecurrentlyfourclassesoforalanti-diabeticagents:i.Biguanidesii.InsulinSecretagoguesSulphonylureasiii.InsulinSecretagoguesNon-sulphonylureasiv.-glucosidaseinhibitorsv.Thiazolidinediones(TZDs),B.OralAnti-DiabeticAgents,Ifglycaemiccontrolisnotachieved(HbA1c6.5%and/or;FPG7.0mmol/Lor;RPG11.0mmol/L)withlifestylemodificationwithin13months,ORALANTI-DIABETICAGENTshouldbeinitiated.Inthepresenceofmarkedhyperglycaemiainnewlydiagnosedsymptomatictype2diabetes(HbA1c8%,FPG11.1mmol/L,orRPG14mmol/L),oralanti-diabeticagentscanbeconsideredattheoutsettogetherwithlifestylemodification.,B.1OralAgentMonotherapy,Asfirstlinetherapy:Obesetype2patients,consideruseofmetformin,acarboseorTZD.Non-obesetype2patients,considertheuseofmetforminorinsulinsecretagoguesMetforministhedrugofchoiceinoverweight/obesepatients.TZDsandacarboseareacceptablealternativesinthosewhoareintoleranttometformin.Ifmonotherapyfails,acombinationofTZDs,acarboseandmetforminisrecommended.Iftargetsarestillnotachieved,insulinsecretagoguesmaybeadded,B.1OralAgentMonotherapy(cont.),Combinationoralagentsisindicatedin:NewlydiagnosedsymptomaticpatientswithHbA1c10Patientswhoarenotreachingtargetsafter3monthsonmonotherapy,B.2CombinationOralAgents,Iftargetshavenotbeenreachedafteroptimaldoseofcombinationtherapyfor3months,consideraddingintermediate-acting/long-actinginsulin(BIDS).Combinationofinsulin+oralanti-diabeticagents(BIDS)hasbeenshowntoimproveglycaemiccontrolinthosenotachievingtargetdespitemaximalcombinationoralanti-diabeticagents.Combininginsulinandthefollowingoralanti-diabeticagentshasbeenshowntobeeffectiveinpeoplewithtype2diabetes:Biguanide(metformin)Insulinsecretagogues(sulphonylureas)Insulinsensitizers(TZDs)(thecombinationofaTZDplusinsulinisnotanapprovedindication)-glucosidaseinhibitor(acarbose)InsulindosecanbeincreaseduntiltargetFPGisachieved.,B.3CombinationOralAgentsandInsulin,DiabetesManagementAlgorithm,OralHypoglycaemicMedications,Inelderlynon-obesepatients,shortactinginsulinsecretagoguescanbestartedbutlongactingSulphonylureasaretobeavoided.Renalfunctionshouldbemonitored.Oralanti-diabeticagentsarenotrecommendedfordiabetesinpregnancyOralanti-diabeticagentsareusuallynotthefirstlinetherapyindiabetesdiagnosedduringstress,suchasinfections.InsulintherapyisrecommendedforboththeaboveTargetsforcontrolareapplicableforallagegroups.However,inpatientswithco-morbidities,targetsareindividualizedWhenindicated,startwithaminimaldoseoforalanti-diabeticagent,whilereemphasizingdietandphysicalactivity.Anappropriatedurationoftime(2-16weeksdependingonagentsused)betweenincrementsshouldbegiventoallowachievementofsteadystatebloodglucosecontrol,GeneralGuidelinesforUseofOralAnti-DiabeticAgentinDiabetes,Short-termuse:Acuteillness,surgery,stressandemergenciesPregnancyBreast-feedingInsulinmaybeusedasinitialtherapyintype2diabetesinmarkedhyperglycaemiaSeveremetabolicdecompensation(diabeticketoacidosis,hyperosmolarnonketoticcoma,lacticacidosis,severehypertriglyceridaemia)Long-termuse:IftargetshavenotbeenreachedafteroptimaldoseofcombinationtherapyorBIDS,considerchangetomulti-doseinsulintherapy.Wheninitiatingthis,insulinsecretagoguesshouldbestoppedandinsulinsensitiserse.g.MetforminorTZDs,canbecontinued.,C.InsulinTherapy,Themajorityofpatientswillrequiremorethanonedailyinjectionifgoodglycaemiccontrolistobeachieved.How