糖尿病专业知识宣贯课件

糖尿病专业知识宣贯Classificationofdiabetes(ADA-1997)Type1

(beta-celldestruction,usuallyleadingtoabsoluteinsulindeficiency)

AutoimmuneIdiopathicType2

(mayrangefrompredominantlyinsulinresistancewithrelativeinsulindeficiencytoapredominantlysecretorydefectwithorwithoutinsulinresistance)

Otherspecifictypes

Gestationaldiabetes**Otherspecifictypes

Pathogenesis

PathologyPathophysiology

AbnormalitiesinmetabolismCarbohydrate：anabolism

，catabolism

、utilizationLipid：anabolism

，catabolism

，ketoplasiaprotein：anabolism

，catabolism

，glyconeogenesisInsulinsecretioncurve:normalanddiabeticsClinicalPresentation

Naturalhistoryoftype2DMAfterthediagnosisoftype2diabetes:IRconstantlyexistsInsulinsecretionabilitygraduallydeclines:WhenFPGreachsthediagnosticcriteria，insulinsecretionabilityhasalreadydeclinedby50%WhenFPG≥7.0mmol/L，-cellinsulinsecretionabilityWhenFPG≥1011.0mmol/L，-CinsulinsecretionabilityhasalreadynearedabsolutedeficiencyModelsoftheonsetoftwophrasesoftype2DMNGTIGR(IFG、IGT)

DM

cellexhaustionInsulinresistanceInsulinresistanceWHOplasmaglucoseguidelineIGTIFGNGTDM75gOGTT2hPG

(mmol/L)FPG(mmol/L)7.06.1FPG7.811.1IGTComparisonoftype1andtype2DM

type1DMtype2DMUsualageofonset<30years>40yearsModeofonsetacutechronicweightnormaloverweightorobesityorweightlosssymptomspolyuria,polydipsia,similarbutusuallyweightlosslessseverepresentationAcutecomplicationsoftenfewChroniccomplicationsLargevesseldiseaselessthentype2DMleadingcauseofdeathRenaldiseaseleadingcauseofdeath5%

10%Insulinandc-peptideloworlackpeakvaluedelayed,highordeficiencyImmunemarkerusually+usually-TherapyinsulindependenceoralantidiabeticagentsareavailableChroniccomplicationsMacrovasculardiseaseMicroangiopathyDiabeticretinopathyDiabeticrenaldiseaseDiabeticneuropathyDiabeticdermatopathyInfectionMechanismofcomplicationsActivationofpolyol（orsorbitol）pathway

Formationofnon-enzymesaccharificationproductsChangeofhemodynamicsActivationofPKCMicroangiopathytheoryHyperglycemiaistheessentialreasonfordiabeticcomplicationsDCCT

DiabetesControlandComplicationsTrialUKPDSUnitedKingdomProspectiveDiabetesStudyUKPTS：resultsHbA1c0.9%，（intensivetherapyvsroutinetherapy）

Intensivetherapygroup:diabetisassociatedcomplications12%，andthefatalnessofmicrovascularcomplications25%。Itcannotevidentlyreducetheincidenceofgreatvesseldisease,suchasmiocardialinfarctionandstrock.Moststimulatingfindings：Biguanidescanpreventorslowtheonsetand/orprogressionofdiabeticcomplicationsinoverweightpatientsTightcontrolofhypertensioncanpreventorslowtheonsetand/orprogressionofdiabeticcomplicationsby24%（144/82mmHgvs154/87mmHg），strokeby44%，microvascularcomplicationsby37%。Epidemiologyofdiabetes

MacrovasculardiseaseDiabeticsareeasytogetatherosclerosisMonckeberg’ssclerosis41.5％Intimalarteriosteogenesis29.3％Coronaryheartdisease、cerebrovasculardisease：24timesRiskofmiocardialinfarction：10timesRiskofstroke:3.8times，especiallyinwomenRiskoflowerlimbamputation：15times，fatalnessHypertensioninDMMorbidityratediabetes:20%

40%DiabetesinEU(35-54years):30%

50%DiabetesinChina:29.2%pathogenesisaortosclerosisArteriolaresistanceHypertensionassociatedwithDNRenalhypertensioncausedbystenosisofrenalartery

DiabeticRetinopathyClassifications(China)BackgroundretinopathyⅠmicroaneurysms、dotsofhemorrhagesⅡyellowandwhitehardexudates,haemorrhagesⅢwhitesoftexudates,haemorrhagesspotsProliferativeretinopathyⅣnewvesselformation、haemorrhageintothevitreousⅤnewvesselformationandfibrosisⅥretinaldetachmentDiabeticnephropathyDNistheleadingcauseofESRD(end-stagerenaldisease)Almost40％ofType1DMdiedofuremiaIncidenceofDNintype2DMisabout20％InEU，DNaccountsfor1/3ofdialysisandkidneytransplantationcasesInChina,DNalsoaccountsforquitealotofdialysesandkidneytransplantationsStagesofdiabeticnephropathy(1)stageIincreasedkidneyDMalreadyfiltrationdiagnosisedGFR↑↑enlargedkidneys(B-ultrasonic)GFR>130ml/minStageIIclinicallysilentphaseDM2

5yearGFR↑20

40％renalenlargement，

withcontinuedglomerularhypertrophy,hyperfiltrationandhypertrophyexpansionofthemesangialmatrix thickeningoftheglomerularbasementmembraneresultinginglomerulosclerosis

StageIIIconcealedDNmicroalbuminuriaDM5

10yearmicroalbuminuria1/5patientswithhypertension(20-200µg/minretinopothy↑,or30

300mg/24h)proteinuria0.15

0.5g/24hGFR>or=normalStagesofdiabeticnephropathy(2)StageIVOvertNephropathy

DM10

25yearalbuminuria>300mg/d60

70％patientsproteinuria>0.5g/d，withhypertentioGFR↓(whenUAER=100andedemamg/24h,GERbegintodecrease，

about1ml/min/month)retinopathy↑↑

StageVend-stagerenaldisease,ESRDDM15

30yearalbuminuriaazotemic→uremiaGFR<1/3ofnormalClassificationofdiabetesneuropathy（1）DiabeticsensabilitymultipleneuropathymorecommoninfemaleAverageageofonsetis58.7yearCourseofDM>15yearsSymptomsofsenseNumbnesstype：largemedullatedfibersPaintype：littlemedullatedfibersandnonmedullatedfibersNumbness-paintype

DiabeticautonomicneuropathyPupildiseaseCardiovascularparafunctionFixedheartratePosturalhypertensionSuddencardiacdeathGestrophageal,diarrheaNeuropathicbladder,erectilefailureAbnormalsweatingDiagnosisCriteriafordiagnosingdiabetesFPGRandomOGTTplasmaglucose2hPGmmol/Lmmol/Lmmol/LDM≥7.0≥11.1≥11.1IGRIFG6.1≤FPG<7.0IGT7.8≤FPG<11.1Normal<6.1<7.8CharacteristicsofnewdiabeticdiagnosticcriteriaPracticalproblemsindiagnosislatentautoimmunediabetesmellitusinadults（LADA）AdultonsetSymptomsareevidentSecretionfunctionofcellislowGADApositiveHLA-DQBchainisnonaspartatehomozygoteManagementGoalsPrincipleoftreatmentEarlyLife-longsynthesisindividualGoalsofcontrol

goodaveragebad

PBG(mmol/L) fasting4.4-6.1

7.0>7.0non-fasting4.4-8.0

10.0>10.0HBA1c(％) <6.56.5-7.5>7.5 BP(mmHg)<130/80>130/80-<140/90 >140/90 BMI(Kg/m2)M<25M<27

27 F<24F<26F

26TC

(mmol/L)

<4.5

4.5

6.0 HDL-c(mmol/L)

>1.11.1-0.9<0.9 TG

(mmol/L)

<1.5 <2.2

2.2 LDL-C

(mmol/L)<2.5 2.6-4.40 >4.0ControlactualityofDMinChina26centers、3965patients28％patientsmeasureHbA1c：8.12.6%，52％>7.5％FPG：9.23.7mmol/L，55%>7.8mmol/LDetermingrateofmicroalbumininurine：20％

DiabetesManagementPlanPatienteducationHealthnutritiontherapyExercisetherapyDrugtherapyMonitoringofbloodglucosePhasestherapyofDMPrinciplesofmedicalnutritiontheraphyrationalcontroloftotalcalorificvalueGoal：KeepidealbodyweightLossweightforobesepatientAddweightforleanpatientStandardbodyweight＝height（cm）－105male：（height－100）×0.9female：（height－100）×0.85Bodymassindex（BMI）：weight（kg）/height2（m2）Adult-onsetdiabetesthermalenergysupplyperday（therm/kgstandardweight

）

Nutritionprinciplesofdiabetics

ModerateweightcontrolThedistributionoftotalcalorficvalue：carbohydrate55%

60%fat20%

25%1/5、2/5、2/5protein15%

20%DrinklimitationAvoiding‘diabetic’foods(whichcontainsorbitolorfrucotose)Aspartameisanacceptablecalorie-freesweetenersalt<10g/d，(<3g/dayifhypertensive)Calculationprotein：0.81.2/kgstandardweightfat：0.61.0/kgstandardweightcarbohydrate：totalcalorificvalue－caloriesofproteinandfatExercisetherapyBenefitsGlycaemiccontrolIncreaseβcellsensitivitytoglucoseBloodlipidWeightreductionEstimationofquantityofexercise：heartrate<170－age(year)DrugtherapySulfonylureasBiguanidesα-glucosidaseinhibitorsTniazolidinedionesMeglitinidesInsulinDry-combinationtherapySulfonylureas:modeofactionTheprincipalactionofthesedrugsistostimulateendogenousinsulinsecretionfromthepancreaticβ-cellsNottoincreasesynthesisofinsulinAlsotoincreaseβ-cellssensitivitytoglucoseandexertsomeinfluenceindiminishinginsulinresistance.Sulfonylureas（SU）：

firstchoiceofnon-obesityT2DMTherapeuticeffectsofSUPrimaryfailuretorespondtoSUoccursin20%to25%ofpatientsFPGand2hPGHbA1c1%

2％Astheperiodoftreatmentprogresses,effectsdecline：

Secondaryfailureoccursattherateof10%to15%peryearAfter5years，onlyhalfofthepatientscankeepidealbloodglucosecontrol. UKPDS：firstyear:bloodglucose，insulinthen:bloodglucoseinsulinthe6thyear:returnedtothestatebeforetherapyIndicationsandcontraindicationsofSUSideeffectsofSUHypoglycemia，mostcommoninOldpatientsLong-termpharmaceuticsSymptomsofdigestivetractLiverdysfunctionTetterChangeofhematologyBiguanides：firstchoiceofobesitytype2DMMechanismsofactionofbiguanidesindicationsandcontraindicationsofBiguanidesIndicationsObesityT2DMPoorcontrolbySUPoorcontrolbyinsulin，includingT1DMSimpleobesityPolycysticovarysyndromeContraindicationsAllergicreactionsRenaldysfunction，serumcreatinine>1.4mg/dlAcuteorchronicacidosisHeart、lungdisease：hypoxia、acidosisinclinationHypohepatiaSeveregastroenteropathyPregnancySideeffectsofBiguanidesDiarrheaAnaphylaxisOvertmacies：commoninelderlypatientsLacticacidosisInhibiting

-glucosidaseDelayingthedigestionofglucose2hPGNotstimulatingthesecretionofInsulinα-glucosidaseinhibitors:modeofactionTherapeuticeffectsofAcarbose2hPGFPGHbA1cabout1％.WhenusedincombinationwithSU,HbA1c:about2％SeruminsulinslightlydeclinedWeightnotafewpatientsWhenusedasmonotherapy,itdonotcausehypoglycemiaWhenusedincombinationwithotheroralantidiabeticagents,itmaycausehypoglyceiaIfhypoglycemiahappens,patientshouldbetreatedbyglucose.OtherkindsofsugarareineffectiveIndicationsandcontraindicationsof

α-glucosidaseinhibitorsthiazolidinedion（TZD）：insulinsensitizersInsulinsensitizers;agonistattheperoxisomeproliferator-activatedreceptor

（PPAR

）;increaseglucoseutilizationinperipheraltissues.Reducinginsulinresistance，hyperglycemiaandhyperlipaemiaandhypertensioncanbeimprovedatvariesdegreesForT2DM:usedasmonotherapyorincombinationwithSU,insulin.WhenusedincombinationwithSUorinsulin,hyperglycemiaWithoutinsulin，itcannotreducehyperglycemiaLiverfunctionshouldbemonitoredfrequently.Stopusingitincaseliverdysfunctionisfound.Incidenceofedema:4

5%ItmaycauseHbslightly↓Meglitinides：repaglinideStimulatePancreaticinsulinsecretion（similarwithSU）：specificcombinitionwith36KDaproteinKpathwaycloseStimulatingthefirstphrasesecretionofinsulinAction:rapidonset，shortduration，suppressingpostloadhyperglycemiaquicklySitesofexcretion:kidney8%，fecal92%Usedasmonotherapyorincombinationwithbiguanides，α-glucosidaseinhibitorsIncidenceofhypoglycemiaislowFactorsinchoosingoralantidiabeticagentsageweightBloodglucoselevelFunctionofliverandkidneyCharacteristicofdrugcostsChooseoforalantihyperglucemicagentsOlderpatients：shorttermSUObesityorhyperinsulinismpatients：biguanidesoracarbose2hPG：α－glucosidaseConcentrationofplasmaglucose：>270

300mg/dl.thesymptomsofhypertensionareevident.InsulintherapyisavailableImpairedliverandkidneyfunction：avoidusingOHALean、fastingandafter-excitationinsulinall：insulinDrug-CombinedtherapyReasonabledietandpoorplasmaglucosecontrolbymonotherapySU、biguanides、TZDandα-glucosidaseinhibitorsallcanbeusedincombinationwitheachotherSmalldosagecombinedwithofallkindsofdrugs;enhancingeffectsofreduceglucaemia;sideeffectsofsingleagentsOralagentswithinsulinDrugsofthesameclasscannotbeusedinacombinedway.InsulintherapyIndicationsofinsulinType1DMType2DMAcutecomplicationsSeverechroniccomplicationsofdiabetesEmergencySeveredysfunctionofliverorkidneyGestationandbleedingwomenWithouttoleranceOHA，curativeeffectofOHA，SUinvalidationDistinctleanWithdiseasestreatedbyglucocorticoidSomespecifictypesofDM：secondarypancreasdisease、endocrinopathies、geneticdiabetesObstaclestousingInsinT2DM

oldnotion：NIDDMThedoctorusesOHAonlyanddoesnotseetheneedtouseIns.ThepatientdoesnotwanttouseInforfearofdevelopinginsulindependenceafteruseingit.HyperinsulinismcanleadAStoCVD？hypoglycemia，BW↑国内常用胰岛素一览表DifferencesbetweenhumanandanimalinsulinDifferenceinpharmacodynamic：CloseactionintensityHumaninsulin:absorptionisfast，timeofonsetofeffectisearlyDifferenceinimmunogenicity:AntigenicitofhumaninsulinisweakerthananimalinsulinAfterusehumaninsulin,antibodytiterofbloodinsulinislowerSynthesizedinsulin：lispro（28proline29proline）Quickabsorption,shorteffecttimeShot-termintensiveinsulin

therapyforT2DMIndications：monotherapyorcombinationtherapyoforalantihyperglycemiatherapyfailtoachieveglucosetargets，overthyperglycemia，fastingandpostprandialC-peptideMethod：useinsulin2timesperday：

NPH/R70/30prebreakfastandpresupper，adjustthedosagewiththemonitoringresultsofbloodsugar.useinsulin4timesperday：

RIpremeal、NPHbeforesleepPeriodoftreatment：severalweeksormonthesShot-termintensiveinsulin

therapyforT2DM

Estimationofinitialdosage：0.2

0.4U/KgweightperdayModeoftherapyRIbeforemeals：RI—RI—RI—O，beforebreakfast＞beforesupper＞beforedinerRIbeforethreemeals+RIbeforesupper：RI—RI—RI—RIRIbeforethreemeals+NPHbeforesupper:RI—RI—RI/NPHRIbeforethreemeals+NPHbeforesleep：RI—RI—RI—NPHmixedinsulin（RI/NPH）beforethreemeals（2/3beforebreakfast，1/3beforesupper），theproportion:10R—50RNPH/R70/30beforebreakfastandsupperSecondaryfailureofOHA:combinationwithinsulinFPG

oralanti-hyperglycemiaagents+NPHbeforesleepPPG

NPHbeforebreakfast+oralanti-hyperglycemiaagentsFPG

PPG

oralanti-hyperglycemiaagents+NPHbeforesleepandbeforebreakfastInsulin：adjustper3~4days ，

onephraseeachtime upfor2~4UeverytimeBeforeyouaddinsulin,hypoglycemiareactionshouldbeexcludedCombinationofOHAandNPHbeforesleepIndication：OHAisinvalidorhasloweffectFPGnotexceeding250

300mg/dlNon-leanLADAStillhavingsomefunctionofinsulinsecretionC-peptide：fasting≥0.2mmol/Lpostload>0.4mmol/LTheeffectofsupplyingoneinjectionofintermediate-actinginsulinbeforesleep

HGP，lipolysisantagonizethesomogyieffectsandthedawnphenomenoncausedbyglucagonFPGreturningtonormalHelpingSUtoeffectindaytime24hourPG，HbA1cSupplyingthedeficiencyofacttimeofformerOHAThepatientsneedstobesuppliedwithoneinjectioneachnightanddoesn’tneedtobehospitalized.It’seasyforthepatienttoaccept.differenceofcomplementarytherapyandsubtitutiontherapyofinsulinComplementarytherapyOHAarebasictherapy，combinationwithinsulinNPHbeforesleep,FPG↓:daytimepostprandialhyperglycemiacanbeimprovedevidentlyNPHperbreakfastwithOHAforpostprandialhyperglycemia(oftenused)SubstitutiontherapyStopusingOHA;substitutedbyinsulinMixedinsulinbeforebreakfastandsupperThreeinjectionsperdayR，R，R+NFourinjectionsperdayR，R，R，RorR，R，R，NSideeffectsofinsulinhypoglycemia localreactionAnaphylaxis systemicreaction insulindrugresistanceLipiddystrophia：atrophyandfleshyArtificialfactorsininfluencingcurativeeffectofinsulinInjectpositionabdomenwall>theupperarm>thigh>buttocksInjectdepthhypodermatic,notmusclePreservationcoldstorage,notfreezeNB(1)Needtoincreasethequantityofinsulin：HyperpyrexiaHyperthyreaPachyacriaKetoacidosisSevereinfectionortraumaSerioussurgeryPregnantwoman，especiallyinmetaphaseoranaphaseofpregnancyAdolescentchildrenNB(2)NB(3)

NB(4)Combinationdrugtherapy（helplowerplasmaglucose）Slowdegradationofinsulinchloroquine、quinidine、quininInsulincombineglobulincompetely，dissociatedinsulinanticoagulativeagents、

salicylate、sulfanilamide、anti-tumoragentscanhelploweringglucemia：OHA、assimilationsteroidandrogenichormones、

monoamineoxidaseinhibitor、NSAIDLowerglucemiaACEI、溴隐停、氯贝特、酮康唑、lithium、甲苯咪唑、theophylline、alcohol、奥曲肽MonitorofDMGlucosuria：associatedwithrenalthresholdofglucose(onlyforclue)FPGHBA1c：2

3monthsbloodsugarlevelFructosamine：2

3weeksbloodsugarlevelOGTT：2hourspecimen

DiabeticKetoacidosis（DKA）summarize(1)OneoftheacutemetaboliccomplicationsofdiabetesCanbeinitialsymptomsofdiabetesOneoftheimportantemergencyofinternalmedicineNeedrapid,reasonabletreatmentFull-scaleexaminationofspecialtyknowledgeofinternistorgeneralpractitionerNeeddoctorsandnursestotakeconcertedactionSummarize(2)KetosisDKAHypoglycaemicketo-acidoticcoma

CompositionandcharacteristicsofketonebodyAcetoaceticacid

isthefirstproduct：strongorganicacid;canreactedwithketonepowderstronglyDimethylketone

：leastquantity、neutral、norenalreabsorptionthreshold;canbeexcretedfromrespiratorytractβ－oxybutyricacid

：strongorganicacid，biggestquantity（70％）

Pathophysiologyglucagon↓↓↑↑Abnormalitiesincarbohydratemetabolismlipolysis↑AcidosisAbnormalnervoussystemCirculationfaliure携氧系统异常ElectrolytedisturbanceAcetonebodyPlasmaglucoseSeveredehydrationInducementofDKA(1)InterrupteddrugtherapyImproperdietFatigueinfectionTraumaoperationpregnancy、deliverydrinkingmiocardialinfarctionelseClinicalpresentationsofDKAIntensivethirsty,diuresisExtremelytired、nausea、vomitingVarieddegreesofdisorderofconsciousnessCirculat