糖尿病英文课件

DiabetesMellitus2023/8/141.DiabetesMellitus2023/8/11.DiabetesMellitusdefinitiontypessymptomsdiagnosisLaboratoryfindingstreatmentcomplications2023/8/142.DiabetesMellitusdefinition202Definition-WHO(4/2000)Thetermdiabetesmellitusdescribesametabolicdisorderofmultipleaetiologycharacterizedbychronichyperglycaemiawithdisturbancesofcarbohydrate,fatandproteinmetabolismresultingfromdefectsininsulinsecretion,insulinaction,orboth2023/8/143.Definition-WHO(4/2000)TheterDefinitionAmetabolicconditioncharacterisedbyhighplasmaglucoselevelsandchronicvascularcomplicationsAvasculardiseaseaffectingsmallandlargearterieswithcoexistentmetabolicdisturbanceparticularlyhighplasmaglucoselevels2023/8/144.DefinitionAmetabolicconditioDiabetesMellitusdefinitiontypessymptomsdiagnosisLaboratoryfindingstreatmentcomplications2023/8/145.DiabetesMellitusdefinition202AetiologicalClassificationofDisordersofGlycaemiaType1

(beta–celldestruction,usuallyleadingtoabsoluteinsulindeficiency):Autoimmune:IdiopathicType2

(mayrangefrompredominantlyinsulinresistancewithrelativeinsulindeficiencytoapredominantlysecretorydefectwithorwithoutinsulinresistance)Otherspecifictypes

Geneticdefectsofbeta–cellfunction GeneticdefectsininsulinactionDiseasesoftheexocrinepancreasEndocrinopathies Drug–orchemical–inducedInfections Uncommonformsofimmune–mediateddiabetes OthergeneticsyndromessometimesassociatedwithdiabetesGestationaldiabetes2023/8/146.AetiologicalClassificationofType1diabetesPreviouslyknownasIDDM(Insulindependentdiabetes)Ketosisprone:Usuallydiagnosedinyoungeragegroup(<30years)(Peakincidence11-13yr)Prevalencehighlyvariablebutapproximately0.20%withanincidenceof15-20per100000populationagedlessthan21Seasonalvariation-withlowestrateinspringandsummer2023/8/147.Type1diabetesPreviouslyknowType1diabetesmellitusImmune-mediatedtype1diabetesacuteLADAlatentautoimmunediabetesinadults

Idiopathictype1diabetesmellitus2023/8/148.Type1diabetesmellitusImmuneType1diabetesmellitusGeneticsEnvironmentalfactorVirusesChemicalagentsAutoimmune

Auto-antibodies:isletcellcytoplasmantibody(ICCA)isletcellsurfaceantibody(ICSA)glutamicaciddecarboxylaseantibodyGADA(64KD)Insulinantibody(IAA)

2023/8/149.Type1diabetesmellitusGenetiType1diabetesThispresentationistheendpointofrecentandcontinuingbetacellfunctionresultinginneartotallossofInsulinproductionHyperglycaemiaitselfbegetsfurtherbetacelldestructionastreatmentwithinsulinoftenresultsina“honeymoon”periodwhenthepatientcanoftenmanagewithoutinsulin2023/8/1410.Type1diabetes2023/8/110.Type1diabetesmellitususuallyautoimmunedestructionof

insulin-producingpancreaticisletcells

overmonthsabsoluteinsulindeficiencyrapidpresentationwith

thirst,polyuria,weightloss,blurredvision

thrush,lethargy,dizziness.nausea,vomiting,abdominalcramps,andsuperficialinfectionusuallythinandketoticatpresentationAuto-antibodiesidentified:antiisletcell(ICCA.ICSA),antiGAD(64KD),antiInsulin(IAA)2023/8/1411.Type1diabetesmellitus2023/8Aprogressivemetabolicdisorder

characterisedby:

InsulinresistanceType2diabetes

-celldysfunction2023/8/1412.AprogressivemetabolicdisordType2diabetesPreviouslyknownasNIDDMNonketosisprone:,diagnosis>30years1in1000populationasnewcaseseachyearInsidiouspresentationwithsymptomsofpolyuria,polydipsia,lethargy,weightloss,nausea,vomiting,abdominalcramps,blurredvisionandsuperficialinfection.OftendiscoveredatroutinemedicalThispresentationistheendpointofthegraduallossofbetacellfunctioninthesettingofInsulinresistanceStrong(90-100%)concordanceinTwinsReavan’ssyndromeorSyndromeX Insulinresistance2023/8/1413.Type2diabetesPreviouslyknowType2diabetesUnderlyinginsulinresistancegeneticandethnicityObesityBMIWHRinactivity/lowphysicalfitnessintrauterine&childhoodfactorssmoking&drugsImpairedinsulinsecretionInsulinsecretionworsenswithtimepost-receptor

cellularmechanismsmechanism

unclearb-cell

exhaustion2023/8/1414.Type2diabetespost-receptor

cType2diabetesPrandialglucoseFastingglucoseInsulinresistanceInsulinsecretionPlasmaglucoseß-cell126mg/dLyears2023/8/1415.Type2diabetesPrandialglucosPancreatic

-cell

InsulinresistanceLiverHYPERGLYCAEMIAIslet

-celldegranulation

ReducedinsulincontentMuscle(PKC

Adiposetissue

Decreasedglucosetransport

&activity(expression)ofGLUT-4IncreasedlipolysisElevatedplasmaNEFA+-LowplasmainsulinIncreasedglucoseoutputElevatedTNF

Insulinresistanceand

-celldysfunctionproducehyperglycaemiaintype2diabetes2023/8/1416.Pancreatic-cellInsulinresTissueResponsestoInsulin

ResistanceorFailure

LIVERa.increasedglycogenhydrolysistoglucoseb.increasedgluconeogenesis.c.increasedtriacylglycerolhydrolysisandconversionofglyceroltoglucosed.increasedconversionofFAandproteintoketones(AcAcandBHB)e.increasedproteinandaminoacidcatabolismf.increasedproductionofurea2023/8/1417.TissueResponsestoInsulin

ReMUSCLE

a.serumglucoseispoorlytakenupbymuscle(decreaseGLUTactivity)b.saturationofhexokinaseactivity,inabilitytoretaincellulargluasglu-6-PO4c.increasedLPLactivityandincreasedFAproductiond.increasedb-oxidation,butTCAisoverwhelmedbecauseATPishighalreadyee.increasedbreakdownofmuscleandserumproteinintoaminoacidsf.increasedtransferofNontoALA/GLNandsentbacktoliver2023/8/1418.MUSCLE

a.serumglucoseispoADIPOSEa.increasedLPLandHSLsendmorefreeFAintobloodstreamb.glucosecannotbetakenintocellviaGLUT4forglycogensynthesisc.activeHSLmeansTAGsarenotbeingmadeandstored2023/8/1419.ADIPOSEa.increasedLPLandInsulinresistanceandinsulin

hypersecretionprecedetype2diabetesInsulinInsulinMacrovascularsensitivitysecretiondisease30%50%50%50%70–100%40%70%150%10%100%100%Type2diabetesIGTImpairedglucosemetabolismNormalglucosemetabolism2023/8/1420.InsulinresistanceandinsulinClinicalReavansSyndromeInsulinresistanceHypertensionDyslipidaemia(increaseLDL,decreasedHDL)ObesityOtherfactors:hyperfibrinogenemia,hyperuricaemia,propensitytomicrovasculardiseases“Metabolicsyndrome”inmostcasesoftype2diabetes2023/8/1421.ClinicalReavansSyndromeInsulabdominalobesityhighbloodpressureHDLcholesterol

VLDLtriglyceride

smalldenseLDL

hyperinsulinaemiaglucoseintolerancediabeteshyperuricaemiaPAI-1

fibrinogen

factorVII

microalbuminuriainsulinresistanceSyndromeofinsulinresistanceAKA Reaven’ssyndrome,syndromeX metabolicsyndrome2023/8/1422.abdominalobesityhighbloodprType1diabetestypicalonset<30yearscanstartatanyagesuddenonsetseveresymptomsrecentweightlossusuallythinspontaneousketosisabsentC-peptidemarkersofautoimmunityType2diabetestypicalonset>20yearscanstartatanyagegradualonsetmaybenosymptomsoftennoweightlossusuallyobesenotketoticdetectableC-peptidenoautoimmunemarkers2023/8/1423.Type1diabetesType2diabetesDiabetesinpregnancyco-existentornewlydiagnosedlifelongdiabetestype1type2(especiallyinSouthAsianwomen)otherspecifictypesofdiabetesgestationaldiabetes2023/8/1424.Diabetesinpregnancy2023/8/12OthertypesofDiabetesGeneticdefectsofbeta–cellfunctionChr’me20,HNF4_(MODY1)Chr’me7,glucokinase(MODY2)Chr’me12,HNF1_(MODY3)Chr’me13,IPF–1(MODY4)MitochondrialDNA3243mutationGeneticdefectsininsulinactionTypeAinsulinresistanceLeprechaunismRabson–MendenhallsyndromeLipoatrophicdiabetes&OthersDiseasesoftheexocrine-pancreasFibrocalculouspancreatopathyPancreatitisTrauma/pancreatectomyNeoplasiaCysticfibrosisHaemochromatosis&OthersEndocrinopathiesCushing’ssyndromeAcromegalyPhaeochromocytomaGlucagonomaHyperthyroidismSomatostatinoma&Others

2023/8/1425.OthertypesofDiabetesGeneticTypes-continuedInfectionsCongenitalrubellaCytomegalovirusOthers

Uncommonformsofimmune–mediateddiabetes

Insulinautoimmunesyndrome(antibodiestoinsulin)Anti–insulinreceptorantibodies“StiffMan”syndromeOthersDrug–orChemical–inducedDiabetes

NicotinicacidGlucocorticoidsThyroidhormoneAlpha–adrenergicagonistsBeta–adrenergicagonistsThiazidesDilantinPentamidineVacorInterferon–alphatherapyOthers2023/8/1426.Types-continuedInfectionsDrug–PathophysiologyBecauseglucoseisnotgettingintocells,metabolismchangesCatabolismoffatsandproteinsinsteadofcarbohydratesLeadstoincreasedfattyacidsandketoacidsKetoacidosisresultsinloweringofpHDiabeticcomaDecompensatedmetabolicacidosisanddeath2023/8/1427.PathophysiologyBecauseglucoseDiabetesMellitusdefinitiontypessymptoms

diagnosisLaboratoryfindingstreatmentcomplications2023/8/1428.DiabetesMellitusdefinition202SymptomsofdiabetesduetohyperglycaemiaHyperglycemiaDehydrationExcessivethirstandurinationExcessivehungerGlycosuria(gluspillsintourine:>180mg/dl)2023/8/1429.SymptomsofdiabetesduetohySymptomsofdiabetesduetohyperglycaemiaplasmaglucose

>renalthresholdabout12mmol/Lglucoseinurine

osmoticdiuresisurinevolumethirstgenitalthrushweightlosshyperglycaemiatiredness2023/8/1430.SymptomsofdiabetesduetohySymptomsofdiabetesduetohyperglycaemiahyperglycaemiaswellingoflens blurredvisioncerebraleffects lightheadedness malaise mentalchanges2023/8/1431.SymptomsofdiabetesduetohyDiabetesMellitusdefinitiontypessymptomsdiagnosisLaboratoryfindingstreatmentcomplications2023/8/1432.DiabetesMellitusdefinition202ADAdiagnosticcriteria(1997)Symptomsofdiabetes&acasualglucoseconcentrationmorethanorequalto200mg/dl(11.1mmol/l);Casualisdefinedasanytimeofdaywithoutregardstotimesincelastmeal.Theclassicsymptomsofdiabetesincludepolyuria,polydipsiaandunexplainedweightloss orFPGmorethanorequalto126mg/dl(7.0mmol/l).Fastingisdefinedasnocaloricintakeforatleast8hours or2hourPGmorethanorequalto200mg/dl(11.1mmol/l)duringanOGTT.ThetestshouldbeperformedasdescribedbyWHO,usingaglucoseloadcontainingtheequivalentof75gglucosedissolvedinwater2023/8/1433.ADAdiagnosticcriteria(1997)WHOdiagnosticcriteria

wholeblood plasmaDiabetesmellitus

(fasting) >6.1mmol/l >7.0mmol/l2hourpostglucoseload >10.0mmol/l >11.1mmol/lIGT

(fasting) <6.1mmol/l <7.0mmol/l & &2hrpostglucoseload >6.7mmol/l >7.8mmol/lIFG

(fasting) >5.6mmol/l >6.1mmol/l &<6.1mmol/l &<7.0mmol/l2hrpostglucoseload ><6.7mmol/l <7.8mmol/lIGHimpairedglucosehomeostasis2023/8/1434.WHOdiagnosticcriteria whChangesfromOldcriteriaTheclass“ImpairedGlucoseTolerance”isnowclassifiedasastageofimpairedglucoseregulation,sinceitcanbeobservedinanyhyperglycaemicdisorder,andisitselfnotdiabetes.Clinicalstageof

ImpairedFastingGlycaemiahasbeenintroduced

toclassifyindividualswhohavefastingglucosevaluesabovethenormalrange,butbelowthosediagnosticofdiabetes.GestationalDiabetesisretainedbutnowencompassesthegroupsformerlyclassifiedasGestationalImpairedGlucoseTolerance(GIGT)andGestationalDiabetesMellitus(GDM).2023/8/1435.ChangesfromOldcriteriaThecDiagnosisofdiabetessymptoms+elevatedbloodglucoselevelORelevatedbloodglucoselevelsontwooccasions2023/8/1436.Diagnosisofdiabetes2023/8/13DifferentialDiagnosisHyperglycemiasecondarytoothercausesNondiabeticglycosuria2023/8/1437.DifferentialDiagnosisHyperglyDiabetesMellitusdefinitiontypessymptomsdiagnosisLaboratoryfindingstreatmentcomplications2023/8/1438.DiabetesMellitusdefinition202FPG:FastingPlasmaGlucoseCPG:CasualPlasmaGlucose(non-fasting)OGTT:OralGlucoseToleranceTest(75g)HemoglobinA1c(glycatedhemoglobin,glycosylatedhemoglobin)IndicatesaverageBGlevelsoverapprox.3months.%oftotalHgbattachedtoglucoseNormal:4-6%(DM:>8%)2023/8/1439.FPG:FastingPlasmaGlucose20Laboratoryfindings

Glucose:FBG,2hrOGTT,FBGissimple,accurate,convenientforpatientGlycohemoglobinCreatinineUrinalysisglucoseketonebodiesMicroalbuminDyslipidemiaInsulinc-peptide2023/8/1440.Laboratoryfindings

Glucose:FDiabetesMellitusdefinitiontypessymptomsdiagnosisLaboratoryfindingstreatmentcomplications2023/8/1441.DiabetesMellitusdefinition202TreatmentofDiabetesNonPharmacologicalExerciseandEducationDiet,Lowinfat,lowrefinedsugars,highcarbohydrate,highfibre,lowcaloriesifobese,spacingofmeals(Healthyeating)LowcholesterolandtriglyceridedietifhyperlipidemiaAllType1patientswillrequireInsulinandtype2canbeondietonly,tabletsorinsulintreated2023/8/1442.TreatmentofDiabetesNonPharmTreatmentofdiabetestype1type2GDMdiet,exercise&insulindiet,exercisemetforminorsulphonylureaalonemetforminandsulphonylureametformin,sulphonylurea&thiazolidinedioneinsulindietinsulin2023/8/1443.Treatmentofdiabetestype1dieDrugstotreathyperglycaemiaInsulinandinsulinanaloguesInsulinsecretagoguessulphonylureanon-sulphonylureaInsulinsensitizersbiguanidethiazolidinedioneIntestinalabsorptioninhibitorsacarboseorlistatlisproinsulinaspartinsulininsulinglarginegliclazide,glibenclamiderepaglinide,nateglinidemetforminrosiglitazone,pioglitazone2023/8/1444.Drugstotreathyperglycaemialsulphonylureaagentsgliclazide,glibenclamide,glimepiridebindtoreceptorsonisletcellsincreaseinsulinsecretionfromisletcellslongdurationofaction12-48hoursAdverseffectincreaseweightcancausehypoglycaemiacancauserashesContraindicationssulfaallergytype1DM,DKA2023/8/1445.sulphonylureaagents2023/8/145Meglitinides

Mechanism:Bindstositeonbeta-cellmembraneleadingtoinsulinreleaseRapidoralabsorptionandeliminationforuseincontrollingpost-prandialhyperglycemia.Examples:repaglinide,nateglinideContraindicationsType1DM,DKAAdverseeffects:Hypoglycemia,weightgain2023/8/1446.MeglitinidesMechanism:Bindsmetforminlowersliverglucoseoutputincreasestissueglucoseuptakeactslikeaninsulinsensitizermildinductionofnauseapossibleinterferencewithfoodabsorptionnoeffectonweightusedalonedoesnotcausehypoglycaemiareducesriskofmyocardialinfarction1/3patientsgetdiarrhoea,windorabdominalpainnotusedinrenalfailure,heartfailureorsevereintercurrentillness2023/8/1447.metformin2023/8/147.MetforminToxicityRenallyexcreted,notmetabolizedPotentiallyfatallacticacidosisContraindications:renalinsufficiency(decreasesdrugclearance)hepaticdysfunction(decreaseslactatemetabolism)tissueanoxia(increaselactateproduction)2023/8/1448.MetforminToxicityRenallyexcracarbose-glucosidaseinhibitorblocksdigestionandabsorptionofsugarsfrombowellowersbloodglucoseandinsulinlevelsaftermealsweakantidiabeticdrugnoeffectonweightusedalonedoesnotcausehypoglycaemianotabsorbedintobody1/2patientsgetdiarrhoea,windorabdominalpain2023/8/1449.acarbose2023/8/149.a-glucosidaseinhibitortoxicityUnabsorbedCHO’s:Bacterialfermentationincolonresultsinabdominalpain,flatulencefromgasOsmoticdiarrheaElevatedserumtransaminasesMetabolizedandexcretedintheGItractSomemetaboliteisabsorbedinGIandrenallyexcretedContraindicatedforpatient’swithchronicorinflammatoryboweldiseaseRelativelyweakantidiabeticeffect,usuallyusedadjunctively.2023/8/1450.a-glucosidaseinhibitortoxicithiazolidinedioneagents

rosiglitazone,pioglitazone

Mechanism—BindtoPPAR-gammareceptorinperipheraltissuesmainlyskeletalmuscleResultinexpressionofcell-surfaceglucosetransporters.CautionsNotrecommendedinNYHAClassIII/IVCHFMaycausefluidretentionandprecipitateCHFMaycausemildanemia(?Dilutionaleffect)2023/8/1451.thiazolidinedioneagents

thiazolidinedioneagentsAssociatedwithweightgainLivertoxicityseeninolderTZD(troglitazone)butnotwithneweragents;recommendedtocheckLFTsq2mofor1styearofuse.AdvantagesNohypoglycemiaPossibleimprovementinvascularfunction2023/8/1452.thiazolidinedioneagentsAssociThiazolidinedionetoxicityMetabolism:hepaticconjugationbytheCYP450systemExcretion:biliaryHepatotoxic,especiallytroglitazone,andcontraindicatedincasesofhepaticdysfunctionCancauseedemaandhypoglycemiawhenusedincombinationwithotherhypoglycemics2023/8/1453.ThiazolidinedionetoxicityMetaTreatinghyperglycaemiaintype2diabetesdietarychangeexerciseobese

metforminnotobese

sulphonylureametformin&sulphonylureaglitazone&metforminOR

glitazone&sulphonylureainsulin±metforminAim:HbA1c<6.5%

Fastingglucose<7mmol/l2023/8/1454.Treatinghyperglycaemiaintypinsulinanditsanaloguestheonlytreatmentfortype1diabetesalsousedfortype2diabetesandGDMcancausehypoglycaemiacausesweightgaincancausefluidretention2023/8/1455.insulinanditsanalogues2023/Threemainprofiles:humanbio-engineered,porkorBovine.Variousregimens:twicedailysolubleandisophane,thricedailysoluble(pre-meal)andeveningisophane,rarelyoncedaily2023/8/1456.Threemainprofiles:humanbio2023/8/1457.2023/8/157.Basal

bolusIntermediateNormalLong30:70mix2023/8/1458.BasalbolusIntermediateNormalLRecommendedTreatment1stline:Dietandexercise2ndlineoralhypoglycemicmonotherapy(glyburide)adjunctiveto1stlinetreatmentSecond,third,andevenafourthclassofhypoglycemicscanactsynergisticallyformorediresituationsWhenallelsefails,backtotheneedle-insulintherapy2023/8/1459.RecommendedTreatment1stline:EarlyAMHyperglycemia—PossibleCausesDawnphenomenonRiseinBGinearlymorningastheresultofpulsatilereleaseofinsulincounter-regulatoryhormones(growthhormoneandcortisol)SomogyiphenomenonPeriodofmorninghyperglycemiafollowingnocturnalhypoglycemia.Studieshavefailedtoshowthatthisoccurscommonly.NPHinsulingivenatdinnerwithwaningeffectbyAMLatenightsnacking2023/8/1460.EarlyAMHyperglycemia—PossiblDiabetesMellitusdefinitiontypesPrevalencesymptomsdiagnosistreatmentcomplications2023/8/1461.DiabetesMellitusdefinition202DiabeticComplicationsAcuteComplication:

hypoglycaemia,ketoacidosisoftenwithcoma(DKA), Hyperosmolarstateoftenwithcoma(HONK)Microvascularcomplications

Diabeticretinopathy,nephropathyandneuropathyMacrovascularcomplication

cerebrovascularaccidents,coronaryarterydisease,hypertension,peripheralvasculardiseasePregnancywithincreasedmaternalandfoetalmorbidity2023/8/1462.DiabeticComplicationsAcuteCoVascularcomplicationsofdiabetesretinopathynephropathyneuropathycoronaryarterydiseasecerebrovasculardiseaseperipheralvasculardisease2023/8/1463.VascularcomplicationsofdiabDiabeticretinopathyleadingcauseofblindness95%ofdiabeticsubjectsshowsome

by15yearsafteronsetriskfactors:

age

diabetesduration

highbloodglucoselevels

highbloodpressure

geneticsmayprogressrapidlyduringpregnancy2023/8/1464.Diabeticretinopathy2023/8/164DiabeticretinopathyCataractformation(glycationα-crystallin)RetinopathyNonproliferative>microaneurysms>edemaProliferative(VEGF)>Newbloodvesselsthatextendintovitreous,bleeding>lossofvisionGlaucoma,intraocularpressure>oculartissuedamage2023/8/1465.DiabeticretinopathyCataractfNon-proliferativediabeticretinopathy(NPDR)EarlieststageMicroaneurismsandintraretinal“dotandblot”hemorrhagesMacularedemaorhardexudatesat/nearmaculacancausevisualimpairmentProliferativediabeticretinopathy(PDR)Nonperfusionofretinaangiogenesisgrowthofabnormalnewvesselsextendingontoinnersurfaceofretinaorintovitreouscavity.Substantialriskforrupturehemorrhageorretinaldetachment.Treatedwithpanretinalphotcoagulation.2023/8/1466.Non-proliferativediabeticretDiabeticnephropathyAffects25%oftype1andtype2diabetespatientsRiskfactorssimilartothoseforretinopathyIsaprogressiveconditionleadingtorenalfailureCharacterisedbyproteinuriaandhighbloodpressure2023/8/1467.Diabeticnephropathy2023/8/167DiabeticnephropathyGlomerulosclerosis(Capillarybasementmembr.thickening)Microalbuminuria(30-300mg/24hr)Hyperfiltration(^GFR)Albuminuria(>300mg/24hr)HypertensionNephroticsyndrome(approx1/3ofType1progresstoendstagerenaldisrequiringdialysis)Renalfailure(

GFR,

Creat)2023/8/1468.DiabeticnephropathyGlomerulosDiabeticneuropathy

TypesofNeuropathySensoryPain/paresthesiasinfeetparticularlyatnightNumbnessin“stockingandglove”distributionHighriskforfootulcerationAutonomicCardiovascular:restingtachycardia,painlessMI,orthostasisGI:esphagealdysfunction,gastroparesis,diabeticdiarrhea,constipation,fecalincontinenceGenitourinaryED,retrogradeejaculation,neurogenicbladderOther“gustatory”sweating,heatintolerance2023/8/1469.Diabeticneuropathy

TypesofNDiabeticneuropathyAffectstype1andtype2diabetespatientssimilarlyRiskfactorssimilartothoseforretinopathymayleadtolossofsensationinfeetfootulcerationerectiledysfunctiongastroparesisandvomitingposturalhypotension2023/8/1470.Diabeticneuropathy2023/8/170.MACROVASCULARCOMPLICATIONSMacrovascular(>70%hosp/deaths)60%ofpatientsdieofcoronarydisease10%ofpatientsdieofstroke10%sufferfromfatalcomplicationsrelatedtoperipheralvasculardisease2023/8/1471.MACROVASCULARCOMPLICATIONSMacCADAnginaMISilentinfarctCCFECGCardiacenzymesTroponinIExercisestresstestEchocardiographyAngiographyAngioplasty/CABG2023/8/1472.CADAnginaECG2023/8/172.CVDTIAsCVAsDementiaCTscanCarotidDopplersTreatriskfactorsCarotidbypasssurgery2023/8/1473.CVDTIAsCTscan2023/8/173.PVDIntermittentClaudicationColdLegsPulselessLegFootUlcersGangreneDopplerStudiesDuplexScanningAngiographyAngioplastyTreatriskfactors2023/8/1474.PVDIntermittentClaudicationDoDiabeticFootNeuropathyPVDCharcotArthropathyUlcerationMRIAngiography2023/8/1475.DiabeticFootNeuropathyMRI2023DiabeticKetoacidosisAcute(severaldaysratherthanhours)CausedbyInadequateinsulinInfectionStressUnderdosingFoodoralcoholbingeResultsinhyperglycemia&mobilizationoflipids2023/8/1476.DiabeticKetoacidosisAcute(seDiabeticKetoacidosis(DKA)Type1Diabetics,SevereInsulinDef.Breakdownoffatstores>^FattyAcidsOxidation>KetoneBodies(^byglucagon)AccumulofAcetoaceticacid/βhydroxybutyricacid>^Plasma[H]>MetabolicKetoacidosis(Hydrationvsdehydration)2023/8/1477.DiabeticKetoacidosis(DKA)TypeDiabeticKetoacidosis(DKA)DKAresultsinalteredlipidmetabolismincreasedconcentrationsoftotallipids,cholesterol,triglycerides,andfreefattyacidsfreefattyacidsareshuntedintoketonebodyformationduetolackofinsulin;therateofformationexceedsthecapacityfortheirperipheralutilizationandrenalexcretionleadingtoaccumulationofketoacids,andthereforemetabolicacidosisWithprogressivedehydration,acidosis,hyperosmolality,anddiminishedcerebraloxygenutilization,consciousnessbecomesimpaired,andthepatientultimatelybecomescomatose2023/8/1478.DiabeticKetoacidosis(DKA)DKAClinicalManifestationsearlymanifestationsaremildandincludevomiting,polyuria,anddehydrationMoreseverecasesincludeKussmaulrespirations,odorofacetoneonthebreathabdominalpainorrigiditymaybepresentandmimicacuteappendicitisorpancreatitiscerebralobtundationandcomaultimatelyensue2023/8/1479.ClinicalManifestationsearlymLaboratoryfindingsLaboratoryfindingsincludeglucosuria,ketonuria,hyperglycemia,ketonemia,andmetabolicacidosis.Serumamylasemaybeelevated.Leukocytosisiscommon2023/8/1480.LaboratoryfindingsLaboratoryDiagnosisDKAexistswhenthereishyperglycemia(>300mg/dL),ketonemia,acidosis,glucosuria,andketonuria2023/8/1481.DiagnosisDKAexistswhenthereDKAmustbedifferentiatedfromacidosisandcomaduetoothercauses:hypoglycemia,uremia,gastroenteritiswithmetabolicacidosis,lacticacidosis,salicylateintoxication,encephalitis2023/8/1482.DKAmustbedifferentiatedfroTreatmentTreatmentisdividedinto3phasestreatmentofketoacidosistransitionperiodcontinuingphaseandguidanceGoalsoftreatmentofDKAintravascularvolumeexpansioncorrectionofdeficitsinfluids,electrolytes,andacid-basestatusinitiationofinsulintherapytocorrectcatabolism,acidosis2023/8/1483.TreatmentTreatmentisdividedKetoacidosisTreatmentAdministerinsulinRehydrateReplaceelectrolytesTreatacidosiswithbicarbonate2023/8/1484.KetoacidosisTreatment2023/8/1Intravascularvolumeexpansiondehydrationismostcommonlyintheorderof10%initialhydratingfluidshouldbeisotonicsalinethisalonewilloftenslightlylowerthebloodglucoseTreatmentofelectrolyteabnormalitiesserumK+isoftenelevated,thoughtotalbodyK+isdepletedK+isstartedearlyasresolutionofacidosisandtheadministrationofinsulinwillcauseadecreaseinserumK+2023/8/1485.Intravascularvolumeexpansion“Maintenance”IVfluidatarateof2000-2400cc/m2/dayconsistsof2/3NS(0.66%)orNSNSisaddedtoIVFwhenbloodglucoseis~250mg/dL5%Dextroseor5%GNSisaddedwhenbloodglucoseis~250mg/dL2023/8/1486.“Maintenance”IVfluidataraInsulinTherapycontinuousinfusionoflow-doseinsulinIV(~0.1U/kg/hr)iseffective,simple,andphysiologica