Diabetes糖尿Dr.AstridWehner,Dipl.ECVIM-Diabetes糖尿Dr.AstridWehner,Dipl.ECVIM-ESAVS,FelineMedicineandSurgery4EndocrinologyandReproductionShanghai,Sept.22nd–26th,Physiologiceffectsof?cellularuptakeofglucose(glycogenPhysiologiceffectsof?cellularuptakeofglucose(glycogen細胞糖的攝取（糖原形成exception:brain,retina,例外：腦、視網(wǎng)膜cellularuptakeofaminoacids,fattyacids,?preventslipolysisandcirculationoffreefattyinhibitsglucogensecretion,glycogenolysis,gluconeogenesisandketoneformation??Biphasicinsulinsecretion雙相性胰島素分Biphasicinsulinsecretion雙相性胰島素分Cats?Prevalence發(fā)病率1-??Type2DMCats?Prevalence發(fā)病率1-??Type2DMInsulinresistenceanddysfunctionalβ-胰島素耐受和β細胞功能不FirstrelativethenabsoluteinsulindeficiencyIncreasingdegenerationofβ-cellsduetoincreasinginsulin??由于胰島素分泌增加造成β細胞變性加Treatmentwithinsulin需要胰島素治Amyloiddesposition??Riskfactorsfortype2?????ObesityRiskfactorsfortype2?????Obesity肥malegender雄Age年Breed品adlibitum隨意喂indoor室內(nèi)飼treatmentwith類固醇治??SecondaryOrtype3III??SecondaryduetoSecondaryOrtype3III??Secondaryduetopresenceofanotherdisease(usuallyofendocrineorigin)由于其他疾病繼發(fā)（通常是內(nèi)分泌問題?growthhormone/glucagon生長激素/insulinresistanceandincreased胰島素耐受和糖異生增?Glucose-and?Longterm↑glycemia,triglycerides,ffa,cholesterindestructionGlucose-and?Longterm↑glycemia,triglycerides,ffa,cholesterindestructionofβ-cells(apoptosis)insulin?Importanttostartearlywith(effective)treatment要盡早開始（有效的）relativeorabsoluteinsulin相對或絕對relativeorabsoluteinsulin相對或絕對胰島素缺decreasedutilizationofglucose,aminoacids,andacidsin組織中血糖、氨基酸和脂肪酸利用下increasedglycogenolysis/gluconeogenesisinthe肝臟中糖原分解和糖異生增Hyperglycemia高血??weightlossdespitegoodfoodintake??weightlossdespitegoodfoodintake盡管食物攝入良好但體(cataract),neuropathy（白內(nèi)障），presenceofketoacidosis:anorexia,lethargy,???cluesforunderlyingdisease:acromegaly,Diagnosis診??clinicalsymptoms臨床癥persistenthyperglycemia(fasted)Diagnosis診??clinicalsymptoms臨床癥persistenthyperglycemia(fasted)持續(xù)高血（禁食??glucosuria,糖尿、酮↑fructosamineorglycosylated(glykosylated果糖胺或糖化血紅蛋白上升（糖化白蛋白irreversiblebindingwith?不可逆轉(zhuǎn)地與葡萄糖結(jié)irreversiblebindingwith?不可逆轉(zhuǎn)地與葡萄糖結(jié)representsglycemiaofprevious1-2代表前1-2周的血糖情Fdoesnotidentifycauseofbad若F上升并不能表明何種原因造成控制不良F<450μmol/L:excellent???若F<450μmol/L：控制極有可能在控制得好/一般/?Glucose葡萄糖Fruktosamine果糖胺Glucose葡萄糖Fruktosamine果糖胺Additionalworkup另外的檢?Important重Hematology血BiochemistryAdditionalworkup另外的檢?Important重Hematology血Biochemistryurinalysis(stick,USG,sediment,???尿檢（尿條、尿比重、沉渣、培養(yǎng)inaddition另???fPLITreatmentgoal???Treatmentgoal???preventionofcomplicationsandremote防止并發(fā)癥和間接損bacteriellpancreatitis(chronic胰腺炎（慢性hepatolipidosisneuropathyiatrogenichypoglycemiadiabeticremission糖尿病復(fù)發(fā)Treatmentoptions???InsulinsoralTreatmentoptions???Insulinsoralantidiabetics??Diet飲Excercise鍛?treat/avoidunderlyingcauseandcomplicatingfactors治療/避免潛在原因和并發(fā)因素???ObesityDrugs藥underlyingdiseases(acromegaly,?cats:proteinrich,complex富含蛋白質(zhì)，復(fù)合碳水化合moderate?cats:proteinrich,complex富含蛋白質(zhì)，復(fù)合碳水化合moderatefiber中等纖catsmayeatthroughouttheday(ifweightreductionisnot貓可能可以一整天都可以吃（如果并不需要減重的話weightreduction??calculationofRERonthebasisofideal以理想體重為基礎(chǔ)計算RER=70(KGkg*0,75)or(30*KGkg)+Cat貓0,8*weightloss:ideal1-2%體重減少：理想的，每周1-2%體???Applicationofinsulin應(yīng)用胰島?insulinsyringes(40IU/100Applicationofinsulin應(yīng)用胰島?insulinsyringes(40IU/100胰島素注射器（40IU/100IUinsulinpen??z.B.?lateralthoracicorabdominalInsulinclassification性NotpotentGlargine甘精胰島素LevemirUltralenteInsulinclassification性NotpotentGlargine甘精胰島素LevemirUltralente長效胰島Lente(Caninsulin?)Long30/70(30%Alt(Rapid-)Insulin,70%NPH)Verypotent??porcinelenteinsulinzincsuspension(30%short??porcinelenteinsulinzincsuspension(30%shortacting,70%cristallineCat?Dose劑量0,25-0,5IU/kgbid(startwith1IU/cat???Peak峰值Efficacy有效性61-84%hypoglycemiapossible可能低血糖0,5Lantus?(Glargine)??syntheticbasalinsulinanalogueprecipitatesinLantus?(Glargine)??syntheticbasalinsulinanalogueprecipitatesinphysiolog.pH–insulinisslowlyCat貓???Dose劑量0,25-0,5IU/kgbid(startwith1IU/cat??peak,duration峰值、持續(xù)時間:after5,3h之后Efficacy效力:Levemir?(Detemir地特胰島素??syntheticbasalinsulinprotractedabsorptionafterLevemir?(Detemir地特胰島素??syntheticbasalinsulinprotractedabsorptionafterinjectionthroughhydrophobicinteractionbetweenfattyacidsdecreasedweightgainandriskfor?Cat????Dose劑量0,1-0,2IU/kgPeak峰值duration持續(xù)時間afterEfficacy效力nodifferencecomparedtoLantus?inhealthycats對于健康貓，和Lantus?相比無差異Insulintherapymonitorthefirstdayfor?Rechecks復(fù)??Insulintherapymonitorthefirstdayfor?Rechecks復(fù)??presenceofsymptomsweight??glucoseregulation?bloodglucosecurveafter5-7days(best)orfructosamineafter2??Bloodglucoseprofile血糖情takebloodsampleevery2-3h每2-3Bloodglucoseprofile血糖情takebloodsampleevery2-3h每2-3??onlymethodtoassesscausesofpoor?inhospitalofatbest“homebloodglucosecosts最佳“家庭血糖監(jiān)測?assesseffectanddurationofinsulin????durationofaction作用VariabilityBloodsampling?v.jugularisorcephalica:stress,hematomaBloodsampling?v.jugularisorcephalica:stress,hematoma頸靜脈或頭靜脈：應(yīng)激、形成血earoffoodpadpuncture:simpleandwell耳部以及腳墊穿刺：簡單且耐受??Lancets?BloodValidatedinWellionBloodValidatedinWellionGlucoMed0,5Alpha 0,3GlucoPet,1,0yesHumanincats0,3Accu-ChekActive,Roche1GlucoMenHumanincats0,3Accu-ChekActive,Roche1GlucoMenLXPlus,0,30,6Bloodglucoseloweringand>150mg/dl(8increaseinsulindose???Bloodglucoseloweringand>150mg/dl(8increaseinsulindose???80mg/dl(4,5mmol/l)lowerinsulindoseoptimalrange最佳范圍50200mg/dl2,811,1NadirBloodGlucoseBlutzuckerDurationofaction持續(xù)作用時optimalrange最佳范圍50200mg/dl(2,811,1durationDurationofaction持續(xù)作用時optimalrange最佳范圍50200mg/dl(2,811,1durationshouldlast12h(Injection?Duration持續(xù)12BloodGlucose血糖Blutzucker胰島素有Noinsulin胰島素劑<8080-150>150<1>1-1,5胰島素有Noinsulin胰島素劑<8080-150>150<1>1-1,5胰島素耐持續(xù)時間Oralantidiabetics?onlyaminorityofcatsOralantidiabetics?onlyaminorityofcatsprogressiveβ-celldestructionwhichresultsincompleteinsulin-dependency進行性β細胞破壞，最終造成完全的胰島素依賴?Oralantidiabetics?mechanismofactionstimulationofOralantidiabetics?mechanismofactionstimulationofinsulinsecretioninthepancreas刺激胰腺分泌胰島素(Sulfonyl-BUN(Glipizide?格列吡嗪),GLP-1analogueGLP-1類似物(Exenatide?艾塞那肽))enhanceinsulinsensitivityoftissuereductionofpostprandialglucoseabsorptioninthebowel?Diabeticremission糖尿病消?remissionrates15-84消退比例15-usuallyinthefirst6Diabeticremission糖尿病消?remissionrates15-84消退比例15-usuallyinthefirst6weeks(upto6relapsepossibleremissionafterketoacidosispossible????favourableprognosisZinietJVIM24:1314,Marshalletagebloodglucose血糖????proteinrichlowcarbdiet富含蛋白，低碳水化合物飲食JFMS11:683HalletJFMS11:125,JVIM22:1326,2008Weaveretal:pretreatmentwithsteroids之前用類固?ComparisonofCaninsulin?vsLantus???study1研究12/8andstudy2研究23/7and?mediansurvival?cat:516貓：516negativeprognostic?mediansurvival?cat:516貓：516negativeprognostic??Hyperkalemia高血鉀?Complicationofinsulin???Owner主Insulin胰島insulinComplicationofinsulin???Owner主Insulin胰島insulinoverdosing胰島素過?hypoglycemia(alsopossibleafter低血糖（也可能在消退后somogyioverswinginsulinunderdosing??persistentorre-occuringsymptoms??shortduration持續(xù)時間Owner??applicationofinsulin/technique應(yīng)用胰島素/Owner??applicationofinsulin/technique應(yīng)用胰島素/技注射器不Insulin?biologicalinactive生物活性差(expired過期,高溫,Insulin?biologicalinactive生物活性差(expired過期,高溫,shaked搖動???changeinjectionsidecatstreatedwithUltralente?shortdurationofaction作用時間短Insulinoverdosing:?causes:??Insulinoverdosing:?causes:??overlappingaction重疊(ifprolongeddurationofaction若持續(xù)Anorexia厭食????resolutionofinsulinresistance胰島素耐Remission消?Symptoms癥狀lethargy,weakness嗜睡???Hypoglycemia低血?Therapy治療GlucosePOor??stopHypoglycemia低血?Therapy治療GlucosePOor??stopinsulinuntilhyperglycemiaandglucosuriare-reducedinsulindose?25-50%insymptomatic10-25%inasymptomatic??Insulinoverdosing:胰島素過Pathophysiology病理生理學(xué)?Insulinoverdosing:胰島素過Pathophysiology病理生理學(xué)?counterregulationinhypoglycemiaorrapidfallofbloodglucose低血糖或血糖迅速下降的反調(diào)節(jié)releaseofdiabetogenichormones(epinephrin,glucagon,釋放致糖尿病激素（腎上腺素、胰高血糖素、可的松stimulationofglycogenolysisintheliver刺激肝臟肝???Causes原因???adjustmentofdoseafterone-timebloodglucosevalueorurineglucoseconcentration基于一次血糖值或尿糖濃度進行劑量調(diào)整Somogyioverswing?Consequence后果?hyperglycemiainthefollowing1-72Somogyioverswing?Consequence后果?hyperglycemiainthefollowing1-72在接下來的1-72小時高血morningbloodglucose早晨血糖400-800viciouscircleifinsulinisincreasedduetohighbloodglucose若因高血糖增加胰島素則產(chǎn)生惡???clinicalsymptoms臨床癥狀???goodregulationfor1-2days1-2天血糖控制良thereafterpersistenthyperglycemia其后持續(xù)fructosaminenothelpful果糖胺?Therapy治療reduceinsulindose減少胰島素劑量25-Insulin?Causes原因???lowdosesidshortInsulin?Causes原因???lowdosesidshortdurationofaction?Therapy治療?increasedose0,5IU/injectioncaution:somogyioverswing?Shortinsulinduration?clinicalsigns臨床癥狀duration<10h??morningShortinsulinduration?clinicalsigns臨床癥狀duration<10h??morningbloodglucose?Diagnosis診斷increaseofbloodglucose>200mg/dlwithin6-10hafterinsulininjection?Therapy治療?changetolonger-actinginsulin?Longinsulin胰島素持續(xù)時間過?mechanism??Duration持續(xù)時Longinsulin胰島素持續(xù)時間過?mechanism??Duration持續(xù)時12h(e.g.catswithCRD患慢性腎病的貓nadirclosetosecondinsulin最低點離第二次胰島素注hypoglycemiaduringnightleadstosomogyi夜間低血糖導(dǎo)致蘇木杰現(xiàn)?morningbloodglucose早晨300??Diagnosis診斷bloodglucosemonitoringTherapy治療??reductionofeveningdoseortreatment減少晚上劑量或治療一天一Insulinresistance??ifeverythingelsehasbeenexcludedsuspect,ifdose>1-1,5IU/kgInsulinresistance??ifeverythingelsehasbeenexcludedsuspect,ifdose>1-1,5IU/kg若排除其??diagnosis:bloodglucose診斷：血糖監(jiān)attention:similarprofilesresultwithstress-inducedhyperglycemia,Somogyioverswing,wronginjectiontechnique,lowinsulindoseCausesofinsulinresistancein貓胰島素耐受的原?Endocrinopathies???Acromegaly肢Causesofinsulinresistancein貓胰島素耐受的原?Endocrinopathies???Acromegaly肢端肥hyperthyroidism甲?infectiousdisease??gingivitis/stomatitis齒齦炎/口腔?Inflammatorydisease??pancreatitis胰腺?Others???Neoplasia腫Evaluationofinsulin胰島素耐受評?????thoroughEvaluationofinsulin胰島素耐受評?????thoroughphysicalHematology,biochemistryurinalysisandculturepancreatitissuspectfPLIhyperthyroidismsuspect懷疑甲亢T4,?acromegalysuspect懷疑肢端肥大癥IGF-IpituitaryMRI垂體cushingsuspect懷疑庫興氏LDDStest(incats0,1mg/kgdexamethasoneIV)低劑量地塞米松試驗（在貓neoplasiascreening:thoracicradiographs,??Case1病例DSH9years9歲m/n,5Case1病例DSH9years9歲m/n,5??Problems:PU/PD/PP,weight問題:多飲多尿多食，體重下diagnosticshematologybiochemistryurinalysiswithculture診斷：血檢、生化檢查、尿檢培養(yǎng)Glucose血糖19,5?Fructosamine果糖胺501Therapy治療1IUCaninsulin?bid1IULantus?bidrechecksafter2weeks2周后復(fù)查symptomsresolved,bodyweight??Case2病例DSH,4,5kg,m/n,12?2Case2病例DSH,4,5kg,m/n,12?2IECaninsulin?ongoingPU/PD/PP(mostlyinthe進行性多飲多尿多食（主要在晚上???F果糖胺548BLZCase2–病例2-解決方?diagnosis:shortinsulin診斷Case2–病例2-解決方?diagnosis:shortinsulin診斷：胰島素持續(xù)時間therapymodification調(diào)整治療changeto2IU?改為2IULantusBLZCase3病例?DLH,14years,f/s,6treatmentCase3病例?DLH,14years,f/s,6treatmentwith2IULantus?biddietweightmanagement(5kg)用2IULantusfollowup???symptomesresolve癥狀解??after8weeksweightlossof1kg8周后體重下降Fructosamine果糖胺:750/601/513/420?Assessement???bloodglucoseprofile:normoglycemia血糖情況，血slowreductionofinsulindose緩慢減少胰島Case4病例?Himalayan,4kg,f/s,10喜馬拉雅貓，4kg，絕育母貓，10??insulinincreasedto6IE