014esavs-貓病專題i-講義糖尿病治療

MichaelE.HerrtageUniversityofCambridgeMANAGEMENTOFFELINEDIABETESMELLITUS貓?zhí)悄虿〉闹委烡IABETESMELLITUS

糖尿病Astateofchronichyperglycaemiacausedbyabnormalitiesofcarbohydrate,proteinandlipidmetabolism,whichmayeitherbeduetoanabsolutelackofinsulinortofactorsthatopposeitsaction.一種慢性高血糖癥，由碳水混合物、蛋白質(zhì)和脂肪代謝異常造成，原因有：胰島素絕對(duì)水平下降胰島素合成拮抗因子WorldHealthOrganisation1980CLASSIFICATIONOFDIABETESMELLITUS

糖尿病分類Type1diabetes1型糖尿病Insulindependentdiabetesmellitus(IDDM)胰島素依賴性糖尿病Juvenile-onsetdiabetes青年發(fā)病型糖尿病Type2diabetes2型糖尿病Non-insulindependentdiabetesmellitus(NIDDM)非胰島素依賴性糖尿病Adult-onsetdiabetes成年發(fā)病型糖尿病Type3diabetes3型糖尿病Secondarycausesofdiabetes繼發(fā)性糖尿病DIABETESMELLITUS

POSSIBLEAETIOLOGIES

糖尿病致病原因Genetics 遺傳Immune-mediatedisletdestruction 免疫介導(dǎo)性胰島破壞Obesity 肥胖Infection 感染Pancreatitis 胰腺炎Currentillness 現(xiàn)有疾病Drugtherapy 藥物治療Isletamyloidosis 胰島淀粉樣變性PATHOGENESISOFTYPE2DIABETESMELLITUS

2型糖尿病的發(fā)病機(jī)理Beta-celldysfunction

β細(xì)胞功能不全I(xiàn)nsulinresistance

胰島素不敏感Obesity

肥胖Chronichyperglycaemia

慢性高血糖癥Environmentalfactors

環(huán)境因素Obesityandphysicalexercise

肥胖和運(yùn)動(dòng)Diet

飲食PATHOGENESISOFTYPE2DIABETESMELLITUS

2型糖尿病的發(fā)病機(jī)理Isletamyloidosis

胰島淀粉樣變性Glucoseandlipidtoxicity

葡萄糖和脂毒性Beta-cellexhaustion

β細(xì)胞耗竭PATHOPHYSIOLOGYOF

DIABETESMELLITUS

糖尿病的病理生理學(xué)Relativeorabsolutedeficiencyofinsulin

胰島素相對(duì)或絕對(duì)不足Decreasedglucoseuptakebyadiposetissueandmuscle

脂肪組織和肌肉攝取葡萄糖減少Increasedcatabolismespeciallyoffats

代謝增加，特別是脂肪代謝增加PATHOPHYSIOLOGYOF

DIABETESMELLITUS

糖尿病的病理生理學(xué)高血糖糖尿滲透性利尿：水、電解質(zhì)流失CLINICALSIGNSOF

DIABETESMELLITUS

糖尿病的臨床表現(xiàn)Polyuria

多尿Polydipsia

煩渴Polyphagia

多食Weightloss

體重下降Liverenlargement肝臟腫大PATHOPHYSIOLOGYOF

DIABETESMELLITUS

糖尿病的病理生理學(xué)血中游離脂肪酸在肝臟代謝為乙酰輔酶A乙酰乙酸丙酮?－羥丁酸PATHOPHYSIOLOGYOFDIABETICKETOACIDOSIS

糖尿病酮酸中毒的病理生理學(xué)AcetylCoA乙酰輔酶AAcetoacetylCoA乙酰乙酰輔酶ATCAcycleFFA游離脂肪酸Acetoaceticacid乙酰乙酸Acetone丙酮b-hydroxybutyricacidβ-羥丁酸Glucose葡萄糖Amino氨基Acids酸PATHOPHYSIOLOGYOFDIABETICKETOACIDOSIS

糖尿病酮酸中毒的病理生理學(xué)CortisolGrowthHormoneCatecholamines兒茶酚胺Lipolysis脂解Ketogenesis酮生成Ketonaemia酮(酸)血癥ReducedglucoseutilisationHyperglycaemia高血糖Glycogenolysis糖原分解ReducedinsulinRelease胰島素分泌減少Gluconeogenesis糖原異生Increasedglucagon:insulinRatio肝醣胰島素比值升高降低糖利用CLINICALSIGNSOFDIABETICKETOACIDOSIS

糖尿病酮酸中毒的臨床表現(xiàn)Vomiting,dehydration 嘔吐、脫水Depression,weakness,collapse 精神沉郁、虛弱、虛脫Tachypnoea,smellofacetone 呼吸急促、有丙酮味Precipitatingcausee.g.infection,concurrentdisease

易感因素：感染/同時(shí)發(fā)生的疾病03/861Domesticshorthairedcat8yrFn‘Ebony’短毛家貓，8月齡DSH8yrFn‘EbonyLivedinGermanyuntil1996 在德國(guó)住到1996年OwnedbyaG.P. 主人：G.PPolydipsicfor6weeks 煩渴達(dá)6周之久Progressivelossofappetitefor2weeks 食欲進(jìn)行性下降2周Completelyanorexicfor7days 厭食7天Noticeableweightloss 明顯的體重下降Vomitingoverlastday 昨天有嘔吐History病史DSH8yrFn‘EbonyDullanddepressed 遲鈍，精神沉郁Unabletostand,butreactstoexamination 無(wú)法站立，但對(duì)檢查有反應(yīng)Mucousmembranesdryandjaundiced 可視粘膜干燥，有黃疸Capillaryrefillslow 毛細(xì)血管充盈減慢Dehydrated,lossofskinturgor 脫水，皮膚失去彈性Markedweightloss6.2kgto3.6kg 明顯的體重減少Palpablyenlargedliver 觸診肝腫大Clinicalexamination臨床檢查DSH8yrFn‘Ebony9/04/03DSH8yrFn‘Ebony9/04/03DSH8yrFn‘Ebony9/04/03DSH8yrFn‘Ebony9/04/03DSH8yrFn‘Ebony9/04/03DSH8yrFn‘EbonyFibrinogen<1g/l9/04/03DSH8yrFn‘Ebony9/04/03Whatnext?

下一步DSH8yrFn‘EbonyHowwouldyoutreatthiscase?

如何治療DSH8yrFn‘Ebony0.9%sodiumchloride(36ml/h)i.v. 0.9%Nacl靜注輸液(36ml/h)5iusolubleinsulin/500ml 5iu可溶性胰島素于500ml溶液中5mmolKCl/500ml 5mmolKcl于500ml溶液中70mgtoldimfossodium(Foston?)s.c. 70mg托定磷鈉s.c.Clavulanatepotentiatedamoxycillini.v. 克拉維酸+阿莫西林i.vSyringe-fedHillsa/devery4hours

注射器餵飼Hillsa/d處方糧，每4小時(shí)1次9/04/03DSH8yrFn‘Ebony10/04/03DSH8yrFn‘Ebony11/04/03DSH8yrFn‘Ebony11/04/03DSH8yrFn‘Ebony11/04/03DSH8yrFn‘Ebony14/04/03DSH8yrFn‘Ebony14/04/03DSH8yrFn‘Ebony14/04/03DSH8yrFn‘EbonyStartedeatingvoluntarily14/04/03 開始愿意采食Stopi.v.fluids 停止靜脈輸液100gRabbitWhiskasBID 100g偉嘉兔肉貓糧，BID3unitsPZIinsulinoncedailys.c. 3單位PZI(長(zhǎng)效型)胰島素,１天１次，s.c.Clavulanatepotentiatedamoxycillinp.o. 克拉維酸+阿莫西林p.o.15/04/03DSH8yrFn‘Ebony17/04/03MANAGEMENTOF

DIABETICKETOACIDOSIS

糖尿病酮酸中毒的處理Intravenousfluidtherapy 靜脈輸液Insulintherapy 胰島素治療Hypokalaemia 低鉀血癥Hypophosphataemia 低磷血癥Acidosis 酸中毒Antibiosis 抗生素MANAGEMENTOF

DIABETICKETOACIDOSIS

糖尿病酮酸中毒的處理Intravenousfluidtherapy 靜脈輸液Normalsalineinitially 開始用生理鹽水ThenalternatewithHartmann’s 然后轉(zhuǎn)用Hartmann液Givefluidsaggressively 大量給予液體Checkurineoutput 檢查尿排量MeasureCVP 測(cè)量中心靜脈壓MANAGEMENTOF

DIABETICKETOACIDOSIS

糖尿病酮酸中毒的處理Insulintherapy胰島素治療Low-doseinsulininfusion 低劑量胰島素輸注Intravenousbolustechnique靜脈內(nèi)團(tuán)注法INSULINPREPARATIONS

胰島素製劑LOW-DOSEINSULININFUSION

低劑量胰島素輸注5unitsofneutralinsulinin500mlofHartmann’s 5單位中性胰島素于500mlHartmann液中Infuse0.1unit/kg/hour(20drops=1ml) 輸0.1單位／kg/h(20滴＝1毫升）Monitorbloodglucoseevery2hours 每2小時(shí)監(jiān)測(cè)血糖水平Stopinfusionwhenbloodglucose<10mmol/l 血糖水平達(dá)10mml/l時(shí)，停止輸液Changetolongeractinginsuline.g.PZI,lente 改為長(zhǎng)效的胰島素，如PZI,lenteINTRAVENOUSBOLUSTECHNIQUE

靜脈內(nèi)注射技術(shù)1unitofneutralinsulinperkg 1單位/kg，中效型胰島素1/4dosegivenIV,3/4givenIM 1/4

劑量靜脈注射，

3/4

肌注Monitorbloodglucoseevery2hours 每２小時(shí)監(jiān)測(cè)血糖Repeatdoseevery4-6hoursuntilbloodglucose<10mmol/l 每4－6小時(shí)重復(fù)此劑量，直到血糖水平<10mmol/l

Changetolongeractinginsuline.g.PZI,lente 改為長(zhǎng)效的胰島素，如PZI,lenteHYPOKALAEMIA低鉀血癥PlasmaKfallsasrenalfunctionimproves 隨腎功能改善，血Ｋ濃度會(huì)下降Kmovesintocellswithglucoseduetoinsulintherapy 胰島素治療時(shí)，Ｋ＋隨葡萄糖進(jìn)入細(xì)胞Hypokalaemiaislesslikelytooccurwithlow-doseinsulininfusion 低劑量胰島素輸注時(shí)很少發(fā)生低鉀血癥Clinicalsignsofhypokalaemiainclude:muscleweakness,intestinalatony,abdominaldistension,andcardiacarrhythmias 臨床上低鉀血癥表現(xiàn)癥狀為：肌無(wú)力，腸遲緩，腹部膨脹，及心律不齊HYPOPHOSPHATAEMIA

低磷酸血癥Phosphatemovesinthesamewayaspotassium 磷酸鹽以同樣的方式進(jìn)入細(xì)胞Insulintherapyandcorrectionofthemetabolicacidosismaycauseadramaticintracellularshiftofphosphate 胰島素療法和矯正代謝性酸中毒可造成磷酸鹽顯著的胞內(nèi)轉(zhuǎn)移Potentiallyseverehypophosphataemia(<0.5mmol/l)mayoccurwithin12-24hours 在12－24小時(shí)內(nèi)可能會(huì)發(fā)生嚴(yán)重的低磷酸血癥HYPOPHOSPHATAEMIA

低磷酸血癥Severehypophosphataemiamaybeasymptomatic 嚴(yán)重的低磷酸鹽血癥可能無(wú)癥狀Butmaycauselifethreateninghaemolyticanaemia 但可能造成致命性的溶血性貧血Weakness 無(wú)力Ataxiaandseizures 共濟(jì)失調(diào)和癲癇ACIDOSIS酸中毒Bicarbonateisnotnecessaryprovidedrenalfunctionisre-establishedandmaintained 只要腎功能可重建并得到維持無(wú)需用碳酸氫鹽Bicarbonateshouldonlybeusediftheacidosisislife-threatening 只在酸中毒有致命危險(xiǎn)時(shí)才用碳酸氫鹽Rapidcorrectionoftheacidosiscanleadto: 迅速矯正酸中毒可導(dǎo)致：metabolicalkalosis代謝性堿中毒tissueanoxia組織缺氧paradoxicalacidosisintheCSF,突發(fā)性腦脊髓液酸中毒ANTIBIOSIS抗生素Infectionisacommonprecipitatingfactorforketoacidosis 感染是酮酸中毒的一個(gè)常見易感因素Diabeticpatientsinintensivecarearepronetoinfection

重癥監(jiān)護(hù)室中的糖尿病患畜易感Providebroadspectrumantibioticcover 應(yīng)用廣譜抗生素FELINEDIABETESMELLITUS

貓?zhí)悄虿ffects1in300cats 發(fā)病率1/300‘Glucosetoxicity’maybereversible 葡萄糖毒性可以是可逆的Mayrespondtodietandoralhypoglycaemics 飲食管理和口服的降血糖藥劑可能有效Exogenousinsulintendstobemetabolisedmorequicklyinthecatthaninthedog 外源性胰島素在貓中比犬中代謝速度更快Profoundhypoglycaemiamaygounnoticed 可能未察覺到嚴(yán)重的低血糖癥ORALHYPOGLYCAEMICDRUGS

口服降血糖藥Impairintestinalglucoseabsorption 小腸對(duì)葡萄糖吸收不良a-glucosidaseinhibitor(acarbose) α－葡糖苷酶抑制劑（阿卡玻糖）Promoteinsulinrelease 促進(jìn)胰島素釋放Glipizide2.5-5.0mgBID 格列吡嗪2.5-5.0mgBIDInhibithepaticglucoseproduction 抑制肝糖生產(chǎn)Metformin2-10mg/kgBID 二甲雙呱2-10mg/kgBIDInsulinsensitizingdrugs 胰島素增敏劑Troglitazone,vanadium,chromium 曲格列酮，釩，鉻GLIPIZIDE(Glibenese?)格列吡嗪Sulphonylurea 硫酰脲類Mostappropriatecases: 適合病例Obesecats 肥胖貓Mildlyaffected,otherwisehealthycats?

癥狀輕微無(wú)其他問(wèn)題的貓Recenthistoryofdiabetogenicdrugs? 最近有使用提高血糖的藥物Usecontra-indicatedin: 禁忌癥CatswithDKA，有酮酸血癥的貓Emaciatedordebilitatedcats瘦弱貓Catswithconcurrentdisease同時(shí)患有其他疾病的貓GLIPIZIDE(Glibenese?)格列吡嗪Initialdose2.5mgBIDwithfoodfor2weeks 拌料食用2周，起始劑量：2.5mg，BIDCheckliverenzymesbeforeandafter1and2weeks 喂食前和喂食后1－2周檢查肝酶Ifnobeneficialresponseincreaseto5mgBID 若療效不明顯，則增加劑量至5mg，BIDRe-assessat2weeklyintervals 2周后再次評(píng)估Ceaseifnobeneficialresponseafter12weeks 服用12周仍無(wú)效果，則停用GLIPIZIDE(Glibenese?)格列吡嗪Usuallywelltolerated 通常接受度良好Occasionallycausesvomiting,hepatotoxicityorjaundice 偶爾有嘔吐，肝毒性或黃疸現(xiàn)象出現(xiàn)Ifgoodcontrolachieved,graduallytaperdoseandeventuallyceaseuse 如果病情控制較好，可逐漸減少劑量， 直到停藥STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩(wěn)定Requiresunderstandingbytheowner 需要主人的理解Requiresaregulardailyroutine 需要常規(guī)治療(每日)Diabetesinthecatmaybeinsulin-dependentornotandmaybepermanentortemporary 貓的糖尿病可能屬胰島素依賴性或非胰島素依賴性，也可能為永久性的或暫時(shí)的Homeversushospitalisationforinitialstabilisation

在家治療或住院以達(dá)到初步的穩(wěn)定STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩(wěn)定Avoidincreasinginsulindosetooquickly 避免過(guò)快增加胰島素劑量Allowatleast3daysforfullresponsetoinsulin 至少需要3天，患畜才會(huì)對(duì)胰島素產(chǎn)生完全反應(yīng)Insulinrequirementsareincreasedbyinfection,concurrentdisease,oestrus,pregnancyandketoacidosis 感染、現(xiàn)有疾病、發(fā)情期，妊娠和酮酸中毒時(shí)胰島素需要量增加Entirequeensshouldbespayed 雌貓需要施行結(jié)育手術(shù)Hypoglycaemiccrisesshouldbeexplainedtoowner 必須向主人解釋有低血糖危象INSULINTHERAPY 胰島素治療Typeofpreparation 準(zhǔn)備的類型Routeofadministration 注射方法Doseofinsulin劑量Timingofinjection時(shí)間Frequencyofadministration次數(shù)INSULINPREPARATIONS

胰島素的配制類型STRUCTUREOFINSULIN

胰島素結(jié)構(gòu)BOVINEINSULINegInsuvetlente?(ScheringPlough)isHOMOLOGOUStofelineinsulin 牛胰島素和貓胰島素是同源的PORCINEINSULINegCaninsulin?(Intervet)is

HETEROLOGOUStofelineinsulindueto2aminoaciddifferencesintheAchain豬胰島素與貓胰島素是異源的，因?yàn)椋伶溣校矀€(gè)氨基酸不同ACHAINBCHAINACHAINBCHAINPROINSULININSULINC-peptidessssssss肽DIETARYMANAGEMENT

飲食管理Consistencyofthediet 保持飲食一致性Compositionofthediet 飲食的成分Fibrecontent 含纖維Caloriecontentandcaloricdensity 卡路里含量Feedingschedule 定時(shí)喂養(yǎng)DIETARYMANAGEMENT

飲食管理Consistencyofthediet 保持飲食一致性Compositionofthediet 飲食的成分Fibrecontent 含纖維Caloriecontentandcaloricdensity 卡路里含量Feedingschedule 定時(shí)喂養(yǎng)STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩(wěn)定

Standardroutineforcats 貓的標(biāo)準(zhǔn)治療方法InjectPZIinsulinsubcutaneously 皮下注射PZI胰島素Feed1/2thedailyration30minuteslater

注射后30分鐘搬料喂食1/2的日量Secondfeed6-8hoursafterinjection

注射后6-8小時(shí)拌料喂食另1/2的日量Keepdailyroutineincludingexerciseconstant 每日程序需一致，包括固定時(shí)間運(yùn)動(dòng)Notit-bitsorscavenging不給零食及人的食物STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩(wěn)定Monitorbloodand/orurineglucose 監(jiān)測(cè)血糖/尿糖水平Monitorfluidintake 觀察水份攝取量Aimfortraceofglucoseinmorningurinesampleorbloodglucosebetween5-10mmol/l 清晨監(jiān)測(cè)尿糖/血糖水平在5-10mml/l之間Bloodglucoseshouldbelowestbeforethesecondfeed,urineglucoseatthattimeshouldbenegative 第二次餵食前血糖水平應(yīng)最低，此時(shí)尿糖測(cè)檢測(cè)應(yīng)呈陰性IDEALDIABETICCURVE

理想的胰島素曲線InsulinFeedMONITORINGTHEIABETICPATIENT

糖尿病患畜的監(jiān)測(cè)Fluidintake 水份攝取Bodyweight 體重Urineglucose/ketones 尿糖/酮Bloodglucose 血糖Serumfructosamine 血清果糖胺Glycosylatedhaemoglobin 硫化血紅蛋白DIABETICRECORD糖尿的記錄BLOODSAMPLINGTHEDIABETICPATIENTATHOME

糖尿病患畜在家中取血樣GLUCOSEMEASUREMENTS

血糖測(cè)量1243COMPARISONOFETERWITHBECKMANASTRA

血糖測(cè)量的比較貝克曼測(cè)量器SERUMFRUCTOSAMINE

血清果糖胺Formedbyanon-enzymaticreactionbetweenglucoseandproteins,mainlyalbumin 葡萄糖和蛋白質(zhì)(主要是白蛋白)轉(zhuǎn)換產(chǎn)生的非酶反應(yīng)物質(zhì)Thereactionisirreversible 反應(yīng)是不可逆的Thustheconcentrationoffructosaminedependsondurationandextentofthehyperglycaemiaandthehalf-lifeofalbumin因此，果糖胺的濃度取決于高血糖的持續(xù)時(shí)間和程度，以及白蛋白的半衰期SERUMFRUCTOSAMINE

血清果糖胺Thehalf-lifeofalbuminisabout8days,thereforeserumfructosaminereflectstheaveragebloodglucoseconcentrationovertheprevious2-3weeks 白蛋白的半衰期約8天，因此血清果糖胺反應(yīng)了2-3周前的平均血糖濃度Itisnotaffectedbyacutechangesinbloodglucoseconcentrationse.g.feeding,sedation,stress 它不受血糖濃度暫時(shí)改變的影響，如飲食、鎮(zhèn)靜劑、應(yīng)激INVESTIGATIONOF

THEUNSTABLEDIABETIC

不穩(wěn)定性糖尿病的診斷Diet 飲食Administrationofinsulin 使用胰島素Correctdoseofinsulin 胰島素正確使用劑量Storageofinsulin 胰島素儲(chǔ)備Urinetesting 尿檢Infection,concurrentdisease,oestrus,pregnancy 感染，伴發(fā)疾病，發(fā)情期，妊娠Ketoacidosis 酮酸中毒Check:檢查INVESTIGATIONOF

THEUNSTABLEDIABETIC

不穩(wěn)定性糖尿病的診斷Checkthediabeticrecord 檢查糖尿病記錄表Monitorbloodglucoseevery2hoursfora24hourperiod 24小時(shí)內(nèi)每2小時(shí)監(jiān)測(cè)一次血糖水平MiniMedcontinuousglucosemonitoringsystem(CGMS)

MiniMed持續(xù)性血糖監(jiān)測(cè)系統(tǒng)(CGMS)Plotgraphoftheresults

畫圖表示結(jié)果TheMiniMedcontinuousglucosemonitoringsystem

MiniMed－血糖監(jiān)測(cè)體系TheMiniMedCGMSwasdesignedforuseinhumandiabeticpatientstominimise: 此儀器被設(shè)計(jì)用于人類糖尿病患以減低：theinconvenienceandfortofrepeatedbloodsampling 重復(fù)采集血液樣本的不便和不適Thepossibilityofmissingapeakortroughinglucosewhichoccursbetween2samplingtimes 錯(cuò)過(guò)常發(fā)生在2次取樣之間的葡萄糖波峰/谷的可能性，MiniMedtechnology

MiniMed技術(shù)TheMiniMedsensormeasuresinterstitialfluidglucoseautomaticallyevery5minutes

MiniMed感受器可自動(dòng)測(cè)量組織間質(zhì)內(nèi)體液葡萄糖（每5分鐘1次）濃度Thesensorisanelectrode,coatedinglucoseoxidase,andthecurrentacrossitisproportionaltothesurroundingglucoseconcentration 感受器是一個(gè)包被葡萄糖氧化酶的電極，產(chǎn)生的電流與葡萄糖濃度成正比Thesubcutaneoussensorisattachedtoasmallpagersizedmonitorandthepatient‘wears’themonitoronaharnessforupto72hours 此皮下感受器接到像BP機(jī)大小的監(jiān)測(cè)器，患畜必須“穿”上置于固定袋內(nèi)監(jiān)測(cè)器達(dá)72小時(shí)Dataaredownloadedtoalaptopcomputerforanalysisduringoraftertherecordingperiod 在記錄期間或記錄后，將數(shù)據(jù)輸入電腦進(jìn)行分析SettinguptheMiniMedsensor

安裝MiniMed感受器Thepatient’sbloodglucosemustbebetween2.2and22.2mmol/latthetimethesensorisinitiated 在感受器誘啟動(dòng)時(shí)，患畜的血糖必須在2.2-22.2mmol/l之間Thesensorisimplantedinsubcutaneoustissueusingaspringloadeddevice 用帶有彈簧的裝置將感受器植入皮下組織TheMinimedsystemCGMSvseter

CGMS（血糖檢測(cè)體系）vs葡萄糖測(cè)量?jī)xSampleMiniMedData

MiniMed樣本數(shù)據(jù)CGMSday-to-dayvariability

CGMS每日變異度CGMSlowerlimitofsensor

CGMS的低限制性CGMSbenefits