MichaelE.HerrtageUniversityofCambridgeMANAGEMENTOFFELINEDIABETESMELLITUS貓糖尿病的治療DIABETESMELLITUS

糖尿病Astateofchronichyperglycaemiacausedbyabnormalitiesofcarbohydrate,proteinandlipidmetabolism,whichmayeitherbeduetoanabsolutelackofinsulinortofactorsthatopposeitsaction.一種慢性高血糖癥，由碳水混合物、蛋白質和脂肪代謝異常造成，原因有：胰島素絕對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成年發病型糖尿病Type3diabetes3型糖尿病Secondarycausesofdiabetes繼發性糖尿病DIABETESMELLITUS

POSSIBLEAETIOLOGIES

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

2型糖尿病的發病機理Beta-celldysfunction

β細胞功能不全Insulinresistance

胰島素不敏感Obesity

肥胖Chronichyperglycaemia

慢性高血糖癥Environmentalfactors

環境因素Obesityandphysicalexercise

肥胖和運動Diet

飲食PATHOGENESISOFTYPE2DIABETESMELLITUS

2型糖尿病的發病機理Isletamyloidosis

胰島淀粉樣變性Glucoseandlipidtoxicity

葡萄糖和脂毒性Beta-cellexhaustion

β細胞耗竭PATHOPHYSIOLOGYOF

DIABETESMELLITUS

糖尿病的病理生理學Relativeorabsolutedeficiencyofinsulin

胰島素相對或絕對不足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高血糖糖尿滲透性利尿：水、電解質流失CLINICALSIGNSOF

DIABETESMELLITUS

糖尿病的臨床表現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CortisolGrowthHormone可的松生長激素Catecholamines兒茶酚胺Lipolysis脂解Ketogenesis酮生成Ketonaemia酮(酸)血癥ReducedglucoseUtilisation降低糖利用Hyperglycaemia高血糖Glycogenolysis糖原分解ReducedinsulinRelease胰島素分泌減少Gluconeogenesis糖原異生Increasedglucagon:insulinRatio肝糖胰島素比值增高CLINICALSIGNSOFDIABETICKETOACIDOSIS

糖尿病酮酸中毒的臨床表現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/同時發生的疾病03/861Domesticshorthairedcat8yrFn‘Ebony’短毛家貓，8月齡DSH8yrFn‘EbonyLivedinGermanyuntil1996 在德國住到1996年OwnedbyaG.P. 主人：G.PPolydipsicfor6weeks 煩渴達6周之久Progressivelossofappetitefor2weeks 食欲進行性下降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 無法站立，但對檢查有反應Mucousmembranesdryandjaundiced 可視粘膜干燥，有黃疸Capillaryrefillslow 毛細血管充盈減慢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 注射器喂飼Hillsa/d處方糧，每4小時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FELINEDIABETESMELLITUS

貓糖尿病Affects1in300cats 發病率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品可能有效Exogenousinsulintendstobemetabolisedmorequicklyinthecatthaninthedog 外源性胰島素在貓中比犬中代謝速度更快Profoundhypoglycaemiamaygounnoticed 可能未觀察到嚴重的低血糖癥ORALHYPOGLYCAEMICDRUGS

口服降血糖藥Impairintestinalglucoseabsorption 小腸對葡萄糖吸收不良a-glucosidaseinhibitor(acarbose) α－葡糖苷酶抑制劑（阿卡玻糖）Promoteinsulinrelease 促進胰島素釋放Glipizide2.5-5.0mgBID 格列吡嗪2.5-5.0mgBIDInhibithepaticglucoseproduction 抑制肝糖生產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，無其他問題的貓Recenthistoryofdiabetogenicdrugs? 最近有服用致糖尿病（提高血糖）的藥物史Usecontra-indicatedin: 禁忌癥CatswithDKA，有糖尿病酮酸中毒的貓Emaciatedordebilitatedcats 瘦弱貓Catswithconcurrentdisease 同時患有其他疾病的貓GLIPIZIDE(Glibenese?)格列吡嗪Initialdose2.5mgBIDwithfoodfor2weeks 拌料食用2周，起始用量：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周后再次評估Ceaseifnobeneficialresponseafter12weeks 服用12周仍無效果，則停用GLIPIZIDE(Glibenese?)格列吡嗪Usuallywelltolerated 通常接受度良好Occasionallycausesvomiting,hepatotoxicityorjaundice 偶爾有嘔吐，肝毒性或黃疸現象出現Ifgoodcontrolachieved,graduallytaperdoseandeventuallyceaseuse 如果病情控制較好，可逐漸減少劑量， 直到停藥STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩定Requiresunderstandingbytheowner 需要主人的理解Requiresaregulardailyroutine 需要常規治療(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的Homeversushospitalisationforinitialstabilisation 在家治療或住院治療以達到初步穩定STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩定Avoidincreasinginsulindosetooquickly 避免過快增加胰島素劑量Allowatleast3daysforfullresponsetoinsulin 患貓對胰島素完全產生作用至少需要3天Insulinrequirementsareincreasedbyinfection,concurrentdisease,oestrus,pregnancyandketoacidosis 感染、現有疾病、發情期，妊娠和酮酸中毒時胰島素需要量增加Entirequeensshouldbespayed 雌貓需要施行節育手術Hypoglycaemiccrisesshouldbeexplainedtoowner 必須向主人解釋有低血糖危象INSULINTHERAPY 胰島素治療Typeofpreparation 準備的類型Routeofadministration 注射方法Doseofinsulin劑量Timingofinjection時間Frequencyofadministration次數INSULINPREPARATIONS

胰島素的配制類型STRUCTUREOFINSULIN

胰島素結構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，因為Ａ鏈有２個氨基酸不同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 定時喂養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 定時喂養STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩定

Standardroutineforcats 貓的標準治療方法InjectPZIinsulinsubcutaneously 皮下注射PZI胰島素Feed1/2thedailyration30minuteslater

注射后30分鐘伴料喂食1/2的日量Secondfeed6-8hoursafterinjection

注射后6-8小時拌料喂食另1/2的日量Keepdailyroutineincludingexerciseconstant 每日程序需一致，包含固定時間運動Notit-bitsorscavenging不給零食和人的食物STABILISATIONOFDIABETESMELLITUS

糖尿病病情的穩定Monitorbloodand/orurineglucose 監測血糖/尿糖水平Monitorfluidintake 觀察水份攝取量Aimfortraceofglucoseinmorningurinesampleorbloodglucosebetween5-10mmol/l 清晨監測尿糖/血糖水平在5-10mml/l之間Bloodglucoseshouldbelowestbeforethesecondfeed,urineglucoseatthattimeshouldbenegative 第二次喂食前血糖水平應最低，此時尿糖測檢測應呈陰性IDEALDIABETICCURVE

理想的胰島素曲線InsulinFeedMONITORINGTHEDABETICPATIENT

糖尿病患畜的監測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

血糖測量1243SERUMFRUCTOSAMINE

血清果糖胺Formedbyanon-enzymaticreactionbetweenglucoseandproteins,mainlyalbumin 葡萄糖和蛋白質（主要是白蛋白）轉換產生的的非酶反應物質Thereactionisirreversible 反應是不可逆的Thustheconcentrationoffructosaminedependsondurationandextentofthehyperglycaemiaandthehalf-lifeofalbumin因此，果糖胺的濃度取決于高血糖的持續時間和程度，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改變的影響，如飲食、鎮靜劑、應激INVESTIGATIONOF

THEUNSTABLEDIABETIC

不穩定性糖尿病的診斷Diet 飲食Administrationofinsulin 使用胰島素Correctdoseofinsulin 胰島素正確使用劑量Storageofinsulin 胰島素儲備Urinetesting 尿檢Infection,concurrentdisease,oestrus,pregnancy 感染，伴發疾病，發情期，妊娠Ketoacidosis 酮酸中毒Check:檢查INVESTIGATIONOF

THEUNSTABLEDIABETIC

不穩定性糖尿病的診斷Checkthediabeticrecord 檢查糖尿病記錄表Monitorbloodglucoseevery2hoursfora24hourperiod 24小時內每2小時監測一次血糖水平MiniMedcontinuousglucosemonitoringsystem(CGMS)

MiniMed持續性血糖監測系統(CGMS)Plotgraphoftheresults 圖示結果TheMiniMedcontinuousglucosemonitoringsystem

MiniMed－血糖監測體系TheMiniMedCGMSwasdesignedforuseinhumandiabeticpatientstominimise: 此儀器被設計用于人類糖尿病患以減低：theinconvenienceandfortofrepeatedbloodsampling 重復采集血液樣本的不便和不適Thepossibilityofmissingapeakortroughinglucosewhichoccursbetween2samplingtimes 錯過發生在2次取樣之間的葡萄糖波峰或波谷TheMinimedsystemCGMSvseter

CGMS（持續性血糖檢測體系）vs葡萄糖測量儀SampleMiniMedData

MiniMed樣本數據CGMSday-to-dayvariability

CGMS每日變異度CGMSlowerlimitofsensor

CGMS的低限制性CGMSbenefitsofacontinuouscurve

CGMS連續曲線的效果INSULIN-INDUCEDHYPERGLYCAEMIA

“Somogyioverswing”

胰島素誘發的高血糖癥InsulinFeedRAPIDMETABOLISMOFINSULIN