沈陽市糖尿教育

1、 2 roper-starch global diabetes reportroper-starch, global diabetes report, 2002. 3 roper-starch global diabetes reportroper-starch, global diabetes report, 2002. 4中國 26 major countries in eu 735,000 4 row 138 millionintensive therapy45%pump therapy7%multiple daily injections38%conventional55%wtype

2、2: 134 millionwtype 1: 4 million 2.2 million (1.2 eu) viable market 33. viable market: eu, wp, sa/la: medtronic minimed market share 24%4. roper starch & ihs eu measured countries: italy, germany, france, netherlands, spain, uk (sweden not included)2001 diabetes prevalence: 154 million worldwide

3、 1u.s. 16 million 2conventional59%intensive therapy41%pump therapy15%multiple daily injections26%conventional59%wtype 2: 15 million 3.5 - 4 million insulin usingwtype 1: 1 million1. international diabetes federation (idf)2. american diabetes association (ada)united states: 1 million20% other80% medt

4、ronic minimed6全球糖尿病患者的人數(shù)預(yù)計將從2000年的1.51億升至2025年3億，增長率可達(dá)到99%。evolution of diabetes management technologiesinsulin injectionsurine test stripsglucose sensorartificialpancreas1999197819221900s1977urine tasting1776bg metersinsulin pump therapy泵的發(fā)展歷史9first pump studyyale ccrc 1979yale university10持續(xù)皮下胰島素輸

5、注法持續(xù)皮下胰島素輸注法 ( csii )continuous subcutaneous insulin infusion程序化界面11儲液器電池12胰島素泵輸注管道系統(tǒng)短針快速分離器13皮下軟管埋放位置14 美國選美冠軍尼可爾.約翰森15 如何攜帶胰島素泵16游泳與洗浴17胰島素泵特點：胰島素泵特點：連續(xù)微量注射短效胰島素連續(xù)微量注射短效胰島素18fpolonsky ks et al. n engl j med. 1988;318:1231-123906000600time of day20406080100 bldnormal daily insulin profileb=breakfas

6、t; l=lunch; d=dinner060008001800120024000600 u/ml19胰島素泵優(yōu)勢基礎(chǔ)率基礎(chǔ)率胰腺釋放胰腺釋放餐前劑量餐前劑量胰島素泵采用持續(xù)微量分泌的胰島素泵采用持續(xù)微量分泌的基礎(chǔ)率基礎(chǔ)率與與三餐前大劑量三餐前大劑量結(jié)合的輸注方式模擬結(jié)合的輸注方式模擬生理性生理性胰島素分泌。胰島素分泌。pharmacokinetic advantages:csii vs mdifuses only regular insulinmore predictable absorption than with modified insulins (variation 3% vs 52

7、%*)fuses one injection site for 2 to 3 daysreduces variations in absorption due to site rotationfeliminates most of the subcutaneous insulin depotfprogrammable insulin delivery allows closest match with physiologic needs* lauritzen: diabetologia 1983; 24:326-921胰島素泵使胰島素精確釋放和良好的吸收胰島素泵使胰島素精確釋放和良好的吸收ma

8、intain normal or near normal glycemiaavoid short-term crisisminimize long-term complications01224hoursgoals of insulin therapynormal pancreasfinsulin is released in response to varying blood glucose levels0.6insulintime24f只使用短效胰島素只使用短效胰島素與中長效胰島素相比，其吸收更可預(yù)與中長效胰島素相比，其吸收更可預(yù)測測 (變異率僅為變異率僅為 3% )f減少因為改換部位所造

9、成的吸收變異減少因為改換部位所造成的吸收變異f消除胰島素在皮下的蓄積消除胰島素在皮下的蓄積f根據(jù)生理需要設(shè)計胰島素的輸注根據(jù)生理需要設(shè)計胰島素的輸注* lauritzen: diabetologia 1983; 24:326-9f提高糖尿病控制水平提高糖尿病控制水平 hba1c水平 低血糖的發(fā)生f改善生活質(zhì)量改善生活質(zhì)量f減少醫(yī)療費用支出減少醫(yī)療費用支出fintermediate & regular insulinlack of consistency between insulin effect causes large variations in bg levelsflexibil

10、ity is a difficult challengeinjections2 injections per day27glucose profile analysis (72 hrs)0 05050100100150150200200250250300300350350400400glucose concentration (mg/dl)glucose concentration (mg/dl) 12:0012:00midnightmidnight 12:0012:00midnightmidnight 12:0012:00midnightmidnight8:00am8:00am 4:00pm

11、4:00pm8:00am8:00am 4:00pm4:00pm8:00am8:00ammdimdicsiicsiicsii vs. mdi28調(diào)查人nhba1c (%)觀察時間 (yrs)bode (96)557.73.1dcct (95)1246.84.5wredling (93)407.64.0-5.62930ukpds: bmj:321:405-412降低 hba1c水平的好處hba1c平均值每下降1%f與糖尿病相關(guān)的死亡下降21%f心梗發(fā)生率下降14%f微血管并發(fā)癥減少37%u k p d s結(jié)論結(jié)論135791113156789101112視網(wǎng)膜病視網(wǎng)膜病變變腎病腎病神經(jīng)病變神經(jīng)病變

12、微血管病微血管病變變風(fēng)險相關(guān)性風(fēng)險相關(guān)性hba1cskyler: endo met cl n am 1996糖尿病并發(fā)癥風(fēng)險與hba1c水平的相關(guān)性數(shù)據(jù)來自dcct potential chroniccomplications of elevated hba1ccontrol33提高糖尿病控制水平:減少低血糖的發(fā)生率13822263936050100150pre csii1 yr2 yr3 yr4 yr- 用泵治療用泵治療-bode et al: diabetes care 1996; 19:324-7n=553435csii: less severe hypoglycemia0 010102

13、02030304040505060607070usual careusual caremdimdicsii (gen)csii (gen)csii (study)csii (study)white et al., journal of pediatric endocrinology and metabolism 2000; 13(suppl 4):1220.severe hypo events in children (2-16 yrs)severe hypo events in children (2-16 yrs)rate per 100 pt years36csii reduces hy

14、poglycemiachantelau, e et al., diabetologia 1989, 32:421-6.bode, bw et al., diabetes care 1996, 19:324-7.boland, ea et al., diabetes care 1999, 22:1779-84.chase hp, et al., pediatrics 2001, 107:351-6.0 02020404060608080100100120120140140pre-pumppre-pumppost-pumppost-pumpn=55mean age 42n=107mean age

15、36n=116mean age 29n=25mean age 14n=56mean age 17events per hundred patient yearsbode rudolph chanteleau boland chase37減少低血糖發(fā)生的好處f降低糖尿病腦病的風(fēng)險降低糖尿病腦病的風(fēng)險f降低意外事件和死亡的風(fēng)險降低意外事件和死亡的風(fēng)險f提高對低血糖的敏感性提高對低血糖的敏感性38采用泵治療的患者可以證明采用泵治療的患者可以證明:f極少的焦慮感和沮喪感極少的焦慮感和沮喪感f更強的家庭凝聚力更強的家庭凝聚力f改善人際關(guān)系改善人際關(guān)系f顯著減少低血糖的不適顯著減少低血糖的不適f對于青少年

16、患者，減少了被冠以對于青少年患者，減少了被冠以“糖尿病糖尿病”所帶來的困難所帶來的困難39泵治療改善健康狀況惡化惡化2%無變化無變化16%改善改善82%association for insulin pump therapy, diabetes 1991:40:#1807n=886患者自我評價結(jié)果40$108,400$130,700$167,800$207,300泵治療泵治療mdi常規(guī)療法常規(guī)療法常規(guī)療法普通人群常規(guī)療法普通人群fhba1c7%8%9%10%f間接支出間接支出0$21,400$44,900$61,700f直接支出直接支出$108,400$109,300$122,900$145,

17、600directcostsdirectcostsdirectcostsdirectcostsassumption: patients follow typical scenario. dollars are expected net present valueassumption: patients follow typical scenario. dollars are expected net present valuesource: quattro csii economic analysis model 1999source: quattro csii economic analys

18、is model 1999美國和加拿大美國和加拿大29個醫(yī)學(xué)中心個醫(yī)學(xué)中心對對1441個個1型糖尿病人的近型糖尿病人的近10年前瞻性研究。年前瞻性研究。常規(guī)治療組常規(guī)治療組 730例例強化治療組強化治療組 711例例34%長期應(yīng)用胰島素泵長期應(yīng)用胰島素泵 （ csii ）其余每日多次胰島素注射（其余每日多次胰島素注射（ mdi）dcct pump usageat conclusion of studydcct: diabetes care 1995; 18:361-376unknown2%pump42%mdi56%60%how diabetes specialists treat their

19、own type 1 diabetesaade membershipn=229industry estimates at time of survey (9/98); graff: diabetes educator 2000; 46:460-4676%52%injectionspump therapycolor key:n=293ada membership目前進行泵治療的比例繼續(xù)繼續(xù)97%中止中止3%n = 165平均持續(xù)時間平均持續(xù)時間= 3.6 years平均中止比例平均中止比例 1%/yrbode, et al.: diabetes 1998; 47 (suppl 1): 392.r

20、elative risk of progression of diabetic complications1dcct research group. n engl j med. 1993;329:977986.2dcct research group. diabetes. 1995;44:968983.3ohkubo y, et al. diabetes res clin pract. 1995;28:103117.4uk prospective diabetes study group (ukpds) 33: lancet. 1998;352:837853.hba1cretinopathyn

21、ephropathyneuropathymacrovascular diseasedcct1,29% to 7% 63% 54% 60% 41%*kumamoto39% to 7% 69% 70%ukpds48% to 7% 1721% 2433% 16%*not statistically significant in intervention analysis.46the factscomplicationsblindnessalbuminuriaend-stage renal disease 24% neuropathylower-limb amputation 7% conventio

22、nal therapy34%46%57%intensive therapy20%15%7%31%4%event cost$53,659$26,894obrien ja, et al., diabetes care 1998, 21:1122-1128.cumulative incidence of diabetes related complications type 1 aged 70 yr.476,6008,70011,40015,00020,00026,50035,00043,00060,00081,000100,000010,00020,00030,00040,00050,00060,

23、00070,00080,00090,000100,000# of patients9091929394959697989900nicole johnson24ys,1-dm5ys.486,6008,70011,40015,00020,00026,50035,00043,00060,00081,000120,000162,000050,000100,000150,00090919293949596979899200020014950induction of long-term glycemic control in newly diagnosed type 2 diabetic patients

24、 by transient intensive insulin treatment hasan ilkova, md1997hebrew university hadassah medical center , jerusalem , israeldiabetes care 1997;20:1353-1356515253研究設(shè)計研究設(shè)計治療治療: :用胰島素泵用胰島素泵csiicsii治療兩周。治療兩周。 后續(xù)治療后續(xù)治療: :繼續(xù)進行常規(guī)鍛煉繼續(xù)進行常規(guī)鍛煉 + + 飲食控制，飲食控制，出院后的第出院后的第1 1、2 2、4 4周和每月監(jiān)測餐前、餐后周和每月監(jiān)測餐前、餐后2 2小小時血糖，胰

25、島素水平、時血糖，胰島素水平、c c肽值。同時，每月檢測肽值。同時，每月檢測hba1chba1c。54研究設(shè)計研究設(shè)計評價標(biāo)準(zhǔn)評價標(biāo)準(zhǔn)非常好非常好 fbg 7.8mmol/l fbg 7.8mmol/l 餐后餐后2 2小時血糖小時血糖 10mmol/l 10mmol/l 較好較好 fbg 8.9mmol/l fbg 8.9mmol/l 餐后餐后2 2小時血糖小時血糖 11.1mmol/l7.0% 反復(fù)出現(xiàn)低血糖反復(fù)出現(xiàn)低血糖 預(yù)防預(yù)防/延緩慢性并發(fā)癥發(fā)生延緩慢性并發(fā)癥發(fā)生 黎明現(xiàn)象黎明現(xiàn)象 胃輕癱胃輕癱 孕前及孕婦孕前及孕婦 生活不規(guī)律生活不規(guī)律 運動量多的人運動量多的人 64泵治療基本步驟f

26、選擇病人的標(biāo)準(zhǔn)f準(zhǔn)備工作f開始帶泵f精確調(diào)整f預(yù)防急性并發(fā)癥f后續(xù)工作65選擇病人的標(biāo)準(zhǔn)f依從性f渴望改善血糖的控制情況f渴望過更正常的生活f有家庭成員的支持f期望值實現(xiàn)f視力問題，能夠自己操作。tanenberg: the insulin pump book, minimed 1995: 21-3066準(zhǔn)備工作f自查血糖自查血糖(smbg)，堅持記錄，堅持記錄f收住院（內(nèi)分泌醫(yī)生、護士）收住院（內(nèi)分泌醫(yī)生、護士）f化驗殘余胰島化驗殘余胰島細(xì)胞功能，指導(dǎo)胰島素泵治療細(xì)胞功能，指導(dǎo)胰島素泵治療f化驗肝功能，腎功能?；灨喂δ埽I功能。f原來應(yīng)用中、長效、預(yù)混胰島素者改為四次強原來應(yīng)用中、長效、預(yù)

27、混胰島素者改為四次強化方案?；桨?。67開始帶泵f設(shè)置泵的參數(shù)設(shè)置泵的參數(shù)f連接泵連接泵f設(shè)定血糖控制目標(biāo)設(shè)定血糖控制目標(biāo)2型糖尿病血糖控制目標(biāo) 良好良好 一般一般 不良不良血漿葡萄糖血漿葡萄糖mmol/l 空腹：空腹： 4.4 - 6.1 7.0 7.0 非 空 腹 ：非 空 腹 ： 4 . 4 - 8 . 0 10.0 10.0糖化血紅蛋白糖化血紅蛋白 7.5 亞太地區(qū)2型糖尿病治療指南第三版首先確定血糖控制目標(biāo)f為每個病人確定個人的血糖控制目標(biāo)。為每個病人確定個人的血糖控制目標(biāo)。f成年病人的一般控制目標(biāo)：成年病人的一般控制目標(biāo)： 餐前：餐前： 4.4- 6.5mmol/l4.4- 6.5

28、mmol/l 餐后餐后2 2小時：小時： 8-8.5mmol/l5mmol/l 5mmol/l f若反復(fù)出現(xiàn)低血糖，適當(dāng)提高控制目標(biāo)：若反復(fù)出現(xiàn)低血糖，適當(dāng)提高控制目標(biāo)： 餐前：餐前： 100-160mg/dl (5.6-8.9mmol/l)100-160mg/dl (5.6-8.9mmol/l)f若懷孕，適當(dāng)降低目標(biāo)血糖值：若懷孕，適當(dāng)降低目標(biāo)血糖值： 餐后：餐后： 120mg/dl (6.7mmol/l) 120mg/dl (6.7mmol/l)安裝胰島素泵的主要參數(shù)f每日胰島素總量每日胰島素總量f基礎(chǔ)率基礎(chǔ)率f三餐前大劑量三餐前大劑量71一日胰島素總量一日胰島素總量f根據(jù)用泵前的用量計算

29、根據(jù)用泵前的用量計算（已經(jīng)注射胰島素的病人）（已經(jīng)注射胰島素的病人）一日總量一日總量用泵前胰島素用量用泵前胰島素用量（707080%80%）f根據(jù)體重計算根據(jù)體重計算 (未用胰島素的病人）未用胰島素的病人）一日總量體重一日總量體重0.440.447250%50%basalbasalpre-pump dosepre-pump dosepump starting dosepump starting dose(70-75% of pre-pump dose)(70-75% of pre-pump dose)50%50%bolusbolus establishing starting basal an

30、d bolus doses western protocolpre-pumppre-pumptotal daily dosetotal daily dosepumppumpstarting dosestarting dosetotaltotalbasal dosebasal dosetotaltotalbolusbolusdosedosereduce by 25%reduce by 25%hourlyhourlybasalbasalrateratebreakfastbreakfastbolusboluslunchlunchbolusbolusdinnerdinnerbolusbolus50%5

31、0%50%50%dividedividedividedividebyby24 hours24 hours20%20%10%10%20%20% establishing starting basal and bolus doses western protocol40 units30 units15 units15 units0.6 u/hr6 units3 units6 unitspre-pumppre-pumptotal daily dosetotal daily dosetotaltotalbasal dosebasal dosetotaltotalbolusbolusdosedoseho

32、urlyhourlybasalbasalrateratebreakfastbreakfastbolusboluslunchlunchbolusbolusdinnerdinnerbolusbolus30- 40%30- 40%60-70%60-70%dividedividedividedividebyby24 hours24 hours20%20%10%10%20%20% establishing starting basal and bolus doses eastern protocol75f從單一基礎(chǔ)率開始，將基礎(chǔ)率總量平均分配到從單一基礎(chǔ)率開始，將基礎(chǔ)率總量平均分配到2424小時內(nèi)小時內(nèi)

33、f根據(jù)夜間的血糖監(jiān)測結(jié)果判斷是否要增加第二根據(jù)夜間的血糖監(jiān)測結(jié)果判斷是否要增加第二個基礎(chǔ)率。個基礎(chǔ)率。f臨床一般分三至五段：臨床一般分三至五段：0 0：00-400-4：00am00am； 4 4：00am-800am-8：00am00am；8 8：00am-12pm00am-12pm。根據(jù)胰島素總量計算起始基礎(chǔ)量起始基礎(chǔ)量 日總量日總量 50 50根據(jù)體重計算起始基礎(chǔ)量體重起始基礎(chǔ)量體重 0.22 0.2276基礎(chǔ)率的精確調(diào)整f檢查三餐前、三餐后、睡前、12am和 2-4am的血糖f停用一餐，查禁食時的血糖 例：調(diào)整夜間基礎(chǔ)率時停用晚餐；調(diào)整日間基礎(chǔ)率時停用早餐或午餐f以 2-4am和早餐前

34、的血糖為基礎(chǔ)，調(diào)整夜間基礎(chǔ)率 f為避免調(diào)整過度，基礎(chǔ)率的調(diào)整以 0.1 u/hr為幅度77bgyxx (x (胰島素敏感系數(shù)胰島素敏感系數(shù)) ) = 1500/= 1500/每日胰島素用量每日胰島素用量胰島素敏感系數(shù)胰島素敏感系數(shù)定義定義：注射：注射1單位胰島素單位胰島素25小時小時 bg降低降低mg/dl數(shù)值。數(shù)值。補充量補充量=bgbg = = 實際血糖實際血糖(mg/dl) y y = = 理想血糖理想血糖(mg/dl) x x = = 胰島素敏感系數(shù)胰島素敏感系數(shù)例：帶泵后每天胰島素例：帶泵后每天胰島素50u，餐前測血糖，餐前測血糖160mg/dl，餐前理想，餐前理想血糖血糖100 m

35、g/dl，需要補充胰島素劑量？，需要補充胰島素劑量？ bg = 160 y=100 x=1500/50=30 補充胰島素劑量補充胰島素劑量 = （160100）/30 = 2 u78quick-serterquick-setsof-sertersof-setsil-sertersilhouetteadvanced infusion sets79glucose monitoring systems - implantable inserted into the central vein leading to the heartfsensor replacement requires minor

36、outpatient procedurefrecords glucose every minutefregulatory approval requiredlong-term sensorartificial pancreasi o n s i n d i a b e t e s81 two pathways to the artificial pancreasfdescription integrates external pump with sensor system displays glucose valuesexternal systemfdescription integrates

37、 implantable pump with long-term sensorimplantable systemautomatically reads glucose levels and administers insulinreferred to as “closed-loop” systemdescription:+mmt 2007b modified for sensor connection (mip-xs)abdominal lead assembly (ala)catheter tip for insulin deliverycatheter header with inlet

38、 port sensor connection to the pumpinlet to pumpsensor tip83 these results are limited to a single subject and are not necessarily indicative of future results, nor can the company provide any assurances that a product will ultimately be commercialized.5010015020025030035040016 wed17 thu18 fri19 sat

39、20 sun21 mon22 tue23 wedaugust 2000glucose (mg/dl) long term implantable systemautomatic glucose regulationin a fully pancreatectomized canineclosed loop controlmanualcontrolmanualcontrolautomatic controlbeginscontrolterminatedimplantable closed loop system“moon”; the first implantable closed loop s

40、ystem86insulin pump vs insulin?87f動物胰島素動物胰島素f單組分動物胰島素單組分動物胰島素f人胰島素人胰島素f胰島素類似物胰島素類似物88f1999年年9月獲得歐盟批準(zhǔn)月獲得歐盟批準(zhǔn)f2000年年6月獲得美國月獲得美國fda批準(zhǔn)批準(zhǔn)f2002年年8月獲得中國月獲得中國sda批準(zhǔn)批準(zhǔn)f2002年年12月在中國上市月在中國上市新一代速效胰島素注射液新一代速效胰島素注射液（中國第一個胰島素類似物）中國第一個胰島素類似物）89prothrglytyrphepheglyarggluglyvalleutyrleualagluvalleuhisserglycysleuhisg

41、lnasnvalpheb1a21b28b30a1asntyrasngluleuglntyrleuserlieserthrcysglngluvalliecyscyscyscysthrlyspro-asp諾和銳諾和銳90 918小時小時3-5小時小時作用持續(xù)時作用持續(xù)時間間1-3小時小時40分鐘分鐘達(dá)峰時間達(dá)峰時間30分鐘分鐘10-20分分鐘鐘起效時間起效時間中性可溶性中性可溶性人胰島素人胰島素諾和銳諾和銳92*p 0.05在胰島素治療中使用諾和銳或人胰島素結(jié)晶情況的對比在胰島素治療中使用諾和銳或人胰島素結(jié)晶情況的對比0.00.20.40.60.81.01.21.41.6泵池泵池導(dǎo)管導(dǎo)管mean

42、(+sd)結(jié)晶情況結(jié)晶情況諾和銳諾和銳 n = 19人胰島素人胰島素 n = 10*93唯一獲得唯一獲得fda批準(zhǔn)在胰島素泵中使批準(zhǔn)在胰島素泵中使用的胰島素類似物用的胰島素類似物94insulin detemir thrglulysvalpheasngluleuglntyrleusercysilesercyscysglngluvalileglytyrcysasnlysprothrtyrphepheargglygluglycysvalleutyrleualavalleuhisserglycysasnglnleuhisb1a21a1b29c14 c14 脂肪酸鏈脂肪酸鏈(myristic acid

43、)(myristic acid)thr95hsa: hsa: 人血清白蛋白人血清白蛋白擴散擴散吸收吸收受體作用受體作用lifetime benefits of effectiveintensive therapy (dcct)fgain of 15.3 years of complication free living compared to conventional therapyfgain of 5.1 years of life compared to conventional therapydcct study group, jama 1996;276:1409-1415.hypogl

44、ycemia treatment guidelinesfif bg is 70 mg/dl or belowtreat with 15 grams of carbohydrates (glucose tabs)check bg in 15 minutes, and if not above 70 mg/dl, repeat treatmentglucagonfcurrent emergency kit readily available and knowledgeable person trained to administer hyperglycemia treatment guidelin

45、esthe key to preventing dkaftake a correction bolus via pump, check again in 1 hourftake correction bolus by syringe and change infusion set, review pump, check bg again in 1 hour fcall physician immediately if nausea and vomiting are presentprevention and treatment of skin irritation and infections

46、preventionfchange infusion set every 2 to 3 daysfuse aseptic technique and cleanse skin with iv prepfcheck site each night before bedfuse “sandwich” techniquetreatmentftape irritation or non-adhesionchange type of tapeftubing irritationuse “sandwich” techniquefinfectionnotify healthcare provider asapfollow-up: the patients rolefcheck bg 4-6 times a day, and al