血糖達(dá)標(biāo)的科學(xué)與藝術(shù)低血糖管理

1、,血糖達(dá)標(biāo)的科學(xué)與藝術(shù) ----低血糖管理,為什么要進(jìn)行嚴(yán)格的血糖控制?,UKPDS - Why Tight Control?,Stratton IM, et al. BMJ. 2000;321(7258):405-412,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,DCCT Group. Lancet. 1998;352:837-853.Ohkubo Y, et al. Diabetes Res Clin

2、Pract. 1995;28:103-117.,胰島素常規(guī)治療與強(qiáng)化治療療效對(duì)比,DCCT – Type 1,Kumamoto Study – Type 2,Normal range,,MedianHbA1c (%),,,10,,9,,8,,7,,6,,5,,0,,1,,2,,3,,4,,5,,6,,7,,8,,9,,10,,Time (years),,Normal range,,,,,,,,,,,ADA action,ADA goa

3、l,,Time (years),MeanHbA1c (%),0,5,1,2,3,4,5,6,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,9,10,8,6,7,HbA1c ~2.3%,,,,,HbA1c ~2.1%,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

4、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Conventional,,,n=1444,n=110,Intensive,血 糖 控 制 現(xiàn) 狀,中國二、三級(jí)醫(yī)院血糖的控制現(xiàn)狀,IDMPS，2005,血糖控制Glycaemic control,32%的病人血糖控制差--HbAIc>7.5%只有47%口服降糖藥治療病人和37%胰島素治療的病人得到很好的血糖控制采用飲食和運(yùn)動(dòng)治

5、療的病人平均HbAIc為7.23%, 口服降糖藥治療的病人為7.43% ， 而胰島素治療的病人為8.25%Message: 需要胰島素治療控制血糖的患者的血糖控制平均水平最差,ISIS Diabetic Therapy Monitor PhVI 2002American Diabetic Association guidelines,,HbA1c,飲食+運(yùn)動(dòng),口服藥單用或聯(lián)合,胰島素,,,,平均HbA1c,

6、平均HbA1c,平均HbA1c,不同治療人群血糖的控制水平和HbA1c的分布,?,各類藥物強(qiáng)化治療達(dá)標(biāo)導(dǎo)致低血糖發(fā)生,UKPDS研究對(duì)2型糖尿病患者6年隨訪結(jié)果,Diabetes 1995;44:1249-1258,,,,,,,,HbA1C=8%,HbA1C=7%,,hypo,,hypo,Control level,強(qiáng)化治療和低血糖,DCCT和UKPDS:強(qiáng)化血糖治療有效，但是低血糖風(fēng)險(xiǎn)增加,UKPDS(2型糖尿病),1.DCCT

7、Research Group. Diabetes 1997; 46:271-286； 2.UKPDS Group (33). Lancet 1998; 352:837-853 .,DCCT (1型糖尿病),DCCT研究：血糖－ HbA1C 水平越接近于正常，低血糖發(fā)生率也就越高。 UKPDS研究：隨著治療時(shí)間的延長，血糖得到控制之后，低血糖 的發(fā)生也會(huì)隨著增加。,,,Rate pf progression of retin

8、opathy(per 100 patient years),Rate of severe hypoglycaemia(per 100 patient years),DCCT Research Group, 1993,,,,,,,,,,,,,,,,Severe hypoglycemia,120,60,0,12,10,8,6,4,2,0,0,,,,,,,,,,,,5.5,6,6.5,7,7.5,8,8.5,9,9.5,10,10.5,H

9、bA1c (%),,,Relative riskof retinopathy,Trade-off Between Hypoglycemia & Complications,,,低血糖風(fēng)險(xiǎn)成為血糖達(dá)標(biāo)的主要障礙!,,,,,,,,,,,,,,,,,,,,,,,,,,,,,血糖管理,有效的低血糖管理,將帶來更好的血糖控制,低 血 糖 管 理,正常人血糖曲線,糖尿病患者血糖曲線,高血糖,,低血糖,,是否發(fā)生低血糖?何時(shí)發(fā)生低血糖及低

10、血糖持續(xù)時(shí)間?低血糖發(fā)生是否有一定的規(guī)律性?低血糖發(fā)生的原因?,,糖尿病患者的低血糖管理,我們首先需要了解,四點(diǎn)指血監(jiān)測-----無低血糖,Case 1:某2型糖尿病患者,一日兩針胰島素治療,CGMS動(dòng)態(tài)血糖監(jiān)測,Case 1:某2型糖尿病患者,一日兩針胰島素治療,,低血糖,Case 2:某1型糖尿病患者, MDI治療CGMS監(jiān)測發(fā)現(xiàn)夜間低血糖及多發(fā)低血糖,,,,,凌晨1：00—5：00,,,CGMS能發(fā)現(xiàn)低血糖發(fā)生時(shí)間及持續(xù)

11、時(shí)間,低血糖曲線下面積,25,30 Children Wearing the CGM for 3 Months,Average A1c of 6.8%,Pediatric Accuracy Study – NIH DirecNet (#391-P, “Accuracy of the FreeStyle Navigator Continuous Glucose Monitoring System in Children with Typ

12、e 1 Diabetes Mellitus),CGMS 能發(fā)現(xiàn)低血糖發(fā)生規(guī)律,,27,Case 3: 某糖尿病患者,CGMS監(jiān)測發(fā)現(xiàn)無感知低血糖,,,Sometimes both the problem and solution are obvious.,1型糖尿病,2型糖尿病,,0.48,2.83,SH發(fā)生率6倍,3.5,3.0,2.5,2.0,1.5,1.0,0.5,0,,0.22,2.15/病人年,SH發(fā)生率9倍,3.5,3.0,

13、2.5,2.0,1.5,1.0,0.5,0,事件/病人/年,事件/病人/年,意識(shí)正常,意識(shí)受損,意識(shí)正常,意識(shí)受損,1.Gold A.E. et al.Diabetes Care 17:697-703,1994 2.Henderson J.N.et al. Diabetic Med 20；1016-1012,2003,無感知低血糖增加了嚴(yán)重低血糖(SH)的發(fā)生危險(xiǎn),n=60*1年,n=215*1年,n=29,n=31,午后14

14、：00—18：00,,Case 4:某糖尿病患者,CGMS監(jiān)測發(fā)現(xiàn)午后14:00—18:00發(fā)生低血糖,大事件功能分析發(fā)現(xiàn),患者午后踢足球兩小時(shí).,運(yùn)動(dòng)引起低血糖事件,CGMS與１型糖尿病低血糖的發(fā)生,Thorsteinsson B,et al. 2006 ADA,2098-POThorsteinsson B,et al. 2006 ADA, 2099-PO.,研究設(shè)計(jì),研究目的：　應(yīng)用CGMS 監(jiān)測1型糖尿病患者低血糖的發(fā)生規(guī)律

15、研究對(duì)象：119名1型糖尿病患者 年齡 46±12歲　　 糖尿病病程　 21±12年　　 HbA1C 8.5±1.0%CGMS 監(jiān)測6天，SMBG監(jiān)測4次/天來校正,Thorsteinsson B,et al. 2006 ADA,2098-POThorsteinsson B,et al. 2006 ADA,

16、 2099-PO.,CGMS提高低血糖的檢出率,Thorsteinsson B,et al. 2006 ADA, 2098, 2099-PO.,SMBG (n=526),CGMS (n=831),,,0.5倍,,,1.1倍,研究對(duì)象：119名1型糖尿病患者,CGMS有助于分析低血糖發(fā)生的原因和時(shí)間分布,Thorsteinsson B,et al. 2006 ADA, 2098, 2099-PO.,,低血糖的時(shí)間分布,低血糖發(fā)生的原因,研

17、究結(jié)果,CGMS可發(fā)現(xiàn)更多的無癥狀低血糖癥狀性低血糖在日間最常見體力活動(dòng)是引起低血糖發(fā)生的最常見原因本研究提示：CGMS有助于分析糖尿病低血糖發(fā)生的類型、時(shí)間分布和誘因,Thorsteinsson B,et al. 2006 ADA,2098-POThorsteinsson B,et al. 2006 ADA, 2099-PO.,糖尿病患者低血糖管理,發(fā)現(xiàn)和了解低血糖,控制和防范低血糖,,CSII在低血糖管理中的作用,

18、CSII 減少嚴(yán)重低血糖的發(fā)生率(episodes / 100 pt yrs),Bode BW:Diabetes Care, 1996; 19:324-327,CSII reduces hypoglycemia,N=55Mean age 42,N=107Mean age 36,,n=25Mean age 14,N=56Mean age 17,Events per hundred patient years,Bell

19、 Rudolph Boland Chase,Chantelau, 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., Pediat

20、rics 2001, 107:351-6.Bell, DSH, et al, Endocrine Practice 2000, 6:357-60.,低血糖減少后反向調(diào)節(jié)激素的恢復(fù),Fanelli, C. et al. Diabetologia (1994) 37: 1265-1276.,Kane, K. et al. Diabetologia 1998, 41: 322-329.,開始CSII治療后反向調(diào)節(jié)癥狀改善,胰島素泵治療與

21、低血糖,胰島素泵治療能恢復(fù)機(jī)體對(duì)低血糖指征的敏感性， 打破低血糖敏感性降低的惡性循環(huán)。,Bode BW: Diabetes Care 1996; 19:324-327,CSII---基礎(chǔ)率和大劑量胰島素輸注,,Basal Insulin,,Pancreas Delivery,,Insulin Meal Response,,基礎(chǔ)胰島素的需要量并非一成不變,基礎(chǔ)胰島素需要量的年齡特征揭示24h期間的顯著變異,Scheiner, Ga

22、ry; Boyer, Bret A.. Diabetes Research and Clinical Practice, 69 (2005) pg. 14-21.,n=322,CSII----靈活多變的基礎(chǔ)率分段設(shè)置,,,,Adapted from Lepore et al. Diabetes 2000;49:2142-8.,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,甘精,,,,

23、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,NPH,皮下注射胰島素,N=20 1型糖尿病均值 ± 標(biāo)準(zhǔn)誤,注射后的時(shí)間 (小時(shí)),30252015105,180150120906030,04812162024,長效,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

24、,,,,,,,,,,,,,,,,,,,,,,,,,CSII,pmol/l,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,基礎(chǔ)胰島素釋放方式的有效性,0.3U/公斤體重,,,Armstrong et al Diabetes 51 (Supplement 2) 373 2002,Less nocturnal hypogl

25、ycemia with CSII vs. Glargine,CSII vs. MDI使用短效/速效胰島素，吸收變異率小(吸收的差異3%比52%*)一個(gè)固定的注射部位,減少因注射部位不同而造成吸收變異,* Lauritzen: Diabetologia 1983; 24:326-9,,CSII---胰島素吸收的有效性和穩(wěn)定性,CSII vs. MDI持續(xù)微劑量皮下輸注,有效減少胰島素皮下蓄積,避免運(yùn)動(dòng)后或熱水浴后低血糖,有效消除日

26、間血糖波動(dòng).,* Lauritzen: Diabetologia 1983; 24:326-9,,表皮,胰島素皮下蓄積,皮下脂肪,肌肉層,CSII---胰島素吸收的有效性和穩(wěn)定性,胰島素泵治療與低血糖,胰島素泵使用短效或超短效胰島素，吸收差異小于2.8%胰島素泵的微量持續(xù)輸注方式不會(huì)在皮下形成蓄積作用，不會(huì)發(fā)生不可預(yù)見的低血糖現(xiàn)象 在運(yùn)動(dòng)、夜間，胰島素的劑量調(diào)節(jié)靈活，立即生效，效果穩(wěn)定 ,嚴(yán)重低血糖的發(fā)生率減

27、少85%,Bode BW: Diabetes Care 1996; 19:324-327,CSII---基礎(chǔ)率和大劑量胰島素輸注,,Basal Insulin,,Pancreas Delivery,,Insulin Meal Response,,Teen suffered from significant delayed gastric emptying Teen went from being an A/B student to

28、D/F student during past semester,Submitted by Pat Pitarra, RN, MSN, CDE,BG was 78 mg/dl when checked – Teen ate snack and took appropriate bolus for.,Hypoglycemia and Delayed Gastric Emptying,,,Patient ate,,Prolonged hy

29、poglycemia of 4.5 hrs,,Rebound Hyperglycemia,對(duì)于有胃輕癱的患者（消化緩慢），胰島素作用曲線峰值較CHO吸收提前。發(fā)生餐后低血糖。,胃排空延遲與餐后低血糖,如果使用方波，胰島素作用曲線和胃輕癱患者的CHO吸收相吻合。這樣就會(huì)更好的控制餐后血糖。,方波大劑量避免餐后低血糖,CSII----Bolus Types,,Boluses can be delivered in one of three

30、ways to accommodate various situations Normalall at once Square Wave gradually over time Dual Wavea portion immediately followed by the remainder over time,55,,,,,,,,0,20,40,60,80,100,120,0,60,120,180,240,300,

31、360,,,,Time (minutes),% peak value,PK,PD,Adapted from Mudaliar SR et al: Diabetes Care 22:1501, 1999,Insulin Action is Longer than People Realize,PK vs. PD for Insulin Aspart,胰島素累積定義,Insulin Stacking （胰島素累積）在使用補(bǔ)充大劑量校正高血

32、糖時(shí)，體內(nèi)仍有顯著的殘留活性胰島素量。,活性胰島素(active insulin)定義：已經(jīng)輸注到體內(nèi)的、尚未使用的大劑量胰島素,,活性胰島素隨時(shí)間的變化曲線,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,

33、,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,0,20,40,60,80,100,0,1,2,3,4,5,6,7,8,,,,,,,,速效型,,,,常規(guī)型,,,,,,殘留量百分比,時(shí)間 (小時(shí)),,速效胰島素不同時(shí)間點(diǎn)活性胰島素（％）,在 2 小時(shí) 40 分時(shí)51% of 胰島

34、素仍有活性,59,Automatically calculates insulin bolus for the patient,7.0 U,200,60 gr,2.0 U,ICR 1:10 gr,200 - 100 = 2.0 u 50 (SF),,6.0 U,,1.0 U,Bolus Calculator: Example,,,Active insulin is subtracted from correction,大

35、劑量向?qū)?--科學(xué)追蹤活性胰島素,避免矯枉過正發(fā)生低血糖,使用大劑量向?qū)У囊徊椒?根據(jù)預(yù)先的個(gè)性化設(shè)置您只需輸入的數(shù)據(jù)——當(dāng)前血糖值 自動(dòng)跟蹤體內(nèi)剩余活性胰島素量，機(jī)器自動(dòng)計(jì)算出估算值，檢查確認(rèn)并輸注,低血糖,,雙C出擊拒絕低血糖,,,第一步:CGMS發(fā)現(xiàn)低血糖及其原因,運(yùn)動(dòng)低血糖,第二步:CGMS指導(dǎo)CSII劑量調(diào)整,治療低血糖,減少基礎(chǔ)率,第三步:CGMS評(píng)估CSII療效,血糖平穩(wěn)達(dá)標(biāo),Information