1、糖尿病與血糖監(jiān)控,,Blood Glucose Levels in Diabetics,糖尿病病因,目前仍不知確實的病因。只知糖尿病為一緩慢漸進性的自體免疫性疾患。自體免疫性疾患指病人體內(nèi)自發(fā)性的產(chǎn)生具破壞性的抗體，而攻擊自己的組織。糖尿病童體內(nèi)可檢測出各種會破壞胰腺中的β細胞的抗體和淋巴球。β細胞因而逐漸遭到破壞。當(dāng)80-90%左右的β細胞被破壞後，臨床上便漸漸出現(xiàn)癥狀。,臨床癥狀,常見的癥狀有多尿、多飲、消瘦、多食、倦怠、夜尿（甚至

2、尿床）、腹痛、嘔吐、口腔或陰部黴菌感染。 嚴(yán)重的會脫水。約有1/3-1/2的病童發(fā)生糖尿病酮酸中毒（diabetic ketoacidosis, DKA） 他的尿液中會有酮體出現(xiàn)，血液會轉(zhuǎn)為酸性（血漿HCO3- ≦15 mEq/L），病童會有嚴(yán)重的脫水，呼吸急促而且用力，稱為糖尿病酮酸中毒。,正常人的血糖標(biāo)準(zhǔn) FPG < 100 mg/dl or 2-h PG (OGTT) <

3、 140 mg/dl,OGTT:Oral Glucose tolerance Test,FPG:Fasting Plasma Glucose,New Diagnostic Criteria for Diabetes,PG > 200 mg/dlor FPG > 126 mg/dlor 2-h PG (OGTT,75 gm) > 200 mg/dl,Pre-diabetes (IFG & IGT

4、) 126 mg/dl 100 mg/dl or 200 mg/dl 140 mg/dl,IFG:Impaired Plasma Glucose,IGT::Impaired Glucose Tolerance,臺灣現(xiàn)況(健保局資料),全民中有4.0%被歸類為糖尿病，但醫(yī)療支出佔11.5 %每位糖

5、尿病患的平均給付金額為其他疾病的3.3倍調(diào)降1/3的嚴(yán)重個案比例，可減少20 %的總支出,糖尿病治療的總體目標(biāo),１）消除糖尿病的癥狀２）避免低血糖和酮酸癥的發(fā)生３）恢復(fù)日常的活力４）預(yù)防血管病變和其他的併發(fā)癥５）確保體格和心理的正常發(fā)展６）維持健全的家庭和人際關(guān)係,監(jiān)測,１）自我血糖監(jiān)測 (self-monitoring of blood glucose, SMBG)理想情形是維持飯前血糖在70-140，飯後≦140 mg/

6、dl。但應(yīng)依 病童 的年紀(jì)和處理低血糖的能力酌情調(diào)整。２）醣化血紅素 (HbA1c) 醣化血紅素反映病童最近２－３個月來血糖的平均值和 糖尿病控制的好壞。最好能維持在 7.0% 以下。３）尿酮：必須為陰性。４）血脂：total Cholesterol, Triglyceride, DHL-Chol 和 LDL-Chol要保持 正常。5）微尿白蛋白(microalbuminuria)：發(fā)病5-

7、6年後，必須 開始測定，期能早期檢出腎病變。,Monitoring Diabetes,Blood glucose: self testing.Hemoglobin A1c (HbA1c) testing: hospital, lab or Dr. office testing.,What is Glycated Hemoglobin?,,,β-chain N端Valine,Glucose,糖化作用也會發(fā)生在α鍵的N端

8、和α，β鍵上的lysin上。 2003,美國ADA建議統(tǒng)一定名為A1C.,,糖化血紅素是葡萄糖和血紅素長期接觸所形成，HbA1c只是眾多糖化血紅素中的一種。,它是血糖代謝的指標(biāo),它是糖尿病併發(fā)癥的危險參數(shù),它是糖尿病管理/治療的指標(biāo),FORMATION OF GLYCATED HEMOGLOBIN,Hemoglobin + GlucoseSchiff Base (labile)

9、HbA1c(stable),,,Fast,Slow,irreversible,Non-enzymatic reaction,糖化血紅素與血糖的關(guān)係,形成速率與血中葡萄糖濃度成正比。 良好的血糖標(biāo)記，可反應(yīng)過去2-3個月來血糖平均值。 較客觀、方便、不受飯後血糖升高的影響。RBC第0-30天的前段生命期反應(yīng)50%的糖化血色素值。美國DCCT已建立各種解讀A1C的臨床數(shù)據(jù)，可供

10、引用。,糖化血紅素(AlC)與平均血糖值的關(guān)係,Mean Glucose vs. HbA1c,Plasma glucose = blood glucose *1.11 (Clin. Chem. 44:3, 655-659),,,,,Non-Diabetic,Target,,Action Required,,,,,,,,最常導(dǎo)致視網(wǎng)膜病變及失明,最常導(dǎo)致非外傷性截肢,為什麼要重視糖尿病?,,糖尿病,,最常導(dǎo)致末期腎臟病及洗腎治療,心血

11、管致死率是一般人的2-4倍,,,,,,這些併發(fā)癥可以控制與預(yù)防嗎?,醫(yī)療面向,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,1,2,3,4,5,6,7,8,9,,,,,,,,,,,5,6,7,8,9,10,11,,,

12、,,,,,Study Time in Years,HbA1c During the DCCTIntensive vs Conventional Treatment,Quarterly HbA1c (%),9.0,7.0,A1C%,DCCT STUDYDiabetes Control and Complications Trial,1982 to 1993.1,441 IDDM patients participated.Over

13、all cost: $165 million.Final report: ADA 1993 annual meeting.Intensive treatment： A1C： 7.0%.Conventional treatment： A1C： 9.5%.,DCCT研究結(jié)果,Retinopathy 發(fā)生率減少76%Nephropathy發(fā)生率減少56%Neuropathy 發(fā)生率減少60%Ps.: Type I and T

14、ype II DM. 有相同結(jié)果。,美國ADA recommendations for Diabetes carequality (2005),Perform the A1C test at least 2 times per year in stable patients.Achieve A1C < 7.0% as goal of glycemic control.Lower A1C is associated

15、with lower risk of cardiovascular diseases.A1C < 6.0% can be considered in individual patients.,UK(英國) Consensus Statement,Glycemic control is best monitored by HbA1cThe assay used should be a DCCT-aligned H

16、bA1c method.The assay used should have acceptable within (<3%) and between (<5%) laboratory imprecision.Results of HbA1c analysis should be reported as %HbA1c or ‘DCCT-equivalent % HbA1c’. Laboratories should de

17、monstrate acceptable performance in an EQA (外部品管)program.,,測定糖化血紅素的方法,1.陽離子交換層析法(Cation exchange HPLC)2.親和力層析法(Boronate affinity HPLC)3.免疫比濁法(Immunoassay),,Cation Exchange HPLC,,,,,,,,,,,No.3,No.2,No.1,A1a, A1b, F

18、 L-A1c, s-A1c A0,,,,使用階段梯度方式分離,Boronate affinity,,,,,CH,2,NH,Hb,,CO,,HCOH,,HOCH,,HOCH,,CH,2,OH,,,,,,,Resin,,,,NH,,,,,B,,,,,OH,,CH,2,NH-,Hb,,CO,,HCOH,,O CH,,O CH,,CH2OH,,,,,,,,,,,,,,Cis-diol,將血紅素

19、分成”糖化”與”非糖化”兩部份,Immunoassay process,利用單株抗體與β-chain N端六個糖化氨基酸結(jié)合,美 國 CAP SURVEY (mean ± 2SD),,美國糖尿病醫(yī)師認(rèn)證後的照護成效,Physicians Achieving Recognition ADA/NCQA Diabetes Physician Recognition Program % of adult patients

20、with,Diabetes Physician Recognition Program, average performance of applicants, 1997-2003 data.* Lower is better for this measure.,照護成效四項指標(biāo)的比較表,DPRP: Diabetes Physician Recognition Program,,結(jié) 論,1.受檢人數(shù)，彰化縣有924人，

21、臺中縣有1,369人。糖化血色素(AlC)的平均值分別為8.10%及7.99%。與去年(93)臺中縣的平均值7.95%相似。離7.0%的目標(biāo)還有一段距里。2.本次普查，兩縣的AlC平均值並無顯著差異。但AlC≧9.5%的人數(shù)，彰化縣比臺中縣多 3.32%。AlC≦7.0%的人數(shù)。彰化縣也比臺中縣低 1.06%。,3.兩縣合計:A1C值≧9.5 % 的病人數(shù)比率, 統(tǒng)計有18.8%，若以此作為評估基準(zhǔn)點 : 彰化縣有13家基層醫(yī)療

22、單位應(yīng)再努力降低A1C值≧9.5%的病人數(shù)比率,臺中縣也有9家。 。 4.兩縣委託的代檢單位，今年表現(xiàn)都不錯，〝不可級〞總數(shù)66件，佔總比對數(shù)的3.7%，比去年的6%進步不少。彰化縣8家中僅有一家,85.71%(未達95%可信度)。臺中縣21家中則有2家未達95%可信度。5. AlC≦7.0%的人數(shù)比率，彰化縣與臺中縣分別為 32%和33%,有待努力空間還很大。,Microalbuminuria Development,

23、Progression,and Regression in Type II Diabetes Patients,,人的腎臟縱切面圖,,腎元的結(jié)構(gòu),腎絲球的結(jié)構(gòu),腎絲球體基底膜是負(fù)電荷、因此它會阻止分子量介於15,000和80,000的負(fù)電荷流動分子通過基底膜。而白蛋白屬負(fù)電荷且分子量是66,000。血糖濃度昇高對腎絲球體基底膜的影響 腎絲球體基底膜的負(fù)電荷損耗

24、 基底膜的寬度增加,腎臟病的分類,一.腎絲球腎炎 二.腎小管間質(zhì)性腎炎 三.急性腎功能不全 四.慢性腎功能不全 依腎臟衰退情況可分為四期 : 一、腎功能僅及正常的50%時 二、腎功能不全 : 腎功能約僅正常的 25%至 50% 。三、腎功能約正常的10%至25%時稱為腎衰竭。四、尿毒癥,腎功能僅及正常的10%以下。,腎臟功能的評估,尿液分析: proteinuri

25、a,hematuria.pyeuria腎絲球過濾率: Creatinine clearance rate; Inulin or PAH clearance rate腎小管功能: Phenolsulfonphthalein dye test, Beta2-microglobulin, Osmolality,What is microalbumin

26、uria,The earliest indicator of renal disease (nephropathy) attributable to diabetes. To be predictive of total mortality, cardiovascular mortality and cardiovascular morbidity.,Microalbuminuria(微白蛋白尿),Who is at risk?1

27、.In both type 1 and type 2 diabetes, the first sign of deteriorating kidney function.2. Hypertention with microalbuminuria is an indicator of declining kidney function.,Microalbuminuria (in diabetes mellitus),Microalbu

28、minuria development precedes persistent albuminuria in type 1 and type 2 diabetics. Antihypertensive therapy slows progression of microalbuminuria to albuminuria in both type of diabetes .Type 1 diabetes with m

29、icroalbuminuria, have a 30% risk of progression to overt albuminuria over a period of 10 year follow-up. If the screening is positive for microalbuminuria in a type 1 diabetic, then an ACE inhibitor should be us

30、ed even if the patient is normotensive.,The American Diabetes Association (ADA) recommends,Microalbumin measurement is recommended when the urine is negative for Dip-stiks protein.4 tests per year were recommended.

31、Microalbuminuria: Two of three abnormal results measured within 3 to 6 month.,Definition of Microalbuminuria,Albumin excretion rate: 20-200 µg/min (30-300 mg/24hr)Albumin

32、 / Creatinine ratio: 30-300 mg/g (30~300ug/mg)Albumin concentration, first voided morning urine: 30-300 mg/L,American Diabetes Association Definition of Microalbuminuria,美國

33、糖尿病協(xié)會定義微白蛋白尿：,Microalbuminuria(微白蛋白尿)albumin : creatinine ratio (ACR),Reference IntervalNormal: 0-30 µg/mg creatinine Microalbuminuria: 30-300 µg/mg creatinine

34、 Clinical albuminuria: >300 µg/mg creatinine,From ADA (American Diabetes Association)criteria,Microalbuminuria(微白蛋白尿),Methodology: Ne

35、phrometry (散色比濁法) Immuno-turbidimetry (免疫比濁法) Immuno-chromatography (免疫層析法)Specimen : at least 2 ml. random urine Limitation : Physical exercise, infection, fever, congestive heart failure, marked hyperg

36、lycemia, and marked hypertension can result in increased microalbumin levels.,Clinical applicationNormal reference range,Age Urine ACR (ug/mg creatinine)Men Women>50 yr. 6.9+/- 4.7 8.2+/-4

37、.4 <50yr. 4.8+/-3.6 6.2+/-4.0,Annals of Clin.&Lab. Science,2005,35,2,p149,Annals of Clin.&Lab. Science,2005,35,2,p149,Normal reference range in age group,Annals of Clin.&Lab. Science,2005,35

38、,2,p149,Microalbuminuria related to CVD and Diabetes,From Diabetes Care,1994,17,8,p891,,From Diabetes Care,2005,28,11p2376,Development of Microalbuminuriaunder Glycemic and Blood pressure control,From Diabetes Care,2005

39、,28,11,p2376,Progression and Regression of Microalbuminuriaunder Glycemic and Blood pressure control,Steno-2 study in type 2 diabetes (with microalbuminuria),Condition:160 high-risk type 2 diabetic patients with microal

40、buminuria aged 55.1 years (average), who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years.Results:44% of patients in the conventional group had a cardiovasc

41、ular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50% the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60%

42、in the intensively treated group,Metabolism. 2003 Aug;52(8 Suppl 1):19-23.,In the intensive group,lifestyle education Goal-oriented pharmacological treatmentReduced-fat diet and exercise Smoking cessation Receive

43、angiotensin-converting enzyme (ACE) inhibitor regardless of blood pressure.Vitamin supplementation and aspirin,我們的調(diào)查數(shù)據(jù),(本縣與臺中縣共 2150 位病人數(shù)),,1－≦6.0% 2－6.1~7.0% 3－7.1~8.0% 4－8.1~9.0% 5－9.1~10.0% 6－10.1~11.0%

44、 7－11.0~12.0% 8－≧12.0%,,ACR and A1C相關(guān)性分析圖(III),1. 34%的受檢者已有蛋白尿(Proteinuria),其中 26%為microalbuminuria.2. Microalbuminuria 與高血壓、HbA1c和罹病年數(shù) 有正比關(guān)係。3. 利用 Blood Creatinine level作為評估早期 腎病變的指標(biāo),敏感度不如microalbu

45、min。,結(jié) 論,NycoCard® U-Albumin - for measurement of low albumin concentrations in human urine,Complete for 24 analysis: 24 tubes of Dilution Liquid 24 Test Devices 2.0 mL Conjugate 2.0 mL Washing Sol

46、ution,NycoCard® U-Albumin kit contents,TD/Test Device,Plastic device sealed with aluminium foilMembrane coated with monoclonal anti-albumin antibodiesLiquid absorbing layer underneath the membrane? Entrapment of

47、 human albumin,,,NycoCard Reader,Stability of kit in use,An opened test kit was stored refrigerated at 4°C. In house reference material and NycoCard® U-Albumin Control were analysed regularly over a 3 months pe

48、riod. No significant change in any kit component was observed during this period.,NycoCard for A1C test,,NycoCard 產(chǎn)品說明,RAPID Result within 3 MINUTES during patient consultationFINGER PRICK, WHOLE BLOOD (5μL) applicable

49、(make use of blood lancet or EDTA tube)STANDARDIZED according to the recommendations of the ERL Laboratory (European Reference Laboratory)Measuring Range: 3-18% HbA1cFDA APPROVAL for Diabetes MonitoringSimilar system