1、糖尿病與血糖監控,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自發性的產生具破壞性的抗體，而攻擊自己的組織。糖尿病童體內可檢測出各種會破壞胰腺中的細胞的抗體和淋巴球。細胞因而逐漸遭到破壞。當80-90%左右的細胞被破壞後，臨床上便漸漸出現症狀。,臨床症狀,常見的症狀有多尿、多飲、消瘦、多食、倦怠、夜尿（甚至尿床）、腹痛、嘔吐、口腔或陰部黴菌感染。 嚴重的會脫水。約有1/3-1/2的病童發生糖尿病酮酸中毒（diabetic ketoacidosis, DKA） 他的尿液中會
2、有酮體出現，血液會轉為酸性（血漿HCO3- 15 mEq/L），病童會有嚴重的脫水，呼吸急促而且用力，稱為糖尿病酮酸中毒。,正常人的血糖標準FPG 100 mg/dlor2-h PG (OGTT) 140 mg/dl,OGTT:Oral Glucose tolerance Test,FPG:Fasting Plasma Glucose,New Diagnostic Criteria for Diabetes,PG 200 mg/dlorFPG 126 mg/dlor2-h PG (OGTT,75 gm) 200 mg/dl,Pre-diabetes (IFG & IGT )126 mg/dl
3、100 mg/dl or200 mg/dl 140 mg/dl,IFG:Impaired Plasma Glucose,IGT:Impaired Glucose Tolerance,台灣現況(健保局資料),全民中有4.0%被歸類為糖尿病，但醫療支出佔11.5 % 每位糖尿病患的平均給付金額為其他疾病的3.3倍 調降1/3的嚴重個案比例，可減少20 %的總支出,糖尿病治療的總體目標,）消除糖尿病的症狀 ）避免低血糖和酮酸症的發生 ）恢復日常的活力 ）預防血管病變和其他的併發症 ）確保體格和心理的正常發展 ）維持健全的家庭和人際關係,監測,）自我血糖監測 (self-monitoring of b
4、lood glucose, SMBG)理想情形是維持飯前血糖在70-140，飯後140 mg/dl。但應依 病童 的年紀和處理低血糖的能力酌情調整。 ）醣化血紅素 (HbA1c)醣化血紅素反映病童最近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。 ）尿酮：必須為陰性。 ）血脂：total Cholesterol, Triglyceride, DHL-Chol和 LDL-Chol要保持 正常。 5）微尿白蛋白(microalbuminuria)：發病5-6年後，必須 開始測定，期能早期檢出腎病變。,Monitoring Diabetes,Blood glucose: sel
5、f testing.Hemoglobin A1c (HbA1c) testing: hospital, lab or Dr. office testing.,What is Glycated Hemoglobin?,-chain N端Valine,Glucose,糖化作用也會發生在鍵的N端和，鍵上的lysin上。2003,美國ADA建議統一定名為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,它是糖尿病併發症的危險參數,它是糖尿病管理/治療的指標,FORMATION OF GLYCATED HEMOGLOBIN,Hemoglobi
6、n + GlucoseSchiff Base (labile)HbA1c(stable),Fast,Slow,irreversible,Non-enzymatic reaction,糖化血紅素與血糖的關係,形成速率與血中葡萄糖濃度成正比。 良好的血糖標記，可反應過去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50%的糖化血 色素值。 美國DCCT已建立各種解讀A1C的臨床數據，可供引用。,糖化血紅素(AlC)與平均血糖值的關係,Mean Glucose vs. HbA1c,Plasma glucose = blood glucose *1
7、.11 (Clin. Chem. 44:3, 655-659),Non-Diabetic,Target,Action Required,最常導致視網 膜病變及失明,最常導致 非外傷性截肢,為什麼要重視糖尿病?,糖尿病,最常導致末期腎臟病及洗腎治療,心血管致死率是一般人的 2-4倍,這些併發症可以控制與預防嗎?,醫療面向,1,2,3,4,5,6,7,8,9,5,6,7,8,9,10,11,Study Time in Years,HbA1c During the DCCT Intensive vs Conventional Treatment,Quarterly HbA1c (%),9.0,7.0
8、,A1C%,DCCT STUDY Diabetes Control and Complications Trial,1982 to 1993. 1,441 IDDM patients participated. Overall cost: $165 million. Final report: ADA 1993 annual meeting. Intensive treatment： A1C： 7.0%. Conventional treatment： A1C： 9.5%.,DCCT研究結果,Retinopathy 發生率減少76%Nephropathy發生率減少56%Neuropathy 發
9、生率減少60%Ps.: Type I and Type II DM. 有相同結果。,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 with lower risk of cardiovascular diseases. A1C 6.0% can be consider
10、ed in individual patients.,UK(英國) Consensus Statement,Glycemic control is best monitored by HbA1c The assay used should be a DCCT-aligned HbA1c method. The assay used should have acceptable within (3%) and between (5%) laboratory imprecision. Results of HbA1c analysis should be reported as %HbA1c or
11、 DCCT-equivalent % HbA1c. Laboratories should demonstrate 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 L-A1c, s-A1c A0,使用階段梯度方式分離,Boronate affinity,CH,2,
12、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,將血紅素分成”糖化”與”非糖化”兩部份,Immunoassay process,利用單株抗體與-chain N端六個糖化氨基酸結合,美 國 CAP SURVEY (mean 2SD),美國糖尿病醫師認證後的照護成效,Physicians Achieving Recognition ADA/NCQA Diabetes Physician Recognition Program% of adult patients w
13、ith,Diabetes Physician Recognition Program, average performance of applicants, 1997-2003 data. * Lower is better for this measure.,照護成效四項指標的比較表,DPRP: Diabetes Physician Recognition Program,結 論,1.受檢人數，彰化縣有924人，台中縣有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)台中縣的平均值7.95%相似。離7.0%的目標還有一段距里。2.本次普查，兩縣的AlC平
14、均值並無顯著差異。但AlC9.5%的人數，彰化縣比台中縣多 3.32%。AlC7.0%的人數。彰化縣也比台中縣低 1.06%。,3.兩縣合計:A1C值9.5 % 的病人數比率, 統計有18.8%，若以此作為評估基準點 :彰化縣有13家基層醫療單位應再努力降低A1C值9.5%的病人數比率,台中縣也有9家。 。 4.兩縣委託的代檢單位，今年表現都不錯，不可級總數66件，佔總比對數的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)。台中縣21家中則有2家未達95%可信度。 5. AlC7.0%的人數比率，彰化縣與台中縣分別為32%和33%,有待努力空間還很大。,
15、Microalbuminuria Development,Progression,and Regression in Type II Diabetes Patients,人的腎臟縱切面圖,腎元的結構,腎絲球的結構,腎絲球體基底膜是負電荷、因此它會阻止分子量介於15,000和80,000的負電荷流動分子 通過基底膜。而白蛋白屬負電荷且分子量是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電荷損耗 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
16、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、尿毒症,腎功能僅及正常的10%以下。,腎臟功能的評估,尿液分析: proteinuria,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 microalbuminuria,The earliest indicator of renal
17、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.In both type 1 and type 2 diabetes, the first sign of deteriorating kidney function. 2. Hypertention with microalbumin
18、uria is an indicator of declining kidney function.,Microalbuminuria (in diabetes mellitus),Microalbuminuria 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 diabet
19、es with microalbuminuria, have a 30% risk of progression to overt albuminuria over a period of 10 yearfollow-up.If the screening is positive for microalbuminuria in a type 1 diabetic, then an ACE inhibitor should be used even if the patient is normotensive.,The American Diabetes Association (ADA) re
20、commends,Microalbumin measurement is recommended when the urine is negative for Dip-stiks protein.4 tests per year were recommended.Microalbuminuria: Two of three abnormal results measured within 3 to 6 month.,Definition of Microalbuminuria,Albumin excretion rate: 20-200 g/min (30-300 mg/24hr)Albumi
21、n / Creatinine ratio: 30-300 mg/g(30300ug/mg) Albumin concentration, first voided morning urine: 30-300 mg/L,American Diabetes Association Definition of Microalbuminuria,美國糖尿病協會定義微白蛋白尿：,Microalbuminuria(微白蛋白尿) albumin : creatinine ratio (ACR),Reference Interval Normal: 0-30 g/mg creatinine Microalbu
22、minuria: 30-300 g/mg creatinine Clinical albuminuria: 300 g/mg creatinine,From ADA (American Diabetes Association)criteria,Microalbuminuria(微白蛋白尿),Methodology:Nephrometry (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 exerc
23、ise, infection, fever, congestive heart failure, marked hyperglycemia, and marked hypertension can result in increased microalbumin levels.,Clinical application Normal reference range,Age Urine ACR (ug/mg creatinine) Men Women 50 yr. 6.9+/- 4.7 8.2+/-4.4 50yr. 4.8+/-3.6 6.2+/-4.0,Annals of Clin.&Lab
24、. 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,2005,35,2,p149,Microalbuminuria related to CVD and Diabetes,From Diabetes Care,1994,17,8,p891,From Diabetes Care,2005,28,11p2376,Development of Microalbuminuria under
25、 Glycemic and Blood pressure control,From Diabetes Care,2005,28,11,p2376,Progression and Regression of Microalbuminuria under Glycemic and Blood pressure control,Steno-2 study in type 2 diabetes (with microalbuminuria),Condition:160 high-risk type 2 diabetic patients with microalbuminuria aged 55.1
26、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 cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50% the
27、relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group,Metabolism. 2003 Aug;52(8 Suppl 1):19-23.,In the intensive group,lifestyle education Goal-oriented pharmacological treatment Reduced-fat diet and ex
28、ercise Smoking cessation Receive angiotensin-converting enzyme (ACE) inhibitor regardless of blood pressure. Vitamin supplementation and aspirin,我們的調查數據,(本縣與台中縣共 2150 位病人數),16.0% 26.17.0% 37.18.0% 48.19.0%59.110.0% 610.111.0% 711.012.0% 812.0%,ACR and A1C相關性分析圖(III),1. 34%的受檢者已有蛋白尿(Proteinuria),其中26
29、%為microalbuminuria.2. Microalbuminuria 與高血壓、HbA1c和罹病年數有正比關係。3. 利用 Blood Creatinine level作為評估早期腎病變的指標,敏感度不如microalbumin。,結 論,NycoCard U-Albumin - for measurement of low albumin concentrations in human urine,Complete for 24 analysis:24 tubes of Dilution Liquid24 Test Devices2.0 mL Conjugate2.0 mL Wash
30、ing Solution,NycoCard U-Albumin kit contents,TD/Test Device,Plastic device sealed with aluminium foil Membrane coated with monoclonal anti-albumin antibodies Liquid absorbing layer underneath the membrane Entrapment of human albumin,NycoCard Reader,Stability of kit in use,An opened test kit was stor
31、ed refrigerated at 4C. In house reference material and NycoCard U-Albumin Control were analysed regularly over a 3 months period. No significant change in any kit component was observed during this period.,NycoCard for A1C test,NycoCard 產品說明,RAPID Result within 3 MINUTES during patient consultation
32、FINGER PRICK, WHOLE BLOOD (5L) applicable (make use of blood lancet or EDTA tube) STANDARDIZED according to the recommendations of the ERL Laboratory (European Reference Laboratory) Measuring Range: 3-18% HbA1c FDA APPROVAL for Diabetes Monitoring Similar system capable to run CRP, D-Dimer & Microalbumin,
