血糖控制过程中的血糖监测策略(强生).ppt

1、血糖控制过程中的血糖监测策略SMBG和HbA1c的应用,血糖控制过程中的血糖监测策略SMBG和HbA1c的应用,H | C = O | OH C H | H C OH | OH C H | H C OH | H C OH | H 糖的线性醛基形式,Hb / C / / C / N H / H HbA 角的颉氨酸游离氨基端, H | C H | C = O | H C OH | OH C H | H C OH | H C OH | H 糖化血红蛋白,Hb / C / / C / N / H,+,HbA1c是如何形成的?,H | = C | OH C H | H C OH | OH C H | H

2、 C OH | H C OH | H 醛糖 (不稳定的Schiff碱),Hb / C / / C / N,Amadoori Molecular rearrangement,血糖监测的关键因素,HbA1c: 糖尿病的重要评估工具 美国糖尿病协会 (1) 美国内分泌学院 (ACE) (2) 英国统一声明 (3) 临床生化协会 英国临床糖尿病协会 英国糖尿病协会 皇家医师学院 皇家儿保学院 皇家病理学院 皇家全科医生学院 加拿大医疗协会 (4),(1) ADA Standards of Medical Care for Patients with Diabetes Diabetes Care vol

3、 26 (supplement 1) Jan 2003 S33-S50. (2) American College of Endocrinology Consensus Statement on Guidelines for Glycemic Control. Endocrine Practice vol 8(Suppl 1) January/February 2002. 5-11. (3) Marshall SM and Barth JH. Standardization of HbA1c measurements: a consensus statement. Ann Clin Bioch

4、em 2000;37:45-46 (4) Canadian Medical Association Journal 1998;159(8 Suppl):S1-29,血糖监测的关键因素,HbA1c 的检测频率 美国内分泌学院(1) 美国糖尿病协会(2) 达标者：2次/年 未达标者和/或需调整用药者：4次/年,(1) ACE Consensus Statement on Guidelines for Glycemic Control. Endocrine Practice vol 8(Suppl 1) January/February 2002. 5-11. (2) ADA Standards o

5、f Medical Care for Patients with Diabetes Diabetes Care vol 26 (supplement 1) Jan 2003 S33-S50.,血糖监测的关键因素,HbA1c 的达标值 ACE(1) 达标值： 0.084,(1)ACE Consensus Statement on Guidelines for Glycemic Control.Endocrine Practice vol 8(Suppl 1) January/February 2002. 5-11. (2) ADA Standards of Medical Care for Pa

6、tients with Diabetes Diabetes Care vol 26 (supplement 1) Jan 2003 S33-S50. (3) Canadian Medical Association Journal-JAMC 1998 Clinical Guidelines,血糖达标值 (血浆参考值),(1) ADA Standards of Medical Care for Patients with Diabetes Diabetes Care vol 26 (supplement 1): S33-S50, 2003. (2) American College of End

7、ocrinology (ACE) Consensus Statement on Guidelines for Glycemic Control. Endocrine Practice Vol 8 (Suppl 1): 5-111, 2002. (4) Canadian Medical Association Journal-JAMC 1998 Clinical Guidelines (5) HEDIS 2000 Guidelines (6) ADA: Standards of Medical Care for Patients with Diabetes. Diabetes Care, vol

8、 23 (supplement 1):S32-S42, 2000.,血糖监测的关键因素,全球关于HbA1c标准化所作的工作 国家糖化血红蛋白标化计划对各个测法及实验室资质作出规定(NGSP)(1) IFCC 正在规定测量流程与校正标准(2),(1) Finke A., Kobold U, Hoelzel W, Weycamp C, Jeppsson JO, Miedema K. Preparation of a candidate primary reference material for the international standardisation of HbA1c determin

9、ations. Clin Chem Lab Med 1998; 36: 299-308 (2) Jeppsson J-O, Kobold U, Barr J, Finke A, Hoelzel W, Hoshino T, Miedema K, Mauri P, Mosca A, Paroni R, Thienpont L, Umemoto M, Weykamp CW. Approved IFCC reference method for the measurement of HbA1c in human blood. Clin Chem Lab Med 2002; 40: 78-89,探讨平均

10、血糖与 HbA1c的关系,注意 下列情况 HbA1c 可能假性升高：氨基甲酰化, 乙酰化, 抗坏血酸化等 实验室(.)的因素也可影响 HbA1c 的准确性,Gabbay KH et al. Glycosylated hemoglobins and long-term blood Glucose control in diabetes mellitus. J Clin Endocrinol Metab 44:859-864, 1977. Koenig RJ et al. Correlation of glucose regulation and hemoglobin HbA1c in diabe

11、tes mellitus. New Eng J Med 295:417-420,1976. Dunn PJ et al. Temporal relationship of glycosylated hemoglobin concentrations to glucose control in diabetes. Diabetologia 17:213-220,1979.,历史回顾平均血糖与 HbA1c的换算,1982: Svendsen PA, Lauritzen T et al.1 HbA1c% = 2.07 x 平均全血 血糖 mmol/l 0.596 (r = 0.98) 1984: G

12、ain TH, Tuphorn I, Botterhorn P. 2 HbA1c% = 0.038 x 平均全血 血糖 mmol/l 3.78 (r = 0.89) 1984: Nathan D; 4-Point taken around 2 meals3 (HbA1c%) x 33.3 86 =平均全血 血糖 mg/dl （每日2次餐前，2次餐后 90-120 min x 2 月 (r = 0.958 ;r2 = 0.92),(1) Svendsen PA, Lauritzen T et al. Diabetologia 1982 vol 23:403-405. (2) Gain TH, T

13、uphorn I, Botterhorn P. Lab Medicine 1984 vol 8 :79-81. (3) Nathan D et al. The Clinical Information Value of the Glycosylated Hemoglobin Assay. N Engl J Med. 310;341-346: 1984.,DCCT,采用强化治疗控制血糖后,各种并发症的发生率大大降低: 首次出现任何视网膜病变的发生率下降 27% 临床意义的视网膜病变的发生率下降 34-76% 微蛋白尿的发生率下降 39% (尿液中排泄 40mg/24 小时) 临床级大蛋白尿的发生

14、率下降 56% 临床的神经病下降 69%,2020/9/13,DCCT: HbA1c和毛细血管血糖水平的降低,在HbA 1c水平存在显著性差异约2% (9.0% vs 7.1%) 常规治疗组 = 12.8 + 3.0mmol/L (231 +55 mg/dL) 强化治疗组 = 8.6 + 1.7mmol/L (155 +30 mg/dL),The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and

15、 progression of long-term complications in insulin-dependent diabetes mellitus (DCCT). New England Journal of Medicine. 329:977986,1993.,DCCT 回顾分析Rohlfing CL and Goldstein DE et al.Defining the Relationship Between Plasma Glucose and HbA1c.Diabetes Care.25;275-278.2002.,1441 名患者 1439个患者 7-点自我监测血糖数据收

16、集 餐前, 餐后90分钟,睡前 每个季度决定 37,058个每季度的HbA1c 测量值 平均参加时间为6.5年 共26,056次 HbA1c测量值用于分析 平均每个病人有18个数据被应用,各点血糖和HbA1c的相关性,Rohlfing CL and Goldstein DE et al.Defining the Relationship Between Plasma Glucose and HbA1c.Diabetes Care.25;275-278.2002.,r-value,平均血浆血糖值与HbA1c的关系式,DCCT: 选取3餐前后和睡前共7点 (HbA1c%) x 35.6 77.3=

17、 餐前、餐后90分钟、睡前的平均血浆血糖值水平 （mg/dl (r = 0.82)* (HbA1c%) x 1.98 4.29=餐前、餐后90分钟、睡前的平均血浆血糖值水平（ mmol/l）,*Rohlfing CL and Goldstein DE et al.Defining the Relationship Between Plasma Glucose and HbA1c.Diabetes Care.25;275-278.2002.,最新的!,平均血浆血糖值 = 7点血浆血糖值的综合平均值 平均血浆血糖值 MPG =( + + + + + + )/7 空腹血糖 早餐后血糖 午餐前血糖 午

18、餐后血糖 晚餐前血糖 晚餐后血糖 睡前血糖,平均血浆血糖值与HbA1c的关系式,HbA1c 275 278.2002. (2) ADA Standards of Medical Care for Patients with Diabetes. Diabetes Care. 26 (supplement 1): S33-S50, 2003. (3) Goldstein DE, Little RR, Lorenz RA, Malone JI, Nathan D, Peterson CM: Tests of Glycemia in Diabetes. Diabetes Care.18:896-909

19、, 1995.,示例 Solution MPG (mg/dl),7-Point DCCT taken around 3 meals and BT: (HbA1c%) x 35.6 77.3= mean plasma blood glucose in mmol/l of pre-meal, 90 minute post-prandial, and bedtime:Pearson correlation coefficient (r = 0.82) (1),X=153 HbA1c=6.47,X=155 HbA1c=6.52,(1) Rohlfing CL and Goldstein DE et a

20、l.Defining the Relationship Between Plasma Glucose and HbA1c. Diabetes Care.25;275-278.2002.,示例 Solution MPG (mmol/l),7-Point DCCT taken around 3 meals and BT: (HbA1c%) x 1.98 4.29= mean plasma blood glucose in mmol/l of pre-meal, 90 minute post-prandial, and bedtime: Pearson correlation coefficient

21、 (r = 0.82) (1),5.17-13.78/6.39-8.89/4.22-14.78/6.28,3.83-14.00/6.17-8.22/6.06-15.39/6.56,X= 8.5 HbA1c= 6.45,X= 8.6 HbA1c= 6.51,(1) Rohlfing CL and Goldstein DE et al.Defining the Relationship Between Plasma Glucose and HbA1c. Diabetes Care.25;275-278.2002.,HbA1c与平均血糖的关系-结论1,HbA1c (%) 和血浆血糖之间的线性关系已经

22、通过DCCT的研究数据加以确定了. 这个计算工具可以帮助向病人解释如何通过控制每天几个特定时刻的特定血糖目标, 来帮助他们实现HbA1c控制目标. 在为病人做HbA1c 测试之前,利用7点的毛细血管血糖值来完成上述等式. 可以利用这个结果为您的病人设立恰当的日常血糖控制目标.,平均血糖与HbA1c的关系相关问题的思考,糖尿病患者餐后的血糖波动超出允许范围的情况有多频繁? HbA1c 受空腹还是受非空腹血糖影响大?,Bonora E. et al. Plasma Glucose Levels Throughout the Day and HbA1c Interrelationships in T

23、ype 2 Diabetes. Diabetes Care 24:2023-2029,Monnier Study探讨餐前及餐后血糖与HbA1c 的关系以口服药治疗的2型糖尿病病人,290 例 (男139, 女151) 治疗(单药/联合治疗) 控制饮食 双胍类: 二甲双胍 (1,700 mg/day) 磺脲类: Glyburide (5-15 mg/day) 未用胰岛素或拜糖平 进餐时间： 8:00 am 与 12:00 am 抽静脉血时间：8:00 am, 11:00 am, 2:00 pm (+ 2 PPG) , 5:00 pm (+ 5 PPG) 所有患者均同时采用持续血糖监测 (CGMS

24、),Monnier L, Lapinski H, Colette C. Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients. Diabetes Care 26: 881-885, 2003.,Monnier Study 分析方法 (1),a: 简单4点法 b: CGMS 9-hour profile (8am-5pm) c: CGMS 24-hour profile * 曲线下面积

25、(AUC1): PPG 曲线下面积 (AUC2): 注意计算的FPG 6.1 mmol/l 110mg/dl (高于正常 ) 曲线下面积 (AUC2) (AUC1),(AUC2),(AUC1),(1) Monnier L, Lapinski H, Colette C. Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients. Diabetes Care 26: 881-885, 2003

26、.,Monnier Study 结果(1),图 A : 多点静脉血糖(mmol/l)的价值 图 A: 4点血糖图 反映 PPG (AUC1) 图 B: 曲线下面积 (AUC) AUC1 (PPG) 注意曲线平坦而 HbA1c AUC2 注意曲线升高而 HbA1c AUC2 (FPG) - AUC1 (PPG),(1) Monnier L, Lapinski H, Colette C. Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia o

27、f Type 2 Diabetic Patients. Diabetes Care 26: 881-885, 2003.,Monnier Study 分析(13) 餐后血糖和空腹血糖对日常高血糖的影响不同,(13) Monnier L, Lapinski H, Colette C. Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal Hyperglycemia of Type 2 Diabetic Patients. Diabetes Care 26: 881-88

28、5, 2003.,黑色: 空腹血糖的贡献率(%) 白色: 餐后血糖的贡献率(%) 50% 线,Monnier Study 分析 (25)高血糖与HbA1c的关系,非胰岛素治疗的2型糖尿病患者其空腹血糖和餐后血糖对HbA1c 的相对贡献 餐后 HbA1c 10.2%时：相对贡献30.5% 空腹 HbA1c 10.2%时：相对贡献69.5%,(25) Monnier L, Lapinski H, Colette C. Contributions of Fasting and Postprandial Plasma Glucose Increments to the Overall Diurnal

29、Hyperglycemia of Type 2 Diabetic Patients. Diabetes Care 26: 881-885, 2003.,HbA1c与平均血糖的关系-结论2,控制餐后血糖与控制空腹血糖同等重要 当患者由轻,中度高血糖逐步发展为严重高血糖时, 空腹高血糖及餐后高血糖对日常高血糖的影响也在逐步变化. 轻, 中度高血糖的糖尿病人的日常高血糖, 以餐后高血糖的影响为主,随着病情的加重,空腹高血糖对日常高血糖的影响也增大了.,HbA1c 和多点血糖的测定,(15) Bonora E. et al. Plasma Glucose Levels Throughout the D

30、ay and HbA1c Interrelationships in Type 2 Diabetes. Diabetes Care 24:2023-2029,2001.,LifeScan Confidential: For Internal Use Only,HbA1c 和多点血糖的测定,(15) Bonora E. et al. Plasma Glucose Levels Throughout the Day and HbA1c Interrelationships in Type 2 Diabetes. Diabetes Care 24:2023-2029, 2001.,HbA1c 和多点

31、血糖测定,(15) Bonora E. et al. Plasma Glucose Levels Throughout the Day and HbA1c Interrelationships in Type 2 Diabetes. Diabetes Care 24:2023-2029,*P 0.001, HbA1c assay performed same day *P 0.001, HbA1c assay performed mid-month, FPG correlation for mean of 5 days worth of SMBG tests during defined ti

32、me period,HbA1c与平均血糖的关系-结论3,全面而详尽的全天血糖水平的描述, 不仅依赖于空腹血糖和/或糖化血红蛋白水平的监测, 而且还要对其余时间, 尤其是餐后时段的血糖监测. 更好地控制糖化血红蛋白, 降低糖尿病慢性并发真的风险, 不仅需要控制好空腹血糖, 而且还需要控制好全天的血糖水平 许多糖尿病人表面上某些糖代谢指标控制良好.实际上, 他们的餐后水平很高和/或餐后高血糖状态持续很长.,测 HbA1c的间期进行自我血糖监测以巩固疗效,患者要遵循 SMBG 方案 并提交 正确数据,患者要会正确服药，调整饮食,评估SMBG 方案 血糖的测量时间与频度,请您推荐:,一种由空腹血糖,

33、餐后血糖和糖化血红蛋白组成的血糖监测方法以获得病人完整的血糖控制图! Source: Bonora E. Calcaterra F. Lombardi S. Bonfante N. Formentini G. Bonadonna R. Muggeo M Plasma Glucose Levels Through the Day and HbA1c Interrelationships in Type 2 Diabetes: Implications for treatment and monitoring of metabolic control. Diabetes Care 2001; 24

34、: 2023-2-29,进一步探讨平均血糖与HbA1c的稳定状态关系,问题? 测试糖化血红蛋白之前一段时间所测得的血糖值及相应的测试时间与糖化血红蛋白是一个什么样的关系1,2,3,4?,1. Gabbay KH et al. Glycosylated hemoglobins and long-term blood Glucose control in diabetes mellitus. J Clin Endocrinol Metab 44:859-864, 1977. 2. Koenig RJ et al. Correlation of glucose regulation and hemo

35、globin HbA1c in diabetes mellitus. New Eng J Med 295:417-420,1976. 3. Dunn PJ et al. Temporal relationship of glycosylated hemoglobin concentrations to glucose control in diabetes. Diabetologia 17:213-220,1979. 4. Saunders AM. Testing assumptions about glycohemoglobin with a retrospective time-resol

36、ved test. Laboratory Hematology 4:142-148,1998.,模式A (55/538),模式 B (172/538),模式 B + (133/538),DAYS AGO,GHb %,糖化血红蛋白累积的发展模式,正常血糖时: 注意低速率的累积,0 30 60 90 120,高血糖时: 注意更高速率的累积,Saunders AM. Testing assumptions about glycohemoglobin with a retrospective time-resolved test. Laboratory Hematology 4:142-148, 19

37、98.,DAYS AGO,GHb %,高血糖,正常血糖,0 30 60 90 120,Saunders AM. Testing assumptions about glycohemoglobin with a retrospective time-resolved test. Laboratory Hematology 4:142-148, 1998.,糖化血红蛋白累积的发展模式,模式 C (30/538),模式 D (38/538),DAYS AGO,GHb %,正常血糖 或 低血糖,高血糖,高血糖,0 30 60 90 120,Saunders AM. Testing assumption

38、s about glycohemoglobin with a retrospective time-resolved test. Laboratory Hematology 4:142-148, 1998.,糖化血红蛋白累积的发展模式,模式 E (36/538),DAYS AGO,GHb %,起初的正常血糖: 注意GHb的低速率的累积,近期的高血糖 注意GHb的高速率的累积,0 30 60 90 120,Saunders AM. Testing assumptions about glycohemoglobin with a retrospective time-resolved test.

39、Laboratory Hematology 4:142-148, 1998.,糖化血红蛋白累积的发展模式,模式 J (26/538),GHb %,DAYS AGO,高血糖,正常血糖,高血糖,正常血糖,高血糖,0 30 60 90 120,Saunders AM. Testing assumptions about glycohemoglobin with a retrospective time-resolved test. Laboratory Hematology 4:142-148, 1998.,糖化血红蛋白累积的发展模式,平均血糖和 HbA 1c的关系的研究实验,Tahara Y 和

40、Shima K* 内科部(YT)、 Meimai 中央医院,明石, 日本 实验室医学部(KS)、 德岛医学院,德岛,日本 应用线性数学动力模型来分析这个现象*,Tahara Y, Shima K. Kinetics of HbA1c, Glycated Albumin and Fructosamine and Analysis of Their Weight Functions Against Preceding Plasma Glucose Level. Diabetes Care 18:440-447. Shi K, Tahara Y, Shima K, Yasukawa K. The R

41、esponse of Glycated Albumin to Blood Glucose Change in the circulation in streptozotocin-diabetic rats, comparison of theoretical values with experimental data. Diab Res Clin Prac 17:153-160, 1992.,HbA1c 的管理目标,HbA1c糖化速率的动力学问题 不同时间段的平均血糖值对HbA1c的贡献比重是不同的! Tahara Y, Shima K. Kinetics of HbA1c, Glycated Albumin, and Fructosamine and Analysis of Their Weight Functions Against Preceding Plasma Glucose Level. Diabetes C