餐后血糖与心血管病

1、.,1,餐后血糖与心血管病,.,2,正常人餐后状态的定义及持续时间,早餐 午餐 晚餐 0:00 4:00 早餐 am am,8:00 11:00 2:00 5:00 am am pm pm,Time of blood sampling to obtain a diurnal blood glucose profile,餐后状态 餐后吸收状态 空腹状态,HbA1C =,PPG,FPG,+,.,4,餐后高血糖对HbA1c有非常大的影响,HbA1c,FBG,餐后高血糖 造成的差,随机化水平,0,3,6,9,Years,.,5,Beta 细胞功能下降,Adapted from UKPDS 16: Di

2、abetes 1995: 44:1249-1258,Beta 细胞功能 (%),自诊断的年份,UKPDS,.,6,2型DM的自然病程与-C功能的关系,-24 -10 0 30年 DM,100%,IGT,.,7,胰岛素抵抗,肝葡萄糖输出,内源性胰岛素,餐后血糖,空腹血糖,内源胰岛素,IGT糖尿病,微血管并发症,大血管并发症, 4-7 年 ,“诊断为糖尿病”,糖尿病的严重性,Clinical Diabetes Volume 18, Number 2, 2000,.,8,2 型糖尿病的三个阶段,阶段 Pathophysiology 指示 第一阶段 -胰岛素抵抗 -胰岛素分泌 - 正常 PG 第二阶段

3、 -更严重的胰岛素抵抗 -早期餐后胰岛素分泌受损IGT(餐后高血糖） 第三阶段 -严重的胰岛素抵抗 -受损的胰岛素分泌 - 空腹高血糖 -增高的内源性葡萄糖代谢 - 餐后高血糖 1.Warram J,et al:Ann Intem Med 1990,113:909-915 2.Mitrakou A,et al: N Engl J Med 1992,326:22-29 3.Ninneen SF: Diabetic Med 1997,14(suppl 3):s19-s24,.,9,“Ticking Clock”(钟摆)假说,钟摆动已始于 微血管并发症 高血糖出现时 大血管并发症 发展在糖尿病前期,

4、Haffner SM et al JAMA 1990; 263: 2893-2898,.,10,IMPORTANDCE OF MEALTIME GLUCOSE EXCURSIONS,Mealtime and postprandial hyperglycemia are typically the earliest clinical manifestations of Type 2 diabetes,Worsens pre-existing prediabetic defects of insulin secretion and action,and contributes to overall

5、 daily hyperglycemia(as reflected in HbA1c) Control of PBG optimizes overall glycemic control “Therapy focused on lowering PBG,not FBG may be superior for lowering HbA1c” (Basyr et al Diabetes Care 23:1236,2000) Leads to reactive hyperinsulinemia Associated with increased risk for macrovascular comp

6、lications - IGT is a risk factor for CVD complications - Epidemiologic studies show a relationships between PBG and risk for CVD complications,.,11,Mealtime Glucose Excursions and risk of Cardiovascular Disease(1),Honolulu heart program,1987 Diabetes Intervention Study,1998 Funagata Diabetes Study,1

7、999 The Rancho Bernardo Study,1998,CHD incidence and mortality increase stepwise with increasing IGT PBG,but not FBG is associated with CHD IGT,but not IFG,is a risk factor for CVD 2-hPBG alone more than doubles the risk of fatal CVD and CVD in older adults “the use of FBG alone for DM screening or

8、diagnosis may fail to identify most older adults at high risk for CVD and should be re-evaluated”,.,12,Mealtime Glucose Excursions and risk of Cardiovascular Disease(2),Paris Prospective Study,1999 Whitehall Study,1999 HOORN Study,1999,Death rates for CHD increasing 2hPBG levels Men in the upper 2.5

9、% of the 2hPBG distribution had significantly higher CHD mortality High PBG levels,especially 2h-load PBG concentrations and to a lesser extent,HbA1c values, indicate a risk for CVD mortality,.,13,Mealtime Glucose Excursions and risk of Cardiovascular Disease(3),Pacific and Indian Ocean Population S

10、tudy,1999 DECODE study,1999 Theodora S. et al, 2000,Isolated 2h PBG challenge increases total mortality and CVD mortality,and carries a greater risk than isolated FBG CHD mortality is more related to 2-h PBG than to FPG.FPG does not identify subjects at risk for CHD PG and PGS are more strongly asso

11、ciated with carotid IMT than FBG and HbA1c,.,14,Importance of mealtime glucose excursions,Mealtime and post-meal hyperglycemia are typically the earliest manifestations of Type 2 diabetes,PBG Contributes to overall daily hyperglycemia(e.g as reflected in HbA1c and microvascular complications) PBG As

12、sociated with increased risk for macrovascular complications -IGT is a risk factor for vascular complications -numerous epidemiologic studies show a relationship between PBG levels and risk for cardiovascular complications,.,15,Adjusted Survival According to Diabetes Category: Pacific and Indian Oce

13、an Population,IFH - isolated fasting hyperglycemia (FPG7mmol/L;2h PG11.1mmol/L) KD - known diabetes,KD,IPH,normal,IFH,males,J.E. Shaw et al. Diabetologia 1999;42: 1050,血压正常的不同糖耐量患者的临床特征（1）,李春霖，潘长玉，陆菊明等 中华内科杂1997;36(8):536-539,血压正常的不同糖耐量患者的 动态血压改变(XSx),为昼夜差值 李春霖，潘长玉，陆菊明等 中华内科杂1997;36(8):536-539,组别 (例

14、) (20) (20) (20) 男/女 12/8 14/6 13/7 年龄（岁） 52.22.3 52.0 1.9 53.2 1.9 0.10 0.9007 FBS (mmol/L) 5.13 0.23 6.940.20 9.58 0.72 22.79 0.0001 PBS2h (mmol/L) 6.37 0.19 8.65 0.26 13.01.13 23.00 0.0001 ch(mmol/L) 3.870.16 5.460.23 5.040.17 17.39 0.0001 HbA1c (%) 5.390.15 7.42 0.21 9.790.71 23.42 0.0001 UAE (m

15、g/L) 4.17/ 9.12/ 17.4 / 4.26 0.0202 0.48 0.43 0.29 FIns(mu/L) 3.63/ 4.47/ 8.13/ 5.90 0.0073 0.28 0.35 0.44 Ins2h(mu/L) 22.4 / 22.9/ 27.5/ 0.27 0.7638 0.33 0.42 00.42 IAI -2.98 -3.35 -4.07 9.69 0.0006 24hSBP(mmHg) 129 4 1272 133 4 0.67 0.5160,NGT IGT DM2 F值 P值,血压正常的不同糖耐量患者的临床特征（XSx）,UAE和Ins呈偏态分布，结果用几

16、何均数/ 可信因素表示， IAI 为胰岛素敏感指数 李春霖，潘长玉，陆菊明等 中华内科杂1997;36(8):536-539,NGT IGTDM2F值P值,组别 (n= ) （20） （20） （20） 昼SBP 921 912 862 3.54 0.0356 夜SBP (mmHg) 1084 1184 1294 3.34 0.425 DBP (%) 37.16.0 46.45.5 42.05.1 0.69 0.5049 SBP (%) 7.12.5 9.92.0 3.7 2.1 2.31 0.0186 MBP (%) 10.0 2.5 11.22.2 4.32.0 3.27 0.0452,血

17、压正常的不同糖耐量患者的动态血压改变（XSx）,李春霖，潘长玉，陆菊明等 中华内科杂1997;36(8):536-539,血糖异常心电图明尼苏达编码分析 检出频率 例（ ）,* * * *,0(0) 10(96.2) 18(173.1) 3(28.8),32(95.2) 228(543.5) 256(579.5) 62(176.8),6(45.8) 18(137.4) 15(114.5) 10(76.3),11(22.5) 112(229.8) 128(261.8) 28(57.3),15(26.9) 98(176.3) 113(203.2) 24(43.2),Q/QS(1-X) ST压低（4

18、-X） T波（5-X） 室内阻滞（7-X),104,合计(176),NOD(131),IGT（489）,DM（556）,与血糖异常比较*0.05 朱艳 陆菊明等 中国糖尿病杂志 1997；5（1）：11-14,血糖异常合并与不合并高血压的 心电图明尼苏达编码分析比较 例(),与正常体重组比 *0.01 朱艳，陆菊明等 中国糖尿病杂志 1997；5（1）：11-14,血糖异常合并与不合并高血压的 心电图明尼苏达编码分析比较 例(),与非高血压组比 *0.05 朱艳，陆菊明等 中国糖尿病杂志 1997；5（1）：11-14,结果显示与正常糖尿病患者相比，IGT组24小时ABPM的变化具有夜间血压增

19、高和昼夜血压差值减小的趋势，表示IGT患者已开始出现早期高血压改变,.,24,DECODE欧洲糖尿病诊断标准的流行病学调查研究,FPG（ADA诊断标准）及OGTT2hPG（WHO）诊断标准与死亡率相关性研究 欧洲实施13项前瞻性研究分析 对象：30岁以上25364名（男：18048，女：7316） 研究开始时非糖尿病患者24089名，糖尿病患者1275名） 追踪时间：7.3年 累积追踪时间：男：132,785人年 女：48,900人年,DECODE study group:Lancet, 354, 617,1999,FPG及2hPG与总死亡率的相对危险度的关系,110110-125126 FP

20、G (mg/dl) 年龄、性别、设施、BMI、SBP、吸烟 DECODE study group:Lancet, 354,617,1999. Tuomilehto J.:17th IDF,Mexico City, November, 2000,200 140-200 140,2hPG(mg/dl),总死亡率的相对危险度,总死亡率与2hPG的关系(DECODE study),4,000 3,000 2,000 1,000 0,0 40 80 120 160 200 240 280 320 360 2hPG(mg/dl) Tuomilehto J.:17th IDF, Mexlco City, N

21、ovember, 2000,FDP126 mg/dl r=0.71099+0.09866X,参 加 试 验 人 数,总死亡率与FPG的关系(DECODE study),8,000 6,000 4,000 2,000 0,0 40 80 120 160 200 240 280 320 360 FPG (mg/dl) Tuomilehto J.: 17th IDF, Mexlco City, November, 2000,2hPG200 mg/dl r=5.24638-1.30249X+0.09802X2,参 加 试 验 人 数,心血管疾患死亡率与2hPG的关系(DECODE study),4,0

22、00 3,000 2,000 1,000 0,4 3 2 1 0,0 40 80 120 160 200 240 280 320 360 2hPG (mg/dl) Tuomilehto J.:17th IDF, Mexlco City, November, 2000,r=0.71099+0.09866X,相对危险度,参 加 试 验 人 数,心血管疾患死亡率与FPG的关系(DECODE study),8,000 6,000 4,000 2,000 0,8 6 4 2 0,0 40 80 120 160 200 240 280 320 360 FPG (mg/dl) Tuomilehto J.:

23、17th IDF, Mexlco City, November, 2000,r=5.24638-1.30249X+0.09802X2,参 加 试 验 人 数,相对危险度,总死亡因子与2hPG的重要性(FPG、HbAIC）比较, 年龄、性、设施、BMI、SBP、LDL-C、HDL-C、 TG、F-IRI、吸烟,总死亡率,2hPG(mg/dl) 6.5) 6.5 6.5) Number 2000 88365 87 分析对象：糖尿病诊断男性1,416名，女性1,277名，平均追踪期间8年， 累积追踪 年数19,980人年 Qiao Q.et al., 17 th IDF,Mexico City, N

24、ovember, 2000,2hPG是与总死亡率相关的因素（与空腹及糖化血红蛋白比较）,各参数上升1个标准偏差与总死亡之间的比较 （*FPG：19mg/dl 2hPG:52mg/dl HbA1c:0.68%),FPG 2hPG HbA1c 男性 各种变数补正1.10 1.17 1.13 血糖值/HbA1c补正 0.94 1.17 1.09 女性 各种变数补正 1.18 1.22 1.13 血糖值/HbA1c补正 1.13 1.19 0.89 全体 各种变数补正 1.13 1.19 1.13 血糖值/HbA1c补正 0.98 1.17 1.04,*年龄、医院、BMI、SBP、LDL-C、HDL-

25、C、TG、F-IRI、吸烟等被正 FPG、2hPG、HbA1c的补正 Qiao Q.et al:17th IDF, Mexico City, November, 2000,IGT是心血管疾病死亡的危险因素，而IFG不是The Funagata Diabetes Study,观察时间（年）,观察时间（年）,观察对象为40岁以上的居民2651名 Tominaga M.et al:Diabetes Care, 22, 920,1999,累积生存率,餐后血糖控制不良是心血管疾病的危险因素,饭后(早饭后1小时) 良好:80-144mg/dl(n=549) 正常:180mg/dl (n=341) 不良:1

26、80mg/dl (n=246) 空腹时血糖(饭前) 良好:80-110mg/dl(n=363) 正常:140mg/dl (n=391) 不良:140mg/dl (n=372),饭后血糖,FPG,对象：新的2型糖尿病，运动疗法的病人1139例追踪11年 Hanefeld M.et al., 17 th IDF, Mexice City, November, 2000,心 肌 梗 塞 的 发 病 率 （千人）,餐后血糖控制不良对心血管疾病死亡影响DIS:糖尿病干预治疗,餐后血糖 良好 正常 不良 各组间差异显著,1.00 .98 .96 生 .94 存 .92 率 .90 .88 .86,0 2

27、4 6 8 10 12 14 16 生存期(年) Hanefeid M.et al.:17th IDF, Mexico City, November, 2000,餐后血糖累积心血管疾患死亡率 追踪期间11年以上(Kaplan-Meter法),餐后高血糖、高血脂症对血管壁的影响,餐后高血糖,餐后高血脂,血管壁血管内皮细胞障碍动脉硬化 Haller H.:Diab. Res. Clin.Prac.,40(Suppl),S43,1998,餐,餐后血糖/空腹血糖的持续时间,餐后,吸收后移行期,餐后,餐后,吸收后移行期,空腹时,吸收后移行期,早餐 午餐 晚餐 0.00am 4.00am 早餐 Monme

28、r L. :Eur.J.Clin. Linvest.,30(Suppl.2),3,2000,.,37,Decode研究的临床意义,Source: DECODE Study Group. Br J Med. 1998; 317: 371 - 375,Postprandial hyperglycaemia,NGT,Low risk,Low risk,High detection,Fasting hyperglycaemia,High detection,High risk,NFG,Low detection,High risk,.,38,DECODE:结论 餐后2小时血糖（2HBG）是糖尿病死亡的

29、独立危险因素。 DECODE Study Group .Lancet 1999;354:617-621,.,39,RAID研究的结果,Adapted from Temelkova-Kurktschiev T et al. Diabetes und Stoffwechsel 1998; 7: 227 - 232,* Significantly different from healthy controls and NGT * Significantly different from healthy controls, NGT and IGT,Healthy controls,IGT,Type 2

30、 diabetes,NGT,N=100,N=152,N=109,N=68,*,*,*,*,.,40,*,*,* *,*,relative risk of CHD,Relative risks of cardiovascular disease for impaired glucose tolerance and diabetes compared with normal glucose tolerance after adjustment for age and sex ( ) and for systolic blood pressure, body mass index, abnormal

31、 electrocardiogram, total and high-density lipoprotein cholesterol, smoking and drinking ( ) . *p0.05 * p0.01 compared with normal individuals. Fujishima Diabetes 1996; 45(suppl 3): 514-516,Relative Risks of CHD for NGT, IGT and Diabetes,.,41,Incidence of myocardial infarction( )and mortality rate (

32、 ) in relation to quality of control of fasting blood glucose postprandial blood glucose, triglycerides, and blood pressure: 11-year follow-up to the Diabetes Intervention Study (DIS), *p0.05,Good,Borderline,Poor,Fasting blood glucose,250 200 150 100 50 0,Good,Borderline,Poor,Postprandial blood gluc

33、ose,Rate per 1000,*,*,*,*,*,*,Hanefeld M.et al, Diabetic Medicine 1997, 14: s6-s11,餐后高血糖与心血管并发症,.,42,餐后高血糖与心血管并发症,25 20 15 10 5 0,Rate per 1000,Borderline,Triglycerides,Good,Borderline,Poor,Blood pressure,Incidence of myocardial infarction( )and mortality rate ( ) in relation to quality of control of fasting blood glucose postprandial blood glucose,triglycerides,and blood pressure: 11-year follow-up to the Diabetes Intervention Study(DIS),*p0.05;*p0.01,Hanefeld M.et al, Diabetic Medicine 1997, 14: s6-s11,*,*,*,*,*,*,Good,Poor,.,43,Other studies which su