2 小时糖耐量试验的临床意义 finnish academy research fellow 芬兰赫尔辛基大学及...
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2 小时糖耐量试验的临床意义
Finnish Academy Research Fellow
芬兰赫尔辛基大学及 国立公共卫生研究院
北大糖尿病论坛 2007 年 5 月 12 日， 北京
乔青 MD, Ph.D
糖尿病诊断试验 : 历史回顾糖尿病
症状尿糖
空腹血糖糖耐量 (1913 年 )
Jacobsen A. Biochem Z 51:443, 1913
Normal Glucose Homeostasis Daytime Profile (N=12, health; Mean + 95%CI)
Owens D ,Zinman B & Bolli G : Lancet 358,739,2001
Meal Times
80
40
0
Insu
lin (
mU
/L)
08.00 13.00 16.00 19.00 h
Glu
co
se
(m
mo
l/L)
8
4
2
6
什么是糖耐量异常 ?
1. 高于均值 +2 标准差可诊断糖尿病 : • 根据年轻 (20-30 岁 ) 健康人群资料 , 纯统
计！不考虑临床，预后及年龄 (50 年代 ) • 2h 全血血糖 >=120mg/dl (100g 糖耐量 ) 诊
断糖尿病 ( 血浆血糖比全血高 14-16%!)• 发病率高• 诊断标准混乱 ( 血样，服糖量，时间 ) • 直到 70 年代
Mosenthal H.O. and Barry E (Ann Intern Med 33: 1175, 1950)
什么是糖耐量异常 ?
1. 均值 +2 标准差
2. 血糖双峰分布 , 小血管病变 ( 眼病，肾病等 ): 糖尿病高发人群 , 如 Pima Indians (1971), Mexican-Americans, Micronesians, Polynesians
Bimodal distribution of glucoseand prevalence of retinopathy and
proteinuria in Pima Indians
Knowler WC etc. Diabetes Metab Rev 6: 1-27, 1990
Copyright ©1994 BMJ Publishing Group Ltd.
McCane, D R et al. BMJ 1994;308:1323-8
5 year cumulative incidence (top) and prevalence (bottom) of retinopathy in relation to tenths of 2hPG, FPG, and HBa1c
现用诊断标准• NDDG1979: FPG>=7.8 mmol/l and 75g OGTT at ½, 1,
1½, 2 hours • WHO 1980: adopted the NDDG criteria, 2h
glucose>=11.1 mmol/l after 75g load as “ 金标准”• WHO 1985: slightly modified the WHO 1980 criteria• ADA 1997: FPG 7.8 mmol/l to 7.0 mmol/l ， Not use
OGTT• WHO 1999: adopted the FPG 7.0 mmol/l, retained the
2h OGTT• WHO/IDF 2006: no changes except for some terms
什么是糖耐量异常 ?
1. 均值 +2 标准差2. 血糖双峰分布 , 小血管病变
3. 大血管病变 : 心脑血管及外周血管病变
Dysglycemia >> Normoglycemia in Acute and Stable CV Disease
• Consecutive pts: 2107 in-pts; 2854 out-pt elective CV consults in Europe (71% men; mean age 66)
• OGTT/old DM in 1587 (75%) acute & 1857 (66%) elective pts before discharge or within 2 mo.
Euro Heart SurveyEuro Heart SurveyBartnik Bartnik M M et al; Eur Ht J 2004;1880et al; Eur Ht J 2004;1880
NGT
IFG
IGT
Known DM
New DM
29%35%
22%22%
31% 30%
15%10%
3%3%
0
20
40
60
80
100%
Acute Elective
The DECODE Study (http://www.ktl.fi/decode/index.html)
Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe
2-hour plasma glucose (mmol/l)2-hour plasma glucose (mmol/l)
<<7.87.8 7.8–11.07.8–11.0 11.111.1 TotalTotal
<<6.16.1
6.1–6.96.1–6.9
21,96821,968
2,0202,020
2,5622,562
893893
316316
206206
24,84624,846
3,1193,119
7.07.0 276276 378378 489489 1,1431,143
FastingFastingplasmaplasmaglucoseglucose(mmol/l)(mmol/l)
TotalTotal 24,26424,264 3,8333,833 1,0111,011 29,10829,108
Adapted from DECODE Study Group. Br Med J 1998;317:371–375 Adapted from DECODE Study Group. Br Med J 1998;317:371–375
Classification of individuals - the DECODE Study
2-hour plasma glucose (mmol/l)
FPG (mmol/l)
<7.8 7.8–11.0 11.1 Total
<6.1
6.1–6.9
12443
621
1984
476
291
255
14718
1352
7.0 101 119 449 669
Total 13165 2579 995 16739
Discrepancy of FPG and 2hPG criteria in the DECODA study
Diabetologia 2000; 43: 1470-1475
0
5
10
15
20
25
30
Both
2hPG>=11.1
FPG>=7.0
30-39 40-49 50-59 60-69 70-79 80-89
Prevalence (%) of newly diagnosed DM in DECODE populations
The DECODE group, Diabetes Care 2003; 26: 61-69.
0
5
10
15
20
25
30
35
40
45IFG&IGT
IGT
IFG
30-39 40-49 50-59 60-69 70-79 80-89
Prevalence (%) of IGT but not IFG increases with age in DECODE population
The DECODE group, Diabetes Care 2003; 26: 61-69.
Hazards ratio for all-cause mortality in subjects without prior history of diabetes
Adj. for age, cohorts, sex, chol, BMI, SBP, smoking
2,011,49
1,77
2-ho
ur p
lasm
a gl
ucos
e
(mm
ol/l)
7.0 6.1–6.9 <6.1
11.1
7.8–11.0
<7.8
Fasting plasma glucose (mmol/l)
2.5
2.0
1.5
1.0
0.5
0.0
Haz
ard
rat
io
Adapted from DECODE Study Group, Lancet 1999;354:617–621
1.00
0.580.520.560.59
0.82
0.47 0.50 0.54
0.660.84
0.92
0.0
0.2
0.4
0.6
0.8
1.0
1.2
Haz
ard
Rat
io (9
5% C
I)
2-hour glucose (mmol/l) Fasting glucose (mmol/l)
All-cause mortality has a linear relationship with 2-hour plasma glucose
DECODE, Diabetes Care 2003; 26: 688-696
0
1000
2000
3000
4000
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 170
1
2
3
4
5
>13.0
<3.0
2-hour plasma glucose (mmol/l)
CVD mortality by 2-hour plasma glucoseF
requ
ency
Hazard ratio
DECODE, Diabetes Care 26: 688-696
CVD mortality by fasting plasma glucose
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 170
1
2
3
4
5
0
2000
4000
6000
8000
10000
>8.5
<4.0
Fasting plasma glucose (mmol/l)
Fre
quen
cyH
azard ratio
DECODE, Diabetes Care 26: 688-696
Hazard ratio for mortality by FPG categories, the DECODA Study
FPG
(mmol/l)
<6.1
(n=5547)
6.1-6.9
(n=462)
7.0
(n=297)
P for trend
CVD
Model 1
Model 2
1
1
1.4 (0.9-2.1)
1.1 (0.7-1.7)
2.0 (1.3-3.1)
0.9 (0.5-1.5)
0.006
0.83
All-cause
Model 1
Model 2
1
1
1.2 (0.9-1.6)
0.9 (0.7-1.3)
1.8 (1.3-2.5)
0.9 (0.6-1.3)
0.001
0.81
Model 1: Adjusted for age, sex, cohort, BMI, sysBP, Chol and smokingModel 2: Additional adjustment for 2hPG
DECODA Study Group, Diabetologia 2004; 47: 385-394
Hazard ratio for mortality by 2hPG categories, the DECODA Study
2hPG
(mmol/l)
<7.8
(n=4753)
7.8-11.0
(n=1106)
11.1
(n=447)
P for trend
CVD
Model 1
Model 2
1
1
1.3 (0.9-1.9)
1.3 (0.9-1.9)
3.2 (2.2-4.7)
3.4 (2.1-5.4)
<0.001
<0.001
All-cause
Model 1
Model 2
1
1
1.3 (1.0-1.7)
1.4 (1.0-1.8)
2.9 (2.2-3.8)
3.0 (2.2-4.2)
<0.001
<0.001
Model 1: Adjusted for age, sex, cohort, BMI, sysBP, Chol and smokingModel 2: Additional adjustment for FPG
DECODA Study Group, Diabetologia 2004; 47: 385-394
Non-diabetic DiabeticFollow-up
Baseline 2hPG NGT IGT Non-diabetic
CHD incidence 5.3 9.7 16.1
CVD mortality 3.1 7.9 8.7
All-cause mortality 7.6 12.8 15.5
Incidence density (no./per 1000 person-years)
Qiao et al. Diabetes Care 2003; 26:2910-2914
Hazard ratio (95% CI) by glucose status at baseline and at follow-up
Follow-up Non-diabetic Diabetic
Baseline 2hPG NGT IGT Non-diabetic
CHD incidence 1 1.5 (1.0-2.3) 1.8 (1.0-3.2)
CVD mortality 1 2.3 (1.4-3.9) 1.7 (0.8-3.5)
All-cause mortality 1 1.7 (1.1-2.4) 1.5 (0.9-2.5)
Adjusted for age, sex, WHR, SBP, Chol, HDL and smoking
Qiao et al. Diabetes Care 2003; 26:2910-2914
Effect of intensive glycemic control on the risk for any type of macrovascular events
C Stettler, Am Heart J 2006; 152:27-38
STOP-NIDDM Trial (1)
0 0,2 0,4 0,6 0,8 1 1,2 1,4
Myocardial infarctionAnginaRevascularization procedureCardiovascular deathCerebrovascular event or strokePeripheral vascular diseaseAny cardiovascular event
FavoursAcarbose
FavoursPlacebo
Chiasson JL JAMA 2003; 23: 290:486-94
The main changes from baseline to 3 years:
AcarbosePlacebo
STOP-NIDDM Trial (3)
Body Weight (kg) -1.15 0.26BMI (kg/m2) -0.60 -0.12Waist (cm) -0.62 0.17SysBP (mmHg) -0.97 -0.05DiasBP (mmHg) -2.8 -1.42hPG (mmol/L) -0.63 0.04Triglycerides (mmol/L) -0.18 -0.04
All p<0.01 for the difference between the two groups
Summary
• Diabetes diagnosed by either FPG or 2h criteria are risk factor for CVD disease, but 2h criteria identify those who are not diabetic by FPG alone
• IGT is over IFG with regard to the prediction of the CVD
• More trials are required to show that intensive treatment of postprandial hyperglycemia can reduce the CVD
RCT Meta-analysis: G LoweringType 1 Diabetes Trials
Am Heart J 2006;152:27
Intensive Insulin Rx & CVD: T1 DM DCCT/EDIC NEJM 2005;353:2643
Participants: 1394 (97% of the original cohort) DCCT participants
Outcome: Nonfatal MI or stroke; OR CV death; OR silent MI; OR documented angina; OR revascularization
Follow-up: Until > 50 conventional pts - CV event 11 yrs post DCCT; 17 yrs altogether
GHb Results:
DCCT End EDIC End
Intensive 7.4 (1.1) 7.9 (1.3)
Conventional 9.1 (1.5) 7.8 (1.3)
Intensive Insulin Rx & CVD: T1 DM
DCCT/EDIC NEJM 2005;353:2643
Primary CV CompositeRRR= 42% (9-63)
RRR after adj. for updated GHb until end of DCCT (or CV event during
DCCT): 16% (-64 – 57) P=0.61
Intensive Insulin Rx & CVD: T1 DM DCCT/EDIC NEJM 2005;353:2643
MI, Stroke, CV DeathRRR= 57% (12-79)
Chronic G Lowering & CVD: IGT STOP NIDDM Analysis: Chiasson et al. JAMA 2003;290:486
HR 0.51 (0.28-0.95)(i.e. 32/686 vs. 15/682 MI, Angina, Revasc, CV Death, CHF, Stroke, or PVD)
Copyright ©1994 BMJ Publishing Group Ltd.
McCane, D R et al. BMJ 1994;308:1323-8
ROC curves for prevalence of retinopathy (top) and nephropathy (bottom) for 2hPG (----), FPG (....), and HbA1 (----) concentrations
1-Specificity
Relative risk (95% CI) of mortality significantly increased in subjects with IGT
Multivariate adjusted: for age, center, sex, cholesterol, BMI, BP, smokingMultivariate adjusted: for age, center, sex, cholesterol, BMI, BP, smoking
MortalityMortality RR, multivariateRR, multivariate
adjustedadjustedRR, adjustedRR, adjusted
also for FPGalso for FPG
CVDCVD 1.341.34 (1.14-1.57)(1.14-1.57)
1.321.32 (1.12-1.56)(1.12-1.56)
CHDCHD 1.281.28 (1.02-1.59)(1.02-1.59)
1.271.27 (1.03-1.58)(1.03-1.58)
StrokeStroke 1.261.26 (0.88-1.80)(0.88-1.80)
1.211.21 (0.84-1.74)(0.84-1.74)
All-causeAll-cause 1.401.40 (1.27-1.54)(1.27-1.54)
1.371.37 (1.25-1.51)(1.25-1.51)
The DECODE group, Arch Intern Med 2001; 161:397-404The DECODE group, Arch Intern Med 2001; 161:397-404
Hazards ratio for mortality in diabetic patients according to FPG
Mortality
FPG
7.0 mmol/l
FPG 7.0 mmol/l adjusted for 2-hour glucose
CVD 1.5 (1.2–1.9) 1.2 (0.9–1.7)
CHD 1.4 (1.0–2.0) 1.1 (0.7–1.7)
Stroke 1.9 (1.2–3.2) 1.7 (0.9–3.1)
All-cause 1.7 (1.4–1.2) 1.2 (1.0–1.4)
The DECODE group, Arch Intern Med 2001; 161:397-404
Adjusted for age, center, sex, cholesterol, BMI, BP, smoking
Hazards ratio for mortality in diabetic patients according to 2-hour glucose
Mortality
2-hour glucose 11.1 mmol/l
2-hour glucose 11.1 mmol/l
adjusted for FPG
CVD 1.6 (1.2–2.0) 1.4 (1.0–1.9)
CHD 1.6 (1.2–2.3) 1.6 (1.0–2.4)
Stroke 1.7 (1.0–3.0) 1.3 (0.7–2.5)
All-cause 1.9 (1.7–2.2) 1.7 (1.5–2.1)
The DECODE group, Arch Intern Med 2001; 161:397-404
Adjusted for age, center, sex, cholesterol, BMI, BP, smoking