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1、2小时糖耐量实验的临床意义小时糖耐量实验的临床意义 Finnish Academy Research Fellow芬芬兰兰赫赫尔尔辛基大学及辛基大学及 国立公共国立公共卫卫生研生研讨讨院院北大糖尿病北大糖尿病论坛论坛2007年年 5 月月12日，日， 北京北京乔青乔青 MD, Ph.D 糖尿病诊断实验糖尿病诊断实验:历史回想历史回想糖尿病糖尿病病症病症尿糖尿糖空腹血糖空腹血糖糖耐量糖耐量 (1913年年) Jacobsen A. Biochem Z 51:443, 1913Normal Glucose Homeostasis Daytime Profile (N=12, health; Mea
2、n + 95%CI)Owens D ,Zinman B & Bolli G : Lancet 358,739,2001Meal Times80400Insulin (mU/L)08.0013.0016.00 19.00 hGlucose (mmol/L)8426什么是糖耐量异常什么是糖耐量异常?1. 高于均值高于均值+2规范差可诊断糖尿病规范差可诊断糖尿病: 根据年轻根据年轻 (20-30 岁岁) 安康人群资料安康人群资料, 纯统计！纯统计！不思索临床，预后及年龄不思索临床，预后及年龄 (50年代年代) 2h全血血糖全血血糖=120mg/dl (100g糖耐量糖耐量)诊断诊断糖尿病糖尿病 (血
3、浆血糖比全血高血浆血糖比全血高14-16%!)发病率高发病率高诊断规范混乱诊断规范混乱 (血样，服糖量，时间血样，服糖量，时间) 直到直到70年代年代Mosenthal H.O. and Barry E (Ann Intern Med 33: 1175, 1950)什么是糖耐量异常什么是糖耐量异常?1. 均均值值+2规规范差范差2. 血糖双峰分布血糖双峰分布,小血管病小血管病变变 (眼病，眼病，肾肾病等病等): 糖尿病高糖尿病高发发人群人群, 如如Pima Indians (1971), Mexican-Americans, Micronesians, Polynesians Bimodal
4、distribution of glucoseand prevalence of retinopathy and proteinuria in Pima Indians Knowler WC etc. Diabetes Metab Rev 6: 1-27, 1990Copyright 1994 BMJ Publishing Group Ltd.McCane, D R et al. BMJ 1994;308:1323-85 year cumulative incidence (top) and prevalence (bottom) of retinopathy in relation to t
5、enths of 2hPG, FPG, and HBa1c 现用诊断规范现用诊断规范NDDG1979: FPG=7.8 mmol/l and 75g OGTT at , 1, 1, 2 hours WHO 1980: adopted the NDDG criteria, 2h glucose=11.1 mmol/l after 75g load as “金金规规范范WHO 1985: slightly modified the WHO 1980 criteriaADA 1997: FPG 7.8 mmol/l to 7.0 mmol/l，Not use OGTTWHO 1999: adopte
6、d the FPG 7.0 mmol/l, retained the 2h OGTTWHO/IDF 2006: no changes except for some terms 什么是糖耐量异常什么是糖耐量异常?1. 均均值值+2规规范差范差2. 血糖双峰分布血糖双峰分布,小血管病小血管病变变3.大血管病大血管病变变: 心心脑脑血管及外周血管病血管及外周血管病变变 Dysglycemia Normoglycemia in Acute and Stable CV DiseaseConsecutive pts: 2107 in-pts; 2854 out-pt elective CV consul
7、ts 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 M et al; Eur Ht J 2004;1880Bartnik M et al; Eur Ht J 2004;1880NGTIFGIGTKnown DMNew DM29%35%22%22%31%30%15%10%3%3%020406080100%Acute
8、ElectiveThe DECODE Study (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) 7.87.87.811.07.811.0 11.111.1TotalTotal 6.16.16.16.96.16.921,96821,9682,0202,0202,5622,562893893316316206206
9、24,84624,8463,1193,119 7.07.02762763783784894891,1431,143FastingFastingplasmaplasmaglucoseglucose(mmol/l)(mmol/l)TotalTotal24,26424,2643,8333,8331,0111,01129,10829,108Adapted from DECODE Study Group. Br Med J 1998;317:371375 Adapted from DECODE Study Group. Br Med J 1998;317:371375 Classification of
10、 individuals - the DECODE StudyDiscrepancy of FPG and 2hPG criteria in the DECODA study Diabetologia 2000; 43: 1470-1475 30-39 40-49 50-59 60-69 70-79 80-89Prevalence (%) of newly diagnosed DM in DECODE populationsThe DECODE group, Diabetes Care 2003; 26: 61-69. 30-39 40-49 50-59 60-69 70-79 80-89 P
11、revalence (%) of IGT but not IFG increases with age in DECODE populationThe 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-hour plasma glucose(mmol/l)7.06.16.96.1 11
12、.111.17.811.07.8Fasting plasma glucose (mmol/l)2.52.01.51.00.50.0Hazard ratioAdapted from DECODE Study Group, Lancet 1999;354:617621All-cause mortality has a linear relationship with 2-hour plasma glucoseDECODE, Diabetes Care 2003; 26: 688-696CVD mortality by 2-hour plasma glucoseFrequencyHazard rat
13、ioDECODE, Diabetes Care 26: 688-696CVD mortality by fasting plasma glucoseFrequencyHazard ratioDECODE, Diabetes Care 26: 688-696Hazard ratio for mortality by FPG categories, the DECODA StudyFPG (mmol/l)6.1(n=5547)6.1-6.9(n=462) 7.0(n=297)P for trendCVDModel 1Model 2111.4 (0.9-2.1)1.1 (0.7-1.7)2.0 (1
14、.3-3.1)0.9 (0.5-1.5)0.0060.83All-causeModel 1Model 2111.2 (0.9-1.6)0.9 (0.7-1.3)1.8 (1.3-2.5)0.9 (0.6-1.3)0.0010.81Model 1: Adjusted for age, sex, cohort, BMI, sysBP, Chol and smokingModel 2: Additional adjustment for 2hPG DECODA Study Group, Diabetologia 2004; 47: 385-394Hazard ratio for mortality
15、by 2hPG categories, the DECODA Study2hPG (mmol/l)7.8(n=4753)7.8-11.0(n=1106) 11.1(n=447)P for trendCVDModel 1Model 2111.3 (0.9-1.9)1.3 (0.9-1.9)3.2 (2.2-4.7)3.4 (2.1-5.4)0.0010.001All-causeModel 1Model 2111.3 (1.0-1.7)1.4 (1.0-1.8)2.9 (2.2-3.8)3.0 (2.2-4.2)0.0010.001Model 1: Adjusted for age, sex, c
16、ohort, BMI, sysBP, Chol and smokingModel 2: Additional adjustment for FPG DECODA Study Group, Diabetologia 2004; 47: 385-394Non-diabetic DiabeticFollow-upBaseline 2hPGNGTIGTNon-diabeticCHD incidence 5.39.716.1CVD mortality3.17.98.7All-cause mortality7.612.815.5Incidence density (no./per 1000 person-
17、years)Qiao et al. Diabetes Care 2003; 26:2910-2914Hazard ratio (95% CI) by glucose status at baseline and at follow-upFollow-upNon-diabeticDiabeticBaseline 2hPGNGTIGTNon-diabeticCHD incidence11.5 (1.0-2.3)1.8 (1.0-3.2)CVD mortality12.3 (1.4-3.9)1.7 (0.8-3.5)All-cause mortality11.7 (1.1-2.4)1.5 (0.9-
18、2.5)Adjusted for age, sex, WHR, SBP, Chol, HDL and smokingQiao et al. Diabetes Care 2003; 26:2910-2914Effect of intensive glycemic control on the risk for any type of macrovascular eventsC Stettler, Am Heart J 2006; 152:27-38STOP-NIDDM Trial (1)Myocardial infarctionAnginaRevascularization procedureC
19、ardiovascular deathCerebrovascular event or strokePeripheral vascular diseaseAny cardiovascular event FavoursAcarboseFavoursPlaceboChiasson JL JAMA 2003; 23: 290:486-94The main changes from baseline to 3 years:AcarbosePlaceboSTOP-NIDDM Trial (3)Body Weight (kg) -1.15 0.26BMI (kg/m2) -0.60 -0.12Waist
20、 (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 -0.04All p 50 conventional pts - CV event 11 yrs post DCCT; 17 yrs altogetherGHb Results: DCCT EndEDIC EndIntensive7.4 (1.1)7.9 (1.3)Conventional9.1 (1.5)7.8 (1.3)Intensive Insulin Rx
21、& CVD: T1 DM DCCT/EDIC NEJM 2005;353:2643Primary CV CompositeRRR= 42% (9-63)RRR after adj. for updated GHb until end of DCCT (or CV event during DCCT): 16% (-64 57) P=0.61Intensive Insulin Rx & CVD: T1 DM DCCT/EDIC NEJM 2005;353:2643MI, Stroke, CV DeathRRR= 57% (12-79)Chronic G Lowering & CVD: IGT S
22、TOP NIDDM Analysis: Chiasson et al. JAMA 2003;290:486HR 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;308:1323-8ROC curves for prevalence of retinopathy (top) and nephropathy (bottom) for
23、2hPG (-), FPG (.), and HbA1 (-) concentrations1-SpecificityRelative risk (95% CI) of mortality significantly increased in subjects with IGTMultivariate adjusted: for age, center, sex, cholesterol, BMI, BP, smokingMultivariate adjusted: for age, center, sex, cholesterol, BMI, BP, smokingMortalityMort
24、alityRR, multivariateRR, multivariateadjustedadjustedRR, adjustedRR, adjustedalso for FPGalso for FPGCVDCVD1.341.34 (1.14-1.57) (1.14-1.57)1.321.32 (1.12-1.56) (1.12-1.56)CHDCHD1.281.28 (1.02-1.59) (1.02-1.59)1.271.27 (1.03-1.58) (1.03-1.58)StrokeStroke1.261.26 (0.88-1.80) (0.88-1.80)1.211.21 (0.84-
25、1.74) (0.84-1.74)All-causeAll-cause1.401.40 (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; 161:397-404Hazards ratio for mortality in diabetic patients according to FPG The DECODE group, Arch Intern Med
26、 2001; 161:397-404Adjusted for age, center, sex, cholesterol, BMI, BP, smoking Hazards ratio for mortality in diabetic patients according to 2-hour glucose The DECODE group, Arch Intern Med 2001; 161:397-404Adjusted for age, center, sex, cholesterol, BMI, BP, smoking nZr$u*x+A2D5H8KcNfQiUlXo#s%v(y0B
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42、&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTlWoZr%u(x+B2E6H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYu(x+A2E5H9KcNfRiUlXp#s&v)y0C3F6IaLdPgSjVnYq!t*w-A1D4G8JbMeQhTkWoZr%u(x+B2E5H9KcOfRiUmXp#s&v)z0C3F7IaLdPgSkVnYq$t*w-A1D5G8JbNeQhTlWo#r%u(y+B2E6H9LcOfRjUmXp!s&w)z0C4F7IaMdPgSkVnZq$t*x-A1D5G8KbNeQiTlWo#r%v(y+B3E6H9LcOgRjUmYp!s&w)z1C4F7JaMdPhSkWnZq$u*x-A2D5H8KbNfQiTlXo#r%v(y0B3E6I9LcOgRjVmYp!t&w)z1C4G7JaMePhSkWnZr$u*x+A2D5H8KcNfQiUlXo#s%v)y0B3F6I9LdOgSjVmYq!t&w-z1D4G7JbMePhTkWnZr$u(
