2小时糖耐量试验的临床意义小时糖耐量试验的临床意义 Finnish Academy Research Fellow北大糖尿病论坛北大糖尿病论坛2007年年 5 月月12日，日， 北京北京MD, Ph.D 小时糖耐量试验的临床意义(6)糖尿病诊断试验糖尿病诊断试验:历史回顾历史回顾糖尿病糖尿病症状症状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, 1913小时糖耐量试验的临床意义(6)Normal Glucose Homeostasis Daytime Profile (N=12, health; Mean + 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小时糖耐量试验的临床意义(6)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标准差可诊断糖尿病标准差可诊断糖尿病: 根据年轻根据年轻 (20-30 岁岁) 健康人群资料健康人群资料, 纯统计！纯统计！不考虑临床，预后及年龄不考虑临床，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标准混乱诊断标准混乱 (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)小时糖耐量试验的临床意义(6)什么是糖耐量异常什么是糖耐量异常?1. 均值均值+2标准差标准差2. 血糖双峰分布血糖双峰分布,小血管病变小血管病变 (眼病，肾病等眼病，肾病等): 糖尿病高发人群糖尿病高发人群, 如如Pima Indians (1971), Mexican-Americans, Micronesians, Polynesians 小时糖耐量试验的临床意义(6)Bimodal distribution of glucoseand prevalence of retinopathy and proteinuria in Pima Indians Knowler WC etc. Diabetes Metab Rev 6: 1-27, 1990小时糖耐量试验的临床意义(6)Copyright 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 tenths of 2hPG, FPG, and HBa1c 小时糖耐量试验的临床意义(6)现用诊断标准现用诊断标准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 “金标准金标准”WHO 1985: slightly modified the WHO 1980 criteriaADA 1997: FPG 7.8 mmol/l to 7.0 mmol/l，Not use OGTTWHO 1999: adopted the FPG 7.0 mmol/l, retained the 2h OGTTWHO/IDF 2006: no changes except for some terms 小时糖耐量试验的临床意义(6)什么是糖耐量异常什么是糖耐量异常?1. 均值均值+2标准差标准差2. 血糖双峰分布血糖双峰分布,小血管病变小血管病变3.大血管病变大血管病变: 心脑血管及外周血管病变心脑血管及外周血管病变 小时糖耐量试验的临床意义(6)Dysglycemia Normoglycemia in Acute and Stable CV DiseaseConsecutive 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;1880NGTIFGIGTKnown DMNew DM29%35%22%22%31%30%15%10%3%3%020406080100%AcuteElective小时糖耐量试验的临床意义(6)The DECODE Study ()Diabetes Epidemiology: Collaborative analysis Of Diagnostic criteria in Europe 小时糖耐量试验的临床意义(6) 2-hour plasma glucose (mmol/l) 2-hour plasma glucose (mmol/l) 7.87.87.811.07.811.0 11.111.1TotalTotal 6.16.16.16.96.16.921,96821,9682,0202,0202,5622,56289389331631620620624,84624,8463,1193,119 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 individuals - the DECODE Study小时糖耐量试验的临床意义(6)Discrepancy of FPG and 2hPG criteria in the DECODA study Diabetologia 2000; 43: 1470-1475小时糖耐量试验的临床意义(6) 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.小时糖耐量试验的临床意义(6) 30-39 40-49 50-59 60-69 70-79 80-89 Prevalence (%) of IGT but not IFG increases with age in DECODE populationThe DECODE group, Diabetes Care 2003; 26: 61-69.小时糖耐量试验的临床意义(6)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 11.17.811.07.8Fasting plasma glucose (mmol/l)2.52.01.51.00.50.0Hazard ratioAdapted from DECODE Study Group, Lancet 1999;354:617621小时糖耐量试验的临床意义(6)All-cause mortality has a linear relationship with 2-hour plasma glucoseDECODE, Diabetes Care 2003; 26: 688-696小时糖耐量试验的临床意义(6)CVD mortality by 2-hour plasma glucoseFrequencyHazard ratioDECODE, Diabetes Care 26: 688-696小时糖耐量试验的临床意义(6)CVD mortality by fasting plasma glucoseFrequencyHazard ratioDECODE, Diabetes Care 26: 688-696小时糖耐量试验的临床意义(6)Hazard 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 (1.3-3.1)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: 385-394小时糖耐量试验的临床意义(6)Hazard ratio for mortality 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, cohort, BMI, sysBP, Chol and smokingModel 2: Additional adjustment for FPG DECODA Study Group, Diabetologia 2004; 47: 385-394小时糖耐量试验的临床意义(6)Non-diabetic DiabeticFollow-upBaseline 2hPGNGTIGTNon-diabeticCHD incidence 5.39.716.1CVD mortality3.17.98.7All-cause mortality7.612.815.5Incidence density (no./per 1000 person-years)Qiao et al. Diabetes Care 2003; 26:2910-2914小时糖耐量试验的临床意义(6)Hazard 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 (0.9-2.5)Adjusted for age, sex, WHR, SBP, Chol, HDL and smokingQiao et al. Diabetes Care 2003; 26:2910-2914小时糖耐量试验的临床意义(6)Effect of intensive glycemic control on the risk for any type of macrovascular eventsC Stettler, Am Heart J 2006; 152:27-38小时糖耐量试验的临床意义(6)STOP-NIDDM Trial (1)Myocardial infarctionAnginaRevascularization procedureCardiovascular deathCerebrovascular event or strokePeripheral vascular diseaseAny cardiovascular event FavoursAcarboseFavoursPlaceboChiasson JL JAMA 2003; 23: 290:486-94小时糖耐量试验的临床意义(6)The main changes from baseline to 3 years:AcarbosePlaceboSTOP-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 -0.04All 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)小时糖耐量试验的临床意义(6)Intensive Insulin Rx & 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=0.61小时糖耐量试验的临床意义(6)Intensive Insulin Rx & CVD: T1 DM DCCT/EDIC NEJM 2005;353:2643MI, Stroke, CV DeathRRR= 57% (12-79)小时糖耐量试验的临床意义(6)Chronic G Lowering & CVD: IGT STOP 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)小时糖耐量试验的临床意义(6)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 2hPG (-), FPG (.), and HbA1 (-) concentrations1-Specificity小时糖耐量试验的临床意义(6)Relative 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, smokingMortalityMortalityRR, 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 (0.84-1.74) (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; 161:397-404小时糖耐量试验的临床意义(6)Hazards ratio for mortality in diabetic patients according to FPG The DECODE group, Arch Intern Med 2001; 161:397-404Adjusted for age, center, sex, cholesterol, BMI, BP, smoking 小时糖耐量试验的临床意义(6)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 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