1、2型糖尿病一级预防糖尿病高危(IGT)人群的干预中日友好医院 李光伟 IDF 主席开幕式演讲主席开幕式演讲YESTERDAY,TODAY AND TOMORROW KGMM Alberti Prevention,Prevention and PreventionX 综合征 死亡四重奏死亡四重奏（Reaven,1988）（Kaplan,1989）胰岛素抵抗胰岛素抵抗 中心性肥胖中心性肥胖糖耐量低减糖耐量低减/DM 糖耐量低减糖耐量低减/DM高胰岛素血症高胰岛素血症高高TG血症血症 高高TG血症血症低低HDL-c血症血症高血压高血压 高血压高血压 胰岛素抵抗胰岛素抵抗综合征（DeFronzo,19
2、91）代代 谢谢 综 合 征（Zimmet,1997）Insulin ResistanceHypertensionType 2 DiabetesThe metabolic syndrome of insulin resistance&cardiovascular diseaseReducedFibrinolysisComplexdyslipidemiaTG,sdLDL HDLEndothelialDysfunctionChronic systemicInflammationAthero-sclerosis&CHDVisceralObesity 2型糖尿病一级预防 糖尿病高危(IGT)人群的干预
3、历史的回顾大庆糖尿病预防研究的由来当前2型糖尿病预防研究的局限 及尚未能解决和正在解决的问题一.历史的回顾Prevention is better than cure糖尿病一级预防研究糖尿病一级预防研究 对象对象 干预措施干预措施 大庆研究大庆研究 IGT 生活方式生活方式DPP IGT 生活方式生活方式+双胍双胍DPS IGT 生活方式生活方式STOP-NIDDM IGT 阿卡波糖阿卡波糖大庆研究中糖尿病每百人年发病率11.510.811.417.2饮食组饮食组运动组运动组饮食饮食+运动运动对照组对照组BMI=255.16.813.38.3饮食组饮食组运动组运动组 饮食饮食+运动运动 对照组
4、对照组BMI100 例例多因素分析多因素分析胰岛素抵抗对干预疗效分析胰岛素抵抗对干预疗效分析目的 （大庆）研究是为了在某一特定人群（IGT)，采取某一特定的方法(生活方式干预），证明某种假设（生活方式干预可预防糖尿病的发生）的正确(合理性和可行性）。然后以这种假设去说服人,让人们采取行动解决问题。（大庆）研究是为了改变现状（降低中国乃至世界的糖尿病糖尿病发病率发病率,当时并当时并未提出代谢综合征未提出代谢综合征）。三.当前2型糖尿病预防研究的局限及尚未能解决和正在解决的问题 生活方式干预预防糖尿病合理性 成本效益?对预防心脑血管病是否有益?可行性 多少人能长期坚持?药物干预预防糖尿病的合理性和
5、可行性最佳剂量？成本效益?耐受性？毒副作用?预防了糖尿病or 提前治疗?Unanswered Questions How to conduct the screening?One step or two-steps?OGTT or standard meal test?How to do the prevention?Lifestyle or pharmacological?HOW to translate these successful findings in Da-Qing Study DPP and DPS and maintain the lifestyle changes in l
6、onger term Targeting insulin resistance or insulin insufficiency?Prevent diabetes or reverse to normal tolerance?Standard protocol or tailored one?How To Increase Effectiveness and Reduce Cost?Lifestyle or Medication?Method of intervention Diet Group:BMI 25 reduce calorie intake to reduce weight 0.5
7、-1.0 kg/month Exercise Group:To increase amount of leisure physical exercise by at least one unit.Diet and Exercise Group:Same as Diet and Exercise group Controls:Only exposed to general information about DM from public health education.No special advice.Table 1.Exercise unitsIntensityTime(minutes)E
8、xerciseMild30Slow walking,taking bus(standing),shopping,cleaning roomsModerate20Faster walking,down stairs,cycling,heavier washing,ballroom dancing(slow),cycling on a lever surface,having a showerHard10Slow running,up stairs,Disco,for oldpeople,volleyball,table tennisVery hard5Rope jumping,basketbal
9、l,swimmmingEach category represents one unitLifestyle:How Intensive is Effective?Da-Qing Study:At least decrease 50 gm of Carbohydrate/day at least increase 50 min physical exercise/day 5 days/week Diabetes Prevention Program:Weight loss 7%and exercise 150min/week Diabetes Prevention Study:Weight lo
10、ss 5%and exercise 4 hours/weekEfficacy of lifestyle intervention Comparison of Da-Qing Study to DPP and DPS Incidence/100pys CONTROL DIET+EXERCISE Da-Qing StudyBMI 22.4 22.2 13.3 6.8 49%Da-Qing StudyBMI 27.5 27.0 17.2 11.4 34%DPPBMI 34.2 33.9 11.1 4.8 58%DPSBMI 31.3 31.0 9.6 4.8 58%Q:Should The Chin
11、ese Need to Use Protocol in DPP or DPS in Their Future Prevention?A:Yes?No!Yes or no!Weight loss 7%Trail for Prevention DM with lifestyle modification in US Trail for weight loss with medication(orlistat)in Chinese Lifestyle OlistatWeight Reduction(Kg)3.00 6.05 Weight Reduction(%)3.67 7.45 过强的生活方式干预
12、会大大增加退出干预的人数，中等强度的干预才能既有效又能为广大人群接受并常年坚持。DA-QING STUDY 未采用过于激烈的强度大的干预，失访率仅8%.DPP，DPS 体重减轻第一年达标率27?)No,For most non-obese Chinese IGT,less intensive prevention protocol than DPP may be working if only for preventing DM,however reversing them to normal glucose tolerance more intensive prevention protoc
13、ol is needed.Pharmacological InterventionPrevention is better than cure糖尿病一级预防研究糖尿病一级预防研究 对象对象 干预措施干预措施 结果结果大庆研究大庆研究 IGT 生活方式生活方式 50DPP研究研究 IGT生活方式生活方式+双胍双胍 58 -31%DPS研究研究 IGT 生活方式生活方式 58STOP-NIDDM IGT 阿卡波糖阿卡波糖 33Lifestyle or Medication?Lifestyle intervention studies have consistently shown that qui
14、te modest changes can reduce the progression from IGT to diabetes by 50-60%.It may,however,be impossible to translate these successful findings in larger cohots or maintain the lifestyle changes in longer term.This has lead to consideration pharmacotherapy.Simpson RW,Shaw JE,Zimmet PZ:Diabetes Res C
15、lin Pract 2003 59:165-80改变生活方式的艰难 说了,但未听见听见了,但未理解理解了,但未接受接受了,但未付诸行动行动了,但能坚持多久?Incidence/pys of DM in IGT subject stratified by Ins-sensitivity024681012141618IGT controlDietExercise D+E SEN RESSensitive IAI-4.73 Resistant IAI-4.73 ie FPG FINS 114Incidence of DM.In IGT subjects with higher degrees of
16、insulin resistance the life-style change alone is less effective in preventing DM and some additional intervention such as metformin may be needed.Diabetes Prevention Program(USA)0 00.020.020.040.040.060.060.080.080.10.10.120.12CONTROLSCONTROLSMETFORMINMETFORMINLIFE-STYLELIFE-STYLE 3000IGT involved,
17、follow-up 3.3 years,2001 presented 3000IGT involved,follow-up 3.3 years,2001 presented5831%STOP NIDDM0 05 510101515202025253030353540404545CONTROLSCONTROLSACRBOSEACRBOSE 1418 IGT involved,follow-up 3 years,2001 presented33%Incidence of Diabetes in Pharmacological intervention group of IGT in China (
18、19972000)11.111.14.14.12 20 02 24 46 68 810101212controlscontrolsMetforminMetforminAcarboseAcarboseIncidence ofDMIncidence ofDM77%88%0.25 tid50mg tidIncidence of Diabetes in Pharmacological intervention group of IGT in China (Yuexin Wang,3 years)11.711.73.63.60 02 24 46 68 8101012121414controlscontr
19、olsn=58n=58AcarboseAcarbosen=58n=58Incidence of DMIncidence of DM69%50mg TID Intervention with A seems more effective in Chinese than that in WesternsSUMMARY How To Increase Effectivenessand Reduce Cost?STRATEGY OF THE INTERVENTIONIncidence/pys Reduction of DM in peoples with IGT stratified by INS-S
20、EN and secretion-49%-42%-31%-27%G1 IAI-4.73 FI/FG2.52G1 IAI-4.73 FI/FG2.52G2 IAI-4.73 FI/FG-4.73 FI/FG2.52G3 IAI5.28G3 IAI5.28G4 IAI-4.73 FI/FG5.28G4 IAI-4.73 FI/FG60 11%BMI 22-30 3%30-35 16%35 53%药物预防的有效性DPP方式干预 与二甲双呱疗效比较25-44 8%45-59 41%60 69%BMI 22-30 63%30-35 53%35 -4%药物预防的有效性DPP 二甲双呱 的有效性PG2H(mg/dl)140-153 41%154-172 38%173-199 26%Targeting Insulin resistance or insulin insufficiency?Prevent diabetes or reverse to normal glucose tolerance?How to Screen?One Step or Two Steps?How can we have IGT clinical trials Get Out Of the Ivory Tower?让临床试验走出神殿任重而道远THANK YOU
