糖尿病高危(IGT)人群的干预.pptx

会计学1糖尿病高危糖尿病高危(IGT)人群的干预人群的干预X 综合征综合征综合征综合征 死亡四重奏死亡四重奏死亡四重奏死亡四重奏（Reaven,1988Reaven,1988）（Kaplan,1989Kaplan,1989）胰岛素抵抗胰岛素抵抗胰岛素抵抗胰岛素抵抗 中心性肥胖中心性肥胖中心性肥胖中心性肥胖糖耐量低减糖耐量低减糖耐量低减糖耐量低减/DM/DM 糖耐量低减糖耐量低减糖耐量低减糖耐量低减/DM/DM高胰岛素血症高胰岛素血症高胰岛素血症高胰岛素血症高高高高TGTG血症血症血症血症 高高高高TGTG血症血症血症血症低低低低HDL-cHDL-c血症血症血症血症高血压高血压高血压高血压 高血压高血压高血压高血压 胰岛素抵抗胰岛素抵抗胰岛素抵抗胰岛素抵抗综合征（综合征（DeFronzo,1991DeFronzo,1991）代代代代 谢谢谢谢 综综 合合 征（征（Zimmet,1997Zimmet,1997）第1页/共50页Insulin ResistanceHypertensionType 2 DiabetesThe metabolic syndrome of The metabolic syndrome of insulin resistance&cardiovascular diseaseinsulin resistance&cardiovascular diseaseReducedFibrinolysisComplexdyslipidemiaTG,sdLDL HDLEndothelialDysfunctionChronic systemicInflammationAthero-sclerosis&CHDVisceralObesity第2页/共50页 2 2型糖尿病一级预防型糖尿病一级预防 糖尿病高危(IGT)人群的干预 历史的回顾历史的回顾 大庆糖尿病预防研究的由来大庆糖尿病预防研究的由来 当前当前2型糖尿病预防研究的局限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及尚未能解决和正在解决的问题第3页/共50页一一.历史的回顾历史的回顾第4页/共50页Prevention is better than cure糖尿病一级预防研究糖尿病一级预防研究 对象对象对象对象 干预措施干预措施干预措施干预措施 大庆研究大庆研究大庆研究大庆研究 IGTIGT 生活方式生活方式生活方式生活方式DPP DPP IGT IGT 生活方式生活方式生活方式生活方式+双胍双胍双胍双胍DPS DPS IGT IGT 生活方式生活方式生活方式生活方式STOP-NIDDM IGTSTOP-NIDDM IGT 阿卡波糖阿卡波糖阿卡波糖阿卡波糖第5页/共50页大庆研究中糖尿病每百人年发病率大庆研究中糖尿病每百人年发病率大庆研究中糖尿病每百人年发病率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第14页/共50页目的目的 （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,当当时并时并未提出代谢综合征未提出代谢综合征）。第15页/共50页三三.当前当前2型糖尿病预防研究的局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限及尚未能解决和正在解决的问题第16页/共50页 生活方式干预预防糖尿病生活方式干预预防糖尿病合理性合理性 成本效益成本效益成本效益成本效益?对预防心脑血管病是否有益对预防心脑血管病是否有益对预防心脑血管病是否有益对预防心脑血管病是否有益?可行性可行性 多少人能长期坚持多少人能长期坚持多少人能长期坚持多少人能长期坚持?第17页/共50页药物干预预防糖尿病的合理性和可行性药物干预预防糖尿病的合理性和可行性药物干预预防糖尿病的合理性和可行性药物干预预防糖尿病的合理性和可行性最佳剂量？最佳剂量？最佳剂量？最佳剂量？成本效益成本效益成本效益成本效益?耐受性？耐受性？耐受性？耐受性？毒副作用毒副作用毒副作用毒副作用?预防了糖尿病预防了糖尿病预防了糖尿病预防了糖尿病or or 提前治疗提前治疗提前治疗提前治疗?第18页/共50页UnansweredUnanswered QuestionsQuestions How to conduct the screening?How to conduct the screening?One step or two-steps?One step or two-steps?OGTT or standard meal test?OGTT or standard meal test?How to do the prevention?How to do the prevention?Lifestyle or pharmacological?Lifestyle or pharmacological?HOW HOW to translate these successful findings in Da-Qing Study DPP and DPS and maintain the lifestyle changes in longer term Targeting insulin resistance or insulin insufficiency?Targeting insulin resistance or insulin insufficiency?Prevent diabetes or reverse to normal tolerance?Prevent diabetes or reverse to normal tolerance?Standard protocol or tailored one?Standard protocol or tailored one?How To Increase Effectiveness and Reduce Cost?How To Increase Effectiveness and Reduce Cost?第19页/共50页Lifestyle or Medication?第20页/共50页Method of interventionn nDiet Group:Diet Group:BMI 25 30 kcal/kg.day:reduce alcohol and sugar BMI 25 reduce calorie intake to reduce weight BMI 25 reduce calorie intake to reduce weight 0.5-1.0 kg/month 0.5-1.0 kg/monthn nExercise Group:To increase amount of leisure physical exercise Exercise Group:To increase amount of leisure physical exercise by at least one unit.by at least one unit.n nDiet and Exercise Group:Same as Diet and Exercise groupDiet and Exercise Group:Same as Diet and Exercise groupn nControls:Only exposed to general information about DM from Controls:Only exposed to general information about DM from public health education.No special advice.public health education.No special advice.第21页/共50页Table 1.Exercise unitsEach category represents one unit第22页/共50页Lifestyle:How IntensiveLifestyle:How Intensive is EffectiveEffective?Da-Qing Study Da-Qing Study:At least decrease 50 gm of Carbohydrate/day At least decrease 50 gm of Carbohydrate/day at least increase 50 min physical exercise/day at least increase 50 min physical exercise/day 5 days/week 5 days/week Diabetes Prevention Program Diabetes Prevention Program:Weight loss 7%and exercise 150min/week Weight loss 7%and exercise 150min/week Diabetes Prevention Study:Diabetes Prevention Study:Weight loss 5%and exercise 4 hours/week Weight loss 5%and exercise 4 hours/week第23页/共50页Efficacy of lifestyle interventionEfficacy of lifestyle intervention Comparison of Da-Qing Study to DPP and DPSComparison 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%第24页/共50页Q:Q:Should The Chinese Need to Use Protocol in DPP or DPS Should The Chinese Need to Use Protocol in DPP or DPS in Their Future Prevention in Their Future Prevention?A:Yes?No!Yes or no!A:Yes?No!Yes or no!Weight loss 7%Trail for Prevention DM with lifestyle modification in US Trail for Prevention DM with lifestyle modification in US Trail for Trail for weight loss with with medication(orlistat)medication(orlistat)in Chinese in Chinese Lifestyle Lifestyle OlistatOlistatWeight Reduction(Kg)3.00 6.05 Weight Reduction(Kg)3.00 6.05 Weight Reduction(%)3.67 Weight Reduction(%)3.67 7.45 第25页/共50页 过强的生活方式干预会大大增过强的生活方式干预会大大增加退出干预的人数，中等强度的干加退出干预的人数，中等强度的干预才能既有效又能为广大人群接受预才能既有效又能为广大人群接受并常年坚持。并常年坚持。第26页/共50页n n DA-QING STUDY 未采用过于激烈的强度大的干预，失访率仅8%.n n DPP，DPS 体重减轻第一年达标率27?)n nNo,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 protocol is needed.第28页/共50页Pharmacological Intervention第29页/共50页Prevention is better than cure糖尿病一级预防研究糖尿病一级预防研究糖尿病一级预防研究糖尿病一级预防研究 对象对象对象对象 干预措施干预措施干预措施干预措施 结结结结果果果果大庆研究大庆研究大庆研究大庆研究 IGTIGT 生活方式生活方式生活方式生活方式 5050DPPDPP研究研究研究研究 IGTIGT 生活方式生活方式生活方式生活方式+双胍双胍双胍双胍 5858 -31%-31%DPSDPS研究研究研究研究 IGTIGT 生活方式生活方式生活方式生活方式 5858STOP-NIDDM IGTSTOP-NIDDM IGT 阿卡波糖阿卡波糖阿卡波糖阿卡波糖 3333第30页/共50页Lifestyle or Medication?Lifestyle intervention studies have Lifestyle intervention studies have consistently shownconsistently shown that quite modest that quite modest changes can changes can reducereduce the progression from IGT to diabetes by 50-60%.the progression from IGT to diabetes by 50-60%.It may,however,be It may,however,be impossible toimpossible to translatetranslate these these successful findingssuccessful findings in in larger cohots or maintain the lifestyle changes in larger cohots or maintain the lifestyle changes in longer termlonger term.This has.This has lead to consideration pharmacotherapy.lead to consideration pharmacotherapy.Simpson RW,Shaw JE,Zimmet PZ:Simpson RW,Shaw JE,Zimmet PZ:Diabetes Res Clin Pract 2003 59:165-80 Diabetes Res Clin Pract 2003 59:165-80第31页/共50页改变生活方式的改变生活方式的艰难艰难 说了说了,但未听见但未听见听见了听见了,但未理解但未理解理解了理解了,但未接受但未接受接受了接受了,但未付诸行动但未付诸行动行动了行动了,但能坚持多久但能坚持多久?第32页/共50页Incidence/pys of DM in IGT subjectIncidence/pys of DM in IGT subject stratified by Ins-sensitivity stratified by Ins-sensitivitySensitive IAI-4.73 Resistant IAI-4.73 ie FPG FINS 114Incidence of DM第33页/共50页.In IGT subjects with In IGT subjects with higherhigher degrees of degrees of insulin resistance insulin resistance the the life-style change life-style change alone is alone is less effectiveless effective in preventing DM in preventing DM and some and some additional interventionadditional intervention such as such as metformin may be metformin may be neededneeded.第34页/共50页Diabetes Prevention Program(USA)Diabetes Prevention Program(USA)3000IGT involved,follow-up 3.3 years,2001 presented5831%第35页/共50页 STOP NIDDMSTOP NIDDM 1418 IGT involved,follow-up 3 years,2001 presented33%第36页/共50页Incidence of Diabetes in Pharmacological Incidence of Diabetes in Pharmacological intervention group of IGT in China (19972000)intervention group of IGT in China (19972000)77%88%0.25 tid50mg tid第37页/共50页Incidence of Diabetes in Pharmacological Incidence of Diabetes in Pharmacological intervention group of IGT in China intervention group of IGT in China (Yuexin Wang,3 years)(Yuexin Wang,3 years)69%50mg TID第38页/共50页 P Pharmacological interventions with harmacological interventions with Acarbose or Metformin could Acarbose or Metformin could reduce reduce the risk of worsening to diabetes by the risk of worsening to diabetes by 6080%6080%in Chinesein Chinese subjects with subjects with IGT.IGT.Intervention with Acarbose seems more effective in Chinese than that in Westerns SUMMARY第39页/共50页 How To Increase EffectivenessHow To Increase Effectivenessand Reduce Cost?and Reduce Cost?STRATEGY OF THE INTERVENTIONSTRATEGY OF THE INTERVENTION第40页/共50页Incidence/pys Reduction of DM in peoples with IGT Incidence/pys Reduction of DM in peoples with IGT stratified by INS-SEN and secretionstratified by INS-SEN and secretionG 4 G3 G2 G1第41页/共50页药物预防的有效性药物预防的有效性DPP二甲双呱 对年轻肥胖者更有效25-44 44%45-59 31%60 11%BMI 22-30 3%30-35 16%35 53%第42页/共50页药物预防的有效性药物预防的有效性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%第43页/共50页药物预防的有效性药物预防的有效性DPP 二甲双呱 的有效性PG2H(mg/dl)140-153 41%154-172 38%173-199 26%第44页/共50页 Targeting Insulin resistance Targeting Insulin resistance or insulin insufficiency?or insulin insufficiency?第45页/共50页Prevent diabetes or reverse to normal glucose tolerance?第46页/共50页How to Screen?One Step or Two Steps?第47页/共50页 How can we have IGT clinical trialsHow can we have IGT clinical trials Get Out Of the Ivory Tower?Get Out Of the Ivory Tower?让临床试验走出神殿让临床试验走出神殿任重而道远任重而道远第48页/共50页THANK YOU第49页/共50页