1、2型糖尿病一級預(yù)防糖尿病高危(IGT)人群的干預(yù),中日友好醫(yī)院 李光偉,IDF 主席開幕式演講 YESTERDAY, TODAY AND TOMORROW KGMM Alberti Prevention, Prevention and Prevention,X 綜合征 死亡四重奏（Reaven,1988） （Kaplan,1989）,胰島素抵抗 中心性肥胖 糖耐量低減/DM 糖耐量低減/DM 高胰島素血癥 高TG血癥 高TG血癥 低HDL-c血癥 高血壓 高血壓 胰島素抵抗綜合征（DeFronzo, 1991） 代 謝 綜 合 征（Zimmet, 1997）,Insulin Resistanc

2、e,Hypertension,Type 2 Diabetes,The metabolic syndrome of insulin resistance & cardiovascular disease,ReducedFibrinolysis,Complexdyslipidemia TG, sdLDL HDL,EndothelialDysfunction,Chronic systemicInflammation,Athero-sclerosis & CHD,VisceralObesity,2型糖尿病一級預(yù)防 糖尿病高危(IGT)人群的干預(yù) 歷史的回顧 大慶糖尿病預(yù)防研究的由來 當(dāng)前2型糖尿病預(yù)防

3、研究的局限 及尚未能解決和正在解決的問題,一. 歷史的回顧,Prevention is better than cure,糖尿病一級預(yù)防研究 對象 干預(yù)措施 大慶研究 IGT 生活方式 DPP IGT 生活方式+雙胍 DPS IGT 生活方式 STOP-NIDDM IGT 阿卡波糖,大慶研究中糖尿病每百人年發(fā)病率,11.5,10.8,11.4,17.2,飲食組,運(yùn)動組,飲食+運(yùn)動,對照組,BMI=25,5.1,6.8,13.3,8.3,飲食組,運(yùn)動組,飲食+運(yùn)動,對照組,BMI25,10.0,9.6,15.7,8.3,飲食組,運(yùn)動組,飲食+運(yùn)動,對照組,總 組,國際上對于大慶研究結(jié)果的評價(jià)肯定

4、大慶研究首次證明生活方式干預(yù)可以在高危人群成功的預(yù)防糖尿病，它將對糖尿病預(yù)防產(chǎn)生不可估量的影響。,國際上對于大慶研究結(jié)果的評價(jià)疑問大慶研究的成功可能是由于：中國不是象西方國家那樣人群體力活動較少的社會。中國人依從健康生活方式的忠告較為容易。西方人比中國更肥胖，人群體力活動更少。強(qiáng)化生活方式干預(yù)在其他人群能否預(yù)防糖尿病尚難肯定。,Prevention is better than cure,糖尿病一級預(yù)防研究 對象 干預(yù)措施 結(jié)果 大慶研究 IGT 生活方式 50 DPP研究 IGT生活方式+雙胍 58 - 31% DPS研究 IGT 生活方式 58 STOP-NIDDM IGT 阿卡波糖 33

5、,The efficacy of lifestyle intervention in Da-Qing Study has recently been confirmed in the DPP and DPS studies and demonstrate that more intensive lifestyle change is more effective to prevent diabetes in the western countries. However it may be impossible to translate these successful findings in

6、larger cohorts or maintain the lifestyle changes in longer term.,Prevention is better than cure,問題： 現(xiàn)實(shí)中糖尿病能預(yù)防嗎？ 我們應(yīng)該篩查糖尿病本身還是糖尿病的危險(xiǎn)因素？ 2型糖尿病預(yù)防研究和預(yù)防實(shí)施之間 相差有多大遠(yuǎn)?,二.大慶糖尿病預(yù)防研究的由來,生活方式與2性糖尿病因果關(guān)系假設(shè),基因治療遙遙無期藥物干預(yù)尚無定論強(qiáng)化生活方式干預(yù)-可行?,5%-10%/年,基因易感性,老齡,營養(yǎng)過剩,體力活動少,細(xì)胞功能受損 胰島素抵抗,糖耐量低減,糖尿病,大慶研究與國外相關(guān)研究(1980-1992)比較,作者

7、,例數(shù),隨訪期,干預(yù),方法,結(jié)果,研究的優(yōu)缺點(diǎn),Sartor G,206,10,年,藥物,飲食,有效,每組少于,50,例,失訪率,47%(23/49),主動干預(yù)不足,單因數(shù)分析,Keen H,241,10,年,D860,飲食,無效,單因數(shù)分析,Erikson k,217,6,年,飲食,+,運(yùn)動,有效,非隨機(jī)分組,單因數(shù)分析,未顯示主動干預(yù)效果,X.R .Pan,576,6,年,飲食,+,運(yùn)動,有效,失訪率,8%,隨機(jī)分組,每組,100,例,多因素分析,胰島素抵抗對干預(yù)療效分析,目的,（大慶）研究是為了在某一特定人群（IGT)，采取某一特定的方法(生活方式干預(yù)），證明某種假設(shè)（生活方式干預(yù)可預(yù)防

8、糖尿病的發(fā)生）的正確 (合理性和可行性）。然后以這種假設(shè)去說服人,讓人們采取行動解決問題。 （大慶）研究是為了改變現(xiàn)狀（降低中國乃至世界的糖尿病發(fā)病率,當(dāng)時(shí)并未提出代謝綜合征）。,三.當(dāng)前2型糖尿病預(yù)防研究的局限及尚未能解決和正在解決的問題,生活方式干預(yù)預(yù)防糖尿病合理性 成本效益? 對預(yù)防心腦血管病是否有益?可行性 多少人能長期堅(jiān)持?,藥物干預(yù)預(yù)防糖尿病的合理性和可行性最佳劑量？成本效益?耐受性？毒副作用?預(yù)防了糖尿病or 提前治療?,Unanswered Questions,How to conduct the screening? One step or two-steps?OGTT or

9、 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 longer term Targeting insulin resistance or insulin insufficiency?Prevent diabetes or reverse to normal tolerance?

10、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 0.5-1.0 kg/month Exercise Group: To increase amount of leisure physical exercise by at least one unit. Diet and

11、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 units,Each category represents one unit,Lifestyle: How Intensive is Effective?,Da-Qing Study : At least decrease 50 gm of Carbohyd

12、rate/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 loss 5% and exercise 4 hours/week,Efficacy of lifestyle intervention Comparison of Da-Qing Study to DPP and DPS,Q: Should The Chi

13、nese 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 Olistat Weight Reduction (Kg) 3.00 6.05 Weight Reduction (%) 3.67

14、7.45,過強(qiáng)的生活方式干預(yù)會大大增加退出干預(yù)的人數(shù)，中等強(qiáng)度的干預(yù)才能既有效又能為廣大人群接受并常年堅(jiān)持。,DA-QING STUDY 未采用過于激烈的強(qiáng)度大的干預(yù)，失訪率僅8%. DPP，DPS 體重減輕第一年達(dá)標(biāo)率50%,Should The Chinese Need to Use Protocol in DPP or DPS in Their Future Prevention?,Yes , Just for obese IGT Chinese (BMI27?) No, For most non-obese Chinese IGT, less intensive prevention

15、protocol than DPP may be working if only for preventing DM, however reversing them to normal glucose tolerance more intensive prevention protocol is needed.,Pharmacological Intervention,Prevention is better than cure,糖尿病一級預(yù)防研究 對象 干預(yù)措施 結(jié)果 大慶研究 IGT 生活方式 50 DPP研究 IGT生活方式+雙胍 58 - 31% DPS研究 IGT 生活方式 58 S

16、TOP-NIDDM IGT 阿卡波糖 33,Lifestyle or Medication?,Lifestyle intervention studies have consistently shown that quite 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

17、changes in longer term.This has lead to consideration pharmacotherapy. Simpson RW,Shaw JE,Zimmet PZ: Diabetes Res Clin Pract 2003 59:165-80,改變生活方式的艱難 說了,但未聽見聽見了,但未理解理解了,但未接受接受了,但未付諸行動行動了,但能堅(jiān)持多久?,Incidence/pys of DM in IGT subject stratified by Ins-sensitivity,Sensitive IAI-4.73 Resistant IAI 114,Inc

18、idence of DM,. In IGT subjects with higher degrees of 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),3000IGT involved ,follow-up 3.3 years,2001 presented,58,31% ,STO

19、P NIDDM,1418 IGT involved, follow-up 3 years,2001 presented,33%,Incidence of Diabetes in Pharmacological intervention group of IGT in China (19972000),77% ,88% ,0.25 tid,50mg tid,Incidence of Diabetes in Pharmacological intervention group of IGT in China (Yuexin Wang ,3 years),69% ,50mg TID,Pharmacological interventions with Acarbose or Metformin could reduce the risk of worsening to diabetes by 6080% in Chinese subjects with IGT. Intervention with Acarbose seems more effective in Chinese than that in Westerns,SUMMAR