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 YESTERDAY, TODAYAND TOMORROWKGMM AlbertiPrevention, Prevention and Prevention,X 综合征 死亡四重奏 （Reaven,1988） （Kaplan,1989）,胰岛素抵抗 中心性肥胖 糖耐量低减/DM 糖耐量低减/DM 高胰岛素血症 高TG血症 高TG血症 低HDL-c血症 高血压 高血压胰岛素抵抗综合征（DeFronzo, 1991） 代 谢 综 合 征（Zimmet, 1997）,Insulin Resistance,
2、Hypertension,Type 2 Diabetes,The metabolic syndrome of insulin resistance & cardiovascular disease,Reduced Fibrinolysis,Complex dyslipidemia TG, sdLDL HDL,Endothelial Dysfunction,Chronic systemic Inflammation,Athero- sclerosis & CHD,Visceral Obesity,2型糖尿病一级预防糖尿病高危(IGT)人群的干预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
3、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对象 干预措施 大庆研究 IGT 生活方式 DPP IGT 生活方式+双胍 DPS IGT 生活方式 STOP-NIDDM IGT 阿卡波糖,大庆研究中糖尿病每百人年发病率,11.5,10.8,11.4,17.2,饮食组,运动组,饮食+运动,对照组,BMI=25,5.1,6.8,13.3,8.3,饮食组,运动组,饮食+运动,对照组,BMI25,10.0,9.6,15.7,8.3,饮食组,运动组,饮食+运动,对照组,总 组,国际上对于大庆研究结果的评价 肯定
4、大庆研究首次证明生活方式干预可以在高危人群成功的预防糖尿病，它将对糖尿病预防产生不可估量的影响。,国际上对于大庆研究结果的评价 疑问 大庆研究的成功可能是由于： 中国不是象西方国家那样人群体力活动较少的社会。 中国人依从健康生活方式的忠告较为容易。 西方人比中国更肥胖，人群体力活动更少。 强化生活方式干预在其他人群能否预防糖尿病尚难肯定。,Prevention is better than cure,糖尿病一级预防研究对象 干预措施 结果 大庆研究 IGT 生活方式 50 DPP研究 IGT 生活方式+双胍58- 31% DPS研究 IGT 生活方式 58 STOP-NIDDM IGT 阿卡波
5、糖 33,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
6、in larger cohorts or maintain the lifestyle changes in longer term.,Prevention is better than cure,问题：现实中糖尿病能预防吗？ 我们应该筛查糖尿病本身还是糖尿病的危险因素？ 2型糖尿病预防研究和预防实施之间 相差有多大远?,二.大庆糖尿病预防研究的由来,生活方式与2性糖尿病因果关系假设,基因治疗遥遥无期 药物干预尚无定论 强化生活方式干预-可行?,5%-10%/年,基因易感性,老龄,营养过剩,体力活动少,细胞功能受损 胰岛素抵抗,糖耐量低减,糖尿病,大庆研究与国外相关研究(1980-1992)比
7、较,作者,例数,随访期,干预,方法,结果,研究的优缺点,Sartor G,206,10,年,药物,饮食,有效,每组少于,50,例,失访率,47%(23/49),主动干预不足,单因数分析,Keen H,241,10,年,D860,饮食,无效,单因数分析,Erikson k,217,6,年,饮食,+,运动,有效,非随机分组,单因数分析,未显示主动干预效果,X.R .Pan,576,6,年,饮食,+,运动,有效,失访率,8%,随机分组,每组,100,例,多因素分析,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
8、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发病率,当时并未提出代谢综合征）。,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-ste
9、ps? 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 longer term Targeting insulin resistance or insulin insufficiency? Prevent diabetes or reverse to norma
10、l 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 0.5-1.0 kg/month Exercise Group: To increase amount of leisure physical exercise by at least one uni
11、t. 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 units,Each category represents one unit,Lifestyle: How Intensive is Effective?,Da-Qing Study :At least decrease 50 gm
12、of Carbohydrate/dayat least increase 50 min physical exercise/day5 days/weekDiabetes Prevention Program:Weight loss 7% and exercise 150min/weekDiabetes 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 Th
13、e Chinese 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 USTrail for weight loss with medication (orlistat) in ChineseLifestyle Olistat Weight Reduction (Kg) 3.00 6.05 Weight Reduction (%) 3.
14、67 7.45,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,糖尿病一级预防研究对象 干预措施 结果 大庆研究 IGT 生活方式 50 DPP研究 IGT 生活方式+双胍58- 31% DPS研究 IGT 生活方式 58 ST
16、OP-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 ch
17、anges in longer term.This has lead to consideration pharmacotherapy.Simpson RW,Shaw JE,Zimmet PZ:Diabetes Res Clin 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-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% ,STOP
19、 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,Pharmacol
20、ogical 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,SUMMARY,How To Increase Effectiveness and Reduce Cost? STRATEGY OF THE INTERVENTION,In
21、cidence/pys Reduction of DM in peoples with IGT stratified by INS-SEN and secretion,G 4 G3 G2 G1,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%,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 trialsGet Out Of the Ivory Tower ? 让临床试验走出神殿 任重而道远,THANK YOU,
