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 Prevention X 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（De
2、Fronzo,1991）代代 谢谢 综 合 征（Zimmet,1997）Insulin Resistance 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
3、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 11.5 10.8 11.4 17.2 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 BM
4、I=25 5.1 6.8 13.3 8.3 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 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
5、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-steps?OGTT or standard meal test?How to do the prevention?Lifestyle or pharmacological?HOW to translate these successful findings in Da-Qing St
6、udy DPP and DPS and maintain the lifestyle changes in longer 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
7、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 Exercise Group:Same as Diet and Exercise group Controls:Only exposed to general information about DM from public health education.No speci
8、al advice.Table 1.Exercise units IntensityTime(minutes)ExerciseMild30Slow 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
9、,volleyball,table tennisVery hard5Rope jumping,basketball,swimmmingEach category represents one unit Lifestyle: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
10、 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 Incidence/100pys CONTROL DIET+EXERCISE Da-Qing Study BMI 22.4 22.2 13.3 6.8 49%Da-Qing Study BMI 27.5 27.0 17.2 11.4 34%DPP BMI 34.2 3
11、3.9 11.1 4.8 58%DPS BMI 31.3 31.0 9.6 4.8 58%Q:Should The 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 US Trail for weight loss with medication(orlistat)in Chinese Lifestyle Olistat Weigh
12、t Reduction(Kg)3.00 6.05 Weight Reduction(%)3.67 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27?)No,For most non-obese Chinese IGT,less intensive prevention protocol than DPP may be working if only for preventing DM,however reversing th
13、em 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 50 DPP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 58 STOP-NIDDM IGT 阿卡波糖阿卡波糖 33 Lifestyle or Medi
14、cation?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 changes in longer term.This has lead to con
15、sideration 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 024681012141618IGT controlDietExercise D+E SEN RESSensitive IAI-4.73 Resistant IAI
16、-4.73 ie FPG FINS 114 Incidence 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)0 00.020.020.040.040.060.060.080.080.10.10.120.12CONTROLSCONTROLSMETFORMINMETFORMINLIFE-STYLELIFE-STYLE 3000IGT involved,follow3000IGT involved,follow-up 3.3 years,2001 presentedup 3.3 years,2001 presented 58 31%STOP NIDDM 0 05 5101015152020252