null2型糖尿病一级预防
糖尿病高危(IGT)人群的干预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null IDF 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
(Reaven,1988) (Kaplan,1989) 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)
The metabolic syndrome of
insulin resistance & cardiovascular diseaseThe metabolic syndrome of
insulin resistance & cardiovascular diseaseInsulin ResistanceHypertensionType 2 DiabetesReduced FibrinolysisComplex dyslipidemia
TG, sdLDL HDL
Endothelial DysfunctionChronic
systemic InflammationAthero- sclerosis &
CHDVisceral Obesitynull 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. 历史的回顾一. 历史的回顾Prevention is better than curePrevention 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大庆研究中糖尿病每百人年发病率11.510.811.417.2饮食组运动组饮食+运动对照组BMI>=255.16.813.38.3饮食组运动组饮食+运动对照组BMI<2510.09.615.78.3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
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
肯定
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。 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 curePrevention 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 阿卡波糖 -33%
null 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 larger cohorts or maintain the lifestyle changes in longer term.Prevention is better than curePrevention 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 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β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)比较大庆研究与国外相关研究(1980-1992)比较作者例数随访期干预
方法
快递客服问题件处理详细方法山木方法pdf计算方法pdf华与华方法下载八字理论方法下载
结果研究的优缺点Sartor G20610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 H24110年D860,饮食无效单因数分析Erikson k2176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 5766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? 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?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 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 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?Lifestyle or Medication?Method of interventionMethod of interventionDiet Group:
BMI < 25 30 kcal / kg.day: reduce alcohol and sugar
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 special advice.Table 1. Exercise unitsTable 1. Exercise unitsEach category represents one unitLifestyle: How Intensive is Effective?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 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 Efficacy of lifestyle intervention
Comparison of Da-Qing Study to DPP and DPS
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
Weight 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。 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。null 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?
Should The Chinese Need to Use Protocol in DPP or DPS in Their Future Prevention?
Yes , Just for obese IGT Chinese (BMI>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 protocol is needed. Pharmacological InterventionPharmacological InterventionPrevention is better than curePrevention 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 阿卡波糖 -33%
Lifestyle or Medication?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 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?
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-sensitivityIncidence/pys of DM in IGT subject
stratified by Ins-sensitivitySensitive IAI>-4.73 Resistant IAI <-4.73
ie FPG × FINS <114 ie FPG × FINS >114Incidence of DMnull.
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)Diabetes Prevention Program (USA) 3000IGT involved ,follow-up 3.3 years,2001 presented58↓31% ↓ STOP NIDDM STOP NIDDM 1418 IGT involved, follow-up 3 years,2001 presented33%↓Incidence of Diabetes in Pharmacological intervention group of IGT in China (1997~2000)Incidence of Diabetes in Pharmacological intervention group of IGT in China (1997~2000)77% ↓88% ↓0.25 tid50mg tidIncidence of Diabetes in Pharmacological intervention group of IGT in China
(Yuexin Wang ,3 years)Incidence of Diabetes in Pharmacological intervention group of IGT in China
(Yuexin Wang ,3 years)69% ↓50mg TIDnull Pharmacological interventions with Acarbose or Metformin could reduce the risk of worsening to diabetes by 60~80% 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
How To Increase Effectiveness
and Reduce Cost?
……
STRATEGY OF THE INTERVENTION
Incidence/pys Reduction of DM in peoples with IGT stratified by INS-SEN and secretion
Incidence/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? Targeting Insulin resistance
or insulin insufficiency?Prevent diabetes or reverse to
normal glucose tolerance?Prevent diabetes or reverse to
normal glucose tolerance?How to Screen…?
One Step or Two Steps?How to Screen…?
One Step or Two Steps?null 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 YOUTHANK YOU