糖尿病高危(IGT)人群的干預(yù)

1、煩惱有何懼怕，既然躲不掉，就調(diào)好心態(tài)與它共存。心向陽光，何懼風(fēng)霜。茫茫人海你我相遇就是緣分，歡迎下載！2021/4/2622型糖尿病一級預(yù)防糖尿病高危(IGT)人群的干預(yù)2021/4/263 IDF 主席開幕式演講主席開幕式演講YESTERDAY, TODAY AND TOMORROW KGMM Alberti Prevention, Prevention and Prevention2021/4/264X 綜合征 死亡四重奏死亡四重奏（Reaven,1988） （Kaplan,1989） 胰島素抵抗胰島素抵抗 中心性肥胖中心性肥胖糖耐量低減糖耐量低減/DM 糖耐量低減糖耐量低減/DM高胰島素

2、血癥高胰島素血癥高高TG血癥血癥 高高TG血癥血癥低低HDL-c血癥血癥高血壓高血壓 高血壓高血壓 胰島素抵抗胰島素抵抗綜合征（DeFronzo, 1991） 代代 謝謝 綜 合 征（Zimmet, 1997） 2021/4/265Insulin ResistanceHypertensionType 2 DiabetesThe metabolic syndrome of insulin resistance & cardiovascular diseaseReducedFibrinolysisComplexdyslipidemiaTG, sdLDL HDLEndothelialDysf

3、unctionChronic systemicInflammationAthero-sclerosis &CHDVisceralObesity2021/4/266 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)防研究的局限 及尚未能解決和正在解決的問題2021/4/267一. 歷史的回顧2021/4/268Prevention is better than cure糖尿病一級預(yù)防研究糖尿病一級預(yù)防研究 對象對象 干預(yù)措施干預(yù)措施 大慶研究大慶研究 IGT 生活方式生活方式DPP IGT 生活方式生活方式+雙胍雙胍DPS IGT 生活

4、方式生活方式STOP-NIDDM IGT 阿卡波糖阿卡波糖2021/4/269大慶研究中糖尿病每百人年發(fā)病率11.510.811.417.2飲食組飲食組運動組運動組飲食飲食+ +運動運動對照組對照組BMI=255.16.813.38.3飲食組飲食組運動組運動組 飲食飲食+ +運動運動 對照組對照組BMI100 例例多因素分析多因素分析胰島素抵抗對干預(yù)療效分析胰島素抵抗對干預(yù)療效分析2021/4/2619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

5、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糖尿病發(fā)病率發(fā)病率,當(dāng)時并當(dāng)時并未提出代謝綜合征未提出代謝綜合征）。 2021/4/2620三.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2021/4/2621 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 多少人能長期堅持?2021/4/2622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?2021/4/2623Unanswered Questions How to conduct the screening? One step

6、 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

7、to normal tolerance? Standard protocol or tailored one? How To Increase Effectiveness and Reduce Cost? 2021/4/2624Lifestyle or Medication?2021/4/2625Method 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 physica

8、l 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.2021/4/2626Table 1. Exercise unitsIntensityTime(minutes)ExerciseMild30Slow walking, taking bus (standing),s

9、hopping, 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, volleyball, table tennisVery hard5Rope jumping, basketball, swimmmingEach category represents

10、one unit2021/4/2627Lifestyle: 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

11、 4 hours/week2021/4/2628Efficacy of lifestyle intervention Comparison 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%2021/4/2629Q: Should

12、 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 OlistatWeight Reduction (Kg) 3.00 6.05 Weight Reduction (%)

13、 3.67 7.45 2021/4/2630 過強的生活方式干預(yù)會大大增加退出干預(yù)的人數(shù)，中等強度的干預(yù)才能既有效又能為廣大人群接受并常年堅持。2021/4/2631 DA-QING STUDY 未采用過于激烈的強度大的干預(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 g

14、lucose tolerance more intensive prevention protocol is needed. 2021/4/2633Pharmacological Intervention2021/4/2634Prevention is better than cure糖尿病一級預(yù)防研究糖尿病一級預(yù)防研究 對象對象 干預(yù)措施干預(yù)措施 結(jié)果結(jié)果大慶研究大慶研究 IGT 生活方式生活方式 50DPP研究研究 IGT生活方式生活方式+雙胍雙胍 58 - 31%DPS研究研究 IGT 生活方式生活方式 58STOP-NIDDM IGT 阿卡波糖阿卡波糖 332021/4/2635Lif

15、estyle 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

16、 has lead to consideration pharmacotherapy. Simpson RW,Shaw JE,Zimmet PZ: Diabetes Res Clin Pract 2003 59:165-802021/4/2636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,但能堅持多久?2021/4/2637Incidence/pys of DM in IGT subject stratified by Ins-sensitivity024681012141618IGT controlDietExercise D+E SEN R

17、ESSensitive IAI-4.73 Resistant IAI -4.73 ie FPG FINS 114Incidence of DM2021/4/2638. 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. 2021/4/2639Diabetes Preventio

18、n Program (USA)0 00.020.020.040.040.060.060.080.080.10.10.120.12CONTROLSCONTROLSMETFORMINMETFORMINLIFE-STYLELIFE-STYLE 3000IGT involved ,follow-up 3.3 years,2001 presented5831% 2021/4/2640 STOP NIDDM0 05 510101515202025253030353540404545CONTROLSCONTROLSACRBOSEACRBOSE 1418 IGT involved, follow-up 3 y

19、ears,2001 presented33%2021/4/2641Incidence of Diabetes in Pharmacological intervention group of IGT in China (19972000)11.111.14.14.12 20 02 24 46 68 810101212controlscontrolsMetforminMetforminAcarboseAcarboseIncidence ofDMIncidence ofDM77% 88% 0.25 tid50mg tid2021/4/2642Incidence of Diabetes in Pha

20、rmacological intervention group of IGT in China (Yuexin Wang ,3 years)11.711.73.63.60 02 24 46 68 8101012121414controlscontrolsn=58n=58AcarboseAcarbosen=58n=58Incidence of DMIncidence of DM69% 50mg TID2021/4/2643 Intervention with A seems more effective in Chinese than that in WesternsSUMMARY2021/4/

21、2644 How To Increase Effectivenessand Reduce Cost? STRATEGY OF THE INTERVENTION2021/4/2645Incidence/pys Reduction of DM in peoples with IGT stratified by INS-SEN and secretion-49%-42%-31%-27%G1 IAI-4.73 FI/FG2.52G1 IAI-4.73 FI/FG2.52G2 IAI-4.73 FI/FG-4.73 FI/FG2.52G3 IAI5.28G3 IAI5.28G4 IAI-4.73 FI/FG5.28G4 IAI-4.73 FI/FG60 11%BMI 22-30 3%30-35 16%35 53%2021/4/2647藥物預(yù)防的有效性DPP方式干預(yù) 與二甲雙呱療效比較25-44 8% 45-59 41% 60 69%BMI 22-30 63%30-35 53%35 -4%2021/4/2648藥物預(yù)防的有效性DPP 二甲雙呱 的有效性PG2H(mg/dl)140-153 41%154-172 38% 173-199 26%2021/4/2649 Targeting Insulin resistance or insulin insufficiency?2021/