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 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） 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 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 BMI100 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-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? 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 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 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 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 33.9 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 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。 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 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 STOP-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 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 ? Incidence/pys of DM in IGT subject stratified by Ins-sensitivity Sensitive IAI-4.73 Resistant IAI 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) 3000IGT involved ,follow-up 3.3 years,2001 presented 58 31% STOP 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 SUMMARY 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 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)