糖尿病伴血脂异常患者的 社区治疗策略

主要内容 糖尿病及冠心病的流行病学 糖尿病脂质异常与冠心病的关系 糖尿病血脂干预治疗的必要性及效果 糖尿病血脂异常的防治策略

2000-2005年全球2型糖尿病的患病率 2000年全球有1.55 亿成年人诊断糖尿病 -- 女性8千3百万，男性 7千2 百万 2000年全球有1.55 亿成年人诊断糖尿病 -- 女性8千3百万，男性 7千2 百万 1995 - 2025, 成年人糖尿病的患病率将增加 35%，糖尿病人数将增加122% 2005年糖尿病人数将达到3亿 EUROPE 2000: 30.8M 2025: 38.5M ASIA 2000: 71.8M 2025: 165.7M USA 2000: 15M 2025: 21.9M JAPAN 2000: 6.9M 2025: 8.5M Type 2 diabetes is a serious problem. About 155 million adults were diagnosed in 2000, and a 110% increase to 300 million is projected by 2025. A combination of current worldwide age-specific type 2 diabetes prevalence estimates, United Nations population estimates, and projections for the number of adults 20 years of age have been used to project the prevalence and number of individuals who will have diabetes by the year 2025.4 The greatest increases in both prevalence and numbers of individuals with diabetes are expected to occur in the developing world. By the year 2025, >75% of people with diabetes will reside in developing countries, compared with 62% in 1995. All of these results support the view that aggressive intervention to prevent the long-term complications of diabetes is, and will continue to be, an urgent priority. AFRICA 2000: 9.2M 2025: 21.5M Ref 4, p 1414, C3, ¶2, L1; p 1416, ¶2, L10; p 1417, C3, ¶2, L3; p 1421, App 2, C1,3,11, L1-3; App 2, C1,11, L6,8, L10, 12 AMERICAS (Ex-US) 2000: 20M 2025: 42M OCEANIA 2000: 0.8M 2025: 1.5M Adapted from King H et al Diabetes Care 1998;21:1414-1431.

糖尿病人的主要死亡原因 67% 2/3 糖尿病人死于心血管疾病 糖尿病人中，大血管并发症包括心血管疾病、脑卒中和外周血管疾病是主要致残、致死原因 Causes of mortality in people with diabetes 67% CHD, stroke, and peripheral vascular disease Other Cardiovascular disease is the leading cause of death among individuals with diabetes.6 Approximately two-thirds of individuals with diabetes die of cardiovascular disease, including CHD, stroke, and peripheral vascular disease.10 Ref 6, p 365, ¶7, L1 Ref 10, p 21, ¶1, L5 Adapted from Alexander CM, Antonello S Pract Diabet 2002;21:21-28.

糖尿病与非糖尿病人发生第一次心梗的死亡率 Many patients with diabetes will not survive their first MI 50 With diabetes Without diabetes 44%* 40 37%* 33% 30 Mortality rate (%) 20% 20 10 Many patients with diabetes will not survive their first myocardial infarction (MI). A study of 620 patients with diabetes and 3442 nondiabetic patients who had their first MI during the period 1988–1992 demonstrated the increased risk for short- and long-term mortality in patients with diabetes.11 Overall mortality rates at one year (hospitalized and nonhospitalized) were significantly higher for both men and women with diabetes (44% for men, 37% for women) than for nondiabetic patients (33% for men, 20% for women; both p<0.001). These results suggest an urgency for vigorous primary and secondary measures to help prevent MI in patients with diabetes. Thus, patients with diabetes should be treated early, for example, with lipid-lowering therapy, before CHD develops. n=437 n=2699 n=183 n=743 Ref 11 p 69, ¶2, L1 p 70, ¶4, L1-5, 16-19; p 73, T3, R3,7, C10-12 Men Women 1 Year, hospitalized and non-hospitalized Time post-first MI MI = myocardial infarction *p<0.001 Adapted from Miettinen H et al Diabetes Care 1998;21:69-75.

Incidence of fatal or nonfatal MI (%) 糖尿病人与心梗病人再发心梗的危险比较 25 20% 19% 20 15 Incidence of fatal or nonfatal MI (%) 10 5 Diabetes (no prior MI) (n=890) Prior MI (no diabetes) (n=69) In the East-West study, people with diabetes and without prior MI had a similar risk of fatal or nonfatal MI as did people without diabetes and with a prior MI. Among the 890 diabetic patients without prior MI, 20% experienced a fatal or nonfatal MI, compared with the 19% rate for nondiabetic patients with prior MI. This and other observations from this study form the basis of the recommendation that patients with diabetes, but without a history of cardiovascular disease, should have the same approach to cardiovascular risk-factor management as nondiabetics with an established history of CHD.8,12 Ref 8, p 232, T2, R1,2, C2,6; p 233, ¶5, L1 Ref 12, p 2494, C2, ¶2, L9 Patient type Patients with diabetes without previous MI have as high of a risk of MI as non-diabetic patients with previous MI. These data provide a rationale for treating cardiovascular risk factors in diabetic patients as aggressively as in non-diabetic patients with prior MI. Adapted from Haffner SM et al N Engl J Med 1998;339:229-234.

糖尿病心梗风险相当于发生过心梗的患者 芬兰人群7年随访期MI发生情况 致命与非致命性MI(%) 45.0 20.2 18.8 Prior MI 18.8 3.5 45.0 20.2 P<0.001 No prior MI No prior MI 无糖尿病 糖尿病 (n=1373) (n=1059) Haffner SM et al. N Engl J Med 1998;339:229-234.

冠心病患者的糖代谢状况欧洲心脏研究 包括2107急性冠心病住院患者和2854例稳定性冠心病门诊患者 糖尿病病史 OGTT* 58 51 Total patients (%) Patients* (%) Abnormal glucose metabolism in CAD 欧洲心脏研究提示, 在包括2107 急性冠心病住院患者和2854例稳定性冠心病门诊患者, 通过OGTT发现糖代谢异常的患者占所有除了有糖尿病病史患者以外群体的60%. 如果加上之前有糖尿病病史的患者, 约占所有患者的80-90%. 而糖尿病患者占所有患者50%. The Euro Heart Survey on diabetes and the heart studied the prevalence of abnormal glucose metabolism in patients with coronary artery disease (CAD). The study included 4961 patients referred to a cardiologist due to CAD; 2107 were hospitalized for acute CAD (inpatients), and 2854 were seen for an elective consultation (outpatients). A history of diabetes was present in 32% of the inpatients and 30% of the outpatients. Additionally, oral glucose tolerance test (OGTT) results, which were available for 1920 of the patients without known diabetes (DM), showed that 58% of patients with acute CAD and 51% with stable CAD had undiagnosed type 2 diabetes (T2DM), impaired fasting glucose (IFG), or impaired glucose tolerance (IGT). Overall findings in the survey clearly show that abnormal glucose regulation is more common than normal glucose regulation in patients with CAD. IGT IFG New DM 无论是冠心病住院患者还是门诊患者，2个中约1个是糖尿病. *n = 1920 without known diabetes OGTT = oral glucose tolerance test; IGT = impaired glucose tolerance; IFG = impaired fasting glucose Bartnik M et al. Eur Heart J. 2004;25:1880-90.

中国冠心病住院患者的糖代谢异常 冠心病住院患者中糖尿病检出率为52.9% 糖调节受损检出率为24.0% 总的糖代谢异常检出率为76.9% 调查包括中国7大城市共52所三级医院3513例冠心病患者 冠心病住院患者中糖尿病检出率为52.9% 糖调节受损检出率为24.0% 总的糖代谢异常检出率为76.9% 单纯FPG检测的漏诊率: 糖尿病 80.5%, IGT: 87.4% 中国7大城市共52所三级医院3513例冠心病患者调查显示冠心病合并有糖尿病异常的患者占冠心病患者52.9% 冠心病:慢性稳定型心绞痛,急性冠脉综合征和陈旧性心肌梗死. 糖代谢状况:对过去已确定诊断糖尿病的患者收集空腹血糖( FPG) 、餐后或随机血糖资料. 未确诊糖尿病的患者均接受口服葡萄糖耐量试验(OGTT) ,急性冠心病患者需在出院前3 ～4 天进行OGTT试验,慢性患者无试验日期的限制; OGTT仅检测FPG和糖负荷后2h血糖( 2hPG)两个点,且OGTT试验只做一次; 全体研究对象中,入院后通过非OGTT方法诊断的糖尿病为97例, OGTT诊断为糖尿病及IGR分别为609和844例,说明全体研究对象入院前有706例合并糖尿病患者未被诊断, 占全部糖尿病患者的38. 0%; IGR的糖尿病前期患者几乎全部被漏诊; 即入院前全部糖代谢异常的患者(包括糖尿病和IGR)中有57. 3% (1 550 / 2 703)被漏诊。 糖尿病包括单纯性空腹高血糖( IFH, FPG≥7. 0 mmol/L且2hPG < 11. 1 mmol/L ) 、单纯性负荷后高血糖( IPH, FPG < 7. 0 mmol/L且2hPG≥11. 1 mmol/L) 、复合性高血糖(CH, FPG≥7. 0 mmol/L 且2hPG≥11. 1mmol/L) 目前,国内大部分机构在进行心血管专科疾病的临床实践中,主要采用FPG检测,OGTT试验的普及率尚不足。研究结果提示,若不进行OGTT试验,单纯的FPG检测将有80. 5%的糖尿病患者被漏诊和87. 4%的IGT患者被漏. 全体3513例：过去确诊糖尿病1153例；入院后2次FPG确诊糖尿病97例； 其余2263例中通过OGTT发现糖尿病609例；所有糖尿病患者为1859例。 中华内分泌和代谢杂志.2006,22(1)7-10

小结： ＊ 在我国糖尿病患病率及死亡率逐年增加 ＊ 冠心病住院患者中糖尿病检出率高

主要内容 糖尿病及冠心病的流行病学 糖尿病脂质异常与冠心病的关系 糖尿病血脂干预治疗的必要性及效果 糖尿病血脂异常的防治策略

糖尿病显著增加心血管疾病风险 ~65%的患者死于CV 冠心病死亡 2-4倍 中风 2-4倍 心衰 2-5倍 2型糖尿病的心血管并发症 Cardiovascular disease and diabetes Cardiovascular (CV) disease is the primary complication of diabetes; approximately 65% of deaths in people with diabetes are due to heart disease and stroke. Adults with diabetes have higher rates of coronary heart disease (CHD), stroke, and heart failure (HF) than nondiabetic adults: CHD death rates are 2 to 4 times higher Risk of stroke is 2 to 4 times higher HF occurs twice as frequently in men and 5 times more frequently in women aged 45 to 74 years In 2004, the estimated prevalence of physician-diagnosed diabetes among adults was 15.2 million; the prevalence of undiagnosed diabetes was 5 million. According to the most recent government statistics, approximately one-third of the US population with diabetes is undiagnosed.(1) 心衰 2-5倍 Bell DSH. Diabetes Care. 2003;26:2433-41. Centers for Disease Control (CDC). www.cdc.gov. 1. American Heart Association. Heart Disease and Stroke Statistics. 2007 Update.

糖尿病是冠心病的等危症 (East West Study) p<0.001 No diabetes (n=1373) Diabetes (n=1059) The results from this study show that patients with diabetes without a previous MI have as high a risk of having an MI as patients with no diabetes and with a previous MI (20% vs. 19%, respectively). The seven-year incidence of MI (fatal and non-fatal) was compared in 1373 patients without diabetes and 1059 patients with diabetes from a Finnish-based population study. These data provide a rationale for treating cardiovascular risk factors in patients with diabetes as aggressively as patients with no diabetes and with a prior MI, and support the NCEP ATP III guidelines that now include diabetes as a CHD risk equivalent.1 Reference 1. Haffner SM, Lehto S, Rönnemaa T et al. N Engl J Med 1998;339:229–234. Adapted from Haffner SM et al. N Engl J Med 1998;339:229–234

2型糖尿病血脂异常的特点 TG 30～40％，其中10％>4.5mmol/L (400mg/dl) HDL-C VLDL(TC)/磷脂比率显著增高 LDL-C －或，但小而密颗粒LDL 

糖尿病患者的心血管疾病预后 与HDL显著相关 Diabetes Care 28:108–114, 2005

小结： 糖尿病患者合并血脂异常时，心血管危险因素显著增加 糖尿病是冠心病的等位症 ＊ ＊

主要内容 糖尿病及冠心病的流行病学 糖尿病脂质异常与冠心病的关系 糖尿病血脂干预治疗的必要性及效果 糖尿病血脂异常的防治策略

糖尿病血脂干预治疗的必要性 在无心血管疾病病史的糖尿病中，突发心血管疾病事件的危险性与已有心血管疾病病史的非糖尿病患者相等 仅仅血糖控制未能完全地消除糖尿病患者过高的冠心病危险性 血脂治疗对降低糖尿病及非糖尿病患者的心血管危险性同样有效

糖尿病血脂异常主要研究 研究 药物及剂量 糖尿病 患者数 随访 时间 糖尿病患者CVD 危险降低 二级预防 4S CARE LIPID VA-HIT 辛伐他汀20-40mg/日 普伐他汀40mg/日 吉非罗齐1200 mg/日 202 586 782 627 5.4年 5.0年 6.0年 7.0年 主要冠心病事件降55% 主要冠心病事件25%  冠心病事件降低19%  24% 一级预防 WOSCOPS AFCAPS/ TexCAPS SENDCAP  DAIS CARDS 洛伐他汀20-40 mg/日 苯扎贝特 400mg/日 非诺贝特400mg/日 阿托伐他汀10mg/日 76 1555 418 2838 4.9年 2.0年 3.0年 3年多 31% 显著降低 不能肯定 统计学效能不够 分析临床 终点 一级/二级预防 HPS 辛伐他汀40mg/日 5963 22%

他汀类研究显示LDL-C水平与冠心病事件的关系 4S-PI Mean LDL-C level at follow-up (mg/dL) 110 130 150 170 190 210 5 10 15 20 25 30 90 % with CHD event 二级预防 4S-Rx LIPID-Rx LIPID-PI CARE-PI WOSCOPS-PI CARE-Rx AFCAPS/TexCAPS-PI 一级预防 WOSCOPS-Rx AFCAPS/TexCAPS-Rx PI=placebo; Rx=treatment Shepherd J et al. N Engl J Med. 1995;333:1301-1307. 4S Study Group. Lancet. 1995;345:1274-1275. Sacks FM et al. N Engl J Med. 1996;335:1001-1009. Downs JR et al. JAMA. 1998;279:1615-1622. Tonkin A. Presented at AHA Scientific Sessions, 1997.

ATPIII建议: 首要目标: 降低LDL-C 重点对象:冠心病和冠心病等危症 LDL-C<2.6mmol/L(100mg/dL) 我国建议 JAMA 2001;285:2486-2497

在他汀类进行的二级预防的研究中 主要冠心病事件发生情况 在他汀类进行的二级预防的研究中 主要冠心病事件发生情况 入选亚组 CHD 事件/患者数(%) Odds Ratio 及研究名称 他汀类 安慰剂 (& CI) 只有CHD 4S 407/ 2116 578/ 2126 CARE 162/ 1799 212/ 1774 LIPID 481/ 4116 627/ 4116 亚组 1050/ 8031 1417/ 8016 30% ± 4 下降 (13%) (18%) CHD + 糖尿病 4S 24/ 105 44/ 97 CARE 50/ 282 62/ 304 LIPID 76/ 396 88/ 386 亚组 150/ 783 194/ 787 29% ± 10 下降 (19%) (25%) 所有 CHD 患者 1200/ 8814 1611/ 8803 30% ± 3 下降 (14%) (18%) (2P<0.00001) 0.25 0.5 0.75 1.0 1.25

降脂研究荟萃分析（主要为他汀研究） N = 80,862 with and without diabetes, 12 trials 糖尿病 非糖尿病 NNT 2006年BMJ上一篇关于同时入选糖尿病和非糖尿病患者降脂研究荟萃分析显示, 降脂研究(绝大部分是他汀研究)可以显著降低糖尿病和非糖尿病患者的心血管风险. 而糖尿病患者无论在一级预防还是二级预防中获益更多. The evidence that lipid lowering drug treatment (especially statins) significantly reduce cardiovascular risk in diabetic and non-diabetic patients is strong and suggests that diabetic patients benefit more, in both primary and secondary prevention. 一级预防 二级预防 糖尿病患者降脂治疗获益显著大于非糖尿病患者 NNT = number needed to treat，需要治疗多少例患者才能避免一次事件 Costa J et al. BMJ. 2006;332:1115-24.

UKPDS 降低冠心病(CHD)危险性 1. LDL 胆固醇 2. 舒张压 3. 吸烟 4. HDL 胆固醇 5. 糖化血红蛋白(HbA1C) Turner RC et al. BMJ 1998; 316: 823-828

UKPDS LDL-C 是糖尿病人心血管危险的最主要标志 % Increase in CHD risk LDL-C  of 1 mmol/L 57 HDL-C  of 0.1 mmol/L –15 Systolic blood pressure  of 10 mmHg 15 HbA1c level  of 1% 11 Smoking was also a major contributor to CHD risk UKPDS clearly demonstrated that in addition to important glucose control for reducing microvascular complications, LDL-C is a primary target for reducing CHD risk in patients with diabetes. The effect of a unit increment in key risk factors (1 mmol/L for LDL-C, 0.1 mmol/L in HDL-C, 10 mmHg in systolic blood pressure [SBP], and 1% in HbA1c) on CHD risk was also determined. For each increment of 1 mmol/L in LDL-C, there was a 1.57-fold (57%) increased risk of CHD. For each positive increment of 0.1 mmol/L in HDL-C, there was a 0.15-fold (15%) decrease in risk. For each increment of 10 mmHg in SBP, there was a 1.15-fold (15%) risk increase, and for each increment of 1% in HbA1c, there was a 1.11-fold (11%) increase in risk.20 This analysis supports the view that elevated LDL-C is the strongest determinant of CHD risk in patients with type 2 diabetes. Ref 20, p 826, C2, ¶3, L1 % increase= risk – 1.00  100 These data support the need for reducing LDL-C to lower CHD risk in people with diabetes mellitus. Glucose control is also important in reducing the risk of micro vascular complications. Adapted from Turner RC et al BMJ 1998;316:823-828.

4S:根据血糖水平各治疗组主要心血管事件 相对危险性下降率 Haffner SM, et al. Arch Intern Med. 1999;159:2661–2667.

HPS研究 2004年ATP III新报告对高危患者提出 更积极的LDL-C治疗目标 HPS 研究证明对广泛的高危患者强化 降脂的益处 对各类高危患者，辛伐他汀均证明有 显著的益处

HPS研究 -- 辛伐他汀治疗主要血管事件危险性下降率 (糖尿病与非糖尿病) 基线特征 他汀 安慰剂 危险性比值和95%可信区间 (10,269) (10,267) 他汀更好 他汀更差 糖尿病 HbA1c < 7.0% 297 365 c Het 2 = 0.0 HbA1c 7.0% 298 374 1 非糖尿病 271 代谢综合征 359 c Het 2 = 0.1 1162 1487 1 其它 24% SE 2.6 所有患者 2042 2606 reduction (19.9%) (25.4%) (2P<0.00001) 0.4 0.6 0.8 1.0 1.2 1.4

HPS研究 辛伐他汀治疗糖尿病患者的益处 40 P 30 P S 20 P S 10 13% 25% 31% 36% 相对风险下降 P值 32.9% 24.5% 18.4% P值 0.0003 <0.0001 0.002 40 S=辛伐他汀组 P=安慰剂组 P S 30 P S 20 -32.9% 发生首次主要心血管事件的比例(%) 辛伐他汀可以显著减少单纯糖尿病患者或糖尿病合并心血管疾病患者的主要血管事件 P -18.4% S 10 9% 13% 20% 25% 31% 36% 单纯糖尿病 单纯阻塞性动脉 病变 兼有糖尿病与 阻塞性动脉病变 Lancet. 2003;361:2005-2016.

SILHOUETTE研究 辛伐他汀可以有效升高对心血管具有更好保护作用的HDL2 ApoAI作为HDL的主要组成蛋白, 在RCT中起了很大作用. ApoAI能诱发ABCA1和卵磷脂胆固醇酰基转移酶的活性, 也是HDL分解代谢(cubilin受体和B链ATP合酶)和胆固醇脂选择性摄取中涉及的膜联受体(SR-B1)的配体. ApoAII存在于部分HDL中.在动物模型中可能有致动脉粥样硬化性.只含有ApoAI(Lp AI)的HDL颗粒主要是HDL2. 与Lp AI+II的HDL相比, HDL2是外周细胞ATP结合盒转运体A1(ABCA1)的游离胆固醇更有效的受体, 也是肝脏细胞SR-B1素胆固醇脂的更有效受体 CURRENT MEDICAL RESEARCH AND OPINION VOL. 20, NO. 7, 2004, 1087–1094

既往他汀类药物在2型糖尿病患者中的研究 既往使用他汀类药物治疗2型糖尿病患者的益 处、仅来源于对他汀类药物进行一级及二级 预防试验的亚组分析 除心脏保护试验(HPS)外, 其它试验中只有极 少数糖尿病患者的数据用于分析、评估 需要专门在大范围糖尿病患者中进行降脂治 疗试验，来更好地评估他汀类药物对糖尿病 病人的益处 尽管已经把糖尿病作为冠心病的等危因素，但是仍然需要一些前瞻性试验数据来强调在糖尿病患者中控制CVD风险的重要性。 目前，关于他汀药物在预防糖尿病患者心血管病的作用方面，只有一些长期大规模临床试验的亚组分析数据。这些试验数据显示，在降低心血管病风险方面，他汀类药物对糖尿病患者的疗效至少和对CHD患者的疗效一样。 除了心脏保护试验（HPS）之外，在这些试验中只有一小部分糖尿病患者的试验数据用于评估分析。因此目前需要大规模的试验，来充分评估他汀类药物对糖尿病患者可能存在的临床获益，尤其是在一级预防中的临床获益。 Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7-22. Collins R, Armitage J, Parish S, Sleigh P, Peto R; Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005-16. Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus ‘usual’ care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary heart-disease Evaluation (GREACE) study. Curr Med Res Opin. 2003;18:220-228. Goldberg RB, Mellies MJ, Sacks FM, et al, for the CARE Investigators. Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the Cholesterol and Recurrent Events (CARE) trial. Circulation. 1998;98:2513-2519. Haffner SM, Alexander CM, Cook TJ, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med. 1999;159:2661-2667. Pyörälä K, Pedersen TR, Kjekshus J, et al, and the Scandinavian Simvastatin Survival Study (4S) Group. Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care. 1997;20:614-620.

入选时无任何血管疾病的糖尿病患者研究结束时的主要血管事件 辛伐他汀 安慰剂 (n=1455) (n=1457) 133 197 (9.1%) (13.5%) 危险性下降率:34% (95% CI: 19-47%), P<0.0001

小结： ＊糖尿病患者合并血脂异常时应积极降脂治疗 ＊有效降脂治疗后，可显著降低主要心血管时间的危险性

主要内容 糖尿病及冠心病的流行病学 糖尿病脂质异常与冠心病的关系 糖尿病血脂干预治疗的必要性及效果 糖尿病血脂异常的防治策略

中国糖尿病预防和治疗指南中 2型糖尿病患者血脂目标值 (mmol/L) 良好 较好 差 TC <4.5 ≥4.5 ≥6.0 HDL-C >1.1 1.1~0.9 <0.9 TG <1.5 <2.2 ≥2.2 LDL-C <2.6 2.6~4.0 >4.0

目前临床上对于2型糖尿病的治疗指南 Joint European Task Force 美国糖尿病协会（ADA） “...糖尿病患者的总CHD风险远高于其它情况相似的非糖尿病患者” “糖尿病患者的血压和脂质紊乱的治疗目标通常都更严格” 美国糖尿病协会（ADA） 鼓励应用他汀治疗，在 “…40岁以上的糖尿病患者… 不需考虑基线LDL水平” 美国胆固醇教育计划（ NCEP ） ATP III “…糖尿病被认为是冠心病等危症，因为糖尿病10年内新发冠心病的风险很高…” “…由于发生过心梗的糖尿病患者，不论在近期还是远期，都具有非常高的死亡率，因此应用更积极的预防策略是合理的” Recent clinical guidelines have recognized the importance of treating CHD in patients with diabetes. The Joint European Task Force1 suggests, that all things being equal, the risk of CHD is greater in patients with type 2 diabetes. A recent update of European guidelines states that treatment goals for blood pressure and lipids are generally more ambitious in patients with diabetes.2 The ADA3 and the Joint European Task Force1,2 have identified LDL-C as the primary target of lipid-lowering therapy to lower the risk of CHD in patients with type 2 diabetes. ADA guidelines also note that an integrated approach to the prevention of CHD in patients with diabetes is necessary.3 The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)4 guidelines classify type 2 diabetes as a “CHD risk equivalent,” ie, patients with diabetes and no CHD should be considered as having a similar risk of future cardiac events as patients with existing CHD. Wood D, De Backer G, Faergeman O, et al. and the members of the Task Force. Task force report: prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. Atherosclerosis. 1998;140:199-270. De Backer G, Ambrosioni E, Borch-Johnsen K, et al, together with members of the Task Force. Executive summary. European guidelines on cardiovascular disease prevention in clinical practice. Third joint task force of European and other societies on cardiovascular disease prevention in clinical practice. Eur Heart J. 2003; 24:1601-1610. American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care. 2003;26(suppl 1):S83-S86. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;285:2486-2497.

美国国家胆固醇教育计划(NCEP)： ATP III 2001 对糖尿病人筛查和检测的新建议 建议最好检测全套脂蛋白水平 空腹总胆固醇、LDL-C、HDL-C、甘油三酯 次选 非空腹总胆固醇和HDL-C 若TC 200 mg/dL 或 HDL-C <40 mg/dL，则检测脂蛋白水平 我国

美国国家胆固醇教育计划(NCEP)： ATP III 2001 冠心病或冠心病危险性等同患者 (糖尿病) LDL-胆固醇目标: <100 mg/dL(2.6mmol/L) 大部分患者需进行药物治疗 首要达到 LDL-胆固醇目标水平 继而调节其它血脂及非血脂危险因素

美国国家胆固醇教育计划(NCEP): ATP III 2001 突出多种危险因素 糖尿病：与冠心病危险性等同 Framingham 10年冠心病危险性预测 对多种危险因素的患者采取更强化的治疗 多重代谢性危险因素(代谢综合征) 给予积极的治疗性生活方式改变

成年糖尿病脂质紊乱的治疗选择(ADA) 1、降低LDL-c 首选HMG-COA还原酶抑制剂（他汀类） 次选胆酸螯合剂（树脂） 2、升高HDL-c 首先进行行为干预，如减肥，活动，戒烟 可考虑贝特类或烟酸类，选择烟酸类应监 测对糖代谢相对不利的影响

成年糖尿病脂质紊乱的治疗选择(ADA) 3、降低TG 首选控制血糖 纤维酸衍生物（贝特类） 同时伴有LDL增高者，大剂量他汀类有中等疗效。 4、混合性高脂血症 首选控制血糖＋他汀类 次选控制血糖＋他汀类*＋贝特类* 再其次控制血糖＋他汀类*＋烟酸*(注意血糖) *合用时可增加肌炎的危险性 ADA Diabetes Care 1998;21(1):179-182

不同危险性分层的LDL-C目标值和 治疗性生活方式改变的分隔界限 190 (160–189: 可考虑用药) 160 <160 0–1危险因素 10-年危险性 10–20%: 130 130 <130 2+ 危险因素 (10-年危险性 20%) 130 (100–129: 可考虑用药) 100 <100 冠心病或其等危症 (10-年危险性 >20%) 考虑药物治疗的LDL 水平 (mg/dL) 启用（TLC）的 LDL-C 水平 (mg/dL) LDL-C 目标值 （mg/dL） 危险分层 10-年危险性<10%: 160 TLC:治疗性生活方式改变 NCEP ATPIII, JAMA. 2001;285:2486-2497

冠心病或冠心病等危症患者的降LDL治疗 基线LDL-C：130 mg/dL 强化生活方式治疗 最大程度地控制所有其他危险因素 NCEP ATPIII, JAMA. 2001;285:2486-2497

冠心病或冠心病等危症患者的降LDL-C治疗 基线LDL-C (或治疗中)：100-129 mg/dL 治疗选择： 降LDL治疗 开始或强化生活方式治疗 开始或强化降LDL-C药物治疗 代谢综合征的治疗 强调减轻体重和增加运动 其它脂质危险因素的药物治疗 高TG/低HDL-C 贝特类或烟酸类 NCEP ATPIII, JAMA. 2001;285:2486-2497

新近的临床试验对NCEP ATPIII指南的影响 2004年7月12日Circulation Grundy SM, et al. Circulation. 2004;110: 227-239

降脂治疗目标 LDL-C：是降脂治疗的首要目标 其他降脂目标 过去及新的研究都已证明了：有效地降低LDL-C水平可持续降低CHD的危险 TG>200mg/dL时 非HDL-C为次要目标 非HDL-C目标值应较LDL-C目标值高30mg/dL Grundy SM, et al. Circulation. 2004;110: 227-239

降LDL-C的百分数与危险的关系: 对治疗的意义 ATP III重视达到目标LDL-C值 近来临床试验显示降脂程度与危险下降程度有关： LDL-C每下降1%，主要冠心病事件相对危险性下降约1% HPS显示此关系在LDL-C低于100mg/dL时仍存在 临床试验中用的标准剂量他汀可使LDL-C下降30-40%，5年危险也降低30-40% 由于已有较安全有效的治疗选择，合理的治疗使主要事件降低30-40%。用小剂量小幅度降脂达到目标值并非谨慎之道。用药至少要达到中度危险降低 Grundy SM, et al. Circulation. 2004;110: 227-239

ATPIII对LDL-C的 治疗方案修改建议的一些注释 治疗性生活方式改变(TLC) 仍是临床处理的必要方式，具有降脂以外的多种机制来减低心血管危险的能力 对高危者，推荐的 LDL-C目标值为 <100mg/dL <70mg/dL为一种推荐治疗，尤其为极高危病人 如 LDL-C ≥100mg/dL，适应药物治疗与 TLC同时应用 如基线 LDL-C <100mg/dL，用药物使LDL-C达到<70mg/dL为一种治疗选择 如高危病人 TG高而HDL-C低，考虑合并用一种贝特类或烟酸。若TG>200mg/dL，非 HDL-C为次级目标，比LDL-C目标值高30mg/dL Grundy SM, et al. Circulation. 2004;110: 227-239

ATPIII对LDL-C的 治疗方案修改建议的一些注释 对中度高危者，LDL-C目标值为 <130mg/dL，而<100mg/dL是一种可选择的目标。如基线或TLC时LDL-C为100-129mg/dL，启用药物使LDL-C达到<100mg/dL是一种选择 高危或中度高危者如有生活方式相关的危险因子如肥胖、体力活动少、高TG、低HDL-C或代谢综合征，不论LDL-C水平高低，均是TLC的考虑者 高危或中度高危者已用药物治疗，建议治疗的强度应足以使LDL-C水平下降至少达30-40% 对低危者，治疗的目标值和切点不作改变 Grundy SM, et al. Circulation. 2004;110: 227-239

糖尿病血脂异常治疗的药物 他汀类 适合于LDL－C增高者 也可降低甘油三酯 可减少其他调脂药物的剂量

现有各种他汀降LDL-C达到30-40%左右 所需的剂量（标准剂量）* 药物 剂量 mg/d LDL 降幅 % 阿托伐他汀 10 † 39 洛伐他汀 40 † 31 普伐他汀 34 辛伐他汀 20-40 † 35-41 氟伐他汀 40-80 25-35 洛苏伐他汀 5-10 ‡ 39-45 所估计的LDL-C降低幅度是基于美国FDA批准的各产品的产品说明书 † 这些药物可用到最大剂量80mg。在标准剂量之上，剂量加倍可再降低LDL-C 6% ‡ 对于罗苏伐他汀，最大剂量为40毫克；5毫克的疗效是在FDA报告的10毫克疗效基础上减去6%估计的 * Grundy SM, et al. Circulation. 2004;110: 227-239

辛伐他汀40mg显著降低接受 Thiazolidinedion治疗的糖尿病患者的血脂 CLINICAL THERAPEUTICS ， 2004 ，VOL. 26, NO. 3,379-389

辛伐他汀40mg使更多接受Thiazolidinedion 治疗的糖尿病患者的血脂达标 LDL-C<100 mg/dL,HDL-C>45 mg/dL,TG<150 mg/dL, *P < 0.001 versus placebo; †P < 0.05 versus placebo. CLINICAL THERAPEUTICS ， 2004 ，VOL. 26, NO. 3,379-389

问题： 1、4S研究中指出：辛伐他汀＿～ ＿mg/d，可降低糖尿病患者主要冠心病事件达55%？ 2、HPS研究一级/二级预防中指出：辛伐他汀＿ ＿ mg/d ，可降低糖尿病患者主要冠心病事件达22%？ 3、ATPIII对LDL-C的治疗方案修改后提出：对高危患者推荐的LDL-C目标值为<＿ ＿ mg/dl？

谢 谢！