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血脂異常 合併 糖尿病 或 代謝症候群

血脂異常 合併 糖尿病 或 代謝症候群. 臺中榮民總醫院 內分泌暨新陳代謝科 主治醫師 李奕德. 糖尿病 and 高血脂. 高血脂是 心臟血管疾病的主因 糖尿病 的角色 ?. Type 2 Diabetes Prevalence Is Projected to Reach 300 Million by 2025. About 155 million adults worldwide diagnosed with diabetes in 2000 83 million women and 72 million men

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血脂異常 合併 糖尿病 或 代謝症候群

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  1. 血脂異常合併糖尿病或代謝症候群 臺中榮民總醫院 內分泌暨新陳代謝科 主治醫師 李奕德

  2. 糖尿病 and 高血脂 • 高血脂是心臟血管疾病的主因 • 糖尿病的角色?

  3. Type 2 Diabetes Prevalence Is Projected to Reach 300 Million by 2025 • About 155 million adults worldwide diagnosed with diabetes in 2000 • 83 million women and 72 million men • Type 2 Diabetes Prevalence will reach 300 million in 2025 ASIA 2000: 71.8M 2025: 165.7M EUROPE 2000: 30.8M 2025: 38.5M USA 2000: 15M 2025: 21.9M JAPAN 2000: 6.9M 2025: 8.5M AFRICA 2000: 9.2M 2025: 21.5M AMERICAS (Ex-US) 2000: 20M 2025: 42M OCEANIA 2000: 0.8M 2025: 1.5M King H et al Diabetes Care 1998;21:1414-1431.

  4. Prevalence of Hyperglycemiaby Age Group in Taiwan Percentage <20 20-29 30-39 40-49 50-59 60-69 70-79 80+ Age Group Definition: glucose>126 or drug. 國民健康局. 2003.

  5. Increased Risk of CV Events Over 7 years in Type 2 Diabetics Myocardial Infarction Stroke CV Death Incidence rate (%) Nondiabetic –MI (n=1,304) Nondiabetic +MI (n=69) Diabetic –MI (n=890) P<0.001* Diabetic +MI (169) P<0.001* P<0.001* -MI +MI -MI +MI -MI +MI -MI +MI -MI +MI -MI +MI Haffner SM et al N Engl J Med 1998;339:229-234.

  6. Prevalence of hyperglycemia with Co-morbid diseases P<0.001 Percentage HTN Hyperlipidemia CHD CVA Definition: glucose>126 or drug. 國民健康局. 2003.

  7. 糖尿病的治療準則 • A1c • Blood pressure • Cholesterol (lipid) • Diet control • Exercise • Factors reduction Therapeutic Life therapy

  8. 心血管死亡風險(MRFIT study): 低膽固醇糖尿病患者比高膽固醇但無糖尿病的人高 糖尿病無糖尿病 160 140 120 100 80 心血管的死亡率/ 10,000 人-年 60 40 20 0 <4.7 4.7–5.1 5.2–5.7 5.8–6.2 6.3–6.7 6.8–7.2 >7.3 總膽固醇 (mmol/L) Stamler J et al Diabetes Care 1993;16:434-444.

  9. 糖尿病合併血脂異常之特性 • 三酸甘油酯(Triglyceride)過高 • 高密度脂蛋白膽固醇(HDL)較低 • 低密度脂蛋白(LDL)顆粒較小、密度較密

  10. 糖尿病的apoB濃度更高 apoB LDL-C No diabetes Diabetes LDL particles LDL particles Small, dense LDL with more apoB “Normal” LDL-C level, however: “Normal” LDL-C level Number of LDL particles Concentration of apoB Higher Lower Risk Austin MA, Edwards KL Curr Opin Lipidol 1996;7:167-171; Austin MA et al JAMA 1988;260:1917-1921; Sniderman AD et al Diabetes Care 2002;25:579-582.

  11. 根據UKPDS 研究中﹕在第二型糖尿病中各種危險因子的重要性 Coronary Artery Disease (n=280) Position in Model First Second Third Fourth Fifth Variable Low-Density Lipoprotein Cholesterol High-Density Lipoprotein Cholesterol Hemoglobin A1c Systolic Blood Pressure Smoking P Value <0.0001 0.0001 0.0022 0.0065 0.056 *Adjusted for age and sex. Turner RC et al. BMJ 1998;316:823-828.

  12. 在 UKPDS 研究中LDL-C 是預測糖尿病患者 CHD 罹病風險時最有力的指標 CHD 罹病風險增加 % LDL-C  1 mmol/L 57 HDL-C  0.1 mmol/L –15 收縮壓  10 mmHg 15 HbA1c濃度  1% 11 抽菸也是增加 CHD 罹病風險的重要因子 這些數據證明，糖尿病患者有必要降低其 LDL-C 濃度，以降低 CHD 的罹病風險。 Turner RC et al BMJ 1998;316:823-828.

  13. Very high cholesterol with CHD or MI Moderately high cholesterol in high risk CHD or MI Normal cholesterol with CHD or MI High cholesterol without CHD or MI No history of CHD or MI The Pyramid of Recent TrialsRelative Size of the Various Segments of the Population 4S LIPID CARE WOSCOPS AFCAPS/TexCAPS

  14. 糖尿病合併高血脂症的藥物治療效果 • 過去對心臟血管疾病的大型介入性（治療性）降血脂臨床試驗的結果對糖尿病患一樣有效嗎？

  15. Statins在大型心血管保護研究中﹕ 針對整個族群的分析(降LDL效果) Downs JR et al. JAMA 1998;279:1615-1622 HPS Investigators. Presented at AHA, 2001 Goldberg RB et al. Circulation 1998;98:2513-2519 Pyorala K et al. Diabetes Care 1997;20:614-620 Haffner SM et al. Arch Intern Med 1999;159:2661-2667 LIPID Study Group. N Engl J Med 1998;339:1349-1357.

  16. Statins在大型心血管保護研究中﹕ 針對糖尿病次族群的分析(降LDL效果) Downs JR et al. JAMA 1998;279:1615-1622 HPS Investigators. Presented at AHA, 2001 Goldberg RB et al. Circulation 1998;98:2513-2519 Pyorala K et al. Diabetes Care 1997;20:614-620 Haffner SM et al. Arch Intern Med 1999;159:2661-2667 LIPID Study Group. N Engl J Med 1998;339:1349-1357.

  17. 結果 • 對心臟血管疾病而言，由過去的大型介入性（治療性）臨床試驗事後分析(post hoc analysis)得知，糖尿病患只要接受積極降低血脂治療（尤其是statins藥物），便可得到與非糖尿病患一樣（甚至更多）的好處。

  18. Atorvastatin 10 mg/day 2,838 patients Placebo Placebo 6-week placebo lead-in Pre-randomization At least 4 years CARDS Study • Patient population: • Enrolled at 132 sites in the UK and Ireland • Type 2 diabetes with no previous MI or CHD • ≥1 other CHD risk factor plus LDL-C ≤4.14 mmol/L (160 mg/dL) and TG ≤6.78 mmol/L (600 mg/dL) • Aged 40-75 years Colhoun HM, et al. Diabet Med. 2002;19:201-211.

  19. Recruitment and Follow Up 3,249 (80%) Entered baseline 4,053 Screened 2,838 (70%) Randomized 1,428 Allocated atorvastatin 10 mg daily 1,410 Allocated placebo 1,398 (99.1%) Complete follow up 1,421 (99.5%) Complete follow up • Mean follow-up of 3.7 years in both groups Colhoun HM, et al. Diabet Med. 2002;19:201-211.

  20. Placebo Atorvastatin TC and LDL-C Levels

  21. Effect of Atorvastatin on the Primary End Point: Major CV Events Including Stroke Relative Risk Reduction 37% 15 P=0.001 Placebo 127 events 10 Atorvastatin 83 events Cumulative hazard (%) 5 0 0 1 2 3 4 Years 4.75 Colhoun HM, Betteridge DJ, Durrington PN, et al. Lancet. 2004;364:685-696.

  22. CARDS Summary • statin provided benefits in type 2 diabetes with no history of CVD and with normal to mildly-elevated cholesterol levels • 37% reduction in major CVD events (P=0.001) • 48% reduction in stroke (P=0.016) • 27% reduction in all-cause mortality (P=0.059) Colhoun HM, et al. Diabet Med. 2002;19:201-211.

  23. Adult Treatment Panel III (ATP III) Guidelines National Cholesterol Education Program

  24. 治療的主要目標 • LDL cholesterol • LDL 的升高是心臟血管疾病的主因 • 降低LDL 可減少心臟血管疾病的風險 • ATP III • 治療的主要目標著重在 LDL.

  25. ATP III 高危險群 • CHD • History of CHD • CHD risk equivalents • Other clinical forms of atherosclerotic disease • peripheral arterial disease • abdominal aortic aneurysm • symptomatic carotid artery disease • Diabetes (糖尿病) • Multiple risk factors with a 10-year risk for CHD >20%

  26. Risk Category CHD and CHD risk equivalents Multiple (2+) risk factors 0 - 1 one risk factor LDL Goal (mg/dL) <100 <130 <160 ATP III Three Categories of Risk that Modify LDL-Cholesterol Goals

  27. Prevalence of the Metabolic SyndromeAge-Specific Prevalence of the Metabolic Syndrome Among 8814 US Adults Aged at Least 20 Years, National Health and Nutrition Examination Survey III, 1988-1994 Harris MI, et al., Diabetes Care 1998; 21:518 Ford ES, et al., JAMA. 2002 Jan 16;287(3):356-9.

  28. Prevalence of the Metabolic Syndrome Ford ES, et al., JAMA. 2002 Jan 16;287(3):356-9.

  29. Difference in Asian WHO Expert consultation. Lancet 2004;363:157-163

  30. 肥胖的判定 國內成人肥胖定義

  31. Metabolic Syndrome, carotid atherosclerosis and LDL size

  32. LDL size in metabolic syndrome Hulthe J et al., Arterioscler Thromb Vasc Biol 2000; 20:2140.

  33. Gemfibrozil for insulin resistance Rubins HB et al., Arch Intern Med. 2002;162:2597

  34. ATP III 代謝症候群 (metabolic syndrome) • 第二個治療目標 • LDL控制之後的目標 • 標準 • 腹部肥胖 • Men (腹圍) >102cm (90cm) • Women (腹圍) > 88cm (80cm) • High triglycemia • TG > 150 mg/dl • Low HDL cholesterol • Men < 40 mg/dl • Women < 50 mg/dl • 血壓高 • >130 / >85 mmHg • 空腹血糖高 • Plasma glucose > 110 mg/dl

  35. ATP III Triglycerides 高 • 可能原因 • 肥胖 (obesity) • 不運動 (physical inactivity) • 抽煙 (cigarette smoking) • 酗酒 (excess alcohol intake) • 高碳水化合物飲食 high-carbohydrate diets (>60% of energy intake) • 疾病 • 糖尿病 Diabetes • 慢性腎衰竭 Chronic renal failure • 腎病症侯群 nephrotic syndrome • 藥物 • corticosteroids, • estrogens, • retinoids, • higher doses of B-adrenergic blocking agents • 基因 • familial combined hyperlipidemia, • familial hypertriglyceridemia • familial dysbetalipoproteinemia

  36. ATP III Triglycerides 嚴重度 • Triglycerides level • Normal < 150 mg/dL • Borderline high 150 – 199 mg/dL • High 200 – 499 mg/dL • Very high 500 mg/dL • Non-HDL Cholesterol • VLDL + LDL = Total cholesterol – HDL • Target: LDL + 30 mg/dl

  37. ATP III 治療triglycerides過高 • 治療的主要目標著重在 LDL • 但當TG > 500 mg/dl • 治療的目標﹕先預防急性胰臟炎 • 低脂肪飲食 Very low fat diets ( 15% of caloric intake) • 使用降Triglyceride 藥物(fibrate or nicotinic acid)

  38. ATP III HDL Cholesterol 過低 - 原因 - • Triglycerides 過高 • 肥胖 (obesity) • 不運動 (physical inactivity) • 糖尿病(type 2 diabetes) • 抽煙 (cigarette smoking) • 高碳水化合物飲食 high-carbohydrate diets • (>60% of energy intake) • 藥物 • beta-blockers, • anabolic steroids, • progestational agents

  39. ATP III HDL Cholesterol 過低 -治療- • 治療的主要目標著重在 LDL • 增加運動及控制體重 • 仍依上述原則 • TG > 500 • Reduce triglycerides before LDL lowering • TG: 200 – 499 • Non-HDL cholesterol is secondary target of therapy • TG < 200 • consider nicotinic acid or fibrates in person with CHD or CHD risk

  40. Therapeutic Lifer therapy- Diet control and Excercise • The Oslo diet-heart study的11-year 追蹤報告：至少三十年前就證實有效地預防心血管疾病　 (Leren P, 1970)

  41. 生活型態與糖尿病 Finnish Diabetes Prevention Study • Subjects • 522 patients, 40-65 y, Caucasians • IGT on 2 occasions • Interventions • 1.Intensified diet and exercise lifestyle 5% reduction in body weight Reduction in dietary fat < 30%, saturated fat < 10% Increase in dietary fiber, fruits and vegetables Increase activity • 2. Usual care N Engl J Med 344: 1343-1349, 2001

  42. 生活型態與糖尿病 Finnish DPS: Development of diabetes in the intervention and control groups Mean follow-up: 3.2 years Risk reduction: 58% N Engl J Med 344: 1343-1349, 2001

  43. US Diabetes Prevention Program • Subjects • 3234 patients, > 25 y, 45% minorities • IGT with fasting plasma glucose > 5.6 mmol/L • Interventions • 1. Intensified diet and exercise lifestyle 7% reduction in body weight increase calorie expenditure 700 kcal per week • 2. Metformin 1700 mg per day • 3. Placebo tablet Diabetes Care 23:1619-1629

  44. US DPP: Effect on diabetes incidence Released early (08/08/01) after a mean follow-up of 3 years • Metformin: 31% decrease in incident diabetes • Lifestyle: 58% decrease in incident diabetes Diabetes Care 23:1619-1629

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