1、血脂異常血脂異常合併糖尿病糖尿病或代謝症候群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?USA 2000:15M2025:21.9MJAPAN 2000:6.9M2025:8.5MEUROPE2000:30.8M2025:38.5MAMERICAS(Ex-US)2000:20M2025:42MAFRICA2000:9.2M2025:21.5MASIA2000:71.8M2025:165.7MOCEANIA2000:0.8M2025:1.5MKing H et al Diabetes Care 1998;21:141
2、4-1431.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 2025PercentagePrevalence of Hyperglycemiaby Age Group in TaiwanAge G
3、roup126 or drug.國民健康局.2003.20-2940-4950-5960-6970-79Incidence rate(%)Increased Risk of CV Events Over 7 years in Type 2 DiabeticsMyocardial Infarction StrokeCV DeathNondiabetic MI(n=1,304)Diabetic+MI(169)Nondiabetic+MI(n=69)Diabetic MI(n=890)P0.001*P0.001*P126 or drug.國民健康局.2003.糖尿病的治療準則 A1c Blood p
4、ressure Cholesterol(lipid)Diet control Exercise Factors reductionTherapeutic Life therapyStamler J et al Diabetes Care 1993;16:434-444.心血管的死亡率心血管的死亡率/10,000/10,000 人人-年年糖尿病糖尿病無糖尿病無糖尿病總膽固醇總膽固醇 (mmol(mmol/L)/L)0204060801001201407.3160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
5、合併血脂異常之特性三酸甘油酯三酸甘油酯(Triglyceride)過高過高高密度脂蛋白膽固醇高密度脂蛋白膽固醇(HDL)較低較低低密度脂蛋白低密度脂蛋白(LDL)顆粒較小、密度較密顆粒較小、密度較密糖尿病的糖尿病的apoB濃度更高濃度更高DiabetesLDL particles“Normal”LDL-C level,however:“Normal”LDL-C levelNo diabetes LDL particlesNumber of LDL particlesConcentration of apoBLowerRiskHigherSmall,dense LDL with more apo
6、BAustin 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.apoB LDL-C根據UKPDS 研究中在第二型糖尿病中各種危險因子的重要性 Low-Density Lipoprotein CholesterolHigh-Density Lipoprotein CholesterolHemoglobin A1cSystolic Blood PressureSmoking2
7、0%ATP IIIRisk CategoryCHD and CHD risk equivalentsMultiple(2+)risk factors0-1 one risk factorLDL Goal(mg/dL)100130 3 of the following criteriaRisk factorsDefining levelAbdominal obesity:Waist circumference 102 cm,Men 88 cm,WomenTriglycerides 150 mg/dLHDL-cholesterol 40 mg/dL,Men 130/85 mm HgFasting
8、glucose 110 mg/dLPrevalence of the Metabolic Syndrome Age-Specific Prevalence of the Metabolic Syndrome Among 8814 US Adults Aged at Least 20 Years,National Health and Nutrition Examination Survey III,1988-1994Harris MI,et al.,Diabetes Care 1998;21:518Ford ES,et al.,JAMA.2002 Jan 16;287(3):356-9.Pre
9、valence of the Metabolic Syndrome Ford ES,et al.,JAMA.2002 Jan 16;287(3):356-9.Difference in AsianWHO Expert consultation.Lancet 2004;363:157-163國內成人肥胖定義身體質量指數(BMI)(kg/m2)腰圍(cm)體重過輕BMI 18.5正常範圍18.5BMI24異常範圍過重：24BMI27輕度肥胖：27BMI30中度肥胖：30BMI35重度肥胖：BMI35 男性：90公分女性：80公分 肥胖的判定肥胖的判定Metabolic Syndrome,carot
10、id atherosclerosis and LDL size LDL size in metabolic syndromeHulthe J et al.,Arterioscler Thromb Vasc Biol 2000;20:2140.Gemfibrozil for insulin resistanceRubins HB et al.,Arch Intern Med.2002;162:2597 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 trig
11、lycemia TG 150 mg/dl Low HDL cholesterol Men 40 mg/dl Women 130/85 mmHg 空腹血糖高 Plasma glucose 110 mg/dlATP IIITriglycerides 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
12、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 ATP IIITriglycerides 嚴重度 Triglycerides levelNormal 500 mg/dl治療的目標先預防急性胰臟炎低脂肪飲食 Very l
13、ow fat diets(15%of caloric intake)使用降Triglyceride 藥物(fibrate or nicotinic acid)ATP IIIHDL 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,progestation
14、al agentsATP IIIHDL 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 therapyTG 200 consider nicotinic acid or fibrates in person with CHD or CHD risk ATP IIITherapeutic Lifer therapy-Diet control an
15、d Excercise The Oslo diet-heart study的的11-year 追蹤追蹤報告：報告：至少三十年前就證實有效地預防心血管疾病(Leren P,1970)Finnish Diabetes Prevention StudySubjectsl522 patients,40-65 y,CaucasianslIGT on 2 occasionsInterventions1.Intensified diet and exercise lifestyle5%reduction in body weightReduction in dietary fat 30%,saturated
16、 fat 25 y,45%minoritieslIGT with fasting plasma glucose 5.6 mmol/LInterventions1.Intensified diet and exercise lifestyle 7%reduction in body weight increase calorie expenditure 700 kcal per week2.Metformin 1700 mg per day3.Placebo tabletDiabetes Care 23:1619-1629US DPP:Effect on diabetes incidence M
17、etformin:31%decrease in incident diabetes Lifestyle:58%decrease in incident diabetesReleased early(08/08/01)after a mean follow-up of 3 yearsDiabetes Care 23:1619-1629Therapeutic Lifestyle ChangesNutrient Composition of TLC DietNutrientRecommended Intake Saturated fatLess than 7%of total calories Po
18、lyunsaturated fatUp to 10%of total calories Monounsaturated fat Up to 20%of total calories Total fat2535%of total calories Carbohydrate5060%of total calories Fiber2030 grams per day ProteinApproximately 15%of total calories CholesterolLess than 200 mg/day Total calories Balance energy intake and exp
19、enditure to maintain desirable body weight/prevent weight gainATP III回顧 三十年前，發表運動者比長期辦公者對insulin反應較好 Bjorntorp et al.Metabolism 1970;19:631-638.數天的不運動即造成insulin反應差。Ruderman et al.Diabetes 1979;28:89-92.單一次的運動即可改善insulin作用，而且甚至可達兩天之久。Mikines et al.Am J Physiol 1988;254:E248-E259 若運動後給醣類飲食後，insulin se
20、nsitivity只維持了15小時Bogardus et al.J Clin Invest 1983;72:1605-1610.但運動當時的catacholamine升高也可能阻礙insulin作用。Kjr et al.J Appl Physiol 1986;61:1693-1700.Insulin增加血糖的吸收及利用 與insulin receptor作用 經由一些protein下傳訊息 Ex:insulin receptor substrate(IRS)其中可經由GLUT4(glucose transporter)移至細胞膜上，以利glucose的傳送運動增加insulin sensiti
21、vity的機轉運動後，肌肉會比以前更強壯 為了應付下一次的運動 增加protein合成 增加glycogen貯存 局部的效果明顯 只運動一腳，發現有運動的一肢比另一肢insulin sensitivity較好。另一肢可能也會改善，只是沒有運動的那肢好。運動增加insulin sensitivityRichter et al.J Appl Physiol 1984;246:E476運動增加insulin sensitivityWojtaszewski et al.Acta Physiol Scand 2003;178:321Glycogen量與insulin sensitivity Glucos
22、e的吸收與消秏的glycogen成正比。Glycogen的合成與肌肉內glycogen量成反相關。因GLUT4到表面的量與glycogen量成反向關係 可能經由AMPK(AMP-activated protein kinase)作用運動增加insulin sensitivity運動增加insulin sensitivityWojtaszewski et al.Acta Physiol Scand 2003;178:321運動與insulin作用機轉不同 運動後改善insulin sensitivity是由於GLUT4出現於肌肉細胞膜上增多。藉由取得glucose增加使合成glycogen增多。
23、由運動增加glucose的傳送與glycogen的合成與insulin經由的機轉可能不同 運動產生GLUT4表現並不一定需要insulin receptor,IR 1/2,PI3K等物質。與AMPK有關運動增加insulin sensitivityConclusionThe clinical approach to treatment of patients with dyslipidaemias-associated Metabolic Syndrome A broad-based strategy reversal of lipid abnormalities(elevated LDL-C)reduction of triglyceride-rich lipoproteins improvement of insulin-resistance.Lifestyle modifications(balanced diet and increased physical exercise)should first be proposed drug therapy targeting hypertriglyceridaemia and low HDL-C could be proposed in association with diet and exercise
