资源描述
Diabetic Dyslipidemia and AtherosclerosisHenry Ginsberg,MDDiabetic Dyslipidemia and AtheInterrelation Between Atherosclerosis and Insulin ResistanceHypertensionHypertensionObesityObesityHyperinsulinemiaHyperinsulinemiaDiabetesDiabetesHypertriglyceridemiaHypertriglyceridemiaSmall,dense LDLSmall,dense LDLLow HDLLow HDLHypercoagulabilityHypercoagulabilityInsulinInsulinResistanceResistanceAtherosclerosisAtherosclerosisInterrelation Between AtheroscnAbdominal obesityn TG+HDL-CnGlucose intolerancenHypertensionnAtherosclerosisnEthnicity Insulin Resistance and Hyperinsulinemia:Clinical CluesAbdominal obesityInsulin ResisnElevated total TGnReduced HDL-CnSmall,dense LDL-C Dyslipidemia in the Insulin Resistance SyndromeElevated total TGDyslipidemia Dyslipidemias in Adults with DiabetesFramingham Heart StudyIncreased cholesterolIncreased LDLDecreased HDLIncreased triglyceridesNormalNormalDMDMNormalNormalDMDM14%11%12%9%13%9%21%19%MENMENWOMENWOMEN21%16%10%8%24%15%25%17%Garg A et al.Diabetes Care 1990;13:153-169.Dyslipidemias in Adults with DMean Plasma Lipids at Diagnosis of Type 2 Diabetes-UKPDSNumber of PtsTC(mg/dl)LDL-C(mg/dl)HDL-C(mg/dl)TG(mg/dl)Type 2Type 2ControlControlMENMENUKPDS Group.Diabetes Care 1997;20:1683-1687.*P0.001,*P0.02 comparing type 2 vs.controll2139 213 139 39*159*5220513243103Type 2Type 2ControlControlWOMENWOMEN1574 224 151*43*159*1432171355595Mean Plasma Lipids at DiagnosiRelation Between Insulin Resistance and HypertriglyceridemiaOlefsky JM et al.Am J Med.1974;57:551-560.*Total area under 3-hour response curve(mean of 2 tests).625500400300200100100 200 300 400 500 600Insulin Response to Oral Glucose*Plasma TG(mg/dL)r=0.73P 0.0001Relation Between Insulin ResisAssociation Between Hyperinsulinemia and Low HDL-CHDL-C(mg/dL)Reaven GM.In:LeRoith D et al.,eds.Diabetes Mellitus.Philadelphia:Lippincott-Raven,1996:509-519.NonobeseHyperinsulinemicNormoinsulinemicObeseP0.005P0.005Association Between HyperinsulMechanisms Relating Insulin Resistance and DyslipidemiaFat CellsFat CellsLiverLiverInsulinInsulinIRIRXXFFAFFAMechanisms Relating Insulin ReMechanisms Relating Insulin Resistance and DyslipidemiaFat CellsFat CellsLiverLiverInsulinInsulinIRIRXX TGTG Apo BApo B VLDLVLDLVLDLVLDLFFAFFAMechanisms Relating Insulin Re(hepatic(hepaticlipase)lipase)Mechanisms Relating Insulin Resistance and DyslipidemiaFat CellsFat CellsLiverLiverKidneyKidneyInsulinInsulinIRIRXX(CETP)(CETP)CECE TGTG Apo BApo B VLDLVLDLVLDLVLDLHDLHDLTGTGApo A-1Apo A-1FFAFFA(hepaticlipase)Mechanisms Rel(hepatic(hepaticlipase)lipase)Mechanisms Relating Insulin Resistance and DyslipidemiaFat CellsFat CellsLiverLiverKidneyKidneyInsulinInsulinIRIRXX(CETP)(CETP)CECE TGTG Apo BApo B VLDLVLDL(CETP)(CETP)VLDLVLDLHDLHDL(lipoprotein or hepatic lipase)(lipoprotein or hepatic lipase)SDSDLDLLDLLDLLDLTGTGApo A-1Apo A-1TGTGCECEFFAFFA(hepaticlipase)Mechanisms RelIncreasedIncreasedDyslipidemia in DiabetesDecreasedDecreasednTriglyceridesnVLDLnLDL and small dense LDLnApo B nHDLnApo A-I IncreasedDyslipidemia in DiabeLDL Subclass Phenotypes in Diabetes MellitusMen*Men*Diabetic NondiabeticWomen*Women*Diabetic Nondiabetic*Selby JV et al.Circulation 1993;88:381-387.IntIntB B *Feingold KR et al.Arterioscler Thromb 1992;12:1496-1502.2987545432847348521293095124366LDL SubclassLDL Subclassn nA APercentPercentLDL Subclass Phenotypes in DinIncreased susceptibility to oxidationnIncreased vascular permeabilitynConformational change in apo BnDecreased affinity for LDL receptornAssociation with insulin resistance syndromenAssociation with high TG and low HDLSmall Dense LDL and CHD:Potential Atherogenic MechanismsAustin MA et al.Curr Opin Lipidol 1996;7:167-171.Increased susceptibility to oxnAccumulation of chylomicron remnantsnAccumulation of VLDL remnantsnGeneration of small,dense LDL-CnAssociation with low HDL-CnIncreased coagulability -plasminogen activator inhibitor(PAI-1)-factor VIIc -Activation of prothrombin to thrombinHypertriglyceridemia and CHD Risk:Associated AbnormalitiesAccumulation of chylomicron reTG Metabolism in CHD:Studies in the Postprandial State4003002001000TG(mg/dL)UncorrectedUncorrectedCorrected for Fasting Corrected for Fasting TG Level*TG Level*Hours after Test Meal3002001000Patsch JR et al.Arterioscler Thromb 1992;12:1336-1345.0246802468CHD CasesControlsControlsError bars=SEMCHD CasesTG Metabolism in CHD:StudiesnIncreased plasma fibrinogennIncreased plasminogen activator inhibitor 1nIncreased platelet aggregabilityFactors Promoting Thromboembolic Disease in DiabetesThompson SG et al.N Engl J Med 1995;332:635-641.Increased plasma fibrinogenFacn nPredisposition to thrombosisPredisposition to thrombosis -Platelet hyperaggregability -Elevated concentrations of procoagulants -Decreased concentration and activity of antithrombotic factorsn nPredisposition to attenuation of fibrinolysisPredisposition to attenuation of fibrinolysis -Decreased t-PA activity -Increased PAI-1 -Decreased concentrations of 2-antiplasminAdverse Effects on Balance Between Thrombosis and Fibrinolysis in Subjects with DiabetesSobel BE.Circulation 1996;93:1613-1615.Predisposition to thrombosisAdPAI-1 Activity in Blood in Patients with Type 2 DiabetesPAI-1 Activity(AU/mL)McGill JB et al.Diabetes.1994;43:104-109.LeanNo DiabetesDiabetesObesePAI-1=plasminogen activator inhibitor type 1PAI-1 Activity in Blood in PatElevation of PAI-1 Induced by Hyperinsulinemia,Hyperglycemia,and Increased FFA in Blood of Normal SubjectsCalles-Escandon J et al.Diabetes.1998;47:290-293.*P0.05 vs saline infusions in same subjectsValues are mean+SDPAI-I(mg/mL)0246812Time(h)10*Infusion of glucose Infusion of glucose and intralipidand intralipidElevation of PAI-1 Induced by First-line agentsFirst-line agentsn nHMG CoA reductase inhibitorHMG CoA reductase inhibitorn nFibric acid derivativeFibric acid derivativeSecond-line agentsSecond-line agentsn nBile acid binding resinsBile acid binding resinsn nNicotinic acidNicotinic acidPharmacologic Agents for Treatment of DyslipidemiaAmerican Diabetes Association.Diabetes Care 2000;23(suppl 1):S57-S60.In diabetic patients,nicotinic acid should be restricted to 2g/day.Short-acting nicotinic acid is preferred.Effect on lipoproteinLDLHDLTriglycerideFirst-line agentsPharmacologicn nLDL cholesterol lowering*LDL cholesterol lowering*-First choice:HMG CoA reductase inhibitor(statin)-Second choice:Bile acid binding resin or fenofibraten nHDL cholesterol raisingHDL cholesterol raising -Behavior interventions such as weight loss,increased physical activity and smoking cessation -Glycemic control -Difficult except with nicotinic acid,which is relatively contraindicated,or fibratesn nTriglyceride loweringTriglyceride lowering -Glycemic control first priority -Fibric acid derivative(gemfibrozil,fenofibrate)-Statins are moderately effective at high dose in hypertriglyceridemic subjects who also have high LDL cholesterol *Decision for treatment of high LDL before elevated triglyceride is based on clinical trial data indicating safety as well as efficacy of the available agents.Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults*Adapted from American Diabetes Association.Diabetes Care 2000;23(suppl 1):S57-S60.LDL cholesterol lowering*Order谢谢您的聆听与观看THANK YOU FOR YOUR GUIDANCE.感谢阅读！为了方便学习和使用，本文档的内容可以在下载后随意修改，调整和打印。欢迎下载！汇报人：XXX日期：20XX年XX月XX日谢谢您的聆听与观看THANK YOU FOR YOUR GU
展开阅读全文