Diabetic Dyslipidemia.ppt
http://www.100md.com
参见附件(888KB)。
ATP III: Management of Diabetic Dyslipidemia
LIPID: Reduction in Nonfatal MI and
CHD Death Risk Stratified by Diabetic Status
Post-CABG: Aggressive LDL-C Lowering Delays Progression of Atherosclerosis in Women, Elderly, and Patients With Selected CHD Risk Factors
Fasting TG and Risk for CHD Death: Paris Prospective Study
CHD Mortality and Hyperinsulinemia:
Paris Prospective Study (n=943)
Prevalence of Macrovascular Disease and CHD According to Quintiles of Fasting C-Peptide
Finnish Diabetes Prevention Study: Treating
the IGT* Patient With Lifestyle Changes
? Study Design
- 522 middle-aged, overweight? subjects
- 172 men, 350 women with IGT
- BMI 31 kg/m2
- mean age: 55 years
- mean duration: 3.2 years
- intervention group: individualized counseling
? reducing weight, total intake of fat and saturated fat
? increasing intake of fiber, physical activity
Finnish Diabetes Prevention Study: Success
in Achieving Treatment Goals at 1 Year
Finnish Diabetes Prevention Study: Reduction in Risk for Diabetes*
Diabetes Prevention Program: Study Design
Progression to Atherosclerotic Clinical Events in Patients With Diabetes
DAIS: Impact of Aggressive Therapy on Atherosclerosis in Patients With Type 2 Diabetes
Study population
? N=418 (305 men, 113 women)
? Type 2 diabetes
? ?1 minimal lesion on angiography
? Mild elevations of LDL-C or TG + TC:HDL-C ?4
Treatment
? 8 weeks on Step I diet
? Randomized, blinded to micronized fenofibrate (200 mg/d)
and placebo
Primary end point
? Progression or regression of CAD on quantitative angiography
DAIS: Mean Baseline Lipoprotein Levels
DAIS: Interim Lipid Results in Patients With Type 2 Diabetes
DAIS: Final Results in Patients
With Type 2 Diabetes
CAD
? Treatment with fenofibrate resulted in 40% reduction in rate
of progression of localized CAD versus placebo
? 23% reduction in combined coronary events following fenofibrate treatment (P=NS*)
Lipids
? Average reductions with fenofibrate: TC, 10%; LDL-C, 6%;
TG, 29%; average increase in HDL-C, 6%
Safety
? Very few serious adverse events; no significant differences in tolerability between fenofibrate and placebo treatments;
95% compliance
Atherosclerosis in Diabetes
Framingham Heart Study 30-Year Follow-Up:
CVD Events in Patients With Diabetes (Ages 35-64)
Women, Diabetes, and CHD
? Diabetic women are at high risk for CHD
? Diabetes eliminates relative cardioprotective effect of being premenopausal
- risk of recurrent MI in diabetic women is three times that of nondiabetic women
? Age-adjusted mean time to recurrent MI or fatal CHD event is 5.1 yr for diabetic women vs 8.1 yr for nondiabetic women
Primary CHD* Prevention in Patients With
Type 2 Diabetes: The Helsinki Heart Study
Insulin Resistance and Atherosclerosis: Posited Relationships
Abnormal Lipid Levels in Men With
Type 2 Diabetes
Abnormal Lipid Levels in Women With Type 2 Diabetes
Significance of Small, Dense LDL
? Low cholesterol content of LDL particles
- ? particle number for given LDL-C level
? Associated with ? levels of TG and LDL-C, and
? levels of HDL2
? Marker for common genetic trait associated with
? risk of coronary disease (LDL subclass pattern B)
? Possible mechanisms of ? atherogenicity
- greater arterial uptake
- ? uptake by macrophages
- ? oxidation susceptibility
Potential Mechanisms of
Atherogenesis in Diabetes
? Abnormalities in apoprotein and lipoprotein particle distribution
? Glycosylation and advanced glycation of proteins in plasma and arterial wall
? "Glycoxidation" and oxidation
? Procoagulant state
? Insulin resistance and hyperinsulinemia
? Hormone-, growth-factor-, and cytokine-enhanced SMC proliferation and foam cell formation
ADA: Glycemic Control, BP, and
Lipid Targets in Type 2 Diabetes
ADA: Treatment Decisions by LDL-C
Levels* in Adults With Type 2 Diabetes
ADA: Order of Priorities for Treatment
of Diabetic Dyslipidemia in Adults
? LDL-C lowering
- first choice: HMG-CoA reductase inhibitors (statins)
- second choice: bile acid binding resin or fenofibrate
? HDL-C raising
- behavioral interventions (weight loss, ? physical activity, smoking
cessation)
- difficult to achieve except with niacin, which should be used with caution,or fibric acid derivative
? TG lowering*
- first priority: glycemic control
- fibric acid derivative (gemfibrozil, fenofibrate)
- statins (moderately effective at high dose in patients with ? TG and
? LDL-C)
ADA: Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults (cont'd)
? Combined hyperlipidemia
- first choice: improved glycemic control plus high-dose statin
- second choice: improved glycemic control plus statin* plus
fibric acid derivative* (gemfibrozil or fenofibrate)
- third choice: improved glycemic control plus resin plus fibric
acid derivative
or
improved glycemic control plus statin* plus niacin*
(glycemic control must be monitored carefully)
ADA: CHD Risk Stratification Based on Lipoprotein
Levels* in Adults With Type 2 Diabetes
Risk Similar in Patients With Type 2 Diabetes and No Prior MI vs Nondiabetic Subjects With Prior MI
Secondary Prevention: CHD Risk Reduction in the 4S Subgroup of Patients With Diabetes
4S: Total Mortality Reduction in a Subgroup of Patients With Diabetes
4S:Major CHD Event Reduction in a Subgroup of Patients With Diabetes
WOSCOPS: Development of
Type 2 Diabetes
Strong Heart Study: Non-HDL-C as CVD
Risk Predictor in Patients With Diabetes
Strong Heart Study: Non-HDL-C
Compared With Other CVD Risk Predictors
Steno-2: Effect of Therapies on Selected Risk Factors
Steno-2: Primary Composite End Point
or Surgery for PAD
HPS Diabetes Substudy: Absolute Effects on 5-Year Rates of First Major Vascular Event
ATP III: Management of Diabetic Dyslipidemia
LIPID: Reduction in Nonfatal MI and
CHD Death Risk Stratified by Diabetic Status
Post-CABG: Aggressive LDL-C Lowering Delays Progression of Atherosclerosis in Women, Elderly, and Patients With Selected CHD Risk Factors
Fasting TG and Risk for CHD Death: Paris Prospective Study
CHD Mortality and Hyperinsulinemia:
Paris Prospective Study (n=943)
Prevalence of Macrovascular Disease and CHD According to Quintiles of Fasting C-Peptide
Finnish Diabetes Prevention Study: Treating
the IGT* Patient With Lifestyle Changes
? Study Design
- 522 middle-aged, overweight? subjects
- 172 men, 350 women with IGT
- BMI 31 kg/m2
- mean age: 55 years
- mean duration: 3.2 years
- intervention group: individualized counseling
? reducing weight, total intake of fat and saturated fat
? increasing intake of fiber, physical activity
Finnish Diabetes Prevention Study: Success
in Achieving Treatment Goals at 1 Year
Finnish Diabetes Prevention Study: Reduction in Risk for Diabetes*
Diabetes Prevention Program: Study Design
Progression to Atherosclerotic Clinical Events in Patients With Diabetes
DAIS: Impact of Aggressive Therapy on Atherosclerosis in Patients With Type 2 Diabetes
Study population
? N=418 (305 men, 113 women)
? Type 2 diabetes
? ?1 minimal lesion on angiography
? Mild elevations of LDL-C or TG + TC:HDL-C ?4
Treatment
? 8 weeks on Step I diet
? Randomized, blinded to micronized fenofibrate (200 mg/d)
and placebo
Primary end point
? Progression or regression of CAD on quantitative angiography
DAIS: Mean Baseline Lipoprotein Levels
DAIS: Interim Lipid Results in Patients With Type 2 Diabetes
DAIS: Final Results in Patients
With Type 2 Diabetes
CAD
? Treatment with fenofibrate resulted in 40% reduction in rate
of progression of localized CAD versus placebo
? 23% reduction in combined coronary events following fenofibrate treatment (P=NS*)
Lipids
? Average reductions with fenofibrate: TC, 10%; LDL-C, 6%;
TG, 29%; average increase in HDL-C, 6%
Safety
? Very few serious adverse events; no significant differences in tolerability between fenofibrate and placebo treatments;
95% compliance
Atherosclerosis in Diabetes
Framingham Heart Study 30-Year Follow-Up:
CVD Events in Patients With Diabetes (Ages 35-64)
Women, Diabetes, and CHD
? Diabetic women are at high risk for CHD
? Diabetes eliminates relative cardioprotective effect of being premenopausal
- risk of recurrent MI in diabetic women is three times that of nondiabetic women
? Age-adjusted mean time to recurrent MI or fatal CHD event is 5.1 yr for diabetic women vs 8.1 yr for nondiabetic women
Primary CHD* Prevention in Patients With
Type 2 Diabetes: The Helsinki Heart Study
Insulin Resistance and Atherosclerosis: Posited Relationships
Abnormal Lipid Levels in Men With
Type 2 Diabetes
Abnormal Lipid Levels in Women With Type 2 Diabetes
Significance of Small, Dense LDL
? Low cholesterol content of LDL particles
- ? particle number for given LDL-C level
? Associated with ? levels of TG and LDL-C, and
? levels of HDL2
? Marker for common genetic trait associated with
? risk of coronary disease (LDL subclass pattern B)
? Possible mechanisms of ? atherogenicity
- greater arterial uptake
- ? uptake by macrophages
- ? oxidation susceptibility
Potential Mechanisms of
Atherogenesis in Diabetes
? Abnormalities in apoprotein and lipoprotein particle distribution
? Glycosylation and advanced glycation of proteins in plasma and arterial wall
? "Glycoxidation" and oxidation
? Procoagulant state
? Insulin resistance and hyperinsulinemia
? Hormone-, growth-factor-, and cytokine-enhanced SMC proliferation and foam cell formation
ADA: Glycemic Control, BP, and
Lipid Targets in Type 2 Diabetes
ADA: Treatment Decisions by LDL-C
Levels* in Adults With Type 2 Diabetes
ADA: Order of Priorities for Treatment
of Diabetic Dyslipidemia in Adults
? LDL-C lowering
- first choice: HMG-CoA reductase inhibitors (statins)
- second choice: bile acid binding resin or fenofibrate
? HDL-C raising
- behavioral interventions (weight loss, ? physical activity, smoking
cessation)
- difficult to achieve except with niacin, which should be used with caution,or fibric acid derivative
? TG lowering*
- first priority: glycemic control
- fibric acid derivative (gemfibrozil, fenofibrate)
- statins (moderately effective at high dose in patients with ? TG and
? LDL-C)
ADA: Order of Priorities for Treatment of Diabetic Dyslipidemia in Adults (cont'd)
? Combined hyperlipidemia
- first choice: improved glycemic control plus high-dose statin
- second choice: improved glycemic control plus statin* plus
fibric acid derivative* (gemfibrozil or fenofibrate)
- third choice: improved glycemic control plus resin plus fibric
acid derivative
or
improved glycemic control plus statin* plus niacin*
(glycemic control must be monitored carefully)
ADA: CHD Risk Stratification Based on Lipoprotein
Levels* in Adults With Type 2 Diabetes
Risk Similar in Patients With Type 2 Diabetes and No Prior MI vs Nondiabetic Subjects With Prior MI
Secondary Prevention: CHD Risk Reduction in the 4S Subgroup of Patients With Diabetes
4S: Total Mortality Reduction in a Subgroup of Patients With Diabetes
4S:Major CHD Event Reduction in a Subgroup of Patients With Diabetes
WOSCOPS: Development of
Type 2 Diabetes
Strong Heart Study: Non-HDL-C as CVD
Risk Predictor in Patients With Diabetes
Strong Heart Study: Non-HDL-C
Compared With Other CVD Risk Predictors
Steno-2: Effect of Therapies on Selected Risk Factors
Steno-2: Primary Composite End Point
or Surgery for PAD
HPS Diabetes Substudy: Absolute Effects on 5-Year Rates of First Major Vascular Event