糖尿病脂代谢紊乱
ATP III: Management of Diabetic Dyslipidemia
Primary target of therapy: identification of LDL-C; goal for persons with diabetes: <100 mg/dL
Therapeutic options:
LDL-C 100–129 mg/dL: increase intensity of TLC; add drug to modify atherogenic dyslipidemia (fibrate or nicotinic acid); intensify risk factor control
LDL-C ?130 mg/dL: simultaneously initiate TLC and LDL-C–lowering drugs
TG ?200 mg/dL: non–HDL-C* becomes secondary target
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497.
Note: Diabetic dyslipidemia is essentially atherogenic dyslipidemia in persons with type 2 diabetes. *Non–HDL-C goal is set at 30 mg/dL higher than LDL-C goal.
? 2001, Professional Postgraduate Services?
www.lipidhealth.org
LIPID: Reduction in Nonfatal MI and CHD Death Risk Stratified by Diabetic Status
-19
-25
30
25
20
15
10
5
0
With diabetes Without diabetes
(n=782) (n=8,232)
LIPID Study Group. N Engl J Med. 1998;339:1349-1357.
%
Baseline Aggressive Rx Moderate Rx P Characteristic (N=1360) (N=1318) Value
Campeau et al. Circulation. 1999;99:3241-3247.
Post-CABG: Aggressive LDL-C Lowering Delays Progression of Atherosclerosis in Women, Elderly, and Patients With Selected CHD Risk Factors
n % n %
Age (y): <60 479 30 513 40 0.003 360 881 27 805 39 <0.0001
Female 88 15 63 24 0.25 Male 1272 29 1255 40 <0.0001
Current smoker: Yes 137 32 139 50 0.01 No 1223 27 1179 38 <0.0001
Hypertension: Yes 655 27 608 39 0.0002 No 705 28 710 39 0.0003
Diabetes mellitus: Yes 122 27 104 43 0.04 No 1238 28 1214 39 <0.0001
n=number of grafts.
Grafts With Substantial Progression
0
2
4
6
Mean annual CHD mortality rate/1,000
Adapted from Fontbonne A et al. Diabetologia. 1989;32:300-304.
Cholesterol (mg/dL)
?220
>220
?220
>220
TG ?123 mg/dL TG ?123 mg/dL
Fasting TG and Risk for CHD Death: Paris Prospective Study
0
1
2
3
CHD mortality (per 1,000)
Fontbonne AM et al. Diabetes Care. 1991;14:461-469.
?29 30-50 51-72 73-114 ?115
Quintiles (pmol) of fasting plasma insulin
P<0.01
CHD Mortality and Hyperinsulinemia: Paris Prospective Study (n=943)
0
10
20
30
40
50
60
1
2
3
4
5
% Macrovascular disease
P
<0.001
0
10
20
30
40
50
60
70
80
1
2
3
4
5
% Macrovascular disease
P
<0.05
0
10
20
30
40
50
60
1
2
3
4
5
% CHD
P
<0.002
0
10
20
30
40
50
60
70
80
1
2
3
4
5
% CHD
Nondiabetic controls (n=178)
Noninsulin-treated type 2 diabetics (n=154)
Fasting C-peptide quintiles (1-5)
Janka HU. Horm Metab Res. 1985;15(suppl):15-19.
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
*Plasma glucose concentration of 140 to 200 mg/dL.
?BMI ?25 kg/m2.
IGT=impaired glucose tolerance; BMI=body mass index.
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
Finnish Diabetes Prevention Study: Success in Achieving Treatment Goals at 1 Year
*P values were determined for the difference between groups. Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
Finnish Diabetes Prevention Study: Reduction in Risk for Diabetes*
Tuomilehto J et al. N Engl J Med. 2001;344:1343-1350.
11%
23%
0
5
10
15
20
25
Intervention
Control
(n=265)
(n=257)
*P<0.001; 4-year results
Diabetes (%)
BMI=body mass index.
DPP Research Group. N Engl J Med. 2002;346:393-403.
Diabetes Prevention Program: Study Design
Entry Criteria
age ?25 years
BMI ?24 kg/m2 (?22 kg/m2 in Asians)
fasting plasma glucose 95-125 mg/dL
postglucose challenge 140-199 mg/dL
Intervention
standard lifestyle recommendations + placebo twice daily
standard lifestyle recommendations + metformin titrated to 850 mg twice daily
intensive lifestyle modification (low-calorie/low-fat diet, moderate physical activity 3150 min/wk)
troglitazone (later withdrawn)
Outcome
type 2 diabetes over average follow-up of 2.8 years
Progression to Atherosclerotic Clinical Events in Patients With Diabetes
AGE=advanced glycation end products; CRP=C-reactive protein; HDL=high-density lipoprotein; HTN=hypertension; IL-6=interleukin-6; LDL=low-density lipoprotein; PAI-1=plasminogen activator inhibitor-1; SAA=serum amyloid A protein; TF=tissue factor; TG=triglycerides; tPA=tissue-type plasminogen activator
Biondi-Zoccai GGL et al. J Am Coll Cardiol. 2003;41:1071-1077.
Subclinical Atherosclerosis
Atherosclerotic Clinical Events
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=Diabetes Atherosclerosis Intervention Study.
Steiner G et al. Am J Cardiol. 1999;84:1004-1010.
mg/dL
* Significant difference between genders.
Steiner G et al. Am J Cardiol. 1999;84:1004-1010.
DAIS: Mean Baseline Lipoprotein Levels
P=0.0005*
P=0.0001*
P=NS
P=NS
Mean % D
*P=0.0001.
Steiner G. Diabetes. 1999;48(suppl 1):A2. Abstract 0005.
DAIS: Interim Lipid Results in Patients With Type 2 Diabetes
*Researchers report that results suggest benefit to patients.
Steiner G. XIIth International Symposium on Atherosclerosis; June 27, 2000; Stockholm, Sweden.
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
Garber AJ. Clin Cornerstone. 2003;5:22-37.
Garber AJ. Med Clin North Am. 1998;82:931-948.
National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995.
Atherosclerosis in Diabetes
Accelerated atherosclerosis is multifactorial and begins years/decades prior to diagnosis of type 2 diabetes
>50% of patients with newly diagnosed type 2 diabetes have CHD
Risk for atherosclerotic events is 2- to 4-fold greater in diabetics than in nondiabetics
Atherosclerosis accounts for ?65% of all diabetic mortality
40% due to ischemic heart disease
15% due to other heart disease