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