710 427
1 2
1
2
2
LDL HDL
TG 2
(LDL<100 mg/dl TG<150 mg/dl HDL > 40 mg/dl > 50 mg/dl)
LDL>100 mg/dl
LDL < 100 mg/dl( 2.6 mmol/l) LDL 30-40%
LDL statins
LDL < 70 mg/dl HDL 40 mg/dl LDL 100 129 mg/dl
fibric acid derivative niacin statin fibrate statin niacin
(LDL HDL TG)
1 2
( Diabetes mellitus, DM ) ( Hyperlipidemia )
( Cardiovascular disease, CVD )
2
2 4
1 -2
5
3
2
East and West
4
( UKPDS )
5
2
2
( )
6
2
2 ( TG ) ( < 400 mg/dl
) ( HDL )
7
( LDL )
L D L
8
( LDL ) ( HDL )
( TG ) 2
( LDL< 100 mg/dl TG< 150 mg/dl HDL > 40 mg/dl
> 50 mg/dl )
9TG
LDL TG
LDL HDL
LDL>100 mg/dl
(
) LDL
L D L <
100 mg/dl ( 2.6 mmol/l ) LDL 30-40%
LDL statins
LDL nicotinic acid, eze- timbe, bile acid sequestrants, fenofibrate
9-102
2 0 0 3 H e a r t
Protection Study
115963 40
( 135 mg/dl )
simvastatin 40 mg
( 116 mg/dl )
LDL 30%
25% 2004 8
LDL 2 ( 2838 )
( Collaborative Atorvastatin Diabetes
Study, CARDS )
122
primary prevention study
2 L D L
( 120 mg/dl ) atorvastatin 10 mg
( 1428 ) ( p=0.001 )
3 7 %
48% statin
( subgroup analysis ) Scandinavian Simvastatin Study ( 4S )
L D L
13-15
Statins LDL< 70 mg/dl
Statins
L D L
< 70 mg/dl
10fibric acid derivative ( TG HDL ) ( Helsinki Heart Study, HHS ) gemfibrozil
(
)
16Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial ( VA-HIT )
17
gemfibrozil ( p=0.004 ) HDL ( 40 mg/dl )
3 2 % (
LDL ) LDL
8
HDL TG
81
Heart Protection
Study 600 1
2
1 2
HDL 40 mg/dl LDL
100 129 mg/dl fibric acid deriva- tive niacin Nicotinic acid
HDL LDL
T G
750- 2000 mg
18,19statin fibrate statin niacin ( LDL HDL TG )
c r e a t i n i n e phosphokinase ( CK )
statin fenofibrate statin gemfibrozil
creatinine fenofibrate
fibrates niacin statins
statins
7
L D L
( 1 ) HMG-Co A reductase ( statin ) l o v a s t a t i n f l u v a s t a t i n pravastatin simvastatin atorvastatin rosu- vastatin
( 2 ) sequestrant cholestyramine colestipol colesevelam
( 3 ) Nicotinic acid nicolar lipo-nicin acipimox
( 4 ) Probucol HDL
( 5 ) Ezetimibe( ezetrol tablets )
( )
1.
statins (
severe myalgia myositis ) 2.
statins 3
statins TG
( 1 ) Fibric acid gemfibrozil bezafi- brate etofibrate micronised fenofibrate
( 2 ) Nicotinic acid nicolar lipo-nicin acipimox
ADA
20
A- Level evidence B- Level evidence C- Level evidence E- Expert consensus
1.
( LDL < 100 mg/dl HDL >
50 mg/dl TG < 150 mg/dl ) ( E ) 2.
( )
( A )
3. 1 2
L D L
40 135 mg/dl
statin LDL
30-40% LDL < 100 mg/dl
( 2.6 mmol/l ) ( A ) 4.
(
)
LDL < 100 mg/dl ( 2.6 mmol/l ) ( C )
5.
statin ( A )
6. (
) statins LDL
70 mg/dl ( 1.8 mmol/l ) ( B )
7.TG 150 mg/dl ( 1.7 mmol/l ) HDL 40 mg/dl ( 1.15 mmol/l ) ( ) 50 mg/dl ( ) ( C )
8. fibric acid derivative ( TG
HDL ) HDL
L D L
( A )
9. statins fibrates niacin
( E )
10. Statin (E)
1.Kannel WB, McGee DL. Diabetes and cardiovascular disease.
The Framingham study. JAMA 1979; 241: 2031-4.
2.Kannel WB, McGee DL. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham Study.
Diabetes Care 1979; 2: 120-6.
3.Herlitz J, Malmberg K, Karlson BW, Ryden L, Hjalmarson A.
Mortality and morbidity during a five-year follow-up of diabet- ics with myocardial infarction. Acta Med Scand 1988; 224: 31- 8.
4.Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M.
Mortality from coronary heart disease in subjects with type 2 di- abetes and in nondiabetic subjects with and without prior my- ocardial infarction. New Engl J Med 1998; 339: 229-34.
5.The UK Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in over- weight patients with type 2 diabetes ( UKPDS 34 ). Lancet 1998;
352: 854-65.
6.American Diabetes Association. Standards of medical care in di- abetes ( Position Statement ). Diabetes Care 2004; 27: S15-35.
7.Haffner SM. Management of dyslipidemia in adults with dia- betes ( Technical review ). Diabetes Care 1998; 21: 160-78.
8.American Diabetes Association. Dyslipidemia management in adults with diabetes ( Position Statement ). Diabetes Care 2004;
27: S68-71.
9.Executive summary of the third report of the national chole- sterol education program: ( NCEP ) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001; 285: 2486-97.
10.Grundy SM, Cleeman JI, Merz CN, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation 2004; 110:
.. .. .. ..
227-39.
11.Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomized placebo-controlled tri- al. Lancet 2003; 361: 2005-16.
12.Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary pre- vention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study ( CARDS ) : multicentre randomised placebo-controlled trial.
Lancet 2004; 364: 685-96.
13.Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syn- dromes. N Engl J Med 2004; 350: 1495-504.
14.De Lemos JA, Blazing MA, Wiviott SD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA 2004; 292: 1307-16.
15.Nissen SE, Tuzcu EM, Schoenhagen P, et al. Effect of intensive compared with moderate lipid-lowering therapy on progression of coronary atherosclerosis: a randomized controlled trial. JA- MA 2004; 291: 1071-80.
16.Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: prima- ry-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987; 317:
1237-45.
17.Rubins HB, Robins SJ, Collins D, et al. Diabetes, plasma in- sulin, and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein inter- vention trial ( VA-HIT ) . Arch Intern Med 2002; 162: 2597-604.
18.Elam MB, Hunninghake DB, Davis KB, et al. Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study:
a randomized trial: arterial disease multiple intervention trial.
JAMA 2000; 284: 1263-70.
19.Grundy SM, Vega GL, McGovern ME, et al. Efficacy, safety, and tolerability of once-daily niacin for the treatment of dys- lipidemia associated with type 2 diabetes: results of the assess- ment of diabetes control and evaluation of the efficacy of nia- span trial. Arch Intern Med 2002; 162: 1568-76.
20.American Diabetes Association. Standards of medical care in
diabetes ( Position Statement ). Diabetes Care 2005; 28: S4-36.
ADA Standard Recommendations for Treatment of Diabetes with Hyperlipidemia
Lyh-Jyh Hao, Chwen-Yi Yang
1, and Ta-Jen Wu
2Patients with type 2 diabetes have an increased prevalence of lipid abnormalities that contributes to high- er rates of CVD (Cardiovascular disease). Lipid management aimed at lowering LDL cholesterol, raising HDL c- holesterol, and lowering triglycerides has been shown to reduce macrovascular disease and mortality in patients with type 2 diabetes, particularly those who have had prior cardiovascular events. Lifestyle intervention includ- ing MNT (Medical nutrition therapy), increased physical activity, weight loss, and smoking cessation should al- low some patients to reach these lipid levels. Pharmacological treatment is indicated if there is an inadequate re- sponse to lifestyle modifications and improved glucose control. However, in patients with clinical CVD and LDL
>100 mg/dl, pharmacological therapy should be initiated at the same time that lifestyle intervention is started. The first priority of pharmacological therapy is to lower LDL cholesterol to a target goal of <100 mg/dl (2.60 mmol/l) or therapy to achieve a reduction in LDL of 30 40%. For LDL lowering, statins are the drugs of choice. A re- duction in LDL to a goal of <70 mg/dl is an option in very-high-risk patients with overt CVD. If the HDL is <40 mg/dl and the LDL is between 100 and 129 mg/dl, a fibric acid derivative or niacin might be used. Combination therapy, with a statin and a fibrate or statin and niacin, may be efficacious for patients needing treatment for all three lipid fractions( LDL,HDL,TG ), but this combination is associated with an increased risk for abnormal transam- inase levels, myositis, or rhabdomyolysis. Consideration should be given to similar lipid-lowering therapy in pa- tients with type 1 diabetes as in type 2 diabetes, particularly if they have other cardiovascular risk factors or fea- tures of the metabolic syndrome. ( J Intern Med Taiwan 2005; 16: 169-174 )
Division of Endocrinology and Metabolism, Yung Kang Veterans Hospital
1
Division of Endocrinology and Metabolism, Department of Internal Medicine, Chi-Mei Foundation Hospital, Tainan, Taiwan
2