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Slide 1

代謝症候群案例說明

Kuo-Chin Huang MD, PhD
Associate Professor
Department of Family Medicine
National Taiwan University Hospital


Slide 2

Metabolic Syndrome

Grundy SM. Nat Rev Drug Discov 2006 Apr;5(4):295-309.


Slide 3

Metabolic Syndrome

Colon cancer ↑1.62 for proximal lesions

Grundy SM. Nat Rev Drug Discov. 2006 Apr;5(4):295-309.


Slide 4

代謝症候群與心血管疾病及死亡率

Am J Med. 2006 Oct;119: 812-9


Slide 5

台灣成年人代謝症候群與死亡率

Huang KC Obesity 2008 Mar;16(3):684-9.


Slide 6

台灣老年人代謝症候群與死亡率

CVD mortality

All-cause mortality

Huang KC, et al. Eur J Clin Invest 2008; 38 (7): 469–475


Slide 7

Circulation 2005;112: 285-90
Lancet. 2005 Sep 24;366(9491):1059-62.


Slide 8

Circulation 2005;112: 285-90


Slide 9

台灣代謝症候群的定義(>=3個)






腹部肥胖:腰圍男性>=90 公分,女性>=80
公分
血壓過高:收縮壓>=130 mmHg and/or 舒
張壓>=85mm Hg或是高血藥物治療中
空腹血糖過高:空腹血糖值>=100 mg/dL或
是糖尿病治療中
三酸甘油脂過高:TG >=150 mg/dL
高密度脂蛋白膽固醇過低:low HDL-C 男性
<40mg/dL, 女性 <50mg/dL
國健局 2006


Slide 10

Limitations of BMI: The Y-Y Paradox

Yajnik & Yudkin, Lancet 2004


Slide 11

成人腰圍測量方法
1. 除去腰部覆蓋衣物,輕鬆站
立,雙手自然下垂。
2. 以皮尺繞過腰部,調整高度
使能通過左右兩側腸骨上緣
至肋骨下緣之中間點(如圖),
同時注意皮尺與地面保持水
平,並緊貼而不擠壓皮膚。
3. 維持正常呼吸,於吐氣結束
時,量取腰圍。

國民健康局, Taiwan


Slide 12

腹部肥胖之盛行率
Prevalence of abdominal obesity by region or country
Men (%)

Women (%)

Total (%)

US1

36.9

55.1

46.0

South Europe2

33.2

43.8

38.5

South Korea3

21.0

42.4

32.5

Australia4

26.8

34.1

30.5

South Africa5

9.2

42.0

27.3

North Europe2

22.8

25.9

24.4

Taiwan6

28.3

28.7

28.5

1. Ford ES et al, 2003; 2 Haftenberger M et al, 2002;
3. Kim MH et al 2004; 4. Cameron AJ et al, 2003;
5. Puoane T et al, 2002; 6. Hwang LC et al, 2006


Slide 13

代謝症候群之防制策略
篩選高危險群
符合診斷標準

成人健檢或其他健康
檢查資料

量腰圍、量血壓、空腹抽血

確立診斷為代謝症候群

評估心血管疾病風險:Framingham 10年風險指數

處理

國健局 2006


Slide 14

代謝症候群申請支付標準流程圖
•腹部肥胖︰男性腰圍≧90cm,女性腰圍≧80cm
•三酸甘油酯︰≧150mg/dl
•血糖︰≧100mg/dl或糖尿病已服藥物治療中
•血壓︰收縮壓≧130mmHg及舒張壓≧85mmHg,或高血壓已服藥治療中
符合M.S. 3項標準
P3701C(申報)
P3702C (收案滿180日,且完成

符合M.S. 2項標準

追蹤及評估事項)

P3703C(不得申報)
一年內做過HDL檢查
(不需重新檢驗)

未做過HDL檢查或
一年前做過HDL檢查
(皆需重新檢驗)

HDL(男性<40mg/dl)
HDL(女性<50mg/dl)

HDL(男性>40mg/dl)
HDL(女性>50mg/dl)

HDL(男性<40mg/dl)
HDL(女性<50mg/dl)

HDL(男性>40mg/dl)
HDL(女性>50mg/dl)

符合M.S. 3項標準
P3701C(申報)
P3702C (收案滿180日,且完成

不符合M.S. 3項標準
P3701C(不得申報)
P3702C(不得申報)
P3703C(不得申報)

符合M.S. 3項標準
P3701C(申報)
P3702C(收案滿180日,且完成

不符合M.S. 3項標準
P3701C(不得申報)
P3702C(不得申報)
P3703C(申報)

追蹤及評估事項)

P3703C(不得申報)

追蹤及評估事項)

P3703C(申報)


Slide 15

編號
P3701C

診療項目
代謝症候群收案管理照護費
註:1.本項目已包含診察費,故不得另行申報。
2.建議診察及照護項目詳附表1。
3.完成「代謝症候群照護」方案記錄表(一)、(二),詳附表2及附表3。
4.須完成個案登錄資料。
5.每一病患於同一院所限申報1次。

支付點數
400

P3702C

代謝症候群評估管理照護費
註:1.本項目已含診察費及09004C三酸甘油酯、09005C血液及體液葡萄糖及09043C高密度脂蛋白膽固醇等3項檢
驗費用,故不得另行申報。
2.建議診察及照護項目詳附表4。
3.須完成「代謝症候群照護」方案記錄表(二)追蹤欄。
4.須提供健康管理建議如附表5。
5.須完成個案登錄資料。
6.每一病患於同一院所限申報1次。

800

P3703C

高密度脂蛋白膽固醇檢查費
(1)須優先篩檢保險對象之腹部肥胖、血糖、三酸甘油酯及血壓等四項危險因子,如其中三項已符合收案條件者,應
直接收案並於完成相關照護後,申請P 3701C及P 3702C (收案滿180日,且完成追蹤及評估事項)費用,不得申報本
項費用。
(2)如上開四項危險因子僅二項符合收案條件,惟一年內曾做過HDL生化檢查且符合男性< 40 mg/dl;女性<
50mg/dl條件者,應直接採用該項生化檢查值作為收案條件,並申報P 3701C及P 3702C (收案滿180日,且完成追蹤
及評估事項)費用,惟不得另行申報本項費用。
(3)如上開四項危險因子僅二項符合收案條件,且一年內曾做過HDL生化檢查,惟其不符合男性< 40 mg/dl;女性<
50mg/dl條件者,不得申報本項費用,亦不得申報P 3701C及P 3702C費用。
(4)如上開四項危險因子僅二項符合收案條件,且未曾做過HDL生化檢查,則得進行本項檢查並申報本項費用,如其
結果符合男性<40 mg/dl;女性<50mg/dl條件者,得再申報P 3701C及P 3702C (收案滿180日,且完成追蹤及評估
事項)費用。
(5)如上開四項危險因子僅二項符合收案條件,但一年前曾做過HDL生化檢查且其符合男性<40 mg/dl;女性<
50mg/dl條件者,可再進行本項檢查並申報本項費用,如其結果符合男性<40 mg/dl;女性<50mg/dl條件者,則得
再申報P 3701C及P 3702C (收案滿180日,且完成追蹤及評估事項)費用。
(6)如上開四項危險因子僅二項符合收案條件,但一年前曾做過HDL生化檢查,惟其不符合男性<40 mg/dl;女性<
50mg/dl條件者,可再進行本項檢查並申報本項費用,如其結果符合男性<40 mg/dl;女性<50mg/dl條件者,則得
再申報P 3701C及P 3702C (收案滿180日,且完成追蹤及評估事項)費用。

200


Slide 16

表一 不同性別與年齡層的代謝症候
群之盛行率(N=124,513)
20-39歲 40-64歲 >=65歲 >=20歲
(%)
(%)
(%)
(%)
全部

10.1

30.8

50.1

22.4



16.6

33.6

41.8

26.0



4.2

28.6

60.0

19.1


Slide 17

表二 有無腹部肥胖在不同性別與年齡
層的代謝症候群之盛行率(N=124,513)
20-39歲(%) 40-64歲(%) >=65歲(%) >=20歲(%)
全部
腹部肥胖

58.3

68.8

79.6

68.5

正常

5.0

16.1

26.0

10.6

腹部肥胖

66.1

73.6

79.2

72.1

正常

9.2

20.1

23.7

14.5

腹部肥胖

43.1

65.6

79.9

65.4

正常

1.7

12.7

30.7

7.1






Slide 18

表三 有無血壓高在不同性別與年齡層
的代謝症候群之盛行率(N=124,513)
20-39歲(%) 40-64歲(%) >=65歲(%) >=20歲(%)
全部
血壓高

35.7

54.0

60.9

50.6

正常


4.7

12.9

19.2

8.1

血壓高

39.7

55.2

52.9

49.4

正常


8.1

16.2

15.6

11.4

血壓高
正常

25.1
2.1

53.0
10.2

69.4
25.2

52.0
5.5


Slide 19

表四 同時有腹部肥胖與血壓高在不同
性別與年齡層的代謝症候群之盛行率
20-39 40-64 >=65歲 >=20歲
歲(%) 歲(%) (%)
(%)
全部

86.4

85.3

86.9

85.8



86.6

87.5

87.4

87.2



85.7

83.8

86.6

84.7


Slide 20

表五 有無肥胖(BMI>=27kg/m2)在不同
性別與年齡層的代謝症候群之盛行率
20-39歲(%) 40-64歲(%) >=65歲(%) >=20歲(%)

全部
肥胖
正常


52.4
6.0

67.8
23.3

81.2
43.4

64.2
16.1

肥胖
正常


55.7
10.4

71.3
25.8

80.8
35.4

65.1
19.0

肥胖
正常

43.2
2.4

64.8
21.3

81.4
54.0

63.0
13.6


Slide 21

表六 同時有肥胖(BMI>=27kg/m2)與血
壓高在不同性別與年齡層的代謝症候群
之盛行率
20-39歲 40-64歲 >=65歲 >=20歲
(%)
(%)
(%)
(%)

全部

77.9

82.4

87.7

82.2



77.3

84.5

88.7

82.5



80.6

80.7

87.0

82.0


Slide 22

40-55歲

男性

女性

90
80
70
60
50
MetS%
40
30
20
10
0

<18 18- 19- 20- 21- 22- 23- 24- 25- 26- 27- 28- 29- ≧30
19 20 21 22 23 24 25 26 27 28 29 30

BMI (kg/m 2)


Slide 23

40-55歲

男性

女性

100
90
80

腹部肥胖

70
60
50
40
30
20
10
0

<18 18- 19- 20- 21- 22- 23- 24- 25- 26- 27- 28- 29- ≧
19 20 21 22 23 24 25 26 27 28 29 30 30

BMI


Slide 24

不同情況下代謝症候群絕對風險之比較

Despres et al. Nature 2006; 444: 881-7


Slide 25

代謝症候群之防制策略(續)
處理
A. 減重

B. 增加體力活動

1. 血脂異常
必要時藥物治療,詳見
http://www.bhp.doh.gov.tw/
BHP/do/chinese/home

C. 健康飲食

2. 血壓異常
必要時藥物治療,詳見
http://www.bhp.doh.gov.tw/
BHP/do/chinese/home

D. 戒菸

3. 血糖異常
必要時藥物治療,詳見
http://www.bhp.doh.gov.tw/
BHP/do/chinese/home

定期追蹤、積極處理
預防心血管疾病及糖尿病

國健局 2006


Slide 26

治療式生活形態改變(TLC)之施行步驟
第1次就診
開始TLC

6週

6週
第2次回診

第3次回診 每3-6個月 第N次回診
評估達到
評估與監測
治療目標否
……
若無

1.評估及討論
1.評估
2.設立治療目標(TLC目標 2.補強第1次就診後之缺失
3.轉介給營養師
及血壓、血脂、血糖
控制目標)
3.鼓勵適度體力運動
4.強調健康飲食
5.轉介給營養師

1.評估及討論
2.再加強TLC
3.考慮使用藥物

國健局 2006


Slide 27

Patient Profile: Ron G.
BP 140/94 mmHg, BMI 28 kg/m2, WC 41"
 TC: 230 LDL: 138 HDL: 36 TG: 280 mg/dL
 Fasting glucose: 114 mg/dL (prediabetes)
 Family history of T2DM with complications
 No clinically evident disease, but clearly at
risk for CVD, T2DM
 What is the best treatment for Ron G. within
the new treatment paradigm?


Data from Prof Jillian Meyer in USA


Slide 28

Comprehensive Management for
Disease Prevention
Current Treatment Paradigm

Treatment

AO ± pre-HTN,
dyslipidemia

HTN, ↑LDL, ↑TG
+
↓HDL, IFG, AO

CVD/T2DM

Delay/prevent?

Treatment
New Treatment Paradigm
Data from Prof Jillian Meyer in USA


Slide 29

Metabolic Syndrome- a lifestyle
disease with genetic predisposition


Slide 30

Etiological categories for the
metabolic syndrome




Obesity and abnormalities of adipose tissue
Insulin resistance
A constellation of independent factors (eg,
molecules of hepatic, vascular and
immunological origin) that mediate specific
components of the metabolic syndrome (FFA,
Cortisol, Estrogen, Leptin, Adiponectin, Resistin,
IGF-1, IL-6, TNF-A, PAI-1)
Carlson LA. Clinician’s Manual on
the Metabolic Syndrome


Slide 31

Medications for this patient
Blood pressure:
148/ 89 mmHg
Diuretics
Beta blocker
ACE-Inhibitors
AT1-blockers
....

Impaired fasting
glucose:
AC sugar: 111 mg/dl
2-h OGTT: 180 mg/dl
Metformin
Acarbose
TZD´s

LDL-Cholesterol:
140 mg/dl
Statin
HDL-Cholesterol:
32 mg/dl
Niacin

Triglycerides:
288 mg/dl
Fibrates

Central obesity:
128 cm
Diet, Exercise
Orlistat,
Sibutramine
Data from Prof. Matthias Blüher in Germany


Slide 32

Mr JP





Now 64 year-old retired taxi driver
Type 2 diabetes mellitus since 1998, age 56
 Diagnosed on screening at GP
 Fasting glucose 9.2 mmol/L (166 mg/dl)
 HbA1c 8.4%
 Total Cholesterol 6.1 mmol/L (236 mg/dl)
 BP 154/88 mm Hg
 Weight 94 kg
 BMI 32.4
Advised on ‘diabetic diet’ (patient description)
 Avoid sugar and fatty foods
Data from Dr Finer in UK


Slide 33

Mr JP








Feb 2000
 HbA1c 9%
 Started on Metformin 500 mg bid
Feb 2001
 HbA1c 7.8%
 Continues on Metformin
 Cholesterol 6.2 mmol/L (240mg/dl): Simvastatin started
Jan 2002
 BP 156/92 mm Hg: Perindopril started
 Weight 98 kg, BMI 34
Oct 2002
 HbA1c 8.5%
 Weight 101 kg, BMI 35
Data from Dr Finer in UK


Slide 34

Mr JP
 What

should he do now?

Accept

current glycaemic control
Re-advise on diet and exercise
Add 2nd hypoglycaemic drug
Start insulin

Data from Dr Finer in UK


Slide 35

Clinical Management of Metabolic
Syndrome


Lifestyle risk factors
Abdominal obesity (7-10% at year 1, BMI<25 kg/m2 finally),
physical inactivity (30-60 min, 5-7 d/wk, RT 2d/wk),
atherogenic diet (reduced saturated fat, trans fat, and
cholesterol), smoking cessation



Metabolic Risk Factors
Atherogenic dyslipidemia (1st LDL-C, 2nd non-HDL-C, 3rd
HDL-C)
Elevated BP
Elevated glucose
Prothrombotic state
Proinflammatory state
Circulation 2005;112: 285-90


Slide 36

(1)代謝症候群之
腹部肥胖的治療


Slide 37

減重的效益
~5%
Weight Loss
1
HbA1c
Blood Pressure
Total Cholesterol

5%-10%
Weight Loss
1

2

2

3

3

3

3

HDL Cholesterol

Triglycerides
1. Wing RR et al. Arch Intern Med. 1987;147:1749-1753.
2. Mertens IL, Van Gaal LF. Obes Res. 2000;8:270-278.
3. Blackburn G. Obes Res. 1995;3 (Suppl 2):211S-216S.
4. Ditschunheit HH et al. Eur J Clin Nutr. 2002;56:264-270.

4


Slide 38

N Engl J Med 2002;346:393-403
31%
58%


Slide 39

Intensive Lifestyle Intervention







The goal is to achieve and maintain a weight
reduction of at least 7 % initial BW through
a healthy low calorie, low-fat diet and physical
activity of moderate intensity, such as brisk
walking, for at least 150 minutes per week.
A 16-lesson curriculum covering diet,
exercise, and behavior modification
one-to-one basis during the first 24 weeks
(flexible, culturally sensitive, and
individualized)
Subsequent individual sessions (usually
monthly) and group sessions with the case
managers were designed to reinforce the
behavioral changes.
N Engl J Med 2002;346:393-403


Slide 40

Development and Resolution of
the Metabolic syndrome (53%)
38%
53%

23%
18%

47%
38%

Development

Resolution
Ann Intern Med. 2005; 142(8):611-9.


Slide 41

XENical in the Prevention of Diabetes
in Obese Subjects (XENDOS) Study

Diabetes Care 2004; 27: 155-61.


Slide 42


Slide 43


Slide 44

N Engl J Med 2004;351:2683-93


Slide 45

N Engl J Med 2004;351:2683-93


Slide 46

N Engl J Med 2004;351:2683-93


Slide 47

減重手術降低重度肥胖病人的死亡率

29%

N Engl J Med 2007;357:741-52


Slide 48

(2)代謝症候群之
血脂異常的治療


Slide 49

Intensive LDL lowering is
recommended in ATP III report (2004)
High Risk
CHD or CHD risk
equivalents

190 -

(10-yr risk >20%)

Moderately High
Risk

≥ 2 risk factors

Moderate Risk

Lower Risk

≥ 2 risk factors

< 2 risk factors

(10-yr risk <10%)

(10-yr risk 10-20%)

Target

160

LDL-C level

mg/dL

160 -

130 -

Target

100
mg/dL

100 -

Target

Target

130

130

mg/dL

mg/dL

or optional

100 mg/dL
台灣健保局治療目標

or optional

70 mg/dL*

70 Circulation. 2004;110:227-239

* Patient who had established CVD combine with acute coronary syndromes or
multiple risk factors (esp. diabetes) or severe and poorly controlled risk factors (e.g.,
cigarette smoking) or metabolic syndrome (high TG, low HDL-C)


Slide 50

Therapeutic Lifestyle Changes
(TLC)for Dyslipidemia





血中膽固醇或壞的膽固醇過高,可藉由改善以
下的生活形態,來降低動脈粥樣硬化的危險:
TLC飲食(TLC diet):
 少吃飽和脂肪
 少吃膽固醇
 多攝取水溶性纖維,例如:全穀類、豆莢、
種子、蔬菜、水果
規律運動
維持理想體重


Slide 51

Very high risk patients…
CHD + at least one of the following conditions:
• Multiple risk factors (especially diabetes)
• Severe and poorly controlled risk factors
(especially continued cigarette smoking)
• Multiple risk factors of the metabolic
syndrome (especially high triglycerides >
200 mg/dl plus non-HDL-C > 130 mg/dl
with low HDL-C < 40 mg/dl)
• Acute coronary syndrome
Circulation. 2004;110:227-239


Slide 52

Circulation 2004;110:227-239


Slide 53

Classification of Serum Triglycerides
Normal
 Borderline high
 High


<150 mg/dL
150–199 mg/dL
200–499 mg/dL

Non-HDL-C is the secondary target
Non-HDL cholesterol goal: LDL-C goal + 30 mg/dL


Very high

500 mg/dL

Goal of therapy: prevent acute pancreatitis
Very low fat diets, Triglyceride-lowering drug
(fibrate or nicotinic acid)
NCEP ATP III. JAMA 2001;285:2486–97.


Slide 54

Combination therapy
Statin based
Statin + ezetimibe
 Statin + niacin
 Statin + resin
 Statin + fenofibrate, not gemfibrozil
 Statin + ezetimibe + fenofibrate


Non-statin based
Fibrate + ezetimibe
 Fibrate + niacin



Slide 55

(3)代謝症候群之
血糖過高的治療


Slide 56

Pathophysiology of T2DM
Impaired glucose tolerance

Insulin sensitivity
Insulin secretion
Plasma glucose

Hyperglycemia

Microvascular
disease
Macrovascular
disease

N Engl J Med 1996;334:777–83
Fortschr Med 1992;110:637–41.


Slide 57

Treatment of Elevated Fasting
Glucose
In MetS patients with IFG ( or IGT if
assessed), weight reduction and/or
increased physical activity will delay or
prevent the onset of DM
 Metformin, TZDs, acarbose will lower risk
for DM in people with IFG or IGT
 Only acarbose reduces the risk of HTN
and CV events in subjects with
dysglycaemia (JAMA 2003)


Circulation 2005;112: 285-90


Slide 58

(4)代謝症候群之
血壓過高的治療


Slide 59

Treatment of Elevated Blood
Pressure







HTN without DM or CKD, the BP goal is <
140/90 mmHg
HTN with DM or CKD, the BP goal is < 130/80
mmHg
DASH (Dietary Approaches to Stop HTN) diet for
mild elevations of BP
ACEIs (ARBs if can’t tolerate ACEIs) as the firstline therapy for HTN in the MetS, especially
when DM or CKD is present
The role of diuretics?
Circulation 2005;112: 285-90


Slide 60

Lifestyle Modification Recommendations

Hypertension. 2003;42:1206


Slide 61

DASH diet







DASH (Dietary Approaches to Stop Hypertension)diet為
高血壓保健飲食。
注意飲食的攝取,包括:飽和脂肪、膽固醇、脂
肪,並特別強調蔬菜水果與低脂乳製品的攝取有
助於降低血壓。
亦強調全穀類、魚肉、雞肉、堅果類、少紅肉、
少單糖及少含糖飲料,富含鉀、鎂、鈣離子、蛋
白質及纖維的食物。
原本並不是設計用來減重的一種飲食,但是因為
此種飲食富含蔬菜類與水果類,藉由這二低熱量
食物的攝取來取代其他高熱量食物,亦可控制體
重。


Slide 62

如何遵循DASH飲食計畫(範例)
食物類別
五穀根莖類

一份

在DASH飲食中的重要性

半片全麥土司
三湯匙燕麥片…

主要的熱量來源,且未精緻加
工的五穀根莖類富含纖維

蔬菜類

一顆大蕃茄
半碗煮熟青菜

富含鉀、鎂與纖維

水果類

一個網球大小新鮮水果

富含鉀、鎂與纖維

低脂乳製品

240毫升牛奶

富含鈣與蛋白質

蛋豆魚肉類

1個蛋
1兩肉、半盒豆腐

富含蛋白質與鎂

堅果種子類

1/3杯堅果類
2湯匙種子

可提供熱量,富含鉀、鎂與纖


油脂類

1茶匙油

可提供熱量、必需脂肪酸



1湯匙糖或果醬


Slide 63

Beneficial effects of DASH on
features of the metabolic syndrome







116 patients with metabolic syndrome
6 months of control diet, a weight-reducing diet,
DASH diet with reduced calories/increased fruit,
vegetables, low-fat dairy, whole grains..2400mg
Na
HDL-C (7/10mg/dl), TG (-18/14mg/dl), SBP (12/11mmHg), DBP (-6/7mmHg), AC (-15/8mg/dl),
WC (-7/5cm), Weight (-16/14kg)
DASH diet can likely reduce most of the metabolic
risks in both men and women
Diabetes Care 2005; 28:2823-31


Slide 64

Other Conditions


Prothrombotic state- low-dose aspirin for
2nd prevention; in 1st prevention, lowered
the risk of stroke in women (N Engl J Med
2005; 352:1293-304), reduction in the risk
of myocardial infarction in men (N Engl J
Med 1989; 321:129–35); DM/MetS



Proinflammatory state- agents to treat other
metabolic risk factors, like statins, nicotinic
acid, fibrates, ACEIs, TZDs
Circulation 2005;112: 285-90


Slide 65

Summary
The metabolic syndrome is a clustering
of amendable risk factors for CVD and
diabetes
 The cornerstone of treatment is TLC,
which stresses on a moderate reduction
of body weight and waist circumference
 Multifaceted drug treatment is indicated
when TLC is not enough



Slide 66

丹麥-最快樂的國家
《禮記》中的大同
世界,在丹麥實現
丹麥人富裕,人
均國民所得三萬四
千六百美元,全球
國家中排名第七。
平均月薪合新台幣
十八萬元,是台灣
的四.七倍,即便
送報生都能拿到月
薪新台幣十幾萬元。
這是一個幾乎沒有
窮人的國家。