DISLIPIDEMIA
SINDROMA METABOLIK
Dr. M a h a t m a SpPD
Fak.Kedokteran UMS
SURAKARTA
Cholesterol balance
Extrahepatic
Organs
LDL
IDL
Cholesterol
Synthesis
900 mg/day
Cholesterol
Synthesis
Transport
via HDL & LDL
VLDL
Dietary
Cholesterol
300 mg/day
25%
Biliary
Cholesterol
75%
Chylomicron transport
50% intestinal
Cholesterol absorbed
Faecal sterols
50% cholesterol
excreted
Triglyceride-rich lipoproteins:
size, structure and composition
5/2/2013
HDL metabolism
Inhibits oxidation
of LDLs
HDL
Inhibits
tissue factor
Inhibits endothelial
adhesion molecules
Stimulates
endothelial NO
production
Enhances reverse
cholesterol transport
Opposes atherothrombosis
Potential mechanisms by which HDLs oppose atherothrombosis.
(Barter. EMCNA (2004):398)
LDL metabolism
Definition
Obesity is caused by imbalance of high
Food intake and or low energy expenditure
Classification of Overweight
and Obesity (WHO,2004)
BMI
Waist Circumference
Eropa
Asia
> 30 kg/m2
> 25 kg/m2
> 90
> 102
> 80 cm
> 90 cm
BMI
Classification
<18.5
Underweight
18.5-24.9
Normal weight
25-29.9
Overweight
30-34.9
Obesity Class I
35-39.9
Obesity Class II
40-49.9
Obesity Class III
50 and above Super Obesity
PATOGENESIS OBESITAS
Faktor genetik :
Parental fatness
7 gen penyebab : - Leptin receptor
- Melanocortin receptor 4
- Alpha-melanocyte stimulating hormone
- Prohormone convertase 1
- Leptin
- Bardert-Biedl
- Dunnigan partial lypodystrophy
Faktor Lingkungan :
- Nutrisional
- Medikasi
Banyak gerak
25 tahun
Hidup santai
50 tahun
Kegemukan (Obesitas)
Android/ central
Gemuk tidak sehat
Ginekoid/ trunkal
Gemuk sehat
16
AKUPUNTUR
Hipertensi
Diabetes
Kolesterol HDL
Trigliserid
Jantung
koroner
19
LIFESTYLE
LIPO SUCTION
LIPOTRIPSY
BYPASS
SURGERYBYPASS
SURGERY
Surgery
5/2/2013
Medical Complications of
Obesity
Pulmonary disease
abnormal function
obstructive sleep apnea
hypoventilation syndrome
Stroke
Cataracts
CHD
Diabetes
Dyslipidemia
Hypertension
Severe pancreatitis
Gynecologic abnormalities
Cancer
abnormal menses
infertility
Osteoarthritis
PCOS
Phlebitis
Gout
venous stasis
Dyslipidemia
Kelainan metabolisme lipid, ditandai
dengan peningkatan serta penurunan
fraksi lipid plasma
TRIAD LIPID
Kol-total/ kol-LDL
Trigliserid (TG)
Kol-HDL.
KLASIFIKASI DISLIPIDEMIA
DISLIPIDEMIA PRIMER
- kelainan pada ensim atau apoprotein
- bersifat genetik
DISLIPIDEMIA SEKUNDER
Secondary Dislipidemi
Pathological states
Diabetes
Hypothyroidism
Cushings syndrome
Nephrotic syndrome
Chronic renal failure
Monoclonal gammapathy
Obstructive liver disease
Lifestyle habits
Obesity
Alcohol
Stress
Merokok
Drugs
Oral estrogens
Progestins
Anabolic steroids
Corticosteroids
Retinoids, such as isotretinoin
Sertraline hydrochloride
ARV protease inhibitors
Non-selective -adrenergic
inhibitor
Cyclosporine
Thiazide diuretics
Dyslipidemia Major of
Atherogenicity
Non modifiable risk factors : Age, gender, family
5/2/2013
MONOSIT
LDL
LUMEN
Glukose
fibrinolisis
agregasi tr.
DM
tissue factor
S
LDL
kecil
S S
i i
PAI-1
PLAQUE
PLAQUE
LDL
ox
Hiperinsulin
SEL BUSA
Radikal
Bebas.
AGEs
INTIMA
Migrasi
Makrofag
Sitokin+ f. pertumbuhan
MEDIA
Proliferasi
SS
PENATALAKSANAAN DISLIPIDEMIA
Target Lipid
Non-farmakologik :
- Life style obesitas
- Terapi nutrisi
- Batasi minuman
beralkohol
- Hindari merokok
Farmakologik :
- obat hipolipidemik
Kolesterol Total
< 200
200 239
240
Kolesterol LDL
< 100
100 129
130 159
160 189
190
Kolesterol HDL
< 40
> 60
Trigliserida
< 150
150 199
200 499
500
yg diinginkan
batas tinggi
tinggi
optimal
di atas optimal
batas tinggi
tinggi
sangat tinggi
rendah
tinggi
normal
batas tinggi
tinggi
sangat tinggi
European
1994
European
2003
European
1998
ATP II
1993
ATP III
2001
ATP III
update
2004
Relative Risk
1%
decrease
in LDL-C
reduces
CHD risk
by 1%1
30
20
25
10
45
85
100
160
85
220
LDL-C (mg/dL)
Update
ATP III
Update 20041
2001
<100 mg/dL:
Patients with
CHD or CHD risk
equivalents
(10-year risk >20%)1
<70 mg/dL:
Therapeutic
option for very
high-risk patients1
<100 mg/dL
<70 mg/dL
AHA/ACC guidelines
for patients with
CHD*,2
2006
Update
<100 mg/dL:
Goal for all
patients with CHD,2
<70 mg/dL:
A reasonable
goal for all patients
with CHD,2
1.
2.
3.
4.
5.
6.
Obat baru :
- NIACIN extended release (NIASPAN)
- Fix kombinasi NIACIN ER + LOVASTATIN (advicor)
LDL
IDL
Cholesterol
Synthesis
900 mg/day
Cholesterol
Synthesis
Transport
via HDL & LDL
VLDL
Biliary
Cholesterol
75%
Chylomicron transport
50% intestinal
Cholesterol absorbed
Statins
Ezetimibe
Dietary
Cholesterol
300 mg/day
25%
Plant stanols
Faecal sterols
50% cholesterol
excreted
Resins
FIBRATES
gemfibrozil, fenofibrates
Glitazones
Eicosanoids
PPAR
PPAR
Nucleus
PPAR
AGGTCA
- Activated PPAR
- Retinoid R
AGGTCA
PPRE
NAMA OBAT
KONTRA INDIKASI
Lovastatin
Pravastatin
Simvastatin
Fluvastatin
Atorvastatin
Rosuvastatin
LDL 18-55%
HDL 5-30%
Trigliserid 7-30%
LDL 15-20%
HDL 1-4%
Trigliserid 5-10%
LDL 15-30%
HDL 3-5%
Trigliserid sqa
Disbetaliproteinemia
Trigliserid > 400 mg/dl
LDL 5-25%
HDL 15-35%
Trigliserid 20-50%
Ezetimibe
Cholestyramin
Colestipol
Colesevalam
Nicotinic acid
Gemfibrozil
Fenofibrate
The NECP ATP III & Physicians Desk Ref, 59th ed. 2005
Dosis
Gol. Statin
- Fluvastatin
- Lovastatin
- Pravastatin
- Simvastatin
40 80 mg malam hari
5 40 mg malam hari
5 40 mg malam hari
5 40 mg malam hari
- Atorvastatin
10 80 mg malam hari
-Rosuvastatin
10 40 mg malam hari
Fenofibrat
Gemfibrozil
Insulin resistance
IV
III
glycemic disorders
( Prediabetes )
<< HDL , >> LDL
Hypertriglyceridemia
Hypertension
Endothel Disfunction
Hiperuricemia
Microalbuminuria
inflammation (hsCRP)
Impaired thrombolysis
PAI-1
DIABETES MELLITUS
HIPERTENSI
P C O S dan NAFLD
HIPERURICEMIA
DISLIPIDEMIA
ATHEROSCLEROSIS
ACANTHOSIS NIGRICANS
II
VI
Central Obesity
JARANG OLAHRAGA
PENUAAN
OBAT OBATAN
SEBAB LAIN
VII
STROKE
CHD
ADIPOCYTE
WEIGHT GAIN
WEIGHT GAIN
IR
JNK
NFB
TNF-
Endothelial
Cell
PREADIPOCYTE
MCP-1
Leptin
VEGF
IL-6
IL-1
TNF-
Angiogenesis
Physical stress/oxidative
damage to endothelium?
FFA
MCP-1
MACROPHAGE
RECRUITMENT
MACROPHAGE PREADIPOCYTE
NORMAL ADIPOCYTE
ADIPOCYTE DYSFUNCTION
ASK-DNC
MACROPHAGE
RECRUITMENT
Autocrine
Paracrine
Endocrine
Leptin
PAI-1
TGF-
?TNF
?IL-6
TF
Sex steroids
Glucocorticoids
Adipsin/ASP
?TNF- /IL-6/Leptin
?Angiotensin
Renin-Angiotensin
system
Steroid hormones
?PAI-1
Adipose tissue
?Adiponectin
?AdipoQ
ESTROGEN
16.
2.
17.
13.
LEPTIN
AGOUTI RELATED PROTEIN
TNF
IL1B
IL-6
ANGITENSINOGEN
ASP
ADIPSIN
FACTORS B,C3
ADHESIVE PROTEIN
PAI-1
TF
14.
RESISTIN
29.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
15.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
30.
VISFATIN
HSL
LIPOTRANSIN
PERILIPINS
FFAs
TGF-
VEGF
IGF-1
PGE2
PGI1
GLUCOCORTICOID
11HSD
AROMATASE
METALLOTHIONIEN
MIF
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
45.
RBP
APO-E
ICAL
LPL
CETP
PLTP
NO
PC-1
AQUAPORINS
FIAF
LACTATE
MONOBUTYRIN
GALACTIN-12
ESM-1
APELIN
ADIPONECTIN
patofisiologi
ANTI INSULIN RESISTANCE
ANTI ATHEROSCLEROSIS
1 TISSUE TG CONTENT
1 ENDOTHELIUM
THE Expression of Adhesion Mol. :
2 UPREGULATE INSULIN
SIGNALING
ACTIVATE PPAR
ACTIVATE AMPK
5 ROLES OF
ADIPONECTIN
2 MACROPHAGE
SRA- 1
Uptake of Ox-LDL, Foam Cell
SMC :
Cell Proliferation
Migration
IV
III
APOPTOSIS
ANTI INFLAMMATION
ANTI OXIDANT
INFLAMMATORY MARKERS
OXIDATIVE STRESS
5/2/2013
WHO
AACE (IRS)
EGIR (IRS)
IGT/HOMA-IR,
IFG/DM and
2 of 4 below
One of **
And 2 of 4
2 of 4
At least 3 of 5
Uirinary alb exc
> 20 g / m
WHR
90 in men
85 in women
male
female
94 cm
80 cm
Waist CF male
female
>102 cm
> 88 cm
Triglycerides
150 mg/dl
150 mg/dl or
150 mg/dl or
2.0 mmol/l or
40 mg/dl
50 mg/dl
35 mg/dl
39 mg/dl
40 mg/dl
50 mg/dl
1.0 mmol/l
Blood pressure
130/8 5mmHg
140/90 mmHg
130/85 mmHg
140/90 mmHg or
treated for Hyp.
Blood glucose
110 mg/dl
FBG 110-125 or
2hpc 140-200
** CVD, hypertension, PCOS, NAFLD, family history of T2DM / hypertension / CVD, history of
gestational diabetes, non Caucasian, sedentary lifestyle, BMI>125 or WC>40 male, >35 female,
age>40yrs
WC male 90 cm
and female 80 cm
1. Fasting Glucose
3. Triglyceride
4. HDL-Chol
2. Blood Pressure
> 130/85 mmHg
Lose weight Losing as little as 5 to 10% of your body weight can reduce insulin levels thus reducing M S
Exercise
Walking just 30 minutes a day can help prevent the serious diseases associated with MS.
Stop smoking Cigarettes increases insulin resistance and worsens health consequences with MS.
Eat fiber
Whole grains, beans, fruits and vegetables, important to lower insulin levels.
Weight loss
drugs
Insulin
sensitizers
Aspirin
Medications to
lower blood
pressure
Medications to
regulate
cholesterol
statins
Pleitropic effect
Definisi
O B E S ITAS
DISLIPIDEMI
SINDROMA
METABOLIK
( pre sakit )
Dx
Terapi
Komplikasi
Cancer, CHD
Hipertensi
Dislipidemia
OsteoArthritis
D M, PCOS
Sleep Apneu
Obesity H S
Gout, Gallstone
Akumulasi FAT di
Jaringan Lemak
berlebihan, baik
Besar dan jumlahnya
BMI
WC
Exercise, Diet
Orlistat
Sibutramine
Akupunktur
Lipotripsy
Liposuction
Surgery
Kelainan
Metabolisme
LIPID
TG
CH
LDL
HDL
Exercise, Diet
STATIN
Ezetimibe
Fibrat, Niacin
Nicotinic
ATHERO
SCLEROSIS
Yang dipercepat
CHD
SNH
KUMPULAN GEJALA
YANG DISEBABKAN
OLEH KARENA
RESISTENSI INSULIN.
DAN...........
RESISTENSI INSULIN
KARENA
OBESITAS SENTRAL
TG
CH
LDL
HDL
WC
AU
GDP
Alb
Tensi
Exercise, Diet
STATIN
Metformin
Glitazone
CCB,BB
ACE Inhibitor
Sibutramine
Orlistat
Allopurinol
Aspilet
CHD
Hipertensi
Dislipidemia
DM
SNH
PCOS, Gout
Gallstone
NAFL
Acanthosis
nigricans
Closing Remark
60