OBESITASOBESITAS
PUGUD SAMODROPUGUD SAMODROSUB BAGIAN ENDOKRIN METABOLIKSUB BAGIAN ENDOKRIN METABOLIK
BAGIAN ILMU PENYAKIT DALAMBAGIAN ILMU PENYAKIT DALAMFKIKFKIK UNSOED/RSUD Prof. Dr. MARGONO UNSOED/RSUD Prof. Dr. MARGONO SOEKARJOSOEKARJO
PURWOKERTOPURWOKERTO
PendahuluanPendahuluan Obesitas asal kata ob = akibat dariObesitas asal kata ob = akibat dari esum = makanesum = makan obesitas = akibat dari makanobesitas = akibat dari makan Definisi obesitas :Definisi obesitas : suatu keadaan dimana ditemukan adanya suatu keadaan dimana ditemukan adanya
kelebihan lemak dalam tubuhkelebihan lemak dalam tubuh Obesitas ~ indeks massa tubuh (IMT)Obesitas ~ indeks massa tubuh (IMT)
Proyeksi Peningkatan Prevalensi Obesitas
05
101520253035404550
1960 1965 1970 1975 1980 1985 1990 1995 2000 2005 2010 2015 2020 2025 2030
Population percentageWith BMI 30 kg/m2
USA
AustraliaEngland
Mauritius
Brazil
Source : IOTF unpublished
Energy Production and Energy Balance
Carbohydrate
Fat
Basal metabolism
Thermic effectof food
Protein
Physicalactivity
Adaptivethermogenesis
PENYEBAB OBESITASMasukan makanan meningkat tajam : makanan tidak sehat (junk food) banyak tersedia, harganya murah, rasanya enak dan didukung iklan yang menarik
Kurangnya aktivitas fisik : baik dalam bekerja maupun bermain, aktivitas fisik semakin berkurang
MENGAPA OBESITAS MENGAPA OBESITAS DIPERMASALAHKAN ??DIPERMASALAHKAN ??
Meningkatkan morbiditas dan mortalitasMeningkatkan morbiditas dan mortalitas Penyakit Jantung Koroner (PJK)Penyakit Jantung Koroner (PJK) HipertensiHipertensi Diabetes Tipe 2Diabetes Tipe 2 KankerKanker OsteorthritisOsteorthritis Gout (Rematik Asam Urat), dllGout (Rematik Asam Urat), dll
Menimbulkan masalah sosial : kurang PDMenimbulkan masalah sosial : kurang PD
Medical Complications of ObesityMedical Complications of Obesity
Coronary heart disease
Pulmonary disease:Abnormal PFTsObstructive sleep apneaHypoventilation syndrome
Gall bladder disease
Gynecological abnormalities:Abnormal mensesInfertilityPCOS
Gout
Stroke
Diabetes
Osteoarthritis
Cancer:Breast, uterus, cervixColon, esophagus, pancreasKidneyProstate
Liver disease:SteatosisNASHCirrhosis Hypertension
Dyslipidemia
Phlebitis
Cataracts
Skin
Borrowed from S. Klein
Medical Complications of ObesityMedical Complications of Obesity
Coronary heart disease
Pulmonary disease:Abnormal PFTsObstructive sleep apneaHypoventilation syndrome
Gall bladder disease
Gynecological abnormalities:Abnormal mensesInfertilityPCOS
Gout
Stroke
Diabetes
Osteoarthritis
Cancer:Breast, uterus, cervixColon, esophagus, pancreasKidneyProstate
Liver disease:SteatosisNASHCirrhosis Hypertension
Dyslipidemia
Phlebitis
Cataracts
Skin
Borrowed from S. Klein
DiagnosisDiagnosis IMT = IMT = BB (Kg)BB (Kg) TB (mTB (m22)) Klasifikasi BB WHO 1998 (orang Eropa/USA)Klasifikasi BB WHO 1998 (orang Eropa/USA) WHO 2000 (orang Asia)WHO 2000 (orang Asia) Klasifikasi berdasar distribusi lemak :Klasifikasi berdasar distribusi lemak : 1. ginekoid ( lemak >> tu bag bawah tubuh/gluteus)1. ginekoid ( lemak >> tu bag bawah tubuh/gluteus) 2. android (obesitas sentral/visceral) 2. android (obesitas sentral/visceral) lemak >> tu bag perutlemak >> tu bag perut berhub erat risiko penyakit kardiovaskulerberhub erat risiko penyakit kardiovaskuler (sindroma metabolik) (sindroma metabolik)
Insulin ResistanceLiver
Muscle
Adiposetissue FPG
IFG
Hyperglicaemia
Pancreas
FFA
HDL
Hypertension
TG
Atherosclerosis
Compensation NGT
IGTDecompensation I
DMHyperinsulinemiaHyperinsulinemia Decompensation II
GeneticFetal malnutrition
Hyperinsulinaemia
GeneticEnvirontment
Obesity
SHK, Sept 2006
Obesitas sentralObesitas sentral Diukur dgn : - CT scanDiukur dgn : - CT scan - MRI- MRI - lingkar pinggang (waist circum- lingkar pinggang (waist circum ference)ference) pria > 90 cm,wanita > 80 cmpria > 90 cm,wanita > 80 cm ( Asia )( Asia )
UKURAN LINGKAR PINGGANG
. . . . . .
cm
. . . . . cm
< 80 cm normal > 80 cm risiko tinggi
< 90 cm normal > 90cm risiko tinggi
Obesitas Sentral lebih berbahaya daripada Obesitas Perifer risiko penyakit lebih tinggi
PENTING !!Lingkar Pinggang >>>menimbulkan berbagai masalah kesehatan karena :• bertambahnya IMT• distribusi lemak sentral (Obesitas Sentral)
Subcutaneous fat
Abdominal muscle layer
Intra-abdominal fat
Abdominal Adiposity:Abdominal Adiposity:The Critical Adipose DepotThe Critical Adipose Depot
M. Davidson, MD.
Is this correct?
PENGUKURAN LINGKAR PINGGANG/PERUT
TULANG RUSUK PALING BAWAH
TULANG PANGGUL
Central AdiposityCentral Adiposity
Global Global cardiometabolic riskcardiometabolic risk
Klasifikasi BB utk orang Eropa Klasifikasi BB utk orang Eropa (WHO 1998)(WHO 1998)
Klasifikasi IMT (kg/mKlasifikasi IMT (kg/m22) Risiko morbiditas) Risiko morbiditasKurus <18,5 rendahKurus <18,5 rendahNormal 18,5-24,9 sedangNormal 18,5-24,9 sedangKegemukan Kegemukan >> 25 25 pre-obes 25-29,9 meningkatpre-obes 25-29,9 meningkat obes I 30-34,9 sedangobes I 30-34,9 sedang obes II 35-39,9 beratobes II 35-39,9 berat obes III obes III >> 40 sangat berat 40 sangat beratWHO Obesity : Preventing and Managing the Global Epidemic, Geneva, WHO Obesity : Preventing and Managing the Global Epidemic, Geneva,
WHO 1998.WHO 1998.
Klasifikasi BB utk orang Asia Klasifikasi BB utk orang Asia (WHO 2000)(WHO 2000)
Klasifikasi IMT (kg/mKlasifikasi IMT (kg/m22) Risiko morbiditas) Risiko morbiditasKurus <18,5 rendahKurus <18,5 rendahNormal 18,5-22,9 sedangNormal 18,5-22,9 sedangKegemukan Kegemukan >> 23 23 pre-obes 23-24,9 meningkatpre-obes 23-24,9 meningkat obes I 25-29,9 sedangobes I 25-29,9 sedang obes II > 30 beratobes II > 30 berat The Asia Pasific Perspective. Redifining Obesity and its treatment, 2000The Asia Pasific Perspective. Redifining Obesity and its treatment, 2000
Penanganan obesitas berdasarkan Penanganan obesitas berdasarkan IMTIMT
nilai IMT pengobatannilai IMT pengobatan18,5-24,9 tidak diterapi, hanya diet & OR18,5-24,9 tidak diterapi, hanya diet & OR25-29,9 diet rendah kalori & OR25-29,9 diet rendah kalori & ORTanpa komorbid Tanpa komorbid 25-29,9 obat-obatan,diet hipokalori,OR25-29,9 obat-obatan,diet hipokalori,ORDgn komorbidDgn komorbid30-39,9 obat-obatan dan behaviour mo-30-39,9 obat-obatan dan behaviour mo- dificationdification>> 40 bedah bila obat-obatan gagal 40 bedah bila obat-obatan gagal
Faktor – faktor komorbidFaktor – faktor komorbid HipertensiHipertensi Penyakit kardivaskulerPenyakit kardivaskuler DislipidemiaDislipidemia HiperinsulinemiaHiperinsulinemia DM tipe 2DM tipe 2 Sleep apnea / obesity hypoventilation syndromeSleep apnea / obesity hypoventilation syndrome OsteoartritisOsteoartritis InfertilitasInfertilitas Kondisi lain : GERD, inkontinensi urin tipe stres,lo-Kondisi lain : GERD, inkontinensi urin tipe stres,lo- wer extremity venous stasis diseasewer extremity venous stasis disease
Clinical Clinical MeasureMeasure
WHOWHO(1998)(1998)
EGIREGIR(1999)(1999)
ATP IIIATP III(2001)(2001)
AACEAACE(2003)(2003)
IDFIDF(2005)(2005)
Insulin Insulin ResistanceResistance
IGT,IFG,T2DM or IGT,IFG,T2DM or Lower insulin sensitivityLower insulin sensitivity
Plus any 2 of the followingPlus any 2 of the following
Plasma Insulin Plasma Insulin > 75> 75thth percentile percentilePlus any 2 of the Plus any 2 of the
followingfollowing
None, But any 3 ofNone, But any 3 of the following 5 the following 5
FeaturesFeatures
IGT or IFG plus any IGT or IFG plus any of following based onof following based on
clinical judgementclinical judgement
NoneNone
Body Body WeightWeight
Men : WHR > 0.90Men : WHR > 0.90Women : WHR > 0.85Women : WHR > 0.85
And/or BMI > 30 kg/mAnd/or BMI > 30 kg/m22
WC WC >>94 cm in men94 cm in menOrOr
>>80 cm in women80 cm in women
WC WC >> 102 cm in men 102 cm in menOrOr
>> 88 cm in women 88 cm in women
BMI BMI >> 25 kg/m 25 kg/m22 Increase WC Increase WC (population specific)(population specific)Plus any 2 of the Plus any 2 of the followingfollowing
LipidLipid TG> 150 mg/.dl or TG> 150 mg/.dl or HDL-C<35 mg/dl in menHDL-C<35 mg/dl in menOr < 39 mg/dl in womenOr < 39 mg/dl in women
TG TG >>150 mg/dl & 150 mg/dl & oror
HDL-C < 39 mg/dlHDL-C < 39 mg/dlIn men or womenIn men or women
TG> 150 mg/.dl or TG> 150 mg/.dl or HDL-C<40 mg/dl in menHDL-C<40 mg/dl in menOr < 50 mg/dl in womenOr < 50 mg/dl in women
TG> 150 mg/.dl or TG> 150 mg/.dl or HDL-C<40 mg/dl in HDL-C<40 mg/dl in
menmenOr < 50 mg/dl in Or < 50 mg/dl in
womenwomen
TG> 150 mg/.dl or TG> 150 mg/.dl or HDL-C<40 mg/dl in menHDL-C<40 mg/dl in menOr < 50 mg/dl in womenOr < 50 mg/dl in women
Blood Blood PressurePressure
>> 140/90 mmHg 140/90 mmHg >> 140/90 mmHg 140/90 mmHg or non hypertensionor non hypertension
>> 130/85 mmHg 130/85 mmHg 130/85 mmHg130/85 mmHg >> 130 mmHg systolic or 130 mmHg systolic or >> 85 mmHg diastolic or 85 mmHg diastolic orNon hypertention RxNon hypertention Rx
GlucoseGlucose IGT, IFG or T2DMIGT, IFG or T2DM IGT or IFGIGT or IFG(but not diabetes)(but not diabetes)
> 110 mg/dl> 110 mg/dl(Include diabetes)(Include diabetes)
FPG FPG >>110 mg/dl (2001)110 mg/dl (2001)FPG FPG >> 100 mg/dl (2004) 100 mg/dl (2004)
IGT or IFGIGT or IFG(but not diabetes)(but not diabetes)
> 100 mg/dl> 100 mg/dl(include diabetes) (include diabetes)
OtherOther MicroalbuminuriaMicroalbuminuria Other features of Other features of Insulin resistanceInsulin resistance
(PCOS,T2DM etc)(PCOS,T2DM etc)
Previous Criteria Proposed for Clinical Diagnosis ofMetabolic Syndrome
(Grundy et al, 2005)
2323
IDF Definitionof MetS
• Present of Visceral obesity (men ≥ 90 cm, women ≥ 80 cm – WC).-
• And at least 2 of the following :- FPG ≥ 100 mg/dl (or T2DM).-- TG ≥ 150 mg/dl.-- HDL-C < 40 mg (men), <50mg (women).-- BP ≥ 130 systolic or ≥ 85 diastolic.-
2424
High waist grith → Visceral obesity → Metabolic Syndrome
Metabolic Syndrome
Inflammation & thrombosis markers :hsCRPCytokines (TNF, IL-6) PAI-1Fibrinogen
Glucose-insulin homeostasis :Insulin resistanceHyperinsulinemiaHyperglycemiaIGT/IFG
Lipoprotein-lipid profile:TriglyceridesHDL-colesterolapo BSmall, dense LDLPostprandial hyperlipidemia
front
back
JARINGAN ADIPOSA/JARINGAN LEMAKJARINGAN ADIPOSA/JARINGAN LEMAK
tempat menyimpantempat menyimpan kelebihan energikelebihan energi
mengeluarkan berbagai mengeluarkan berbagai protein yang disebutprotein yang disebut
ADIPOSITOKINADIPOSITOKIN yang berfungsiyang berfungsi mengaturmengatur keseimbangankeseimbangan energienergi
JARINGAN ADIPOSA
SEL ADIPOSIT
AdipocytokinesAdipocytokines
Factors Released From Factors Released From AdipocytesAdipocytes
2828
Adiponectin(AdipoQ, Acrp30, GBP28)
• Adiponectin merupakan adipositokin yang secara ekslusif diproduksi oleh sel adiposit.-
• Adiponectin memiliki efek yang baik karena terlibat dalam mempertahankan keseimbangan metabolisme gula dan lemak, meningkatkan sensitivitas insulin dan menurunkan inflamasi
Adiponectin
InsulinSensitivity
↓ FFA Influx
↓ VascularInflammation↓ Glucose ↓ TG
InsulinSensitivity
FFA Oxidation
AdiposeTissue
FFA Oxidation
↓ TG
(Ouchi N, et al, Curr Opin in Lipidol 2003)
KERJA ADIPONEKTINKERJA ADIPONEKTIN
3030
Inflammation
CVD T2DM
ADIPONECTIN
Adiponectin Hypothesis for insulin resistance, the metabolic syndrome, and atherosclerosis
J Clin Invest, 2006.-
Hypoadiponectinemia
Insulin Resistance
ATHEROSCLEROSIS
Metabolic Syndrome
Genetic factorAdiponectin gene
polymorphism
Lifestyle ChangesHigh-fat Diet,
Sedentary Lifestyle
Hyperlipidemia HypertensionT2DM
Obesity promotes the parallel progression of insulin resistance to type 2 diabetes and endothelial
dysfunction to atherosclerosis
Endocrin, 2003.-
InsulinResistance
MetabolicSyndrome
Impaired GlucoseTolerance
Type 2Diabetes Atherosclerosis
Atherosclerosis
Atherosclerosis
EndothelialDysfunction
Visceral Adiposity
Proinflammatorymileu
Adiponectin
3333
Visceral FatAccumulation
T2DM
Hypertension
Atherosclerosis
CHF
NASHCancers
Genetic Variations
MetS ADIPONECTIN
Conclusion :
Obat-obatanObat-obatan OrlistatOrlistat hambat enzim lipase (absorbsi lemak)hambat enzim lipase (absorbsi lemak) MazindolMazindol hambat sinapsis reuptake norepinefrin & dopahambat sinapsis reuptake norepinefrin & dopa minmin Dietil propionDietil propion Leptin rekombinanLeptin rekombinan Terapi gen masa depanTerapi gen masa depan
Terimakasih Terimakasih
Terima kasih
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