OBESITAS

SUB BAGIAN ENDOKRIN METABOLIK BAGIAN ILMU PENYAKIT DALAM FKIK UNSOED/RSUD Prof. Dr. MARGONO SOEKARJO PURWOKERTO

PUGUD SAMODRO

Pendahuluan

ob = akibat dari esum = makan obesitas = akibat dari makan Definisi obesitas : suatu keadaan dimana ditemukan adanya kelebihan lemak dalam tubuh Obesitas ~ indeks massa tubuh (IMT)

Obesitas asal kata

Proyeksi Peningkatan Prevalensi Obesitas

USA Australia England Mauritius
50 45 40 35 30 25 20 15 10 5 0
1990 1995 2000 2005 2010 2015 2020 2025 2030

Population percentage With BMI 30 kg/m2

Brazil

1960

1965

1970

1975

1980

1985

Source : IOTF unpublished

PENYEBAB OBESITAS
Masukan 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 DIPERMASALAHKAN ??

Meningkatkan morbiditas dan mortalitas

Penyakit Jantung Koroner (PJK) Hipertensi Diabetes Tipe 2 Kanker Osteorthritis Gout (Rematik Asam Urat), dll

Menimbulkan masalah sosial : kurang PD

Medical Complications of Obesity

Pulmonary disease: Abnormal PFTs Obstructive sleep apnea Hypoventilation syndrome Liver disease: Steatosis NASH Cirrhosis Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension

Gall bladder disease

Gynecological abnormalities: Abnormal menses Infertility PCOS Osteoarthritis Skin Cancer: Breast, uterus, cervix Colon, esophagus, pancreas Kidney Prostate Phlebitis
Borrowed from S. Klein

Gout

Medical Complications of Obesity

Pulmonary disease: Abnormal PFTs Obstructive sleep apnea Hypoventilation syndrome Liver disease: Steatosis NASH Cirrhosis Stroke Cataracts Coronary heart disease Diabetes Dyslipidemia Hypertension

Gall bladder disease

Gynecological abnormalities: Abnormal menses Infertility PCOS Osteoarthritis Skin Cancer: Breast, uterus, cervix Colon, esophagus, pancreas Kidney Prostate Phlebitis
Borrowed from S. Klein

Gout

Diagnosis

IMT = BB (Kg) TB (m2) Klasifikasi BB WHO 1998 (orang Eropa/USA) WHO 2000 (orang Asia) Klasifikasi berdasar distribusi lemak : 1. ginekoid ( lemak >> tu bag bawah tubuh/gluteus) 2. android (obesitas sentral/visceral) lemak >> tu bag perut berhub erat risiko penyakit kardiovaskuler (sindroma metabolik)

Genetic Environtment Genetic Fetal malnutrition

Obesity
Insulin Resistance
Liver Muscle

Hyperglicaemia

Pancreas
Adipose tissue

Hyperinsulinaemia

FFA TG HDL

FPG

IFG
Atherosclerosis

Hypertension
Compensation Hyperinsulinemia
SHK, Sept 2006

NGT IGT DM

Decompensation I Decompensation II

Hyperinsulinemia

Obesitas sentral

Diukur dgn : - CT scan - MRI - lingkar pinggang (waist circum ference) pria > 90 cm,wanita > 80 cm ( Asia )

UKURAN LINGKAR PINGGANG

PENTING !!
Lingkar Pinggang >>> menimbulkan berbagai masalah kesehatan karena : bertambahnya IMT distribusi lemak sentral (Obesitas Sentral)

cm

.. ... .

< 80 cm normal > 80 cm risiko tinggi < 90 cm normal > 90cm risiko tinggi

cm

.....

Obesitas Sentral lebih berbahaya daripada Obesitas Perifer risiko penyakit lebih tinggi

Abdominal Adiposity: The Critical Adipose Depot

Subcutaneous fat Abdominal muscle layer Intra-abdominal fat

Is this correct?
M. Davidson, MD.

PENGUKURAN LINGKAR PINGGANG/PERUT

TULANG RUSUK PALING BAWAH TULANG PANGGUL

Central Adiposity

Global cardiometabolic risk

Klasifikasi BB utk orang Eropa (WHO 1998)

Klasifikasi Kurus Normal Kegemukan pre-obes obes I obes II obes III IMT (kg/m2) <18,5 18,5-24,9 > 25 25-29,9 30-34,9 35-39,9 > 40 Risiko morbiditas rendah sedang

meningkat sedang berat sangat berat

WHO Obesity : Preventing and Managing the Global Epidemic, Geneva, WHO 1998.

Klasifikasi BB utk orang Asia (WHO 2000)

Klasifikasi Kurus Normal Kegemukan pre-obes obes I obes II IMT (kg/m2) <18,5 18,5-22,9 > 23 23-24,9 25-29,9 > 30 Risiko morbiditas rendah sedang meningkat sedang berat

The Asia Pasific Perspective. Redifining Obesity and its treatment, 2000

Penanganan obesitas berdasarkan IMT

nilai IMT 18,5-24,9 25-29,9 Tanpa komorbid 25-29,9 Dgn komorbid 30-39,9 > 40 pengobatan tidak diterapi, hanya diet & OR diet rendah kalori & OR

obat-obatan,diet hipokalori,OR
obat-obatan dan behaviour modification bedah bila obat-obatan gagal

Faktor faktor komorbid

Hipertensi Penyakit kardivaskuler Dislipidemia Hiperinsulinemia DM tipe 2 Sleep apnea / obesity hypoventilation syndrome Osteoartritis Infertilitas Kondisi lain : GERD, inkontinensi urin tipe stres,lower extremity venous stasis disease

Previous Criteria Proposed for Clinical Diagnosis of Metabolic Syndrome

Clinical Measure
Insulin Resistance Body Weight

WHO (1998)
IGT,IFG,T2DM or Lower insulin sensitivity Plus any 2 of the following Men : WHR > 0.90 Women : WHR > 0.85 And/or BMI > 30 kg/m2

EGIR (1999)
Plasma Insulin > 75th percentile Plus any 2 of the following WC >94 cm in men Or >80 cm in women

ATP III (2001)

None, But any 3 of the following 5 Features WC > 102 cm in men Or > 88 cm in women

AACE (2003)
IGT or IFG plus any of following based on clinical judgement BMI > 25 kg/m2 None

IDF (2005)

Increase WC (population specific) Plus any 2 of the following

Lipid

TG> 150 mg/.dl or HDL-C<35 mg/dl in men Or < 39 mg/dl in women

TG >150 mg/dl & or HDL-C < 39 mg/dl In men or women

> 140/90 mmHg or non hypertension IGT or IFG (but not diabetes)

TG> 150 mg/.dl or HDL-C<40 mg/dl in men Or < 50 mg/dl in women

TG> 150 mg/.dl or HDL-C<40 mg/dl in men Or < 50 mg/dl in women

130/85 mmHg

TG> 150 mg/.dl or HDL-C<40 mg/dl in men Or < 50 mg/dl in women

Blood Pressure Glucose

> 140/90 mmHg

> 130/85 mmHg

> 130 mmHg systolic or > 85 mmHg diastolic or Non hypertention Rx > 100 mg/dl (include diabetes)

IGT, IFG or T2DM

Other

Microalbuminuria

> 110 mg/dl (Include diabetes) FPG >110 mg/dl (2001) FPG > 100 mg/dl (2004)

IGT or IFG (but not diabetes)

Other features of Insulin resistance (PCOS,T2DM etc)

(Grundy et al, 2005)

IDF Definition of 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.23

Metabolic Syndrome
front
Glucose-insulin homeostasis :
Insulin resistance Hyperinsulinemia Hyperglycemia IGT/IFG

Lipoprotein-lipid profile:

Triglycerides HDL-colesterol apo B Small, dense LDL Postprandial hyperlipidemia

Inflammation & thrombosis markers :

back

hsCRP Cytokines (TNF, IL-6) PAI-1 Fibrinogen

High waist grith Visceral obesity Metabolic Syndrome

24

JARINGAN ADIPOSA/JARINGAN LEMAK

tempat menyimpan kelebihan energi mengeluarkan berbagai protein yang disebut ADIPOSITOKIN yang berfungsi mengatur keseimbangan energi

JARINGAN ADIPOSA

SEL ADIPOSIT

Adipocytokines

Factors Released From Adipocytes

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
28

KERJA ADIPONEKTIN
Adipose Tissue

Adiponectin

FFA Oxidation TG

FFA Influx

FFA Oxidation

Insulin Sensitivity

Glucose TG Insulin Sensitivity

Vascular Inflammation

(Ouchi N, et al, Curr Opin in Lipidol 2003)

Inflammation

ADIPONECTIN

CVD

T2DM

30

Adiponectin Hypothesis for insulin resistance, the metabolic syndrome, and atherosclerosis
Genetic factor Adiponectin gene polymorphism Lifestyle Changes High-fat Diet, Sedentary Lifestyle

Hypoadiponectinemia

Insulin Resistance

Hyperlipidemia

T2DM

Hypertension

Metabolic Syndrome

ATHEROSCLEROSIS
J Clin Invest, 2006.-

Obesity promotes the parallel progression of insulin resistance to type 2 diabetes and endothelial dysfunction to atherosclerosis
Visceral Adiposity
Proinflammatory mileu

Adiponectin

Insulin Resistance

Endothelial Dysfunction

Metabolic Syndrome
Impaired Glucose Tolerance Type 2 Diabetes

Atherosclerosis

Atherosclerosis

Atherosclerosis

Endocrin, 2003.-

Conclusion :
Visceral Fat Accumulation T2DM Hypertension

MetS

Atherosclerosis
ADIPONECTIN

CHF NASH Cancers Genetic Variations

33

Obat-obatan

Orlistat hambat enzim lipase (absorbsi lemak) Mazindol hambat sinapsis reuptake norepinefrin & dopa min Dietil propion Leptin rekombinan Terapi gen masa depan

Terimakasih