OBESITY OBESITY ((Criteria, etiology, and managementCriteria, etiology, and management))

ANDANDMETABOLIC SYNDROMEMETABOLIC SYNDROME((Criteria and managementCriteria and management))

John MF AdamJohn MF Adam

Division of Endocrinology and MetabolismDivision of Endocrinology and MetabolismDept. of Internal Medicine, Faculty of MedicineDept. of Internal Medicine, Faculty of MedicineHasanuddin UniversityHasanuddin University

MakassarMakassar

OBESITYOBESITYCriteria, etiology, and managementCriteria, etiology, and management

John MF AdamJohn MF Adam

Division of Endocrinology and MetabolismDivision of Endocrinology and MetabolismDept. of Internal Medicine, Faculty of MedicineDept. of Internal Medicine, Faculty of MedicineHasanuddin UniversityHasanuddin University

Makassar 2006Makassar 2006

Obesity is defined as a condition in Obesity is defined as a condition in which therewhich there is an excess of body is an excess of body fatfat.. The operational definitions of The operational definitions of obesity and overweight however obesity and overweight however are based on are based on BMIBMI which is closely which is closely correlated with body fatnesscorrelated with body fatness

DEFINITIONDEFINITION

CAUSE OF CAUSE OF OBESITYOBESITY

Primary Primary Genetic / overeatingGenetic / overeating

SecondarySecondary HypotyroidismHypotyroidism Cushing syndromeCushing syndrome Metabolic syndromeMetabolic syndrome Diabetes melitusDiabetes melitus EtcEtc

In many countries in the world, the prevalence In many countries in the world, the prevalence of obesity are rapidly rising, reflecting an overall of obesity are rapidly rising, reflecting an overall increase in general fatnessincrease in general fatness

There is aThere is a “global epidemic of obesity”.“global epidemic of obesity”. WHO report launched in 1998 signifying the WHO report launched in 1998 signifying the seriousness of this problemseriousness of this problem

Sorensen TIA. Diabetes Care 2000;23 (Suppl. 2):B1-B4

EPIDEMIOLOGYEPIDEMIOLOGY

Obesity as a Risk Factor for CAD • Obesity as a Risk Factor for CAD • The Importance of Abdominal FatThe Importance of Abdominal Fat

GynGynececoidoid ObesityObesity

AndroidAndroid ObesityObesity

Sharma 2002Sharma 2002

1.1. Body Mass Index Body Mass Index

BMIBMI ==Weight in kgWeight in kg

(Height in meters)(Height in meters)22

2. Body Fat Distribution2. Body Fat Distribution Android type (central obesity = visceral obesity) Ginecoid type (perifer obesity)

MEASUREMENT of OBESITYMEASUREMENT of OBESITY

PROPOSED CLASSIFICATION of WEIGHT PROPOSED CLASSIFICATION of WEIGHT by BMI in ADULT ASIANS (WHO 2000)by BMI in ADULT ASIANS (WHO 2000)

BMI (kg/mBMI (kg/m22) ) Risk of co-morbidities Risk of co-morbidities Classification Classification

Underweight Underweight < 18.5 < 18.5 Low ( but Increased risk Low ( but Increased risk of other clinical problems) of other clinical problems)

Normal Range 18.5 – 22.9Normal Range 18.5 – 22.9 Average AverageOverweightOverweight >> 23 23 At RiskAt Risk 23 - 24.9 Increase 23 - 24.9 IncreaseObese I 25 - 29.9 ModerateObese I 25 - 29.9 ModerateObese IIObese II >> 30 30 Severe Severe

Regional Office for the Western Pacific of the World Organization, The International Regional Office for the Western Pacific of the World Organization, The International Association for the Study of Obesity, The International Obesity Task Force. The Asia-Association for the Study of Obesity, The International Obesity Task Force. The Asia-Pacific perspective: Redefining obesity and its treatment. WHO Collaborating Centre for Pacific perspective: Redefining obesity and its treatment. WHO Collaborating Centre for the epidemiology of Diabetes and Health Promotion for Noncommunicable Disease, the epidemiology of Diabetes and Health Promotion for Noncommunicable Disease, Melbourne 2000Melbourne 2000

The Asia-Pacific Perspective: Redefining Obesity and its Treatment. The Asia-Pacific Perspective: Redefining Obesity and its Treatment. Assessment Diagnosis. 2000Assessment Diagnosis. 2000

Country Obese(BMI >30 kg/m2)

Overweight (BMI 25-29,9 kg/m2)

Korea (1995)

Thailand

Malaysia

Japan

Indonesia

1,5%

4,0%

4,7% (men)7,7% (women)

<3,0%

???

20,5%

16,0%

24,3% (men)20,2% (women)

PREVALENCE of OVERWEIGHT / PREVALENCE of OVERWEIGHT / OBESITY in SOME ASIAN COUNTRIESOBESITY in SOME ASIAN COUNTRIES

Imaging Imaging CT-scanningCT-scanningMRIMRIDEXADEXA

AnthropometricAnthropometricWaist circumferenceWaist circumference

(N: Men < 90 cm, Women <80 cm)(N: Men < 90 cm, Women <80 cm)

Waist-to-hip ratioWaist-to-hip ratio(N: Men (N: Men ≤ 1.0, Women ≤ 0.85)≤ 1.0, Women ≤ 0.85)

MEASUREMENT OF CENTRAL MEASUREMENT OF CENTRAL OBESITYOBESITY

Waist?Waist?

WaistWaist

Body Mass IndexBody Mass Index

Waist-to-Hip RatioWaist-to-Hip Ratio

Waist circumferenceWaist circumference??

OBESITYOBESITY

Desprs JP, dkk. BMJ 2001;322:716-720Desprs JP, dkk. BMJ 2001;322:716-720

WaistWaist

HipHip

20 years20 years

BMIBMI = = 3535Waist = Waist = 100 cm100 cmHip = Hip = 125 cm125 cmWH Ratio = 0.80WH Ratio = 0.80

BMIBMI = = 2424WaistWaist = = 80 cm80 cmHip =Hip = 100 cm 100 cmWH Ratio = 0.80WH Ratio = 0.80

Waist circumference identifies risk of Waist circumference identifies risk of CHD independent of BMICHD independent of BMI

140140

120120

100100

8080

6060

4040

2020

00

Waist C

ircum

ference

Waist C

ircum

ference

Tertiles (cm

)T

ertiles (cm)

High (High (>>81.8) 81.8) Medium (73.7-81.7) Medium (73.7-81.7)

Low (Low (<<73.6)73.6)

High High ((>>25.2)25.2)

Medium Medium (22.2-25.1)(22.2-25.1)

Low Low (>22.1)(>22.1)

Ag

e-A

dju

sted

CH

D

Ag

e-A

dju

sted

CH

D

Inci

den

ce/1

00,0

00 P

erso

n-y

ears

Inci

den

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00,0

00 P

erso

n-y

ears

BMI Tertiles (kg / mBMI Tertiles (kg / m22))

8383

7777

128128

4646

8989

110110

5555

9797

106106

IS OBESITY A DISEASEIS OBESITY A DISEASE

PROPORTION of DISEASE PROPORTION of DISEASE PREVALENCE ATTRIBUTABLE to PREVALENCE ATTRIBUTABLE to

OBESITYOBESITY

Type 2 diabetes 57%Gallbladder disease 30%Hypertension 17%Coronary heart disease 17%Osteoarthritis 14%Breast cancer 11%Uterine cancer 11%Colon cancer 11%

DiabetesHypertensionDyslipidemiaAlbuminuria

MENMEN

66

55

44

33

22

11

0022 23 24 25 26 27 28 29 30

OD

DS

RA

TIO

OD

DS

RA

TIO

BMI (kg/m2)

Risk of diabetes, hypertension, dyslipidemia or albuminuria according to selected BMI cut-off in Hong Kong Chinese

ModerateModerateRiskRisk

Relationship of BMI, cholesterol, and blood pressure to risk of ill health. The vertical lines accepted subdivisions for low, moderate, and high risk. All three

curves show a curvilinear increase with increasing level of risk factor

Bray GA, et al. Handbook of obesity, 1998Bray GA, et al. Handbook of obesity, 1998

2.5 21.5 10.5 0

LowRisk

HighRisk

20 25 30 35Body Mass Index

4 3 2 1 0

150 170 200 210 220 230 240 250 290

Cholesterol (mg/dl)Cholesterol (mg/dl)

Rel

ativ

e R

isk

5 4

3 2 1

Diastolic Blood Pressure 75 80 85 90 95 100 105 110 115 120

TREATMENT OF OBESITYTREATMENT OF OBESITY

Change of lifestylesChange of lifestyles - Diet- Diet - Physical activity- Physical activity

PharmacotherapyPharmacotherapy - Orlistat (Xenical)- Orlistat (Xenical) - Sibutramine (Reductil)- Sibutramine (Reductil)

SurgerySurgery

TREATMENT OF OBESITYTREATMENT OF OBESITY

CriteriaCriteria Treatment successTreatment success

Reduction of excess weightReduction of excess weight

Maintenance of BMIMaintenance of BMI

Blood pressureBlood pressure

Blood glucoseBlood glucose

Glycaemic control (HbA1c) Glycaemic control (HbA1c) † †† †

Other risk factorsOther risk factors

5-6 kg or 10% of initial body weight5-6 kg or 10% of initial body weight

< 23 kg/m< 23 kg/m2 † 2 †

any reductionany reduction

any reductionany reduction

any improvementany improvement

any reductionany reduction

† † For Asian populations. BMI cut-of will be higher in Pacific IslandersFor Asian populations. BMI cut-of will be higher in Pacific Islanders† † † † Haemoglobin A1cHaemoglobin A1c

WHO, Februari 2000WHO, Februari 2000

OBESITY : TREATMENT GUIDELINE FOR BMI

BMIBMI TreatmentTreatment

18.5 - 24.9

25 - 29.9 - without disease25 - 29.9 - with disease

30 - 39.9

> 40

No treatment, diet and exercise to maintain body weightHypocaloric diet and exercise to reduce body weightHypocaloric diet and exercise, anti-obesity drug

Hypocaloric diet and exercise, anti-obesity drugSurgery

Physicians guide to the management of obesity with Xenical (4)Physicians guide to the management of obesity with Xenical (4)

TREATMENT OF OBESITY TREATMENT OF OBESITY RESULTS OF RESULTS OF ORLISTATORLISTAT

JMFA 52

>> 5% weight loss 5% weight loss >> 10% weight loss 10% weight loss

Percentage of obese patients achieving weight loss of Percentage of obese patients achieving weight loss of >> 5% or 5% or >> 10% after 1 10% after 1 year of treatment with Xenical 120 mg or placebo tid plus a mildly hypocaloric year of treatment with Xenical 120 mg or placebo tid plus a mildly hypocaloric diet. diet. Sjostrom L, Rissanen A, Andersen T. Lancet 1998;352:167-72Sjostrom L, Rissanen A, Andersen T. Lancet 1998;352:167-72

8080

6060

4040

2020

00

49.2%49.2%

68.5%68.5%

17.6%17.6%

38.8%38.8%

Placebo (n=340)Placebo (n=340)Orlistat Orlistat 120 mg tid (n=343120 mg tid (n=343

P > 0.05P > 0.05

Pat

ien

t (%

)P

atie

nt

(%)

TREATMENT OF OBESITY TREATMENT OF OBESITY RESULTS OF SIBUTRAMINE RESULTS OF SIBUTRAMINE

TRIALSTRIALS

JMFA 52

STORM: Waist CircumferenceSTORM: Waist CircumferenceReduction and Maintenance Over 2 Reduction and Maintenance Over 2

YearsYearsSibutramineSibutramine PlaceboPlacebo

Wais

t cir

cu

mfe

ren

ce (

cm

)W

ais

t cir

cu

mfe

ren

ce (

cm

)

MonthMonth

109109

107107

105105

103103

101101

9999

9797

959500 121222 44 66 88 1010 1414 1616 1818 2020 2222 2424

James WPT, Lancet 2000;356:2119-25James WPT, Lancet 2000;356:2119-25

JMFA 53

Sudden death is more common in those Sudden death is more common in those who are naturally fat than in the slenderwho are naturally fat than in the slender

Hippocrates 410 B.C.Hippocrates 410 B.C.

Messerli et al Arch Intern Med 1987; 147: 1725 - 1728Messerli et al Arch Intern Med 1987; 147: 1725 - 1728 JMFA 4JMFA 4

METABOLIC SYNDROME METABOLIC SYNDROME

John MF Adam

Division of Endocrinology and MetabolismDept. of Internal Medicine, Faculty of MedicineHasanuddin University

Makassar

DEFINITION

Metabolic syndrome is a constellation of lipid and nonlipid risk factors of metabolic origin. This syndrome is closely linked to a generalized metabolic disorder called insulin resistance in which the normal actions of insulin are impaired

World Health Organization, 1999World Health Organization, 1999

National Cholesterol Education Program, National Cholesterol Education Program, Adult Treatment Panel III, 2001Adult Treatment Panel III, 2001

International Diabetes Federation, 2005International Diabetes Federation, 2005

CRITERIA of METABOLIC SYNDROME

JMFA 21

COMPONENTS OF THE METABOLIC SYNDROME

Glucose intolerance, impaired glucose tolerance (IGT) or diabetes mellitus and/or insulin resistance together with two or more of the following :

Raised arterial pressure

Raised plasma triglycerides

Central obesity

Microalbuminuria

World Health Organization, 1999

World Health Organization. Definition, diagnosis and classification of diabetes World Health Organization. Definition, diagnosis and classification of diabetes mellitus and its complication. Part 1: Diagnosis and classification of diabetes mellitus and its complication. Part 1: Diagnosis and classification of diabetes mellitus. Department of Noncommunicable Disease Surveillance, World Health mellitus. Department of Noncommunicable Disease Surveillance, World Health Organization, Geneva 1999Organization, Geneva 1999 JMFA 22

CLINICAL IDENTIFICATION OF THE METABOLIC SYNDROME NCEP – ATP III 2001

Metabolic syndrome > 3 risk factors

Risk factor Defining level

• Abdominal obesity* (waist circumference)†

Men > 102 cm (> 40 in) Women > 88 cm (> 35 in)• Triglycerides > 150 mg/dl• High-density lipoprotein cholesterol Men < 40 mg/dl Women < 50 mg/dl• Blood pressure > 130 / > 85 mmHg• Fasting glucose > 110 mg/dl

Executive summary of the third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel Ill). JAMA 2001;285:2486-2497 JMFA 23

Classification BMI (kg/m2) Risk of co-morbidilities

waist circulumference

< 90 cm (men) > 90 cm (men)

< 80 cm (women) > 80 cm (women)

Underweight < 18,5 Low (but increased risk Averageof other clinical problems)

Normal range 18.5-22.9 Average Increased

Overweight: > 23At risk 23-24.9 Increased ModerateObese I 25-29.9 Moderate SevereObese II > 30 Severe Very severe

Co-morbidities risk associated with different levels of BMI and suggested waist circumference in adult Asians

CLINICAL IDENTIFICATION OF THE METABOLIC SYNDROME Modified NCEP – ATP III 2001 for Asian Adults

Metabolic syndrome > 3 risk factors

Risk factor Defining level

• Abdominal obesity* (waist circumference)†

Men > 90 cm Women > 80 cm Triglycerides > 150 mg/dl• High-density lipoprotein cholesterol Men < 40 mg/dl Women < 50 mg/dl• Blood pressure > 130 / > 85 mmHg• Fasting glucose > 110 mg/dl

JMFA 24

IDF CriteriaIDF Criteria of Metabolic of Metabolic SyndromeSyndrome

>> 150 150 mg/dlmg/dl< 40 < 40 mg/dlmg/dl< 50 mg/dl< 50 mg/dl

>> 130 / 130 / >> 85 85 mmHgmmHg > 115 > 115 mg/dlmg/dl

• Abdominal obesity*

(waist circumference)†

Men

Women

Plus two of the following :

• Triglycerides

• HDL – chol Men

Women

• Blood pressure

• Fasting plasma glucose

>> 90 90 cmcm>> 80 80 cmcm

PREVALENCE OF METABOLIC PREVALENCE OF METABOLIC SYNDROMESYNDROME

USA 22% of adult population, 47 million

In Asian countries as well as other developing countries metabolic syndrome suggest to be higher

In Makassar :

Adriansjah and Adam (2003) 30,8% among males

Adam and Adriansjah (2003) difference between two criteria 24,2% NCEP-ATP III, 35,7%

modified NCEP-ATP III

Pre

vale

nce (

%)

20

20-29 30-39 40-49 50-59 60-69 >70

10

40

30

50

0

Ford ES et al. JAMA 2002; 287: 356-359

Age-Specific Prevalence of the Metabolic Syndrome Among 8,814 US Adults (Age > 20 Years)

(NHANES III., 1988-1994)

WomenMen

Mean ± SE

JMFA 26

RELATION BETWEEN OBESITY AND METABOLIC

SYNDROME

CENTRAL OBESITY AND METABOLIC SYNDROME

HHyypepertensionrtension

DDiabetes mellitus /iabetes mellitus /Impaired glucose toleranceImpaired glucose tolerance

DDyyslipidaemiaslipidaemia(HyperTG, low HDL-C)(HyperTG, low HDL-C)

CentralObesity

JMFA 27

Effect of Metabolic Syndrome

METABOLIC

SYNDROME

CVD

DM

TREATMENT OF METABOLIC SYNDROME

JMFA 41

DIET - EXERCISE

TREATMENT OF METABOLIC SYNDROME

Treatment of Dyslipidemia

LDL-cholesterol, Triglycerides, HDL-cholesterol

Treatment of Obesity

Calorie restriction, Exercise, Pharmacotherapy

Treatment of Hyperglicemia

Treatment of Hypertension

JMFA 43

Diabetes Mellitus Metformin, Thiazolidinedione

TREATMENT OF METABOLIC SYNDROME

DyslipidemiaStatins, Fibrate, Nicotinic acid

HypertensionACE – inhibitor, Ca – Channel blocker, HCT

JMFA 44