Obesity: A Metabolic Perspective

Obesity Trends* Among U.S. AdultsBRFSS, 1985

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends* Among U.S. AdultsBRFSS, 1986

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends* Among U.S. AdultsBRFSS, 1987

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends* Among U.S. AdultsBRFSS, 1988

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends* Among U.S. AdultsBRFSS, 1989

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends* Among U.S. AdultsBRFSS, 1990

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14%

Obesity Trends* Among U.S. AdultsBRFSS, 1991

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. AdultsBRFSS, 1992

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. AdultsBRFSS, 1993

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. AdultsBRFSS, 1994

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. AdultsBRFSS, 1995

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. AdultsBRFSS, 1996

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19%

Obesity Trends* Among U.S. AdultsBRFSS, 1997

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. AdultsBRFSS, 1998

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. AdultsBRFSS, 1999

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. AdultsBRFSS, 2000

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. AdultsBRFSS, 2001

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

Obesity Trends* Among U.S. AdultsBRFSS, 2002

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. AdultsBRFSS, 2003

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. AdultsBRFSS, 2004

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% ≥25%

Obesity Trends* Among U.S. AdultsBRFSS, 2005

(*BMI ≥30, or ~ 30 lbs overweight for 5’ 4” person)

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity as a Risk Factor for CAD

The Importance of Abdominal Fat

Gynoid Obesity

Android Obesity

Sharma 2002Sharma 2002

Android Obesity

Obesity and Metabolic Risk

Abdominal vs. Peripheral Obesity

Small Insulin-SensitiveSmall Insulin-SensitiveAdipocytesAdipocytes

Gynoid Obesity

Large Insulin-ResistantLarge Insulin-ResistantAdipocytes Adipocytes

Sharma 2002Sharma 2002

Obesity and Cardiovascular Risk

HypertensionHypertensionLeft ventricular Left ventricular

hypertrophyhypertrophyCongestive heart Congestive heart

failurefailure

ProthrombosisProthrombosisFibrinogen Fibrinogen

PAI-1 PAI-1

Insulin resistance Insulin resistance Glucose intoleranceGlucose intolerance

HyperglycaemiaHyperglycaemiaType 2 diabetesType 2 diabetes

EndothelialEndothelialdysfunctiondysfunction

DyslipidaemiaDyslipidaemiaTotal-C Total-C • • LDL-C LDL-C

Triglycerides Triglycerides Apo-B Apo-B •• HDL-C HDL-C

RenalRenalHyperfiltrationHyperfiltrationAlbuminuriaAlbuminuria

InflammatoryInflammatoryResponse Response

VisceralVisceralObesityObesity

“Corpulence is not only a disease itself, but the harbinger of others”

Hippocrates

                            10 March 2004     

Common Morbidities linked with Obesity

Cardiovascular risk factors

Sleep Apnoea

Heart disease

Gall bladder disease

Hormonal abnormalities

Hyperuricaemiaand gout

Stroke

Diabetes

Osteoarthritis

Cancer

Consequences

PortugalPortugal

1.5%1.5%

LuxembouLuxembourgrg

3.3%3.3%

Prevalence of Obesity in 15-24 Year Old Europeans (BMI>30)

IrelandIreland

8.0%8.0%

BelgiumBelgium

4.1%4.1%

Spain Spain

1.4%1.4%Italy Italy

1.0%1.0%Greece Greece

11.0%11.0%

Austria Austria

5.2%5.2%

DenmarkDenmark

2.5%2.5%

FinlandFinland

1.2%1.2%

SwedenSweden

2.0%2.0%

NetherlandNetherlandss

4.8%4.8%

UKUK

3.5%3.5%GermanyGermany

3.0%3.0%

FranceFrance

1.8%1.8%Martinez JA, Public Health Nutr 1999;2(1A):125-33Martinez JA, Public Health Nutr 1999;2(1A):125-33

Case

s of

Type 2

Dia

bete

s/100,0

00

Case

s of

Type 2

Dia

bete

s/100,0

00

ADA - Consensus statement reported in Diabetes Care 2000;22(12):381ADA - Consensus statement reported in Diabetes Care 2000;22(12):381

Incidence of Type 2 Diabetes inJunior High School Japanese Children

1414

1212

1010

88

66

441976-801976-80 1981-851981-85 1991-951991-95

“Most of these persons

will not stay in treatment for obesity.

Of those who stay in treatment

most will not lose weight.

Of those who do lose weight,

most will regain it”.

Stunkard 1972

Treating obesity: how and why

Treatment efficacy?

• There is no community intervention programme worldwide that has successfully allowed long term weight loss (maintenance)

• Overall failure rate after 4 years is 96%• Minnesota ‘Pound of Prevention’ study

indicated the mean weight gain prevented was <1kg

Treatment efficacy?

• Long term studies indicate only a small proportion of people lose and then maintain lost weight

• Predictors of success: – Continuous consumption of low-energy, low-fat

food, <25%– Food diary– Breakfast

Management GoalsModerate weight loss of 5 to 10 kg willhave a major effect on obesity co-morbidities -

• impaired glucose metabolism• hypertension• dyslipidaemia• sleep apnea• polycystic ovary syndrome

The weight loss needs to be sustained

Treatment benefits?Diabetes Prevention Program (USA) N=3234 (67% female); IGT50.6 years, Weight 94.8kgBMI 34 kg/m2

2.8 yearsLifestyle interventionMetforminPlacebo

Treatment benefits?

Diabetes Prevention Program Research Group 346 (6): 393, Figure 2     February 7, 2002

Treatment benefits?

Diabetes Prevention Program Research Group 346 (6): 393, Figure 1     February 7, 2002

Goal weight loss: 7% (6.6kg)

Treatment benefits?

Diabetes Care 28:888-894, 2005

Treatment benefits?

Diabetes Care 28:888-894, 2005

Obesity management strategies

• Diet

• Physical activity

• Pharmacotherapy

• Surgery

Obesity management strategies

• Diet – Best achieved by a combination of

hypocaloric/low fat diet– Aim to reduce intake by 2000-2500 kJ/day– 32000 kJ = 1kg– 0.5kg / week

Obesity management strategies

• Diet

• Physical activity– 30 mins 3 times a week is not sufficient to

allow weight loss or to maintain lost weight– Current recommendations: 60-80 mins

moderate intensity exercise daily

Obesity management strategies

• Diet• Physical activity• Pharmacotherapy

– Duromine– Fluoxetine– Sibutramine– Xenical– Optifast

Sibutramine: mechanism of action

• Serotonin (5-HT) and noradrenaline reuptake inhibitor.

• Dual mode of action: – reduces food intake by enhancing satiety– increases energy expenditure by enhancing

resting metabolic rate• Side effects

– Hypertension, tachycardia– Serotonin syndrome (SSRI’s, anti-psychotics)

McNeely and Goa. Drugs 1998.

Xenical :

mechanism of action

• Inhibits gastrointestinal lipases which are required for the systemic absorption of dietary fat

• Prevents the absorption of 30% of dietary fat

• Safe with minimal systemic absorption and no accumulation

• Significant GI side effects

Xenical

(n=8)

Sibutramine (n=8)

Kg -1kg -4kg

HbA1c -0.7% 0%

SCGH prescriptions for Xenical and Sibutramine

6 months therapy

10% lose >10 kg at 6-12 months

Management of Obesity: Objectives

• Prevention of weight gain• Encourage sustainable weight loss over longer

term

• Promotion of weight loss• 0.5 to 1.0kg per month is reasonable

• Up to a 10% reduction in body weight over a 12 month period

• Improvement of co-morbidities• Attainable with a weight loss as low as 5%

• Encouragement of active lifestyle• Broaden concepts of activity

• Improvement in quality of life• Enhance feelings of “well-being”

* NHLBI Clinical Guidelines 1998