Complications of

Obesity & Overweight

A Bornstein, MD, FACC

Assistant Professor of Public Health
Weill Cornell Medical College
 Obesity & Overweight as a Public Health Problem

 The rapidly growing epidemic of adult overweight & obesity is

shows no sign of abating

 According to the American Public Health Association, in the US,

overweight & obesity is associated with 300,000 deaths/year

 The APHA also reported that in 2000, economic cost of overweight

& obesity in the US exceeded $115,000,000,000

 Tremendous health consequences and expenditures are a direct

result of this epidemic; figures are likely to grow exponentially if the
problem is not adequately addressed and abated
Global Projections for the DM Epidemic: 2000-
2010

26.5
26.5
32.9
32.9

14.2 24%
24%
14.2
17.5
17.5 84.5
84.5
23%
23% 132.3
132.3
57%
57%
9.4
9.4
14.1
14.1
50%
50%

1.0
1.0
15.6
15.6 1.3
1.3
22.5
22.5 33%33%

44%
44% World
2000 = 151 million
2010 = 221 million
 46%
Trends in Child and Adolescent Overweight
Overweight & Obesity
Overweight & Obesity
 Medical Complications of Obesity

Doctors generally agree that the more obese a person is, the more likely he or she is
to have health problems

People who are 20% or more overweight get large health benefits from losing weight
Lancet. 2002; 360: 475
 Complications of Childhood Obesity

Obesity is not just a cosmetic problem…it's a health hazard with a multitude of

associated health problems

Someone who is 40% overweight is 2X as likely to die prematurely as is an

average-weight person Lancet. 2002; 360: 475
 What is Heart Disease?
 Heart disease, also known as cardiovascular disorder, a term that
includes a number of different diseases which affect the heart

 Most common cause of heart disease in developed nations is

coronary artery disease, narrowing or blockage of the coronary
arteries which supply blood to the heart muscle; usually caused by
atherosclerosis, which occurs when fatty material and a substance
called plaque builds up in the walls of your arteries

 Other causes of heart disease include hypertension, abnormal heart

valve function, abnormal heart rhythm, weakening of the pumping
ability of the heart (heart failure) which may be caused by either
progressive atherosclerosis, infection, or toxins
What is a Heart Attack?
 What is Coronary Artery Disease?
 CAD happens when the arteries that supply blood to heart muscle
become hardened & narrowed due to the buildup of cholesterol &
plaque, in the inner lining of the walls of the arteries

 As the buildup grows, less blood can flow through the arteries
resulting in the heart muscle not being able to get the blood or
oxygen it needs

 This can lead to chest pain (angina) or a heart attack (MI); most heart
attacks happen when a plaque ruptures causing a blood clot to form
which, along with plaque, suddenly totally cuts off the hearts' blood
supply, causing permanent heart muscle damage
What is Coronary Artery Disease?

Normal Artery
What is Coronary Artery Disease?
 What is Coronary Artery Disease?

Frequency of Plaque
 What is Coronary Artery Disease?
 Over time, CAD (repeated heart attacks or unstable angina) can also
weaken the heart muscle and contribute to heart failure and
arrhythmias

 It is difficult to estimate exactly how common heart attacks are

because as many as 200,000-300,000 people in the US die each year
before medical help is sought, or before medical help arrives

 It is estimated that approximately 1 million patients visit the

hospital each year with a heart attack

 About 1 death out of every 5 deaths are due to a heart attack

 What is a Heart Attack?

 It is difficult to estimate exactly

how common heart attacks are
because as many as 200,000 to
300,000 people in the U.S. die
each year before medical help is
sought or medical help arrives

 Approximately 1 million patients

visit the hospital each year with a
heart attack

 About 1 death out of every 5

deaths are due to a heart attack
Heart Failure Symptoms
 What is a Stroke?

A stroke is the rapidly developing loss of

brain functions due to a disturbance in the
blood vessels supplying blood to the brain
 CAD & Heart Attack Risk Factors
1) Bad genes (hereditary factors, family history)
2) Age
3) Being male
4) Menopause in females
5) High blood pressure
6) Smoking
7) Diabetes
8) Obesity
9) Low levels of physical activity
10) Poor diet; high stress

111  LDL (‘bad’) cholesterol &  HDL (‘good’) cholesterol

111  Homocysteine, CRP, &/or fibrinogen

 CAD & Heart Attack Risk Factors
1) Bad genes (hereditary factors, family history)
2) Age
3) Being male
4) Menopause in females
5) High blood pressure
6) Smoking
7) Diabetes
8) Obesity
9) Low levels of physical activity
10) Too much fat in your diet

111  LDL (‘bad’) cholesterol &  HDL (‘good’) cholesterol

111  Homocysteine, CRP, &/or fibrinogen

 How Is Obesity Linked to Heart Disease & Stroke?
 Heart disease & stroke are the leading causes of death and disability
in the US

 Overweight people are 2X as likely to have high BP, a major risk

factor for heart disease & stroke, than people not overweight

 High blood cholesterol levels can also lead to heart disease & often
linked to being overweight

 Being overweight also contributes to angina (chest pain caused by

decreased oxygen to the heart) & sudden death from heart disease
without any signs or symptoms

 The good news is that losing a small amount of weight can reduce
your chances of developing heart disease or stroke (reducing weight
by just 10% can dramatically decrease your chance of developing
heart disease or stroke)
 Obesity: An Ill-Defined Modifiable CVD Risk Factor

Obesity Others
BMI Hypertension
Hypertension Cholesterol
Cholesterol Diabetes
Diabetes Smoking
Smoking
LDL HDL

Global CVD Risk

BMI: body mass index

HDL: high-density lipoprotein
LDL: low-density lipoprotein
 How Is Obesity Linked to Diabetes?

 Type 2 diabetes  the body's ability to control blood sugar,

which is a major cause of heart disease, stroke, blindness,
kidney failure, & early death

 Overweight people are more than 2X as likely to develop

type 2 diabetes compared to normal weight people

 You can reduce your risk of developing type 2 diabetes by

losing weight & exercising more; if you already have type 2
diabetes, losing weight & becoming more physically active can
help control your blood sugar levels & may also allow you to
reduce the amount of diabetes medication you need
 Relative Risk of Mortality, CHD,
and Type 2 Diabetes According to BMI

Relative Risk of:

Mortality CHD Diabetes

2.0 4.0 8

1.5 3.0 6

1.0 2.0 4

0.5 1.0 2

0.0 0.0 0
<19.0 >32.0 <21.0 >29.0 <22.0 >35.0

BMI (kg/m2) BMI (kg/m2) BMI (kg/m2)

Manson JE, et al. N Engl J Med. 1995;333:677–685.

Willett WC, et al. JAMA.

1995;273:461–465.

Colditz GA, et al. Ann Intern Med. 1995;122:481–486.

 Natural History of Type 2 Diabetes

1) Genetic Onset of
susceptibility diabetes
Complications
2) Environmental
factors
a) Nutrition
b) Obesity Disability
c) Physical
inactivity
Insulin resistance IGT Ongoing hyperglycemia Death

Hyperinsulinemia Atherosclerosis Retinopathy Blindness

 HDL-C Hyperglycemia Nephropathy Renal failure
 Triglycerides Hypertension Neuropathy CHD
Atherosclerosis Amputation
Hypertension
 Burden of Diabetes in the U.S.

 17 million Americans have diabetes

 16 million Americans have prediabetes

 210,000 diabetes-related deaths/year

 Leading cause of blindness, kidney failure, amputation

 65% of patients suffer cardiovascular disease-related deaths

 Cost: $132 billion in 2008

Mokdad, et al, JAMA . 2001 286,1195

 Diabetes Prevalence Among
Minority Populations in the U.S.
20
Percentage of each population with diabetes
Non-Hispanic Whites

15

African Americans

10

Latinos

Native Americans
& Alaska Natives
0
7.8%
7.80% 10.2%
10.20% 13%
13% 15.1%
15.10%
(11.4 million) (2 million) (2.8 million) (105,000) Asian Americans and
 Pacific Islanders are 2-5
times more likely to have
diabetes than Non-
Hispanic Whites
Centers for Disease Control and Prevention (CDC) 1999 www.cdc.gov/diabetes
 Obesity as a Risk Factor for Type 2 Diabetes
Importance of Abdominal Fat Accumulation

15.2
13.5-year 12.5
incidence of 9.1
Type 2 Diabetes 9.1
(%) 2.9
0.5 2.9
0.5 III (Overweight)
(Overweight) III 0.5 II
II
I I Waist/Hip Ratio
BMI (Lean) (Lean) (Tertiles)
(Tertiles)

Ohlson LO, et al. Diabetes. 1985;34:1055-1058.

 Managing the High-Risk Patient with
Type 2 DM &/or ‘Hypertriglyceridemic Waist’

Type 2 Coronary
Diabetic Patient: Risk Factors Heart Disease
Hypertriglyceridemic
Waist

Hypertension
Dyslipidemia

Type 2
Diabetes

Management of Coronary
Treating Heart Disease Risk
Treating the Cause the Complications

Després JP et al. BMJ. 2001;322:716-720.

 Type 2developing
Percent Diabetesdiabetes
Prevention
All participants
Risk Reduction
Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
40 Metformin (n=1073,
31%p<0.001 vs. Plac)
by Metformin
Placebo (n=1082)
Cumulative incidence (%)

58% by Lifestyle Changes

30 Placebo Metformin

20

Lifestyle Changes
10

0
0 1 2 3 4
Years from randomization

The DPP Research Group, NEJM. 346:393-403, 2002

 What is BMI?
 Body Mass Index (BMI) is a number calculated from a person’s
weight & height that provides a reliable indicator of body fatness
& is an inexpensive & easy-to-perform method of screening for
weight categories that may lead to health problems

 BMI does not measure body fat directly, but research has shown that
BMI correlates to direct measures of body fat

 BMI is not a diagnostic tool; a person may have a high BMI, but, to
determine if excess weight is a health risk, a physician would need to
perform further assessments including skin-fold thickness measurement,
evaluations of diet, physical activity, family history, and other
appropriate health screenings
 What is BMI?
 Calculating BMI is one of the best methods for population assessment
of overweight and obesity

 Because calculation requires only height & weight, it is inexpensive

and easy to use for clinicians and for the general public; BMI allows
people to compare their own weight status to that of the general
population

 Other methods to measure body fatness include skin fold thickness

measurements (with calipers), underwater weighing, bioelectrical
impedance, dual-energy x-ray absorptiometry (DXA), and
computerized tomography, but, these methods are not always readily
available, expensive &/or need highly trained personnel
 Obesity: Body Mass Index (BMI)

Weight (kg)
BMI =
Height (m2)

BMI (kg/m2) Risk of Comorbidities

Healthy weight 18.5 – 24.9 Normal

Overweight 25.0 – 29.9 Increased

Obese Class I 30.0 – 34.9 High
Obese Class II 35.0 – 39.9 Very High
Obese Class III > 40.0 Extremely High

Adapted from the World Health Organization. Obesity: Preventing and Managing the Global Epidemic. Geneva: WHO; 2000.
Saving and Overconsuming Energy
Android (Apple) vs. Gynoid (Pear) Obesity

Tribute
to a Pioneer:

Jean Vague (1947)

Vague J. Presse Med 1947;30:339–340.

Intra-abdominal (Visceral) Fat:
The Dangerous Inner Fat
Visceral adipose
tissue
Front

Subcutaneous
adipose tissue

Lemieux l, et al. Ann Endocrinol. 2001;62:255-261.

 Inflammation and Cardiovascular Disease:
Is Abdominal Obesity the Missing Link?

 CRP
TNF-α ?

?
IL-6

?
 Risk of ACS
Atherogenic,
Visceral (acute
insulin resistant
Adipose coronary
‘dysmetabolic
Tissue syndrome)
milieu’

Després JP. Int J Obes Relat Metab Disord. 2003;27:S22-S24.

 What is The Metabolic Syndrome?
 The Metabolic syndrome is a group of health problems that include
visceral obesity (too much fat around the waist),  blood pressure,
 triglycerides,  HDL cholesterol, &  blood sugar; together, this
group of health problems increases your risk of heart attack, stroke,
& diabetes

 Metabolic syndrome is caused by an unhealthy lifestyle that includes

eating too many calories, being inactive, & gaining weight, particularly
around the waist

 This lifestyle can lead to insulin resistance, a problem with the body's
metabolism where your body cannot use insulin properly, &, as a
result, blood sugar will begin to rise; over time, this can lead to type 2
diabetes
 Features of the Metabolic Syndrome Commonly
Found in Viscerally Obese Patients

• Hypertriglyceridemia • Insulin resistance

• Low HDL cholesterol • Hyperinsulinemia

• Elevated apolipoprotein B • Glucose intolerance

• Small, dense LDL particles • Impaired fibrinolysis

• Inflammatory profile • Endothelial dysfunction

Genetic susceptibility to hypertension, type 2 diabetes, and coronary heart

disease ultimately affects the clinical features of the metabolic syndrome

Adapted from Lemieux l , Després JP. In: Management of Obesity and Related Disorders. 2001:45-63.
 The Atherogenic Metabolic Triad
Hyperinsulinemia

The
Atherogenic
Triad

Small, dense  apo B

LDL particles concentrations

Beyond LDL cholesterol, blood pressure, type 2 diabetes…

LDL: low-density lipoprotein

 Potential Contribution of Ectopic Fat Deposition to
Cardiometabolic Risk of Viscerally Obese Patients

 Visceral Insulin-resistant  LPL

adipose tissue subcutaneous Insulin resistance
adipose tissue  Systemic
FFAs Skeletal
Muscle

 PAI-1 ?

 Portal  IL-6
FFAs  TNF-α
 Hepatic lipase  Adiponectin
Lipid deposition
Altered Cardiometabolic
Liver  Insulin
Risk Profile
 Glucose
 Triglyceride  HDL
 Apolipoprotein B Coronary Atherosclerosis
Unstable Plaque
FFAs = Free Fatty Acids
Després JP. Ann Med. 2006;38:52-63.
Prevalent Form of the Metabolic Syndrome
as Defined by NCEP ATP III and IDF

Atherogenic
Atherogenic
Dyslipidemia
Dyslipidemia

Insulin
Insulin
Resistance
Resistance

Thrombotic
Thrombotic
State
State

Inflammatory
Inflammatory
State
State

Adapted from JAMA. 2001;285:2486-2497.

Alberti KG, et
al. Lancet. 2005;366:1059-1062.
Grundy SM, et al.
Circulation. 2005;112:2735-2752.
 Weight Gain: Subcutaneous Adipose Tissue

Subcutaneous
adipose tissue
Visceral
adipose
tissue PPAR-γ Agonists

Deteriorated Lipid Profile Improved

 Triglycerides 
 HDL cholesterol 
 Cholesterol/HDL cholesterol 
? LDL cholesterol ?
LDL Particle Concentration
? and Size ?
Deteriorated Insulin Sensitivity Improved
Viscerally Obese
 Insulinemia 
Obese
 Glycemia 
 HbA1C 
HIGH Coronary Heart Disease Risk LOW

HDL = high-density lipoprotein; LDL = low-density lipoprotein

 New Markers of CHD Risk:
What to Look for; What to Target?
Atherogenic
AtherogenicDyslipidemia
Dyslipidemia
 Triglycerides
 Triglycerides
 HDL
 HDLcholesterol
cholesterol
Inflammation
 Cholesterol/HDLcholesterol
Cholesterol/HDL cholesterolratio
ratio
‘Normal’
‘Normal’ LDL cholesterol but  apoBB
LDL cholesterol but  apo
Small,
Small,dense
denseLDL
LDLand
and HDL
HDL
Postprandial hyperlipidemia
Postprandial hyperlipidemia
Insulin
InsulinResistance
Resistance
Insulin
Insulinresistance
resistance
Hyperinsulinemia
Hyperinsulinemia
Hyperglycemia Thin fibrous Lipid
Hyperglycemia cap core
Type
Type22diabetes
diabetes
Thrombotic Coronary
ThromboticState
State
 PAI-1
 PAI-1 atherosclerosis
 Fibrinogen
 Fibrinogen Unstable plaque

Inflammatory
InflammatoryState
State
 CRP
 CRP
 Cytokines
 Cytokines
Abdominal  Risk of Acute Coronary
Obesity Metabolic Risk Factors Syndrome

Does
DoesItItMake
MakeaaDifference??
Difference?? We
WeShould
ShouldNot
NotTreat
TreataaBlack
BlackBox!
Box!
Adapted from Després JP, et al. Progress in Obesity Research: 9; 2003:29-35.
 Managing CVD Risk in Patients With
Type 2 Diabetes or the Metabolic Syndrome
Beyond lowering LDL cholesterol, BP, glycemia....

Diet
Weight loss
Physical activity

Improves the  TG -  HDL cholesterol,

and small dense LDL dyslipidemia

Fixes a dysmetabolic state

(including inflammation)

HDL = high-density lipoprotein

LDL = low-density lipoprotein
TG = triglycerides
Prevention…
It could work!!!
 Cumulative Incidence of Diabetes
According to Study Group: DPP

Placebo
Cumulative Incidence
of Diabetes (%)

28.8
Metformin
21.7
Lifestyle
14.4

0 1 2 3 4

Years from Randomization

Diabetes Prevention Program Research Group. N Engl J Med. 2002;346:393-403.

 ‘Normal’ Weight (BMI = 25 kg/m2)
But Viscerally Obese Patient…

Before
After....
a weight loss of only 5 kgms

• Moderate weight loss (5-10%) by diet and/or exercise can induce a

substantial (~30%) loss of atherogenic visceral fat and substantially
improve the risk profile status of these patients

• Thus, the importance of waist rather than weight management is

emphasized

Després JP, et al. Int J Obes. 1995;19(suppl 1):S76-S86.

 Acute & Chronic Effects of
Regular Physical Activity/Exercise

Sedentary Physically Active Physically Active

Viscerally Viscerally Obese Nonviscerally Obese
Obese
Improvements
of lipoprotein – Additional physical
lipid profile & and metabolic
insulin/glucose improvements
metabolism

Mobilization Mobilization
of visceral AT of visceral AT
without significant and significant
changes in adiposity weight loss
Glycogen
level Glycogen Glycogen
level level

Després JP, et al. In: Handbook of Exercise in Diabetes. 2nd ed. 2002:197-234.
Elevated Waist Circumference: A Key Feature
in Patients with the Metabolic Syndrome