Obesity: Pathophysiology, Risk

Assessment, and Prevalence

Krishna W Sucipto
Endocrine and Metabolic Division of Internal Department
Faculty of Medicine Syiahkuala University dr Zainoel Abidin Hospital
Banda Aceh
Obesity
Excessive amount of body fat
Women with > 35% body fat
Men with > 25% body fat
Increased risk for health problems
Are usually overweight, but can have
healthy BMI and high % fat
Measurements using calipers
Desirable % Body Fat
Men: 8-25%
Women 20-35%
Regional Distribution
The regional distribution of body fat affects
risk factors for the heart disease and type 2
diabetes
Body Fat Distribution: Gynecoid
Lower-body obesity--Pear shape
Encouraged by estrogen and progesterone
Less health risk than upper-body obesity
After menopause, upper-body obesity
appears
Body Fat Distribution: Android

Upper-body obesity--apple shape

Associated with more heart disease, HTN, Type
II Diabetes
Abdominal fat is released right into the liver
Encouraged by testosterone and excessive
alcohol intake
Defined as waist measurement of > 40 for men
and >35 for women
Body Fat Distribution
Weight Management
Balancing energy intake and energy
expenditure is the basis of weight
management throughout life
Set Point Theory
Body tends to preserve a given weight
Energy expenditure increases and decreases
with weight loss and gain
Effect may be temporary, e.g. energy needs
drop during calorie restriction and
normalize when energy balance is achieved
Component of Energy Expenditure
Components of Energy
Expenditure
Resting energy expenditure: expressed as
RMR
Energy expended in voluntary activity
Thermic effect of food (TEF) or diet-induced
thermogenesis (DIT)
Related to energy value of food consumed
and adaptive response to overeating
TEF may decline as day progresses
(Romon, AJCN, 1993)
Resting Metabolic Rate
Increases with increased muscle mass
Declines with age
Declines during restriction of energy intake
(up to 15%)
Explains 60-70% of total energy
expenditure
Voluntary Energy Expenditure
(activity thermogenesis)
The most variable component of energy
expenditure
Accounts for 15-30% of total
Most of us will require increasing voluntary
energy expenditure as we age to offset
declining fat free mass and RMR in order to
maintain weight
Role of Brain Neurotransmitters
Neurotransmitters govern the bodys response to
starvation and dietary intake
Decreases in serotonin and increases in
neuropeptide Y are associated with an increase in
carbohydrate appetite
Neuropeptide Y increases during deprivation; may
account for increase in appetite after dieting
Cravings for sweet high-fat foods among obese
and bulimic patients may involve the endorphin
system
Hormonal Regulation of Body
Weight
Norepinephrine and dopaminereleased by
sympathetic nervous system in response to
dietary intake
Fasting and semistarvation lead to decreased
levels of these neurotransmittersmore
epinephrine is made and substrate is
mobilized.
Hormones and Weight
Hypothyroidism may diminish adaptive
thermogenesis
Insulin resistance may impair adaptive
thermogenesis
Leptin is secreted in proportion to percent
adipose tissue and may regulate (decrease)
appetite
Hunger vs. Satiety
Satietypostprandial state when excess food
is being stored
Hungerpostabsorptive state when stores are
being mobilized
Short-term regulation affected
Hunger vs. Satietycontd
Feedback mechanism with signal from
adipose mass when weight loss occurs
eating is the natural result
Not always identified in the elderly
This occurs mostly in young people
Long-term regulation affected
Nature vs Nurture
Identical twins raised apart have similar
weights
Genetics account for ~40%-70% of weight
differences
Genes affect metabolic rate, fuel use, brain
chemistry, body shape
Thrifty metabolism gene allows for more fat
storage to protect against famine
Nature vs Nurture
Obesity tends to run in families
If both parents are normal weight 10%
chance of obesity in offspring
If one parent is obese 40% chance
If both parents obese 80% chance

Is it genetics or learned eating behavior?

 Nurture vs Nature
Environmental factors influence weight
Learned eating habits
Activity factor (or lack of)
Poverty and obesity
Female obesity is rooted in childhood
obesity
Male obesity appears after age 30
Nurture vs Nature
Overeating learned early in childhood
Bottle vs breast
Urging children to eat more, clean their
plates
Use of food as a reward
 Food = Love

Shelly Thorene Photography

 Nature and Nurture
Obesity is nurture allowing nature to
express itself
Location of fat is influenced by genetics
A child of obese parents must always be
concerned about his weight
Nature and Nurture
The influence of
environment is apparent in
the fact that the prevalence
of obesity has increased
dramatically in the US in
the past 40 years
Causes of Obesity
Causes of Excessive Energy Intake
Active: large portion sizes, frequent meals and
snacks
Passive: excessive intake of energy-dense
foods containing hidden calories
Variety of options: the greater the variety of
foods offered, the greater the intake
Sensory-specific satiety: as foods are
consumed they become less appealing
Low Energy Expenditure
There is a mismatch between our thrifty
metabolic genetic heritage and the sedentary
American lifestyle
Obesity: A Major Health Issue
Obesity is the No. 2 preventable cause of death and
disability (smoking is #1)
Obesity is associated with increased risk of heart
disease, stroke, gallbladder disease, cancer,
osteoarthritis, sleep apnea
Obesity-related health problems cost $75 billion
annually (2003 data)
The public pays about $39 billion a year -- or about
$175 per person -- for obesity through Medicare and
Medicaid programs
Health Problems Associated with
Excess Body Fat
Surgical risk Type 2 diabetes
Lung (pulmonary) Gallstones
disease Cancers (breast, colon,
Sleep apnea pancreas, gallbladder)
HTN Infertility
CVD Pregnancy- difficult
delivery
Bone and joint disorders
(gout, osteoarthritis) Reduced agility
Early death
 NHANES III Prevalence of Hypertension*
Percent According to BMI

*Defined as mean systolic blood pressure 140 mm Hg, mean diastolic 90

mm Hg, or currently taking antihypertensive medication .
Brown C et al. Body Mass Index and the Prevalence of
Hypertension and Dyslipidemia. Obes Res. 2000;8:605-619.
Incidence of New Cases
per 1,000 Person-Years Obesity and Diabetes Risk

BMI Levels

Knowler WC et al. Am J Epidemiol 1981;113:144-156.

 Weight Gain and Diabetes Risk
Weight Change Since Age 21
Relative Risk

Body Mass Index at Age 21

Adapted from Chan JM et al. Diabetes Care 1994;17:960-
969.
Metabolic Syndrome Criteria*
Three or more of the following abnormalities:
Waist circumference >102 cm (40 inches) in men and >
88 cm (35 inches) in women
Serum triglycerides of at least 150 mg/dL
High density lipoprotein level <40 mg/dL in men and
<50 mg/dL in women
Blood pressure >=135/85 mm/hg
Serum glucose >=110 mg/dl
Includes 47 million US residents (27.7% of the
population

*ATP III Guidelines. National Cholesterol Education Program, 2001

Polycystic Ovary Syndrome (PCOS)
Endocrine disorder characterized by
hyperandrogenism and insulin resistance
Associated with android obesity
Affects 5-10% of reproductive age women
Erratic menstrual periods, chronic anovulations
resulting in multiple ovarian cysts; infertility, acne,
hirsutism and alopecia
Increased risk of heart disease, type 2 diabetes,
reproductive cancers
Management of PCOS
Symptom oriented, as etiology is unclear
Individualized diet and exercise plan to
promote weight loss and normalize insulin
levels
Medications to alleviate symptoms
 26 -Year Incidence of
Incidence/1,000
Coronary Heart Disease in Men

BMI Levels
Adapted from Hubert HB et al. Circulation 1983;67:968-977.
Metropolitan Relative Weight of 110 is a BMI of approximately
25.
 26 -Year Incidence of
Incidence/1,000 Coronary Heart Disease in Women

BMI Levels
Adapted from Hubert HB et al. Circulation 1983;67:968-977.
Metropolitan Relative Weight of 110 is a BMI of approximately 25.
 Hypertension

60

50
Percentage

40

30

20

10

20 25 30 35 40
BMI
Relationship between BMI and crude percentage of women reporting
medical problems, surgical procedures, symptoms, and health care utilization.

Brown WJ et al. Int J Obes 1998;22:520-528.

 Diabetes

15
Percentage

10

20 25 30 35 40
BMI
Relationship between BMI and crude percentage of women reporting
medical problems, surgical procedures, symptoms, and health care utilization.

Brown WJ et al. Int J Obes 1998;22:520-528.

 Cholescystectomy

25

20
Percentage

15

10

20 25 30 35 40
BMI

Relationship between BMI and crude percentage of women reporting

medical problems, surgical procedures, symptoms, and health care utilization.

Brown WJ et al. Int J Obes 1998;22:520-528.

 Back Pain

35

30
Percentage

25

20

15

20 25 30 35 40
BMI

Relationship between BMI and crude percentage of women reporting

medical problems, surgical procedures, symptoms, and health care utilization.

Brown WJ et al. Int J Obes 1998;22:520-528.

 Body Mass Index and Mortality
Risk

(Adapted from Bray GA. Gray DS, Obesity, part 1: Pathogenesis. West J Med 149:429, 1988; and Lew EA, Garfinkle L; Variations
in mortality by weight among 750,000 men and women. J Clin Epidemiol 32:563, 1979.)
BMI and Health
Below 18.5 Underweight

18.5 24.9 Normal

25.0 29.9 Overweight

Monitor for risk
30.0 and Above Obese
Increased health risk
40.0 and above Severely obese
Major health risk
The Key Features of Nutrient System
Can be Summarized as Follows:
1. Oxidation is continuous; nutrient intake is periodic
2. Oxidation rate is influenced by age, gender, metabolic
size, physical activity, hormonal status, nutritional
status and ambient temperature.
3. Diets provide carbohydrate, protein, fat, alcohol and
micronutrients.
4. Food intake is influenced by its availability and
individual preference.
The Key Features of Nutrient System
Can be Summarized as Follows:
5. Macronutrient preference may be regulated separately
for each macronutrient.
6. Carbohydrate can be oxidized, stored as glycogen, or
converted to fat
7. Lipogenesis from carbohydrate is energy expensive, and
can occur in liver or fat.
8. Carbohydrate is the preferred fuel of brain and nerve and
is used for bursts of muscular contraction.
9. Fat can be stored or oxidized, but is not converted to
carbohydrate.
The Key Features of Nutrient System
Can be Summarized as Follows:
10. For nutrient balance, i.e. weight stability, fat and
carbohydrate oxidized or respiratory quotient (RQ)
must equal the carbohydrate to fat ratio or food
quotient (FQ) in the diet.
11. When the fat to carbohydrate ratio in the diet rises (FQ
falls) the oxidation of carbohydrate falls (RQ falls) and
fat oxidation rises.
12. If the fall in carbohydrate oxidation is not sufficient to
match the fall in dietary carbohydrate, then food intake
will rise to provide carbohydrate.
The Key Features of Nutrient System
Can be Summarized as Follows:
13. A high RQ (high carbohydrate oxidation) predicts
weight gain.
14. A low metabolic rate may predict future weight gain.
15. Fat is stored primarily in fat cells.
16. Fat cells synthesize and secrete peptides including
complement D (Adipsin), cytokines, angiotensinogen
and ob protein (leptin).
17. The sympathetic nervous system may modulate
adaption to a low carbohydrate diet.