What is Obesity

1
What is Obesity?

• Obesity means excess accumulation of fat in the
  body
• Once it develops it is difficult to cure and
  usually persists throughout life
• Obesity is usually diagnosed on the basis of
  calculation of
• Body mass index
• Measurement of waist-hip ratio

2
Classification of Overweight and Obese by Body
Mass Index
BMI Weight (kg) Height (m)2

• BMI (kg/m2)
• WHO guidelines
  Proposed Asia Pacific guidelines Underweight
  lt 18.5
  lt 18.5
• Normal 18.5-24.9
  18.5-22.9
• Overweight 25.0-29.9
  gt 23
• At risk -
  23-24.9
• Obesity 30-34.9 (Class I)
  25-29.9 (Class I)
• 35-39.9 (Class
  II) gt 30 (Class II)
• Extremely Obese gt 40 (Class III)
  -

3
Waist-to-hip ratio
WAIST
Ratio
HIPS
Desired Ratio Women lt0.8 Men lt 1.0
Risk increases if waist circumference is gt94 cm
in men and gt80 cm in women
TO FIND RATIO
Waist Measure at
narrowest point with
stomach relaxed
Hips Measure at
fullest point
4
Co-morbidities risk associated with different
levels of BMI and suggested waist circumference
in adult Asians

• Classification BMI Risk of
  co-morbidities
• Waist circumference
• lt 90 cm (men) gt 90 cm (men)
• lt 80 cm (women) gt 90 cm (women)
• Underweight lt 18.5 Low
  Average
• Normal range 18.5-22.9 Average Increased
• Overweight gt 23
• At risk 23-24.9 Increased Moderate
• Obese I 25-29.9 Moderate Severe
• Obese II gt 30 Severe Very
  severe

5
Obesity An imbalance in energy intake and
energy expenditure
Proteins (20)
BMR (60-65)
Thermic effect
ENERGY INTAKE
ENERGY EXPENDITURE
Fats (25)
of food (10)
Carbohydrates (55)
Physical activity (25-30)
6
Role of hypothalamus in mediation ofhunger and
satiety
Periventricular
Thalamus
Neuroendocrine
Paraventricular
HO conserv
Dorsomedial
2
Oxytocin rel.
GI stimuli
Anterior
Lateral
hypothalamic
hypothalamic
Body temp
Hunger, thirst
Supraoptic
Optic tract
Vasopresin rel.
Arcuate
Fornix
Ventromedial
Neuroendocrine
Rage,
Satiety
Hunger
7
Classification of obesity as per fat distribution

• Android (or abdominal or central, males)
• Collection of fat mostly in the abdomen (above
  the waist)
• apple-shaped
• Associated with insulin resistance and heart
  disease
• Gynoid (below the waist, females)
• Collection of fat on hips and buttocks
• pear-shaped
• Associated with mechanical problems

8
Diseases and conditions forwhich obesity is a
risk factor

• Gallbladder disease
• Osteoarthritis
• Infertility
• Venous circulatory disease
• Increased anaesthetic risk
• Low back pain
• Polycystic ovary disease
• Cancer (ovarian, breast, endometrial,
  gallbladder, prostate, colon)

• Coronary artery disease
• Type II Diabetes Mellitus
• Hypertension
• Dyslipidemia
• Respiratory disease
• Gout
• Reflux disease
• Psychological problems

9
Prevalence of overweight and obesity in different
income groups of Delhi (Nutrition Foundation of
India Study)

• Prevalence ()
• Slums Middle-Class Total
• Overweight (BMI gt 25)
• Males ND ND 19.6 Females ND ND 44.5
• Obesity (BMI gt 30) Males 1 32.3 ND Females 4 50
  ND
• Abdominal obesity Males ND 49.7 ND Females ND 34
  .9 ND
• ND Not determined

http//www.nutritionfoundationin.org/NEW/OBESITY.H
TM
10
The Five City Study

• n3257 aged 25-64 yrs
• Cities Moradabad (n902), Trivandrum (n760),
  Calcutta (n410), Nagpur (n405), Bombay (n780)
• Social Class BMIgt27 WHRgt0.85 Sedentary life
  style
• I (n985) 21.2 96.9 92.2
• II (n790 16.4 57.2
  71.4
• III (n674) 8.9 39.3
  42.3
• IV (n602) 3.0 11.9
  14.9
• V (n206) 3.8 8.7
  8.7
• Int J Cardiol 199969139-147

11
Advantages of weight loss

• Weight loss of 0.5-9 kg (n43,457) associated
  with 53 reduction in cancer-deaths, 44
  reduction in diabetes-associated mortality and
  20 reduction in total mortality
• Survival increased 3-4 months for every kilogram
  of weight loss
• Reduced hyperlipidemia, hypertension and insulin
  resistance
• Improvement in severity of diseases
• Person feels fit and mentally more active
•  

12
Treatment goals

• Prevention of further weight gain
• Weight loss to achieve a realistic, target BMI
• Long-term maintenance of a lower body-weight

13
How much weight loss is significant?

• A 5-10 reduction in weight (within 6 months) and
  
• weight maintenance should be stressed in any
  weight
• loss program and contributes significantly to
• decreased morbidity

14
Approaches to obesity management
15
Drug therapy

• Appetite suppressants
• Adrenergic agents (e.g. amphetamine,
  methamphetamine, phenylpropanol amine,
  phentermine)
• Serotonergic agents (e.g. fenfluramine,
  dexfenfluramine, SSRIs like sertraline,
  fluoxetine)
• Thermogenic agents
• ephedrine, caffeine
• New ones
• Sibutramine Orlistat

16
Sibutramine inhibits serotonin andnoradrenaline
reuptake
Noradrenaline
Serotonin
17
STORM Study Effect of sibutramine on weight loss
104
Placebo
102
100
98
Bodyweight (kg)
96
94
92
90
Sibutramine
0
12
22
24
20
18
16
14
10
8
6
4
2
Month
Weight loss
Weight maintenance
Lancet 2000 3562119-2125
18
STORM StudyMean Weight Loss at Two Years
Mean Weight Loss (Kg)
19
STORM Study Proportion of patients maintaining
at least 5 and 10 weight loss
5 responders
10 responders
Sibutramine
Placebo
100
80
60
Proportion of patients ()
40
20
0
6
12
18
24
6
12
18
24
Lancet 2000 3562119-2125
20
STORM StudyEffect on Waist Circumference and
Waist/Hip Ratio
(a) Waist Circumference
(b) Waist/Hip Ratio
Decrease in waist circumference (cm)
Change
21
STORM Study Effects on lipids
Triglycerides
VLDL cholesterol
5
5
Placebo
Placebo
0
0
e
e
g
-5
g
n
-5
n
a
a
h
-10
-10
c
h

c
-15


-15

-20
-20
Sibutramine
-25
Sibutramine
-25
18
0
24
12
6
0
0
24
18
12
6
Lancet 2000 3562119-2125
22
STORM Study Effects on lipids (Contd.)
HDL cholesterol
30
25
e
Sibutramine
g
20
n
a
15
h
c
Placebo

10

5
0
18
0
24
12
6
Month of assessment
Weight loss
Weight maintenance
Lancet 2000 3562119-2125
23
STORM Study Effect on Insulin and HbA1c
HbA1c
Insulin
Placebo
Placebo
.
Change
Change
Sibutramine
Sibutramine
Month of Assessment
Month of Assessment
Lancet 2000 3562119-2125
24
STORM study Other metabolic effects

• Variable Baseline Month 6
  Month 24
• SIB PLAC SIB PLAC SIB PLAC
• Uric acid 0.32 0.33 0.29
  0.30 0.30 0.32
• Glucose 5.20 5.11 5.07
  5.01 5.13 5.17
• Insulin 17.7 16.7 12.7
  12.4 13.8 16.2
• C-peptide 3.21 3.05 2.54
  2.46 2.38 2.69
• HbA1c 5.86 5.75
  5.56 5.50 5.56 5.66

25
STORM study Conclusions

• Almost all patients who persist with a weight
  management program consisting of sibutramine,
  diet and exercse can achieve at least a 5 weight
  loss with sibutramine
• Over half can lose more than 10 weight within 6
  months
• Weight loss was sustained in most patients
  continuing therapy for two years

26
Sibutramine vs. Dexfenfluramine
Sibutramine 10 mg
Dexfenfluramine 30 mg
0
-0.5
-1
-1.5
-2
Weight loss (kg)
-2.5
-3
-3.5
-3.2
-4
-4.5
-4.5
n226 12 wks
-5
Int J Obes 1995 19. Suppl 2 144
27
Adverse effects occurring in gt5 of patients
treated with Sibutramine compared with placebo

• Sibutramine Placebo Adverse
  Effects Incidence (n2068) Incidence (n884)
• Headache 30.3 18.6
• Dry Mouth 17.2 4.2
• Anorexia 13.0 3.5
• Constipation 11.5 6.0
• Insomnia 10.7 4.5
• Dizziness 7.0 3.4
• Nausea 5.9 2.8
• Nervousness 5.2 2.9
• Dyspepsia 5.0 2.6

Ann Pharmacother 199933968-978
28
Sibutramine Safety

• Discontinuation rates 9 with placebo and 7
  with sibutramine
• Has been associated with a mean increase in BP
  and heart rate of approximately 1-3mmHg and 4-5
  beats/min
• Cardiac side effects viz. hypertension,
  tachycardia and palpitations lt 2.6 vs 0.6-0.9
  in placebo group
• Caution to be exercised in patients with history
  of hypertension and should not be given to
  patients with uncontrolled or poorly controlled
  hypertension
• Not associated with cardiac valve abnormalities
  or primary pulmonary hypertension

29
STORM Study Withdrawals due to BP increase

• Dose of Sibutramine patients who withdrew due
  to increase in BP
• 10 mg 1
• 15 mg 2
• 20 mg 3

Lancet 2000 3562119-2125
30
Indications Dosage

• Recommended for obese patients with a BMI gt 30
  kg/m2 or gt 27 kg/m2 in the presence of other
  risk factors (e.g. hypertension, diabetes,
  dyslipidemia)
• In Indian patients, sibutramine could be
  considered in patients with BMI gt 25 kg/m2 or
  those with BMI of 23 kg/m2 with comorbid
  conditions
• Recommended starting dose is 10 mg once daily.
• If there is inadequate weight loss, the dose may
  be titrated after four weeks to a total of 15 mg
  once daily.
• The 5 mg dose should be reserved for patients who
  do not tolerate the 10 mg dose.