History Taking on Obesity
History of drugs which increase weight, eg. Steroids,
tricyclic antidepressants and atypical antipsychotics
History of alcohol and food preferences
Whether emotionally triggered
Depression, anxiety, mental illness, psychological trauma
Drug abuse or smoking
Measurement of Obesity
A. Body weight- In epidemiological studies it is
conventional to accept +2 Standard deviation from median
weight for Height as a cut off point for obesity.
Example: What is the ideal weight for a man weighing
Height = 185 cm
B. Skin fold thickness
Measured with harpender skin
calipers, at 4 sites - mid triceps, biceps, sub scapular and
suprailiac regions. The sum should be less than 40 in boys
and 50 in girls.
Body Mass Index or BMI
It is the measurement of choice for many physicians
and researchers studying obesity. BMI uses a mathematical
formula that takes into accounts both a person's height
and weight. BMI equals a person's weight in kilograms
divided by height in meters squared (BMI=kg/m2)
Table 1: Obesity Classification
Causes of Obesity
Genetic syndromes causing obesity
Leptin mutation causing Leptin deficiency
Melanocortin four mutation
Prader willi syndrome
Bardet ? Biedl syndrome
Positive caloric balance
Visceral, pericardial, perivascular and other periorgan
Growth of adipose tissue beyond its vascular supply
Increased number of adipose tissue cells
Ectopic fat deposition in other body organs
Increased free fatty acid
Increased leptin TNF-a and increased mineral corticoids
Increased pro-inflammatory responses
High blood pressure
Increased VLDL, triglycerides and apo B (small dense
Hyperandrogenemia in men
Table 3: Clinical manifestations and condition associated with PCOS
Medical conditions triggered by obesity
Obstructive sleep apnoea
Polycystic ovary disease
Differential diagnosis of obesity
Hormonal changes in obesity
Low SHBG and free testosterone
Low LH, FSH
Vitamin D deficiency
Adipose tissue produces the following
Hazards of Obesity
1. The increased body fat, increased central fat deposits
and increased weight gain are all associated with increased
risk of death. Four large and many smaller epidemiologic
studies have supported these findings. The studies include.
a. Build and BP study of 1979.
b. American Cancer Society Study.
c. Norwegian population study.
d. Nurses health trial.
A. Obesity and Heart Disease:
Data from nurse?s health
trial, the risk of CAD in US females increase 3.3 fold
with Body Mass Index > 29 Kg/m2 when compared with
females with Body Mass Index< 21Kg/m2. Of more
importance is the inverse relationship between HDL
cholesterol and Body Mass Index. Low HDL increase risk
of CAD. Obesity increases the cardiac work which will
lead to cardiomyopathy and heart failure.
B.Obesity and Respiratory System:
The major effects
are increased residual volume associated with increased
abdominal pressure on diaphragm. Sleep apnea is
associated with obesity. The hypothesis is that the increase
neck circumference and fat deposits in pharyngeal area
may lead to sleep apnea.
C. Obesity and DM
Obesity is strongly associated with
D. Gall Bladder Disease
Obesity leads to Cholelithiasis.
If there is 10 Kg increase in body fat, the cholesterol
increases to the tune of as much cholesterol in yolk of one
egg. This goes in bile and leads to stone formation.
E.Certain cancers are significantly increased in obesity
In Males - Neoplasms of colon, rectum and prostate.
In Females - Neoplasm's of reproductive tract and gall
This may be due to increased production of
estrogen by adipose tissue.
F. Changes in Bones, joints, muscles, connective tissue
and skin. Obesity leads to:-
Hirsutism may reflect altered reproduction status.
The most important are reproductive.
Irregular menses and frequent anovulatory cycles are seen.
H. Psychosocial function
Obesity is a stigmatized
condition. They are exposed to the consequences of public
Leptin In Pathogenesis of Obesity and Type-2 DM
Leptin is a product of the ob?gene and is secreted
by fat cells. It has role in appetite regulation, energy
expenditure and possibly modulation of insulin sensitivity.
The site of action seems to be hypothalamus. Leptin is
closely related to body mass index and waist circumference
and also to fasting and two hour insulin levels. Studies also
suggest its role in type-2 DM and insulin resistance. The
hypothalamic mediated resistance to leptin causes a rise in
leptin and initiates hyperinsulinemia and insulin resistance
Increased insulin levels leads to increased body
fat, dyslipidemia (due to lipogenesis and selective insulin
resistance in muscles). The increase adipose tissue
produces more leptin but due to down regulation of leptin
receptors in hypothalamus unregulated and continuous
feedings occurs and vicious cycle of hyperinsulinemia,
more fat and more leptin resistance is perpetuated. Other
possible mechanism is that increased fat predominantly
central accumulated due to insulin resistance may be
responsible for increased leptin production. This leads to
down regulations of leptin receptor and loss of appetite
control and hence perpetuation of vicious cycle.
Obesity is frequently associated with low grade
inflammation of adipose tissue and the increase in adipose
tissue macrophages is linked to an increased risk of type-2
Fat People Have More Fat Cells than Skinny
Obese subjects have on the average a 40% increase
in cell size and an increase of 190% in cell number. Studies
document that the number of adipocytes remain constant
in an adult.
Thus caloric deprivation results in a decrease
in cell size to normal, but the adipose hypercellularity
persists. In man, it is estimated that adipose cells are still
increasing in number upto early adolescence. Thus the cell
numbers increase in infancy and adolescence. The obese
patient has an excess number of adipocytes which are
enlarged as well; it is the effect of early feeding experience
and the interplay of such experience with genetic and early
psychological events really where the answers to endemic
obesity are to be found.
It was Jules Harsh who devised the method of
determining both the number and size of human adipocytes.
Could restriction and reformulation of early feeding aid in
the prevention of obesity in adult life? Answers to such
questions are still being sought.
Hormonal Changes in Obesity
Table 4: Factors that mediate the intersection of metabolism and immunity in obesity
FA= fatty acid; MCP-1 = monocyte chemotactic protein-1; MIF= macrophage migration inhibitory factor.
Ref: Kathryn E, Wellen and Gokhan S. Hotamisligil,
Inflammation, stress and diabetes, The Jr. of Clinical
Investigation, Vol.115,No.5,pg 1111-1119
DM & Obesity
A central body fat distribution with a high waist
hip ratio and an android and apple shaped habitu's in
association with increase insulin resistance, type-2,
hyperlipidemia and premature mortality.
A peripheral gynaecoid or pear shaped distribution
with low waist hip ratio is found in individuals who
exercise and does not carry these diseases.
The insulin resistance has been demonstrated
in obese patients using hyperglycemic and euglycemic
insulin clamp technique. The insulin mediated glucose
metabolism is decreased by 50% in obesity. Fatty acid
metabolism is enhanced in obesity and type-2 DM and
this may interfere with glucose utilization. Overweight
in a super imposed factor which perhaps by demanding
excessive insulin secretion to overcome insulin resistance
contributes to β cell exhaustion and a final decline to type-
2 DM. This is supported by the demonstration that insulin
secretion in impaired in all patients with type-2.
Adipose Tissue as an "Endocrine Organ"
I. Leptin - It is a 16-K dalton protein produced exclusively
in the adipocytes.
II. Tumor Necrosis factor alpha - Secreted by not only the
classic inflammatory cells but also by adipocyte. It has
been postulated to be responsible for insulin resistance
by alternation in the phosphorylation status of insulin
receptors substrate one (IRS-1) and to after insulin receptor
The relationship between body mass index and
risk of diabetes was shown by the Health Professionals
study. It was found that when body mass index was less
than 24 Kg/m2. The risk was lowest. At a body mass index
of 35 Kg/m2. The relative risk increased 40 fold of 4000%.
Management of Obesity
Approaches can be conservative like diet therapy,
pharmacotherapy, behavior modification.
Bariatric surgery, gastrointestinal electrical
stimulation, invasive endoscopic techniques like
intragastric balloons, bezoars.
Low carbohydrate, high protein diet, vegetarian
diet, diet based on plant and fibrous foods rich in complex
carbohydrates with low glycemic index when used,
increase satiety and lowers BMI. Fiber based dietary
supplement also helps. But diet regimen has very little
sustainability. 5% weight reduction for more than a year is
considered a success.
Reasons for inability to lose weight
If patient is on steroids, tricyclic antidepressants and
Emotionally triggered disordered eating behavior
History of depression, anxiety, mental illness and
psychological trauma or abuse, smoking, alcohol and
Table 5 : A) Effect of weight reduction on glucose tolerance
A) Effect of weight reduction on glucose tolerance
Using the body mass index at age 15 years, Colditz
and Coworkers showed that a 20 kg weight gain increased
risk for diabetes by 15 fold where as a weight reduction of
20 kg decreased risk to almost zero.
In a Swedish obesity study; Sizostrone and
colleagues observed that diabetes was present in 13%
to 16% of their obese subjects. Of those who underwent
gastric by pass and subsequently lost weight 60% of
subjects with diabetes were cured and diabetes developed
in only 0.5% of those who did not have diabetes at baseline.
In contrast in the obese control group who lost no weight
there was a small (16%) cure rate and a 7.8% incidence of
new cases of diabetes.
Thus we see that weight reduction decrease the
incidence of diabetes.
B) Role of Diet and Exercise
Diet - The standard weight reduction diet is of 1000 cal/
day. This diet helps patients to loose 1 to 2 pound/wk.
Under very careful medical supervision in hospitalized
patient 200 cal. Semi starvation diets can be used for 1
week followed either by diet containing 1200 cal or very
low protein sparing diet 600 to 800 cal/day.
Very low calories (protein sparing) modified diet (600 to 80 cal/day) includes
1. 1.5 gm protein/kg or 75 gm protein 50gms carbohydrates.
2. Potassium 30 mEq/day.
3. Multivitamins and minerals.
4. Sodium Chloride 5gms.
5. Calcium Carbonate 4 tab/day.
6. 1.5L fluids.
Patients on very low caloric diet should monitor
urine for ketosis biweekly electrolyte estimation. Should
undergo Electrocardiography after every 3 months,
particularly after losing 50 1bs (22.5 kg) to check cardiac
From their Meta analysis Epstein and Wing
reported that exercise training was modestly effective at
reducing body weight (0.09Kg/wk). Exercise induced
weight loss was dependent on weekly exercise energy
expenditure, initial body mass and frequency of exercise.
Table 6 Other Studies
Recently it has been found that high intensity
exercise but not prolonged endurance type training increase
skeletal muscle beta hydroxyacyl CoA dehydrogenase
activity, a key enzyme in beta oxidation pathway of fatty
acid metabolism. This can promote the oxidation of fatty
acids not only during exercise but during non exercising
periods, thereby promoting further fat loss.
Exercise training can reduce adiposity. Obese
patients should have minimum of 150 minutes of moderate
exercise per week. Bariatric surgery is becoming more
useful treatment for obesity. It helps to reach BMA target,
improve metabolic parameters, reduce inflammatory
markers and improve insulin sensitivity.
Metformin is a dimethylbiguanide. It belongs to
the class of biguanides.
Mechanism of action - Metformin therapy improves
insulin sensitivity as shown by a reduction in fasting plasma
glucose and insulin concentration. It is not effective in
absence of insulin. In patients of type-2 glucose lowering
is attributed mainly to low hepatic glucose output and
increased peripheral glucose uptake. Several other actions
may contribute such as increased intestinal use of glucose
and decreased fatty acid oxidation. Metformin also
increase translocation of GLUT-1 and GLUT-4 isoarm
of glucose transporters in different types of cells, and it
prevents the development of insulin resistance in cultured
hepatocytes and adipocytes for long periods to high insulin
Comparison of Sulphonylurea and Metformin
Metformin and Sulphonylurea cause similar
decrease in fating plasma glucose concentration in patients
with Type-2 DM.
Both sulphonylurea and insulin can cause
weight gain but this does not occur with metformin.
Sulphonylurea can induce hypoglycemia, whereas this
is rare with metformin therapy. Therefore metformin
has antihypoglycemia action where as sulphonylurea
and insulin has hypoglycemic action. Sulphonylurea
increase fasting plasma insulin concentration where as
metformin may decrease it. In theory, the reduced plasma
concentration of insulin or plasminogen activator inhibitor
type I could decrease the risk of macrovascular disease.
Thus we see that metformin is complimentary to
sulphonylurea and dietary therapy and represents a useful
additional drug for management of type-2.
Appetite reducing agents in obesity
There are several groups of drugs used as appetite
Bulk e.g. - psyllium promotes gastric filing
Psychogenic e.g. - impramine and amitryptylline
Anorexia (amphetamines) - most effective anorexics e.g. - Dextroampheteramine and methamphetamin.
Anticonvulsant - Phenytoin
Anti-histamines - Chlorpheniramine
Grape Fruit Pill
A) Anterior pituitary hormones. Human Chorionic
C) Starch Blockers (alpha amylase inhibitors)
D) Thyroid hormones.
Hypolipidemic agents - Gemfibrozil - 600mg twice daily
Antidepressive drugs like fluoxitine hydrochloride
may be useful in some and help in weight reduction. Oral
sustained release fenfluramine 20 mg was used to suppress
appetite. Now the drug is banned due to its side effect
Pioglitazone and Ramipril improve adipose
tissue function by increasing adiponectin secretion and
may contribute to reduction in vascular disease. But
pioglitazone causes weight gain.
Table 7: Newer drugs in obesity management
Insulin required in type-2 only when
1 Oral hypoglycemic Agent failure
2 Intercurrent illnesses
Problem of insulin therapy in obese DM
As seen earlier due to insulin resistance they
require a higher dose of insulin. With hyperinsulinemia
patient gets weight gain.
The dyslipidemia of obesity is best managed with
total fat reduction, TG levels are reduced with weight loss
and if necessary, fibrate therapy. RNYGB, LAGB and
LSG are most commonly performed procedures, each of
which has different anatomic and physiological properties.
Most useful procedure is RNYGB which is superior for
achieving weight loss as well as in improving metabolic
V-Block Therapy in diabetes and obesity
Vagal Nerve Modulation device is thought to
be effective for the treatment of obesity. By using very
high frequency but low energy electrical pulses, effects of
vagotomy are obtained. The maestro rechargeable system
consists of electrical pulse generator, wire and electrodes
implanted surgically in the abdomen. Stomach emptying
and fullness signaling goes by vagus nerve to brain to
satiety and hunger centre. Adverse effects of this device
are nausea, pain at the site of implantation, heart burn,
problems in swallowing, belching and chest pain.
Adrenergic or serotonin agonist produce appetite
suppression. Plain Phentermine, Phentermine Plus,
Topiramite are used. Side effects include rise of BP and
Drugs deactivating pancreatic lipase ? Orlisitat.
Invasive antiobesity therapy
Laparoscopic adjustable gastric banding, verticalhorizontal gastroplasty, gastric bypass (more effective)
Cost, invasiveness, reversibility, adjustability,
complications rate, recovery period, abrupt change in
lifestyle and eating habits are important facts influencing
selection of type of bariatric surgery.
Gastric lumen reduction
Transoral, endoluminal, gastroplasty. Food
malaborption (duodeno, jejuna bypass) is an endoscopically
implantable, impermeable polyethlene sleeve mimicking
bariatric surgery. Short term weight loss and metabolic
benefits occur. Complications are device migration and
anchor dislocation. Continuous abdominal pain and
Space occupying devices
They are endoluminal, non-surgical, reversible
and repeatable treatment of obesity devices which reduce
gastric volume and decrease food intake. Other effects are
change in gastric motility and hormonal profile. There is
10% weight loss, patient adopts new eating habits. Balloons
are inflated with 500-700 cc of saline or methylene
blue solution. Other balloons are totally implantable.
Intragastric prostheses - endogut, semistationary antral
balloon, slimmed gastric balloon and butterfly.
Gastrointestinal electrical stimulation of stomach
delay gastric emptying, affect vagal efferent impulses,
antral muscle contraction and cause 40% weight loss.
Improves Gherelin secretion in appetite disorders.
They are collection of foreign bodies, can be
located in oesophagus, stomach, intestine, colon and
rectum. Pharmoco Bezoars are made up of Aluminium
Hydroxy Antacid, bulk forming laxatives, cellulose
based tablets and vitamin. Complications are epigastric
discomfort, nausea and vomiting. Complications like
bleeding, gastric outlet obstruction, pressure necrosis
and gastric ulcer can occur. Small bowel bezoars cause
Rapunzel syndrome. There is mechanical obstruction at
hepato pancreatic ampulla, iron deficiency, anaemia and
frontal alopecia. Digestive resistant polyethylene bezoars
are used recently.
A Sugar Tax - A Bitter Pill to reduce Obesity
WHO recently urged the Governments to levy
taxes on sugar sweetened beverages to end childhood
obesity. Other interventions suggested are increasing
physical activity and improving access to healthy food.
Hungary, France, Finland and Mexico are among
the many countries that have taken to such measures. 34
US states and Districts of Columbia have food taxes that
affect sugar sweetened drinks. Mexico which has highest
prevalence rates for obesity in the world (33% between
ages of 2 to 8) has demonstrated significant reduction in
consumption of sugar after taxation. It was found there
is 6% drop in average quantity of purchase of unhealthy
drinks. The risk of childhood obesity is greater in low
socio-economic group. In 2014, 41 million children were
either overweight or obese.
India may be one of the biggest contributors
to the global pool of childhood obesity. India also has
underweight children - 14% in Sikkim and 44% in Bihar.
This is a big concern. Children who are at low birth weight
are at a greater risk of becoming overweight and obese
when they consume energy rich diets and have a sedentary
How diabetes improves with bariatric surgery ?
Caloric or energy restriction
Increased GLP-1 secretion
What are the complications of bariatric surgery ?
Gastric pouch dilatation due to disordered eating traits
Late dumping syndrome causing post prandial reactive
hypoglycemia due to dense carbohydrate intake
How will you treat late dumping syndrome?
Treated by dietary modifications, acarbose, calcium
channel antagonist and somatostatin analogue
What histopathological changes are seen in pancreatic
islets after bariatric surgery?
Extensive hypertrophy of islets and development of
What is Edmonton Obesity staging system?
This is a clinical tool to compliment BMI.
Pathogenesis and hazards of obesity are
discussed. Type 2 DM patient may be obese. If they lose
nesidioblastosis (insulinoma like symptoms with excessive
islet cells hyperplacia of pancreas)
What are the psychosocial problems after bariatric surgery?
Depression, suicide, self harm and divorce
What is a liver shrinkage diet?
t is a low caloric diet given to shrink liver glycogen
weight diabetes status may be improved. When diet fails
metformin is the drug of choice. Obese type 2 Diabetics
may need insulin occasionally due to sepsis or during
surgery. When insulin is used it is required in higher dose
due to peripheral insulin resistance [1, 2, 3, 4, 5, 6, 7, 8, 9].