obesity - pathophysiology, etiology and management
TRANSCRIPT
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Obesity
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Origin of the problem
Food supplies used to be intermittent Storing energy in excess of what is required for immediate use was
and is essential for survival. Adipose tissue - stores excess energy efficiently as triglycerides Releases stored energy as free fatty acids for use when needed This physiologic system, orchestrated through endocrine and neural
pathways, permits humans to survive starvation for as long as several months.
Now however… nutritional abundance & a sedentary lifestyle, and influenced importantly by genetic this system increases adipose energy stores and produces adverse health consequences.
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Definition
Def: Obesity is a state of excess adipose tissue mass. Although often viewed as equivalent to increased body
weight need not be the caseAlthough not a direct measure of adiposity, the most
widely used method to gauge obesity is the body mass index (BMI) i.e. kg/cm2
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Definition
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Dwayne (The Rock) Johnson
Height: 190 cmWeight: 113 kgBMI: 31.3
Is he obese??
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Introduction
Other approaches to quantify obesityAnthropometry (skinfold thickness)Densitometry (underwater weighing)Computed tomography (CT)Magnetic resonance imaging (MRI)Electrical impedanceOther indices
Lean mass index Fat percentage
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Introduction
The distribution of adipose tissue in different anatomic depots also has substantial implications for morbidity
This distinction is made clinically by the waist-to-hip ratio (WHR)
>0.9 in women >1.0 in men
ABNORMAL
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Prevalence
Estimated that over 12% of the world’s adult population is obese
Estimations in India reveal that 5-12% are obese
⅓ of the adult population of the US Obese
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Physiological regulation of energy balance
Body weight is regulated by both endocrine and neural components Alterations in stable weight by forced overfeeding or food deprivation
induce physiologic changes that resist these perturbations
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The Leptin Pathway
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Effects of Leptin
Leptin resistance
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Factors affecting appetite
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Etiology of obesity
LIFESTYLE
PSYCHOLOGICAL MEDICAL
GENETIC
OBESITY
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Environmental/Psychosocial
Increased caloric intake▪Availability, price▪Extra 50 cal/day (1 tsp
sugar) = 2.25 kg/year = 25 kg over 10 years
More sedentary▪Television/Computer▪Emphasis on
academics
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Medical causes
Cushing’s syndrome Hypothyroidism Insulinoma Craniopharyngioma and other disorders
involving the hypothalamus Drug induced
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Complications of Obesity
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Complications of Obesity
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Complications associated with Obesity
Hypertriglyceridemia
Hypertension
Hyperuricemia
Venous insufficiency
DM
Cardiovascular disease
CholelithiasisCarcinomas
Pickwickian syndrome
Cardiac failure
Death
BMI
Duration of obesity
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Management of Obesity
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Work up
Physical exam – Focus on possible complications Investigations:
Blood sugar, lipid profile, liver function tests
Other tests based on clinical features TSH, Sleep studies Dexamethasone suppression test for Cushing’s syndrome*
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Treatment
PreventionDietIncreased physical activityBehavior modificationMedicines
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Guide to treatment options
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Weight loss & weight maintenance
Diet
, nu
triti
on
Phys
ical
activ
ity
Lifes
tyle
mod
ifica
tion
Phar
mac
o-th
erap
y
Integrated weight management
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Behaviour modification
Self monitoring of weightStress managementSocial support
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Diet
The primary focus of diet therapy is to reduce overall calorie consumption Very low energy diets (e.g., 400 to 600
kcal/d) Low-calorie diets, >800 kcal/d very low fat diets very low carbohydrate “Atkins” style diets
Guidelines recommend initiating treatment with a calorie deficit of 500–1000 kcal/d compared with the patient's habitual diet.
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Diet
The revised Dietary Reference Intakes for Macronutrients released by the Institute of Medicine recommends
45–65% of calories from carbohydrates, 20–35% from fat, and 10–35% from protein. daily fiber intake of 38 g (men) and 25 g (women) for
persons over 50 years of age and 30 g (men) and 21 g (women)for those under age 50.
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Diet
Low-carbohydrate, high-protein diets appear to be more effective in lowering BMI;
improving coronary heart disease risk factors, including an increase in HDL cholesterol and a decrease in triglyceride levels;
controlling satiety in the short term compared with low-fat diets
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Diet
Occasionally, very low calorie diets (VLCDs) are prescribed as a form of aggressive dietary therapy.
The primary purpose of a VLCD is to promote a rapid and significant (13–23 kg) short-term weight loss over a 3- to 6-month period.
These propriety formulas typically supply 800 kcal, 50–80 g protein, and 100% of the recommended daily intake for vitamins and minerals.
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Exercise
Increased energy expenditure is the most obvious mechanism for an effect of exercise
Exercise appears to be a valuable means to sustain diet therapy
Valuable in the obese individual for its effects on cardiovascular tone and blood pressure
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Pharmacotherapy
Recommended if BMI >/= 27 with comorbidities or BMI >/= 30
Facts:Drugs alone cause modest weight lossDiet with drugs improves efficacyEffects maintained for duration of treatment
onlyLong term safety data not available
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Pharmacotherapy
Medications for obesity have traditionally fallen into two major categories:
1. Appetite suppressants (anorexiants) 2. Gastrointestinal fat blockers
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Pharmacotherapy
Centrally Acting Anorexiant MedicationAnorexiants increases satiety and decreases hunger,
these agents help patients reduce caloric intake without a sense of deprivation.
Targets the ventromedial and lateral hypothalamus
Eg PHEN/TPM (Phenteramine and Topiramate) 9.3% and 8.6% weight lost in 2 large trials
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Pharmacotherapy
Centrally Acting Anorexiant Medication Lorcaserin is a selective 5-HT2C receptor agonist thought to decrease food intake through the pro-
opiomelanocortin system of neurons.
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Pharmacotherapy
Peripherally Acting Medications (Gastrointestinal fat blockers)
Orlistat is a synthetic hydrogenated derivative of a naturally occurring lipase inhibitor, lipostatin
Potent, slowly reversible inhibitor of pancreatic, gastric, and carboxylester lipases and phospholipase A2 required for the hydrolysis of dietary fat into fatty acids.
Acts in the lumen of the stomach and small intestine Blocks the digestion and absorption of ~30% of dietary
fat Weight loss of ~9–10%
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Pharmacotherapy
In developmentBupropion and naltrexoneLiraglutide
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Surgery
IndicationsBMI > 35 with an associated comorbidity or a BMI > 40
(irrespective) Repeated failures of other therapeutic approachesCapability of tolerating surgery
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Surgery
Weight loss surgeries have traditionally been classified into 3 categories on the basis of anatomic changes: Restrictive Restrictive-malabsorptive Malabsorptive
Clinical benefits of bariatric surgery in achieving weight loss and alleviating metabolic comorbidities have been attributed largely to changes in the physiologic responses of gut hormones and in adipose tissue metabolism.
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Surgery
Restrictive surgeries limit the amount of food the stomach can hold and slow the rate of gastric emptying.
Malabsorptive surgeries reduce the amount of absorption
A. Laparoscopic gastric band (LAGB)
B. The Roux-en-Y gastric bypass.
C. Biliopancreatic diversion with duodenal switch.
D. Biliopancreatic diversion.vertical-banded gastroplasty
E. Biliopancreatic diversion
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Surgery
These procedures generally produce a 30–35% average total body weight loss that is maintained in nearly 60% of patients at 5 years.
Significant improvement in multiple obesity-related comorbid conditions, including type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, quality of life and long-term cardiovascular events.
The most common surgical complications include stomal stenosis or marginal ulcers
The restrictive-malabsorptive procedures carry an increased risk for micronutrient deficiencies of vitamin B12, iron, folate, calcium, and vitamin D.
Patients with restrictive-malabsorptive procedures require lifelong supplementation with these micronutrients.
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