obesity - pathophysiology, etiology and management

Obesity

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.

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

Definition

Dwayne (The Rock) Johnson

Height: 190 cmWeight: 113 kgBMI: 31.3

Is he obese??

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

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

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

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

The Leptin Pathway

Effects of Leptin

Leptin resistance

Factors affecting appetite

Etiology of obesity

LIFESTYLE

PSYCHOLOGICAL MEDICAL

GENETIC

OBESITY

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

Medical causes

Cushing’s syndrome Hypothyroidism Insulinoma Craniopharyngioma and other disorders

involving the hypothalamus Drug induced

Complications of Obesity

Complications of Obesity

Complications associated with Obesity

Hypertriglyceridemia

Hypertension

Hyperuricemia

Venous insufficiency

DM

Cardiovascular disease

CholelithiasisCarcinomas

Pickwickian syndrome

Cardiac failure

Death

BMI

Duration of obesity

Management of Obesity

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*

Treatment

PreventionDietIncreased physical activityBehavior modificationMedicines

Guide to treatment options

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

Behaviour modification

Self monitoring of weightStress managementSocial support

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.

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.

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

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.

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

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

Pharmacotherapy

Medications for obesity have traditionally fallen into two major categories:

1. Appetite suppressants (anorexiants) 2. Gastrointestinal fat blockers

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

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.

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%

Pharmacotherapy

In developmentBupropion and naltrexoneLiraglutide

Surgery

IndicationsBMI > 35 with an associated comorbidity or a BMI > 40

(irrespective) Repeated failures of other therapeutic approachesCapability of tolerating surgery

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.

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

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.