Obesity – a 2014 Overview

Tim Greenaway PhD, FRACPDirector Clinical Endocrinology

Royal Hobart Hospital

Scope of Talk

• Definition• Prevalence• Significance• Pathophysiology of weight regulation• Treatment – difficult! (recidivism)

Obesity

• Excess body fat• Defined anthropometrically by Body Mass

Index (BMI) > 30kg/m2

• Prevalence increasing (63.4% Australian adult population overweight or obese –Australian Health Survey 2011-12)

• Associated with increased morbidity/mortality

Venus of Willendorf. c.24,000-22,000 BCE (Naturhistorisches Museum, Vienna)

Australian Health Surveys Obesity Data

Trends in the Number of Obese Persons, According to Region

Ezzati M, Riboli E. N Engl J Med 2013;369:954-964

Medical Consequences of Obesity

Deaths and Burden of Disease Attributable to Selected Behavioral and Dietary Risk Factors in 2010 and the

Metabolic and Physiological Mediators of Their Hazardous Effects

Ezzati M, Riboli E. N Engl J Med 2013;369:954-964

Hepatic steatosis

Insulin resistance

-cell dysfunction

Diabetes

Atherogenesis

Metabolic effects of Visceral WAT accumulation

Nat Rev Immunol, 2006

The March of Civilisation?

The “Lucky” Country

Activity is Declining

First Law of Thermodynamics

• The first Law of Thermodynamics, or energy balance, states that in a closed system, energy can neither be created nor destroyed, only transformed or transferred

• “Calories in = calories out”However,• Humans are not closed systems

Weight is Regulated by the Brain

Arcuate NucleusNPY CARTAGRP aMSH

Lateral HypothalamusOrexin MCH

Paraventricular Hypothalamic NucleusOxytocin CRH

Brain Stem

FOOD INTAKE

ENERGY EXPENDITURE

Cerebral Cortex conscious will

StomachGhrelin

+

FatLeptin

IntestineCCKPYY3-36

GLP-1Oxyntomodulin

-

PancreasInsulinAmylinPP

OpioidsDopamine EndocannabinoidsSerotoninNoradrenaline

- -

Obesity is Familial

BMI o

f Sub

ject

s

21

22

23

24

25

26

27

Adoptee Weight Class

Stunkard AJ, N Engl J Med 1986;314(4):193-8

Genes and the Environment:Danish Twin Adoption Studies

ThinI MedianII OverweightIII ObeseIV

I II III IV

Biological Parents

I II III IV

Adoptive Parents

FatherMother

Why is weight nearly always regained?

Diet and behavioural intervention

Very-low-calorie diet

Modified diet plusbehaviour therapy

Very-low-calorie diet plusbehaviour therapy

Years after intervention

0

-5

-10

-15

-20

5

1intervention 2 3 4 5

Wei

ght c

hang

e (k

g)

Ghrelin levels after weight loss

Cummings DE et al. N Engl J Med. 346:1623-30 2002

Original Article

Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet

Iris Shai, R.D., Ph.D., Dan Schwarzfuchs, M.D., Yaakov Henkin, M.D., Danit R. Shahar, R.D., Ph.D., Shula Witkow, R.D., M.P.H., Ilana Greenberg, R.D., M.P.H., Rachel Golan, R.D., M.P.H.,

Drora Fraser, Ph.D., Arkady Bolotin, Ph.D., Hilel Vardi, M.Sc., Osnat Tangi-Rozental, B.A., Rachel Zuk-Ramot, R.N., Benjamin Sarusi, M.Sc., Dov Brickner, M.D., Ziva Schwartz, M.D., Einat

Sheiner, M.D., Rachel Marko, M.Sc., Esther Katorza, M.Sc., Joachim Thiery, M.D., Georg Martin Fiedler, M.D., Matthias Blüher, M.D., Michael Stumvoll, M.D., Meir J. Stampfer, M.D., Dr.P.H.,

for the Dietary Intervention Randomized Controlled Trial (DIRECT) Group

N Engl J MedVolume 359(3):229-241

July 17, 2008

Weight Changes during 2 Years According to Diet Group

Shai I et al. N Engl J Med 2008;359:229-241

Physical activity, dietary energy intake, and smoking in Cuba, 1980-2010

©2013 by British Medical Journal Publishing Group

Franco M et al. BMJ 2013;346:bmj.f1515

Prevalence of obesity and diabetes, incidence, and mortality in Cuba, 1980-2010

Franco M et al. BMJ 2013;346:bmj.f1515

©2013 by British Medical Journal Publishing Group

Distributions of body mass index as recorded by national surveys conducted in Cienfuegos

in 1991, 1995, 2001, and 2010

Franco M et al. BMJ 2013;346:bmj.f1515

©2013 by British Medical Journal Publishing Group

Original Article Bariatric Surgery versus Intensive Medical Therapy for Diabetes — 3-Year OutcomesPhilip R. Schauer, M.D., Deepak L. Bhatt, M.D., M.P.H., John P. Kirwan, Ph.D., Kathy Wolski, M.P.H., Stacy A. Brethauer, M.D., Sankar D. Navaneethan, M.D., M.P.H., Ali

Aminian, M.D., Claire E. Pothier, M.P.H., Esther S.H. Kim, M.D., M.P.H., Steven E. Nissen, M.D., Sangeeta R. Kashyap, M.D., for the STAMPEDE Investigators

N Engl J MedVolume 370(21):2002-2013

May 22, 2014

Mean Changes in Measures of Diabetes Control from Baseline to 3 Years

Schauer PR et al. N Engl J Med 2014;370:2002-2013

Polar Chart of Scores for Quality of Life at Baseline and 3 Years after Randomization

Schauer PR et al. N Engl J Med 2014;370:2002-2013

Anatomical sites of brown, white and beige adipocytes

Phenotypes of Adipose Tissue Depots

a. White Adipose Tissueb. Brown Adipose Tissuec. Browning of WATd. Transmission EM beige adipocytes within WAT depot

Adipocyte plasticity: browning of adipose tissue is an adaptive and reversible response to environment

Obesity management – What does the future hold?

• Population health Built environmentFood – cost, accessActivityChildhood obesity?

• IndividualMultidisciplinary approachBehaviour modificationPharmacological intervention (phentermine/topiramate,

lorcaserin, GLP-1 analogues, orlistat)Bariatric surgery