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Obesity – a 2014 Overview
Tim Greenaway PhD, FRACPDirector Clinical Endocrinology
Royal Hobart Hospital
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Scope of Talk
• Definition• Prevalence• Significance• Pathophysiology of weight regulation• Treatment – difficult! (recidivism)
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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
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Venus of Willendorf. c.24,000-22,000 BCE (Naturhistorisches Museum, Vienna)
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Australian Health Surveys Obesity Data
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Trends in the Number of Obese Persons, According to Region
Ezzati M, Riboli E. N Engl J Med 2013;369:954-964
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Medical Consequences of Obesity
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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
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Hepatic steatosis
Insulin resistance
-cell dysfunction
Diabetes
Atherogenesis
Metabolic effects of Visceral WAT accumulation
Nat Rev Immunol, 2006
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The March of Civilisation?
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The “Lucky” Country
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Activity is Declining
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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
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Weight is Regulated by the Brain
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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
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Obesity is Familial
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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
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Why is weight nearly always regained?
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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)
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Ghrelin levels after weight loss
Cummings DE et al. N Engl J Med. 346:1623-30 2002
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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
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Weight Changes during 2 Years According to Diet Group
Shai I et al. N Engl J Med 2008;359:229-241
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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
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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
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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
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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
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Mean Changes in Measures of Diabetes Control from Baseline to 3 Years
Schauer PR et al. N Engl J Med 2014;370:2002-2013
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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
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Anatomical sites of brown, white and beige adipocytes
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Phenotypes of Adipose Tissue Depots
a. White Adipose Tissueb. Brown Adipose Tissuec. Browning of WATd. Transmission EM beige adipocytes within WAT depot
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Adipocyte plasticity: browning of adipose tissue is an adaptive and reversible response to environment
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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