niddk obesity and diabetes research
TRANSCRIPT
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Prodigal versus Frugal Phenotype:
A Parable
Jonathan Krakoff, M.D.
Chief, besity and Diabetes Clini!al "esear!h #e!tion
Phoeni$ %pide&iology and Clini!al "esear!h 'ran!h, (ational )nstitute of Diabetes,
Digestive and Kidney Diseases
(ational )nstitutes of *ealth
Phoeni$, Ari+ona
For the National Press Foundation
February -rd, /0
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A brief overvie1 of the ()DDK !lini!al resear!h unit:2&ore up !lose and personal vie1s on our tour34
Inpatient unit
5 Metaboli! kit!hen
5 6hole "oo& )ndire!t Calori&eters 24
5 'o&b !alori&etry
5 Auto&ated vending &a!hines
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7he %nergy 'alan!e %8uation
)ntake
Expenditu
re
Body Weight
*o1 &u!h you eat
*o1 &u!h you absorb
*o1 &u!h energy you 9burn
e.g. Metaboli! rate ;
Physi!al a!tivity
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Measuring %nergy %$penditure
/aurent de
>avoisier theori+ed:'urning !andle needs o$ygen
; releases heat
#o do organis&s need o$ygen
and release heat as they !o&bust
food
An early e$a&ple of Dire!t Calori&etry
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%nergy %$penditure
5 (utrient &etabolis& !reates energy
5 %$tra!tion of !he&i!al energy o!!urs via o$idation
29burning4 of fuels to C and *
5 Measure gas 1hole body !onsu&ption ; Crelease
5 %nergy produ!tion?energy liberated fro& o$idi+ing
!arbohydrates @ lipids @ proteins
6hen you &easure the !hange in and C?
)ndire!t Calori&etry
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)ndire!t Calori&etry Modalities
5 "esting energy e$penditure
#upine
*ood pla!ed over parti!ipant
5 B hour energy e$penditure
6hole roo& indire!t !alori&eter 2"espiratory
!ha&ber4
#ealed roo& but 1ith air inair outA!tivity is li&ited but not resting
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Schematic of Whole Room Calorimeter
"avussin et al. JC) /E0
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7otal
Daily %%
"esting
Metaboli!
"ate
7her&i!
effe!t of
food
A!tivity
related
Components of Energy Expenditure
%nergy fro&
physi!al a!tivity
%nergy fro& food
!onsu&ption
%nergy fro& organ
fun!tion
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Energy Expenditure (as measured in our whole room
calorimeter) is strongly tied to body size
Weyer C et al !"# $%%%
'igger people
9burn &ore energy
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7he 7hrifty enotypePhenotype
Proposed an underlying genotype that lead to insulin overprodu!tion
fro& food intake
)&portant in energy !onservation, as 1ould favor adipose storage
'enefi!ial in ti&es of fa&ine
2allo1 hunter=gatherer populations to in!rease fat &ass during ti&es of food
availability for storage during food s!ar!ity4
verti&e, this hypothesis has been revised:
Fo!us on evolutionary thriftiness 2energy !onservation4
in fa!e of repeated fa&ine
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Energy expenditure may ha&e a role in future weight
gain
iaggi and Krakof JCEM 2013
r=-0.16, p=0.00
B' he effect is &ery &ery modest
So for e&ery $** +cal lower EE
this corresponds to only *,-+g.yr more weight gain
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7otal
Daily %%
"esting
Metaboli!
"ate
7her&i!
effe!t of
food
A!tivity
related
/eople do not spend their li&es in 0energy balance1
We o&ereat2 we diet3
%nergy fro&
physi!al a!tivity
%nergy fro& food
!onsu&ption
%nergy fro& organ
fun!tion
What happens to EE
when we o&ereat4
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%nergy e$penditure in hu&ans does not !hange
nearly as &u!hG
=/
=H
H
/
/H
=
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: B: E: /: /0: :/
/.
/.B
/.0
/.E
.
.B
*ours in !alori&eter 2h4
%% per &in 2k!al4
%nergy e$penditure over B hours: !o&parison of fasting vs.
energy balan!e
% ? %nergy 'alan!eF#7 ? fasting
$un"%
Enter
&inner 'na"k
'(eep
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verfeeding in!reases energy e$penditure
0:00 4:00 8:00 12:00 16:00 20:00
1
1.2
1.4
1.6
1.8
2
2.2
2.4
6ours in calorimeter (h)
EE per min (+cal)
E) = Energ*+a(an"e
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Spendthrift &s, hrifty /henotypes
hrifty
Spendthrift
r=0.1,p0.01
#t d tli
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#tudy outline
Screening
"ral 7lucose olerance est to assure did not ha&e diabetes
Baseline
wo wee+ period of weight maintaining diet
ndirectCalorimetry
8cclimation whole room indirect calorimeter stay (eucaloric) -nd eucaloric calorimeter stay for precise determination of -9 h EE in
energy balance "&erfeeding (-**5) and fasting chamber (in random order)
9- days
caloric
restriction
:ed ;*5 of weight maintaining energy needs (Ensure) :ood in duplicate collected daily for bomb calorimetry Stool and urine collected wee+ly (< days per wee+) for
bomb calorimetry 8ctical monitors worn on wrists.an+les and at hip
continuously Calorimeter stays wee+ly
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=ess decrease in energy expenditure with fasting was
associated with greater weight loss
r=-0.84, p=0.0006
Reinhardt & Votruba, Diabetes 2015
#t d tli
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#tudy outline
Screening "ral 7lucose olerance est to assure >ormal 7lucose Regulation
Baseline /eriod on weight maintaining diet
ndirectCalorimetry
8cclimation whole room indirect calorimeter stay (eucaloric)
-nd eucaloric calorimeter stay for precise determination of -9 h EE inenergy balance
nter&ention?iets
; x -**5 o&erfeeding $ :asting Random order
< day wash out period with weight maintaining diet between calorimeterstays
=ong term:ollow 'p
@ A months 8nnual x years
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Predi!tors of 1eight !hange at 0 &onths
=0.32 kg! EE de"rea#e ad4u#ted/or 5a#e(ine eig%t, age, #ex and ra"e
=0.72 kg! EE in"rea#e ad4u#ted/or 5a#e(ine eig%t, age, #ex and
ra"e#!hloegl, Piaggi, 7hearle, Diabetes /0revie1
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#u&&ary
5 %nergy e$penditure &easured in energy balan!e
is a very 1eak predi!tor of 1eight gain
5 6e have identified spendthrift and thrifty
phenotypes defined by fasting and overfeeding1hi!h:
)dentify individuals likely to do less 1ell 1ith !alori!
restri!tion
Are at risk for future 1eight gain
Follo1 us on t1itter: ()DDKgov
Media !onta!t: ()DDKMedianiddk.nih.gov
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uestions4