niddk obesity and diabetes research

7/26/2019 NIDDK Obesity and Diabetes Research

1/23

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


2/23

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


3/23

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


4/23

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


5/23

%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


6/23

)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


7/23

Schematic of Whole Room Calorimeter

"avussin et al. JC) /E0


8/23

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


9/23

Energy Expenditure (as measured in our whole room

calorimeter) is strongly tied to body size

Weyer C et al !"# $%%%

'igger people

9burn &ore energy


10/23

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


11/23

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


12/23

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


13/23"oth1ell ; #to!k, (ature, /


14/23

%nergy e$penditure in hu&ans does not !hange

nearly as &u!hG

=/

=H

H

/

/H

=


15/23

: 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


16/23

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


17/23Weyer et al# nt, !, "besity# -**$

Spendthrift &s, hrifty /henotypes

hrifty

Spendthrift

r=0.1,p0.01

#t d tli


18/23

#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


19/23

=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


20/23

#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


21/23

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


22/23

#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


23/23

uestions4

niddk obesity and diabetes research

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