High-intensity interval training: a review of its impact ... · High-intensity interval training: a review of its impact on glucose control and cardiometabolic health ... HIIT is

REVIEW

High-intensity interval training: a review of its impact on glucosecontrol and cardiometabolic health

Sophie Cassidy1 & Christian Thoma2 & David Houghton1& Michael I. Trenell1

Received: 26 April 2016 /Accepted: 17 August 2016 /Published online: 28 September 2016# The Author(s) 2016. This article is published with open access at Springerlink.com

Abstract Exercise plays a central role in the manage-ment and treatment of common metabolic diseases, butmodern society presents many barriers to exercise.Over the past decade there has been considerable in-terest surrounding high-intensity interval training(HIIT), with advocates claiming it can induce healthbenefits of similar, if not superior magnitude tomoderate-intensity continuous exercise, despite reducedtime commitment. As the safety of HIIT becomes clearer,focus has shifted away from using HIIT in healthy individualstowards using this form of training in clinical populations. Thecontinued growth of metabolic disease and reduced physicalactivity presents a global health challenge and effective ther-apies are urgently required. The aim of this review is to ex-plore whether the acclaim surrounding HIIT is justified byexamining the effect of HIIT on glucose control, its ability toaffect cardiovascular function and the underlying mechanismsof the changes observed in those with common metabolicdiseases. It also explores translation of the research into clin-ical practice.

Keywords Cardiovascular system . Exercise . Exercisetherapy .Metabolic diseases . Metabolism . Physical fitness .

Review .Weight loss

AbbreviationsEDV End-diastolic volumeFMD Flow mediated dilationHIIT High-intensity interval trainingHRmax Maximum heart rateMICT Moderate-intensity continuous trainingNAFLD Non-alcoholic fatty liver diseasePGC-1α Peroxisome proliferator-activated receptor

gamma, coactivator 1, alphaRPE Rate of perceived exertionV:O2max Maximal oxygen consumption

V:O2peak Peak oxygen consumption

Why exercise?

Before the agricultural, industrial and digital ages, humansexpended large amounts of energy in activities centred onmaintaining shelter and procuring food and water [1]. Fastforward some 350 generations and the barriers to exerciseand physical activity in the 21st century are enormous.Sedentary behaviours, such as the use of mechanised transportand screen-based leisure pursuits have become the norm inmodern society. There is an urgent need therefore to find prac-tical, attractive and effective exercise therapies to combat thewave of inactivity sweeping through the western world.

Not only is exercise part of our nature, it is strongly associ-ated with reduced chronic disease risk. Globally, metabolic dis-orders such as themetabolic syndrome, non-alcoholic fatty liverdisease (NAFLD), type 2 diabetes and the closely associatedcluster of cardiovascular diseases are rapidly increasing [2].European and US treatment algorithms for these obesity drivenepidemics recommend weight loss and maintenance as a mainpriority across all stages [3, 4]. Conceivably, this can beachieved through energy restriction and/or physical exercise.

* Michael I. [email protected]

1 MoveLab, Institute of Cellular Medicine, The Medical School,Newcastle University, 4th Floor William Leech Building,Framlington Place, Newcastle upon Tyne NE2 4HH, UK

2 School of Interprofessional Health Studies, Auckland University ofTechnology, Auckland, New Zealand

Diabetologia (2017) 60:7–23DOI 10.1007/s00125-016-4106-1

http://crossmark.crossref.org/dialog/?doi=10.1007/s00125-016-4106-1&domain=pdf

Current management guidelines for these common meta-bolic conditions advise individuals to undertake around150 min of moderate-to-vigorous aerobic exercise per week,spread over most days of the week, in addition to resistancetraining on at least 2 days of the week [5, 6]. The emphasisremains on moderate-intensity continuous training (MICT);however there is mounting evidence that high-intensity inter-val training (HIIT) provides an alternative means of achievingthe same or greater health benefits vs MICT, provided thereare no medical contraindications to engaging in HIIT and thatit is well tolerated and preferred by the individual taking part.We refer readers to recent meta-analyses for a comprehensiveanalysis of the metabolic [7] and cardiorespiratory [8] benefitsof HIIT in patient groups. The aim of this review is to assim-ilate existing evidence and provide a clinically relevant narra-tive of the cardiometabolic benefits of HIIT in those withcommon metabolic diseases, before moving onto discussingits safety profile, tolerability and practical considerations fortranslation into clinical care. The information presented in thisreview is not part of a formal systematic review and, therefore,may not have been subjected to the rigor required for such asummary of the data currently available on HIIT.

What is HIIT?

HIIT can be described as ‘brief intervals of vigorous activityinterspersed with periods of low activity or rest’, which in-duces a strong acute physiological response (Fig. 1) [9]. Anumber of HIIT protocols have been adopted in the literature(see Table 1), but the majority of interventions use high-intensity intervals lasting between 1 and 4 min. The goal ofHIIT is to accumulate activity at an intensity that the partici-pant would be unable to sustain for prolonged periods (i.e. 80–95% of peak oxygen consumption (V

:O2peak ) or >90% of

maximum heart rate (HRmax), therefore the recovery time

should be sufficient to allow the subsequent interval to becompleted at the desired intensity. The total duration of aHIIT session tends to be ≥20 min, which actually makes itcomparable with recommendations for MICT, in terms of du-ration. There is also a sub-category of HIIT involving 10–30second intervals and intensities often exceeding 100%V:O2peak, i.e. ‘all-out’ exercise at a workload that is above

maximal aerobic capacity [10]. This is often called sprint in-terval training and has not been substantially tested in clinicalpopulations and will therefore not be covered further.

The vast majority of the published HIIT research, particu-larly in clinical populations, has used exercise modalitiesinvolving cycling, walking, and running, mostly carried outon stationary cycles and treadmills (see Table 1). However,other equipment, such as cross-trainers/ellipiticals [11], arereasonable options for some. Evidently there is clear variationthroughout the literature and it still remains to be determinedwhether an optimal HIIT protocol exists for metabolic diseasemanagement.

HIIT and metabolic health

Skeletal muscle molecular adaptations

A number of molecular adaptations have been identified with-in skeletal muscle following HIIT (Fig. 2). Skeletal muscle isthe primary site for glucose disposal via insulin- and non-insulin-mediated glucose uptake; the latter stimulated by mus-cular contraction. It therefore plays a large role in regulatingmetabolism.

Increased GLUT-4 content GLUT-4 content in the vastuslateralis increased by 369% following six sessions of HIITin type 2 diabetes patients [12]. Insulin resistance underliesmetabolic disease and although decreased GLUT-4 content is

Work Rest5 min warmup Work Rest Work Rest Work Rest Work3 min

cool down

RPE (Borg scale)

20

19

18

17

16

15

14

13

12

11

10

9

8

7

6

100

Heart rate(% HRpeak)

80

60

40

20

0

Fig. 1 An example of a HIITprotocol. Schematic of the HIITprotocol adopted by our group inadults with NAFLD [39] and type2 diabetes [38]. Intensity wasbased upon the perceived rate ofexertion (RPE), inducing a strongacute physiological response inheart rate (shown as % peak heartrate [HRpeak]), which increasesacross intervals

8 Diabetologia (2017) 60:7–23

Tab

le1

Effecto

fHIITon

insulin

andglucosemetabolism

inpatientswith

themetabolicsyndrome,NAFL

Dor

type

2diabetes

CG

M: s

ee a

bove

Ref

eren

ceB

asel

ine

popu

lati

onP

roto

cola

Cha

nges

in m

etab

olis

m

Acu

te (

sing

le s

essi

on)

effe

ct

Tjø

nna

et a

l 20

11 [

26]

4 m

en/7

wom

en, t

he m

etab

olic

syn

drom

e, 5

5±13

yea

rs,

BM

I 30

±2,

2m

axO

V34

±3

HII

T: 4

× 4

min

incl

ine

trea

dmill

wal

king

at 9

0–95

% H

Rm

axw

ith 3

m

in r

ecov

ery

peri

ods

at 7

0% H

Rm

ax

FG ↓

~15%

bel

ow b

asel

ine

for

72 h

vs

CO

N

4 m

en/4

wom

en, t

he m

etab

olic

syn

drom

e, 5

2±11

yea

rs,

BM

I 29

±2,

2m

axO

36±

3M

ICT

: 47

min

at 7

0% H

Rm

ax(m

atch

ed f

or e

nerg

y ex

pend

iture

with

H

IIT

)FG

↓~1

5% b

elow

bas

elin

e fo

r 24

h v

s C

ON

5 m

en/4

wom

en, t

he m

etab

olic

syn

drom

e, 5

0±9

year

s,

BM

I 32

±1,

2m

axO

32±

3C

ON

: res

ting

FG n

.s.

Gill

en e

t al

2012

[23

]7

adul

ts (

sex

n.r.

), ty

pe 2

dia

bete

s, 6

3±3

year

s, B

MI

31±

2,

2pea

kO

n.r.

HII

T: 1

0 ×

1 m

in c

yclin

g at

~89

% W

Rpe

akw

ith 6

0 s

pass

ive

rest

pe

riod

s R

elat

ive

to v

alue

s on

a n

on-e

xerc

isin

g co

ntro

l day

: 3 h

pos

tpra

ndia

l A

UG

C ↓

~35%

. Pos

t-mea

l pea

k gl

ucos

e ↓1

6% a

nd ti

me

in

hype

rgly

caem

ia ↓

65%

Kar

stof

t et a

l 20

14 [

25]

7 m

en/3

wom

en, t

ype

2 di

abet

es, 6

0±2

year

s, B

MI

28±

1,

2pea

kO

30±

3 (c

ross

over

des

ign)

HII

T: w

alki

ng a

t 89%

2p

eak

Ofo

r 3

min

inte

rval

s an

d 54

%

2pea

kO

for

3 m

in r

ecov

ery

× 1

h

MM

T: m

ean

gluc

ose

↓12%

vs

CO

N a

nd ↓

6% v

s M

ICT

. Mea

n in

crem

enta

l glu

cose

↓40

% v

s C

ON

and

↓29

% v

s M

ICT

CG

M: s

ame

day

mea

n gl

ucos

e ↓1

2% v

s M

ICT

and

n.s

. vs

CO

N.

Nex

t day

pos

t exe

rcis

e n.

s. v

s C

ON

and

MIC

T

MIC

T: w

alki

ng a

t 73%

2p

eak

O×

1 h

(m

atch

ed f

or e

nerg

y

expe

nditu

re w

ith H

IIT

)

MM

T: m

ean

gluc

ose

n.s.

vs

CO

N

CG

M: s

ame

day

mea

n gl

ucos

e n.

s. v

s C

ON

. Nex

t day

mea

n gl

ucos

e ↑8

% v

s C

ON

CO

N: r

estin

gM

MT

and

CG

M: s

ee a

bove

Litt

le e

t al

2014

[22

]2

men

/8 w

omen

, 6 w

ith I

FG, 4

1±11

yea

rs, B

MI

36±

7,

2pea

kO

22±

2H

IIT

: (m

orni

ng)

10 ×

1 m

in c

yclin

g in

terv

als

at ~

90%

WR

peak

with

1

min

rec

over

y pe

riod

s at

15%

WR

peak

CG

M: d

inne

r A

UG

C ↓

32%

vs

CO

N. D

inne

r po

stpr

andi

al g

luco

se

peak

↓41

% a

nd 3

9% v

s C

ON

and

MIC

T, r

espe

ctiv

ely.

Bre

akfa

st

AU

GC

↓36

% a

nd ↓

33%

vs

CO

N a

nd M

ICT

,resp

ectiv

ely.

B

reak

fast

pos

tpra

ndia

l glu

cose

pea

k ↓3

0% v

s C

ON

and

MIC

T

MIC

T: (

mor

ning

) cy

clin

g m

atch

ed w

ith H

IIT

for

tota

l wor

k at

~3

5% W

Rpe

ak

CG

M: d

inne

r A

UG

C ↓

22%

vs

CO

N. n

.s. f

or o

ther

mea

sure

d va

riab

les

CO

N: n

o ex

erci

se

V V

V

V V

V

V

V

Diabetologia (2017) 60:7–23 9

Tab

le1(continued)

Ref

eren

ceB

asel

ine

popu

lati

onP

roto

cola

Cha

nges

in m

etab

olis

m

Ter

ada

etal

20

16 [

24]

8 m

en/2

wom

en, t

ype

2 di

abet

es, 6

0±6

year

s, B

MI

31±

5,

2pea

kO

23±

7 H

IIT

fast

ed: (

exer

cise

pre

-bre

akfa

st)

trea

dmill

wal

king

1 m

in a

t 100

%

2pea

kO

with

3 m

in a

t 40%

2p

eak

O, f

or 6

0 m

in (

15 h

igh-

inte

nsity

inte

rval

s)

CG

M: 2

4 h

mea

n gl

ucos

e ↓1

6% v

s C

ON

. Tim

e >

10 m

mol

/l ↓5

8%.

Lun

ch p

ostp

rand

ial a

nd to

tal p

ost-m

eal A

UG

C ↓

88%

and

↓37

% v

s C

ON

, res

pect

ivel

y. B

reak

fast

and

din

ner

AU

GC

n.s

.

HII

Tfe

d: (

exer

cise

pos

t-br

eakf

ast)

, as

abov

eC

GM

: n.s

. for

all

mea

sure

s

MIC

Tfa

sted

: (ex

erci

se p

re-b

reak

fast

) tr

eadm

ill w

alki

ng a

t 55%

2pea

kO

for

60 m

inC

GM

: lun

ch a

nd d

inne

r po

stpr

andi

al a

nd to

tal p

ost-m

eal A

UG

C

↓44%

, ↓95

% a

nd ↓

53%

vs

CO

N, r

espe

ctiv

ely.

n.s

. for

24

h m

ean

gluc

ose,

tim

e >

10 m

mol

/l an

d br

eakf

ast p

ostp

rand

ial A

UG

C

MIC

Tfe

d: (

exer

cise

pos

t-br

eakf

ast)

, as

abov

eC

GM

: tot

al p

ost-

mea

l AU

GC

↓31

%. n

.s. f

or a

ll ot

her

mea

sure

s

CO

N: n

o ex

erci

seC

GM

: see

abo

ve

Cum

ulat

ive

(mul

tiple

ses

sion

) ef

fect

Litt

le e

t al

2011

[12

]8

adul

ts (

sex

n.r.

), ty

pe 2

dia

bete

s, 6

3±8

year

s, B

MI

32±

6,

2pea

kO

n.r.

H

IIT

: 10

× 1

min

inte

rval

s at

~90

% H

Rm

axw

ith 1

min

res

t per

iods

; 3

sess

ions

/wee

k fo

r 2

wee

ksC

GM

(24

h): m

ean

gluc

ose

↓13%

, 24

h r

AU

GC

↓14

%, s

um o

f 3

h po

stpr

andi

al A

UG

C ↓

30%

Tjø

nna

et a

l 20

08 a

nd

2011

[20

,26]

4 m

en/7

wom

en, t

he m

etab

olic

syn

drom

e, 5

5±13

yea

rs,

BM

I 30

±2,

2m

axO

34±

3H

IIT

: 4 ×

4 m

in in

clin

e tr

eadm

ill w

alki

ng a

t 90–

95%

HR

max

with

3

min

rec

over

y pe

riod

s at

70%

HR

max

; 3 s

essi

ons/

wee

k fo

r 16

wee

ksIS

(fr

om H

OM

A)

↑24%

vs

MIC

T a

nd C

ON

FG ↓

4.3%

4 m

en/4

wom

en, t

he m

etab

olic

syn

drom

e, 5

2±11

yea

rs,

BM

I 29

±2,

2m

axO

36±

3M

ICT

: 47

min

at 7

0% H

Rm

ax. 3

ses

sion

s/w

eek

for

16 w

eeks

(m

atch

ed f

or e

nerg

y ex

pend

iture

with

HII

T)

IS (

from

HO

MA

) n.

s.

FG n

.s.

5 m

en/4

wom

en, t

he m

etab

olic

syn

drom

e, 5

0±9

year

s,

BM

I 32

±1,

2m

axO

32±

3C

ON

: no

inte

rven

tion

IS (

from

HO

MA

) n.

s.

FG n

.s.

Sten

svol

d et

al

201

0 [3

5]11

adu

lts (

sex

n.r.

), th

e m

etab

olic

syn

drom

e, 5

0±10

yea

rs,

BM

I 31

±4,

2p

eak

O34

±10

, str

atif

ied

by a

ge a

nd s

exH

IIT

: tre

adm

ill w

alki

ng/r

unni

ng a

t 90–

95%

HR

peak

for

4 m

in ×

4

bout

s w

ith a

ctiv

e re

cove

ry p

erio

ds o

f 3

min

at 7

0% H

Rpe

ak;3

se

ssio

ns/w

eek

for

12 w

eeks

IS (

from

HO

MA

) n.

s.

FG n

.s.

HbA

1cn.

s.

11 a

dults

(se

x n.

r.),

the

met

abol

ic s

yndr

ome,

51±

8 ye

ars,

B

MI

32±

4,

2pea

kO

32±

5R

ET

: 3 s

ets

of 8

–12

repe

titio

ns ×

3–5

exe

rcis

es; 3

ses

sion

s/w

eek

for

12 w

eeks

IS (

from

HO

MA

)n.s

.FG

n.s

. H

bA1c

n.s.

VV

V

V

V

V V V V V


Tab

le1(continued)

Ref

eren

ceB

asel

ine

popu

lati

onP

roto

cola

Cha

nges

in m

etab

olis

m

10 a

dults

(se

x n.

r.),

the

met

abol

ic s

yndr

ome,

53±

10 y

ears

, B

MI

30±

4,

2pea

kO

28±

6H

IIT

+R

ET

: HII

T a

s ab

ove,

2 s

essi

ons/

wee

k, 3

res

ista

nce

exer

cise

s fo

r 8–

12 r

epet

ition

s, 1

ses

sion

/wee

k, a

ll fo

r 12

wee

ksIS

(fr

om H

OM

A)

n.s.

FG n

.s.

HbA

1cn.

s.

11 a

dults

(se

x n.

r.),

the

met

abol

ic s

yndr

ome,

47±

10 y

ears

, B

MI

32±

4,

2pea

kO

34±

10C

ON

: no

exer

cise

IS (

from

HO

MA

) n.

s.

FG n

.s.

HbA

1cn.

s.

Ter

ada

et a

l 20

13 [

46]

4 m

en/4

wom

en, t

ype

2 di

abet

es, 6

2±3

year

s, B

MI

28±

4,

2pea

kO

23±

5H

IIT

: cyc

ling

1 m

in 1

00%

2r

eser

veO

+ 3

min

20%

2p

eak

Ofo

r 30

min

in w

eeks

1–4

, 45

min

in w

eeks

5–8

, 60

min

in w

eeks

9–1

2; 5

se

ssio

ns/w

eek

for

12 w

eeks

FG n

.s.

HbA

1cn.

s.

4 m

en/3

wom

en, t

ype

2 di

abet

es, 6

3±5

year

s, B

MI

33±

5,

2pea

kO

23±

5M

ICT

: 40%

2r

eser

veO

for

30 m

in in

wee

ks 1

–4, 4

5 m

in in

wee

ks

5–8,

60

min

in w

eeks

9–1

2; 5

ses

sion

s/w

eek

for

12 w

eeks

(m

atch

ed

for

ener

gy e

xpen

ditu

re w

ith H

IIT

)

FG n

.s.

HbA

1cn.

s.

Ear

nest

et a

l 20

13 [

33]

21 m

en, ‘

at r

isk

of ty

pe 2

dia

bete

s’, 4

8±9

year

s, B

MI

30+

2,

2pea

kO

30±

3H

IIT

: cyc

ling

6 w

eek

MIC

T r

un-i

n ph

ase,

then

2 m

in in

terv

als

at

90–9

5%

2pea

kO

and

2 m

in 5

0%

2pea

kO

reco

very

, sta

rtin

g at

2

inte

rval

s/se

ssio

n an

d in

crea

sed

by 2

inte

rval

s pe

r w

eek

until

8

inte

rval

s/se

ssio

n in

wee

k 9;

3–4

ses

sion

s/w

eek

for

12 w

eeks

24 h

pos

t exe

rcis

e: 2

h g

luco

se ↓

13%

, HO

MA-

IR ↓

22%

and

fas

ting

insu

linn.

s.

72 h

pos

t exe

rcis

e: H

OM

A-I

R ↓

16%

, 2 h

glu

cose

and

fas

ting

insu

lin n

.s.

16 m

en, ‘

at r

isk

of ty

pe 2

dia

bete

s’, 4

9±9

year

s, B

MI

31±

3,

2pea

kO

28±

5M

ICT

: 40%

2p

eak

O, 3

–4 s

essi

ons/

wee

k fo

r 12

wee

ks (

mat

ched

for

ener

gy e

xpen

ditu

re w

ith H

IIT

)

24 h

pos

t exe

rcis

e: 2

h g

luco

se ↓

12%

, HO

MA-

IR n

.s

72 h

pos

t exe

rcis

e: 2

h g

luco

se, H

OM

A-I

R a

nd f

astin

g in

sulin

n.s

.

Kar

stof

t et a

l 20

13 a

nd

2014

[36

,14]

7 m

en/5

wom

en, t

ype

2 di

abet

es, 5

8±2

year

s, B

MI

29±

1,

2pea

kO

27±

2H

IIT

: wal

king

at >

70%

pea

k en

ergy

exp

endi

ture

× 3

min

inte

rval

s,

<70

% o

f pe

ak e

nerg

y ex

pend

iture

× 3

min

rec

over

y, f

or 1

h; 5

se

ssio

ns/w

eek

for

16 w

eeks

CG

M: 4

8–72

h p

ost e

xerc

ise:

mea

n gl

ucos

e ↓9

% a

nd m

axim

um

gluc

ose

↓20%

vs

CO

N

96–1

20 h

pos

t exe

rcis

e: f

astin

g in

sulin

↓19

% v

s C

ON

. FG

, 2 h

gl

ucos

e, A

UG

C a

nd H

bA1c

n.s.

8 m

en/4

wom

en, t

ype

2 di

abet

es, 6

1±2

year

s, B

MI

30±

2,

2pea

kO

26±

1M

ICT

: wal

king

at >

55%

of

peak

ene

rgy

expe

nditu

re f

or 1

h; 5

se

ssio

ns/w

eek

for

16 w

eeks

(mat

ched

for

ene

rgy

expe

nditu

re w

ith

HII

T)

CG

M: 4

8–72

h p

ost e

xerc

ise:

n.s

. cha

nges

.

96–1

20 h

pos

t exe

rcis

e: f

astin

g in

sulin

, FG

, 2 h

glu

cose

, AU

GC

an

d H

bA1c

n.s.

5 m

en/3

wom

en, t

ype

2 di

abet

es, 5

7±3

year

s, B

MI

30±

2,

2pea

kO

25±

2C

ON

: no

exer

cise

CG

M: 4

8–72

h p

ost e

xerc

ise:

mea

n gl

ucos

e ↑1

7% v

s ba

selin

e

96–1

20 h

pos

t exe

rcis

e: f

astin

g in

sulin

, FG

, 2 h

glu

cose

, AU

GC

and

H

bA1c

n.s.

V V

VV

V

V

VV

V

VV

V V VV


Tab

le1(continued)

Ref

eren

ceB

asel

ine

popu

lati

onP

roto

cola

Cha

nges

in m

etab

olis

m

Hol

leki

m-

Stra

nd e

t al

2014

[44

]

20 a

dults

(se

x n.

r.),

type

2 d

iabe

tes,

59±

5 ye

ars,

BM

I 30

±3,

2p

eak

O32

±6

HII

T: 4

× 4

min

inte

rval

s at

90–

95%

HR

max

for

40 m

in; 3

se

ssio

ns/w

eek

for

12 w

eeks

(ex

erci

se m

ode

n.r.

)H

bA1c

↓6%

HO

MA

-IR

n.s

.

17 a

dults

(se

x n.

r.),

type

2 d

iabe

tes,

55±

5 ye

ars,

BM

I 30

±4,

2p

eak

O33

±7

MIC

T: ≥

10 m

in/b

out,

210

min

/wee

k ×

12

wee

ks (

sess

ions

wer

e do

ne a

t hom

e w

ithou

t sup

ervi

sion

, exe

rcis

e m

ode

n.r.

) H

bA1c

and

HO

MA

-IR

n.s

.

Mitr

anun

et a

l 20

14 [

41]

5 m

en/9

wom

en, t

ype

2 di

abet

es, 6

1±3

year

s, B

MI

30±

1,

2pea

kO

n.r.

HII

T: t

read

mill

50%

2p

eak

Oor

20 m

in in

wee

ks 1

–2. 4

× 1

min

inte

rval

s at

80%

2p

eak

Ow

ith 4

min

rec

over

y at

50%

2p

eak

Oin

wee

ks 3

–6. 6

× 1

min

inte

rval

s at

85%

2p

eak

Ow

ith 4

min

reco

very

at 6

0%

2pea

kO

in w

eeks

7–1

2; 3

ses

sion

s/w

eek

for

12

wee

ks

48–7

2 h

post

exe

rcis

e: H

OM

A-I

R ↓

19%

vs

CO

N. H

bA1c

↓10%

vs

CO

N. F

G ↓

14%

5 m

en/9

wom

en, t

ype

2 di

abet

es, 6

2±3

year

s, B

MI

30±

1,

2pea

kO

n.r.

MIC

T: t

read

mill

50%

2p

eak

Ofo

r20

min

in w

eeks

1–2

, 60%

VO

2pea

kfo

r 20

min

in w

eeks

3–6

and

65%

2p

eak

Ofo

r 30

min

s in

wee

ks 7

–12;

3 s

essi

ons/

wee

k fo

r 12

wee

ks (

mat

ched

for

ene

rgy

expe

nditu

re w

ith H

IIT

)

48–7

2 h

post

exe

rcis

e: H

OM

A-I

R ↓

18%

vs

CO

N. F

G ↓

13%

. HbA

1c

n.s.

5 m

en/1

0 w

omen

, typ

e 2

diab

etes

, 61±

2 ye

ars,

BM

I 30

±0.

4,

2pea

kO

n.r.

CO

N: n

o ex

erci

se48

–72

h po

st e

xerc

ise:

HO

MA

-IR

, FG

and

HbA

1cn.

s.

Shab

an e

t al

2014

[37

]3

men

/6 w

omen

, typ

e 2

diab

etes

, 40±

10 y

ears

, BM

I 34

±5,

2pea

kO

20±

4 H

IIT

: 30

s cy

clin

g at

100

% e

stim

ated

pea

k w

orkl

oad

× 4

with

4

min

rec

over

y at

25%

est

imat

ed p

eak

wor

kloa

d; 3

ses

sion

s/w

eek

for

2 w

eeks

Glu

cose

imm

edia

tely

pos

t exe

rcis

e ↓0

.95

mm

ol/l

(mea

sure

d af

ter

each

of

the

six

sess

ions

). F

G, f

astin

g in

sulin

, HO

MA

-IR

n.s

.

Hal

lsw

orth

et

al 2

015

[39]

6 m

en/6

wom

en, N

AFL

D, 5

4±10

yea

rs, B

MI

31±

4,

2pea

kO

22±

6H

IIT

: cyc

ling

5 in

terv

als

at R

PE o

f 16

–17

(‘ve

ry h

ard’

), in

terv

alle

ngth

2 m

in in

wee

k 1,

incr

easi

ng 1

0 s/

wee

k, r

ecov

ery

was

3 m

in

incl

udin

g 1

min

ligh

t res

ista

nce

exer

cise

; 3 s

essi

ons/

wee

k fo

r 12

w

eeks

2h g

luco

se ↓

15%

. FG

, fas

ting

insu

lin, H

bA1c

an

d H

OM

A2-

IR n

.s.

10 m

en/1

wom

an, N

AFL

D, 5

2±12

yea

rs, B

MI

31±

5,

2pea

kO

25±

6C

ON

: no

exer

cise

2h g

luco

se, F

G, f

astin

g in

sulin

, HbA

1c an

d H

OM

A2-

IR n

.s.

V V

V V

V

V V V

V

V

V

V

V

V

V


Tab

le1(continued)

HbA

1c↓4

% a

nd 2

h g

luco

se ↓

6% v

s C

ON

. FG

, 2 h

AU

GC

and

H

OM

A2-

IR n

.s.

Ref

eren

ceB

asel

ine

popu

lati

onP

roto

cola

Cha

nges

in m

etab

olis

m

Rob

inso

n et

al

201

5 [4

5]3

men

/17

wom

en, ‘

elev

ated

ris

k of

type

2 d

iabe

tes

base

d on

HbA

1c’,

52±

10 y

ears

, BM

I 33

±7,

2p

eak

O20

±3

HII

T: (

self

-sel

ecte

d m

ode)

1 m

in in

terv

als

at 8

5–90

% W

max

an

d 1

min

rec

over

y at

20%

Wm

ax ×

4 in

ses

sion

1 (

4 in

terv

als

in s

essi

on 1

an

d 10

inte

rval

s by

ses

sion

10,

incr

emen

t n.r

.); 5

ses

sion

s/w

eek

for

2 w

eeks

48–7

2 h

post

exe

rcis

e: F

ruct

osam

ine

↓22%

. FG

, fas

ting

insu

lin a

nd

HO

MA

-IR

n.s

.

4 m

en/1

4 w

omen

, ‘el

evat

ed r

isk

of ty

pe 2

dia

bete

s ba

sed

on H

bA1c

’, 5

2±10

yea

rs,

BM

I 31

±4,

2p

eak

O21

±5

MIC

T: (

self

-sel

ecte

d m

ode)

at 6

0–65

% W

max

for

20 m

in in

ses

sion

1

(inc

reas

ing

to 5

0 m

in in

ses

sion

10

to m

atch

tota

l wor

k of

HII

T

grou

p). 5

ses

sion

s/w

eek

for

2 w

eeks

(m

atch

ed f

or e

nerg

y ex

pend

iture

with

HII

T)

48–7

2 h

post

exe

rcis

e: F

G ↓

5% v

s H

IIT

. Fru

ctos

amin

e ↓1

3%.

Fast

ing

insu

lin a

nd H

OM

A-I

R n

.s.

Fex

et a

l 201

5 [1

1]4

men

/12

wom

en, I

FG o

r ty

pe 2

dia

bete

s, 6

0±6

year

s,

BM

I 35

±5,

2p

eak

O40

±8

HII

T: e

llipt

ical

/cro

ss-t

rain

er 3

0 s

inte

rval

at 8

0–85

% H

Rm

ax a

nd 9

0 s

activ

e re

cove

ry (

inte

nsity

n.r

.) ×

20

min

; 3 s

essi

ons/

wee

k fo

r 12

w

eeks

FG ↓

8%H

bA1c

n.s

.

Mad

sen

et a

l 20

15 [

34]

3 m

en/7

wom

en, t

ype

2 di

abet

es, 5

2±2

year

s, B

MI

31±

1,

2pea

kO

22±

1H

IIT

: cyc

ling

10 ×

1 m

in in

terv

als

at ~

90%

HR

max

with

1 m

in r

est

(1:1

res

t: in

terv

al r

atio

); 3

ses

sion

s/w

eek

for

8 w

eeks

FG ↓

~11%

. 2 h

glu

cose

↓~1

3%. H

bA1c

↓~4

%. H

OM

A-I

R ↓

~17%

5 m

en/8

wom

en, ‘

heal

thy

cont

rol’

, 56±

2 ye

ars,

BM

I 31

±1,

2p

eak

O26

±2

FG, 2

h g

luco

se a

nd H

bA1c

n.s.

H

OM

A-I

R n

.s.

Cas

sidy

et a

l 20

16 [

38]

10 m

en/2

wom

en, t

ype

2 di

abet

es, 6

1±9

year

s, B

MI

31±

5,

2pea

kO

22±

5H

IIT

: cyc

ling

5 in

terv

als

at R

PE o

f 16

–17

(‘ve

ry h

ard’

), in

terv

al

leng

th 2

min

in w

eek

1 in

crea

sing

10

s/w

eek,

rec

over

y w

as 3

min

in

clud

ing

1 m

in li

ght r

esis

tanc

e ex

erci

se; 3

ses

sion

s/w

eek

for

12

wee

ks

8 m

en/3

wom

en, t

ype

2 di

abet

es, 5

9±9

year

s, B

MI

32±

6,

2pea

kO

20±

6C

ON

: no

exer

cise

FG ↑

17%

. 2 h

glu

cose

↑10

%. 2

h r

AU

GC

↑13

%. H

bA1c a

nd

HO

MA

2-IR

n.s

.

V V

V

V

V

V

V

Studypopulatio

ndemographics(sam

plesize

bysex,healthor

activ

itydescription,age,body

massindex(kg/m

2),andV: O

2peak(m

lkg−

1min−1)o

rV: O

2max

(mlkg−

1min−1)asreported

bystudyauthorsare

provided

asmeans

±SDandroundedto

nearestw

holenumber

Samplesizesarebasedon

thoseincluded

inthefinalanalysis

Resultshave

been

convertedto%

change

from

baselin

eifthechange

was

statisticallysignificant,andalso

notedifthiswas

significantrelativetocomparisongroup(s).W

heredatawas

reported

ingraph

form

itmay

noth

avebeen

feasibleto

accurately

calculate%

change,thusapproxim

ate%

aregiven

a Coreexercise

with

outw

arm

upandcool

downprotocols,consistin

gpredom

inantly

of5–10

min

periodsof

light-to-moderate-intensity

continuous

activ

ity

AUGC,areaunderthe

glucosecurve;CGM,contin

uous

glucosemonito

ring;C

ON,controlgroup;FG

,fastin

gglucose;IFG,impaired

fastingglucose;IS,insulinsensitivity;M

MT,mixed

mealtest;n.r.,not

reported;n.s.,no

statisticallysignificantchange/difference;R

ER,respiratory

exchange

ratio

atrest;R

ET,resistance

exercise

training

group;WRpeak,peakworkload;W

max,m

axim

alworkload;↑,increase;

↓,decrease


not the cause of insulin resistance, any increase in this proteinimproves glucose transport within skeletal muscle [13].Another study found that 16 weeks of HIIT in type 2 diabetespatients induced higher membrane-bound GLUT-4 andGLUT-4 mRNA levels in comparison with energy matchedMICT, but no rise in overall GLUT-4 protein content wasobserved [14]. The reduced intensity of intervals in this study

(70% V:O2peak) compared with other HIIT protocols is worth

noting, however, as is the fact that biopsies were obtained5–6 days post-training.

Mitochondrial adaptations Reduced mitochondrial content[15], mitochondrial function [16] and markers of mitochon-drial biogenesis in skeletal muscle are commonly observed inindividuals with metabolic disease [17] and have been sug-gested to contribute to insulin resistance. In adults with type 2diabetes, 2 weeks of HIIT (90% HRmax) significantlyincreased mitochondrial capacity evidenced by an increasein citrate synthase activity and raised content of electron trans-port chain complexes [12]. In contrast, 16 weeks of intervalwalking (70% V

:O2peak) only elicited changes in citrate syn-

thase mRNA expression but not in citrate synthase activity.However, as stated above, this could be due to the lowerintensity of intervals used in this study compared with tradi-tionally adopted HIIT protocols and because muscle biopsieswere obtained 5–6 days post-training [14].

Peroxisome proliferator-activated receptor, gamma, coactiva-tor 1, alpha (PGC-1α) regulates muscle mitochondrial

biogenesis [18]. Following HIIT, increases in nuclear PGC-1αlevels have been observed [19], as well as increases in totalPGC-1α vastus lateralis content in biopsy samples. Similarchanges were not observed following energy matched MICT[20]. It has been proposed that the fluctuations in ATP turnoverduring interval training, which differs from the usual steady stateconditions of ATP production, could activate signalling path-ways that lead to this increase in PGC-1α following HIIT [21].

Sarcoplasmic reticulum Sarcoplasmic reticulum Ca2+

handling plays an important role in muscle fatigue andincreased Ca2+ reuptake into the sarcoplasmic reticulum hasbeen demonstrated following HIIT, but not MICT in adultswith the metabolic syndrome [20]. Increases as large as50–60% were observed in Ca2+ reuptake, significantly im-proving the work capacity of the muscle and thereby contrib-uting to improvements in fitness following HIIT. This studyindicates that HIIT provides a more potent stimulus comparedwith MICT to induce skeletal muscle adaptations. However,definite conclusions cannot be drawn from one small study,with a total sample size of 32 participants.

HIIT and glucose control

Key studies on the impact of HIIT on glucose control havebeen summarised in Table 1. These adopt a range of protocolsand cover both the acute and training responses to HIIT.

Cardiometabolic effects of HIIT

3

1

2

Changes to cardiovascular system

1 Torsion = myocardial damage 2 EDV = preload 3 Ca2+ handling = SV + EF4 FMD = O2 supply

3

2

41

Changes in skeletal muscle

1 Ca2+ reuptake into SR = muscle work capacity 2 Mitochondria biogenesis = oxidative capacity 3 GLUT4 = glucose transport

Ca2+

Ca2+

Ca2+

Ca2+

Ca2+

Ca2+ Ca2+

Ca2+

Ca2+

NO

NO

NO

Fig. 2 Cardiometabolic effects ofHIIT. The figure depicts thepreviously reported muscular andcardiovascular impact of HIIT inthose with common metabolicdiseases. In boxes of text: upwardarrow, increase; downward arrow,decrease. EDV, end diastolicvolume; EF, ejection fraction;FMD, flowmediated dilation; SR,sarcoplasmic reticulum; SV,stroke volume


The acute response Few studies have assessed the acuteresponse to HIIT in patients with metabolic disorders andthose that have are summarised in Table 1. Relative to no ex-ercise, a single session of HIIT reduces same-day postprandialarea under the glucose curve in those with impaired fastingglucose [22] or type 2 diabetes [23, 24]. Similarly, HIIT isassociated with reduced time of glucose being ≥10 mmol/L[23, 24]. However, studies assessing the effect of HIITon mean24 h glucose levels have been less consistent, with some indi-cating no effect [22, 23, 25], and one showing a reduction butonly when the exercise was performed in a fasted state [24].When comparedwith energymatchedMICT, HIIT tended to beslightly superior [22, 25, 26] (see Table 1). As measurementswere not reported much past 24 hours post exercise, the dura-tion of these effects is uncertain. Earlier work relying on chang-es in fasting glucose to assess impact, suggests a measurableeffect may last as long as 72 h post HIIT, but for a shorter periodfollowing MICT [26].

Since postprandial glucose excursions are strong predictorsof cardiovascular disease [27], which may be due to possibleinductions of oxidative stress and micro/macrovascular dam-age [28], the above findings are of clinical relevance.Unfortunately, the available research does not provide clarityon dose–response in terms of intensity, duration or total ener-gy expenditure. Further head-to-head comparisons of differentprotocols are required. However, it is worth noting that a pro-tocol of 1 min intervals with 1 min recovery, repeated tentimes (a modest time investment), improves acute glucosecontrol [22, 23].

The transient nature of changes in glucose metabolism inresponse to exercise is well documented. Insulin-independentglucose disposal is increased during and for approximately60 min post exercise [29]. Insulin-dependent glucose disposalincreases for several hours to a few days following exercise[29, 30]. These effects are localised to contracting muscle[29], thus exercise involving a larger muscle mass is prefera-ble. Higher-intensity exercise has been shown to recruit alarger proportion of muscle fibres compared with moderate-intensity exercise [31], which may explain greater improve-ments in glucose regulation following HIIT. In light of theseacute adaptations, patients should be recommend not tohave more than two exercise-free days, in accordance withguidelines [32].

The training response Of the studies assessing the effects oflonger-term HIIT (≥2 weeks), some report reduced fastingglucose [11, 20, 26, 33, 34], while others report no change[35–39] (Table 1). Where reductions in fasting glucose areobserved, they appear to be similar to those seen followingMICT [7]. Fasting glucose is predominantly a marker ofhepatic insulin sensitivity. After just 1 week of a diet verylow in energy (very low calorie diet; 2510 kJ/day [600 kcal/day]), liver fat content decreased by 30%, hepatic insulin

sensitivity significantly improved and fasting glucose fell by35% in adults with type 2 diabetes [40]. The reduction in fastingglucose following participation in HIIT is generally smaller [11,20, 26, 34, 41], (≤14%, see Table 1), suggesting that exercise(whether HIIT or MICT), lacks potency for improving hepaticinsulin sensitivity, when compared with consumption of a verylow calorie diet. This is most likely because exercise elicits asmaller energy deficit than that achieved with a modest changein eating behaviour. For example, to achieve an energy deficitsimilar to that achieved by reducing energy intake by the equiv-alent of the energy in a blueberry muffin (∼1891 kJ [452 kcal]),a 68 kg female would need to run approximately 38 min at apace of 9.7 km/h [42]. We did, however, show that HIIT wasable to significantly reduce liver fat and, thereby, fasting glu-cose in some type 2 diabetes individuals [38], but the averagereduction in liver fat did not result in a significant reduction infasting glucose levels. Whether an increase in the duration ofthe HIIT intervention (i.e. >12 weeks) would achieve a reduc-tion in fasting glucose levels in this cohort is yet to bedetermined.

HIIT has been shown to improve peripheral insulin sensitiv-ity in those with impaired metabolic control. The molecularadaptations to HIIT described above, including raised GLUT-4content, increased aerobic enzyme capacity and mitochondrialbiogenesis, have all been associated with improved peripheralinsulin sensitivity [13, 43]. Studies assessing the metabolic im-pact of HIIT in those with common metabolic diseases havefound no change in HOMA-IR [37–39, 44, 45], whereas othershave shown an approximate 20% improvement compared witha control group [20, 33, 34, 41] (Table 1). When compared withMICT, HIIT seems to have a small but significant benefit oninsulin resistance [7].

HIIT can also decrease HbA1c [34, 38, 41, 44], yetsome studies have reported no change [11, 36, 39, 46](Table 1). Although there have been a number of studies pub-lished since, a meta-analysis found that a 0.47% absolute re-duction in HbA1c is observed with HIIT in adults with com-mon metabolic diseases, compared with controls [7]. This isslightly lower than the 0.6% absolute HbA1c reductionobserved following aerobic and resistance exercise in type 2diabetes [47]. Both HIIT and other forms of exercise comparewell with improvements achieved throughmetformin [48] andare likely to have clinical benefits, since a 1% absolute rise inHbA1c leads to a 21% increased risk of diabetes related death,a 14% increased risk of myocardial infarction and a 37% in-creased risk of myocardial infarction [47].

Other indicators of glucose control, such as 2 h glucosefollowing an oral glucose challenge and glucose AUC aresimilarly inconsistent across studies (see Table 1). Severalexplanations for the reported inconsistencies across studiesinclude differences in study populations, exercise protocolsand the degree of volunteer supervision during exercise.However, the most plausible explanation is the variation in


time of post-intervention measures relative to the last bout ofexercise. Studies reporting both the acute and cumulativeeffect of HIIT have consistently shown that changes in indi-cators of glucose control last between 24 and 72 h post exer-cise [25, 26, 33, 36] (Table 1). Only one study has demon-strated a longer-term adaptation, in which fasting insulin wasreduced 96–120 h post exercise [36]. Greater inter-study con-sistency in the timing of post exercise assessments is warrant-ed in the future; continuous glucose monitoring for at least72 h post exercise and HbA1c assessments may also allowus to gauge benefit better.

Collectively, the improvements in glucose control follow-ing HIIT are clinically relevant but do not surpass those seenfollowing the traditionally used MICT with regards to fastingglucose, HbA1c and fasting insulin [7]. HIIT does seem to leadto greater improvements in peripheral insulin sensitivity [7],but overall the use of HIIT for improving glycaemic outcomesshould not be over-emphasised compared with other forms ofexercise training.

HIIT and cardiovascular health

Cardiovascular complications are the leading cause of mortal-ity in those with common metabolic diseases [49, 50]. Theinterval design of HIIT to include rest periods enables patientsto accumulate time at higher exercise intensities, thereby chal-lenging the cardiovascular system. Limited evidence indicatesthat HIIT provides a stronger stimulus thanMICT for elicitingmyocardial improvements. Alongside the beneficial impact ofHIIT on vascular and cardiorespiratory fitness, this suggeststhat the cardiovascular benefit of HIIToutweighs the metabol-ic benefit.

Cardiac adaptations: molecular mechanisms

Because of the difficulty of obtaining human myocardial tissue,most evidence for the molecular adaptations to high-intensityexercise comes from experimental rodent models, the hearts ofwhich bear similarities to human hearts and mimic the humancardiac response to exercise training [51, 52]. The db/dbmouse model provides a good representation of the humanheart in diabetic patients. Following 13 weeks of HIIT, contrac-tility and Ca2+ handling were restored to normal levels as aresult of raised transverse tubule (T-tubule) density, sarcoplas-mic reticulum synchrony of Ca2+ release and sarcoplasmic re-ticulum Ca2+-ATPase (SERCA2a; Ca2+ transporter) activity[53]. These adaptations occurred despite no improvement inglucose or insulin levels, demonstrating the direct impact ofHIIT upon the myocardium. Similar adaptations have been ob-served in heart failure and healthy rodent models [54, 55], withgreater changes occurring following high-intensity exercise

(85–90% maximal oxygen consumption [V:O2max]) compared

with moderate-intensity exercise (65–70% V:O2max) [55].

Exercise also activates the phosphoinositol-3 kinase/Akt/mammalian target of rapamycin (mTOR) signal transductionpathway that leads to higher ribosomal biogenesis and proteinsynthesis, and thus induces physiological hypertrophy toa greater extent following high- (85–90% V

:O2max) vs

moderate- (65–70% V:O2max) intensity exercise [52, 55]. The

exercise-induced pathways activated in disease models maydiffer [54], but both healthy and disease rodent modelsindicate that exercise stimulates important transcription-al, translational and post-translational regulatory mecha-nisms that lead to structural remodelling of cardiac tis-sue and, thereby, improved strength of cardiac contrac-tions [52].

Cardiac structure

Adults with common metabolic diseases display left ventric-ular concentric remodelling, which represents a reduction inend-diastolic volume (EDV) and is also known as pathologi-cal hypertrophy [56, 57]. This reduction in EDV occurs inresponse to stress signals and is reflective of a build-up ofcollagen in the myocardium [58]. HIIT, on the other hand,has been shown to induce physiological hypertrophy [38],increasing left ventricular wall mass and EDV by means of aphysiological response to growth signals [58]. The number ofstudies investigating cardiac structure following HIIT is small;our group showed an 8 ml increase in EDV following12 weeks of HIIT in type 2 diabetes patients [38], but noimprovements in NAFLD patients [39]. Both of these studiescompared HIITwith a non-exercise control, rather thanMICT.That being said, HIIT has been shown to be superior to energymatched MICT in eliciting structural remodelling in thosewith hypertension [59] and heart failure [60].

Cardiac function

Systolic function Stroke volume and ejection fraction, twomeasures of the contractile capabilities of the heart, arereduced in those with metabolic disease [57]. Twelve weeksof HIIT induces systolic improvements in adults with type 2diabetes [38, 44], hypertension [59] and heart failure [60].Following 12 weeks of HIIT in heart failure patients, Wisløffet al [60] demonstrated a 35% and 17% relative increase inejection fraction and stroke volume, respectively, but nochange in these variables following energy matched MICT.These improvements are equal to those seen with commonlyused prescription medications, such as ACE inhibitors or betablockers [61]. Twelve weeks of HIIT in hypertensive patientsimproved early events in systole, which correlate to contrac-tility and are load independent [59]. Furthermore, 12 weeks of


HIIT in heart failure patients led to a 22% increase in globalcontractility [60]. These improvements were not observedfollowing energy matched MICT [60].

Cardiac torsion describes the twisting motion of the heartduring contraction and reflects the dominance of epicardialfibres over endocardial fibres. In adults with metabolic dis-ease cardiac torsion is raised [62], reflecting damage toendocardial fibres. Interestingly, we observed reductionsin cardiac torsion in adults with type 2 diabetes andNAFLD who partook in 12 weeks of HIIT, when comparedwith controls [38, 39], suggesting a reduction in endocar-dial damage following HIIT.

Diastolic function Diastolic dysfunction is often reportedin those with common metabolic diseases [57, 63].Impaired early filling of the left ventricle is indicative ofstiffer, damaged myocardial fibres that are less compliantduring relaxation; yet evidence suggests that HIIT has thecapacity to target these abnormalities. Two studies havedemonstrated significant improvements in early fillingrates following 12 weeks of HIIT in adults with type 2diabetes [38, 44], which were sustained 1 year later [44].Similar diastolic improvements were also observed inadults with NAFLD [39]. These HIIT-induced elevationsin early filling rate have been demonstrated to be as largeas 49%. In contrast, 12 weeks of MICT fails to have anyimpact upon diastolic variables [44, 59, 60]. These datasuggest that exercise intensity is an important characteris-tic for inducing diastolic improvements. Diastolic dys-function is an independent predictor of mortality [64],therefore any improvements in function are likely to beclinically significant.

Vascular function

Endothelial dysfunction is associated with metabolic dis-ease [65] and considered one of the earliest pathophysio-logical processes in the progression to atherosclerosis.Flow mediated dilation (FMD) is a measure of endothelialdysfunction and is regulated by NO availability. In thosewith common metabolic disease, HIIT has been shown tobe superior [44] or similar [35] to MICT for improvingFMD. Although not limited to common metabolic dis-eases, a meta-analysis of 182 participants demonstratedtwice the improvement in FMD following HIIT, comparedwith MICT [66]. This is most likely due to the greatershear stress experienced during higher-intensity exercise,since shear stress is the main stimuli for increasing NOavailability in the endothelium [59]. Consequently, im-proved FMD results in greater perfusion and oxygen sup-ply to peripheral tissue.

Findings with respect to the effect of HIIT on bloodpressure in individuals with common metabolic diseases

have been inconsistent; some studies demonstrate im-provements [11, 20, 35, 45], whereas some show nochange [36, 38, 39, 44] in blood pressure, despite pos-itive cardiac remodelling [38]. Exercise guidelines forthe treatment of hypertension advise low- to moderate-intensity exercise [67], but these findings suggest furtherwork is required to better define the role of HIIT inhypertension therapy.

Skeletal muscle and cardiac adaptations combine toimprove V

:O2peak following HIIT

It could be argued that the most important outcome fol-lowing HIIT is cardiorespiratory fitness, as measured by

V:O2peak. Large prospective studies have demonstrated fit-

ness to be more important than established risk factors formortality [68], and low V

:O2peak is independently associat-

ed with incident type 2 diabetes [69]. While the exercise-induced increase in V

:O2peak has never been directly linked

to mortality, large scale studies indicate that improvementsin fitness over time leads to significant reductions in mor-tality risk [70, 71].

V:O2peak is the gold standard measure of fitness and a strong

indicator of how well the cardiac, pulmonary, vascularand peripheral systems are working together. A numberof meta-analyses have demonstrated the substantial bene-fits of HIIT for V

:O2peak and its superiority in comparison

to MICT in healthy [72], coronary artery disease [73] andcardiometabolic disease patients [8]. In those with elevat-ed cardiometabolic risk, the increase in V

:O2peak with HIIT

(19.4%) was almost twice that of MICT (10.3%) [8]. Onaverage, V

:O2peak increases by 5.4 ml kg−1 min−1 follow-

ing HIIT, and even a smal le r improvement of3.5 ml kg−1 min−1 has been predicted to improve survivalby 10–25% [74].

Figure 2 provides an overview of the skeletal muscleand cardiac adaptations that are likely to contribute to theimprovements in V

:O2peak observed with HIIT. As dem-

onstrated in the figure, HIIT improves the capacity ofboth aspects of the oxygen supply and demand chain,but it is the cardiovascular adaptations in response toHIIT that are more likely to contribute to these V

:O2peak

improvements [75].

HIIT and weight loss

HIIT induces moderate weight loss (0.5–4 kg reduction)in adults with common metabolic diseases [11, 20, 34,36, 41, 46]. When compared with MICT, however, HIIT


provides no additional benefit as an exercise therapy forweight loss [7]. The ability of HIIT to induce reductionsin body weight should therefore not be overstated inthose with common metabolic diseases.

Although weight loss is strongly associated with re-duced metabolic complications [76], it does not reflectchanges in body composition; HIIT generally reduceswhole body fat mass by 1–3 kg, even when body weightremains stable [14, 35, 36, 41, 46, 77, 78]. Significantreductions in visceral and hepatic fat have also beenshown with HIIT [14, 38, 39]. These findings are impor-tant since these fat depots increase cardiovascular diseaserisk [79], and metabolic dysfunction [40, 80]. Three pos-sible mechanisms for HIIT-induced fat loss have beensuggested:

1. increased mitochondrial density and capacity fol-lowing HIIT leading to increased fat oxidation[81]

2. large elevations in catecholamines, which have beenshown to drive lipolysis [82], especially in the ab-dominal tissue where there are significantly more β-adrenergic receptors, compared with subcutaneousfat [83]

3. appetite suppression: energy intake the day after HIITwas∼1255 kJ (300 kcal) lower than after MICT, and ∼2510 kJ(600 kcal) lower than after rest [84]

It remains unclear whether HIIT is superior to MICTfor fat loss, with some studies supporting this notion [14,36, 46] and some not [34, 35, 41, 45, 78]. To date, evi-dence to support HIIT over other types of exercise for themanagement of body fat levels is unfounded, but there isenough proof to suggest that HIIT can induce positivechanges in body composition in adults with common met-abolic diseases.

A summary of the effects of HIIT can be found in the textbox ‘Summary of HIIT’.

Is HIIT safe?

Given the strong cardiovascular-focused physiological re-sponse to HIIT, it is appropriate to define the safety ofhigh-intensity activity in those at elevated cardiometabolicrisk. The acute cardiac response to HIIT has beenassessed in a few studies. In patients with coronary heartdisease, no contraindications to HIIT were observed andundesirable changes, such as ST-segment depression, re-covered during interval recovery periods [85, 86]. Also, inpatients with chronic heart failure, cardiac stress (asassessed by rate pressure product) stayed within accept-able values [87]. Furthermore, the studies mentionedabove did not report any serious adverse events withHIIT.

The largest available dataset assessing the safety ofHIIT was derived from a clinical audit of 4846 cardiacrehabilitation patients. It identified two non-fatal cardiacarrests in 46,364 h of supervised HIIT, and one fatalcardiac arrest in 129,456 h of supervised MICT [88].Although the low frequency of events makes the com-parison between the two exercise modalities inconclu-sive, it also highlights that the risk of either approachis low. It is important to note that all patients werereferred to cardiac rehabilitation by their general practi-tioner or hospital cardiologist and underwent a full med-ical screening and cardiopulmonary exercise test prior totaking part, to rule out recurrent ischaemia or chest painduring exercise.

The risk of sudden cardiac death and acute myocardialinfarction is increased following vigorous activity in suscep-tible individuals, including those with structural heart diseaseand congenital complications [89]. The American College ofSports Medicine and the American Heart Association provideguidelines for identifying high risk patients and carrying outpre-exercise screening in such individuals [6, 89]. Accordingto these guidelines those with common metabolic diseases areautomatically considered ‘high risk’. On the whole, however,

Summary of HIIT

1 Leads to modest improvements in metabolic control, of similar magnitude to other forms of exercise training

2 Should not be overstated for its role in weight loss

3 Has strong cardiovascular benefits

4 Leads to large improvements in cardiorespiratory fitness, often superior to other forms of exercise training


mounting clinical evidence supports HIITas a safe therapy forthe majority of individuals with elevated cardiometabolic risk.

Tolerability of HIIT in patients

The trials published to date illustrate the tolerability ofHIIT among diverse clinical populations and with varyingstudy durations (see Table 1). Although large-scale trialsare lacking, attempts have been made to assess the palat-ability of HIIT in previously sedentary populations. Agroup of obese women, some with type 2 diabetes, werenoted to prefer a HIIT approach to MICT [90], as didvolunteers with coronary heart disease [85]. Within HIITprotocols, enjoyment decreases with increasing intervallength [91]. Specifically, intervals of 30 or 60 s resultedin greater enjoyment than 120 s intervals.

Good adherence to free-living, non-supervised HIIT(<3 months) has been demonstrated in those with type 2 dia-betes [38], NAFLD [39] and those with either impaired glu-cose tolerance or impaired fasting glucose [92]. Good adher-ence was also observed with interval walking (3 min alterna-tive fast and slow walking) in a free-living environment over4 months in patients with type 2 diabetes [36] and over22 months in older adults [93]. Additional longer-term studiesare required but, nonetheless, these results indicate good ad-herence and tolerability to independent HIIT exercise.

Considerations when prescribing HIIT

Beyond the plethora of specific protocols to choose from,the way in which HIIT protocols are often described is, initself, a barrier to clinical implementation. The text box,‘Recommendations for HIIT prescription’ provides a sum-mary of our recommendations for prescribing HIIT in aclinical setting.

In research, HIIT is most commonly carried out asthree sessions per week (Table 1). Such a frequency isconsistent with the probable duration of the metaboliceffects observed. As previously mentioned, the durationof intervals also varies from 1–4 min (see Table 1).Since longer intervals have not been conclusively shownto yield better clinical outcomes but have been shown toreduce enjoyment [91], it makes sense to start at theshorter end of the range. The accumulated time at high-intensity during HIIT has varied from 10–20 min; startingat the lower end of this range allows for greater progres-sion. Likewise, ratios of interval:recovery time also vary,with a 1:1 ratio offering a simple starting point. Last,keeping the intensity of the recovery period to a minimumis likely to increase enjoyment, at least initially.

Intensity is commonly measured using HRmax. At firstglance, heart rate appears like a feasible option given the rel-ative ubiquity of heart rate monitors. However, heart rate risesacross intervals, as shown in Fig. 1. In our research, we haveadopted a very practical approach, using the Rate of PerceivedExertion (RPE) 6–20 Borg scale as a guide of intensity; aspreviously reported, participants were asked to work at a16–17 on the scale (or ‘very hard’) during each interval(Fig. 1) [38, 39]. RPE is an accurate predictor of exerciseintensity in diabetes patients [94], however, like heart rate, itdoes have its limitations. Agreement between RPE and moreobjective measures of intensity is known to suffer both inter-and intra-individual variation. For example, when RPEwas assessed during a set workload protocol, RPE in-creased from the first to the last interval [12]. Thus, usingRPE trades some objectivity, but the benefit is a great dealof practicality.

Exercise selection is ultimately limited by what is available

to the patient. Since peripheral metabolic adaptions are limited

to the muscles undergoing forceful contractions during exer-

cise [29], it is preferable to choose activities involving a large

muscle mass.

Recommendations for HIIT prescription

Frequency: 3 HIIT sessions per week

Intensity: Most easily measured by rating of perceived exertion (although may be variable in practice)

Time: Intervals should last between 1 and 4 minutes, with intervals at the shorter end being preferred by patients. The total time spent doing intervals should be 10–20 minutes per session

Type: Activities involving a large muscle mass


What’s next for HIIT?

HIIT leads to modest improvements in metabolic control andweight loss. This is in contrast to calorie restriction, whichleads to significant weight loss and improvements in metabol-ic control [40]. Combining HIITwith calorie restriction wouldaccrue the cardiac benefits of HIITand the weight loss benefitsof calorie restriction. Additionally, exercise and calorie restric-tion together have been shown to improve glucose regulationby two-fold compared with the same amount of weight lossinduced by exercise or calorie restriction alone [95]. Thus,there may be additive benefits for metabolic control if HIITwas used adjunct with energy restriction.

The myriad of different HIIT protocols adopted in the lit-erature needs to be addressed. A standardised and consistentapproach for prescribing HIIT protocols is missing, making itdifficult to detect dose–response effects and the thresholdsnecessary to elicit desired changes. Most clinical HIIT studieshave been short term (<4 months, see Table 1) and performedin a laboratory setting. The feasibility, acceptability and effi-cacy of longer-term HIIT in a real world setting requires in-vestigation before it can be accepted as an alternative therapyfor those with elevated cardiometabolic risk.

Conclusion

In circumstances where HIIT is not feasible, considered poten-tially unsafe or not well tolerated by an individual , MICT iseffective at eliciting important health benefits. However,throughout this review we have shown that, provided unstablecardiovascular disease is excluded, HIIT appears to have a goodsafety profile and is well tolerated. Compared with other formsof exercise training, the use of HIIT for improving metaboliccontrol and inducing weight loss should not be overstated.However, there are strong positive cardiovascular adaptationsto HIIT that confer benefit to a population at risk of cardiaccomplications and therein lies the importance of HIIT for meta-bolic disease management. For optimal clinical benefit (im-proved glycaemic control and cardiovascular function), the valueof HIIT appears likely to be adjunct to energy restriction,allowing HIIT to certainly make a hit.

Acknowledgements We thank L. Taylor (MoveLab, NewcastleUniversity, Newcastle, UK) for assistance with creating the images forthis manuscript.

Funding MITwas supported by a Senior Fellowship from the NationalInstitute for Health Research.

Duality of interest The authors declare that there is no duality of inter-est associated with this manuscript.

Contribution statement All authors were involved in drafting the ar-ticle and revising it critically for important intellectual content, and ap-proving the final version for publication.

Open Access This article is distributed under the terms of theCreative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,distribution, and reproduction in any medium, provided you give appro-priate credit to the original author(s) and the source, provide a link to theCreative Commons license, and indicate if changes were made.

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High-intensity interval training: a review of its impact ... · High-intensity interval training: a review of its impact on glucose control and cardiometabolic health ... HIIT is