Accumulated or continuous exercise for glycaemic regulation and control: A systematic review with meta-analysis

Abstract

Objective
To compare the effectiveness of accumulating exercise in multiple bouts of at least 10 min throughout a day with exercise completed in a single bout (continuous or interval), or no exercise, on glycaemic control and regulation in inactive people without diagnosed glycaemic dysfunction.

Design
Systematic review and meta-analysis.

Data sources
Seven electronic databases were searched: CINAHL (EBSCO), Cochrane Library, EMBASE (Ovid), MEDLINE 1948-(Ovid), SCOPUS (Elsevier), SPORTDiscus (EBSCO) and Web of Science (ISI) with no restrictions on date and included all titles indexed up to February 2018.

Eligibility criteria for selecting studies
Articles reporting insufficiently active adults (19 to 64 years) without metabolic dysfunction, measuring glycaemic control or regulation following at least 6 weeks of aerobic exercise.

Results
Only one study compared accumulated exercise to single-bout exercise with no significant effect on fasting glucose (95% CI: −0.04 to 0.24 mmol·L ⁻¹ ) or fasting insulin (95% CI: −1.79 to 9.85 pmol·L ⁻¹ ) reported 48 hours after the final bout. No studies compared accumulated exercise with no-exercise. Compared with no-exercise, single-bout exercise reduces insulin resistance (mean difference (MD): −0.53 pmol·L ⁻¹ ; 95% CI: −0.93 to −0.13). Insulin resistance was clearly reduced with moderate-intensity (−0.68 (−1.28 to −0.09)) but not with high-intensity (−0.38 (−1.20 to 0.44)) exercise. Single-bout exercise was not statistically more beneficial than no-exercise for glycated haemoglobin (HbA 1c ) (MD: −0.11 %; 95% CI: −0.24 to 0.02) in metabolically healthy individuals.

Summary/conclusion
The glycaemic response to accumulated exercise or single-bout exercise might not be different, however exercise intensity might influence the mechanisms generating the response.

PROSPERO registration number
CRD42015025042.

Full text

ShambrookP, etal. BMJ Open Sport Exerc Med 2018;4:e000470. doi:10.1136/bmjsem-2018-000470 1
Open access Review
Accumulated or continuous exercise for
glycaemic regulation and control: a
systematic review with meta-analysis
Philip Shambrook,1 Michael Kingsley,1 Nicholas Taylor,2 Brett Gordon1
To cite: ShambrookP,
KingsleyM, TaylorN, etal.
Accumulated or continuous
exercise for glycaemic
regulation and control: a
systematic review with
meta-analysis. BMJ Open
Sport & Exercise Medicine
2018;4:e000470. doi:10.1136/
bmjsem-2018-000470
►Additional material is
published online only. To view
please visit the journal online
(http:// dx. doi. org/ 10. 1136/
bmjsem- 2018- 000470).
Accepted 14 November 2018
1Discipline of Exercise
Physiology, La Trobe Rural
Health School, La Trobe
University, Bendigo, Victoria,
Australia
2Department of Rehabilitation,
Nutrition and Sport, La Trobe
University, Bundoora, Victoria,
Australia
Correspondence to
Dr Brett Gordon; b. gordon@
latrobe. edu. au
© Author(s) (or their
employer(s)) 2018. Re-use
permitted under CC BY-NC. No
commercial re-use. See rights
and permissions. Published by
BMJ.
What is already known?
►Exercise has a benecial effect on glucose regula-
tion and control.
►Regular exercise inhibits the progression of glycae-
mic dysfunction among people without a diagnosed
health condition.
What are the new ndings?
►Practitioners can prescribe exercise in shorter, mul-
tiple bouts per day, however, there is limited evi-
dence for this relating to glucose regulation.
►Exercise should be prescribed at moderate-intensi-
ty or high-intensity to regulate glucose for up to 48
hours.
►Exercise must be completed regularly as improve-
ments to glucose regulation might not translate to
improved glucose control otherwise.
ABSTRACT
Objective To compare the effectiveness of accumulating
exercise in multiple bouts of at least 10 min throughout a
day with exercise completed in a single bout (continuous
or interval), or no exercise, on glycaemic control and
regulation in inactive people without diagnosed glycaemic
dysfunction.
Design Systematic review and meta-analysis.
Data sources Seven electronic databases were
searched: CINAHL (EBSCO), Cochrane Library, EMBASE
(Ovid), MEDLINE 1948-(Ovid), SCOPUS (Elsevier),
SPORTDiscus (EBSCO) and Web of Science (ISI) with no
restrictions on date and included all titles indexed up to
February 2018.
Eligibility criteria for selecting studies Articles
reporting insufciently active adults (19 to 64 years)
without metabolic dysfunction, measuring glycaemic
control or regulation following at least 6 weeks of aerobic
exercise.
Results Only one study compared accumulated exercise
to single-bout exercise with no signicant effect on fasting
glucose (95% CI: −0.04 to 0.24 mmol·L-1) or fasting insulin
(95% CI: −1.79 to 9.85 pmol·L-1) reported 48 hours after
the nal bout. No studies compared accumulated exercise
with no-exercise. Compared with no-exercise, single-bout
exercise reduces insulin resistance (mean difference
(MD): −0.53 pmol·L-1; 95% CI: −0.93 to −0.13). Insulin
resistance was clearly reduced with moderate-intensity
(−0.68 (−1.28 to −0.09)) but not with high-intensity
(−0.38 (−1.20 to 0.44)) exercise. Single-bout exercise
was not statistically more benecial than no-exercise for
glycated haemoglobin (HbA1c) (MD: −0.11 %; 95% CI:
−0.24 to 0.02) in metabolically healthy individuals.
Summary/conclusion The glycaemic response to
accumulated exercise or single-bout exercise might not be
different, however exercise intensity might inuence the
mechanisms generating the response.
PROSPERO registration number CRD42015025042.
INTRODUCTION
Exercise has long been accepted as an effective
method to reduce the risk of developing type
2 diabetes mellitus (T2DM) due to its positive
effects on glycaemic regulation and control.1
Strong and consistent evidence demon-
strates that undertaking at least 30–60 min of
moderate to high intensity aerobic exercise
most days of the week substantially reduces
the risk of developing T2DM.2 3 Consequently,
there has been broad adoption of public health
guidelines that recommend adults undertake
a minimum of 150 min of moderate-intensity
or 75 min of vigorous-intensity aerobic exer-
cise each week.4–6 The guidelines recommend
completing exercise in a single bout or accumu-
lating these exercise durations in multiple bouts
of at least 10 min throughout a day.4–6 However,
the guidelines from Australia do not suggest a
minimum bout duration, only that at least 150
min of moderate-intensity exercise be accumu-
lated per week.7 Either continuous or interval
exercise can constitute a single bout of exer-
cise. Despite the recommendations contained
in current exercise guidelines, only one review8
has summarised the evidence relating to accu-
mulating exercise in multiple shorter bouts.
Limited information relating to glycaemic
control and regulation was reported, and
the majority of studies considered contained
exercise programmes of less than 6 weeks in
duration.8
In addition to T2DM risk reduction, exer-
cise also reduces the risk of developing
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Open access
cardiovascular disease, primarily through improved meta-
bolic function.9 Exercise-based improvements to glycaemic
control and regulation occur via several different and
complex pathways involving a range of muscle contrac-
tion, regulatory and counter-regulatory biochemical
mechanisms.2 Muscle contraction-mediated pathways are
known to remain active for only a short period following
exercise.10 Sensitivity to insulin is also increased following
exercise, and this insulin-mediated pathway might remain
elevated for several days.11 Therefore, more frequent bouts
of exercise might result in greater amounts of contrac-
tion-mediated glucose uptake without interfering with
improvements in insulin sensitivity. Concepts of exercise
snacking (very short but frequent exercise bouts)12 and
breaking up sedentary behaviour13 have been shown to
benefit glycaemic regulation. However, these studies have
only investigated the response to one-off or short duration
exercise programmes that are unable to provide evidence
relating to long-term glycaemic control and regulation. In
addition to exercise bout duration, different exercise inten-
sities have been recognised to induce changes to glycaemic
control and regulation through different mechanistic path-
ways. Although all exercise guidelines recommend either
(or a combination of) moderate or vigorous exercise inten-
sity, it remains unclear whether the metabolic response to
different intensity exercise is different in people without
known metabolic dysfunction.
Accumulating aerobic exercise in bouts of at least 10
min throughout a day is beneficial for cardiorespira-
tory health and fitness, although it might not be more
beneficial than completing single-bout aerobic exercise
(continuous or interval).14 Accumulating exercise in
shorter bouts might also be an effective strategy to over-
come the frequently cited barrier to exercise, “lack of
time”15 and improve exercise compliance. Although exer-
cise participation and cardiorespiratory fitness might be
improved through accumulating exercise, the evidence
for this prescription of exercise to improve glycaemic
control and regulation has not been adequately reviewed.
Before recommending exercise participation in shorter,
multiple bouts a day, it is important to collate the
evidence and ascertain if changes in glycaemic regula-
tion and control are similar or different to those attained
from single-bout exercise.
Therefore, the primary aim of this review and meta-anal-
ysis was to identify studies to compare the effects of
aerobic exercise, completed in a single bout (contin-
uous or interval) or accumulated in multiple short bouts
throughout a day, on glycaemic control and regulation in
a young to middle-aged, insufficiently active adult popu-
lation. The secondary aim was to assess whether exercise
completed at different intensities resulted in different
glycaemic responses.
METHODS
This review protocol was prospectively registered with the
PROSPERO International register of systematic reviews
(registration number CRD42015025042). It is reported
in accordance with the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses statement.16
A systematic literature search of CINAHL (EBSCO),
Cochrane Library, EMBASE (Ovid), MEDLINE 1948-
(Ovid), SCOPUS (Elsevier), SPORTDiscus (EBSCO) and
Web of Science (ISI) databases was undertaken with no
restrictions on date and included all titles indexed up to
February 2018. The PICO approach was used to focus the
search on Population (sedentary or inactive adults aged
19 to 64 years); Intervention (any type of aerobic exercise
intervention using accumulated, interval or continuous
exercise); Comparator (single-bout exercise or no-ex-
ercise) and Outcome (measures of glycaemic control
or regulation such as glycated haemoglobin (HbA1c),
glucose, insulin and indices of insulin sensitivity).
Keywords for the search terms, including appropriate
MeSH terms for these constructs, were determined and
combined with OR and AND Boolean operators in elec-
tronic databases (online supplementary table 1. Titles,
abstracts and keywords were searched. Only English
language studies and those for which an English language
translation was available were included. The search was
limited to peer-reviewed studies involving human partici-
pants aged 19 to 64 years.
As it was anticipated that a small number of studies
would provide direct comparison between accumulated
exercise and single-bout exercise, an a priori decision
was made to include studies that compared either accu-
mulated aerobic exercise or single-bout aerobic exercise
against a no-exercise control. Studies were excluded
according to the following criteria: (1) participants
consuming medication known to affect glycaemic regu-
lation or diagnosed with a glucose metabolism disorder;
(2) participants known to be active or exceeding current
guidelines as any changes to measures of glycaemic
regulation or control are likely to be minimal; (3) inter-
ventions <6 weeks duration as the effects of exercise
on HbA1c are likely to be minimal with short duration
exercise programmes; (4) studies that did not include a
measure of glycaemic control or glucose regulation; (5)
studies with interventions that combined additional inter-
ventions with accumulated and/or single-bout exercise;
(6) resistance or strength exercise only and (7) reviews,
commentaries, editorials, conference abstracts or studies
without original data.
Studies were initially excluded by one author (PS)
based on title. Two authors (PS, BG, MK, NT) conducted
reviews of abstracts independently. In the instance of
disagreements between reviewers, a third author (BG,
MK, NT) provided a majority decision on whether the
article was included for full-text review or excluded. Full-
text review occurred in the same manner as the abstract
review. Included studies were further reviewed (PS) to
identify randomised controlled trials (RCTs) for inclu-
sion in meta-analyses.
One author (PS) extracted data from identified full-
text studies for the meta-analyses, with the validity of
these data checked by another author (BG). Means and
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measures of variance (SD, SE, 95% CI) relating to the spec-
ified outcomes (HbA1c, plasma glucose, plasma insulin,
indices of insulin resistance and insulin sensitivity) were
extracted. When required, measures of variance were
converted into SD and then entered into RevMan V.5
software for synthesis and analysis. Requests were sent to
authors of articles with missing or incomplete data, with
studies excluded from those meta-analyses if data were
not obtained or verified.
The meta-analysis for glycaemic control (HbA1c) was
stratified by exercise intensity. Fasting glucose, fasting
insulin, homeostatic model assessment of insulin resis-
tance (HOMA-IR) and insulin sensitivity index were
reported in sufficient numbers to allow meta-analyses for
short-term glycaemic regulation 12–24 hours and 36–48
hours after the final exercise bout and were also strati-
fied by exercise intensity. Acute phase insulin secretion,
glucose effectiveness, insulin sensitivity index (M value),
1 hour glucose concentration, 1 hour insulin concentra-
tion, glucose 2-hour area under the curve (AUC), insulin
2-hour AUC, quantitative insulin sensitivity check index,
postprandial glucose concentration and oral glucose
insulin sensitivity outcome measures were not reported
in sufficient numbers to be subject to meta-analysis, as a
minimum, two studies are required.17
Studies containing more than one relevant exer-
cise intervention group at the same exercise intensity
were combined to create single pairwise comparisons
using formulae contained in the Cochrane Handbook
for Systematic Reviews of Interventions.17 Studies were
stratified by exercise intensity into low-intensity, moder-
ate-intensity and high-intensity using criteria from
the American College of Sports Medicine.18 The stan-
dardised mean difference (SMD) or mean difference
(MD) with 95% CI were calculated between interven-
tions from postintervention measures. Meta-analyses
for outcomes were created using random effects models
where heterogeneity was substantial (I2 >50%).17 Data
contained in the meta-analyses were assessed for study
and outcome quality using GRADEpro GDT computer
software (GRADEpro GDT, McMaster University) by one
author (PS) and validated by another (BG). Risk of Bias
was assessed using Review Manager V.5.3 computer soft-
ware (RevMan V.5.3).
RESULTS
The search strategy identified 5919 unique articles, of
which 149 articles met the inclusion criteria (figure 1).
Sixteen of the 56 RCTs retrieved were included in
meta-analyses (figure 1). Two separate studies reported
in one article were treated as separate studies, one of
which was included in the meta-analyses.19 Duplicated
data were not included in meta-analyses if reported in
multiple articles from the same study, the available data
were incomplete or in a format that could not be used, the
control group received an intervention likely to affect the
measured outcomes, or when outcomes were measured
beyond 48 hours, or not adequately specified, after the
final exercise bout (online supplementary table 2). One
RCT was identified that directly compared accumulated
exercise with single-bout exercise.19 Apart from Asika-
inen et al,19 zero studies were identified that compared
accumulated exercise with no-exercise. Including the
no-exercise arm of Asikainen et al,19 16 RCTs compared
single-bout exercise, either continuous or interval, with
no-exercise.19–34 The 16 RCTs included in the meta-anal-
yses contained 1133 participants (392 males, 683 females
and 58 not identified to a specific sex; table 1). Inter-
ventions consisted of 30 to 90 min of exercise for 3 to
5 days per week over durations between 6 weeks and
12 months. One study included in the meta-analyses
assessed glycaemic outcomes 24 hours, 72 hours and 2
weeks following the final exercise bout; only the results at
24 hours were included in meta-analyses.26
The single study that compared accumulated exer-
cise and single-bout exercise did not assess glycaemic
control.9 This single study with 87 female participants
compared measures of glycaemic regulation between
accumulated exercise (2×15 min bouts, 5 days per
week at 65%
V
O2max) and single-bout continuous exer-
cise (1×30 min bout, 5 days per week at 65%
V
O2max)
approximately 48 hours after the final exercise bout, and
reported no significant difference between accumulated
(net change −0.21 mmol·L-1, 95% CI −0.33 to 0.16) or
single-bout exercise (−0.13 mmol·L-1, −0.25 to −0.010)
for fasting glucose, or fasting insulin (accumulated: −3.34
pmol·L-1, −7.30 to 0.63: single-bout: −2.43 pmol·L-1, −6.46
to 1.53).19 Compared with the no-exercise control group,
there was a reduction in glucose concentration 2 hours
after an oral glucose challenge following single-bout
exercise (−0.48 mmol·L-1, −0.89 to −0.08) and accumu-
lated exercise (−0.43 mmol·L-1, −0.83 to −0.02), but no
change in insulin concentration.
The evidence comparing single-bout exercise with
no-exercise for fasting glucose was of low to moderate
quality (18 RCTs, 1058 participants; online supplemen-
tary table 3). Fasting glucose was not reduced 12–24 hours
after the final exercise bout (10 RCTs, 740 participants,
MD: −0.10 mmol·L-1; 95% CI: −0.22 to 0.02; figure 2A)
but was reduced 36–48 hours after the final exercise bout
(8 RCTs, 318 participants, MD: −0.24 mmol·L-1; 95% CI:
−0.45 to −0.04; figure 2B). However, in comparison to
no-exercise, low-intensity, moderate-intensity or high-in-
tensity exercise did not demonstrate a clear benefit for
reducing fasting glucose concentration (figure 2A,B).
The evidence comparing single-bout exercise with
no-exercise for fasting insulin was of low to moderate
quality (15 RCTs, 1042 participants; online supplemen-
tary table 3). Exercise reduced fasting insulin 12–24
hours after the final exercise bout (9 RCTs, 797 partic-
ipants, MD: −15.69 pmol·L-1; 95% CI: −25.06 to −6.33;
figure 3A) but not 36–48 hours after the final exercise
bout (6 RCTs, 245 participants, MD −11.97 pmol·L-1;
95% CI: −24.26 to 0.32; figure 3B). High-intensity exer-
cise reduced insulin concentration at both 12–24 hours
and 36–48 after the final exercise bout (figure 3A,B).
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Figure 1 Preferred Reporting Items for Systematic Reviews and Meta-Analyses study ow chart.
However, moderate-intensity exercise only reduced
insulin concentration at 12–24 hours after the final exer-
cise bout (figure 3A).
The evidence comparing single-bout exercise with
no-exercise for HOMA-IR and insulin sensitivity (using
the methods of McAuley et al35 in O'Donovan et al30 and
methods of Bergman et al36 in Houmard et al25) was of
low to moderate quality (online supplementary table 3).
HOMA-IR (7 RCTs, 493 participants, MD: −0.53; 95%
CI: −0.93 to −0.13; figure 4A) and insulin sensitivity (3
studies, 162 participants, SMD −0.62; 95% CI: 0.12 to
1.12; figure 5A) were improved 12–24 hours after the
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Table 1 Studies included in meta-analyses
Study Participants Interventions
Intervention
duration
Time measured after
final exercise bout Outcome measures
Aldred et al20 Sedentary.
n=26 f
Age EXE (y) 50±5
Age CON (y) 49±5
Moderate-intensity walking, 74% HRmax,
Control maintained habitual sedentary lifestyle.
12 wk, 20–50 min per day,
accumulating 180 min/wk.
48 h Fasting glucose.
Fasting insulin.
Asikainen et al19 Sedentary, postmenopausal.
n=121 f
Age (y) EXE 55±4
Age (y) CON 56±4
Moderate-intensity walking, 45%–55%
V
O2max).
Control, no exercise.
24 wk, 5 days per wk, 1 session,
duration dependant on exercise
expenditure.
48 h Fasting glucose.
Fasting insulin.
Azarbayjani et al21 Sedentary.
n=20 m
Age (y) EXE 23±1
Age (y) CON 23±2
Treadmill, 60%–70% HRR.
Control, no programmed physical activity, maintain diet.
12 wk, 3 days per wk, 30 min per day. 24 h Fasting glucose.
Fasting insulin
HOMA-IR.
Coghill and Cooper22 Hypercholesterolaemic.
n=67 m
Age (y) EXE 55±5
Age (y) CON 56±5
Moderate-intensity walking 60%–75% HRmax.
Control, no exercise.
12 wk, 5 days per wk, 30 min per day. 24 h Fasting glucose.
Fasting insulin
HOMA-IR.
Friedenreich et al23 Inactive, postmenopausal
n=320 f
Age (y) EXE 61±5
Age (y) CON 61±6
Vigorous intensity various aerobic exercise 70%–80%
HRR.
Control, maintain activity levels and diet.
12 months, 5 days per wk, 45 min per
day.
24 h Fasting glucose.
Fasting insulin
HOMA-IR.
Halse et al24 Sedentary.
n=40 f
Age (y) EXE 34±5
Age (y) CON 32±3
Moderate-intensity cycling.
Control, no change to diet and lifestyle.
6 wk, 5 sessions per day, 45 min per
session.
48 h Fasting glucose.
Fasting insulin
2 hglucose (after OGTT)
HbA1c.
Houmard et al25 Sedentary, overweight or obese.
n=154 (69 m, 85 f)
Age (y) EXE 52±1
Age (y) CON 51±1
All walking, low volume moderate intensity 40%–50%
VO2peak, low volume high intensity and high volume high
intensity 65%–80% VO2peak.
Control, no exercise.
6 months,~3 sessions per wk,~45 min
per session.
24 h Fasting glucose.
Fasting insulin.
Insulin sensitivity index.
Jabbour et al26 Obese
n=33 (15 m, 18 f)
Age (y) EXE 23±2
Age (y) CON
23±3
Aerobic interval cycling, 6 sets of supramaximal
intervals, 2 min recovery.
Control, no training.
6 wk, 3 sessions per wk, approximately
15 min per session.
24 h , 72 h and 2 wk Fasting glucose.
Fasting insulin
HOMA-IR.
Moghadasi et al27 Sedentary, overweight, obese.
n=16 m middle-age
High-intensity treadmill 75%–85% VO2max.
Control, no change to diet or activity levels.
25 wk, 4 days per wk, 45 min per day. 48 h Fasting glucose.
Fasting insulin
HOMA-IR.
Nordby et al28 Sedentary, moderately overweight.
n=48 m
Age (y) EXE 28±4
Age (y) CON 31±7
High-intensity cycling, running, cross-training, rowing,
65%–85% HRR.
Control, maintain lifestyle and diet.
18 months, 3–4 sessions per wk,
durations dependant on energy
expenditure required.
24 h Fasting glucose.
Fasting insulin
2 h glucose (after HIC)
2 h insulin (after HIC)
HbA1c
HOMA-IR.
Nualnim et al29 Pre-hypertensive or stage 1
hypertension.
n=43 (11 m, 32 f)
Age (y) EXE 58±10
Age (y) CON 61±9
Moderate-intensity swimming 60%–75% HRmax
Control, maintain usual lifestyle and dietary habits.
21 wk, 3–4 days per wk,~45 min per
session.
24 h Fasting glucose
HbA1c.
Continued
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Study Participants Interventions
Intervention
duration
Time measured after
final exercise bout Outcome measures
O'Donovan et al30 Sedentary.
n=67 m
Age(y) MOD 42±2
Age(y) HIE 41±4
Age(y) CON 41±3
Moderate-intensity and high-intensity cycling 60%
V
O2max, and 80%
V
O2max respectively.
Control, maintain diet and lifestyle.
24 wk, 3 sessions per wk, time as
required to expend 400 kcal per
session.
24 h Fasting glucose.
Fasting insulin
HOMA-IR.
Insulin sensitivity.
Reichkendler, et al31 Moderately overweight.
n=53 m
Age (y) EXE 29±2
Age (y) CON 31±1
High-intensity 62%–72%
V
O2max, treadmill, rowing,
elliptical machine, cycling.
Control, maintain sedentary lifestyle.
10–12 wk, duration dependent on
time required to meet desired energy
expenditure.
36 h Fasting glucose.
Fasting insulin.
HbA1c
2 hour glucose (after OGTT)
2 hour insulin (after OGTT).
Peripheral insulin sensitivity.
Stensvold et al32 Metabolic syndrome.
n=43 (26 m, 17 f)
Age (y) EXE 50±10
Age (y) CON 47±10
Aerobic interval training, 4 min 90% HRpeak, exercise
cycle.
Control, unclear.
12 wk, 3 sessions per wk, 43 min total. 48 h Fasting glucose.
Fasting insulin.
Weiss et al33 Sedentary.
n=58 (m/f)
Age (y) 50–60
Moderate-intensity walking, elliptical machine, cycling
and running 62%–80% HRmax.
Control, no instructions.
12 months,~6 sessions per wk,~60 min
per session.
48 h Fasting glucose.
Fasting insulin.
Glucose 2h-AUC.
Insulin 2h-AUC.
Insulin sensitivity index.
Zehsaz et al34 Sedentary, obese.
n=24 f
Age (y) EXE 35±4
Age (y) CON 35±6
Moderate-intensity treadmill and exercise cycling,
60%–75% HRmax.
Control, non-training.
12 wk, warm up plus ~45 min, 5 times
per week.
48 h Fasting glucose.
Fasting insulin
HOMA-IR.
AUC, area under the curve; CON, control group; EXE, exercise group; HIC, hyperinsulinemic isoglycemic clamp; HOMA-IR, homeostatic model assessment of insulin resistance; HRR, heart rate reserve; HRmax, maximum heart rate; HRpeak, peak
heart rate; HbA1c, glycosylated haemoglobin; OGIS, oral glucose insulin sensitivity; OGTT, oral glucose tolerance test; ∨O2max, maximum volume of oxygen; ∨O2peak , peak volume of oxygen; f, female; h, hour; m, male; min, minute; wk, week; y, year.
Table 1 Continued
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Figure 2 Forest plot stratied by exercise intensity of the fasting glucose response measured (A) up to 24 hours after the nal
exercise bout and (B) 36–48 hours after the nal exercise bout.
final exercise bout. HOMA-IR was also improved 36–48
hours after the final exercise bout (two studies, 56
participants, MD: 1.35; 95% CI: 2.01 to 0.70; figure 4B).
Moderate-intensity, but not high-intensity exercise bene-
fited insulin resistance (figure 4A), while high-intensity
but not moderate-intensity exercise benefited insulin
sensitivity (figure 4C) 12–24 hours after exercise. Both
moderate-intensity (Zehsaz et al34 and high-intensity
(Moghadasi et al27) exercise showed clear favourable
effects for insulin resistance 36–48 hours after the final
exercise bout (figure 4B). Single-bout moderate to
high-intensity exercise was reported to be beneficial for
insulin sensitivity 36–48 hours following the final exercise
bout.33
The evidence comparing single-bout exercise with
no-exercise for HbA1c was of moderate quality (5 RCTs,
182 participants, online supplementary table 4) but failed
to demonstrate a clear favourable effect (MD: −0.11%;
95% CI: −0.24 to 0.02; figure 5). Neither moderate nor
high-intensity exercise demonstrated differing effects for
the reduction of HbA1c (figure 5).
DISCUSSION
Despite previous calls to increase the evidence base, there
remains a lack of evidence to determine whether different
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Figure 3 Forest plot stratied by exercise intensity of the fasting insulin response measured (A) up to 24 hours after the nal
exercise bout and (B) 36–48 hours after the nal exercise bout.
metabolic health effects occur with accumulating exercise
in short bouts throughout a day or by completing single-
bout exercise in insufficiently active younger adults.
Only one study reported a direct comparison for glucose
regulation between accumulating exercise in multiple
shorter bouts throughout a day and single-bout contin-
uous exercise.19 While a number of studies reported
beneficial metabolic health effects of single-bout exercise
(continuous or interval) compared with no-exercise, no
studies were identified comparing accumulated exercise
with no-exercise. Thus, it was not possible to supplement
the limited direct evidence for the efficacy of accumu-
lated exercise with indirect evidence comparing exercise
accumulated in multiple short bouts with a no-exercise
control.
Accumulating exercise in shorter bouts throughout a
day provided similar benefits to single-bout exercise in
the single study identified, although measures of long-
term glycaemic control were not assessed.19 The two
programmes of exercise did not produce significant
differences for short-term measures of glycaemic regula-
tion: fasting glucose and insulin, or insulin concentrations
following an oral glucose tolerance test.19 Only fasting
glucose improved with both accumulated and single-bout
exercise when compared with a no-exercise control.19
This single study did not offer any evidence to determine
the efficacy of accumulating exercise in shorter bouts,
possibly because the interventions were not sufficiently
different to elicit a significantly different outcome. The
exercise prescription was to expend 1255 kJ of energy per
day, through either two, 15 min bouts or one, 30 min bout
of moderate-intensity walking. Despite the recommenda-
tion from Murphy et al,8 that the benefits of accumulating
exercise in shorter bouts be a focus for future research,
evidence for the chronic effects of accumulated exercise
on metabolic health outcomes, particularly those related
to glycaemic regulation, remain limited, both in quantity
and quality. Further investigations of the chronic effects
of accumulating exercise in multiple bouts of at least 10
min duration, as recommended in current guidelines,5
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ShambrookP, etal. BMJ Open Sport Exerc Med 2018;4:e000470. doi:10.1136/bmjsem-2018-000470
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Figure 4 Forest plot stratied by exercise intensity of HOMA-IR measured (A) up to 24 hours after the nal exercise bout and
(B) 36–48 hours after the nal exercise bout and (C) insulin sensitivity measured up to 24 hours after the nal exercise bout.
are required to provide evidence-based information for
public health advocates and the wider public.
The therapeutic benefit of aerobic exercise for
glycaemic control is likely to occur in people without
diagnosed metabolic disease, despite the limitations in
the quality of these data. Although not statistically signif-
icant, the outcome from this meta-analysis suggests that
HbA1c can beneficially change in people without estab-
lished T2DM. Aerobic exercise is accepted to reduce
HbA1c by approximately 0.7% in people with T2DM
and generally poor glycaemic control.37 Relatively small
reductions in HbA1c (of approximately 1%) substan-
tially reduces diabetes-related mortality in people with
T2DM.38 Similarly, in a previous meta-analysis of partic-
ipants with and without diabetes, a weighted mean
reduction of 0.28% for HbA1c along with improvements
to insulin resistance were identified following exercise
compared with no-exercise.9 This meta-analysis of only
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10 ShambrookP, etal. BMJ Open Sport Exerc Med 2018;4:e000470. doi:10.1136/bmjsem-2018-000470
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Figure 5 Forest plot stratied by exercise intensity of HbA1c.
individuals without metabolic dysfunction has identi-
fied a mean reduction in HbA1c of 0.11%. Since the
risk of developing cardiovascular disease and diabetes
rises concomitantly with any increase in glycaemic levels
above normal,39 any improvement to glucose metabo-
lism following exercise will contribute to reduced risk
for individuals without known metabolic health dysfunc-
tion. Interestingly, the meta-analyses conducted from this
review failed to produce evidence of a clear difference
in response between moderate-intensity and high-inten-
sity exercise. High-intensity interval training compared
with continuous exercise training (mostly conducted at
moderate intensity) has been reported to reduce insulin
resistance, suggesting that intensity might be important.40
It has been purported that greater intensity exercise
delivers improved metabolic regulation, however the
evidence base for this is poor.41 In contrast, at least for
individuals with T2DM, exercise frequency rather than
exercise intensity seems to be important for improving
glycaemic control.42
The complexity of glucose transport suggests that
the response to moderate-intensity or high-intensity
exercise probably occurs via different mechanistic path-
ways. This might account for the similarity in outcomes
between the different exercise intensities identified in
this meta-analysis. The prescription for moderate-inten-
sity continuous exercise in the included studies ranged
from 60% to 75% HRmax (or equivalent measures).
Muscle contraction-stimulated glucose uptake is the
main mechanism responsible for regulating glucose
during moderate-intensity exercise and can occur despite
depressed concentrations of insulin.43 The prescription
for continuous high-intensity exercise in the included
studies was relatively consistent, ranging from 80% to
85% HRmax. Studies involving interval protocols utilised
high-intensity workloads of 80%–90% of HRmax (or
equivalent measures) or bouts of undefined supramax-
imal intensity.26 32 44 45 During high-intensity exercise, the
increased catecholamine secretion signals a rapid hepatic
glucose response.43 Furthermore, since the individuals
involved in the studies were insufficiently active, young
to middle-aged adults with baseline HbA1c levels between
the accepted healthy levels of 4.5% to 6.0%, only small
(potentially not statistically significant) changes would be
expected in response to exercise. Small statistically signif-
icant reductions in HbA1c of between 0.01% and 0.04%
occur with every additional week of exercise in individ-
uals with T2DM.37 Furthermore, since a 1% reduction in
HbA1c is associated with a 37% reduction in the devel-
opment of macrovascular complications among people
with T2DM,39 46 this might suggest the mean change of
0.11% in the population included in this meta-analysis
is clinically meaningful to reduce the risk of developing
conditions such as T2DM.
This meta-analysis identified no significant effect on
fasting glucose concentration up to 24 hours following
the final exercise bout, although significant reduc-
tions to fasting insulin concentration occurred in the
same period. This indicates that in response to exercise
training, maintenance of glucose concentration occurs
with a lower insulin requirement. Being able to main-
tain glucose concentrations with less insulin suggests
improved insulin sensitivity, which various indices of
insulin resistance and insulin sensitivity confirmed up
to 48 hours following the final exercise bout. Although
contraction-mediated glucose uptake effects are only
likely to persist for a short time following exercise,10 insu-
lin-dependent glucose uptake can persist for up to 10
days.11 The outcomes from the meta-analyses conducted,
suggest improved glucose regulation with exercise
at both 12–24 hours and 36–48 hours after exercise;
although of interest was the difference between moder-
ate-intensity and high-intensity at 12–24 hours after the
final exercise bout. Moderate-intensity exercise seemed
to reduce insulin resistance, while high-intensity exer-
cise increased insulin sensitivity. The initial difference
did not persist though, with both moderate-intensity
and high-intensity exercise improving insulin resistance
and insulin sensitivity 36–48 hours after the final session.
This evidence needs to be interpreted cautiously though,
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ShambrookP, etal. BMJ Open Sport Exerc Med 2018;4:e000470. doi:10.1136/bmjsem-2018-000470
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as no studies measured glucose regulation at both time
points, and few studies evaluated insulin sensitivity 36–48
hours after the final exercise bout. Regardless, the find-
ings might suggest that aerobic exercise needs to be
completed at least every second day, with data from Davey
and colleagues reporting insulin sensitivity was increased
24 hours after the final session but had returned to near
normal levels after 5 days.47 This of course might be
dependent on the mode and/or intensity of exercise.
While no change was reported for glycaemic regulation
following continuous exercise at ~75%
V
O2peak either
24 hours or 14 days following the final exercise bout,48
significant improvements were reported 24 hours and
14 days after the final supramaximal intensity interval
training exercise bout.26 It is possible that the inherent
differences of exercise intensity and session duration are
significant contributing factors to changes in glycaemic
control and regulation. Along with the broad variations
in exercise intensity noted, the duration of each exercise
session also ranged from 30 min to 90 min. Longer dura-
tion exercise provides the opportunity for an increased
number of muscle contractions, and thus possibly greater
energy requirements, which might lead to greater glucose
uptake.
The evidence presented in this review is of low-to-mod-
erate quality largely due to randomisation methods not
clearly outlined, or difficulties in blinding participants
and assessors. Additionally, wide variations in the exercise
interventions employed in terms of frequency, intensity,
time and type contributed to substantial levels of hetero-
geneity. Despite the growing interest in high-intensity
interval training, only four studies have implemented this
type of intervention for at least 6 weeks with the purpose
of improving metabolic health in people without meta-
bolic health dysfunction.26 32 44 45 Interval training is an
area of exercise prescription that guidelines have not
yet adequately considered and presents an opportunity
for new investigation. The lack of consistent outcome
measures also meant that only 16 of 56 RCT studies
were able to be included in some of the meta-analyses.
Opportunities exist for future research to use a more stan-
dardised approach to determine how best to accumulate
exercise in multiple bouts throughout a day to improve
or prevent the decline of metabolic function among indi-
viduals without known metabolic dysfunction. However,
this requires broad agreement on individual components
of the exercise prescription; frequency, intensity, time
and type.
CONCLUSION
It is uncertain whether exercise accumulated throughout
a day is as, or more, effective than single-bout exercise to
reduce the risk of developing metabolic disease in insuf-
ficiently active, young to middle-aged adults. However,
based on the findings from a single study, it might not be
worse. This review supports the general observation that
glycaemic control (as measured by HbA1c) improves with
at least 30 min of continuous exercise, even among adults
with glycaemic control below the diagnostic threshold
for T2DM. It is not clear whether exercise training
programmes provide additive effects on glycaemic regu-
lation, as outcomes are only regularly measured up to 48
hours after the final exercise bout. Regular single bouts
of exercise, whether of moderate-intensity or high-inten-
sity, have a clear benefit for regulating glucose for up to
48 hours after the final exercise bout, despite potentially
inducing different degrees of glycaemic control.
Acknowledgements The authors would like to thank Paul Xanthos who provided
technical support for the project.
Contributors PS, MIK, NT, BAG: contributed to the development of the research
questions, study design and literature search strategy. PS: conducted the literature
search. PS, MIK, NT, BAG: reviewed articles and performed study selection. PS, BG:
performed methodological quality assessment and data extraction. PS, MIK, NT,
BAG: contributed to data interpretation. PS: drafted the manuscript. MIK, NT, BAG:
provided critical review. All authors read and approved the nal manuscript.
Funding PS was supported by an Australian Government Research Training
Program Scholarship. The authors have not declared any other grant from any
funding agency in the public, commercial or not-for-prot sectors.
Competing interests None declared.
Patient consent Not required.
Provenance and peer review Not commissioned; internally peer reviewed.
Open access This is an open access article distributed in accordance with the
Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which
permits others to distribute, remix, adapt, build upon this work non-commercially,
and license their derivative works on different terms, provided the original work is
properly cited, appropriate credit is given, any changes made indicated, and the
use is non-commercial. See: http:// creativecommons. org/ licenses/ by- nc/ 4. 0/
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