the impact of training modalities on the clinical benefits of exercise intervention in patients with...

The Impact of Training Modalities on theClinical Benefits of Exercise Interventionin Patients with Cardiovascular DiseaseRisk or Type 2 Diabetes MellitusDominique Hansen,1,2,3 Paul Dendale,1,2 Luc J.C. van Loon4 and Romain Meeusen5

1 Jessa Hospital/Heart Centre Hasselt, Hasselt, Belgium

2 Faculty of Medicine, Hasselt University, Diepenbeek, Belgium

3 Rehabilitation & Healthcare Research Centre, Department of Healthcare, PHL-University College,

Hasselt, Belgium

4 Department of Human Movement Sciences, Nutrition and Toxicology Research Institute (NUTRIM),

Maastricht University Medical Centre, Maastricht, the Netherlands

5 Department of Human Physiology and Sports Medicine, Vrije Universiteit Brussel, Brussels, Belgium

Contents

Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9211. Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9222. Literature Search . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9233. General Clinical Benefits of Endurance-Type Exercise Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923

3.1 Obesity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9233.2 Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9243.3 Type 2 Diabetes Mellitus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9243.4 Heart Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 925

4. Impact of Training Modalities on Clinical Benefits of Exercise Intervention . . . . . . . . . . . . . . . . . . . . . . 9254.1 Programme Duration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9264.2 Additional Resistance-Type Exercise . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9264.3 Continuous Exercise Training Intensity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9294.4 High-Intensity Interval Exercise Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9314.5 Training Session Volume/Duration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9324.6 Training Frequency . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 933

5. General Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 934

Abstract Exercise training intervention represents an effective means to reduce adiposetissue mass, improve glycaemic control and increase whole-body oxygenuptake capacity (

.VO2peak) in obesity, metabolic syndrome, type 2 diabetes

mellitus (T2DM) and heart disease patients. In this manuscript, we review theimpact of different exercise training modalities on clinical benefits of pro-longed exercise intervention in these patient (sub)populations. By changingtraining modalities, significantly greater clinical benefits can be obtained.

REVIEWARTICLE Sports Med 2010; 40 (11): 921-9400112-1642/10/0011-0921/$49.95/0

ª 2010 Adis Data Information BV. All rights reserved.

Greater training frequency and longer programme duration is associatedwith greater reduction in adipose tissue mass in obesity patients. A greatertraining frequency (up to 2 days/week) and a longer programme duration (upto 38 weeks) seems to be associated with greater improvements in

.VO2peak in

heart disease patients. Longer programme duration and addition of resistance-type exercise further improve glycaemic control in T2DM patients. The firstline of evidence seems to indicate that high-intensity interval exercise traininghas a greater impact on

.VO2peak in heart disease patients and insulin sensi-

tivity in subjects with metabolic syndrome, but not on adipose tissue mass inobese subjects. However, it remains unclear whether addition of resistance-type exercise and continuous higher-intensity endurance-type exercise train-ing are accompanied by greater improvements in

.VO2peak in heart disease

patients. Furthermore, the impact of training session duration/volume onadipose tissue mass loss and glycaemic control in obesity and T2DM patients,respectively, is currently unknown. The impact of training frequency onglycaemic control remains to be investigated in T2DM patients.

1. Introduction

Over the past 2 decades, the world has expe-rienced an increased incidence of obesity, result-ing in a global obesity epidemic.[1] A key reasonbehind this epidemic is the lack of habitual phy-sical activity and food abundance. Our genomewas probably selected in the late Palaeolithic pe-riod (50 000–10 000BC) from criteria that favouredsurvival in a physically demanding environment,such as our ancestors’ hunter and gatherer soci-ety.[2] Fluctuations between feast and famine werecommon, resulting in oscillations in endogenousfuel storage, plasma insulin and metabolic reg-ulatory proteins, which in turn may have drivenselection of a metabolic genotype optimal for suchconditions. The ‘thrifty genes’ theory states thatthese feast-famine cycles are required for optimalmetabolic function.[2,3] Those individuals in thelate Palaeolithic period who were capable ofconverting joules into adipose tissue and couldeasily store lipids during feasting were more likelyto have higher survival rates during famine andwere capable of passing their genes onto the nextgeneration. It is evident that most individualswithin our modern society are carriers of this so-called thrifty genotype. Therefore, overfeeding incombination with a sedentary lifestyle, as seen inthe modern era, is the main cause for the increasedprevalence of obesity.[4]

In addition to increased mortality risk, obesity isclosely linked to development of insulin resistance,metabolic syndrome, type 2 diabetes mellitus(T2DM) and heart disease.[4] Recent estimationsindicate that the incidence of T2DM will con-tinue to increase, with an estimated rise in num-ber of T2DM patients up to 366 million in theyear 2030.[5] It is expected that economic costsrelated to treatment of these diseases will increaseexponentially. Clinical guidelines have been pub-lished to optimize primary and secondary pre-vention of T2DM and heart disease in an attemptto suppress this epidemic.[6,7] Besides medicationprescription and food intake modification, exer-cise training interventions are considered a cor-nerstone in prevention and care of individuals withobesity, metabolic syndrome, T2DM and/or heartdisease. According to current clinical guidelines,significant health benefits can be obtained when per-forming a minimum of 150 minutes of moderate-intensity exercise per week, with a progressiveincrease to 200–300 minutes per week.[6,7] Theseexercises should be executed on at least 3, andpreferably 5, days per week, and be accompaniedby resistance-type exercise. These guidelines pro-vide an effective strategy for the care of these pa-tient populations. Tjønna and colleagues[8] recentlyshowed a 24% lower cardiovascular mortality riskin patients with cardiovascular disease risk factorswho were more physically active than in their se-

922 Hansen et al.

ª 2010 Adis Data Information BV. All rights reserved. Sports Med 2010; 40 (11)

dentary counterparts. Nonetheless, a more de-tailed prescription of training modalities is lackingin the current guidelines.

More detailed information is necessary becausea different selection of training modalities mightbe instrumental to further optimize clinical ben-efits of exercise intervention. In people with obesity,metabolic syndrome, T2DM and/or heart disease,healthcare professionals should aim to maximizeclinical benefits of exercise intervention. It is im-portant to reduce adipose tissue mass, improveglycaemic control and increase whole-body oxy-gen uptake capacity (

.VO2peak) as effectively as

possible. For this purpose, the impact of differenttraining modalities during long-term exercise in-tervention needs to be examined. Factors such astraining intensity and frequency, session and pro-gramme duration, and the need to also implementresistance-type exercise are likely key factors thatmodulate clinical benefits of exercise intervention.

Besides changes in body composition, glycae-mic control and

.VO2peak, exercise intervention has

a profound impact on other parameters related tocardiovascular health. Exercise intervention im-proves blood rheology and endothelial function,lowers low-grade inflammation and oxidative stress,reduces coronary atherosclerosis and facilitatesvascular remodelling, angiogenesis and arteriogen-esis.[9-13] Though all of these changes are of greatrelevance for patients with obesity, metabolic syn-drome, T2DM and/or heart disease, they will notbe discussed in great detail in this review. Here,we present the current state of knowledge on theproposed effects of training modalities on changesin adipose tissue mass, metabolic syndrome, glycae-mic control and

.VO2peak in obese subjects, subjects

with metabolic syndrome, patients with T2DMand/or heart disease.

2. Literature Search

PubMed was used to search for manuscriptsanalysing the effects of exercise intervention inpatients with obesity, metabolic syndrome, T2DMand/or heart disease (from 1970 to September 2010).Combinations of the following keywords wereused: exercise intervention, exercise training, re-habilitation, obesity, fat mass, metabolic syndrome,

diabetes, insulin sensitivity, heart disease, PCI,CABG, myocardial infarction, oxygen uptake, ex-ercise capacity, fitness. From these abstracts, weincluded those studies that examined obese in-dividuals (body mass index >30 kg/m2), metabolicsyndrome and/or T2DM patients or patients withheart disease (coronary artery disease, myocar-dial infarction, coronary revascularisation) fol-lowing long-term (>4 weeks) exercise intervention(endurance-type exercise intervention with or with-out additional resistance-type exercise). Adiposetissue mass, glycaemic control and/or

.VO2peak had

to be assessed directly at entry and completion ofexercise intervention. In this review, we specifi-cally focus on those studies examining the impactof different training modalities (exercise inten-sity, session duration and frequency, programmeduration, addition of resistance-type exercise) onadipose tissue mass, glycaemic control or

.VO2peak.

Most patients with cardiometabolic disease donot achieve the criteria to determine maximumoxygen uptake (

.VO2max) during incremental ex-

ercise testing, which limits the use of.VO2max. On

the other hand,.VO2peak can always be properly

determined in these patients. In order to avoidconfusion by using

.VO2max and

.VO2peak inter-

changeably in this manuscript, we have chosen touse only ‘

.VO2peak’.

3. General Clinical Benefits ofEndurance-Type Exercise Training

3.1 Obesity

In obese individuals, adipose tissue mass losscan be effectively achieved by combining energyintake restriction with endurance-type exercisetraining. As a result of 16 weeks of combinedendurance-type exercise training and energy intakerestriction, an average weight loss of ~11 kg canbe achieved in obese individuals.[14] Even withoutdietary restriction, endurance-type exercise effec-tively lowers bodyweight in obese subjects, althoughto a lesser extent (on average ~3 kg).[14] However,many studies report that inclusion of endurance-type exercise, in addition to energy intake restric-tion, does not further augment adipose tissue massloss.[14] It seems that a compensatory reduction in

Exercise Training Modalities 923


habitual physical activity due to energy intakerestriction was not prevented by implementationof structured endurance-type exercise training.[15]

This compensatory behaviour might have sup-pressed the clinical efficacy of exercise training,and should be monitored closely. Besides changesin habitual activity outside the exercise trainingfacilities, certain baseline factors determine lossof adipose tissue mass as a result of endurance-type exercise intervention in obese subjects, andshould be taken into account: lower baselineadipose tissue mass and female gender predictsmaller effects.[16-18] When a reduction in adiposetissue mass is achieved as a result of endurance-type exercise training, this is accompanied bysecondary positive effects. Combined enduranceand resistance-type exercise interventions seemeffective to reduce or even prevent the decline inskeletal muscle mass that is generally observedduring energy intake restriction.[19] In addition, arelatively greater decline in visceral adipose tissuemass was observed in a combined energy intakerestriction/endurance training programme.[20] Thesefindings imply a preferential loss of central adipo-sity following a combined energy intake restrictionand endurance-type exercise training interven-tion. This would represent a major health benefit,as there is a strong relationship between visceralobesity and cardiovascular disease risk or insulinresistance.[21,22] Most obesity patients have low-ered insulin sensitivity or have already progressedto T2DM. In these patients, additional clinicalbenefits can be obtained by means of exercisetraining intervention.

3.2 Metabolic Syndrome

The metabolic syndrome is a cluster of cardio-vascular disease risk factors, including dyslipidae-mia, elevated blood pressure, impaired glycaemiccontrol and/or abdominal obesity. The metabolicsyndrome is often regarded as a precursor forT2DM. It might be questioned whether exerciseintervention affects the components of metabolicsyndrome: blood lipid profile, blood pressure,glycaemic control and bodyweight.[23-33]

The effects of exercise intervention on bloodlipid profile in metabolic syndrome patients re-

main controversial. Yassine et al.[33] and Rousselet al.[32] report a significant reduction in plasmalow-density lipoprotein and total cholesterol con-tent, and an increase in plasma high-density lipo-protein content, as a result of exercise intervention.Conversely, many other studies have failed to re-produce significant changes in plasma lipid profileas a result of an exercise regimen in patients withmetabolic syndrome.[24,25,27,28] Changes in theplasma lipid profile following exercise interven-tion could be camouflaged by prescribed med-ication[29] and/or different training modalities.[23]

Establishing a reduction in blood pressure seemsdifficult by means of exercise intervention in pa-tients with metabolic syndrome. Most, but notall,[23] studies report no change in this parameteras a result of exercise intervention.[25,27,29] On theother hand, glycaemic control seems to be posi-tively affected by exercise intervention in thesepatients. Studies unequivocally indicate that ex-ercise training improves insulin sensitivity[24,33]

and/or reduces fasting plasma insulin levels.[25]

In line with glycaemic control, bodyweight isalso positively affected by exercise intervention.Many studies report a significant decrease in body-weight, waist circumference and/or adipose tissuemass (assessed by an imaging technique or hy-drostatic weighing) as a result of prolonged ex-ercise intervention in patients with metabolicsyndrome.[24-26,28,32,33] Moreover, a reduction inbodyweight correlates with improvements in in-sulin sensitivity[24] and postprandial insulin res-ponses[25] in patients with metabolic syndrome.Even though

.VO2peak is not considered a compo-

nent of the metabolic syndrome, studies unequi-vocally report an increase in

.VO2peak following

prolonged exercise training in patients with themetabolic syndrome.[23,25,27,29,31,33]

In conclusion, exercise intervention representsan effective therapeutic strategy to improve gly-caemic control, reduce bodyweight and increasephysical fitness in subjects with the metabolicsyndrome.

3.3 Type 2 Diabetes Mellitus

Exercise intervention is well capable of improv-ing glycaemic control.[34-37] A recent meta-analysis

924 Hansen et al.


reported a decrease in blood glycosylated haemo-globin (HbA1c) content by 0.8% as a result of>12 weeks’ combined resistance and endurance-type exercise training in T2DM patients.[38]

Considering the significant relationship betweenblood HbA1c content and risk of cardiovasculardisease and premature death, such a decline inblood HbA1c content would translate into a sub-stantial reduction in risk of micro- and macrovas-cular disease and premature death.[39,40] Besideslowering blood HbA1c content in T2DM patients,exercise training interventions improve exerciseperformance capacity.[41] Exercise training alsodecreases adipose tissue mass, improves bloodplasma lipid profile and reduces mean arterialblood pressure.[42-44] Even enhanced pancreaticb-cell function has been observed as a result ofexercise training in T2DM patients with moder-ate baseline insulin-secretory capacity.[45] There-fore, exercise training interventions should forma cornerstone in the care of T2DM patients. Va-rious baseline parameters seem to affect the im-provements in glycaemic control following exercisetraining. It seems that higher baseline blood HbA1c

content and/or fasting glycaemia level, and femalegender, are related to better outcome results.[42,46]

Whether baseline adipose tissue mass affects thechange in glycaemic control is currently under dis-cussion.[46,47] When an improvement in glycaemiccontrol is achieved as a result of exercise trainingin T2DM patients, it seems, for the greater part,attributable to a reduction in visceral adiposetissue mass.[48-52] Even though some studies showan improvement in skeletal muscle oxidative ca-pacity and/or changes in muscle fibre type com-position in T2DM patients, correlations betweenthese changes and improvement in glycaemiccontrol have not been established.[53-56]

3.4 Heart Disease

In many T2DM patients, evidence for coronaryatherosclerosis and/or stenosis is present.[57] Whensuch cardiovascular co-morbidity is present, imple-mentation of exercise training intervention mightbe of even greater importance. In patients withheart disease, it is important to increase

.VO2peak

by exercise intervention, as this is significantly

related to a reduction in all-cause mortality risk.[58,59]

A recent meta-analysis indicates significant sur-vival benefits, and lowering of recurrent cardio-vascular event incidence, when exercise traininginterventions are implemented in the care ofheart disease patients.[60] In addition,

.VO2peak

reflects the clinical effectiveness of exercise inter-vention without influence of medication pre-scription (as opposed to glycaemic control, bloodlipid profile and blood pressure). In general, moststudies report an increase in

.VO2peak ranging

from 7% to 87% (mean 23 – 13%) following ex-ercise training in heart disease patients.[61] How-ever, some studies report no increase in exerciseperformance capacity as result of exercise train-ing.[62] Certain factors, such as baseline exerciseperformance capacity and skeletal muscle me-tabolism, presence of hibernating myocardiumand R-wave amplitude changes during incremen-tal exercise, seem to affect training outcome.[63-66]

Age, gender, ethnic origin and b-adrenoceptorantagonist (b-blocker) treatment do not seem tointerfere with exercise training outcome.[67-69]

When improvements in exercise performance ca-pacity in heart disease patients are achieved, theyare generally accompanied by increased mito-chondrial volume density and oxidative capacityin leg muscle tissue, peripheral oxygen extraction,peripheral vasodilatory muscular capacity andcardiac output, and decreased restenosis inci-dence and left ventricular end-diastolic pres-sure.[64,70-75] Both cardiac as well as peripheralskeletal muscle adaptive responses seem associ-ated with improvements in exercise performancecapacity in heart disease patients following ex-ercise intervention.

4. Impact of Training Modalities onClinical Benefits of Exercise Intervention

When implementing exercise training interven-tions in the care of patients with obesity, meta-bolic syndrome, T2DM and/or heart disease, theclinical effectiveness might be dependent on selec-tion of training modalities (session and trainingprogramme duration, addition of resistance-typeexercise, training intensity and session frequency).In sections 4.1–4.6, a detailed review of the impact



of different exercise training modalities on clinicalbenefits of exercise intervention is provided.

4.1 Programme Duration

According to current clinical guidelines, life-longparticipation in an exercise intervention prog-ramme is advised in patients with obesity, meta-bolic syndrome, T2DM and/or heart disease.[6,7]

It is suggested to incorporate habitual physicalactivity/exercise training into the daily routine ofpatients once supervision from healthcare pro-fessionals is no longer present.[6,7]

This suggestion is supported by many investi-gations (see table I). It seems that prolonged exer-cise training programmes result in a significantlygreater reduction in adipose tissue mass in obe-sity patients, improvement in glycaemic controlin T2DM patients and increase in

.VO2peak in

heart disease patients.[17,73,75-103] In the longterm, these greater clinical benefits might result inlower risk for micro- and macrocardiovascularevents, reduction in healthcare costs and greaterlife expectancy as well as improvements in qualityof life.[33,58-60] It seems necessary to stimulate pa-tients to continue to implement physical activityand/or exercise in their daily routine throughouttheir life. Exercise training programmes with limitedduration, as is currently often the case because offinancial/governmental restrictions, do not pro-vide durable improvements in health or pro-tection from development of chronic metabolicdisease.

Longer exercise programme duration is accom-panied by greater clinical benefits, but when the in-tervention continues, further improvements inpatients’ physical condition are generally not ob-served. For example, in heart disease patients,.VO2peak does not increase further after 38 weeksof exercise intervention.[103] It seems importantto warn the patient that such stabilization (or even asmall decline) of clinical benefits as a result oflong-term exercise intervention is to be expected.At the same time, efforts should be made to en-courage patients to adhere to the programme andto maintain motivation to continue exercising.

In conclusion, prolongation of exercise inter-ventions results in greater clinical benefits. Rela-

tively smaller clinical benefits are expected after acertain timeframe.

4.2 Additional Resistance-Type Exercise

Clinical guidelines suggest adding resistance-type exercise to an endurance-type exercise regimenin patients with obesity, metabolic syndrome,T2DM and/or heart disease.[6,7] Whether addi-tion of resistance-type exercise augments clinicalbenefits as a result of prolonged endurance-typeexercise training depends on intervention targets(see table II).

The effect of implementation of resistance-type exercise training within an endurance ex-ercise training programme on adipose tissue massloss has been intensively studied in the obese.Even though energy expenditure is increased asa consequence of additional use of resistance-type exercise training, this generally does not in-duce greater adipose tissue mass loss in obesitypatients.[11,17,82,83,105,106] However, addition ofresistance-type exercise to an endurance exercisetraining intervention programme does attenuatethe loss of skeletal muscle tissue and, as such,prevents a decline in resting metabolic rate due toenergy intake restriction.[83,116] This represents animportant clinical benefit as it improves long-term weight maintenance.

The implementation of additional resistance-type exercise within an endurance-type exercisetraining programme is accompanied by impor-tant clinical benefits for T2DM patients. Cuffet al.[50] compared the effects of 16 weeks of en-durance versus combined endurance and resistance-type exercise training in T2DM patients. Insulinsensitivity improved with significantly greater mag-nitude in the combination-trained group, whencompared with the endurance-trained group (asassessed by glucose infusion rate: 77% increasein combination-trained group, 20% increase inendurance-trained group). Sigal et al.[42] observeda 0.9% decline in blood HbA1c content following22 weeks of combined endurance and resistance-type exercise training, when compared with a 0.4%decline following endurance-type exercise train-ing. Some authors propose that an increase inskeletal muscle mass as a result of resistance-type

926 Hansen et al.


Table I. Impact of training programme duration on clinical benefits of exercise training

Study Age

(years)

No. of

subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Wadden et al.[17] 43 29 Obesity patients Adipose

tissue mass

8 vs 24 vs 48 weeks

(repeated assessment)

Greater reduction

with longer duration

Van Loan et al.[76] 25 5 Obesity patients Bodyweight 5 vs 8 vs 11 vs 24 weeks


Greater reduction


van Dale and Saris[77] 33 7 Obesity patients Adipose

tissue mass

5 vs 14 weeks


Greater reduction


Kukkonen et al.[78] 41 95 Obesity patients Bodyweight 8 vs 20 vs 44 vs

68 weeks


Greater reduction


Jeffery et al.[79] 42 84 Obesity patients Bodyweight 24 vs 52 vs 72 weeks


Greater reduction


Hays et al.[80] 65 12 Obesity patients Adipose

tissue mass

7 vs 14 weeks


Greater reduction


Fox et al.[81] 65 16 Obesity patients Adipose

tissue mass

12 vs 24 weeks


Greater reduction


Donnelly et al.[82] 54 11 Obesity patients Adipose

tissue mass

36 vs 64 weeks


Greater reduction


Sweeney et al.[83] 38 5 Obesity patients Adipose

tissue mass

12 vs 24 weeks


Greater reduction


Perri et al.[84] 49 25 Obesity patients Bodyweight Frequently repeated

assessment over

60 weeks

Greater reduction


Pasman et al.[85] 36 12 Obesity patients Adipose

tissue mass

16 vs 40 vs 64 weeks


Greater reduction


Hammer et al.[86] 32 14 Obesity patients Adipose

tissue mass

4 vs 8 vs 12 weeks


Greater reduction


Ozcelik et al.[87] 39 12 Obesity patients Adipose

tissue mass

4 vs 8 weeks


Greater reduction


Lehmann et al.[88] 54 16 T2DM patients HbA1c 12 vs 24 weeks


No effect found

Saltin et al.[89] 48 25 T2DM patients AUC during

OGTT

12 vs 24 weeks


No further reduction

after 12 weeks of

intervention

Bourn et al.[90] NA 20 T2DM patients HbA1c Repeated assessment

during 104 weeks

Ceased to

decrease after

84 weeks of

intervention

Uusitupa[91] NA 18 T2DM patients HbA1c 12 vs 60 weeks


Reduced more with

longer duration

Tokmakidis et al.[92] 55 9 T2DM patients AUC during

OGTT

4 vs 16 weeks


Reduced more with

longer duration

Brubaker et al.[93] 54 vs 62 25 vs 25 Heterogeneous.VO2peak

12 vs 52 weeks Greater

improvement with

longer duration

Dubach et al.[94] 56 12 CHF.VO2peak

4 vs 8 weeks


Greater

improvement with

longer duration

Demopoulos et al.[73] 61 16 CHF.VO2peak

6 vs 12 weeks


Greater

improvement with

longer duration

Continued next page



exercise, leading to an increase in blood glucosedisposal capacity, might be responsible for greaterimprovements following combined resistance-and endurance-type exercise training in T2DMpatients.[117,118] Furthermore, it should be notedthat greater muscle strength and increased func-tional performance capacity increases the capa-city to lead a more active, healthy lifestyle.

In patients with heart disease, the effect ofadditional resistance-type exercise on an increasein

.VO2peak within an endurance-type training pro-

gramme is presently under intense debate. Studieshave reported a greater increase in

.VO2peak as a

result of the addition of resistance-type exer-cise.[107-111] However, other studies indicate that

the addition of resistance-type exercise does notresult in greater improvements in

.VO2peak in

heart disease patients.[112-115] An explanation forthe contradiction in results between studies re-mains to be provided. The effects of additionalresistance-type exercise on improvement in

.VO2peak

in heart disease patients might be dependent onpatient population (magnitude of skeletal muscleatrophy, baseline exercise performance capacityand/or hospitalization period), resistance-typeexercise modalities and/or presence of cardiovas-cular co-morbidities.

In conclusion, addition of resistance-type ex-ercise to endurance-type exercise does not aug-ment adipose tissue mass loss in obesity patients.

Table I. Contd

Study Age

(years)

No. of

subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Lan et al.[75] 52 9 PCI.VO2peak

6 vs 12 weeks


Greater

improvement with

longer duration

DeBusk et al.[95] NA 30 vs 31 AMI METmax 8 vs 23 weeks Greater

improvement with

longer duration

Belardinelli et al.[96] 56 50 CHF.VO2peak

8 vs 56 weeks


Greater

improvement with

longer duration

Foster et al.[97] 56 19 CABG METmax 2 vs 8 vs 24 weeks


Greater

improvement with

longer duration

Kiilavuori et al.[98] 52 12 CHF.VO2peak

12 vs 24 weeks


No further increase

after 12 weeks of

intervention

Keteyian et al.[99] 52 15 CHF.VO2peak

12 vs 24 weeks


Greater

improvement with

longer duration

Ades et al.[100] NA 11 Heterogeneous.VO2peak

12 vs 52 weeks


Greater

improvement with

longer duration

Dugmore et al.[101] NA 62 AMI.VO2peak

16 vs 32 vs 52 weeks


Greater

improvement with

longer duration

Kavanagh et al.[102] 62 21 CHF.VO2peak

Frequently repeated

assessment during

52 weeks

No further increase

after 16 weeks of

intervention

Hamm et al.[103] 60 623 Heterogeneous.VO2peak

Repeated monthly

assessment during

52 weeks

No further increase

after 38 weeks of

intervention

AMI = acute myocardial infarction; AUC = area under the concentration-time curve; CABG = coronary artery bypass graft surgery;

CHF = congestive heart failure; HbA1c = glycosylated haemoglobin; METmax = maximal metabolic equivalent; NA= not available; OGTT = oral

glucose tolerance test; PCI = percutaneous coronary intervention; T2DM = type 2 diabetes mellitus;.VO2peak= whole-body oxygen uptake

capacity.

928 Hansen et al.


In T2DM patients, such addition results in a greaterimprovement in glycaemic control. The addition-al benefit of resistance-type exercise training on.VO2peak in heart disease patients remains unclear.

4.3 Continuous Exercise Training Intensity

Clinical guidelines suggest selecting continuousexercise intensities between 40% and 85%

.VO2peak

during training interventions in patients with obe-sity, metabolic syndrome, T2DM and/or heart

disease.[6,7] Because of the large range betweenlower and upper limits of intensity, it remains spe-culative at what intensity these patients shouldexercise (see table III).

Historically, in obese individuals, low-intensityendurance-type exercise has been prescribed tomaximize skeletal muscle fat oxidation[126] and,as such, to maximize adipose tissue mass loss. Asa consequence, many studies have aimed to assessthe impact of exercise training intensity on adiposetissue mass loss in obese patients. These studies

Table II. Impact of the addition of resistance-type exercises on clinical benefits of endurance-type exercise training

Study Age (years) No. of

subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Ashutosh et al.[104] 41 vs 45 8 vs 9 Obesity patients Adipose

tissue mass

Endurance vs

endurance + strength

Equal reduction

Donnelly et al.[82] NA 16 vs 9 Obesity patients Adipose

tissue mass

Endurance vs


Equal reduction

Donnelly et al.[105] NA 18 vs 21 Obesity patients Adipose

tissue mass

Endurance vs


Equal reduction

Marks et al.[106] 39 vs 40 10 vs 10 Obesity patients Adipose

tissue mass

Endurance vs


Equal reduction

Sweeney et al.[83] 32 vs 29 5 vs 6 Obesity patients Adipose

tissue mass

Endurance vs


Equal reduction at 6 months

of intervention

Wadden et al.[17] 41 vs 43 31 vs 29 Obesity patients Adipose

tissue mass

Endurance vs


Equal reduction

Cuff et al.[50] 63 vs 59 10 vs 9 T2DM patients Glucose

infusion

rate

Endurance vs


Greater increase of glucose

infusion rate

Sigal et al.[42] 53 vs 54 64 vs 60 T2DM patients HbA1c Endurance vs


Greater reduction of HbA1c

Stewart et al.[107] 52 vs 57 12 vs 11 AMI.VO2peak

Endurance vs


Greater increase when

resistance exercises added

Delagardelle et al.[108] 60 vs 54 10 vs 10 CHF.VO2peak

Endurance vs




Gayda et al.[109] NA 8 vs 8 Heterogeneous.VO2peak

Endurance vs




Marzolini et al.[110] 58 vs 61

vs 63

16 vs 19

vs 18

Heterogeneous.VO2peak

Endurance vs




Pierson et al.[111] 61 vs 59 10 vs 10 Heterogeneous.VO2peak

Endurance vs




Daub et al.[112] 49 vs 47

vs 51

14 vs 13

vs 15

AMI.VO2peak

Endurance vs


Equal increase

Santa-Clara et al.[113] 55 vs 57 13 vs 13 Heterogeneous.VO2peak

Endurance vs


Equal increase

Arthur et al.[114] NA 46 vs 46 Heterogeneous.VO2peak

Endurance vs


Equal increase

Beckers et al.[115] 58 vs 59 28 vs 30 CHF.VO2peak

Endurance vs


Equal increase

AMI = acute myocardial infarction; CHF = congestive heart failure; HbA1c= glycosylated haemoglobin; NA = not available; T2DM = type 2

diabetes mellitus;.VO2peak = whole-body oxygen uptake capacity.



unequivocally report no difference in adiposetissue mass loss when comparing continuous low-versus high-intensity exercise training program-mes (with matched energy expenditure betweentrials).[119-121] These data suggest that exercisevolume as opposed to training intensity forms themain factor that determines adipose tissue massloss during exercise intervention in obese subjects.However, compliance to an exercise interventionregimen has been reported to be associated withthe impact of the training workload.[127] Becausecompliance to a continuous high-intensity exer-cise training programme is generally lower thanlower-intensity exercise intervention regimens,[127]

selecting higher intensities during early stagesof such interventions is not advised. In patientswith metabolic syndrome, on the other hand, asignificantly different change in adipose tissuewas found between exercise regimens applyingdifferent exercise intensities.[31] After 16 weeks ofintervention, Irving et al.[31] reported a significantloss in adipose tissue mass, abdominal adiposetissue area, as well as subcutaneous adipose tissuearea as a result of continuous high-intensity ex-

ercise training, but not as a result of continuouslow-intensity exercise training. So far, there is noapparent explanation for the discrepancy be-tween studies.[31,119-121]

Exercise intensity has been suggested to repre-sent one of the more important exercise mod-alities that determine the clinical outcome of anexercise intervention in T2DM patients.[27,122]

This has been attributed to the inverse relation-ship between exercise intensity and muscle gly-cogen use.[128,129] The magnitude of increase ininsulin sensitivity following an acute bout ofendurance-type exercise has been associated withthe extent of muscle glycogen depletion and sub-sequent glycogen repletion rate.[130] However,recent studies indicate that different continuousexercise intensities do not modulate improvementsin glycaemic control during long-term exerciseinterventions in T2DM patients.[122] We havecompared the clinical benefits of 6 months of con-tinuous low-intensity (50%

.VO2peak) versus high-

intensity (75%.VO2peak) exercise training in T2DM

patients.[122] Blood HbA1c content decreased to asimilar extent as a result of exercise regimens with

Table III. Impact of continuous exercise intensity on clinical benefits of exercise training


subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Ballor et al.[119] NA 14 vs 13 Obesity patients Adipose tissue

mass

40–50% vs

80–90%.VO2peak

Equal reduction

Leutholtz et al.[120] 43 vs 40 20 vs 20 Obesity patients Adipose tissue

mass

40% vs 60% HRR Equal reduction

van Aggel-Leijssen

et al.[121]

43 vs 40 12 vs 12 Obesity patients Adipose tissue

mass

40% vs 70%.VO2peak

Equal reduction

Irving et al.[31] 51 15 vs 12 Metabolic

syndrome

patients

Adipose tissue

mass

<LT vs >LT Greater reduction in HI

Hansen et al.[122] 58 vs 59 25 vs 25 T2DM patients Blood HbA1c

content

50% vs 75%.VO2peak

Equal reduction

Johnson et al.[26] 54 vs 53 41 vs 45 Metabolic

syndrome

patients

Insulin

sensitivity

40–55% vs

65–80%.VO2peak

Improved in LI, but not in HI

Blumenthal et al.[123] 51 vs 52 23 vs 23 AMI.VO2peak

<45% vs 65–75%.VO2peak

Equal improvement

Jensen et al.[124]/Oberman et al.[125]

55 vs 53 83 vs 103 Heterogeneous.VO2peak

50% vs 50–85%.VO2peak

Greater improvement in HI

Adachi et al.[62] 62 vs 51 11 vs 10 CABG.VO2peak

80% vs 120% VT Greater improvement in HI

AMI = acute myocardial infarction; CABG = coronary artery bypass graft surgery; HbA1c = glycosylated haemoglobin; HI = high-intensity

intervention; HRR = heart rate reserve; LI = low-intensity intervention; LT = lactate threshold; NA= not available; T2DM = type 2 diabetes

mellitus;.VO2peak = whole-body oxygen uptake capacity; VT = ventilatory threshold.

930 Hansen et al.


different intensities. Moreover,.VO2peak, skeletal

muscle oxidative capacity and fat-free mass in-creased in both low- and high-intensity exerciseregimens, with no difference between programmes.As mentioned previously, higher exercise inten-sities are generally associated with a greater drop-out rate during long-term training regimens inpreviously sedentary individuals.[127] It mighttherefore be suggested to encourage lower exer-cise intensities during the early stages of imple-menting an exercise training regimen in T2DMpatients. The latter suggestion seems also applic-able to patients with the metabolic syndrome.Johnson et al.[26] compared the effects of 6 monthsof exercise training at 40–55% versus 65–80% of.VO2peak on insulin sensitivity. Their results showedsignificant improvements in insulin sensitivityfollowing low-intensity as opposed to high-intensityexercise training.[26] Therefore, when exercisebouts are prolonged, low-intensity exercise in-tervention is at least as effective as high-intensityexercise intervention to improve glycaemic con-trol in subjects with the metabolic syndrome.

In patients with heart disease, the proper se-lection of training intensity is currently a matterof intense debate. Several studies have investi-gated effects of continuous training intensities onchange in

.VO2peak during exercise intervention in

heart disease patients. Data from these investi-gations were equivocal: continuous high-intensity

exercise training was found to be of greater orequal impact on change in

.VO2peak compared with

continuous low-intensity exercise training.[62,123-125]

A systematic review indicated no threshold effectof training intensity on change in

.VO2peak in a

cohort of cardiac patients.[131] Large-cohort ran-domized trials are required to assess the impactof continuous exercise intensities on increasein

.VO2peak in heart disease patients.In conclusion, exercise intensity does not mo-

dulate adipose tissue mass loss in obese patients,and/or effect a change in glycaemic control inT2DM patients during continuous endurance-type exercise training. In patients with metabolicsyndrome, higher exercise intensities seem to beaccompanied by greater reductions in adiposetissue mass but lower improvements in insulinsensitivity. Studies are required to assess the im-pact of continuous exercise intensity during long-term endurance-type exercise interventions onchange in

.VO2peak in heart disease patients.

4.4 High-Intensity Interval Exercise Training

In recent studies, effects of high-intensity inter-val training have been assessed in obesity, meta-bolic syndrome and heart disease patients (seetable IV). This training methodology is differentfrom more continuous exercise training.[137] Inter-val training is characterized by sessions consisting

Table IV. Impact of high-intensity interval exercise training on clinical benefitsa

Study Age

(years)

No. of

subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Schjerve et al.[132] 44 vs 47 13 vs 14 Obesity patients Adipose tissue

mass

60–70% HRmax

vs interval

Equal reduction

Tjønna et al.[23] 52 vs 55 8 vs 11 Metabolic

syndrome patients

Insulin

sensitivity

70% HRmax

vs interval

Greater improvement

in interval training

Warburton et al.[133] 55 vs 57 7 vs 7 CABG and PCI.VO2peak

65% HRR vs

interval

Equal improvement

Rognmo et al.[134] and

Amundsen et al.[135]

63 vs 61 9 vs 8 Cardiac patients.VO2peak 50–60%

.VO2peak

vs interval

Greater improvement


Moholdt et al.[136] 60 vs 62 28 vs 31 CABG.VO2peak

70% HRmax

vs interval

Equal improvement at

4 weeks

Wisloff et al.[138] 74 vs 76 9 vs 9 CHF.VO2peak

70–75% HRmax

vs interval

Greater improvement


a No studies executed in T2DM patients.

CABG = coronary artery bypass graft surgery; CHF = congestive heart failure; HRmax= maximal heart rate; HRR = heart rate reserve;

PCI = percutaneous coronary intervention; T2DM = type 2 diabetes mellitus;.VO2peak = whole-body oxygen uptake capacity.



of successive bouts of short duration (1–4 minutes)at a relatively high-intensity workload (80–100%.VO2peak), alternated with small periods of activerest (1–4 minutes at 50–60%

.VO2peak).

Schjerve et al.[132] compared the effects of high-intensity interval training versus a more moderate-intensity exercise regimen (matched for energyexpenditure) in a cohort of obese adults. After12 weeks of intervention, total-body adipose tis-sue mass had declined to a similar extent (by 2.2%vs 2.5%, respectively). Therefore, it is not neces-sary to apply repeated bouts of greater exerciseintensities to modify adipose tissue mass in obe-sity patients. This is important because this typeof exercise regimen could be seen as more difficultby these patients, and could thus lower exercisemotivation. Therefore, high-intensity exercisebouts (85–95% maximal heart rate) do not seemto be required to increase the loss in adipose tis-sue mass in obesity patients.

The effect of high-intensity interval exercisetraining on glycaemic control in T2DM patientsis unknown. Tjønna and colleagues[23] evaluatedthe effect of high-intensity interval versus con-tinuous moderate-intensity endurance-type exer-cise training on insulin sensitivity in patients withmetabolic syndrome. After 16 weeks of interven-tion, insulin sensitivity increased significantly as aresult of high-intensity interval training, but notas a result of the continuous moderate-intensityendurance-type exercise training programme.[23]

Consequently, this study indicates that interval-type exercise training might be of greater benefitto improve glycaemic control than more routine-ly used endurance-type exercise training.

The interval-type exercise training methodol-ogy is believed to induce more rapid physiologi-cal adaptations in skeletal muscle tissue thanmore continuous high-intensity endurance-typeexercise training.[137] Most, but not all, data in-deed seem to indicate that high-intensity intervalexercise training is more effective in increas-ing

.VO2peak than continuous low-intensity exer-

cise training in heart disease patients.[133-135,138]

Moholdt et al.[136] found similar increases in.VO2peak

when comparing four weeks of supervised high-intensity interval vs continuous moderate-intensityexercise training in coronary artery bypass sur-

gery patients. However, greater gains in.VO2peak

were observed as result of subsequent 6 monthsof home-based (unsupervised) high-intensity in-terval vs continuous moderate-intensity exercisetraining. Such an effect might be of importantlong-term clinical benefit. Nonetheless, these stud-ies are generally limited by small sample sizes,and the effect of high-intensity interval exercisetraining on intervention adherence remains to beexamined.

In conclusion, the first line of evidence indi-cates that high-intensity interval exercise trainingmight be more effective in increasing

.VO2peak

in heart disease patients than exercise regimensof continuous exercise intensities. Reduction inadipose tissue mass does not seem to be affectedby the application of high-intensity interval exer-cise regimens in obesity patients. The effect of high-intensity interval exercise training on glycaemiccontrol in T2DM patients remains unknown, eventhough studies in patients with the metabolic syn-drome seem to suggest that greater improvementsin insulin sensitivity are to be expected as result ofhigh-intensity interval training.

4.5 Training Session Volume/Duration

Clinical guidelines suggest that patients withT2DM, metabolic syndrome and/or heart diseaseshould exercise for at least 40 minutes per session,and increase session time up to 60 minutes duringthe course of long-term training interventions.[6,7]

In cases of obesity, even longer training sessionsare advised.[6,7] Although clinical guidelines areoften used as a reference to design exercise inter-ventions, there seems to be great lack of data onimpact of training session volume/duration (seetable V).

In obese individuals, effects of training sessionvolume/duration on adipose tissue mass loss arerarely studied. Prolonged exercise is associated withan increase in adipose tissue lipolysis and avail-ability of plasma free fatty acids for oxidation.However, it remains to be examined whether suchexercise prolongation would result in greateradipose tissue mass loss in obesity patients. In astudy by Bond Brill et al.,[139] the dose-dependenteffect of walking (30- vs 60-minute sessions) on

932 Hansen et al.


body composition was analysed during energyintake restriction intervention. After 12 weeks ofexercise training, no difference in adipose tis-sue mass loss was observed between groups. Theauthors speculated that energy intake restrictionintervention is of much greater impact on adiposetissue mass loss than different exercise volume.Additional study seems required to assess theeffect of training session volume/duration on de-crease in adipose tissue mass in obesity patients.

In T2DM patients, no single study has examinedthe effect of training session volume/duration onthe change in glycaemic control during exerciseintervention. From the few data that are currentlyavailable, it seems that when applying greaterexercise bout volumes in T2DM patients, short-term glycaemic control improves with greater mag-nitude. Sriwijitkamol et al.[141] found a greaterdecrease in plasma glucose levels in T2DM pa-tients when cycling for 40 minutes at 70%

.VO2max

compared with 40 minutes at 50%.VO2peak. These

changes were accompanied by greater skeletal mus-cle glycogen depletion and peroxisome proliferator-activated receptor g coactivator 1-a (PGC-1a)expression in cases of greater exercise bout vol-ume. However, because a change in glycaemiccontrol during the first 24 hours following ex-ercise is of greater clinical relevance, the impact oftraining session volume with 24-hour continuousglucose monitoring needs to be assessed.[142]

Whether a greater exercise bout volume will contri-bute to greater improvement in glycaemic controlduring long-term intervention remains presentlyunknown in T2DM patients. For example, dur-ing a 6-month exercise intervention in patientswith metabolic syndrome, a greater exercise vol-

ume (175 minutes of exercise/week) did not seemto contribute to greater improvements in insulinsensitivity when compared with a lower exercisevolume (114 minutes of exercise/week).[26]

In heart disease patients, the impact of exercisesession volume/duration has been investigated byour laboratory.[140] We compared effects of 40- vs60-minute exercise bouts during a 7-week exerciseintervention in coronary artery disease patients.Even though different exercise volumes were ap-plied,

.VO2peak increased with a similar magnitude.

As a result, the time investment in exercise boutscan be reduced significantly without affectingthe change in

.VO2peak. This might contribute to

greater working efficiency of cardiac rehabilita-tion centres.

In conclusion, the effects of training sessionvolume/duration on clinical benefits of long-termexercise intervention remain presently uncertainin patients with obesity or T2DM. In patientswith heart disease, exercise session volume doesnot affect change in

.VO2peak.

4.6 Training Frequency

Obesity, metabolic syndrome, T2DM and/orheart disease patients are advised to exercise atleast 3, and preferably 5, days a week.[6,7] Theseexercise bouts should best be distributed equallyover the week.

Only a few studies assessed the influence oftraining frequency on clinical benefits as a resultof long-term exercise intervention in obesity andheart disease patients (see table VI).

Whatley et al.[143] compared the effects of twoexercise frequencies (3 vs 5 days a week) during a

Table V. Impact of training session volume/duration on clinical benefits of exercise traininga


subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Bond Brill

et al.[139]

39 vs 40 21 vs 19 Obesity patients Adipose tissue

mass

30 vs 60 minute/session

Equal reduction

Johnson

et al.[26]

53 vs 51 45 vs 44 Metabolic syndrome

patients

Insulin

sensitivity

114 vs 175 minute/week

Equal improvement

Hansen

et al.[140]

63 vs 63 67 vs 67 CAD patients.VO2peak

40 vs 60 minute/session

Equal improvement


CAD = coronary artery disease; HRmax= maximal heart rate; T2DM = type 2 diabetes mellitus;.VO2peak= whole-body oxygen uptake capacity.



12-week intervention programme in obese females,during which energy intake was restricted. In thisstudy, the high-frequency training group lostconsiderably more adipose tissue mass than thelow-frequency training group (16 – 4 vs 13 – 4 kg).A significant correlation between adipose tissuemass loss and total work duration was reported.[143]

A greater exercise frequency seems associatedwith a greater adipose tissue mass loss in obeseindividuals. Nonetheless, further study is war-ranted to verify these findings.

In heart disease patients, similar effects werefound for change in

.VO2peak. Dressendorfer et al.[144]

reported a significantly greater improvement in.VO2peak when increasing training frequency (onevs two vs three sessions a week) in a cohort ofacute myocardial infarction patients. A greaterimprovement in maximal cycling power outputwas reported by Tygesen et al.[145] when heartdisease patients exercised for six sessions a week,compared with two sessions a week. No such ef-fect was found in a study by Nieuwland et al.,[146]

where effects of two versus six sessions a week onincrease in

.VO2peak were compared. It might be

speculated that.VO2peak increases by a greater

magnitude when increasing exercise frequency upto 2 days/week, while no further improvementsin

.VO2peak are expected with exercise frequencies

>2 days/week.Data seem to indicate that T2DM patients

should exercise on a regular basis to improve gly-caemic control. This suggestion results from thefinding that increased insulin sensitivity as a result

of an exercise bout disappears within approxi-mately 48 hours in T2DM patients.[147] It seemsessential for T2DM patients to exercise at leastthree times a week (with one recovery day in be-tween) to maintain increased insulin sensitivitythroughout the week. However, studies directlycomparing effects of a low- or high-frequencyexercise training intervention on glycaemic con-trol in T2DM patients are not present. It remainsto be investigated whether training frequency af-fects the change in glycaemic control in this sub-set of patients.

In conclusion, greater exercise frequency dur-ing long-term exercise intervention seems asso-ciated with greater adipose tissue mass loss andimprovement in

.VO2peak in obesity and heart dis-

ease patients, respectively. The effect of this train-ing modality on changes in glycaemic controlremains to be examined in T2DM patients.

5. General Conclusions

Exercise training interventions represent aneffective means to reduce adipose tissue mass,improve glycaemic control and increase

.VO2peak

in obesity, T2DM and heart disease patients, res-pectively. By changing training modalities, signif-icantly greater clinical benefits can be obtained.Greater training frequency and longer programmeduration is associated with a greater reduction inadipose tissue mass in obesity patients. A greatertraining frequency (up to 2 days/week) and a longerprogramme duration (up to 38 weeks) seems to be

Table VI. Impact of training frequency on clinical benefits of exercise traininga


subjects

Subject

characteristics

Effect

parameter

Comparison Effect

Whatley et al.[143] 39 vs 36 8 vs 8 Obesity patients Bodyweight 3 vs 5

sessions/week

Greater reduction with

higher frequency

Dressendorfer et al.[144] 54 vs 55

vs 56

13 vs 13

vs 12

AMI.VO2peak

1 vs 2 vs 3

sessions/week

Greater increase with

higher frequency

Tygesen et al.[145] 56 vs 57 33 vs 29 AMI and CABG Wmax 2 vs 6

sessions/week

Greater increase with

higher frequency

Nieuwland et al.[146] 52 vs 53 63 vs 67 Heterogeneous.VO2peak

2 vs 10

sessions/week

Equal increase


AMI = acute myocardial infarction; CABG = coronary artery bypass graft surgery; T2DM = type 2 diabetes mellitus;.VO2peak = maximal whole-

body oxygen uptake capacity; Wmax = maximal cycling power output.

934 Hansen et al.


associated with greater improvements in.VO2peak

in heart disease patients. Longer programme du-ration and the addition of resistance-type exer-cises further improves glycaemic control in T2DMpatients. The first line of evidence suggests thathigh-intensity interval exercise training has agreater impact on

.VO2peak in heart disease pa-

tients and insulin sensitivity in patients with me-tabolic syndrome. The latter does not seem to bethe case when looking at changes in adipose tissuemass following exercise interventions in obesesubjects. Healthcare professionals have the op-portunity to improve the clinical efficacy of ex-ercise training intervention by implementing suchprogramme modifications. Intense debate con-tinues as to whether changes in certain trainingmodalities can alter the clinical outcome duringlong-term exercise intervention in these patients.It remains speculative whether the addition ofresistance-type exercise and higher continuousendurance-type exercise training at certain work-load intensities are accompanied by greater im-provements in

.VO2peak in heart disease patients.

The effect of training session duration/volume onadipose tissue mass in obesity patients, and gly-caemic control in T2DM patients, is currentlyunknown. The impact of training frequency re-mains to be investigated in T2DM patients.

Acknowledgements

This review was supported by an unrestricted grant fromthe clinical research foundation Hartcentrum Hasselt. Therehas been no previous presentation and the authors have noconflicts of interest that are directly relevant to the contents ofthis review.

References1. Chopra M, Galbraith S, Darnton-Hill I. A global response

to a global problem: the epidemic of overnutrition. BullWorld Health Organ 2002; 80 (12): 952-8

2. Chakravarthy MV, Booth FW. Eating, exercise, and ‘thrif-ty’ genotypes: connecting the dots towards an evolu-tionary understanding of modern diseases. J Appl Physiol2004 Jan; 96 (1): 3-10

3. Booth FW, Chakravarthy MV, Gordon SE, et al. Wagingwar on physical inactivity: using modern molecular am-munition against an ancient enemy. J Appl Physiol 2002Jul; 93 (1): 3-30

4. Andersen RE. Obesity; etiology, assessment, treatment,and prevention. Champaign (IL): Human Kinetics, 2003

5. Wild S, Roglic G, Green A, et al. Global prevalence ofdiabetes: estimates for the year 2000 and projections for2030. Diabetes Care 2004 May; 27 (5): 1047-53

6. Fletcher GF, Balady GJ, Amsterdam EA, et al. Exercisestandards for testing and training: a statement for health-care professionals from the American Heart Association.Circulation 2001 Oct; 104 (14): 1694-740

7. Sigal RJ, Kenny GP, Wasserman DH, et al. Physical activity/exercise and type 2 diabetes. Diabetes Care 2006 Jun; 29 (6):1433-8

8. Tjønna AE, Lund Nilsen TI, Slørdahl SA, et al. The asso-ciation of metabolic clustering and physical activity withcardiovascular mortality: the HUNT study in Norway.J Epidemiol Community Health 2010 Aug; 64 (8): 690-5

9. Erbs S, Linke A, Hambrecht R. Effects of exercise trainingon mortality in patients with coronary heart disease.Coron Artery Dis 2006 May; 17 (3): 219-25

10. Church ST, Lavie CJ, Milani RV, et al. Improvements inblood rheology after cardiac rehabilitation and exercisetraining in patients with coronary heart disease. Am Heart J2002 Feb; 143 (2): 349-55

11. Gielen S, Schuler G, Hambrecht R. Exercise training incoronary artery disease and coronary vasomotion. Circu-lation 2001 Jan 2; 103 (1): E1-6

12. Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise oncoronary endothelial function in patients with coronaryartery disease. N Engl J Med 2000 Feb 17; 342 (7): 454-60

13. Nicklas JN, You T, Pahor M. Behavioural treatments forchronic systemic inflammation: effects of dietary weightloss and exercise training. CMAJ 2005 Apr 26; 172 (9):1199-209

14. Miller WC, Koceja DM, Hamilton EJ. A meta-analysis ofthe past 25 years of weight loss research using diet, exer-cise or diet plus exercise intervention. Int J Obes RelatMetab Disord 1997 Oct; 21 (10): 941-7

15. Kempen KP, Saris WH, Westerterp KR. Energy balanceduring an 8-wk energy-restricted diet with and withoutexercise in obese women. Am J Clin Nutr 1995 Oct; 62 (4):722-9

16. Dengel DR, Hagberg JM, Coon PJ, et al. Effects of weightloss by diet alone or combined with aerobic exercise onbody composition in older obese men. Metabolism 1994Jul; 43 (7): 867-71

17. Wadden TA, Vogt RA, Andersen RE, et al. Exercise in thetreatment of obesity: effects of four interventions on bodycomposition, resting energy expenditure, appetite, andmood. J Consult Clin Psychol 1997 Apr; 65 (2): 269-77

18. Ballor DL, Keesey RE. A meta-analysis of the factors af-fecting changes in body mass, fat mass and fat-free mass inmales and females. Int J Obes 1991 Nov; 15 (11): 717-26

19. Ballor DL, Poehlman ET. Exercise-training enhances fat-free mass preservation during diet-induced weight loss: ameta-analytical finding. Int J Obes 1994 Jan; 18 (1): 35-40

20. Ross R, Rissanen J, Pedwell H, et al. Influence of diet andexercise on skeletal muscle and visceral adipose tissue inmen. J Appl Physiol 1996 Dec; 81 (6): 2445-55

21. Ohlsen LO, Larsson B, Svardsudd K, et al. The influence ofbody fat distribution on the incidence of diabetes mellitus:



13.5 years of follow-up of the participants in the study ofmen born in 1913. Diabetes 1985 Oct; 34 (10): 1055-8

22. Peiris AN, Sothmann MS, Hoffmann RG, et al. Adiposity,fat distribution, and cardiovascular risk. Ann Intern Med1989 Jun; 110 (11): 867-72

23. Tjønna AE, Lee SJ, Rognmo Ø, et al. Aerobic intervaltraining versus continuous moderate exercise as a treat-ment for the metabolic syndrome. Circulation 2008 Jul 22;118 (4): 346-54

24. Dumortier M, Brandou F, Perez-Martin A, et al. Low in-tensity endurance exercise targeted for lipid oxidationimproves body composition and insulin sensitivity inpatients with the metabolic syndrome. Diabetes Metab2003 Nov; 29 (5): 509-18

25. Watkins LL, Sherwood A, Feinglos M, et al. Effects ofexercise and weight loss on cardiac risk factors associatedwith syndrome x. Arch Intern Med 2003 Sep 8; 163 (16):1889-95

26. Johnson JL, Slentz CA, Houmard JA, et al. Exercisetraining amount and intensity effects on metabolic syn-drome (from studies of a targeted risk reduction interven-tion through defined exercise). Am J Cardiol 2007 Dec 15;100 (12): 1759-66

27. Anderssen SA, Carroll S, Urdal P, et al. Combined diet andexercise intervention reverses the metabolic syndrome inmiddle-aged males: results from the Oslo Diet and Ex-ercise Study. Scand J Med Sci Sports 2007 Dec; 17 (6):687-95

28. Aloulou I, Varlet-Marie E, Mercier J, et al. Hemorheologiceffects of low intensity endurance training in sedentarypatients suffering from the metabolic syndrome. ClinHemorheol Microcirc 2006; 35 (1-2): 333-9

29. Green JS, Stanforth PR, Rankinen T, et al. The effects ofexercise training on abdominal visceral fat, body composi-tion, and indicators of the metabolic syndrome in post-menopausal women with and without estrogen replacementtherapy: the HERITAGE Family Study. Metabolism 2004Sep; 53 (9): 1192-6

30. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targetingthe metabolic syndrome with exercise: evidence from theHERITAGE Family Study. Med Sci Sports Exerc 2003Oct; 35 (10): 1703-9

31. Irving BA, Davis CK, Brock DW, et al. Effect of exercisetraining intensity on abdominal visceral fat and body com-position. Med Sci Sports Exerc 2008 Nov; 40 (11): 1863-72

32. Roussel M, Garnier S, Lemoine S, et al. Influence of awalking program on the metabolic risk profile of obesepostmenopausal women. Menopause 2009 May-Jun; 16 (3):56-75

33. Yassine HN, Marchetti CM, Krishnan RK, et al. Effects ofexercise and caloric restriction on insulin resistance andcardiometabolic risk factors in older obese adults: a ran-domized clinical trial. J Geront A Biol Sci Med Sci 2009Jan; 64 (1): 90-5

34. Praet SF, Jonkers RA, Schep G, et al. Long-standing, insulin-treated type 2 diabetes patients with complications re-spond well to short-term resistance and interval exercisetraining. Eur J Endocrinol 2008 Feb; 158 (2): 163-72

35. Praet SF, van Loon LJ. Exercise: the brittle cornerstone oftype 2 diabetes treatment. Diabetologia 2008 Mar; 51 (3):398-401

36. Praet SF, van Loon LJ. Optimizing the therapeutic benefitsof exercise in type 2 diabetes. J Appl Physiol 2007 Oct; 103 (4):1113-20

37. De Feyter HM, Praet SF, van den Broek NM, et al. Exer-cise training improves glycemic control in long-standinginsulin-treated type 2 diabetic patients. Diabetes Care2007 Oct; 30 (10): 2511-3

38. Snowling NJ, Hopkins WG. Effects of different modes ofexercise training on glucose control and risk factors forcomplications in type 2 diabetic patients. Diabetes Care2006 Nov; 29 (11): 2518-27

39. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin comparedwith conventional treatment and risks of complications inpatients with type 2 diabetes (UKPDS 33). Lancet 1998Sep; 352 (9131): 837-53

40. Khaw K, Wareham N, Luben R, et al. Glycated haemo-globin, diabetes and mortality in men in Norfolk cohort ofEuropean Prospective Investigation of Cancer and Nutri-tion (EPIC-Norfolk). BMJ 2001 Jan; 322 (7277): 15-8

41. Boule NG, Kenny GP, Haddad E, et al. Meta-analysis ofthe effect of structured exercise training on cardiorespira-tory fitness in type 2 diabetes mellitus. Diabetologia 2003Aug; 46 (8): 1071-81

42. Sigal RJ, Kenny GP, Boule NG, et al. Effects of aerobictraining, resistance training, or both on glycemic con-trol in type 2 diabetes. Ann Intern Med 2007 Sep; 147 (6):357-69

43. Dunstan DW, Mori TA, Puddey IB, et al. The independentand combined effects of aerobic exercise and dietary fishintake on serum lipids and glycaemic control in NIDDM.Diabetes Care 1997 Jun; 20 (6): 913-21

44. Praet SF, van Rooij ESJ, Wijtvliet A, et al. Brisk walkingcompared with an individual medical fitness programmefor patients with type 2 diabetes: a randomised controlledtrial. Diabetologia 2008 May; 51 (5): 736-46

45. Dela F, von Linstow ME, Mikines KJ, et al. Physical train-ing may enhance b-cell function in type 2 diabetes. AmJ Physiol Endocrinol Metab 2004 Nov; 287 (5): E1024-31

46. Tessier D, Menard J, Fulop T, et al. Effects of aerobicphysical exercise in the elderly with type 2 diabetes melli-tus. Arch Geron Geriatr 2000 Oct; 31 (2): 121-32

47. Poirier P, Tremblay A, Broderick T, et al. Impact of mod-erate aerobic exercise training on insulin sensitivity in type2 diabetic men treated with oral hypoglycemic agents: isinsulin sensitivity enhanced only in nonobese subjects?Med Sci Monit 2002 Feb; 8 (2): CR59-65

48. Mourier A, Gautier JF, De Kerviler E, et al. Mobilizationof visceral adipose tissue related to the improvement in in-sulin sensitivity in response to physical training in NIDDM:effects of branched-chain amino acid supplements. DiabetesCare 1997 Mar; 20 (3): 385-91

49. Boudou P, Sobngwi E, Mauvais-Jarvis F, et al. Absence ofexercise-induced variations in adiponectin levels despitedecreased abdominal adiposity and improved insulinsensitivity in type 2 diabetic men. Eur J Endocrinol 2003Nov; 149 (5): 421-4

50. Cuff DJ, Meneilly GS, Martin A, et al. Effective exercisemodality to reduce insulin resistance in women with type 2diabetes. Diabetes Care 2003 Nov; 26 (11): 2977-82

936 Hansen et al.


51. Giannopoulou I, Fernhall B, Carhart R, et al. Effects ofdiet and/or exercise on the adipocytokines and inflamma-tory cytokine levels of postmenopausal women with type 2diabetes. Metabolism 2005 Jul; 54 (7): 866-75

52. Giannopoulou I, Ploutz-Snyder LL, Carhart R, et al. Exer-cise is required for visceral fat loss in postmenopausalwomen with type 2 diabetes. J Clin Endocrinol Metab2005 Mar; 90 (3): 1511-8

53. Toledo GS, Menshikova EV, Ritov VB, et al. Effects ofphysical activity and weight loss on skeletal muscle mi-tochondria and relationship with glucose control in type 2diabetes. Diabetes 2007 Aug; 56 (8): 2142-7

54. Allenberg K, Johansen K, Saltin B. Skeletal muscle adap-tations to physical training in type II (non-insulin-dependent)diabetes mellitus. Acta Med Scand 1988; 223 (4): 365-73

55. Bruce CR, Kriketos AD, Cooney GJ, et al. Dissociation ofmuscle triglyceride content and insulin sensitivity afterexercise training in patients with type 2 diabetes. Diabe-tologia 2004 Jan; 47 (1): 23-30

56. Fritz T, Kramer DK, Karlsson HKR, et al. Low-intensityexercise increases skeletal muscle protein expression ofPPARd and UCP3 in type 2 diabetic patients. Diab MetabRes Rev 2006 Nov-Dec; 22 (6): 492-8

57. Lim S, Choi SH, Choi EK, et al. Comprehensive evalua-tion of coronary arteries by multidetector-row cardiaccomputed tomography according to the glucose level ofasymptomatic individuals. Atherosclerosis 2009 Jul;205 (1): 156-62

58. Vanhees L, Fagard R, Thijs L, et al. Prognostic value oftraining-induced change in peak exercise capacity in pa-tients with myocardial infarcts and patients with coronarybypass surgery. Am J Cardiol 1995 Nov; 76 (14): 1014-9

59. Kavanagh T, Mertens DJ, Hamm LF, et al. Prediction oflong-term prognosis in 12169 men referred for cardiacrehabilitation. Circulation 2002 Aug; 106 (6): 666-71

60. Suaya JA, Stason WB, Ades PA, et al. Cardiac rehabilita-tion and survival in older coronary patients. J Am CollCardiol 2009 Jun; 54 (1): 25-33

61. Hansen D, Dendale P, Berger J, et al. Rehabilitation incardiac patients: what do we know about training mod-alities? Sports Med 2005; 35 (12): 1063-84

62. Adachi H, Koike A, Obayashi T, et al. Does appropriateendurance exercise training improve cardiac function inpatients with prior myocardial infarction? Eur Heart J1996 Oct; 17 (10): 1511-21

63. Sakuragi S, Takagi S, Suzuki S, et al. Patients with largemyocardial infarction gain a greater improvement in ex-ercise capacity after exercise training than those withsmall to medium infarction. Clin Cardiol 2003 Jun; 26 (6):280-6

64. Uchida I, Takaki H, Kobayashi Y, et al. O2 extractionduring exercise determines training effect after cardiacrehabilitation in myocardial infarction. Circ J 2002 Oct;66 (10): 891-6

65. Belardinelli R, Georgiou D, Purcaro A. Low dose dobu-tamine echocardiography predicts improvement in func-tional capacity after exercise training in patients withischemic cardiomyopathy: prognostic implication. J AmColl Cardiol 1998 Apr; 31 (5): 1027-34

66. Willenheimer R, Ernhardt L, Cline C, et al. Exercisetraining in heart failure improves quality of life and ex-ercise capacity. Eur Heart J 1998 May; 19 (5): 774-81

67. Balady GJ, Jette D, Scheer J, et al. Changes in exercisecapacity following cardiac rehabilitation in patients stra-tified according to age and gender: results of the Massa-chusetts Association of Cardiovascular and PulmonaryRehabilitation Multicenter Database. J Cardiopulm Re-habil 1996 Jan-Feb; 16 (1): 38-46

68. Cannistra LB, O’Malley CJ, Balady GJ. Comparison ofoutcome of cardiac rehabilitation in black women andwhite women. Am J Cardiol 1995 May; 75 (14): 890-3

69. Pavia L, Orlando G, Myers J, et al. The effect of beta-blockade therapy on the response to exercise training inpostmyocardial infarction patients. Clin Cardiol 1995Dec; 18 (12): 716-20

70. Hambrecht R, Niebauer J, Fiehn E, et al. Physical trainingin patients with chronic heart failure: effects on cardio-respiratory fitness and ultrastructural abnormalities of legmuscles. J Am Coll Cardiol 1995 May; 25 (6): 1239-49

71. Belardinelli R, Georgiou D, Scocco V, et al. Low intensityexercise training in patients with chronic heart failure.J Am Coll Cardiol 1995 Oct; 26 (4): 975-82

72. Dziekan G, Myers J, Goebbels U, et al. Effects of exercisetraining on limb blood flow in patients with reduced ven-tricular function. Am Heart J 1998 Jul; 136 (1): 22-30

73. Demopoulos L, Bijou R, Fergus I, et al. Exercise training inpatients with severe congestive heart failure: enhancingpeak aerobic capacity while minimizing the increase in ven-tricular wall stress. J Am Coll Cardiol 1997 Mar; 29 (3):597-603

74. Sullivan MJ, Higginbotham MB, Cobb FR. Exercise train-ing in patients with severe left ventricular dysfunction:hemodynamic and metabolic effects. Circulation 1988Sep; 78 (3): 506-15

75. Lan C, Chen SY, Chiu SF, et al. Poor functional recoverymay indicate restenosis in patients after coronary angio-plasty. Arch Phys Med Rehabil 2003 Jul; 84 (7): 1023-7

76. Van Loan MD, Keim NL, Barbeiri TF, et al. The effects ofendurance exercise with and without a reduction of energyintake on fat-free mass and the composition of fat-freemass in obese women. Eur J Clin Nutr 1994 Jun; 48 (6):408-15

77. van Dale D, Saris WHM. Repetitive weight loss and weightregain: effects on weight reduction, resting metabolic rate,and lipolytic activity before and after exercise and/or diettreatment. Am J Clin Nutr 1989 Mar; 49 (3): 409-16

78. Kukkonen K, Rauramaa R, Siitonen O, et al. Physical train-ing of obese middle-aged parsons. Ann Clin Res 1982;14 Suppl. 34: 80-5

79. Jeffery RW, Wing RR, Sherwood NE, et al. Physical activ-ity and weight loss: does prescribing higher physical ac-tivity goals improve outcome? Am J Clin Nutr 2003 Oct;78 (4): 684-9

80. Hays NP, Starling RD, Kiu X, et al. Effects of an ad libitumlow-fat, high-carbohydrate diet on body weight, body com-position, and fat distribution in older men and women.Arch Intern Med 2004 Jan; 164 (2): 210-7

81. Fox AA, Thompson JL, Butterfield GE, et al. Effects ofdiet and exercise on common cardiovascular disease risk



factors in moderately obese older women. Am J Clin Nutr1996 Feb; 63 (2): 225-33

82. Donnelly JE, Pronk NP, Jacobsen DJ, et al. Effects of avery-low-calorie diet and physical-training regimens onbody composition and resting metabolic rate in obese fe-males. Am J Clin Nutr 1991 Jul; 54 (1): 56-61

83. Sweeney ME, Hill JO, Heller PA, et al. Severe vs moderateenergy restriction with and without exercise in the treat-ment of obesity: efficiency of weight loss. Am J Clin Nutr1993 Feb; 57 (2): 127-34

84. Perri MG, Martin D, Leermakers EA, et al. Effects ofgroup- versus home-based exercise in the treatment ofobesity. J Cons Clin Psychol 1997 Apr; 65 (2): 278-85

85. Pasman WJ, Westerterp-Platenga MS, Saris WHM. Theeffect of body weight changes and endurance training on24h substrate oxidation. Int J Obes 1999 Dec; 23 (12):1223-32

86. Hammer RL, Barrier CA, Roundy ES, et al. Calorie-restricted low-fat diet and exercise in obese women. AmJ Clin Nutr 1989 Jan; 49 (1): 77-85

87. Ozcelik O, Dogan H, Kelestimur H. Effects of eight weeksof exercise training and orlistat therapy on body compo-sition and maximal exercise capacity in obese females.Publ Health 2006 Jan; 120 (1): 76-82

88. Lehmann R, Vokac A, Niedermann K, et al. Loss of ab-dominal fat and improvement of the cardiovascular riskprofile by regular moderate exercise training in patientswith NIDDM. Diabetologia 1995 Nov; 38 (11): 1313-9

89. Saltin B, Lindgarde F, Houston M, et al. Physical trainingand glucose tolerance in middle-aged men with chemicaldiabetes. Diabetes 1979; 28 Suppl. 1: 30-2

90. Bourn DM, Mann JI, McSkimming BJ, et al. Impairedglucose tolerance and NIDDM: does a lifestyle interven-tion program have an effect? Diabetes Care 1994 Nov;17 (11): 1311-9

91. Uusitupa MI. Early lifestyle intervention in patients withnon-insulin-dependent diabetes mellitus and impairedglucose tolerance. Ann Med 1996 Oct; 28 (5): 445-59

92. Tokmakidis SP, Zois CE, Volaklis KA, et al. The effects ofa combined strength and aerobic exercise program onglucose control and insulin action in women with type 2diabetes. Eur J Appl Physiol 2004 Aug; 92 (4-5): 437-42

93. Brubaker PH, Warner Jr JG, Rejeski WJ, et al. Compar-ison of standard- and extended-length participation incardiac rehabilitation on body composition, functionalcapacity, and blood lipids. Am J Cardiol 1996 Oct; 78 (7):769-73

94. Dubach P, Myers J, Dziekan G, et al. Effect of high inten-sity exercise training on central hemodynamics responseto exercise in men with reduced left ventricular function.J Am Coll Cardiol 1997 Jun; 29 (7): 1591-8

95. DeBusk RF, Haskell WL, Miller NH, et al. Medically di-rected at-home rehabilitation soon after clinically uncom-plicated acute myocardial infarction: a new model forpatient care. Am J Cardiol 1985 Feb; 55 (4): 251-7

96. Belardinelli R, Georgiou D, Cianci G, et al. Randomised,controlled trial of long-term moderate exercise training inchronic heart failure: effects on functional capacity, qual-ity of life, and clinical outcome. Circulation 1999 Mar;99 (9): 1173-82

97. Foster C, Pollock ML, Anholm JD, et al. Work capacityand left ventricular function during rehabilitation aftermyocardial revascularization surgery. Circulation 1984Apr; 69 (4): 748-55

98. Kiilavuori K, Sovijarvi A, Naveri H, et al. Effect of physi-cal training on exercise capacity and gas exchange in pa-tients with chronic heart failure. Chest 1996 Oct; 110 (4):985-91

99. Keteyian SJ, Levine AB, Brawner CA, et al. Exercisetraining in patients with heart failure: a randomised con-trolled trial. Ann Intern Med 1996 Jun; 124 (12): 1051-7

100. Ades PA, Waldmann ML, Poehlman ET, et al. Exerciseconditioning in older coronary patients: submaximal lac-tate response and endurance capacity. Circulation 1993Aug; 88 (2): 572-7

101. Dugmore LD, Tipson RJ, Philips MH, et al. Changes incardiorespiratory fitness, psychological wellbeing, qualityof life, and vocational status following a 12 month cardiacexercise rehabilitation programme. Heart 1999 Apr; 81 (4):359-66

102. Kavanagh T, Myers MG, Baigrie RS, et al. Quality of lifeand cardiorespiratory function in chronic heart failure:effects of 12 months’ aerobic training. Heart 1996 Jul; 76 (1):42-9

103. Hamm LF, Kavanagh T, Campbell RB. Timeline for peakimprovements during 52 weeks of outpatient cardiac re-habilitation. J Cardiopulm Rehabil 2004 Nov-Dec; 24 (4):374-82

104. Ashutosh K, Methrotra K, Fragale-Jackson J. Effects ofsustained weight loss and exercise on aerobic fitness inobese women. J Sports Med Phys Fitness 1997 Dec; 37 (4):252-7

105. Donnelly JE, Jacobsen DJ, Jakicic JM, et al. Very lowcalorie diet with concurrent versus delayed and sequentialexercise. Int J Obes 1994 Jul; 18 (7): 469-75

106. Marks BL, Ward A, Morris DH, et al. Fat-free mass ismaintained in women following a moderate diet and ex-ercise program. Med Sci Sports Exerc 1995 Sep; 27 (9):1243-51

107. Stewart KJ, McFarland LD, Weinhofer JJ, et al. Safety andefficacy of weight training soon after acute myocardialinfarction. J Cardiopulm Rehabil 1998 Jan-Feb; 18 (1):37-44

108. Delagardelle C, Feiereisen P, Autier P, et al. Strength/endurance training versus endurance training in conges-tive heart failure. Med Sci Sports Exerc 2002 Dec; 34 (12):1868-72

109. Gayda M, Choquet D, Ahmaida S. Effects of exercisetraining modality on skeletal muscle fatigue in men withcoronary heart disease. J Electromyogr Kinesiol 2009 Apr;19 (2): e32-9

110. Marzolini S, Oh PI, Thomas SG, et al. Aerobic and resis-tance training in coronary disease: single versus multiplesets. Med Sci Sports Exerc 2008 Sep; 40 (9): 1557-64

111. Pierson LM, Herbert WG, Norton HJ, et al. Effects ofcombined aerobic and resistance training versus aerobictraining alone in cardiac rehabilitation. J CardiopulmRehabil 2001 Mar-Apr; 21 (2): 101-10

938 Hansen et al.


112. Daub WD, Knapik GP, Black WR. Strength training earlyafter myocardial infarction. J Cardiopulm Rehabil 1996Mar-Apr; 16 (2): 100-8

113. Santa-Clara H, Fernhall B, Mendes M, et al. Effect of a1 year combined aerobic- and weight-training exerciseprogramme on aerobic capacity and ventilatory thresholdin patients suffering from coronary artery disease. EurJ Appl Physiol 2002 Oct; 87 (6): 568-75

114. Arthur HM, Gunn E, Thorpe KE, et al. Effect of aerobic vscombined aerobic-strength training on 1-year, post-cardiacrehabilitation outcomes in women after a cardiac event.J Rehabil Med 2007 Nov; 39 (9): 730-5

115. Beckers PJ, Denollet J, Possemiers NM, et al. Combinedendurance-resistance training vs. endurance training inpatients with chronic heart failure: a prospective randomi-zed study. Eur Heart J 2008 Aug; 29 (15): 1858-66

116. Bryner RW, Ullrich IH, Sauers J, et al. Effects of resistancevs. aerobic training combined with an 800 calorie liquiddiet on lean body mass and resting metabolic rate. J AmColl Clin Nutr 1999 Apr; 18 (2): 115-21

117. Dunstan DW, Daly RM, Owen N, et al. High-intensity resis-tance training improves glycemic control in older patientswith type 2 diabetes. Diabetes Care 2002 Oct; 25 (10): 1729-36

118. Eriksson J, Taimela S, Eriksson K, et al. Resistance train-ing in the treatment of non-insulin-dependent diabetes.Int J Sports Med 1997 May; 18 (4): 242-6

119. Ballor DL, McCarthy JP, Wilterdink EJ. Exercise intensitydoes not affect the composition of diet- and exercise-inducedbody mass loss. Am J Clin Nutr 1990 Feb; 51 (2): 142-6

120. Leutholtz BC, Keyser RE, Heusner WW, et al. Exercisetraining and severe caloric restriction: effect on lean bodymass in the obese. Arch Phys Med Rehabil 1995 Jan; 76 (1):65-70

121. van Aggel-Leijssen D, Saris WHM, Wagenmakers AJM,et al. Effect of exercise training at different intensitieson fat metabolism of obese men. J Appl Physiol 2002 Mar;92 (3): 1300-9

122. Hansen D, Dendale P, Jonkers RA, et al. Continuous low-to-moderate intensity exercise is equally effective as moderate-to-high intensity exercise training at lowering bloodHbA1c content in obese type 2 diabetes patients. Diabe-tologia 2009 Sep; 52 (9): 1789-97

123. Blumenthal JA, Rejeski WJ, Walsh-Riddle M, et al. Com-parison of high- and low-intensity exercise training earlyafter acute myocardial infarction. Am J Cardiol 1988 Jan;61 (1): 26-30

124. Jensen BE, Fletcher BJ, Rupp JC, et al. Training level com-parison study: effect of high and low intensity training onventilatory threshold in men with coronary artery disease.J Cardiopulm Rehabil 1996 Jul-Aug; 16 (4): 227-32

125. Oberman A, Fletcher GF, Lee J, et al. Efficacy of high-intensity exercise training on left ventricular ejection frac-tion in men with coronary artery disease (the training levelcomparison study). Am J Cardiol 1995 Oct; 76 (10): 643-7

126. Friedlander AL, Jacobs KA, Fattor JA, et al. Contribu-tions of working muscle to whole body lipid metabolismare altered by exercise training and intensity. Am J Physiol2007 Oct; 292 (4): E107-12

127. Perri MG, Anton SD, Durning PE, et al. Adherence toexercise prescriptions: effects of prescribing moderate

versus higher levels of intensity and frequency. HealthPsychol 2002 Sep; 21 (5): 452-8

128. Kang J, Robertson RJ, Hagberg JM, et al. Effect of exer-cise intensity on glucose and insulin metabolism in obeseindividuals and obese NIDDM patients. Diabetes Care1996 Apr; 19 (4): 341-9

129. Kang J, Kelley DE, Robertson RJ, et al. Substrate utiliza-tion and glucose turnover during exercise of varying in-tensities in individuals with NIDDM. Med Sci SportsExerc 1999 Jan; 31 (1): 82-9

130. Garcia-Roves PM, Han DH, Song Z, et al. Prevention of gly-cogen supercompensation prolongs the increase in muscleGLUT4 after exercise. Am J Physiol 2003 Oct; 285 (4);E729-36

131. Swain DP, Franklin BA. Is there a threshold intensity foraerobic training in cardiac patients? Med Sci Sports Exerc2002 Jul; 34 (7): 1071-5

132. Schjerve IE, Tyldum GA, Tjønna AE, et al. Both aerobicendurance and strength training programmes improvecardiovascular health in obese adults. Clin Sci 2008 Nov;115 (9): 283-93

133. Warburton DE, McKenzie DC, Haykowski MJ, et al.Effectiveness of high-intensity interval training for therehabilitation of patients with coronary artery disease.Am J Cardiol 2005 May; 95 (9): 1080-4

134. Rognmo O, Hetland E, Helgerud J, et al. High intensityaerobic interval exercise is superior to moderate intensityexercise for increasing aerobic capacity in patients withcoronary artery disease. Eur J Cardiovasc Prev Rehabil2004 Jun; 11 (3): 216-22

135. Amundsen BH, Rognmo O, Hatlen-Rebhan G, et al. High-intensity aerobic exercise improves diastolic function incoronary artery disease. Scand Cardiovasc J 2008 Apr;42 (2): 110-7

136. Moholdt TT, Amundsen BH, Rustad LA, et al. Aerobicinterval training versus continuous moderate exerciseafter coronary artery bypass surgery: a randomized studyof cardiovascular effects and quality of life. Am Heart J2009 Dec; 158 (6): 1031-7

137. Gibala MJ, McGee SL. Metabolic adaptations to short-term high-intensity interval training: a little pain for a lotof gain? Exerc Sport Sci Rev 2008 Apr; 36 (2): 58-63

138. Wisloff U, Stoylen A, Loennechen JP, et al. Superior cardio-vascular effect of aerobic interval training versus moderatecontinuous training in heart failure patients: a random-ized study. Circulation 2007 Jun; 115 (24): 3086-94

139. Bond Brill J, Perry AC, Parker L, et al. Dose-response ef-fect of walking exercise on weight loss: how much is en-ough? Int J Obes 2002 Nov; 26 (11): 1484-93

140. Hansen D, Dendale P, Berger J, et al. Importance of train-ing session duration in the rehabilitation of coronary ar-tery disease patients. Eur J Cardiovasc Prev Rehabil 2008Aug; 15 (4): 453-9

141. Sriwijitkamol A, Coletta DK, Wajcberg E, et al. Effect ofacute exercise on AMPK signalling in skeletal muscle ofsubjects with type 2 diabetes. Diabetes 2007 Mar; 56 (3):836-48

142. Praet SF, Manders RJ, Lieverse AG, et al. Influence ofacute exercise on hyperglycaemia in insulin-treated type 2diabetes. Med Sci Sports Exerc 2006 Dec; 38 (12): 2037-44



143. Whatley JE, Gillespie WJ, Honig J, et al. Does the amount ofendurance exercise in combination with weight training and avery-low-energy diet affect resting metabolic rate and bodycomposition? Am J Clin Nutr 1994 May; 59 (5): 1088-92

144. Dressendorfer RH, Franklin BA, Cameron JL, et al. Exer-cise training frequency in early post-infarction cardiacrehabilitation: influence on aerobic conditioning. J Cardio-pulm Rehabil 1995 Jul-Aug; 15 (4): 269-76

145. Tygesen H, Wettervik C, Wennerblom B. Intensive home-based exercise training in cardiac rehabilitation increasesexercise capacity and heart rate variability. Int J Cardiol2001 Jul; 79 (2-3): 175-82

146. Nieuwland W, Berkhuysen MA, van Veldhuizen DJ, et al.Differential effects of high-frequency versus low-frequency

exercise training in rehabilitation of patients with coro-nary artery disease. J Am Coll Cardiol 2000 Jul; 36 (1):202-7

147. Henriksen EJ. Exercise effects of muscle insulin signal-ling and action: effects of acute exercise and exercise train-ing on insulin resistance. J Appl Physiol 2002 Aug; 93 (2):788-96

Correspondence: Prof. Dr Romain Meeusen, Vrije Uni-versiteit Brussel (VUB), Faculty LK, Department of HumanPhysiology and Sportsmedicine, Pleinlaan 2, 1050 Brussels,Belgium.E-mail: [email protected]

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