J Appl Physiol 103: 1113–1120, 2007.
First published July 26, 2007; doi:10.1152/japplphysiol.00566.2007.
Invited Review
Optimizing the therapeutic benefits of exercise in Type 2 diabetes
Stephan F. E. Praet and Luc J. C. van Loon
Department of Movement Sciences, Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University,
Maastricht, The Netherlands
Type 2 diabetes; exercise; energy expenditure; body composition; sarcopenia;
neuropathy
ESTIMATES OF GLOBAL DIABETES PREVALENCE and most recent
projections for the future indicate that diabetes now affects 246
million people worldwide and is expected to affect some 380
million by 2025, representing as much as 7.1% of the global
adult population (58). The increase in Type 2 diabetes prevalence can only partly be attributed to the changing population
demographics, since epidemiological data show diabetes prevalence to increase progressively in young and middle-aged
people (2). The latter implies that, in the near future, Type 2
diabetes-related complications, like nephropathy, retinopathy,
neuropathy, myocardial infarction, stroke, and even death, will
be experienced more frequently and at a much earlier age (94).
The greater incidence and prevalence of overt clinical complications in a vastly expanding diabetes population will impose
an enormous burden on our healthcare system and on the
quality of life of the Type 2 diabetes patient (2, 16). Much
effort is currently put into the discovery of novel pharmacological solutions that might improve metabolic control and
prevent diabetes-related comorbidities. Although intense blood
pressure and blood glucose-lowering therapy has been shown
to reduce (microvascular) complications in Type 2 diabetes
(120, 124), enhanced glycemic control with either sulphonylureas, glitazones, or exogenous insulin therapy does not necessarily prevent the number of cardiovascular events (87, 124).
Address for reprint requests and other correspondence: S. Praet, Dept. of
Movement Sciences, Maastricht Univ., PO Box 616, 6200 MD Maastricht, The
Netherlands (e-mail: [email protected]).
http://www. jap.org
Apparently, further reductions in glycosylated hemoglobin
(HbA1c) levels and blood pressure are needed to improve
long-term cardiovascular outcome. The Steno-2 study provides
good evidence that this can only be achieved through multifactorial intervention, consisting of both well-structured lifestyle and pharmaceutical measures (46). Also, in populations at
risk for developing Type 2 diabetes, it is now well established
that increased physical activity levels and long-term weight
loss reduce the prevalence of metabolic syndrome (49, 63, 90)
and prevent or delay the progression toward Type 2 diabetes
(67, 73, 91). In accordance, lifestyle intervention programs
consisting of regular exercise with (35, 73) or without (35, 122,
128) dietary modulation and/or oral blood glucose-lowering
medication (11, 65) have proven an effective therapeutic strategy in Type 2 diabetes. As such, the current increase in Type
2 diabetes incidence and concomitant cardiovascular comorbidities can only be reversed by dramatic lifestyle changes.
Current guidelines from the American Diabetes Association
(ADA), the European Association for the Study of Diabetes
(EASD), or the American College of Physicians (ACP) all
firmly recognize the therapeutic strength of exercise intervention (5, 84, 114). The ADA states that “to improve glycemic
control, assist with weight maintenance, and reduce risk of
cardiovascular disease, at least 150 min/week of moderateintensity aerobic physical activity is recommended and/or at
least 90 min/week of vigorous aerobic exercise . . . distributed
over at least 3 days/week and with no more than 2 consecutive
days without physical activity” (5). Since 2006, the ADA
8750-7587/07 $8.00 Copyright © 2007 the American Physiological Society
1113
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
Praet SF, van Loon LJ. Optimizing the therapeutic benefits of exercise in Type
2 diabetes. J Appl Physiol 103: 1113–1120, 2007. First published July 26, 2007;
doi:10.1152/japplphysiol.00566.2007.—Other than diet and medication, exercise is
considered one of the three cornerstones of good diabetes treatment. Nevertheless,
current clinical guidelines on Type 2 diabetes provide no detailed information on
the modalities of effective exercise intervention in the treatment of Type 2 diabetes.
Based on a review of currently available literature, exercise modalities are being
identified to maximize the benefits of exercise intervention in the treatment of
different Type 2 diabetes subpopulations. Both endurance and resistance types of
exercise have equal therapeutic strength to improve metabolic control in patients
with Type 2 diabetes. When applying endurance-type exercise, energy expenditure
should be equivalent to ⬃1.7–2.1 MJ/exercise bout on 3 but preferably 5 days/wk.
In sarcopenic or severely deconditioned patients with Type 2 diabetes, focus should
lie on the implementation of resistance-type exercise to attenuate and/or reverse the
decline in skeletal muscle mass and strength. Before choosing the most appropriate
exercise modalities, the patient’s disease stage should be well characterized, and an
ECG-stress test should be considered. Based on baseline aerobic fitness, level of
co-morbidities, body composition, and muscle strength, patients should be provided
with an individually tailored exercise intervention program to optimize therapeutic
value. A multidisciplinary individualized approach and continued exercise training
under personal supervision is essential to enhance compliance and allow long-term
health benefits of an exercise intervention program.
Invited Review
1114
EXERCISE AND TYPE 2 DIABETES
guidelines explicitly mention and recognize that “in the absence of contraindications, people with type 2 diabetes should
be encouraged to perform resistance exercise 3 times a week,
targeting all major muscle groups, progressing to 3 sets of
8 –10 repetitions at a weight that cannot be lifted more than
8 –10 times” (114). However, these clinical guidelines generally do not include detailed information on the preferred type
and intensity of exercise that should be applied to maximize the
benefits of exercise for different subgroups of patients with
Type 2 diabetes.
More than 20 years ago, it was already reported that there
is an urgent need to define the characteristics of appropriate
exercise prescription in chronic metabolic disease (106). The
present review aims to identify the exercise modalities that
define an effective interventional strategy in the treatment of
different Type 2 diabetes subpopulations.
RESISTANCE- VS. ENDURANCE-TYPE EXERCISE
J Appl Physiol • VOL
INTENSITY VS. DURATION OF EXERCISE
Clinical practice guidelines on the application of exercise
intervention in Type 2 diabetes do not provide much detail
regarding the duration and/or intensity of exercise that should
be applied to maximize subsequent health benefits for different
subpopulations (5, 57). As exercise intensity is increased,
muscle glycogen becomes a more important substrate source
(61). The depletion of muscle glycogen stores and subsequent
postexercise muscle glycogen resynthesis is coupled to the
postexercise improvement in glucose tolerance and/or insulin
sensitivity (48, 126). Therefore, when considering the more
acute glucoregulatory effects of exercise, higher exercise intensities should theoretically be more effective to stimulate
insulin sensitivity and improve glucose homeostasis. However,
data from a limited number of studies (32, 66, 71, 72, 127) are
inconclusive, and several factors, such as release of counterregulatory hormones (66), training status (64), and exercise
performed either in the postabsorptive (66) or postprandial
state (72), may explain these contradictory findings. Nevertheless, the energy equivalent of the exercise bout appears to
represent the major determinant of the exercise-induced
changes in glucose homeostasis (71, 72). Therefore, a lesser
exercise intensity should be compensated for by an increase in
exercise duration.
Although less evident for resistance-type exercise, energy
expenditure for endurance type exercise can be estimated by
using metabolic equivalent tables (1). Endurance-type exercise
programs should entail at least 3 exercise sessions/wk in which
the energy equivalent of each exercise bout should represent
⬃1.7 MJ (⬇400 kcal), or rather 4 –5 sessions/wk with an
energy equivalent of ⬃2.1 MJ (⬇500 kcal) per exercise bout
(52, 56, 88). In the average overweight/obese patient with
uncomplicated Type 2 diabetes, this minimum of 5 MJ/wk
(⬇1,200 kcal) would be equivalent to a minimum of 170 –200
min or ⬃19 km of brisk walking per week (20, 59, 115).
When applying resistance-type exercise, strength improvements tend to follow a linear dose-response relationship, at
least in healthy subjects (47, 98). If the therapeutic aim of
resistance-type exercise is to stimulate muscle glycogen storage depletion and net muscle mass gain, both exercise intensity
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
Both a single bout of endurance- (31) as well as resistancetype exercise (43, 101) have been shown to improve whole
body insulin sensitivity and/or oral glucose tolerance. Therefore, both types of exercise are of therapeutic use in an
insulin-resistant state (116). The acute effects of exercise on
skeletal muscle insulin sensitivity are attributed to the prolonged activation of the skeletal muscle glucose transporter
system (48), depletion of muscle and liver glycogen stores (96,
103), and/or increased skeletal muscle blood flow following
the cessation of exercise (13). The glucoregulatory benefits of
either type of exercise training is represented by the sum of the
effects of each successive bout of exercise. In addition, more
prolonged exercise training is accompanied by a more structural adaptive response. Apparent differences exist in the
long-term adaptive response to endurance- or resistance-type
exercise training. Prolonged endurance-type exercise training
has been shown to improve insulin sensitivity in both young
(28), elderly (60), and/or insulin-resistant subjects (27, 29, 97,
107). The latter is attributed to the concomitant induction of
weight loss, the upregulation of skeletal muscle GLUT4 expression, improved nitric oxide-mediated skeletal muscle
blood flow (76), reduced hormonal stimulation of hepatic
glucose production (112), and the normalization of blood lipid
profiles (17). Long-term resistance-type exercise interventions
have also been reported to improve glucose tolerance and/or
whole body insulin sensitivity (33, 43, 54). Other than the
consecutive effects of each successive bout of exercise, resistance-type exercise training has been associated with a substantial gain in skeletal muscle mass, thereby improving whole
body glucose-disposal capacity (43). Besides the attenuation of
the loss of muscle mass with aging, resistance-type exercise
training also improves muscle strength and functional capacity,
thereby allowing a healthier, more active lifestyle. Some studies report even greater benefits of resistance- as opposed to
endurance-type exercise training on glycemic control and insulin sensitivity in long-standing patients with Type 2 diabetes
(19). As such, it has been firmly established that both endurance- and resistance-type exercise training can be applied to
improve metabolic control and quality of life in patients with
Type 2 diabetes (116).
In most lifestyle intervention programs, the focus generally
lies on the implementation of endurance-type exercise activity.
The latter can be explained by the fact that endurance-type
exercise has been known for its efficacy to reduce body fat
mass and its subsequent effects on whole body insulin sensitivity. Since many patients with Type 2 diabetes suffer from
muscle weakness (6, 108, 129), cardiovascular comorbidities
(117, 130), and reduced exercise tolerance (42), it has been
proven difficult to engage patients with Type 2 diabetes into
adhering to strict endurance-type exercise intervention programs (34, 111). Alternatively, endurance-type exercise combined with resistance (i.e., intermittent intensity-type exercise)
forms a lower cardiovascular challenge (81) and improves
functional performance capacity to a similar extent (79).
Therefore, the combination of endurance- and resistance-type
exercise is preferred since it augments the diversity and, as
such, the adherence to the exercise intervention program. To
maximize the benefits of exercise intervention, the emphasis to
apply either more endurance- or more resistance-type exercise
should be tailored to the level of comorbidity present in a
specific diabetes subpopulation (see below).
Invited Review
EXERCISE AND TYPE 2 DIABETES
FREQUENCY AND TIMING OF EXERCISE
The enhanced insulin sensitivity following an acute bout of
exercise has been reported to persist for a period ranging from
2 (83), 4 – 6 (132), 12–16 (31, 89), 24 (24, 110), and to up to
48 h following the cessation of exercise (83). As such, the
benefits of exercise on glycemic control can largely be attributed to the cumulative effects of each successive bout of
endurance- or resistance-type exercise rather than the structural
adaptive response to prolonged exercise training (110). In fact,
long-term training effects on glycemic control may be lost
entirely 6 –14 days after cessation of training (27, 53). Therefore, it is preferred to perform exercise everyday. The ACP
guidelines prescribe an exercise frequency of at least three
times per week with no more than 2 consecutive days without
physical activity (4). Indeed, the ADA (5) now recognizes that
these guidelines need to be considered a minimal therapeutic
dosis and, therefore, a less than optimal therapy.
Furthermore, current guidelines on exercise prescription as
therapeutic strategy (3, 5) do not consider an optimal timing of
a daily exercise routine. In this respect, it is interesting to note
that, in patients with Type 2 diabetes, hyperglycemic episodes
during the day are most predominant in the morning in the
postprandial state (51, 102). This so-called “dawn-phenomenon” (15) seems to be related to the diurnal variation in
endogenous glucose production (104). Since moderate-intensity exercise suppresses endogenous glucose production, it
might be advantageous to schedule moderate-intensity endurance exercise sessions in the morning, preferably in the postprandial state. More research is warranted to assess the impact
of timing of exercise and nutrition on daily hyperglycemia in
patients with Type 2 diabetes (71, 101).
STAGE OF DISEASE AND COMORBIDITY
The prolonged application of either endurance or a combination of resistance- and endurance-type exercise training has
J Appl Physiol • VOL
been shown to increase whole body glucose tolerance and/or
insulin sensitivity (56) and can prevent the development of
Type 2 diabetes (67, 123). The implementation of resistanceand endurance-type exercise improves glycemic control (11,
74, 75, 121), blood pressure (11, 74), body composition (11,
23, 74), and blood lipid profile (11, 75). Furthermore, exercise
training has been reported to modify the progression of peripheral neuropathy (10) and attenuates the progressive increase in
blood glucose-lowering medication requirements (11). However, when implementing endurance- and resistance-type exercise intervention in the treatment of Type 2 diabetes, we also
need to consider the stage of the disease, body composition,
and the presence of comorbidities. In recently diagnosed, obese
patients with Type 2 diabetes, the main therapeutic target of
lifestyle intervention should be a durable reduction in fat mass
and a concomitant improvement in aerobic fitness and whole
body insulin sensitivity (5), a conclusion well in line with
exercise recommendations for normoglycemic obese subjects
(50). As such, obese patients with Type 2 diabetes would
benefit most from a program mainly consisting of moderateintensity endurance exercise, aiming for an energy expenditure
of at least 5 MJ (⬇1,200 kcal) (56, 88) but preferably ⬎8.4 MJ
(⬇2,000 kcal) per week (52). In these patients, endurance-type
exercise should be combined with dietary restriction (14, 62,
133). To prevent the loss of lean body mass due to the energy
intake restriction, at least one resistance exercise session
should be included per week (25).
Another expanding Type 2 diabetes subpopulation is formed
by the long-standing, insulin-treated patients with Type 2
diabetes (30). These patients generally suffer from severe
exercise intolerance due to low oxidative capacity (42), neuropathy-related muscle weakness (6, 100, 108, 129), sarcopenia
(18), and/or micro- and macrovascular disease (37, 100). Since
generic exercise intervention programs are too demanding for
most of these patients, it is of utmost importance to implement
intermediate exercise intervention programs. Such intermediate programs are needed to bring patients to a level at which
they are able to participate in more generic diabetes intervention programs. Such intermediate programs should implement
short, relatively high-intensity exercise bouts applied in an
intermittent fashion with the intention to increase muscle
strength and functional performance. These so-called short
“in-and-out” exercises do not produce feelings of dyspnea or
discomfort and have been proven safe and effective in cardiac
(79, 80) and insulin-treated patients with Type 2 diabetes (101)
with a high-cardiovascular risk profile. The efficacy of such
intermediate programs remains to be established, since exercise intervention studies have generally excluded long-standing, insulin-treated patients with Type 2 diabetes.
Another vastly expanding diabetes subgroup is formed by
the elderly (⬎70 yr) patients with Type 2 diabetes. Aging is
associated with the loss of skeletal muscle mass and represents
one of the main factors responsible for the increase in Type 2
diabetes incidence at an advancing age (95). The loss of muscle
mass is proportionally related to the reduction in blood glucose
disposal capacity and the decline in muscle strength (92). The
latter prevents many elderly diabetes patients from participating in lifestyle intervention programs. Although even lowimpact endurance-type exercise has been reported to improve
glycemic control in elderly patients with Type 2 diabetes (70,
121), it has been suggested that the insulin-sensitizing response
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
and volume should be kept high (21, 68). However, studies
assessing the impact of exercise intensity in resistance-type
exercise interventions in patients with Type 2 diabetes
remain lacking. It has been established that progressively
intensified moderate- to high-impact resistance training over
a period of 6 wk (3 ⫻ 30 min exercise/wk) upregulates the
activity of key proteins in the insulin-signaling cascade,
resulting in enhanced insulin-stimulated blood glucose disposal in muscle (54). In accordance, resistance-type exercise
training has been shown to reduce blood HbA1c levels with
0.4 – 0.8% in patients with Type 2 diabetes (116). Until more
information becomes available, it is advised to implement
resistance-type exercise training with exercise volume and
intensity being progressively increased toward three sets of
8 –10 repetitions performed at 70 – 80% of 1 repetition
maximum per muscle group (114).
Many patients with Type 2 diabetes experience some musculoskeletal (6, 100, 108, 129) and/or cardiorespiratory deconditioning (42). Therefore, exercise intensity, duration,
and volume should be gradually increased over a period of
6 –12 wk. In addition, endurance- and resistance-type exercise of the same muscle group on the same day should be
avoided to reduce the risk of overuse injuries and subsequent dropout.
1115
Invited Review
1116
EXERCISE AND TYPE 2 DIABETES
to exercise is attenuated with an advancing age (82, 113). Since
Type 2 diabetes patients show an accelerated decline in muscle
mass and strength with aging (93), it would be preferable to
focus more on increasing skeletal muscle mass and strength
when designing exercise intervention programs for the elderly
patients with Type 2 diabetes (26, 131). Effective exercise
intervention programs for the elderly patient with Type 2
diabetes should include resistance-type exercise, with exercise
volume and intensity being progressively increased toward
three sets of 8 –10 repetitions with intensities ranging from 50
to 80% 1 repetition maximum for 7–10 exercises and/or muscle
groups (9, 33, 43, 55). Dietary cointerventions might further
improve the benefits of resistance-type exercise training in
elderly patients (38, 69).
Furthermore, when prescribing exercise intervention in patients with Type 2 diabetes, it should be noted that long-term
adherence to an exercise intervention program may vary
with the presence of comorbidities, the level of deconditioning,
and/or orthopedic limitations (7, 92). Therefore, a multidisciplinary team should consider the level of impaired exercise tolerance and individualize the exercise intervention
program to prevent dropout and empower the patient to
adhere to such lifestyle changes (34, 73, 111).
J Appl Physiol • VOL
SAFETY ASPECTS
Before exposing patients with Type 2 diabetes to more
vigorous exercise programs, the ADA and US Preventive
Services Task Force recommend exercise testing for silent
myocardial ischemia (SMI) if 10 years’ cardiovascular risk
exceeds 10% (45, 114). Cardiac dysfunction (41) and SMI are
estimated to be present between 6 and 22% (130) of the
patients with Type 2 diabetes, with cardiac autonomic dysfunction, disease duration, and male gender being the best predictors for SMI (130). Moreover, poor physical fitness (78),
scintigraphy abnormalities (39), diabetic retinopathy (39), and
an advancing age ⬎60 yr (125) in combination with the
traditional cardiac risk factors also represent good predictors
for the likelihood of a cardiac event. The UKPDS Risk Engine
version 2.0 (available free of charge at http://www.dtu.ox.
ac.uk/) can be of help to calculate an individual patient’s risk
for coronary heart disease (118). Although arbitrary, the
UKPDS Risk Engine indicates that ECG stress testing in Type
2 diabetes is useful in most patients with ⬎2 cardiovascular
risk factors, in middle-aged patients with a diabetes duration
⬎5 yr, as well in elderly patients ⬎70 yr of age. Although a
stress ECG is not the most sensitive diagnostic tool to detect
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
Fig. 1. Clinical approach and proposed exercise program for different Type 2 diabetes subpopulations. Before exercise, intervention exercise testing, including
a stress ECG, is recommended. If oxygen consumption is not measured during the exercise test, maximum oxygen uptake (V̇O2max) may be estimated, using the
equations by Storer et al. (77, 119) for cycle ergometry or Foster et al. (44, 99) for treadmill testing. Reference values for predicted (pred) V̇O2max in a healthy
nondiabetic population are based on age, sex, body weight (in kg), and height (in cm) according to Fairbarn et al. (40). CVR, cardiovascular risk; BMI, body
mass index; T2DM, Type 2 diabetes; Wmax, maximum power output during cycle ergometry testing; 1-RM, 1 repetition maximum based on repetitive strength
testing (105); n, number of sets; reps, repetitions; END, endurance training; RES, resistance training aiming at 7–10 different muscle groups; INT, interval
training.
Invited Review
EXERCISE AND TYPE 2 DIABETES
SMI (86) and predict coronary events (85), it is still the most
cost effective when trying to minimize the risk of a coronary
event (22). In case SMI is expected, more sensitive diagnostic
tests such as myocardial perfusion scintigraphy (12), electron
beam computerized tomography (109), and/or coronary angiography (8) should be considered before more vigorous
exercise is prescribed. Even in the absence of SMI, a stress test
will detect chronotropic incompetence (36) as well as exerciserelated hypertension and provide more objective information
on the individual fitness level (42). This information should be
used to further tailor an exercise program for the individual
(Fig. 1).
CONCLUSION AND RECOMMENDATIONS
GRANTS
The authors’ salaries are funded by a research grant from the Dutch
Ministry of Health, Welfare & Sport (S. F. E. Praet) and Maastricht University
(L. J. C. van Loon). The funding agencies have played no role in the
submission and/or preparation of this manuscript.
REFERENCES
1. Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM,
Strath SJ, O’Brien WL, Bassett DR Jr, Schmitz KH, Emplaincourt
PO, Jacobs DR Jr, Leon AS. Compendium of physical activities: an
update of activity codes and MET intensities. Med Sci Sports Exerc 32:
498 –504, 2000.
J Appl Physiol • VOL
2. Alberti G, Zimmet P, Shaw J, Bloomgarden Z, Kaufman F, Silink M.
Type 2 diabetes in the young: the evolving epidemic: the international
diabetes federation consensus workshop. Diabetes Care 27: 1798 –1811,
2004.
3. Albright A, Franz M, Hornsby G, Kriska A, Marrero D, Ullrich I,
Verity LS. American College of Sports Medicine position stand. Exercise and type 2 diabetes. Med Sci Sports Exerc 32: 1345–1360, 2000.
4. American College of Physicians. Type 2 diabetes. Ann Intern Med 146:
1–16, 2007.
5. American Diabetes Association. Standards of medical care in diabetes2007. Diabetes Care 30, Suppl 1: S4 –S41, 2007.
6. Andersen H, Nielsen S, Mogensen CE, Jakobsen J. Muscle strength in
type 2 diabetes. Diabetes 53: 1543–1548, 2004.
7. Ardic F, Soyupek F, Kahraman Y, Yorgancioglu R. The musculoskeletal complications seen in type II diabetics: predominance of hand
involvement. Clin Rheumatol 22: 229 –233, 2003.
8. Bacci S, Villella M, Villella A, Langialonga T, Grilli M, Rauseo A,
Mastroianno S, De Cosmo S, Fanelli R, Trischitta V. Screening for
silent myocardial ischaemia in type 2 diabetic patients with additional
atherogenic risk factors: applicability and accuracy of the exercise stress
test. Eur J Endocrinol 147: 649 – 654, 2002.
9. Baldi JC, Snowling N. Resistance training improves glycaemic control
in obese type 2 diabetic men. Int J Sports Med 24: 419 – 423, 2003.
10. Balducci S, Iacobellis G, Parisi L, Di Biase N, Calandriello E,
Leonetti F, Fallucca F. Exercise training can modify the natural history
of diabetic peripheral neuropathy. J Diabetes Complications 20: 216 –
223, 2006.
11. Balducci S, Leonetti F, Di Mario U, Fallucca F. Is a long-term aerobic
plus resistance training program feasible for and effective on metabolic
profiles in type 2 diabetic patients? Diabetes Care 27: 841– 842, 2004.
12. Bax JJ, Bonow RO, Tschope D, Inzucchi SE, Barrett E. The potential
of myocardial perfusion scintigraphy for risk stratification of asymptomatic patients with type 2 diabetes. J Am Coll Cardiol 48: 754 –760, 2006.
13. Bisquolo VA, Cardoso CG Jr, Ortega KC, Gusmao JL, Tinucci T,
Negrao CE, Wajchenberg BL, Mion D Jr, Forjaz CL. Previous
exercise attenuates muscle sympathetic activity and increases blood flow
during acute euglycemic hyperinsulinemia. J Appl Physiol 98: 866 – 871,
2005.
14. Bogardus C, Ravussin E, Robbins DC, Wolfe RR, Horton ES, Sims
EA. Effects of physical training and diet therapy on carbohydrate
metabolism in patients with glucose intolerance and non-insulin-dependent diabetes mellitus. Diabetes 33: 311–318, 1984.
15. Bolli GB, Gerich JE. The “dawn phenomenon”: a common occurrence
in both non-insulin-dependent and insulin-dependent diabetes mellitus.
N Engl J Med 310: 746 –750, 1984.
16. Booth FW, Chakravarthy MV, Gordon SE, Spangenburg EE. Waging war on physical inactivity: using modern molecular ammunition
against an ancient enemy. J Appl Physiol 93: 3–30, 2002.
17. Bruce CR, Hawley JA. Improvements in insulin resistance with aerobic
exercise training: a lipocentric approach. Med Sci Sports Exerc 36:
1196 –1201, 2004.
18. Castaneda C, Janssen I. Ethnic comparisons of sarcopenia and obesity
in diabetes. Ethn Dis 15: 664 – 670, 2005.
19. Cauza E, Hanusch-Enserer U, Strasser B, Kostner K, Dunky A,
Haber P. Strength and endurance training lead to different post exercise
glucose profiles in diabetic participants using a continuous subcutaneous
glucose monitoring system. Eur J Clin Invest 35: 745–751, 2005.
20. Chambliss HO. Exercise duration and intensity in a weight-loss program. Clin J Sport Med 15: 113–115, 2005.
21. Chapman J, Garvin AW, Ward A, Cartee GD. Unaltered insulin
sensitivity after resistance exercise bout by postmenopausal women. Med
Sci Sports Exerc 34: 936 –941, 2002.
22. Cosson E, Paycha F, Paries J, Cattan S, Ramadan A, Meddah D,
Attali JR, Valensi P. Detecting silent coronary stenoses and stratifying
cardiac risk in patients with diabetes: ECG stress test or exercise
myocardial scintigraphy? Diabet Med 21: 342–348, 2004.
23. Cuff DJ, Meneilly GS, Martin A, Ignaszewski A, Tildesley HD,
Frohlich JJ. Effective exercise modality to reduce insulin resistance in
women with type 2 diabetes. Diabetes Care 26: 2977–2982, 2003.
24. Cusi K, Maezono K, Osman A, Pendergrass M, Patti ME, Pratipanawatr T, DeFronzo RA, Kahn CR, Mandarino LJ. Insulin resistance
differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest 105: 311–320, 2000.
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
In the present review, we have identified the modalities of
effective exercise intervention in the treatment of Type 2
diabetes. Before choosing the most appropriate exercise modalities, the patient’s disease stage should be well characterized, and an ECG-stress test should be considered. Based on
baseline aerobic fitness, level of comorbidities, appendicular
skeletal muscle mass, and strength, patients should be provided
with a fitting exercise intervention program to optimize its
therapeutic value. Recently diagnosed obese patients with
Type 2 diabetes will benefit most from daily, intense moderateintensity endurance training in combination with energy intake
restriction. The latter should be combined with at least one
resistance-type exercise session per week to prevent the loss of
fat-free mass. Long-standing, insulin-treated patients with
Type 2 diabetes, in whom comorbidities generally prevail,
should be prescribed with an exercise program containing
intermittent, relatively high-intensity resistance- and endurance-type exercise. After substantial improvement in muscle
strength and functional performance, more generic exercise
intervention programs (with more intense endurance-type exercise training) should be considered. In an expanding population of elderly onset patients with Type 2 diabetes, focus
should lie on the implementation of resistance-type exercise to
attenuate and/or reverse the decline in skeletal muscle mass
and strength. When applying endurance-type exercise, energy
expenditure should be equivalent to ⬃1.7–2.1 MJ (⬇400 –500
kcal) per exercise bout on 3 but preferably 4 –5 days/wk, since
many of the benefits of exercise are temporarily. More vigorous exercise in uncomplicated insulin-resistant states will further improve glycemic control and enhance cardiorespiratory
fitness and microvascular function. Most patients with Type 2
diabetes find it difficult to adhere to structural exercise intervention programs. Compliance to an exercise intervention
program can be enhanced by a multidisciplinary approach and
continued exercise training under strict personal supervision.
1117
Invited Review
1118
EXERCISE AND TYPE 2 DIABETES
J Appl Physiol • VOL
46. Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH, Pedersen O.
Multifactorial intervention and cardiovascular disease in patients with
type 2 diabetes. N Engl J Med 348: 383–393, 2003.
47. Galvao DA, Taaffe DR. Resistance exercise dosage in older adults:
single- versus multiset effects on physical performance and body composition. J Am Geriatr Soc 53: 2090 –2097, 2005.
48. Garcia-Roves PM, Han DH, Song Z, Jones TE, Hucker KA, Holloszy
JO. Prevention of glycogen supercompensation prolongs the increase in
muscle GLUT4 after exercise. Am J Physiol Endocrinol Metab 285:
E729 –E736, 2003.
49. Hamalainen H, Ronnemaa T, Virtanen A, Lindstrom J, Eriksson JG,
Valle TT, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Rastas M,
Aunola S, Uusitupa M, Tuomilehto J. Improved fibrinolysis by an
intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study. Diabetologia 48: 2248 –
2253, 2005.
50. Hansen D, Dendale P, Berger J, van Loon LJ, Meeusen R. The effects
of exercise training on fat-mass loss in obese patients during energy
intake restriction. Sports Med 37: 31– 46, 2007.
51. Hay LC, Wilmshurst EG, Fulcher G. Unrecognized hypo- and hyperglycemia in well-controlled patients with type 2 diabetes mellitus: the
results of continuous glucose monitoring. Diabetes Technol Ther 5:
19 –26, 2003.
52. Helmrich SP, Ragland DR, Leung RW, Paffenbarger RS Jr. Physical
activity and reduced occurrence of non-insulin-dependent diabetes mellitus. N Engl J Med 325: 147–152, 1991.
53. Hittel DS, Kraus WE, Tanner CJ, Houmard JA, Hoffman EP.
Exercise training increases electron and substrate shuttling proteins in
muscle of overweight men and women with the metabolic syndrome.
J Appl Physiol 98: 168 –179, 2005.
54. Holten MK, Zacho M, Gaster M, Juel C, Wojtaszewski JF, Dela F.
Strength training increases insulin-mediated glucose uptake, GLUT4
content, and insulin signaling in skeletal muscle in patients with type 2
diabetes. Diabetes 53: 294 –305, 2004.
55. Honkola A, Forsen T, Eriksson J. Resistance training improves the
metabolic profile in individuals with type 2 diabetes. Acta Diabetol 34:
245–248, 1997.
56. Houmard JA, Tanner CJ, Slentz CA, Duscha BD, McCartney JS,
Kraus WE. Effect of the volume and intensity of exercise training on
insulin sensitivity. J Appl Physiol 96: 101–106, 2004.
57. Hu FB, Sigal RJ, Rich-Edwards JW, Colditz GA, Solomon CG,
Willett WC, Speizer FE, Manson JE. Walking compared with vigorous
physical activity and risk of type 2 diabetes in women: a prospective
study. JAMA 282: 1433–1439, 1999.
58. International Diabetes Foundation. Diabetes: A Global Threat. Brussels, Belgium: International Diabetes Foundation, 2006, p. 1–15.
59. Jakicic JM, Marcus BH, Gallagher KI, Napolitano M, Lang W.
Effect of exercise duration and intensity on weight loss in overweight,
sedentary women: a randomized trial. JAMA 290: 1323–1330, 2003.
60. Kahn SE, Larson VG, Beard JC, Cain KC, Fellingham GW,
Schwartz RS, Veith RC, Stratton JR, Cerqueira MD, Abrass IB.
Effect of exercise on insulin action, glucose tolerance, and insulin
secretion in aging. Am J Physiol Endocrinol Metab 258: E937–E943,
1990.
61. Kang J, Robertson RJ, Hagberg JM, Kelley DE, Goss FL, DaSilva
SG, Suminski RR, Utter AC. Effect of exercise intensity on glucose and
insulin metabolism in obese individuals and obese NIDDM patients.
Diabetes Care 19: 341–349, 1996.
62. Kaplan RM, Hartwell SL, Wilson DK, Wallace JP. Effects of diet and
exercise interventions on control and quality of life in non-insulindependent diabetes mellitus. J Gen Intern Med 2: 220 –228, 1987.
63. Katzmarzyk PT, Leon AS, Wilmore JH, Skinner JS, Rao DC,
Rankinen T, Bouchard C. Targeting the metabolic syndrome with
exercise: evidence from the HERITAGE Family Study. Med Sci Sports
Exerc 35: 1703–1709, 2003.
64. Keizer HA, Kuipers H, de Haan J, Beckers E, Habets L. Multiple
hormonal responses to physical exercise in eumenorrheic trained and
untrained women. Int J Sports Med 8, Suppl 3: 139 –150, 1987.
65. Kishimoto H, Taniguchi A, Fukushima M, Sakai M, Tokuyama K,
Oguma T, Nin K, Nagata I, Hayashi R, Kawano M, Hayashi K,
Tsukamoto Y, Okumura T, Nagasaka S, Mizutani H, Nakai Y. Effect
of short-term low-intensity exercise on insulin sensitivity, insulin secretion, and glucose and lipid metabolism in non-obese Japanese type 2
diabetic patients. Horm Metab Res 34: 27–31, 2002.
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
25. Daly RM, Dunstan DW, Owen N, Jolley D, Shaw JE, Zimmet PZ.
Does high-intensity resistance training maintain bone mass during moderate weight loss in older overweight adults with type 2 diabetes?
Osteoporos Int 16: 1703–1712, 2005.
26. Dela F, Kjaer M. Resistance training, insulin sensitivity and muscle
function in the elderly. Essays Biochem 42: 75– 88, 2006.
27. Dela F, Larsen JJ, Mikines KJ, Ploug T, Petersen LN, Galbo H.
Insulin-stimulated muscle glucose clearance in patients with NIDDM.
Effects of one-legged physical training. Diabetes 44: 1010 –1020, 1995.
28. Dela F, Mikines KJ, von Linstow M, Secher NH, Galbo H. Effect of
training on insulin-mediated glucose uptake in human muscle. Am J
Physiol Endocrinol Metab 263: E1134 –E1143, 1992.
29. Dela F, Ploug T, Handberg A, Petersen LN, Larsen JJ, Mikines KJ,
Galbo H. Physical training increases muscle GLUT4 protein and mRNA
in patients with NIDDM. Diabetes 43: 862– 865, 1994.
30. Detournay B, Raccah D, Cadilhac M, Eschwege E. Epidemiology and
costs of diabetes treated with insulin in France. Diabetes Metab 31: 3–18,
2005.
31. Devlin JT, Hirshman M, Horton ED, Horton ES. Enhanced peripheral
and splanchnic insulin sensitivity in NIDDM men after single bout of
exercise. Diabetes 36: 434 – 439, 1987.
32. DiPietro L, Dziura J, Yeckel CW, Neufer PD. Exercise and improved
insulin sensitivity in older women: evidence of the enduring benefits of
higher intensity training. J Appl Physiol 100: 142–149, 2006.
33. Dunstan DW, Daly RM, Owen N, Jolley D, De Courten M, Shaw J,
Zimmet P. High-intensity resistance training improves glycemic control
in older patients with type 2 diabetes. Diabetes Care 25: 1729 –1736,
2002.
34. Dunstan DW, Daly RM, Owen N, Jolley D, Vulikh E, Shaw J,
Zimmet P. Home-based resistance training is not sufficient to maintain
improved glycemic control following supervised training in older individuals with type 2 diabetes. Diabetes Care 28: 3–9, 2005.
35. Dunstan DW, Mori TA, Puddey IB, Beilin LJ, Burke V, Morton AR,
Stanton KG. The independent and combined effects of aerobic exercise
and dietary fish intake on serum lipids and glycemic control in NIDDM.
A randomized controlled study. Diabetes Care 20: 913–921, 1997.
36. Elhendy A, Mahoney DW, Khandheria BK, Burger K, Pellikka PA.
Prognostic significance of impairment of heart rate response to exercise:
impact of left ventricular function and myocardial ischemia. J Am Coll
Cardiol 42: 823– 830, 2003.
37. Estacio RO, Regensteiner JG, Wolfel EE, Jeffers B, Dickenson M,
Schrier RW. The association between diabetic complications and exercise capacity in NIDDM patients. Diabetes Care 21: 291–295, 1998.
38. Evans WJ. Protein nutrition, exercise and aging. J Am Coll Nutr 23:
601– 609, 2004.
39. Faglia E, Favales F, Calia P, Paleari F, Segalini G, Gamba PL, Rocca
A, Musacchio N, Mastropasqua A, Testori G, Rampini P, Moratti F,
Braga A, Morabito A. Cardiac events in 735 type 2 diabetic patients
who underwent screening for unknown asymptomatic coronary heart
disease: 5-year follow-up report from the Milan Study on Atherosclerosis
and Diabetes (MiSAD). Diabetes Care 25: 2032–2036, 2002.
40. Fairbarn MS, Blackie SP, McElvaney NG, Wiggs BR, Pare PD,
Pardy RL. Prediction of heart rate and oxygen uptake during incremental and maximal exercise in healthy adults. Chest 105: 1365–1369, 1994.
41. Fang ZY, Schull-Meade R, Leano R, Mottram PM, Prins JB, Marwick TH. Screening for heart disease in diabetic subjects. Am Heart J
149: 349 –354, 2005.
42. Fang ZY, Sharman J, Prins JB, Marwick TH. Determinants of
exercise capacity in patients with type 2 diabetes. Diabetes Care 28:
1643–1648, 2005.
43. Fenicchia LM, Kanaley JA, Azevedo JL Jr, Miller CS, Weinstock
RS, Carhart RL, Ploutz-Snyder LL. Influence of resistance exercise
training on glucose control in women with type 2 diabetes. Metabolism
53: 284 –289, 2004.
44. Foster C, Crowe AJ, Daines E, Dumit M, Green MA, Lettau S,
Thompson NN, Weymier J. Predicting functional capacity during treadmill testing independent of exercise protocol. Med Sci Sports Exerc 28:
752–756, 1996.
45. Fowler-Brown A, Pignone M, Pletcher M, Tice JA, Sutton SF, Lohr
KN. Exercise tolerance testing to screen for coronary heart disease: a
systematic review for the technical support for the US Preventive
Services Task Force. Ann Intern Med 140: 9 –24, 2004.
Invited Review
EXERCISE AND TYPE 2 DIABETES
J Appl Physiol • VOL
87.
88.
89.
90.
91.
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
nondiabetic patients: assessment by exercise thallium scintigraphy. Ann
Intern Med 108: 170 –175, 1988.
Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial
infarction and death from cardiovascular causes. N Engl J Med. In press.
O’Donovan G, Kearney EM, Nevill AM, Woolf-May K, Bird SR. The
effects of 24 weeks of moderate- or high-intensity exercise on insulin
resistance. Eur J Appl Physiol 95: 522–528, 2005.
O’Gorman DJ, Karlsson HK, McQuaid S, Yousif O, Rahman Y,
Gasparro D, Glund S, Chibalin AV, Zierath JR, Nolan JJ. Exercise
training increases insulin-stimulated glucose disposal and GLUT4
(SLC2A4) protein content in patients with type 2 diabetes. Diabetologia
49: 2983–2992, 2006.
Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, Fowler S. The effect of metformin and intensive lifestyle
intervention on the metabolic syndrome: the Diabetes Prevention Program randomized trial. Ann Intern Med 142: 611– 619, 2005.
Pan XR, Li GW, Hu YH, Wang JX, Yang WY, An ZX, Hu ZX, Lin
J, Xiao JZ, Cao HB, Liu PA, Jiang XG, Jiang YY, Wang JP, Zheng
H, Zhang H, Bennett PH, Howard BV. Effects of diet and exercise in
preventing NIDDM in people with impaired glucose tolerance. The Da
Qing IGT and Diabetes Study. Diabetes Care 20: 537–544, 1997.
Park SW, Goodpaster BH, Strotmeyer ES, de Rekeneire N, Harris
TB, Schwartz AV, Tylavsky FA, Newman AB. Decreased muscle
strength and quality in older adults with type 2 diabetes: the health, aging,
and body composition study. Diabetes 55: 1813–1818, 2006.
Park SW, Goodpaster BH, Strotmeyer ES, Kuller LH, Broudeau R,
Kammerer C, de Rekeneire N, Harris TB, Schwartz AV, Tylavsky
FA, Cho YW, Newman AB. Accelerated loss of skeletal muscle strength
in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes Care 30: 1507–1512, 2007.
Pavkov ME, Bennett PH, Knowler WC, Krakoff J, Sievers ML,
Nelson RG. Effect of youth-onset type 2 diabetes mellitus on incidence
of end-stage renal disease and mortality in young and middle-aged Pima
Indians. JAMA 296: 421– 426, 2006.
Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU,
Eldrup E, Dela F, Pedersen BK. Circulating levels of TNF-alpha and
IL-6-relation to truncal fat mass and muscle mass in healthy elderly
individuals and in patients with type-2 diabetes. Mech Ageing Dev 124:
495–502, 2003.
Pencek RR, Fueger PT, Camacho RC, Wasserman DH. Mobilization
of glucose from the liver during exercise and replenishment afterward.
Can J Appl Physiol 30: 292–303, 2005.
Perseghin G, Price TB, Petersen KF, Roden M, Cline GW, Gerow K,
Rothman DL, Shulman GI. Increased glucose transport-phosphorylation and muscle glycogen synthesis after exercise training in insulinresistant subjects. N Engl J Med 335: 1357–1362, 1996.
Peterson MD, Rhea MR, Alvar BA. Applications of the dose-response
for muscular strength development: a review of meta-analytic efficacy
and reliability for designing training prescription. J Strength Cond Res
19: 950 –958, 2005.
Peterson MJ, Pieper CF, Morey MC. Accuracy of V̇O2max prediction
equations in older adults. Med Sci Sports Exerc 35: 145–149, 2003.
Petrofsky JS, Stewart B, Patterson C, Cole M, Al Malty A, Lee S.
Cardiovascular responses and endurance during isometric exercise in
patients with Type 2 diabetes compared to control subjects. Med Sci
Monit 11: 470 – 477, 2005.
Praet SF, Manders RJ, Lieverse AG, Kuipers H, Stehouwer CD,
Keizer HA, van Loon LJC. Influence of acute exercise on hyperglycemia in insulin-treated Type 2 diabetes. Med Sci Sports Exerc 38:
2037–2044, 2006.
Praet SFE, Manders RJF, Meex RCR, Lieverse AG, Stehouwer
CDA, Kuipers H, Keizer HA, van Loon LJC. Glycemic instability is
an underestimated problem in type 2 diabetes. Clin Sci (Colch) 111:
119 –126, 2006.
Price TB, Rothman DL, Shulman RG. NMR of glycogen in exercise.
Proc Nutr Soc 58: 851– 859, 1999.
Radziuk J, Pye S. Diurnal rhythm in endogenous glucose production is
a major contributor to fasting hyperglycaemia in type 2 diabetes. Suprachiasmatic deficit or limit cycle behaviour? Diabetologia 49: 1619 –1628,
2006.
Reynolds JM, Gordon TJ, Robergs RA. Prediction of one repetition
maximum strength from multiple repetition maximum testing and anthropometry. J Strength Cond Res 20: 584 –592, 2006.
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
66. Kjaer M, Hollenbeck CB, Frey-Hewitt B, Galbo H, Haskell W,
Reaven GM. Glucoregulation and hormonal responses to maximal
exercise in non-insulin-dependent diabetes. J Appl Physiol 68: 2067–
2074, 1990.
67. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin
JM, Walker EA, Nathan DM. Reduction in the incidence of type 2
diabetes with lifestyle intervention or metformin. N Engl J Med 346:
393– 403, 2002.
68. Koopman R, Manders RJ, Jonkers RA, Hul GB, Kuipers H, van
Loon LJ. Intramyocellular lipid and glycogen content are reduced
following resistance exercise in untrained healthy males. Eur J Appl
Physiol 96: 525–534, 2006.
69. Koopman R, Verdijk L, Manders RJ, Gijsen AP, Gorselink M,
Pijpers E, Wagenmakers AJ, van Loon LJ. Co-ingestion of protein
and leucine stimulates muscle protein synthesis rates to the same extent
in young and elderly lean men. Am J Clin Nutr 84: 623– 632, 2006.
70. Kubota M, Nagasaki M, Tokudome M, Shinomiya Y, Ozawa T, Sato
Y. Mechanical horseback riding improves insulin sensitivity in elder
diabetic patients. Diabetes Res Clin Pract 71: 124 –130, 2006.
71. Larsen JJ, Dela F, Kjaer M, Galbo H. The effect of moderate exercise
on postprandial glucose homeostasis in NIDDM patients. Diabetologia
40: 447– 453, 1997.
72. Larsen JJ, Dela F, Madsbad S, Galbo H. The effect of intense exercise
on postprandial glucose homeostasis in type II diabetic patients. Diabetologia 42: 1282–1292, 1999.
73. Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG,
Hemio K, Hamalainen H, Harkonen P, Keinanen-Kiukaanniemi S,
Laakso M, Louheranta A, Mannelin M, Paturi M, Sundvall J, Valle
TT, Uusitupa M, Tuomilehto J. Sustained reduction in the incidence of
type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet 368: 1673–1679, 2006.
74. Loimaala A, Huikuri HV, Koobi T, Rinne M, Nenonen A, Vuori I.
Exercise training improves baroreflex sensitivity in type 2 diabetes.
Diabetes 52: 1837–1842, 2003.
75. Maiorana A, O’Driscoll G, Goodman C, Taylor R, Green D. Combined aerobic and resistance exercise improves glycemic control and
fitness in type 2 diabetes. Diabetes Res Clin Pract 56: 115–123, 2002.
76. Maiorana A, O’Driscoll G, Taylor R, Green D. Exercise and the nitric
oxide vasodilator system. Sports Med 33: 1013–1035, 2003.
77. Malek MH, Berger DE, Housh TJ, Coburn JW, Beck TW. Validity of
V̇O2max equations for aerobically trained males and females. Med Sci
Sports Exerc 36: 1427–1432, 2004.
78. McAuley PA, Myers JN, Abella JP, Tan SY, Froelicher VF. Exercise
capacity and body mass as predictors of mortality among male veterans
with type 2 diabetes. Diabetes Care 30: 1539 –1543, 2007.
79. Meyer K, Lehmann M, Sunder G, Keul J, Weidemann H. Interval
versus continuous exercise training after coronary bypass surgery: a
comparison of training-induced acute reactions with respect to the effectiveness of the exercise methods. Clin Cardiol 13: 851– 861, 1990.
80. Meyer K, Samek L, Schwaibold M, Westbrook S, Hajric R, Beneke
R, Lehmann M, Roskamm H. Interval training in patients with severe
chronic heart failure: analysis and recommendations for exercise procedures. Med Sci Sports Exerc 29: 306 –312, 1997.
81. Meyer K, Samek L, Schwaibold M, Westbrook S, Hajric R, Lehmann M, Essfeld D, Roskamm H. Physical responses to different
modes of interval exercise in patients with chronic heart failure: application to exercise training. Eur Heart J 17: 1040 –1047, 1996.
82. Middlebrooke AR, Elston LM, Macleod KM, Mawson DM, Ball CI,
Shore AC, Tooke JE. Six months of aerobic exercise does not improve
microvascular function in type 2 diabetes mellitus. Diabetologia 49:
2263–2271, 2006.
83. Mikines KJ, Farrell PA, Sonne B, Tronier B, Galbo H. Postexercise
dose-response relationship between plasma glucose and insulin secretion.
J Appl Physiol 64: 988 –999, 1988.
84. Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B. Management of hyperglycaemia in type 2 diabetes: a
consensus algorithm for the initiation and adjustment of therapy. A
consensus statement from the American Diabetes Association and the
European Association for the Study of Diabetes. Diabetologia 49: 1711–
1721, 2006.
85. Nesto RW. Screening for asymptomatic coronary artery disease in
diabetes. Diabetes Care 22: 1393–1395, 1999.
86. Nesto RW, Phillips RT, Kett KG, Hill T, Perper E, Young E, Leland
OS Jr. Angina and exertional myocardial ischemia in diabetic and
1119
Invited Review
1120
EXERCISE AND TYPE 2 DIABETES
J Appl Physiol • VOL
121.
122.
123.
124.
125.
126.
127.
128.
129.
130.
131.
132.
133.
of complications in type 2 diabetes: a prospective observational study
(UKPDS 75). Diabetologia 49: 1761–1769, 2006.
Tessier D, Menard J, Fulop T, Ardilouze J, Roy M, Dubuc N, Dubois
M, Gauthier P. Effects of aerobic physical exercise in the elderly with
type 2 diabetes mellitus. Arch Gerontol Geriatr 31: 121–132, 2000.
Torjesen PA, Birkeland KI, Anderssen SA, Hjermann I, Holme I,
Urdal P. Lifestyle changes may reverse development of the insulin
resistance syndrome. The Oslo Diet and Exercise Study: a randomized
trial. Diabetes Care 20: 26 –31, 1997.
Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen
H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M. Prevention of type
2 diabetes mellitus by changes in lifestyle among subjects with
impaired glucose tolerance. N Engl J Med 344: 1343–1350, 2001.
UK Prospective Diabetes Study Group U. Intensive blood-glucose
control with sulphonylureas or insulin compared with conventional
treatment and risk of complications in patients with type 2 diabetes
(UKPDS 33). Lancet 352: 837– 853, 1998.
Valensi P, Paries J, Brulport-Cerisier V, Torremocha F, Sachs RN,
Vanzetto G, Cosson E, Lormeau B, Attali JR, Marechaud R, Estour
B, Halimi S. Predictive value of silent myocardial ischemia for cardiac
events in diabetic patients: influence of age in a French multicenter study.
Diabetes Care 28: 2722–2727, 2005.
van Loon LJ, Manders RJ, Koopman R, Kaastra B, Stegen JH,
Gijsen AP, Saris WH, Keizer HA. Inhibition of adipose tissue lipolysis
increases intramuscular lipid use in type 2 diabetic patients. Diabetologia
48: 2097–2107, 2005.
Van Vrancken C, Bopp CM, Reis JP, DuBose KD, Kirtland KA,
Ainsworth BE. The prevalence of leisure-time physical activity among
diabetics in South Carolina. South Med J 97: 141–144, 2004.
Vanninen E, Uusitupa M, Siitonen O, Laitinen J, Lansimies E.
Habitual physical activity, aerobic capacity and metabolic control in
patients with newly-diagnosed type 2 (non-insulin-dependent) diabetes
mellitus: effect of 1-year diet and exercise intervention. Diabetologia 35:
340 –346, 1992.
Volpato S, Blaum C, Resnick H, Ferrucci L, Fried LP, Guralnik JM.
Comorbidities and impairments explaining the association between diabetes and lower extremity disability: The Women’s Health and Aging
Study. Diabetes Care 25: 678 – 683, 2002.
Wackers FJ, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett
EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner
RE, Iskandrian AE. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study. Diabetes Care 27: 1954 –
1961, 2004.
Willey KA, Singh MA. Battling insulin resistance in elderly obese
people with type 2 diabetes: bring on the heavy weights. Diabetes Care
26: 1580 –1588, 2003.
Wojtaszewski JF, Hansen BF, Gade Kiens B, Markuns JF, Goodyear
LJ, Richter EA. Insulin signaling and insulin sensitivity after exercise in
human skeletal muscle. Diabetes 49: 325–331, 2000.
Yamanouchi K, Shinozaki T, Chikada K, Nishikawa T, Ito K,
Shimizu S, Ozawa N, Suzuki Y, Maeno H, Kato K, et al. Daily
walking combined with diet therapy is a useful means for obese NIDDM
patients not only to reduce body weight but also to improve insulin
sensitivity. Diabetes Care 18: 775–778, 1995.
103 • OCTOBER 2007 •
www.jap.org
Downloaded from http://jap.physiology.org/ by 10.220.33.4 on June 18, 2017
106. Richter EA, Galbo H. Diabetes, insulin and exercise. Sports Med 3:
275–288, 1986.
107. Rogers MA, Yamamoto C, Hagberg JM, Martin WH 3rd, Ehsani
AA, Holloszy JO. Effect of 6 d of exercise training on responses to
maximal and sub-maximal exercise in middle-aged men. Med Sci Sports
Exerc 20: 260 –264, 1988.
108. Sayer AA, Dennison EM, Syddall HE, Gilbody HJ, Phillips DI,
Cooper C. Type 2 diabetes, muscle strength, and impaired physical
function: the tip of the iceberg? Diabetes Care 28: 2541–2542, 2005.
109. Schmermund A, Mohlenkamp S, Berenbein S, Pump H, Moebus S,
Roggenbuck U, Stang A, Seibel R, Gronemeyer D, Jockel KH, Erbel
R. Population-based assessment of subclinical coronary atherosclerosis
using electron-beam computed tomography. Atherosclerosis 185: 177–
182, 2006.
110. Schneider SH, Amorosa LF, Khachadurian AK, Ruderman NB.
Studies on the mechanism of improved glucose control during regular
exercise in type 2 (non-insulin-dependent) diabetes. Diabetologia 26:
355–360, 1984.
111. Schneider SH, Khachadurian AK, Amorosa LF, Clemow L, Ruderman NB. Ten-year experience with an exercise-based outpatient lifestyle modification program in the treatment of diabetes mellitus. Diabetes
Care 15: 1800 –1810, 1992.
112. Segal KR, Edano A, Abalos A, Albu J, Blando L, Tomas MB,
Pi-Sunyer FX. Effect of exercise training on insulin sensitivity and
glucose metabolism in lean, obese, and diabetic men. J Appl Physiol 71:
2402–2411, 1991.
113. Short KR, Vittone JL, Bigelow ML, Proctor DN, Rizza RA, CoenenSchimke JM, Nair KS. Impact of aerobic exercise training on agerelated changes in insulin sensitivity and muscle oxidative capacity.
Diabetes 52: 1888 –1896, 2003.
114. Sigal RJ, Kenny GP, Wasserman DH, Castaneda-Sceppa C, White
RD. Physical activity/exercise and type 2 diabetes: a consensus statement
from the American Diabetes Association. Diabetes Care 29: 1433–1438,
2006.
115. Slentz CA, Aiken LB, Houmard JA, Bales CW, Johnson JL, Tanner
CJ, Duscha BD, Kraus WE. Inactivity, exercise, and visceral fat.
STRRIDE: a randomized, controlled study of exercise intensity and
amount. J Appl Physiol 99: 1613–1618, 2005.
116. Snowling NJ, Hopkins WG. Effects of different modes of exercise
training on glucose control and risk factors for complications in type 2
diabetic patients: a meta-analysis. Diabetes Care 29: 2518 –2527, 2006.
117. Spijkerman AM, Dekker JM, Nijpels G, Adriaanse MC, Kostense
PJ, Ruwaard D, Stehouwer CD, Bouter LM, Heine RJ. Microvascular
complications at time of diagnosis of type 2 diabetes are similar among
diabetic patients detected by targeted screening and patients newly
diagnosed in general practice: the hoorn screening study. Diabetes Care
26: 2604 –2608, 2003.
118. Stevens RJ, Kothari V, Adler AI, Stratton IM. The UKPDS risk
engine: a model for the risk of coronary heart disease in Type II diabetes
(UKPDS 56). Clin Sci (Lond) 101: 671– 679, 2001.
119. Storer TW, Davis JA, Caiozzo VJ. Accurate prediction of V̇O2max in
cycle ergometry. Med Sci Sports Exerc 22: 704 –712, 1990.
120. Stratton IM, Cull CA, Adler AI, Matthews DR, Neil HA, Holman
RR. Additive effects of glycaemia and blood pressure exposure on risk