Aerobic and resistance training effects compared to aerobic

training alone in obese type 2 diabetic patients on diet

treatment
Pietro Lucotti
a
, Lucilla D. Monti
b
, Emanuela Setola
a
, Elena Galluccio
b
, Roberto Gatti
c,d
,
Emanuele Bosi
a,b,d
, PierMarco Piatti
a,b,d,
*
a
San Raffaele Scientic Institute, Cardio-Metabolic and Clinical Trials Unit, Internal Medicine Department, and Metabolic and Cardiovascular
Science Division, Milan 20132, Italy
b
San Raffaele Scientic Institute, Cardio-Diabetes and Core-Lab, Metabolic and Cardiovascular Science Division, Milan 20132, Italy
c
San Raffaele Scientic Institute, Laboratory of Movement Analysis, School of Physiotherapy, Milan 20132, Italy
d
San Raffaele Scientic Institute, Vita-Salute San Raffaele University, Milan 20132, Italy
d i a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3
a r t i c l e i n f o
Article history:
Received 9 June 2011
Received in revised form
20 July 2011
Accepted 1 August 2011
Published on line 3 September 2011
Keywords:
Insulin resistance
Endothelium
Inammation
Adipokine
Glucose metabolism
a b s t r a c t
Aims: The study was designed to compare a combined aerobic and resistance training (ART)
with an aerobic training (AT) over hemodynamic, glucose metabolism and endothelial
factors, adipokines and pro-inammatory marker release in a population of obese type 2
diabetic patients.
Methods: Forty-seven patients were randomly assigned to aerobic (27 patients) or aerobic
plus resistance (20 patients) exercise trainings, on the top of a diet regime. Anthropometric,
metabolic, hormonal and inammatory variables were measured at hospitalization and
discharge.
Results: Both exercise programs equally improved body weight and fructosamine levels
however ART only partially decreased HOMA index compared with AT (ART: 25% vs AT:
54%, p < 0.01). Mean blood pressure (AT: 3.6 mmHg vs ART: +0.6 mmHg, p < 0.05) and
endothelin-1 (ET-1) incremental areas during walking test (AT: 11% vs ART: +30%,
p < 0.001) decreased after AT while increased after ART. Adiponectin levels increased by
54%after AT while decreased by 13%after ART ( p < 0.0001) and matrix metalloproteinase-2
(MMP-2), tumor necrosis factor-alpha (TNF-alpha) and monocyte chemoattractan protein-1
(MCP-1) levels signicantly decreased in AT while increased in ART group.
Conclusions: Compared with AT, ART similarly enhanced body weight loss but exerted less
positive effects on insulin sensitivity and endothelial factors, adipokines and pro-inam-
matory marker release.
# 2011 Elsevier Ireland Ltd. All rights reserved.
* Corresponding author at: Cardio-Diabetes and Clinical Trials Unit, Internal Medicine Department and Metabolic and Cardiovascular
Science Division, Vita-Salute San Raffaele University, Scientic Institute San Raffaele, Via Olgettina 60, Milan 20132, Italy.
Tel.: +39 02 2643 2819; fax: +39 02 2643 3839.
E-mail address: piermarco.piatti@hsr.it (P. Piatti).
Abbreviations: AT, aerobic training; ART, aerobic and resistance training; RT, resistance training; HOMA, homeostasis model assess-
ment; MMP-2, matrix metalloproteinase-2; TNF-alpha, tumor necrosis factor-alpha; MCP-1, monocyte chemoattractan protein-1; FM, fat
mass; FFM, fat free mass; NO, nitric oxide; FFA, free fatty acids; ET-1, endothelin-1.
Cont ent s l i st s avai l abl e at Sci enceDi r ect
Diabetes Research
and Clinical Practice
j ournal homepage: www. el sevi er. com/ l ocate/ di abres
0168-8227/$ see front matter # 2011 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.diabres.2011.08.002
1. Introduction
Aerobic exercise has shown many positive effects on insulin
sensitivity and glucose homeostasis [1]. A chronic aerobic
training (AT), even without changes in body composition,
improves insulin sensitivity up to 30% both in impaired
glucose tolerant (IGT) and type 2 diabetic patients [1]. Exercise
intervention in adults with type 2 diabetes induces a mean fall
in HbA1c percentage of 0.74 compared with control group,
independently to body weight change [2]. In addition it
promotes mobilization of visceral adipose tissue so reducing
insulin resistance [3]. AT improves as well some cardiovascu-
lar risk factors such as hypertension, dyslipidemia and
brinolytic activity [4]. According to these benets daily AT
was listed in guidelines for exercise in type 2 diabetes [5].
Resistance training (RT) shows potential benets in
rehabilitation, thanks to its ability in avoiding disease-related
muscle wasting. Further, muscle contraction increases glu-
cose uptake and improves insulin sensitivity in skeletal
muscle thereby providing a rationale for its use in disease
like type 2 diabetes [6,7]. RT enhances muscular strength and
changes in body composition by increasing lean body mass
and decreasing visceral and total body fat [8]. In particular,
light to moderate loads (4060% of 1 RM) are recommended for
local muscular endurance training performed at high repeti-
tion using short resting period (<90 s) [9]. In addition, 3 days
per week (3 d w
1
) training frequency has been recently shown
to be superior to 12 days per week for improving muscular
endurance, coordination, balance and cardiorespiratory t-
ness in older women [10], conrming meta-analytical data
showing that strength gains in untrained individuals were
highest with a frequency of 3 d w
1
[11]. In this light, recently
published studies investigating the effect of aerobic and
resistance training in patients with cardiovascular disease like
chronic heart failure and stroke, adopted a 5 d w
1
training
frequency in order to provide further evidence for the use of
exercise as a clinical therapy in these patients [12,13].
Actually, few studies investigated the effect of a short
program (about 3 weeks) of combined high frequency AT plus
RT on glucose homeostasis and insulin sensitivity. In
particular, there is small evidence of additional benet from
combining RT and AT on some related risk factors for diabetes
complications (endothelial function and sub-clinical inam-
mation) in obese type 2 diabetic patients [14].
Therefore, the present study was designed to evaluate the
effects of a short high frequency (5 d w
1
) RT and AT added to a
program of hypocaloric diet compared with a high frequency
AT with a similar program of hypocaloric diet, on fat and lean
body mass distribution, glucose levels, insulin levels and
sensitivity, endothelial factors, adipokines and pro-inam-
matory markers releases in obese type 2 diabetic patients.
2. Subjects
2.1. Informed consent
Fifty middle-aged patients (30 males, 20 females) were
included in the experimental protocol. All patients gave
informed consent to participate into the study that was
approved by the local Ethics Committee.
2.2. Study population
Patients were severely obese (body mass index, 38.6 5.6;
waist circumference, 113.1 12.7 cm), with type 2 diabetes
mellitus and metabolic syndrome according to ATPIII [15].
Before hospitalization, all were treated by diet alone for type 2
diabetes and the 2 study groups had comparable treatments
for hypertension and dyslipidemia and no changes were made
during the study period.
3. Materials and methods
3.1. Diet program
Patients were hospitalized for 21 days and submitted to a
hypocaloric diet regime that consisted of 1000 kcal/day with
55% carbohydrate, 2530% fat (saturated fat 7%) and 1520%
protein (animal protein 54 g) subdivided as follows: 15% for
breakfast, 50% for lunch and 35% for dinner, administered
under a daily supervision of a dietician. Diet was controlled
not only for carbohydrate but also for cholesterol and natural
ber content (176 mg and 25 mg, respectively).
The diet provided about 50% of their estimated daily caloric
needs, according with [16]. It was previously seen that obese
patients who receive 3370% of their estimated caloric needs
during critical illness have better clinical outcomes [17]. The
nal goal was to induce a superimposable loss in FM and FFM
and a minor decrease in insulin resistance as previously
demonstrated by our group [18]. All in all, a moderate weight
loss (5%) was achieved in our patients in the attempt not to
overshadow the results obtained through different exercise
programs on insulin resistance and inammation. In fact,
recent data suggest that there may be a doseresponse effect
between the degree of weight loss and its capacity to attenuate
chronic inammation. In particular, it was found that at least
10% weight reduction is needed to achieve a signicant
reduction in C-reactive protein levels [19].
3.2. Exercise training program
Patients were randomly assigned to AT or ART group with a 3:2
ratio in order to generate additional metabolic, inammatory
and ET-1 data for AT group. This was done since we considered
the possibility to have higher drop-out number in the group
submitted to AT treatment during hospitalization, a program
usually done in a home setting. The tests consisted in two
different 3-weeks exercise program: AT alone (30 patients) and
aerobic plus resistance exercise training (ART, 20 patients). AT
program consisted of 30 min bid session of whole body
exercise for 5 days a week. Each training session consisted
in 30 min of aerobic exercise divided into row ergometer
(15 min) and bicycle ergometer (15 min). The training program
was performed at 70% of the individual age-predicted HR
max
according to Tanaka et al. [20]. Patients exercised under the
supervision of a physician. ART program consisted in 45 min
bid session composed by an aerobic session comparable to
di a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3 396
that performed by aerobic training group followed by a
resistance training session consisting in 9 resistance exercise
for 15 min: 5 exercises for the upper part of the body (arm
curls, military press, push-ups, upright rowing, back exten-
sion) and 4 exercises for the lower part of the body (squats,
knee extensions, heel raises and bent knee sit-ups). Resistance
loads were 4050% of one repetition maximum testing (1RM)
performed at baseline and at the end of the study. The subjects
performed 10 repetitions per set for all upper body exercises
and 20 repetitions per set for lower body exercises. One set for
each exercise was performed, at a moderate contraction
velocity (2 s concentric, 2 s eccentric). The resting interval
between sets was <1 min. Weights were adjusted throughout
the training program as strength level increased.
Both exercise trainings were associated with a similar
hypocaloric diet (1000 kcal/die) to achieve a greater improve-
ment in physical function, as recently demonstrated [21].
3.3. Experimental protocol
According to protocol design, patients were evaluated at
baseline and after 21 days of hypocaloric diet and exercise
training program. After an overnight fast, blood pressure,
heart rate and anthropometric measurements were evaluated
after at least 30 min of rest in the supine position by the same
examiner including waist circumference. Then, FM and FFM
percentage, total body water content and basal metabolism
were measured by bio-impedance using TANITA body fat
analyzer (model SC3315, TANITA Corporation, Tokyo, Japan),
which applies the principle of bioelectrical impedance
measurements of voltage drop from foot-to-foot when a small
alternative current is applied through contact with two metal
foot pads. Previous studies showed a high correlation between
bio-impedance analysis and DEXA results [22]. After this
period, a 20 gauge plastic cannula was inserted in an
antecubital vein of the arm for blood sampling and an exercise
test was started which consisted in 6 min walking test (6MWT)
at 85% of age-predicted HR
max
[23] conducted accordingly to
American Thoracic Statement Guidelines [24]. The test was
performed 24 h after the last bout of ART or AT exercises trying
to avoid the effects on plasma volume changes and on
metabolism of the previous single exercise bout which could
have modied the measured parameters. Systolic and diastol-
ic blood pressure and heart rate were assessed immediately at
the end of the test and after 5 min of rest. Basal samples for
glucose, insulin, lipids, adipokines and pro-inammatory
factors were withdrawn immediately before the exercise test
while endothelin-1, nitrate/nitrite (NOx), c-GMP, FFA and TNF-a
were measured during the ergometric walking test at time 0,
6 min (end of the exercise) and 11 min (recovery). Since 6 min
walking test is a functional manner to evaluate the benecial
effects of exercise trainings, the choice to measure insulin
sensitivity, endothelial function and inammation before and
during the test was, in our opinion, a way to strengthen possible
differences on the effects of ART compared to AT. HOMA model
has been used to yield an estimate of insulin resistance from
fasting plasma insulin(FPI) and glucose concentration (FPG) and
calculated as follows: HOMA-IR = (FPI mU/l FPG mmol/l)/22.5
[25]. At baseline 4050% of 1RM was determined before exercise
program start by means of dynamometry. Maximum strength
was determined by one repetition maximum (1RM) in kp
through a maximum of three attempts, the best score counts
were recorded. The representative exercises for the determina-
tion of 1RM included knee extension and military press,
performed in a seated position.
3.4. Analytical measurements
Blood glucose, HDL cholesterol, total cholesterol and trigly-
cerides were measured with spectrophotometric methods
adapted to Cobas MIRA using commercial kits (ABX, Mon-
tpellier, France). FFA levels were measured using automated
enzymatic spectrophotometric techniques adapted to Cobas
MIRA using commercial kits (NEFA C, Wako Chemicals GmbH,
Neuss). Serum insulin levels were assayed with a microparti-
cle enzyme immunoassay (IMX, Abbott Laboratories). NOx
levels were evaluated through the measurement of metabolic
end products, i.e., nitrite and nitrate, using enzymatic
catalysis coupled with Griess reaction. ET-1 samples were
extracted on SepPack C18 minicolumn (Amprep, Amersham
International, Buckinghamshire, UK) and assayed by a RIA kit
(NEN Life Science Products, Boston, USA).
Human leptin and adiponectin levels were assayed with an
ELISA kit and a RIA kit (LINCO Research, St. Charles, Missouri,
USA), respectively. Resistin levels were assayed with an ELISA
kit (Chemicon International, Demecula, Canada). Human TNF-
alpha and MCP-1 levels were assayed with ELISA kits (Bender
Med Systems GmbH, Vienna, Austria).
3.5. Statistical analysis
All values are expressed as Mean SD at each time interval.
Incremental areas of variables during ergometric walking test
were calculated by the trapezoidal rule. All data were tested
for normal distribution with the KolmogorovSmirnov test.
Comparison between the two groups at baseline was
performed by using the unpaired Students t-test. The
treatment effects were determined by a repeated measured
ANOVA. An adjusted p value of less than 0.05 was taken to
indicate a signicant difference. Pearson correlations were
conducted on change scores (differences between after minus
basal levels). All analyses were performed using SPSS version
15.0 software (SPSS Inc., Chicago, IL).
4. Results
Three patients of AT group withdrawn the study and all the
results are related to 47 patients, i.e. 27 patients in AT group and
20 patients in ART group and in Table 1 are reported
anthropometric parameters, systolic and diastolic blood pres-
sure, lipids levels and glucose metabolism measurements for
these patients. Before training period, no statistically signicant
differences in anthropometric and metabolic variables were
observed between the two groups as shown by Students t-test
(Table 1). After 21 days of exercise training, a signicant
decrement of body weight was achieved in both groups which
consisted predominantly in FM loss since FFM was preserved in
both groups, especially after ART training. Consistent with
weight reduction, waist and hip circumferences comparably
d i a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3 397
decreased in both groups of treatment. Mean blood pressure
showed a signicant reduction after AT training compared with
ART ( p < 0.05).
Although fructosamine, fasting blood glucose and insulin
levels improved after both AT and ART, AT group showed a
more signicant reduction in fasting blood glucose ( p < 0.03)
and insulin levels ( p < 0.01, Fig. 1). Consequently, as compared
with ART, AT induced a twofold decrement in HOMA-IR
( p < 0.01, Fig. 1). In addition, fasting FFA levels signicantly
decreased in AT group while did not change after ART
( p < 0.05, Table 1). Finally, total cholesterol and triglycerides
levels similarly decreased in both groups while HDL-choles-
terol remained unchanged.
In Table 1 and Fig. 2 are shown endothelial variables,
adipokines and pro-inammatory markers before and after
training programs. After 21 days of treatment, fasting ET-1 and
NOx did not change signicantly in both groups. Interestingly,
adiponectin levels signicantly increased by 54% after AT
while decreased by 13% after ART; leptin levels signicantly
decreased in AT group while remaining unchanged in ART.
Consequently, leptin to adiponectin ratio, an index of
atherosclerosis, signicantly decreased by 52% after AT but
increased by 26% after ART ( p < 0.0003). Similarly, TNF-a,
resistin, MMP-2 and MCP-1 levels showed a different behavior
depending on type of training, being reduced after AT and
increased after ART ( p < 0.009; p < 0.04; p < 0.0001; p < 0.003,
respectively).
After the period of diet and exercise training, the
ergometric walking test demonstrated a signicant and
similar increment in walked meters (AT: from 461.8 77.1
to 501.0 76.7 vs. ART: from 496.7 83.3 to 544.7 81.3, Table
1). Compared with baseline, mean blood pressure at the end of
the 6 min walking test decreased in both groups, even if in AT
there was a deeper decrement than in ART ( p < 0.01; Fig. 3)
Interestingly, endothelin-1 incremental areas during ergo-
metric walking test decreased by 11% after AT while increased
by 30% after ART ( p < 0.01; Fig. 3). Conversely, NOx incremen-
tal areas during ergometric test increased in AT while
decreased in ART group ( p < 0.05, Fig. 3).
5. Discussion
The present study investigates the effects of high frequency
resistance exercise added to an aerobic exercise intervention
carried on in controlled conditions as add-on to a strict diet
regime administered under a daily supervision of a dietician in
a population of obese type 2 diabetic patients; results observed
after 3 weeks of therapy show at least three major aspects that
need to be discussed: (1) a combination of aerobic and
resistance high frequency exercise training improves overall
glucose metabolism but partially blunt the benecial effects
over glucose metabolism which is achieved by an aerobic high
frequency exercise training; (2) the addition of resistance to
aerobic high frequency exercise may have a deleterious effect
over endothelial function and hemodynamic balance through
a stimulation of endothelin-1 release and a concomitant
increase in mean blood pressure levels; nally (3) aerobic and
Table 1 Changes in anthropometric, metabolic, and hormonal variables before and after aerobic alone (AT) training or
aerobic plus resistance (ART) training (Mean W SD).
AT ART Students t-test Treatment effect
Before After Before After
Anthropometric and clinical variables
Patients (F/M) 27 (17/10) 20 (13/7)
Age (year) 58.1 9.9 61.5 11.5 p < 0.33
Body weight (kg) 103.9 17.7 100.5 16.4
b
106.6 20.8 103.2 20.3
b
p < 0.34 p < 0.29
BMI (kg/m
2
) 38.8 4.5 37.5 4.2
b
39.9 7.3 38.6 7.2
b
p < 0.51 p < 0.58
Free fat mass (kg) 57.6 11.1 55.7 12.6 57.9 10.5 57.6 10.7 p < 0.92 p < 0.29
Fat mass (kg) 45.5 12.4 43.6 10.7
a
49.3 16.2 46.5 15.0
a
p < 0.34 p < 0.29
Waist (cm) 114.3 10.4 106.3 14.9
b
118.6 11.6 112.6 11.9
b
p < 0.30 p < 0.59
Hip (cm) 121.2 7.5 119.1 7.4
b
125.0 15.5 121.5 14.9
b
p < 0.35 p < 0.09
Syst. BP (mmHg) 124.4 11.6 118.6 12.3
b
127.0 15.0 126.7 14.0 p < 0.51 p < 0.17
Diast. BP (mmHg) 78.0 6.4 75.2 6.5 78.5 8.7 79.5 8.8 p < 0.82 p < 0.17
Mean BP (mmHg) 93.5 7.0 89.7 7.7
b
94.7 9.1 95.3 9.2 p < 0.62 p < 0.05
Walk test distaice (m) 461.8 77.1 501.0 76.7
b
496.7 83.3 544.7 81.3
b
p < 0.14 p < 0.56
Metabolic and hormonal variables
Fructos. (mmol/1) 272.0 57.0 219.1 44.6
b
294.8 61.6 244.8 36.1
b
p < 0.20 p < 0.46
HbAlc (%) 7.3 1.8 6.9 1.3 7.9 1.9 7.3 1.9 p < 0.28 p < 0.85
F. FFA (mmol/1) 0.81 0.20 0.65 0.20
a
0.80 0.19 0.79 0.24 p < 0.89 p < 0.05
AUC FFA (mmol/l*6 min) 8.53 1.9 7.16 1.9
a
7.77 1.7 7.98 1.9] p < 0.17 p < 0.03
F. Total chol. (mg/dl) 200.6 37.2 174.4 33.4 194.9 44.8 171.9 39.2
a
p < 0.62 p < 0.99
F. HDL chol. (mg/dl) 38.5 8.5 39.5 10.2 41.3 15.8 40.1 8.4 p < 0.61 p < 0.61
F. Triglyc. (mg/dl) 187.1 63.2 126.4 44.5 172.8 62.0 125.4 32.1
b
p < 0.36 p < 0.70
F. NOx (mmol/1) 15.3 5.9 13.4 4.8 16.3 7.0 17.7 8.4 p < 0.60 p < 0.13
F. ET-l (pg/ml) 10.0 2.8 10.2 5.3 9.85 5.6 11.7 5.1 p < 0.88 p < 0.42
BP, blood pressure; Fructos, fructosamine; F., fasting; FFA, free fatty acids; Chol, cholesterol; Triglyc., triglyceride; NOx, nitrite and nitrate; ET-1,
endothelin-1.
a
p < 0.05 after vs before.
b
p < 0.01 after vs before.
di a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3 398
resistance high frequency exercise training seems to have a
pro-inammatory effect as suggested by an increment of their
circulating markers. Interestingly all these results become
evident even after a short, although intensive, training period
in controlled conditions.
The different impact observed over glucose metabolism
and other metabolic parameters could not be ascribed entirely
to weight loss as both AT and ART groups have the same
weight loss (3 kg). The relative short duration of the study
period could explain the blunted ART effect on fat free mass as
compared with AT, as expected. A possible alternative
explanation may come from the prevalence of contraction
type, concentric vs. eccentric, followed in the resistance
exercise protocol. It is known that an eccentric contraction
compared with a concentric one induces a disproportionate
increase in protein synthesis resulting in largest improvement
in muscle size [26]. Resistance exercises were performed in
order to equally distribute the concentric and eccentric
exercise component, suggesting a rationale to explain the
weak impact of combined exercise on free fat mass amount.
Both training regimens showed similar improvement in
overall glucose metabolism consisting in 20% reduction of
fructosamine levels, on the contrary the two type of trainings
showed a different impact over insulin resistance. In fact,
fasting glucose and insulin levels reduction observed after AT
was partially blunted after ART resulting in only a modest
reduction in HOMA index as compared with AT group. In this
light recent evidence support a role of resistance exercise in
modulating muscle signaling pathways in fasting conditions
through an inhibition of Akt/PKB pathway [27]. Akt/PKB
signaling represents a primary molecular mechanism by
which insulin regulates glucose transport in skeletal muscle.
Therefore, it is possible that a reduction in Akt/PKB signaling
in human skeletal muscle by resistance exercise may explain
the only slight improvement in insulin sensitivity observed in
ART group while with AT insulin sensitivity was greatly
increased. In addition, acute resistance training has been
shown to induce a rapid increase in FFA secondary to
enhanced lipolysis [28], a well known cause of insulin
resistance. Although improvement in cardio-respiratory t-
ness appears to be linked with improvement in HbA1c in type 2
diabetes mellitus [29], recent data suggest that combined
aerobic and resistance training do not provide additional
benet compared with resistance training alone in physical
tness evaluated by means of maximal treadmill exercise test.
In addition results from the DARE trial show that the
association between changes in strength (muscle cross-
sectional area) and HbA1c was signicant only after resistance
training, falling just near to statistical signicance with
combined exercise suggesting that greater work volumes
(i.e. up to three sessions per week of resistance exercise
training) may be necessary for people with type 2 diabetes to
achieve signicant improvements in HbA1c [30]. Accordingly,
results from our study show no further gains in glucose
metabolism indices (HbA1c and fructosamine) following
combined exercise compared with aerobic exercise alone
probably due to the lack in free fat mass gain. Further, recently
it was demonstrated an improvement of HbA1c in type 2
diabetic patients when a combination of aerobic and resis-
tance training was performed compared with the non-
exercise control group in a study lasting 9 months [31,32].
Thus, it is possible that a longer period of study is needed to
achieve favorable results after resistance training in our study
groups but this was not possible in our study design since
patients were hospitalized.
Although resistance training alone is known to potentially
increase arterial stiffness with a raise in blood pressure [33],
few data are available concerning vascular function following
a combination of resistance and aerobic exercise. In the
present study a direct measurement of vascular function was
not performed but samples for endothelial vasopeptides like
ET-1 and end product of nitric oxide metabolism, i.e. nitrite
and nitrate (NOx) were obtained both in resting condition and
during ergometric walking test. ET-1 incremental areas
increased while NOx incremental areas decreased during
walking test in ART group. This nding is in agreement with
recent studies investigating the relationship between plasma
ET-1 concentrations and cardiovascular response during
resistance exercise. In particular, it was demonstrated that
resistance exercise, especially when consisting in concentric
contractions, is associated with ET-1 production and with a
greater increase in blood pressure levels [34]. Although
patients of both groups signicantly improved their individual
Fig. 1 Glucose (A), insulin (B) and HOMA-IR (C) before and
after 21 days of AT (left) or ART (right) in obese type 2
diabetic patients. Data are presented as Mean W SD.
*p < 0.03 for treatment effect; **p < 0.01 for treatment effect;
(a) p < 0.05 after vs before.
d i a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3 399
performance in terms of meters walked at nal walking test,
compared with AT, ART group showed a concomitant increase
in mean basal blood pressure, known as the result of heart rate
and peripheral resistance interaction. This nding is of
particular interest in order to better investigate the hemody-
namic effects that follow the association of resistance to
aerobic exercise.
In the present study leptin to adiponectin ratio, a novel pro-
atherosclerotic index, was halved after 21 days of AT as a
consequence of the marked increase in adiponectin levels
while in ART group L/A ratio signicantly increased mainly
since, in this group, adiponectin levels did not change.
Accordingly, in a recent study, Fernandez-Real et al. did not
found signicant changes in adiponectin levels in obese
women after diet plus resistance training [35]. A possible
explanation of the differences between AT and ART trainings
on adiponectin levels could be related to the fact that TNF-a
were higher in ART than in AT and it was demonstrated that
TNF-a down-regulates adiponectin levels in vivo [36].
AT determined also a signicant improvement in pro-
inammatory markers consisting in about 20% reduction in
TNF-a, and MMP-2 and 10% reduction in MCP-1 levels in
agreement with previous studies. In particular, recently
Balducci et al. showed that an intensive physical intervention
comprehensive of aerobic and resistance training was able to
improve inammatory markers irrespective of weight loss in a
population of type 2 diabetic patients with metabolic
syndrome [37]. In line with our data, Reed et al. demonstrated
Fig. 2 Leptin (A), adiponectin (B), resistin (C), TNF-a (D), MCP-1 (E) and MMP-2 (F) before and after 21 days of AT (left) or ART
(right) in obese type 2 diabetic patients. Data are presented as Mean W SD. *p < 0.01 for treatment effect; **p < 0.0001 for
treatment effect; (a) p < 0.05 after vs before; (b) p < 0.01 after vs before.
di a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3 400
that weight loss after 4-month moderate to vigorous aerobic
exercise training (4 times per week) and caloric restriction (20
35% of the estimated baseline energy needs) was effective in
reducing inammatory markers [38]. Surprisingly, the addi-
tion of resistance to aerobic exercise did not further improve
inammation and on the contrary, induced a signicant
increment in inammation. Contradictory results were found
comparing resistance exercise and inammatory mediators.
In fact, although previous studies, investigating of inamma-
tory mediators changes after resistance exercise, found a
slight increase in these indices [39], Kohut et al. showed that
only cardiovascular but not exibility/strength exercise
showed positive effects over serum IL-6, IL-18 and CRP levels
[40]. In our study, several factors like exercise intensity,
different duration of ART than AT time of exercise and
frequency or adaptation to exercise may have inuenced the
extent to which serum inammatory markers was altered in
the two groups. In particular, short recovery periods between
resistance exercises may impair specic anabolic processes
for up to 48 h after exercise and generate an acute inamma-
tory response [41].
A possible limitation of the present study is the short
duration of treatment (3 weeks) since previous studies
evaluating the effect of resistance training alone over
metabolic parameters for longer period showed a positive
effect in terms of glucose, insulin sensitivity, blood pressure
control and free fat mass preservation in type 2 diabetic
patients [42,43]. This might have inuenced the lack of
additional benecial effects of ART than AT alone in our
group of obese, type 2 diabetic patients. Further, training
modality may have inuenced our results and more studies
with longer follow-up are needed to better investigate clinical
benets of training modalities (inclusive of frequency, dura-
tion and volume) in the same class of patients [44].
Due to our short (3 weeks) study design in hospitalized
patients, we are not able to rule out the specic contribution
of diet alone on amelioration of insulin sensitivity and
inammatory markers and the lack of a personalized dietary
restriction might have inuenced the nal results, as negative
energy balance could have been higher for certain patients
with high BMI compared to others with lower BMI. However, it
is known that hypocaloric diet alone resulted in specic
reduction of inammatory markers and improvement in
metabolic measurements [45]. In addition, recently it has
been published data suggesting that caloric restriction can
inuence protein metabolism and FFM maintenance irre-
spective of obesity level [46]. Conversely, in our opinion, the
strength of the present study was that all patients were
hospitalized and study was conducted in highly controlled
condition both for the diet treatment and for exercise
training.
In conclusion, 3 weeks of high frequency AT alone have
benecial effects on insulin sensitivity, endothelial function,
and adipokine release while 3 weeks of high frequency ART on
Fig. 3 Mean blood pressure at the end of the walking test (A), ET-1 incremental area (B), TNF-alpha incremental area (C),
NOx incremetal area (D), during walking test before and after 21 days of AT (left) or ART (right) in obese type 2 diabetic
patients. Data are presented as Mean W SD. *p < 0.05 for treatment effect; **p < 0.01 for treatment effect; (a) p < 0.05 after vs
before; (b) p < 0.01 after vs before.
d i a b e t e s r e s e a r c h a nd c l i ni c a l p r a c t i c e 9 4 ( 2 0 1 1 ) 3 9 5 4 0 3 401
sequential day, even if similarly improved body weight loss as
high frequency AT alone, exerted less positive effects on
insulin sensitivity, additionally having an adverse effect on
endothelial function, hemodynamic balance with a greater
pro-inammatory response in obese type 2 diabetic patients.
In clinical perspective, even if ART remains an important
tool in the therapy of obese type 2 diabetic patients, duration
and mostly frequency of ART may adversely impact its
benecial effects inducing a more pro-inammatory pathway,
especially in a population of sedentary, severely obese,
diabetic patient at the beginning of a physical activity
program. The negative results of combined ART exercise on
sequential days achieved in the present study strongly support
ACSM/ADA Guidelines suggesting that such patients should
exercise on alternate days.
Acknowledgment
The excellent technical support of Ms. Sabrina Costa and
Barbara Fontana is gratefully acknowledged.
Conict of interest
There are no conicts of interest.
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