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Effects of exercise intervention on vascular endothelium functions of patients

with impaired glucose tolerance during prediabetes mellitus

Article  in  Experimental and Therapeutic Medicine · June 2013

DOI: 10.3892/etm.2013.1064 · Source: PubMed

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 EXPERIMENTAL AND THERAPEUTIC MEDICINE 5: 1559-1565, 2013

Effects of exercise intervention on vascular

endothelium functions of patients with impaired
glucose tolerance during prediabetes mellitus
YIPING LIU1,2, JIANWEI LI3, ZHENGHONG ZHANG2,
YEDONG TANG2, ZUOSONG CHEN1 and ZHENGCHAO WANG2

1
Laboratory of Sport Physiology and Biomedicine, School of Physical Education and Sport Sciences;
2
Provincial Key Laboratory for Developmental Biology and Neurosciences, College of Life Sciences,
Fujian Normal University, Fuzhou, Fujian 350007; 3Department of Ultrasound, Fujian Provincial Hospital,
Provincial Clinical College of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China

Received January 8, 2013; Accepted March 19, 2013

DOI: 10.3892/etm.2013.1064

Abstract. Endothelial dysfunction (ED) is an early patho- dependent dysfunction in middle-aged patients with IGT. This
physiological change in patients with impaired glucose study also provided direct clinical data supporting the use of
tolerance (IGT) during prediabetes mellitus. This study was exercise intervention to prevent diabetes mellitus (DM) during
designed to test the hypothesis that exercise intervention the early stage.
contributes to the reversal of vascular endothelium-dependent
dysfunction in middle-aged patients with IGT. Following Introduction
exercise intervention, significant changes in endothelin
(ET)-1, C-type natriuretic peptide (CNP), Δ Dia-P, oral Impaired glucose tolerance (IGT) is an early characteristic
glucose tolerance test (OGTT)2h, fasting insulin, homeostasis of prediabetes mellitus, in addition to the elevated postpran-
model of assessment-insulin resistance (HOMA-IR), body fat dial glucose (1,2). Insulin resistance (IR) is often detected
percentage, waist circumference and waist to hip ratio were in patients with glucose metabolism disorders (3). IR is the
measured. However, no marked changes in carotid artery compensatory excessive secretion of insulin for maintaining
intima-media thickness (IMT), fasting blood glucose and normal physiological functions and subsequently results
BMI were observed following exercise intervention. Validity in hyperinsulinemia (3). In general, the important factors
analysis of index changes in the two exercise intervention affecting IR (1) include being overweight or obese, low levels
groups further confirmed there was no change. Exercise of physical exercise and genetic factors (2). Currently, the
intervention increased CNP levels, decreased ET-1 levels and physically less active modern lifestyle is a significant factor
increased ΔDia-P, indicating improved vascular endothelium leading to the increased incidence of IGT and diabetes mellitus
function. Decreased HOMA-IR following exercise suggests (DM) with IR (4-6).
enhanced insulin sensitivity. Exercise intervention also IR may coexist with hepatic resistance leading to increases
improved glucose metabolism via decreased OGTT2h and of glycogen production and output, and postprandial hyper-
fasting insulin. In addition, decreased waist circumference, glycemia. IR may also coexist with muscular resistance
ratio of waist to hip and body fat percentage following exercise leading to the reduction of insulin-stimulated glucose uptake
intervention improved changes of body composition, including or manifestations and of dystrophin-glycoprotein genera-
BMI, body fat and waist circumference. These results indicate tion/storage. Finally, the insulin suppression of lipolysis is
that exercise intervention may reverse vascular endothelium- attenuated (2,7,8). In the 1980s, an early study concerning the
prevention of diabetes in individuals with IGT was performed
in Daqing, China (9). Subsequently, several diabetes preven-
tion studies, including a diabetes prevention study (DPS) in
Finland (10) and a diabetes prevention program (DPP) in the
Correspondence to: Dr Zhengchao Wang, Provincial Key
United States of America (11) showed that the incidence of
Laboratory for Developmental Biology and Neurosciences, College
of Life Sciences (Qishan Campus), Fujian Normal University,
diabetes was significantly reduced via lifestyle intervention
8 Shangsan Road, Fuzhou, Fujian 350007, P.R. China during IGT. Therefore, intervention during IGT may be an
E-mail: [email protected] important method for the prevention of DM.
By contrast, the risk of cardiovascular disease (CVD) is
Key words: exercise intervention, impaired glucose tolerance, similar to that of DM in patients with IGT (12,13). Therefore,
diabetes mellitus the main harmful effect of IGT is not only the transformation
to diabetes, but also the increased risk of CVD (13). IGT is also
an important indicator of CVD in patients with endothelial
1560 LIU et al: ENDOTHELIUM-DEPENDENT VASODILATION

dysfunction (ED) as the early important pathophysiological (HR)max, 4 times a week for 60 min each time, including 5 min
marker (14). ED in functional performance is the attenuated stretching and warming-up, 50 min walking exercise and
resilience and vasodilation of large vessels (14). ED is also 5 min relaxation. The walking exercise was performed on a
strongly correlated with obesity and IR. IR is a vascular running machine. The exercise intensity started from 50-60﹪
complication of DM and plays an important role in CVD HRmax, and then gradually increased to 60-70﹪ HRmax.
pathogenesis (3,13,14). Therefore, it is extremely important to For the walking plus resistance exercise group, the exer-
prevent DM cardiovascular complications and to reverse ED cise included 30 min resistance exercise following 20 min
via early IGT intervention. walking exercise. The resistance exercise focused on weight
At present, exercise is the best treatment for metabolic reduction, and included upper arm, chest and waist exercises
syndrome, and has remarkable effects on the prevention (15 pulls on the lateral pulldown device with 2-3 repeats and
of DM and CVD with IGT (5,6). Previous studies indicated 15 straight‑arm forwards using the abdominal machine with
that exercise increases energy consumption, reduces body 3-4 repeats), abdominal exercises (15-20 sit-ups on the sit-up
fat, increases muscle mass and also has a profound effect on apparatus with 2-3 repeats and 15-20 presses on the leg press
the endocrine system (4-6,11). Compared with other methods machine with 2-3 repeats) and leg exercises (15 leg presses on
for controlling IGT, exercise therapy is a low cost, simple, the leg press machine with 2-3 repeats and 15 extensions on
properly implemented and safe strategy without side-effects. the leg extension machine with 2-3 repeats).
These advantages have attracted much attention in recent
years (4-6,11). In addition, the population affected by DM Implementation and monitoring of exercise. Adaptive training
pathogenesis has gradually become younger (2,4,8,10), which was implemented for one week prior to the formal exercises.
increasingly affects the working population at its prime age. The number of heart beats within 10 sec (HR10sec) at the
It is necessary to further investigate the effects of exercise on different stages was recorded during the exercise process.
middle-aged patients with IGT and IR in order to provide a The HR was calculated as six times HR10sec. The exercise
clinical basis for exercise in the prevention of DM. intensity was adjusted and controlled based on self-reporting
Walking is one of the most simple and commonly used and the body reactions of the participants. Physiological and
fitness exercises, and resistance exercise has gained increasing biochemical indices were detected before and after the whole
attention since it is able to increase the basal metabolic rate, exercise intervention.
facilitate energy consumption and thereby increase insulin
sensitivity (5,6,11). In the current study, two different exercise Physiological and biochemical indices. Morphological param-
interventions (moderate intensity walking exercise and walking eters were measured using a body composition resistance
plus resistance exercise) were used for 24 weeks. The serum measurement instrument Biospace InBody 3.0 (Biospace
physiological and biochemical indices and vascular endothelial Co. Ltd. Soul, South-Korea) according to the national
function changes were monitored in the middle‑aged patients physiological constitution monitoring requirements, which
with IGT. The vascular endothelial function‑improving effects included BMI, body fat percentage and other variables (16).
of exercise interventions were studied, which provide a clinical The biochemical indices were detected with a variety of kits.
and theoretical basis for the prevention of early DM. The oral glucose tolerance test (OGTT) was performed for
the diagnosis of normal glucose tolerance (NGT) and IGT
Subjects and methods according to the guidelines of 2004 China diabetes prevention
and control (17). Homeostasis model assessment (HOMA):
Study subjects and groups. In this study, 61 patients with IGT HOMA-IR = fasting plasma insulin concentration (FINS,
(mean age 49.8±4.8 years) were selected based on medical mIU/l) x fasting blood glucose (FBG, mmol/l)/22.5. Brachial
screening from two residential communities (the Cangshan artery endothelium dependent vasodilation was measured
and Gushan Districts in Fuzhou, the capital city of Fujian using color Doppler supersonic diagnostic equipment
Province, China). The patients had no cardiopulmonary or (IU-22; Phillips-Medisize Corporation, Hudson, WI, USA)
systematic diseases affecting fitness to exercise. Patients with a L17-5 transducer of 17 to 5 MHz extended frequency
from a non-sport orientated population undertook a 24 week- range. Brachial artery endothelium‑dependent vasodilation:
long course of fitness exercises. The IGT participants were ΔDia-P% = (maximum diameter inside brachial artery with
randomly divided into three groups: the control group without 1 min decompression - basic diameter)/basic diameter x100.
exercise, walking exercise group and walking plus resistance
exercise group. This study followed International Journal of Statistical analysis. All experimental data are presented as
Sports Medicine's (IJSM's) ethical standards (15) and was mean ± SD. The differences in mean values between multiple
approved by the Institutional Review Board of Fujian Normal groups were evaluated using a two-way ANOVA. A paired
University and Fujian Medical University (Fuzhou, China). Student's t-test was used to evaluate statistical differences due
All participants signed a written informed consent document. to the intervention. P<0.05 was considered to indicate a statis-
tically significant result and P<0.01 was considered to indicate
Exercise models and methods. Participants in the control a notable statistical significance.
group did not participate in exercise. In the walking exercise
group, participants were requested to look straight ahead and Results
keep their stomach in, chest out, head out and shoulders back,
but relax and swing their arms rhythmically as they walked. Equilibrium analysis of vascular endothelium functions prior
The exercise intensity was at 60~70﹪ maximum heart rate to exercise intervention among the three groups. Fifty patients
 EXPERIMENTAL AND THERAPEUTIC MEDICINE 5: 1559-1565, 2013 1561

Table I. Analysis of vascular endothelium functions prior to exercise intervention in patients with IGT.

Group n CNP (pg/ml) ET-1 (pg/ml) Carotid artery IMT (mm) ΔDia-P (%)

Control 21 14.553±3.296 140.829±32.379 1.056±0.181 10.829±1.597

Walking exercise 20 14.099±2.283 141.955±32.797 1.051±0.206 10.853±1.634
Walking + resistance exercise 20 14.736±4.561 148.756±39.149 1.039±0.206 10.493±1.533
F 0.019 0.306 0.038 0.324
P-value 0.982 0.737 0.963 0.724

P<0.05 was considered to indicate a statistically significant result among the three groups. IGT, impaired glucose tolerance; CNP, C-type natri-
uretic peptide; ET-1, endothelin-1; IMT, intima-media thickness; ΔDia-P, the percentage changes in artery diameter after a 5-min compression.

Table II. Analysis of HOMA-IR and glucose metabolism prior to exercise intervention in patients with IGT.

Group n FBG (mmol/l) OGTT2h (mmol/l) Fasting insulin (mIU/l) HOMA-IR

Control 21 5.771±0.310 9.352±0.623 27.018±8.009 6.967±2.279

Walking exercise 20 5.670±0.264 9.345±0.575 26.747±8.022 6.948±2.288
Walking + resistance exercise 20 5.755±0.265 9.345±0.568 26.936±7.869 6.981±2.241
F 0.761 0.001 0.006 0.001
P-value 0.472 0.999 0.994 0.999

P<0.05 was considered to indicate a statistically significant result among the three groups. IGT, impaired glucose tolerance; FBG, fasting blood
glucose; OGTT, oral glucose tolerance test; HOMA, homeostasis model assessment; IR, insulin resistance.

Table III. Analysis of body composition prior to exercise intervention in patients with IGT.

Group n BMI (kg/m2) Body fat (%) Waist circumference (cm) Waist to hip ratio

Control group 21 27.211±1.296 25.367±2.140 91.229±4.791 0.899±0.028

Walking exercise 20 27.100±1.283 25.415±1.945 90.990±4.777 0.897±0.027
Walking + resistance exercise 20 26.523±1.259 25.630±1.272 89.161±4.269 0.898±0.023
F 1.691 0.119 1.212 0.035
P-value 0.193 0.888 0.305 0.966

P<0.05 was considered to indicate a statistically significant result among the three groups. IGT, impaired glucose tolerance.

with IGT completed the whole experiment out of 61 patients differences (P>0.05) prior to and following exercise interfer-
who began the study. Four from the control group, three from ence in the control group, with the exception of FBG (P<0.05;
the walking group and four from the walking plus resistance Table IV). The comparison of indices showed there were
group did not complete the experiment; the drop out rate was significant differences (P<0.05) for C-type natriuretic peptide
18.03%. There were no significant differences (P>0.05) in (CNP), endothelin (ET)-1, ΔDia-P, OGTT2h, fasting insulin,
each index of vascular endothelium function among the three HOMA-IR, body fat percentage, waist circumference and
groups prior to the exercise intervention (Table I). No signifi- waist to hip ratio prior to and following exercise intervention
cant differences (P>0.05) were observed in FBG, OGTT2h, in the walking exercise group, however, FBG, carotid artery
fasting insulin and HOMA-IR prior to the exercise intervention intima-media thickness (IMT) and BMI were not significantly
among the three groups (Table II). No significant differences different (P>0.05; Table V).
(P>0.05) were observed in BMI, body fat percentage, waist A comparison of indices prior to and following exercise
circumference and waist to hip ratio prior to exercise interven- intervention in the walking plus resistance exercise group
tion among the three groups (Table III). was performed. The comparison of all indices showed there
were significant differences (P<0.05) for CNP, ET-1, ΔDia-P,
Comparison of all indices prior to and following exercise OGTT2h, fasting insulin, HOMA-IR, body fat percentage,
intervention. The comparison of indices showed no significant waist circumference and waist to hip ratio prior to and
1562 LIU et al: ENDOTHELIUM-DEPENDENT VASODILATION

Table IV. Comparison of all indices before and after the exercise intervention in the control group.

Index Before intervention After intervention t P-value

ET-1 (pg/ml) 140.829±32.380 143.125±40.424 0.719 >0.05

CNP (pg/ml) 14.553±4.675 14.397±4.536 0.797 >0.05
ΔDia-P (%) 10.830±1.597 10.326±1.799 0.471 >0.05
Carotid artery IMT (mm) 1.056±0.188 1.054±0.189 0.227 >0.05
Fasting blood glucose (mmol/l) 5.771±0.310 5.676±0.259 2.197 <0.05
OGTT2h (mmol/l) 9.352±0.623 9.371±0.574 0.677 >0.05
Fasting insulin (mIU/l) 27.018±8.009 26.999±7.904 0.247 >0.05
HOMA-IR 6.967±2.279 7.010±2.249 0.289 >0.05
BMI (kg/m2) 27.211±1.296 27.162±1.283 1.214 >0.05
Body fat percent (%) 25.367±2.140 25.314±1.951 0.845 >0.05
Waist circumference (cm) 91.229±4.791 91.239±4.794 0.279 >0.05
Waist to hip ratio 0.899±0.028 0.898±0.027 1.595 >0.05

P<0.05 was considered to indicate a statistically significant result. CNP, C-type natriuretic peptide; ET-1, endothelin-1; IMT, intima-media
thickness; ΔDia-P, the percentage changes in artery diameter after a 5-min compression; OGTT, oral glucose tolerance test; HOMA, homeo-
stasis model assessment; IR, insulin resistance.

Table V. Comparison of all indices before and after exercise intervention in the walking exercise group.

Index Before intervention After intervention t P-value

ET-1 (pg/ml) 141.955±32.797 148.006±34.183 4.389 <0.01

CNP (pg/ml) 14.825±4.622 16.275±4.691 11.747 <0.01
ΔDia-P (%) 10.853±1.635 12.653±1.705 2.233 <0.05
Carotid artery IMT (mm) 1.051±0.197 1.048±0.203 1.314 >0.05
Fasting blood glucose (mmol/l) 5.670±0.564 5.585±0.528 1.091 >0.05
OGTT2h (mmol/l) 9.345±0.575 8.825±0.434 7.218 <0.01
Fasting insulin (mIU/l) 26.747±8.022 25.022±6.742 5.435 <0.01
HOMA-IR 6.948±2.288 6.224±2.019 7.857 <0.01
BMI (kg/m2) 27.138±1.749 26.332±1.779 1.443 >0.05
Body fat percent (%) 25.415±1.945 23.850±2.118 9.457 <0.01
Waist circumference (cm) 90.990±4.777 88.313±3.828 3.535 <0.01
Waist to hip ratio 0.897±0.027 0.879±0.025 11.307 <0.01

P<0.05 was considered to indicate a statistically significant result. CNP, C-type natriuretic peptide; ET-1, endothelin-1; IMT, intima-media
thickness; ΔDia-P, the percentage changes in artery diameter after a 5-min compression; OGTT, oral glucose tolerance test; HOMA, homeo-
stasis model assessment; IR, insulin resistance.

following exercise intervention in the walking plus resistance Effect on vascular endothelium functions following exercise
group, but no significant differences in FBG, carotid artery intervention. Variance analysis of vascular endothelium func-
IMT and BMI (P>0.05; Table VI). tions showed that exercise intervention significantly increased
The effect of exercise on brachial endothelium- CNP levels (P<0.05; Table VII) compared with those of the
dependent vasodilation was also assessed. Brachial artery control group. The CNP level in the walking plus resistance
endothelium‑dependent vasodilation was improved by exer- exercise group was further increased compared with that in
cise intervention in one patient. Brachial artery diameters the walking group (P<0.05; Table VII). Exercise intervention
measured at three randomly selected sites by ultrasound were markedly decreased ET-1 levels compared with those in the
0.440, 0.443 and 0.450 cm prior to exercise intervention. control group. In addition, the ET-1 level in the walking plus
However, following intervention the diameters measured at resistance exercise group was significantly lower than that in
these three sites were 0.514, 0.501 and 0.483 cm, respectively. the walking group (P<0.05, Table VII). Significant changes in
These results indicate that brachial artery vasodilation may be the percentage changes in artery diameter following a 5-min
improved by the exercise intervention. compression (ΔDia-P) were observed following exercise
 EXPERIMENTAL AND THERAPEUTIC MEDICINE 5: 1559-1565, 2013 1563

Table VI. Comparison of all indices before and after exercise intervention in the walking plus resistance exercise group.

Index Before intervention After intervention t P-value

ET-1 (pg/ml) 148.756±39.149 141.947±36.550 2.492 <0.05

CNP (pg/ml) 14.736±4.561 17.015±4.623 -9.778 <0.01
ΔDia-P (%) 10.493±1.533 13.196±2.065 2.333 <0.05
Carotid artery IMT (mm) 1.039±0.206 1.032±0.207 1.896 >0.05
Fasting blood glucose (mmol/l) 5.755±0.565 5.600±0.515 1.808 >0.05
OGTT2h (mmol/l) 9.345±0.568 8.675±0.463 11.719 <0.01
Fasting insulin (mIU/l) 26.936±7.869 24.967±6.922 7.855 <0.01
HOMA-IR 6.981±2.241 6.209±2.035 8.680 <0.01
BMI (kg/m2) 26.523±1.359 25.978±1.286 1.252 >0.05
Body fat percent (%) 25.630±1.272 23.855±1.008 11.335 <0.01
Waist circumference (cm) 89.161±4.270 87.847±3.045 2.443 <0.05
Waist to hip ratio 0.898±0.023 0.884±0.019 7.590 <0.01

P<0.05 was considered to indicate a statistically significant result. CNP, C-type natriuretic peptide; ET-1, endothelin-1; IMT, intima-media
thickness; ΔDia-P, the percentage changes in artery diameter after a 5-min compression; OGTT, oral glucose tolerance test; HOMA, homeo-
stasis model assessment; IR, insulin resistance.

Table VII. Analysis of vascular endothelium functions following exercise intervention in patients with IGT.

Group n CNP (pg/ml) ET-1 (pg/ml) Carotid artery IMT (mm) ΔDia-P (%)

Control group 17 0.156±0.898 -2.296±14.635 0.002±0.029 0.004±0.037

Walking exercise 17 -1.450±0.552b -6.051±6.165 0.003±0.019 -0.800±1.602
Walking exercise + resistance exercise 16 -2.280±1.043b,c -6.810±12.221a,c 0.007±0.011 -1.104±2.116a
F 43.003 6.479 0.508 2.924
P-value 0.000 0.003 0.605 0.062
a
P<0.05 vs. control group; bP<0.01 vs. control group; cP<0.01 vs. walking exercise group. IGT, impaired glucose tolerance; CNP, C-type natri-
uretic peptide; ET-1, endothelin-1; IMT, intima-media thickness; ΔDia-P, the percentage changes in artery diameter after a 5-min compression.

Table VIII. Analysis of HOMA-IR and glucose metabolism following exercise intervention in IGT patients.

Group n FBG (mmol/l) OGTT2h (mmol/l) Fasting insulin (mIU/l) HOMA-IR

Control group 17 0.095±0.199 -0.019±0.129 0.019±0.353 -0.043±0.681

Walking exercise 17 0.085±0.075 0.520±0.322a 1.725±1.419a 0.724±0.412a
Walking exercise + resistance exercise 16 0.155±0.182 0.670±0.256a 1.970±1.121a 0.772±0.398a
F 1.093 44.299 20.911 16.159
P-value 0.342 0.000 0.000 0.000
a
P<0.01 vs. control group. IGT, impaired glucose tolerance; FBG, fasting blood glucose; OGTT, oral glucose tolerance test; HOMA, homeo-
stasis model assessment; IR, insulin resistance.

intervention (P<0.05; Table VII), but no significant changes levels (P<0.05; Table VIII) but not the FBG level (P>0.05;
were observed between the two exercise intervention groups Table VIII). However, there were no marked changes between
(P>0.05; Table VII). the two exercise intervention groups (P>0.05, Table VIII).

Effect analysis of HOMA-IR and glucose metabolism following Effect analysis of body composition following exercise inter-
exercise intervention. Variance analysis of HOMA-IR and vention. Variance analysis of body composition demonstrated
glucose metabolism showed that exercise intervention signifi- that the exercise intervention significantly increased body
cantly decreased OGTT2h, fasting insulin and HOMA-IR fat percentage and the waist to hip ratio (P<0.05; Table IX).
1564 LIU et al: ENDOTHELIUM-DEPENDENT VASODILATION

Table IX. Analysis of body composition following exercise intervention in patients with IGT.

Group n BMI (kg/m2) Body fat (%) Waist circumference (cm) Waist to hip ratio

Control group 17 0.050±0.187 0.052±0.284 -0.010±0.164 0.001±0.003

Walking exercise 17 0.305±0.327 1.565±0.740a 2.963±3.749a 0.018±0.007a
Walking + resistance exercise 16 0.345±0.482 1.775±0.701a 1.314±2.404b 0.014±0.008a
F 1.622 49.577 6.975 37.442
P-value 0.310 0.000 0.002 0.000

P<0.01 vs. control group. bP<0.05 vs. walking exercise group. IGT, impaired glucose tolerance.
a

However, there were no significant differences between the amine levels and excess post-exercise oxygen consumption,
two exercise intervention groups (P>0.05; Table IX). Marked and improves glucose metabolism levels (5,6,20,21). Previous
changes of waist circumference were observed among the studies indicated that aerobic exercise may improve the
three groups (P<0.05; Table IX), while there were no signifi- vascular endothelial function of patients with coronary
cant differences between the two exercise intervention groups diseases (19), while resistance exercise may also improve the
(P>0.05; Table IX). symptoms of CVD (21).
A number of studies have demonstrated that exercise
Discussion may improve insulin sensitivity by increasing energy
consumption (5,6,9). In the present study, we demonstrated
Numerous studies have demonstrated that lifestyle interven- that exercise improved glucose metabolism in middle-aged
tion is able to significantly decrease the occurrence of DM patients with IGT and caused significant differences in BMI,
in the population with IGT, and that IGT is a critical stage at body fat percentage, waist circumference, waist to hip ratio,
which to prevent DM (9,12,13). Our study clearly demonstrated OGTT2h blood glucose, fasting insulin and HOMA-IR prior
that exercise intervention significantly improved endothe- to and following exercise intervention. These results indicate
lium-dependent vascular functions through enhancing the that exercise intervention may enhance insulin sensitivity,
physiological constitution, increasing insulin sensitivity and which is further supported by the findings of Smutok et al (8)
preventing further vascular deterioration during prediabetes and Melby et al (21). Notably, increased nitric oxide (NO)
mellitus. levels and decreased IR were observed in IR rats during
The patients with IGT may be considered as sub-healthy, exercise experiments, suggesting that exercise may promote
since IGT may transform into DM and increase the CVD the release of vasodilatory substances and enhance insulin
risk (9,12,13). Dysfunction of the vascular endothelium is receptor sensitivity (19,22). ED plays an important role in
closely correlated with CVD (3,13) and is also a key link of the pathogenesis of diabetic vascular complications and
DM complications (14). Usually, patients with IGT do not CVD (14,22), since vascular endothelial cells (ECs) are able to
have clear clinical symptoms and do not receive sufficient synthesize and secrete a variety of bioactive factors, including
attention. We used outpatient and physical examination ET-1 and CNP (22,23). ET-1 is a small vasoactive polypep-
records of local residents to enhance the detection of patients tide that has the strongest effect and the longest duration of
with IGT. The results showed that IGT may be the last key action as a vasoconstrictor via binding to the ET receptor in
stage at which to prevent DM. To understand the possible vivo (23,24). CNP is another vasoactive peptide that inhibits
mechanism of the transformation of IGT into DM, patients the proliferation and migration of vascular smooth muscle
with IGT were randomly divided into three groups with cells and extracellular matrix formation, in addition to acting
different exercise interventions in order to investigate the as a vasodilator (23,24). The results of the present study have
DM preventive effects. Epidemiological surveys have shown demonstrated that ET-1 levels were reduced but CNP levels
that lack of exercise is closely correlated with CVD and increased following exercise intervention. Exercise interven-
appropriate exercise is an important method for reducing the tion improved endothelial functions in middle-aged patients
risk of CVD by improving endothelial functions (11,18,19). with IGT, particularly in the walking plus resistance exercise
Therefore, the effects of two different types of exercise on group.
endothelium‑dependent vasodilation were examined in In conclusion, exercise intervention improved endothe-
patients with IGT. In general, fitness exercise included aerobic lium‑dependent vasodilation in middle-aged patients with
and resistance exercise. Aerobic exercise may increase the IGT. Walking and resistance exercise improved the body
lipoprotein lipase (LPL) activity and promote lipolysis in composition of the patients, reversed IR and increased
vivo leading to the consumption of more fat but less glycogen the ability of insulin to bind with its receptor in the target
with improved vascular endothelial functions in patients with organs (23). Furthermore, exercise reduces OGTT2h glucose
CVD (6,19). By contrast, the most significant feature of resis- changes and improves glucose tolerance (13). In the current
tance exercise is the improvement of skeletal muscle quality study, the effects of physical exercise intervention provided
and the enhancement of cardiovascular endurance (20,21). direct clinical evidence of the effectiveness of this approach
Resistance exercise increases fat oxidation, plasma catechol- for preventing early DM in patients with IGT.
 EXPERIMENTAL AND THERAPEUTIC MEDICINE 5: 1559-1565, 2013 1565

Acknowledgements 12. Rewers M, Shetterly SM, Baxter J, Marshall JA and Hamman RF:

Prevalence of coronary heart disease in subjects with normal and
impaired glucose tolerance and non-insulin-dependent diabetes
This study was supported by the National Natural Science mellitus in a biethnic Colorado population. The San Luis Valley
Foundation of China (No. 31101032 and 31271255), Fujian Diabetes Study. Am J Epidemiol 135: 1321-1330, 1992.
13. Schnell O and Standl E: Impaired glucose tolerance, diabetes,
Province Science and Technology Key Project (No. and cardiovascular disease. Endocr Pract 12 (Suppl 1): S16-S19,
2013Y01010200) and Fujian Provincial Natural Science 2006.
Foundation (No. 2008J0272 and 2011J01144). The authors 14. Bonetti PO, Lerman LO and Lerman A: Endothelial dysfunction:
a marker of atherosclerotic risk. Arterioscler Thromb Vasc
wish to thank the staff in the Affiliated Hospitals of Fujian Biol 23: 168-175, 2003.
Medical University, who contributed to this study. 15. Harriss DJ and Atkinson G: Update - ethical standards in sport
and exercise science research. Int J Sports Med 32: 819-821, 2011.
16. Jiang CM and Zhang YM: The advancement and developing
References trend of physical fitness study in China. China Sport Sci 28:
25-32, 2008 (In Chinese).
 1. Mazzali G, Di Francesco V, Zoico E, et al: Interrelations between 17. The Writing Group of Guidelines of China Diabetes Prevention
fat distribution, muscle lipid content, adipocytokines, and insulin and Control: The diagnosis and classification of diabetes. In:
resistance: effect of moderate weight loss in older women. Am J Guidelines of China Diabetes Prevention and Control. Guidelines
Clin Nutr 84: 1193-1199, 2006. of China Diabetes Prevention and Control Writing Group (ed).
 2. Pratley RE and Gilbert M: Clinical management of elderly 1st edition, Peking University Medical Press, Peking, pp10-12,
patients with type 2 diabetes mellitus. Postgrad Med 124: 2004.
133-143, 2012. 18. Brendle DC, Joseph LJ, Corretti MC, Gardner AW and Katzel LI:
 3. Reaven GM: Insulin resistance: the link between obesity and Effects of exercise rehabilitation on endothelial reactivity in
cardiovascular disease. Med Clin North Am 95: 875-892, 2011. older patients with peripheral arterial disease. Am J Cardiol 87:
 4. Haque N, Salma U, Nurunnabi TR, Uddin MJ, Jahangir MF, 324-329, 2001.
Islam SM and Kamruzzaman M: Management of type 2 diabetes 19. Georgiou D and Belardinelli R: Exercise and coronary endo-
mellitus by lifestyle, diet and medicinal plants. Pak J Biol Sci 14: thelial function. N Engl J Med 343: 147-148, 2000.
13-24, 2011. 20. Eriksson J, Taimela S, Eriksson K, Parviainen S, Peltonen J and
 5. O'Gorman DJ and Krook A: Exercise and the treatment of Kujala U: Resistance training in the treatment of non-insulin-
diabetes and obesity. Med Clin North Am 95: 953-969, 2011. dependent diabetes mellitus. Int J Sports Med 18: 242-246, 1997.
 6. Ryan AS: Exercise in aging: its important role in mortality, 21. Melby C, Scholl C, Edwards G and Bullough R: Effect of acute
obesity and insulin resistance. Aging health 6: 551-563, 2010. resistance exercise on postexercise energy expenditure and
 7. Martins AR, Nachbar RT, Gorjao R, et al: Mechanisms resting metabolic rate. J Appl Physiol 75: 1847-1853, 1993.
underlying skeletal muscle insulin resistance induced by fatty 22. Hamed S, Brenner B and Roguin A: Nitric oxide: a key factor
acids: importance of the mitochondrial function. Lipids Health behind the dysfunctionality of endothelial progenitor cells in
Dis 11: 30, 2012. diabetes mellitus type-2. Cardiovasc Res 91: 9-15, 2011.
 8. Smutok MA, Reece C, Kokkinos PF, et al: Effects of exercise 23. Emori T, Hirata Y, Imai T, Eguchi S, Kanno K and Marumo F:
training modality on glucose tolerance in men with abnormal Cellular mechanism of natriuretic peptides-induced inhibition of
glucose regulation. Int J Sports Med 15: 283-289, 1994. endothelin-1 biosynthesis in rat endothelial cells. Endocrinology
 9. Pan XR, Li GW, Hu YH, et al: Effects of diet and exercise in 133: 2474-2480, 1993.
preventing NIDDM in people with impaired glucose tolerance. 24. Evans JJ, Youssef AH, Yandle TG, Lewis LK and Nicholls MG:
The Da Qing IGT and Diabetes Study. Diabetes Care 20: Effects of endothelin-1 on release of adrenomedullin and C-type
537-544, 1997. natriuretic peptide from individual human vascular endothelial
10. Tuomilehto J, Lindström J, Eriksson JG, et al: Prevention of type cells. J Endocrinol 175: 225-232, 2002.
2 diabetes mellitus by changes in lifestyle among subjects with
impaired glucose tolerance. N Engl J Med 344: 1343-1350, 2001.
11. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF,
Lachin JM, Walker EA and Nathan DM: Reduction in the
incidence of type 2 diabetes with lifestyle intervention or
metformin. N Engl J Med 346: 393-403, 2002.

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