Original Article Clinical Care/Education INTRODUCTION DIABETES & METABOLISM JOURNAL

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1 Originl Article Clinicl Cre/Eduction pissn eissn DIABETES & METABOLISM JOURNAL Arteril Stiffness by Aerobic Exercise Is Relted with Aerobic Cpcity, Physicl Activity Energy Expenditure nd Totl Ft but not with Insulin Sensitivity in Obese Femle Ptients with Type 2 Dibetes Ji Yeon Jung 1, *, Kyung Wn Min 2, *, Hee Jung Ahn 1, Hwi Ryun Kwon 1, Je Hyuk Lee 2, Kng Seo Prk 2, Kyung Ah Hn 2 1 Dibetes Center, Eulji Generl Hospitl, Seoul, 2 Deprtment of Internl Medicine, Eulji University School of Medicine, Dejeon, Kore Bckground: Arteril stiffness is n importnt fctor in therosclerosis. Thus we exmined whether erobic exercise could reduce rteril stiffness in obese women with type 2 dibetes without dibetic compliction. Methods: A totl of 35 women with type 2 dibetes (body mss index, 26.6±2.8 kg/m 2 ; ge, 56.4±1.9 yers; durtion of dibetes, 4.7±4.8 yers) were ssigned to erobic exercise group (AEG) or control group (CG). AEG completed 12-week exercise progrm (3.6 to 5.2 metbolic equivlents, 3 dy/week, 60 min/dy), with their exercise ctivities monitored by ccelerometers. We mesured bdominl totl ft re (TFA), viscerl ft re (VFA), nd subcutneous ft re (SFA) by computed tomogrphy, insulin sensitivity by insulin tolernce test (KITT), nd ugmenttion index (AIx) by SphygmoCor t bseline nd t the end of the 12-week progrm. Results: The AIx ws improved in the AEG compred with the CG (P<0.001). The percent chnge of AIx hd significnt correltion with the improvement of physicl ctivity energy expenditure (PAEE), erobic cpcity, TFA, nd SFA (r= 0.416, P=0.013; r=0.560, P<0.001; r=0.489, P=0.003; r=0.531, P=0.001, respectively), but not with insulin sensitivity, energy intke, or VFA. Conclusion: Improvement in ortic stiffness by erobic exercise is relted with the improvement of erobic cpcity, PAEE, nd totl ft but not with insulin sensitivity or energy intke in obese women with type 2 dibetes. Keywords: Abdominl ft; Augmenttion index; Dibetes mellitus, type 2; Moderte erobic exercise; Vsculr stiffness INTRODUCTION Dibetes is mjor globl public helth concern tht ffects 347 million people hve dibetes worldwide [1], which is correlted with incresing crdiovsculr disese tht is responsible for 52% deths in type 2 dibetes [2]. In ddition, people with type dibetes re lso t 2 to 4 times higher risk of developing crdiovsculr diseses compred with the norml popultion [3]. The highest prevlence of crdiovsculr disese occurred mong people with dibetes when hyperglycemi is ccompnied by other risk fctors such s hypertension, dyslipidemi, hyperinsulinemi, nd obesity [4]. Especilly, obesity is n independent risk fctor for crdiovsculr diseses [5]. However, reducing weight in obese ptients with type 2 dibetes hs been shown to be effective in minimizing crdiovsculr disese-relted deths [5]. Therefore, losing weight in obese ptients with Corresponding uthor: Kyung Ah Hn Deprtment of Internl Medicine, Eulji University School of Medicine, 77 Gyeryong-ro 771beon-gil, Jung-gu, Dejeon , Kore E-mil: hk1114@yhoo.co.kr *Ji Yeon Jung nd Kyung Wn Min contributed eqully to this study s first uthors. Received: Dec. 18, 2013; Accepted: Apr. 10, 2014 This is n Open Access rticle distributed under the terms of the Cretive Commons Attribution Non-Commercil License ( which permits unrestricted non-commercil use, distribution, nd reproduction in ny medium, provided the originl work is properly cited. Copyright 2014 Koren Dibetes Assocition

2 Jung JY, et l. type 2 dibetes will be effective in preventing crdiovsculr diseses. In ptients with type 2 dibetes, incresed rteril stiffness is regrded s n erly stge of rteriosclerosis nd it is lso regrded s risk fctor nd prognostic mrker for crdiovsculr diseses [6]. Recently, method of mesuring ugmenttion index (AIx) nd centrl ortic pressure noninvsively by nlyzing the pulse wves of peripherl rtery ws introduced [7], nd lrge rndomized study reported tht AIx nd centrl ortic pressure re ssocited with the development of crdiovsculr diseses [8]. It is well known tht dequte exercise, regrdless of ny chnges in weight, independently improves crdic function nd rteril complince, either preventing or stopping the progression of coronry rtery diseses [9]. Kingwell et l. [10] compred the pulse wve velocity (PWV) of thletes nd norml people nd found tht regulr nd constnt exercise decreses PWV, nd DeSouz et l. [11] showed tht helthy dults who prticipted in moderte erobic exercises for 2 to 3 months hd improved rteril intim-medi thickness nd rteril complince. The subjects of previous studies regrding rteril complince only included norml popultion or ptients with hypertension. However rteril stiffness my increse not only by hypertension but lso by other risk fctors of crdiovsculr diseses such s old ge, obesity, dibetes, nd dyslipidemi. Furthermore, reserch regrding the correltion between reduced bdominl ft from exercises nd improved rteril complince in dibetic ptients is still lcking. Therefore, the ims of this study were to (1) exmine whether erobic exercise cn llevite rteril stiffness in ptients with type 2 dibetes; (2) identify the correltion between the chnges in rteril stiffness nd physicl ctivity level, erobic cpcity, bdominl ft, nd insulin resistnce. METHODS Study subjects A totl of 35 type 2 dibetes ptients in the Dibetes Center t Eulji Hospitl were enrolled from Mrch to July in Subjects tht were 45 to 65 yers old nd overweight with body mss index (BMI) over 23 kg/m 2 or obese femle ptients with hemoglobin A1c (HbA1c) levels less thn 10% were included in this study. At bseline, 24, 10, nd 1 of the 35 ptients were under exercise nd diet, orl hypoglycemic gent, nd insulin tretments, respectively. The exclusion criteri were: type 1 dibetes ptients, congestive hert filure, uncontrollble rrhythmi, severe vlvulr disese, ptients with mlignnt tumor, ptients under renl replcement therpy, ptients tht were difficult to perform trcking observtions, ptients refusing to be investigted, smokers, nd ptients who chnged the medicine tht they were tking. The Institutionl Review Bord of the Clinicl Reserch Institute t Eulji Hospitl pproved the study protocol nd informed consent ws obtined from ech subject. Study design During the 2 weeks of screening period, we requested tht prticipnts mintin their dily routine physicl ctivity nd dietry intke before beginning of the study. Two weeks lter, the subjects were rndomized into erobic exercise group (AEG) or control group (CG). AEG group ws performed wlking exercise 3 dy/week for 60 min/dy t n exercise intensity of higher thn 4 ccording to n ccelerometer, corresponding to 3 to 5 metbolic equivlents (METs) [8] for 12 weeks, which corresponds to n energy expenditure of pproximtely 500 kcl/dy. During 12 weeks, the subjects were monitored every 2 weeks for ccurte mesurements of their complince, energy intke (EI), nd physicl ctivity energy expenditure (PAEE). Mesured ctegories nd methods Anthropometry nd biochemicl tests The subjects height, weight, nd wist circumference were mesured t bseline nd fter the 12-week period. The height nd weight were mesured when subjects were only wering light clothing, nd BMI ws clculted by dividing weight (kg) by the squre of height (m 2 ). Wist circumference ws mesured between the lower ribs nd ilic crest fter exhle with tpe mesure, nd blood pressure ws mesured fter 10 minutes of rest while sitting with mercury sphygmomnometer (Ymsu, Tokyo, Jpn). As for biochemicl tests, venous blood ws collected 10 hours of fsting, which ws centrifuged t 3,000 rpm for 15 minutes to seprte the serum tht ws stored t 70 C before being nlyzed. Fsting glucose ws mesured by glucose oxidtion method nd HbA1c level ws mesured using highperformnce liquid chromtogrphy bsed on ion-exchnge resin. Cholesterol, triglyceride, high density lipoprotein cholesterol, nd low density lipoprotein cholesterol (LDL-C) were mesured by enzyme-linked immunosorbent ssy using n utomtic chemistry nlyzer (Hitchi 7170; Hitchi, Tokyo, Jpn). 440

3 Improvement in rteril stiffness by exercise Insulin resistnce ws clculted using insulin tolernce test (KITT) [12]. After 10 hours of fsting, n insulin tolernce test ws performed. A 20-guge ctheter ws inserted into vein in one hnd of the subject for blood collection nd nother ctheter into the vein on the other side for insulin injection nd glucose infusion t the end of the test. The pproprite insulin concentrtion (0.1 U per 1 kg) ws clculted nd prediluted insulin (Humulin R; Eli Lilly, Indinpolis, IN, USA) ws injected into the ntebrchil vein t resting stte, while blood ws collected from the vein in the opposite hnd t bseline, 3, 6, 9, 12, nd 15 minutes fterwrds. One hundred milliliter of 20% glucose solution ws infused 15 minutes fter blood collection to prevent hypoglycemi, while the blood ws immeditely centrifuged to mesure blood glucose levels. The glucose concentrtions tht were mesured t different time points during insulin resistnce test were entered into computer softwre, where they were converted to ech respective nturl logrithm nd the slope of regression line ws mesured using the vlues t 3 to 15 minutes. From this the hlf-life (t1/2) which is the time tken for bseline glucose level to drop by hlf ws clculted nd the rte constnt for plsm glucose disppernce (KITT), the insulin resistnce index, ws obtined using the formul: KITT=0.693/(t1/2) 100 (%/min). AIx ws cquired by mesuring rteril stiffness nd pulse wve reflection using SphygmoCor system (SphygmoCoR; At- Cor Medicl Pty Ltd., Sydney, Austrili). The pulse pressure (PP) wveform of peripherl rtery ws mesured with pplntion tonometer. All mesurements were tken fter t lest 5 minutes of rest while sitting with either right rdil rtery for right-hnded subjects or left trnsrdil coronry rtery for left-hnded subjects. When 40 continuous wveforms were recorded, vlidted trnsform function ws used to obtin the PP wveform of ort, nd PWV ws used s n evlution index for ort stiffness. At lest two mesurements per subject were performed. These mesurements were checked whether the qulity index provided by the softwre ws over 80% nd whether the vritions between ort PP wveforms were miniml by three medicl doctors, fter which only the vlid mesurements were included. Definitions of mjor hemodynmic indices [13]: (1) Augmenttion pressure (AP): mximum blood pressure (mm Hg) t the inflection point of systolic blood pressure; (2) AIx: AIx is this ortic AP expressed s percentge of ortic PP: AIx=AP/ PP 100 (%); (3) high AIx vlues denote severe ortic stiffness; (4) AIx djusted to her rte of 75% (AIx@75): since AIx is ffected by hert rte (HR), it is djusted to stndrd HR of 75 bpm, the SphygomoCor Px softwre utomticlly decreses AIx by 4.8% per every 10 bpm rise in HR. This only pplies to HR from 40 to 110 bpm. Exercise intervention The CG did not prticipte in ny exercise progrms, while AEG performed 60 minutes of wlking exercise t n exercise intensity between 3.6 nd 5.2 METs (Lifecorder ctivity levels 4 to 6) [14] three times per week to consume 500 kcl every dy for 12 weeks. Both groups received one dietry eduction progrm t the beginning of the intervention. Mesurements of physicl ctivity level nd energy intke To estimte the physicl ctivity level of ech subject, n ccelerometer (Lifecorder; Suzuken Co., Ngoy, Jpn) ws used. The ge, gender, height, weight, nd mesurement strt dte nd time of ech subject t bseline were entered. All subjects were requested to ttch n ccelerometer to their belt t ll times except during sleep or shower during the intervention period nd chnges in weight were recorded every 2 weeks. Totl energy expenditure (TEE), PAEE, nd energy expenditure of ech ctivity intensity levels were nlyzed. The subjects were instructed to fill out 3-dy mel record (twice during weekdys nd once during weekend) nd visited the hospitl every 4 weeks to review their intke records nd investigte their overll dietry intke. All subjects prticipted in prior eduction progrm bout how to fill out the mel record, where they were instructed to record ll the food tht they hve eten in one dy nd their ingredients for ech mel, s well s ny dietry supplements or sncks. To increse the ccurcy of the records, professionl dietitins used life-size food models (Kore Mirge Replic Inc., Incheon, Kore), mesuring cups, mesuring spoons, nd estimted food size by eye mesurements of food photos (The Koren Dietetic Assocition, 1999) to review the mel records with the subjects when the dietry questionnires were collected. Mel record dt were nlyzed with computer-ided nutritionl nlysis progrm (CAN-Pro version 2.0; Koren Nutrition Society, Seoul, Kore) to be converted to dietry intke. Grded exercise test The grded exercise test ws performed using sttionry bicycle (ER 900, D Bits; JAGER, Wuerzburg, Germny), incresing the power by 20 W in every 2 minutes until the sub- 441

4 Jung JY, et l. jects could not continue exercising. Subjects hert bets per minute, oxygen uptke, work done, nd brething rte were utomticlly recorded s numbers nd grphs every 15 seconds, while blood pressure ws recorded every 2 minutes by n utomtic sphygmomnometer before, during, nd fter exercise. We mesured nerobic threshold using Jeger Oxycon Delt system. Computed tomogrphy Computed tomogrphy (GE, Milwukee, WI, USA) of bdominl ft ws mesured bsed on methods used in previous studies, rdiogrphic imges were tken from the 4th to 5th lumber body to belly button with 10 mm bove nd below the rnge. Ft density ws mesured in Hounsfield unit in the rnge from 150 to 50 nd ws reconstructed. In other words, the totl bdominl ft re within the bdominl cvity ws clculted using computer nd the viscerl ft re (VFA) ws obtined by mesuring the inner re with the bdomen nd the dorsl peritoneum s the boundry. The subcutneous ft re (SFA) ws clculted by subtrcting the totl bdominl ft by VFA [15]. Sttisticl nlysis The men nd stndrd devition for different vribles in this study were performed using SPSS version 15.0 (SPSS Inc., Chicgo, IL, USA). The sttisticl differences in physicl chrcteristics, biochemicl test results, bdominl ft, nd insulin resistnce of both CG nd AEG before nd fter the 12-week period were determined using pired t-test, nd the differences between the groups were determined using independent t-test nd nlysis of covrince, nd finlly bivrite correltion test ws used. Sttisticl significnce ws set t P<0.05. RESULTS Bseline clinicl chrcteristics A totl of 35 (CG=18, AEG=17) subjects were enrolled for this study. The verge ge ws 56.5±3.4, verge dibetes durtion ws 4.7±4.8 yers, nd verge BMI ws 26.6±1.9 kg/m 2. Although there were no significnt differences in ge (P=0.072), dibetes durtion (P=0.488), nd BMI (P=0.071) between the two groups (Tble 1), the wist circumference ws higher in CG compred with AEG (P=0.006). Furthermore, the verge HbA1c (P=0.986), KITT (P=0.628) which is the insulin resistnce index, nd AIx@75 (P=0.115) were similr in both groups (Tble 1). There were no chnges in drug intke of subjects in ttempt to Tble 1. Clinicl chrcteristics t the bseline Chrcteristic AEG (n=17) CG (n=18) P vlue Age, yr 55.4± ± Dibetes durtion, yr 4.1± ± BW, kg 63.4± ± BMI, kg/m ± ± WC, cm 85.9± ± Lb finding FPG, mg/dl HbA1c, % KITT, %/min SBP, mm Hg DBP, mm Hg TC, mg/dl TG, mg/dl HDL-C, mg/dl LDL-C, mg/dl Abdominl ft, cm 2 TFA VFA SFA 134.3± ± ± ± ± ± ± ± ± ,361.3±7, ,175.2±4, ,186.1±5, ± ± ± ± ± ± ± ± ± ,090.1±6, ,757.1±2, ,333.0±6, Aerobic cpcity, AT-VO ± ± AIx@75, % 26.3± ± Vlues re presented s men±stndrd devition. P vlues re obtined by independent t-test. AEG, erobic exercise group; CG, control group; BW, body weight; BMI, body mss index; WC, wist circumference; FPG, fsting plsm glucose; HbA1c, hemoglobin A1c; KITT, insulin sensitivity by insulin tolernce test; SBP, systolic blood pressure; DBP, distolic blood pressure; TC, totl cholesterol; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TFA, totl ft re; VFA, viscerl ft re; SFA, subcutneous ft re; AT-VO2, nerobic threshold-oxygen consumption; AIx@75, ugmenttion index 75%. prevent hypoglycemi during the 12-week period. At bseline, 13 nd 9 subjects, 3 nd 7 subjects, nd 1 nd 0 subjects in AEG nd CG were receiving exercise nd diet, orl hypoglycemic gent, nd insulin therpies, respectively, but there were no significnt differences in receiving different types of therpy between the groups. Chnges in energy expenditure nd energy intke There were no significnt difference in the TEE (P=0.741), PAEE (P=0.539), nd EI (P=0.419) t bseline between groups. After 12 weeks, the TEE (P=0.042) nd PAEE (P=0.001) of AEG incresed from bseline, but no differences were observed in CG (P=0.651, P=0.572, respectively). After 12 weeks, the 442

5 Improvement in rteril stiffness by exercise Tble 2. Totl nd physicl ctivity energy expenditure nd dietry energy intke in ech group t the bseline nd during the 12 weeks intervention (kcl/dy) TEE Bseline During intervention % Chnge b PAEE Bseline During intervention % Chnge b EI Bseline During intervention % Chnge b AEG CG P vlue 1,876.0± ,195.5± ± ± ± ±46.3 1,909.0± ,634.5± ±10.8 1,898.4± ,910.2± ± ± ± ±22.2 1,956.9± ,730.1± ± < Vlues re presented s men±stndrd devition. P vlues re obtined by independent t-test. AEG, erobic exercise group; CG, control group; TEE, totl energy expenditure; PAEE, physicl ctivity energy expenditure; EI, energy intke. P<0.05 compred to bseline within group, b Chnge (percent chnge) ws clculted s (12 weeks vlue bseline vlue) 100/bseline vlue. chnges in TEE (P=0.027) nd PAEE (P=0.001) were significntly higher in AEG compred with CG (Tbles 2 nd 3). In CG, EI decresed significntly from 1,956.9±176.8 to 1,730.1±284.9 kcl/dy (P<0.001), nd AEG lso showed significnt decrese in EI, from 1,909.0±169.0 to 1,634.5±253.0 kcl/dy (P<0.001), but the chnges in EI were not significntly different between the two groups (Tbles 2 nd 3). While chnge in AIx@75 ws ssocited with chnges in TEE (r= 0.376, P=0.026) nd PAEE (r= 0.416, P=0.013), it ws not correlted with the chnge in EI (Tble 4). Chnges in nthropometric nd biochemicl indices After 12 weeks, both AEG nd CG showed significnt decreses in weight (P<0.001 nd P=0.01, respectively), BMI (P<0.001 nd P=0.02, respectively), nd wist circumference (P<0.001 nd P=0.04, respectively) from bseline (Tble 3, Fig. 1). After 12 weeks, the decreses in weight, BMI, nd wist circumference were significntly were greter in AEG compred with CG (P=0.039, P=0.039, nd P=0.020, respectively), nd the decreses in triglyceride level ws lso greter in AEG thn in CG (P=0.034). However the chnge in insulin resistnce ws not significntly different between two groups (Tble 3, Fig. 1). Although the chnge in AIx@75 ws significntly correlted with chnge in wist circumference (r=0.348, P=0.044), it ws not ssocited with insulin resistnce improvement significntly (Tble 4). Tble 3. Chnges in nthropometric, insulin sensitivity, regionl ft, erobic cpcity, nd AIx mong two groups Anthropometric BW, kg BMI, kg/m 2 WC, cm Abnorml ft re, cm TFA VFA SFA Aerobic cpcity (AT-VO2), ml/min/kg Insulin sensitivity (KITT), %/min AEG Bseline After % Chnge Bseline After % Chnge 63.4± ± ±3.3 35,090.1±6, ,757.1±2, ,333.0±6, ±5.8 b 24.8±1.4 b 81.0±3.9 b 4.9± ± ±3.2 30,730.8±6,991.1 b 13.8±7.9 14,757.1±2,708.5 b 17.6± ,217.4±6,310.8 b 11.3± ± ± ±5.8 39,361.3±7, ,175.2±4, ,186.1±5,858.8 CG 65.9±7.1 b 26.5±2.4 b 87.9±5.9 b 2.8± ± ±3.8 37,402.2±6, ± ,175.2±4, ± ,957.2±5,563.5 b 4.8±10.2 P vlue ± ±5.4 b 88.3± ± ± ±43.1 < ± ± ± ± ± ± AIx@75, % 30.2± ±9.9 b 27.4± ± ±7.1 b 20.5±25. 1 <0.001 Vlues re presented s men±stndrd devition. P vlues re obtined by independent t-test between groups. AIx, ugmenttion index; AEG, erobic exercise group; CG, control group; BW, body weight; BMI, body mss index; WC, wist circumference; TFA, totl ft re; VFA, viscerl ft re; SFA, subcutneous ft re; AT-VO2, nerobic threshold-oxygen consumption; KITT, insulin sensitivity by insulin tolernce test; AIx@75, ugmenttion index 75%. % Chnge (percent chnge) ws clculted s (12 weeks vlue bseline vlue) 100/bseline vlue, b P<0.05 significnce from pired t-test within group. 443

6 Jung JY, et l. Tble 4. Fctors ssocited with percent chnge of including ll groups Fctor Chnges in bdominl ft After 12 weeks intervention, AEG showed significnt decreses in totl ft re (TFA; P<0.001), VFA (P<0.001), nd SFA (P<0.001) from bseline. On the other hnd, CG showed no significnt differences in TFA (P=0.103) or VFA (P=0.356), but their SFA decresed significntly (P=0.047) from bseline. After 12 weeks, the chnges in TFA (P=0.010), VFA (P=0.017), nd SFA (P=0.044) decresed significntly in AEG compred with CG (Tble 3, Fig. 1). Although the chnge in ws significntly relted to the chnges in SFA (r=0.531, P=0.001) nd TFA (r=0.489, P=0.003), it ws not ssocited with VFA (Tble 4). R ΔAIx@75 P vlue ΔBW ΔBMI ΔWC ΔTFA ΔVFA ΔSFA ΔFPG ΔHbA1c ΔKITT ΔTC ΔTG ΔHDL-C ΔLDL-C ΔSBP ΔDBP ΔTEE ΔPAEE ΔEI ΔAT-VO <0.001 AIx@75, ugmenttion index 75%; BW, body weight; BMI, body mss index; WC, wist circumference; TFA, totl ft re; VFA, viscerl ft re; SFA, subcutneous ft re; FPG, fsting plsm glucose; HbA1c, hemoglobin A1c; KITT, insulin sensitivity by insulin tolernce test; TC, totl cholesterol; TG, triglyceride; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; SBP, systolic blood pressure; DBP, distolic blood pressure; TEE, totl energy expenditure; PAEE, physicl ctivity energy expenditure; EI, energy intke; AT-VO2, nerobic threshold-oxygen consumption. % Chnge of BMI nd bdominl ft BMI TFA VFA SFA Chnges in erobic cpcity nd AIx After 12 weeks, the erobic cpcity significntly incresed in AEG from bseline (P<0.001), while CG did not show ny differences, nd the chnge in erobic cpcity incresed significntly in AEG compred with CG (P<0.001). The differences in erobic cpcity between the two groups ws still significnt even fter djusting for subjects bseline ge, weight, wist circumference, totl cholesterol, LDL-C, nd erobic cpcity (P=0.002) (Tble 3, Fig. 2). After 12 weeks, the ortic AIx@75 decresed significntly in AEG from bseline (P<0.001), while it ws incresed in CG from bseline (P<0.001). The difference in chnges of ortic AIx@75 AEG CG Fig. 1. Chnge in body weight nd bdominl ft fter 3 months intervention mong two groups. BMI, body mss index; TFA, totl ft re; VFA, viscerl ft re; SFA, subcutneous ft re; CG, control group; AEG, erobic exercise group. P<0.05 from independent t-test. % Chnge of Alx, AC, nd PAEE AIx@75 AC PAEE AEG CG Fig. 2. Chnge in ugmenttion index 75% (AIx@75), erobic cpcity nd physicl ctivity energy expenditure (PAEE) fter 3 months intervention mong two groups. AEG, erobic exercise group; CG, control group; AC, erobic cpcity. P<0.05 from independent t-test. 444

7 Improvement in rteril stiffness by exercise % Chnge of AIx@ Fig. 3. Correltion between physicl ctivity energy expenditure (PAEE), erobic cpcity (AC), nd ugmenttion index 75% (AIx@75). of AEG nd CG fter 12 weeks ws significnt (P<0.001) (Tble 3), nd this significnce ws mintined even fter djusting for ge, weight, wist circumference, totl cholesterol, nd LDL-C (P<0.001). The chnge in ortic AIx@75 hd significnt correltion with the chnge in crdiorespirtory fitness (r= 0.560, P<0.001) (Tble 4, Fig. 3). DISCUSSION % Chnge of AC nd PAEE AC PAEE Incresed rteril stiffness gives rise to left ventriculr overlod nd increses the tension of blood vessel wll, consequently leding to incresed risks of crdiovsculr diseses. Arteril stiffness cn be chnge fter exercise. Indeed, Lee et l. [16] showed tht n cute tredmill exercise (60% HRmx) in ptients with hypertension cn led to decresed blood pressure nd improved vsculr complince. Furthermore, improvements of vsculr complince ws greter in the 12 weeks compred with t the 6 weeks mong subjects with hypertension tking ntihypertensive drugs, which indicted prolonged erobic exercise showed much effectiveness lthough temporry erobic exercise does improve vsculr complince [17]. Also, Mustt et l. [18] reported tht erobic exercise 60 min/dy for 3 dy/week for 12 weeks hd n effect of significntly decresing rteril stiffness in ptients with predilysis chronic kidney disese. In line with previous studies, this study showed AIx ws significntly decresed in AEG compred with CG. The possible reson for the restortion of vsculr complince fter exercise is the ugmented blood flow nd blood pressure during exercise helps mintin the norml functions of ortic endothelium nd efficiently supplies blood to rteriole [19]. In ddition, the incresed production of nitric oxide in vsculr endothelium with exercise might be possible reson for the benefits of exercise-induced decrese in rteril stiffness [20]. In generl, rteril stiffness cn be ffected by ge, obesity, hypertension, nd dibetes, which re ll risk fctors for crdiovsculr diseses [21]. Arteril stiffness hs lso shown to be correlted with insulin resistnce becuse incresed insulin resistnce hs been known to induce rteril stiffness through vrious mechnisms such s ccelerted sympthetic nervous system, incresed sodium uptke in kidneys, impired vsculr diltion, nd ccelerted renin-ngiotensin-ldosterone system. These hve been known to show significnt correltion with AIx nd fsting blood glucose [22], nd Wilkinson et l. [23] showed tht AIx is incresed in dibetes. However, no differences in chnges of fsting blood glucose, HbA1c, nd KITT were observed between AEG nd CG in this study, nd no correltion between these vribles nd rteril stiffness ws observed. A previous study reported tht intense exercise is required to increse insulin sensitivity [24], while long-term period of exercise is required for moderte intense exercise [25,26]. Furthermore, Mustt et l. [18] reported tht only 12 weeks of erobic exercise is not sufficient to increse homeostsis model ssessment of insulin resistnce (HOMA-IR), nd mny other fctors re involved in incresing HOMA-IR. However this study did not hve enough exercise intensity, mount, nd durtion to increse insulin sensitivity, which might be reson tht chnges in insulin sensitivity hd no correltion with chnges in AIx in this study. Further study tht studies the ssocition between enhnced insulin sensitivity nd rteril stiffness with vrying exercise intensity nd durtion is wrrnted. Arteril stiffness nd bdominl ft re known to show significnt correltion. An qurobics exercise for 60 min/dy for 3 dy/week for 8 weeks mong middle-ged obese women reduced body ft nd incresed vsculr complince [27], while Kim et l. [28] showed significnt reltionship between rteril stiffness mesured by PWV nd wist circumference but not with weight nd BMI. In line, this study lso showed correltion between chnges in AIx nd chnges in wist circumference but not with weight nd BMI. As such, weight nd BMI 445

8 Jung JY, et l. hs, until now, filed to show ny consistent correltion with long-term rteril clcifiction nd rteril stiffness becuse BMI does not only reflect body ft but lso muscle mss [29]; therefore, the ssocition between BMI nd rteril stiffness cn differ depending on the rtio of ft nd muscle. Furthermore, we found tht AEG hd significntly higher reductions in totl bdominl ft, viscerl ft, nd subcutneous ft compred with CG, of which chnges in totl bdominl ft nd subcutneous ft showed significnt correltion with chnges in AIx, suggesting tht bdominl ft hs lrger implictions on AIx thn weight. Although chnges in viscerl ft did not such significnt correltion, its P vlue ws 0.059, which is very close to being significnt, therefore further study with lrger cohort nd longer durtion my be required to confirm this results. Most studies regrding exercise reported tht exercise lone does not hve lrge effect on weight reduction [30,31], but here we showed not only the significnt reduction in weight of AEG ( 3.1 kg) but lso significnt reduction in subcutneous ft of CG, unlike the previous studies. We speculte tht the reson for such controversy is becuse both groups hd reduced food intke t the end of study compred with bseline. However there ws no difference in clorie intke in both groups. Arteril stiffness hs been shown to be ssocited with incresed erobic exercise cpcity through regulr erobic exercise [32]. Yoon et l. [33] showed tht crotid-femorl rtery PWV ws negtively ssocited with VO2mx which is n index of crdiorespirtory fitness mong old-ged women (r= 0.533). Mustt et l. [18] lso showed significnt ssocition between the incresed VO2mx nd AIx fter 12 weeks of erobic exercise with 40% to 60% intensity. This study lso showed tht AEG hd incresed erobic cpcity compred with CG, nd the enhnced crdiorespirtory fitness showed negtive correltion with reduced rteril stiffness (r= 0.560), similrly to previous studies, nd this hd the highest correltion mong other fctors. As such, rteril complince enhncement fter exercise is known to be due to the incresed ortic complince, reduced peripherl blood vessel resistnce, restortion of complince, chnges in plsm volume, nd chnges in endocrine system [34,35]. Aerobic exercise cpcity is strong predictor of totl mortlity due to crdiovsculr diseses [36], nd lthough this is gretly reduced in ptients with type 2 dibetes [37], regulr exercise cn restore crdiorespirtory fitness nd reduce risk fctors for crdiovsculr diseses. The Americn Dibetes Assocition prticulrly emphsizes the dvntges of regulr physicl ctivities in dibetes prevention nd tretment nd recommends more thn 30 minutes of moderte exercise every dy [38]. They re lso recommending more thn 150 minutes of moderte exercise (50% to 70% of HRmx) every week nd more thn three times per week of erobic exercise, especilly to control blood glucose levels, mintin weight, nd reduce risks of crdiovsculr diseses [39]. In ddition, this study showed tht chnges in AIx does not hve significnt reltionship with chnges in clorie intke but does hve negtive correltion with TEE nd PAEE. The limittions of this study were tht the cohort size ws smll nd tht this ws only preliminry study. Also, this study does not provide ny clues regrding how exercise intensity, mount, nd durtion cn ffect weight reduction nd insulin resistnce. Therefore further study with lrger cohort with differing exercise intensity, mount, nd durtion is needed. In conclusion, 12 weeks of moderte erobic exercise cn reduce weight nd bdominl ft, llevite rteril stiffness, nd improves erobic cpcity but does not decrese insulin resistnce. In ddition, chnges in rteril stiffness ws more ssocited with wist circumference nd chnges in bdominl ft rther thn weight, nd with chnges in PAEE rther thn chnges in EI. These suggested tht moderte intensity exercise improved rteril stiffness with reltion to crdiorespirtory fitness nd lso with centrl obesity in type 2 dibetes. CONFLICTS OF INTEREST No potentil conflict of interest relevnt to this rticle ws reported. REFERENCES 1. Dnei G, Finucne MM, Lu Y, Singh GM, Cown MJ, Pciorek CJ, Lin JK, Frzdfr F, Khng YH, Stevens GA, Ro M, Ali MK, Riley LM, Robinson CA, Ezzti M; Globl Burden of Metbolic Risk Fctors of Chronic Diseses Collborting Group (Blood Glucose). Ntionl, regionl, nd globl trends in fsting plsm glucose nd dibetes prevlence since 1980: systemtic nlysis of helth exmintion surveys nd epidemiologicl studies with 370 country-yers nd 2.7 million prticipnts. Lncet 2011;378: Morrish NJ, Wng SL, Stevens LK, Fuller JH, Keen H. Mortlity nd cuses of deth in the WHO Multintionl Study of Vsculr Disese in Dibetes. Dibetologi 2001;44 Suppl 2:S

9 Improvement in rteril stiffness by exercise 3. Stmler J, Vccro O, Neton JD, Wentworth D. Dibetes, other risk fctors, nd 12-yr crdiovsculr mortlity for men screened in the Multiple Risk Fctor Intervention Tril. Dibetes Cre 1993;16: Alexnder CM, Lndsmn PB, Teutsch SM, Hffner SM; Third Ntionl Helth nd Nutrition Exmintion Survey (NHANES III); Ntionl Cholesterol Eduction Progrm (NCEP). NCEPdefined metbolic syndrome, dibetes, nd prevlence of coronry hert disese mong NHANES III prticipnts ge 50 yers nd older. Dibetes 2003;52: O Brien MJ, Alos VA, Dvey A, Bueno A, Whitker RC. Acculturtion nd the prevlence of dibetes in US Ltino Adults, Ntionl Helth nd Nutrition Exmintion Survey Prev Chronic Dis 2014;11:E Cruickshnk K, Riste L, Anderson SG, Wright JS, Dunn G, Gosling RG. Aortic pulse-wve velocity nd its reltionship to mortlity in dibetes nd glucose intolernce: n integrted index of vsculr function? Circultion 2002;106: Hope SA, Ty DB, Meredith IT, Cmeron JD. Use of rteril trnsfer functions for the derivtion of ortic wveform chrcteristics. J Hypertens 2003;21: Willims B, Lcy PS, Thom SM, Cruickshnk K, Stnton A, Collier D, Hughes AD, Thurston H, O Rourke M; CAFE Investigtors; Anglo-Scndinvin Crdic Outcomes Tril Investigtors; CAFE Steering Committee nd Writing Committee. Differentil impct of blood pressure-lowering drugs on centrl ortic pressure nd clinicl outcomes: principl results of the Conduit Artery Function Evlution (CAFE) study. Circultion 2006;113: Esposito K, Pontillo A, Di Plo C, Giuglino G, Msell M, Mrfell R, Giuglino D. Effect of weight loss nd lifestyle chnges on vsculr inflmmtory mrkers in obese women: rndomized tril. JAMA 2003;289: Kingwell BA, Cmeron JD, Gillies KJ, Jennings GL, Drt AM. Arteril complince my influence broreflex function in thletes nd hypertensives. Am J Physiol 1995;268(1 Pt 2):H DeSouz CA, Shpiro LF, Clevenger CM, Dinenno FA, Monhn KD, Tnk H, Sels DR. Regulr erobic exercise prevents nd restores ge-relted declines in endothelium-dependent vsodiltion in helthy men. Circultion 2000;102: Bonor E, Moghetti P, Zncnro C, Cigolini M, Queren M, Cccitori V, Corgnti A, Muggeo M. Estimtes of in vivo insulin ction in mn: comprison of insulin tolernce tests with euglycemic nd hyperglycemic glucose clmp studies. J Clin Endocrinol Metb 1989;68: Izzo JL Jr. Pulse contour nlysis nd ugmenttion index: it s time to move beyond cuff blood pressure mesurement. Am J Hypertens 2005;18(1 Pt 2):1S-2S. 14. Kumhr H, Schutz Y, Aybe M, Yoshiok M, Yoshitke Y, Shindo M, Ishii K, Tnk H. The use of unixil ccelerometry for the ssessment of physicl-ctivity-relted energy expenditure: vlidtion study ginst whole-body indirect clorimetry. Br J Nutr 2004;91: Borkn GA, Gerzof SG, Robbins AH, Hults DE, Silbert CK, Silbert JE. Assessment of bdominl ft content by computed tomogrphy. Am J Clin Nutr 1982;36: Lee JH, Hwng BY, Nm SN. The chnge of post tredmill exercise on blood pressure nd vsculr complince in essentil hypertension ptients. Koren J Phys Educ 2004;43: Lee JH. Effects of erobic exercise on rteril pulse wve velocity nd vessel pressure in ptients with nti-hypertensives gents [mster s thesis]. Seoul: Hnyng University; Mustt S, Groeneveld S, Dvidson W, Ford G, Kilnd K, Mnns B. Effects of exercise trining on physicl impirment, rteril stiffness nd helth-relted qulity of life in ptients with chronic kidney disese: pilot study. Int Urol Nephrol 2011;43: Stewrt KJ, Sung J, Silber HA, Fleg JL, Kelemen MD, Turner KL, Bcher AC, Dobrosielski DA, DeRegis JR, Shpiro EP, Ouyng P. Exggerted exercise blood pressure is relted to impired endothelil vsodiltor function. Am J Hypertens 2004; 17: Gielen S, Schuler G, Adms V. Crdiovsculr effects of exercise trining: moleculr mechnisms. Circultion 2010;122: Lurent S, Cockcroft J, Vn Bortel L, Boutouyrie P, Ginnttsio C, Hyoz D, Pnnier B, Vlchopoulos C, Wilkinson I, Struijker- Boudier H; Europen Network for Non-invsive Investigtion of Lrge Arteries. Expert consensus document on rteril stiffness: methodologicl issues nd clinicl pplictions. Eur Hert J 2006;27: Lee JI, Sohn TS, Kwon HS, Lee JM, Chng SA, Ch BY, Son HS. The chnges of centrl ortic pulse wve nlysis in metbolic syndrome. Koren Dibetes J 2008;32: Wilkinson IB, McCllum H, Rooijmns DF, Murry GD, Cockcroft JR, McKnight JA, Webb DJ. Incresed ugmenttion index nd systolic stress in type 1 dibetes mellitus. QJM 2000; 93: Jung JY, Hn KA, Ahn HJ, Kwon HR, Lee JH, Prk KS, Min KW. Effects of erobic exercise intensity on bdominl nd thigh dipose tissue nd skeletl muscle ttenution in over- 447

10 Jung JY, et l. weight women with type 2 dibetes mellitus. Dibetes Metb J 2012;36: Short KR, Vittone JL, Bigelow ML, Proctor DN, Rizz RA, Coenen-Schimke JM, Nir KS. Impct of erobic exercise trining on ge-relted chnges in insulin sensitivity nd muscle oxidtive cpcity. Dibetes 2003;52: DiPietro L, Dziur J, Yeckel CW, Neufer PD. Exercise nd improved insulin sensitivity in older women: evidence of the enduring benefits of higher intensity trining. J Appl Physiol (1985) 2006;100: K SH. The impct of qurobics on the body composition nd vsculr complince of middle-ged obese women [disserttion]. Dejeon: Chungnm Ntionl University; Kim TS, Seo YY, Lee SH, Hong YH, Kim DY, Won HS, Yng MS, Shin HH. Correltion between pulse wve velocity nd crdiovsculr risk fctors in Koren women. Koren J Lipidol Atheroscler 2008;18: Mckey RH, Sutton-Tyrrell K, Vitkevicius PV, Skkinen PA, Lyles MF, Spurgeon HA, Lktt EG, Kuller LH. Correltes of ortic stiffness in elderly individuls: subgroup of the Crdiovsculr Helth Study. Am J Hypertens 2002;15(1 Pt 1): Despres JP. Abdominl obesity s importnt component of insulin-resistnce syndrome. Nutrition 1993;9: Dekker MJ, Lee S, Hudson R, Kilptrick K, Grhm TE, Ross R, Robinson LE. An exercise intervention without weight loss decreses circulting interleukin-6 in len nd obese men with nd without type 2 dibetes mellitus. Metbolism 2007;56: Vitkevicius PV, Fleg JL, Engel JH, O Connor FC, Wright JG, Lktt LE, Yin FC, Lktt EG. Effects of ge nd erobic cpcity on rteril stiffness in helthy dults. Circultion 1993; 88(4 Pt 1): Yoon ES, Jung SJ, Je SY. Assocition between crdiorespirtory fitness nd rteril stiffness in older women. Exerc Sci 2009; 18: Chndler MP, DiCrlo SE. Acute exercise nd gender lter crdic utonomic tonus differently in hypertensive nd normotensive rts. Am J Physiol 1998;274(2 Pt 2):R Shen W, Zhng X, Zho G, Wolin MS, Sess W, Hintze TH. Nitric oxide production nd NO synthse gene expression contribute to vsculr regultion during exercise. Med Sci Sports Exerc 1995;27: Cole CR, Foody JM, Blckstone EH, Luer MS. Hert rte recovery fter submximl exercise testing s predictor of mortlity in crdiovsculrly helthy cohort. Ann Intern Med 2000;132: Poirier P, Grneu C, Bogty P, Ndeu A, Mrois L, Brochu C, Gingrs C, Fortin C, Jobin J, Dumesnil JG. Impct of left ventriculr distolic dysfunction on mximl tredmill performnce in normotensive subjects with well-controlled type 2 dibetes mellitus. Am J Crdiol 2000;85: Klein S, Sherd NF, Pi-Sunyer X, Dly A, Wylie-Rosett J, Kulkrni K, Clrk NG; Americn Dibetes Assocition; North Americn Assocition for the Study of Obesity; Americn Society for Clinicl Nutrition. Weight mngement through lifestyle modifiction for the prevention nd mngement of type 2 dibetes: rtionle nd strtegies: sttement of the Americn Dibetes Assocition, the North Americn Assocition for the Study of Obesity, nd the Americn Society for Clinicl Nutrition. Dibetes Cre 2004;27: Sigl RJ, Kenny GP, Wssermn DH, Cstned-Scepp C, White RD. Physicl ctivity/exercise nd type 2 dibetes: consensus sttement from the Americn Dibetes Assocition. Dibetes Cre 2006;29: