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1 대한비만학회지 : 제 20 권제 4 호 2011 원저 폐쇄성수면무호흡환자에서비수술적체중감량치료전 후의주간졸림증및피로도변화 가톨릭대학교의과대학성빈센트병원가정의학교실, 이비인후과학교실 (1) 강성구 김세홍 박서진 김하나 박용진 (1)* 송상욱 * The Effects of Non-surgical Weight Reduction on Daytime Sleepiness and Fatigue in Patients with Obstructive Sleep Anpea Sung-Goo Kang, Se Hong Kim, Seo Jin Park, Ha Na Kim, Yong Jin Park *, Sang-Wook Song * Department of Family Medicine, Department of ENT (1), St. Vincent's Hospital, College of Medicine, The Catholic University of Korea 요 약 연구배경 : 비만으로생길수있는합병증은다양한데, 특히호흡기계합병증으로가장흔하게볼수있는것이수면중상기도폐쇄로인한증상, 즉코골이이고, 이것이지속될경우수면무호흡증으로이어질수있다. 이번연구에서폐쇄성수면무호흡환자에서비수술적체중감량을통한주간졸림증, 피로도개선양상및동맥경화도와활성산소, 항산화능력의변화여부를살펴보고자한다. 방법 : 이비인후과에서폐쇄성수면무호흡증으로진단되어체중감량을위해의뢰된 21명의성인을대상으로 12 주간의비수술적체중감량치료를시행하였다. 식이요법과운동요법을기본으로하여약제가필요하다고판단될경우약물요법 (orlistat, Xenical R 또는 Sibutramine, Reductil R ) 을시행하였다. 치료전, 후의주간졸림증의평가는 ESS (Epworth Sleepiness Scale) 로, 피로도평가는 FSS (Fatigue Severity Scale) 로평가하였고, 그외동맥경직도, 활성산소및항산화력을측정하여비교하였다. 결과 : 본연구에참여한환자들에대한체중감량치료 12주후, 1~12.9 kg까지 ( 원래체중의 1.5~14.2% 감량 ) 대부분체중감량이이루어졌다. 체중감량치료후 ESS는치료전에비해유의하게개선되었으며 ( 치료전 9.42 ± 3.78, 치료후 5.67 ± 3.77, P = 0.001), FSS 역시치료전에비해치료후유의하게감소되었다.( 치료전 3.42 ± 1.59, 치료후 2.52 ± 1.10, P = 0.041) 동맥경직도및활성산소, 항산화력은치료전과후에차이를보이지않았다. 결론 : 본연구를통해폐쇄성수면무호흡을호소하는환자에서 12주간의비수술적체중감량치료를통해주간졸림증및피로도개선을확인할수있었다. 추후활성산소나항산화력, 동맥경직도의치료전, 후의변화등에대한추가적인연구가필요할것으로생각된다. ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ 중심단어 : 폐쇄성수면무호흡, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), 동맥경직도, 활성산소 ꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏꠏ 접수일자 : 2011 년 5 월 30 일, 심사일자 : 2011 년 6 월 28 일, 게재승인일자 : 2011 년 8 월 30 일교신저자 : 송상욱, ( ) 경기도수원시팔달구지동 93-6 성빈센트병원가정의학과 Tel: , Fax: , sswkoj@unitel.co.kr, Mobile: 박용진, ( ) 경기도수원시팔달구지동 93-6 성빈센트병원이비인후과 Tel: , Fax: , yp@catholic.ac.kr, Mobile: * 본연구는가톨릭대학교성빈센트병원임상의학연구소연구비에의하여이루어진것임

2 - 대한비만학회지 : 제 20 권제 4 호 서론비만으로생길수있는합병증은다양한데, 특히호흡기계합병증으로가장흔하게볼수있는것이수면중상기도폐쇄로인한증상, 즉코골이이고, 이것이지속될경우수면무호흡증으로이어질수있다. 폐쇄성수면무호흡 (Obstructive sleep apnea, OSA) 이건강에미치는영향은다양하게알려져있으며치료를하지않으면지나친주간졸림이나, 인지장애, 직업수행능력의감소, 삶의질이하락하게되며, 최근연구들에의해고혈압, 심혈관계질환, 당대사의이상을유발함이밝혀지고있다. 1-3) 수면무호흡증환자들은수면중상기도폐쇄를극복하기위해흡기시노력으로잠에서자주깨고정상적인수면패턴이단절되어과도한주간졸림증을유발하게된다. 뿐만아니라최근연구에따르면다음의기전으로심혈관질환을유발하게된다. 첫째, 만성적인교감신경의활성화, 둘째, 동맥경화증과연관된염증유발성변화, 셋째, 내피세포의기능이상, 넷째, 과응고성및 renin-angiotensin system 의자극등이며그외최근들어제기되는기전이산화적스트레스 (oxidative stress) 이다. 즉, 수면중무호흡으로인한간헐적인저산소증에이어재산소화가일어나는과정은활성산소를증가시켜이로인해심혈관질환의위험성을증가시킬수있다는것이다. 4) 폐쇄성수면무호흡증에대한치료로는지속성기도양압 (continuous positive airway pressure, CPAP) 의효과가잘알려져있으나고가의비용과코마름등의부작용으로환자의순응도가떨어진다는단점이있고, 수술요법은효과가다양하게나타나며수술후에재발할수있다는단점이있다. 5) 따라서체중감량을통한치료가보다근본적이면서환자의순응도를높일수있다는측면에서지속적으로시도되고있다. 6) 하지만현재까지는체중감량이수면무호흡증에특징적인주간졸림증이나피로도를어느정도호전시키는지에관한체계적인이해가부족한실정이다. 또한수면무호흡증의치료 (CPAP) 전, 후또는수술후동맥경화도 7) 및활성산소변화 8,9) 를비교한연구는있으나비수술적체중감량치료전, 후의변화를분석한연구는국내나국외에도거의없다. 따라서이번연구에서수면무호흡을호소하는환자에서비수술적체중감량을통한주간졸림증, 피로도개선양상및동맥경화도와활성산소, 항산화능력의변화여부를살펴보고자한다. 연구대상및방법 1. 연구대상본연구는소속병원임상시험윤리위원회 (Institutional Review Board) 의승인을받아윤리및안전지침을준수하면서시행되었다 (VCMC07MI072, VCMC07MI073). 2010년 1년간본원이비인후과에서체중감량을위해가정의학과로의뢰된폐쇄성수면무호흡증환자중연구에동의한환자들을대상으로하였다. 총 28명의수면무호흡환자들중동의철회한환자 4명, 중간연락이두절된환자 3명을제외한 21명을대상으로하였다. 키, 체중, 허리둘레등의신체계측, 혈압측정을하였고, 체성분분석기기 (Inbody720, Biospace Co., Ltd, south korea) 를이용하여근육량, 지방량, 지방분율을측정하였다. 2. 주간졸림증및피로도조사도구체중감량을시행하기전에주간졸림증을평가하기위해 ESS (Epworth sleepiness scale) 를시행하였다. 이도구는 8개문항으로이루어진자가설문도구이며각각의문항은 0점부터 3점까지의 Likert Scale로이루어져있다. 주간생활중졸거나쉽게잠에빠져드는정도를측정하며, 점수는 0점부터 24점까지이고점수가높아질수록주간졸림증이심해지는것을의미하고 10점이넘으면과도한주간졸림증이있는것으로평가한다. 10,11) 피로도평가를위해 Krupp 등에의해서개발된 Fatigue Severity Scale (FSS) 12) 을이용하였다. FSS는 9개의문항으로이뤄진자가설문도구로서, 각각의문항에대해전혀장애가없다고판단되면 1점, 장애가아주심하다고생각되면 7점으로하여느끼는장애의정도에따라 1에서 7까지의점수를선택한후설문지의총점을문항수인 9로나누어평균점수로표시한다. 이는국내에서변역되어임상적유용성이보고된바있다. 13) 3. 혈액학적검사및동맥경직도평가 CBC (WBC, hemoglobin, hematocrit, platelet) 및 blood chemistry (glucose, urea nitrogen, creatinine, AST, ALT, g-gtp, uric acd, total cholesterol, triglyceride, HDL-cholesterol, hs-crp) 를측정하였다. 산화적스트레스의수준을평가하기위해산화적스트레스분석기 (FORM, Free Oxygen Radicals Monitor, Callegari, Italy) 를이용하여손가락끝부위에서 20 ul의혈액을채취하여 FORT (Free Oxygen Radicals Test) 방법으로측정하였다. 동맥의경직도평가는맥파속도를측정하여평가할수있는데최근 oscillometric method를응용한자동파형분석기를이용하여비침습적으로간편하게측정하는방법이많이사용되고있고, 본연구에서도이방법에의해측정된 CAVI (cardio-vascular index, VxSera V-1000, Fukuda Denshi, Tokyo, Japan) 을이용하였다

3 - 폐쇄성수면무호흡환자에서비수술적체중감량치료전 후의주간졸림증및피로도변화 - 4. 체중감량의전후비교체중감량을위해식이요법과운동요법을기본으로하여약제가필요하다고판단될경우약물요법 (orlistat, Xenical R 또는 Sibutramine, Reductil R ) 을시행하면서 4주간격으로신체계측및혈압측정을시행하였다. 12주후설문지를통한주간졸림증및피로도를재평가하였고, 동맥경화도검사, 활성산소측정, 체성분분석검사, 혈액검사중 glucose, total cholesterol, triglyceride, HDL-cholesterol, hs-crp를다시측정하여체중감량전과후를비교분석하였다. 5. 자료의분석자료의분석은 SPSS (Statistical Package for Social Science) / PC version 12.0 for Windows을사용하였다. 체중감량치료전, 후의값을비교하기위해먼저정규성검정을시행한후, 변수가정규분포를보일경우 paired t-test 를, 정규분포를보이지않을경우 Wilcoxon signed rank test를시행하였다. P값이 0.05 이하일때통계적으로유의하다고판정하였다. Table 1. Comparison of clinical parameters pre-treatment and post-treatment Pre-treatment Post-treatment P-value * Body mass index (kg/m 2 ) ± ± 2.52 < Weight (kg) ± ± 9.11 < Body fat (%) ± ± 5.92 < Viceral fat ± ± Waist circumference (cm) ± ± 7.40 < Fasting blood sugar (mg/dl) ± ± Creatinine (mg/dl) 0.78 ± ± Uric acid (mg/dl) 5.95 ± ± Total cholesterol (mg/dl) ± ± Triglycerides (mg/dl) ± ± HDL cholesterol(mg/dl) ± ± hs-crp(mg/dl) 0.21 ± ± FORT ± ± FORD 0.83 ± ± R-ABI 1.14 ± ± L-ABI 1.15 ± ± R-CAVI 7.54 ± ± L-CAVI 7.10 ± ± * Statistical significance was evaluated by paired t-test. Statistical significance was evaluated by Wilcoxon signed rank test. Abbreviation: FORT, free oxygen radicals tests; FORD, free oxygen radicals defense; ABI, ankle brachial index; CAVI, cardio ankle vascular index. Fig. 1. BMI and body weight comparison between Pre-treatment and post-treatment. Statistical significance was evaluated by paired t-test

4 - 대한비만학회지 : 제 20 권제 4 호 결과 1. 연구대상자들의일반적인특성 (Table 1, Fig. 1) 연구대상자들은총 21명 ( 남자 16명, 여자 5명 ) 이었고평균나이는 44.5 ± 8.2세 ( 남자 43.0 ± 8.7세, 여자 49.4 ± 3.6세 ) 였다. 첫방문시평균체질량지수는 ± 2.90 ( 남자 ± 2.74 kg/m 2, 여자 ± 3.60 kg/m 2 ) kg/m 2 이었다. 체중감량치료 12주후평균체질량지수는 ± 2.52 ( 남자 ± 2.18 kg/m 2, 여자 ± 3.52 kg/m 2 ) kg/m 2 이었다. 2. 주간졸림증및피로도 (Fig. 2) 12주후체중감량정도는 21명평균 6.55 ± 3.28 kg( 최소 1 kg, 최대 12.9 kg) 이었다. 체중감량치료전과후에대한주간졸림증설문조사 (ESS) 에대한 paired T-test결과, 치료전에비해치료후평균 3.75 ± 2.70점낮아졌으며, 이는통계적으로유의한결과를보이고있었다 (P = 0.001). 또한, 피로도설문결과 (FSS) 치료전에비해치료후평균 0.90 ± 1.41점감소하였고, 통계적으로유의한차이를보였다 (P = 0.041). 3. 혈액학적검사 12주체중감량치료전, 후로시행한혈액검사에대해 paired t-test를시행했을때, Total Cholesterol은통계적으로유의하지는않았으나체중감량후감소되는경향을보였다 ( 평균 ± 34.01, P = 0.095). 그외검사결과는체중감량치료전, 후에유의한변화는보이지않았다 (Table 1) 체중감량정도에대한연관성을보기위한상관분석결과, 총콜레스테롤수치만체중감소정도에따라감소되는경향을보였고 (r = 0.697, P = 0.012), 그외검사들은체중감소정도와연관성을보이지않았다. 4. 동맥경화도및활성산소 (Table 1) 12주간체중감량치료후동맥경화도 (CAVI) 에대한 paired t-test결과오른쪽 (P = 0.992), 왼쪽 (P = 0.387) 모두통계적으로유의한차이를보이지않았다. ABI (ankle-brachial index) 또한오른쪽 (P = 0.964), 왼쪽 (P = 0.806) 모두통계적으로유의한차이를보이지않았다. 체내활성산소 (FORT) 수치의체중감량전후비교도통계적으로유의하지않은결과를보였으며 (P = 0.977), 체내총항산화력 (FORD) 검사또한통계적으로유의하지않았다 (P = 0.639). 고찰비만은이미많은선진국에서중요한건강위험인자중하나이며수면무호흡증에서도중요한위험인자로작용한다. 14) 비만한아시아인을대상으로한연구에서 ESS가폐쇄성수면무호흡증의독립적인예측인자로작용한다는연구도있었다. 15) 수면무호흡환자중주간졸림증을호소한경우는서양인을대상으로한연구에서 76%, 동양인을대상으로한연구에서 87.2% 로보고하여, 주간졸림증은동 서양인에서폐쇄성수면무호흡증의흔한증상으로알려져있다. 16,17) 폐쇄성수면무호흡증의치료중행동요법에는운동, 자기전술이나신경안정제를피하는것, 체중감량이중요한치료전략이될수있는데, 체중감량은이상적으로는 BMI 가 25 kg/m 2 이하로조절하는것을권장한다. 외국의연구에서체중이정상범위보다 10% 증가할때마다무호흡 -저호흡지수 (Apnea-hypopnea index, AHI) 가약 30% 증가하고, 10~15% 의체중감량이이루어지면 AHI가약 50% 까지도감소하는것으로보고되고있다 ) 폐쇄성수면무호흡증 Fig. 2. ESS and FSS comparison between Pre-treatment and post-treatment. Statistical significance was evaluated by paired t-test

5 - 폐쇄성수면무호흡환자에서비수술적체중감량치료전 후의주간졸림증및피로도변화 - 을가진비만환자에서식이요법만으로성공적인체중을감량한경우수면다원화검사에서 AHI가개선이되었다는보고도있었다. 22) 따라서, 모든비만한폐쇄성수면무호흡증환자는일차적인치료에반드시체중감량을같이시행하는것을추천하도록권고하고있다. 22) 본연구에참여한환자들에대한체중조절치료 12주후, 작게는 1 kg에서많게는 12.9 kg까지 ( 원래체중의 1.5~ 14.2% 감량 ) 정도의차이는있었지만대부분체중감량이이루어졌다. 체중감량치료전과후의 ESS를비교했을때, 치료전 9.42 ± 3.78점에서치료후 5.67 ± 3.77로통계적으로유의하게개선된점을볼수있었다. 유럽의한연구에서 ESS가 10점이상인중증의비만환자를 bariatric surgery를시행한후 1년뒤관찰했을때 77.5% 의환자가 ESS점수가 10점이하로감소하였다. 23) 미국에서도비슷한연구가있었는데, 폐쇄성수면무호흡증을가진중증의비만한환자를 gastric bypass를통해체중감량을한경우 OSA 증상이많이개선이됐으며 ESS의경우수술전 12.0 ± 0.1점에서수술후 6.0 ± 1.0으로개선되었다. 24) 이처럼수술적치료를통해극단적인체중감량을이루고, 주간졸림증의개선을보고한연구는많이있지만 25), 비수술적체중감량치료후주간졸림증의개선을보고한연구는거의없어본연구가어느정도의의를가진다고할수있겠다. 폐쇄성수면무호흡증을가진환자들은주간졸림증만큼이나흔하게피로를호소한다. 26) 수면무호흡을호소하는환자에서피로증상을치료하는것은중요하지만, 치료전과후의피로증상에대해평가한연구는거의없었다. 외국의경우 14명의폐쇄성수면무호흡증환자를대상으로시행한비무작위연구에서치료받지않은군에비해 CPAP 로치료받은군에서 Profile of Mood States (POMS) fatigue subscale이개선된보고가있었고 27), 또다른연구에서는 1~2주간 therapeutic CPAP를받은군과 placebo CPAP를받은군에서의피로증상의감소정도를비교한연구에서두군모두에서 POMS fatigue 점수가개선되었다. 28) 최근잘디자인된무작위대조연구에서 3주동안 therapeutic CPAP를받은군과 placebo CPAP를받은군에서의피로의변화를측정했을때, Multidimensional Fatigue Symptom Inventory-Short Form (MFSI-sf) Score와 POMS fatigue Score 모두 therapeutic CPAP를받은군에서더많이개선되었고, 이러한효과는처음피로가심한경우더두드러졌다. 29) 본연구에서폐쇄성수면무호흡증의증상개선을위한 12주간의체중감량치료전, 후의 FSS를측정한결과, 치료전에는 3.42 ± 1.59점이었으나치료후에는 2.52 ± 1.10 점으로유의하게감소되었다. 폐쇄성수면무호흡증에서의피로증상에대한치료전, 후비교연구는거의대부분 CPAP 치료에국한되어있었다. 그러나본연구에서는폐쇄 성수면무호흡증의증상개선의방법으로비수술적체중감량치료를시행하였고, 체중감량치료 12주후유의한피로증상개선을확인할수있었다. 본연구의이러한결과는수술적치료나 CPAP가아니더라도비수술적체중감량이폐쇄성수면무호흡증환자에서피로의개선에도움이될수있다는단서를제시하는것이라고여겨진다. 폐쇄성수면무호흡증과동맥경화도, 고혈압, 심혈관질환과의밀접한관련성에대한보고는많이있어왔다. 1,2,30) 동맥경화나고혈압등의원인에의해동맥경직도가증가하고, 동맥경직도는상완-발목맥파속도 (Brachial ankel Pulse Wave Velocity, BaPWV) 를측정함으로써비침습적으로평가할수있다. 하지만 BaPWV는대동맥의맥파속도를적게반영할수있고혈압에영향을받는단점이있어 31) 이를보완할새로운방법으로 CAVI (cardio ankle vascular index) 가새로대두되었다. 32) CAVI는대동맥의맥파속도를잘반영하는것으로알려져있으며, 혈압의변동에도불구하고이를보정할필요없이동맥혈관고유의경직도를나타낼수있다. 32) 543명의폐쇄성수면무호흡증환자를대상으로 CAVI의임상적유용성을평가한연구에서경도의폐쇄성수면무호흡증환자에비해중등도이상의환자에서 CAVI 수치가더높은것으로나타나 CAVI가폐쇄성수면무호흡증환자의동맥경직도평가에유용한지표로서역할을하는것으로나타났다. 33) 본연구에서는체중감량치료전과치료후의 CAVI는좌측과우측모두변화가없었다. 폐쇄성수면무호흡증치료전, 후의 CAVI를비교한연구는거의없는데, 한연구에서맥파속도평가를통해폐쇄성수면무호흡증은독립적으로동맥경직도증가와연관이있고, CPAP로치료를했을때동맥경직도가호전이되었다고보고한연구가거의유일하다. 34) 본연구에서체중감량치료전, 후 CAVI변화가없었던것이치료기간이짧았기때문인지, 아니면체중감량보다는수면무호흡이동맥경직도에더강한영향을미치기때문인지는알수없다. 향후이에대한연구가더필요할것으로생각된다. 최근폐쇄성수면무호흡증과관련된몇가지병태생리학적인기전을제시한연구가있었는데, 폐쇄성수면무호흡증환자들은염증반응증가, 활성산소생성증가, 항산화능력감소및혈관내피세포기능부전으로직접적으로혈관손상이진행되고이것이추후심혈관질환과강한연관성을가지게된다. 35,36) 그리고 CPAP로치료했을때이러한반응을개선시켰다. 35) 그러나비수술적체중감량치료전, 후의활성산소및항산화력의변화를관찰한연구는거의없다. 본연구에서체중감량치료전, 후활성산소나항산화력을측정하였으나유의한변화를보이지않았다. 이러한결과가 CAVI가변화가없었던결과와마찬가지로치료기간이나체중감량이더필요한지, 아니면체중감량치료자체가 CPAP에비해병태생리학적인기전을호전시키기에는

6 - 대한비만학회지 : 제 20 권제 4 호 효과가미약한지등을고려한추가적인연구가더필요할것으로사료된다. 이번연구에는몇가지제한점이있다. 연구대상자수가적었고, 본연구는비교군이없어치료전후를비교하는것에대한결과의해석에한계가있고, 치료의효과가있었다는것을객관적으로말하기에는제한이있다. 그리고주간졸림증을평가하는데있어 ESS 지수만을이용했는데, 수면무호흡증환자에서주간졸림증을측정하는데는 ESS보다는다중수면잠복기검사가더정확하다는연구도있고 37), ESS가상황에따라서는주간졸림증을객관적으로반영하지못할수도있다. 38) 또 ESS는아직우리나라에서타당도검사가이루어지지않았다. 그러나타당도검사는이루어지지않았지만주간졸림증을평가하는데 ESS는이미우리나라에서과거부터많이사용되어져왔다는것도고려되어야할것이다. 결론적으로본연구를통해폐쇄성수면무호흡증환자에서 12주간의비수술적체중감량치료를통해주간졸림증및피로도개선을확인할수있었다. 추후활성산소나항산화력, 동맥경직도의치료전, 후의변화등에대한추가적인연구가필요할것으로생각된다. Results: The patients lost 1 kg to 12.9 kg (from 1.5% to 14.2% of basal body weights) of weight after the 12-week non-surgical weight reduction program. ESS were significantly decreased from 9.42 ± 3.78 to 5.67 ± 3.77 (P = 0.001) and FSS were decreased from 3.42 ± 1.59 to 2.52 ± 1.10 (P = 0.041) after the treatment. There were no significant changes on oxidative stress, antioxidant capacity and arterial stiffness. Conclusion: Daytime sleepiness and fatigue of patients with OSA were improved after the 12-week non-surgical weight reduction. Further research, of a larger scale, on the effects of non surgical weight reduction on oxidative stress, antioxidant capacity and arterial stiffness for patients with OSA is needed. Key words: Obstructive sleep apnea, Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), Arterial stiffness, Oxidative stress 참고문헌 ABSTRACT The Effects of Non-surgical Weight Reduction on Daytime Sleepiness and Fatigue in Patients with Obstructive Sleep Anpea Background: Among the many complications caused by obesity, the most common respiratory complication is upper respiratory obstruction during sleep caused by snoring. Long term snoring may lead to obstructive sleep apnea (OSA). The purpose of this research is to study the effects of non-surgical weight reduction on daytime sleepiness, fatigue, arterial stiffness, oxidative stress and antioxidant capacity of patients with OSA. Methods: Twenty-one adults who were diagnosed with OSA by the ENT department were enrolled. They underwent a 12-week non-surgical weight reduction program based on diet and exercise. The patients were also treated with either Orlistat (Xenical R ) or Sibutramine (Reductil R ), when it was necessary. The effects of this treatment on daytime sleepiness and fatigue were measured by ESS (Epworth Sleepiness Scale) and FSS (Fatigue Severity Scale) respectively. Arterial stiffness, oxidative stress and antioxidant capacity were also measured and analyzed. 1. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342: Peker Y, Carlson J, Hedner J. Increased incidence of coronary artery disease in sleep apnoea: a long-term follow-up. Eur Respir J 2006;28: Punjabi NM, Polotsky VY. Disorders of glucose metabolism in sleep apnea. J Appl Physiol 2005;99: Kim WS. Cardovascular Impacts of Sleep-disordered Breathing. Tuberc Respir Dis 2009;66: Epstein LJ, Kristo D, Strollo PJ, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med 2009;5: Tuomilehto HP, Seppa JM, Partinen MM, Peltonen M, Gylling H, Tuomilehto JO, et al. Lifestyle Intervention with Weight: Reduction First-line Treatment in Mild Obstructive Sleep Apnea. Am J Respir Crit Care Med 2009;179: Lü YH, He ZM, Dong XS, Li J, Han X, An P, et al. Effects of short-term continuous positive airway pressure treatment on arterial stiffness in patients with

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R