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1 지속적근력운동자에서운동량감소가인슐린저항성및당뇨병치료경과에미치는영향 연세대학교대학원의학과김경민

2 지속적근력운동자에서운동량감소가인슐린저항성및당뇨병치료경과에미치는영향 지도교수차봉수 이논문을석사학위논문으로제출함 2008 년 6 월 연세대학교대학원의학과김경민

3 김경민의석사학위논문을인준함 심사위원 인 심사위원 인 심사위원 인 연세대학교대학원 2008 년 6 월

4 감사의글 이논문이완성되기까지깊은관심을가지고지도를해주신차봉수교수님께진심으로감사드리며, 본연구를위하여세심한조언을아끼지않으신이현철교수님과박상욱교수님께도깊은감사를드립니다. 아울러연구계획수립및자료수집에도움을주신박세은선생님께도감사의말씀을드리며함께해온내과동기들, 그리고항상저를보살펴주시는부모님과가족께도감사드립니다. 저자씀

5 < 차례 > 국문요약 1 Ⅰ. 서론 4 II. 대상및방법 8 1. 연구대상 8 2. 연구방법 8 가. 신체계측및혈압측정 9 나. 혈청학적검사 9 3. 통계분석 10 III. 결과 연구대상자의진단당시의임상적특성 당뇨병의치료기간에따른혈당강하효과 당뇨병의치료기간에따른인슐린저항성지표의변화 지질대사개선효과 혈청간효소수치의변화 17 IV. 고찰 19 V. 결론 24 참고문헌 25 영문요약 31

6 그림차례 Figure 1. Mean percent changes of HbA1c from baseline 13 Figure 2. Mean percent changes of fasting glucose and postprandial 2 hour glucose 14 Figure 3. Changes in liver enzymes 18

7 표차례 Table 1. Baseline clinical characteristics and biochemical parameters of subjects 12 Table 2. Changes of fasting insulin, postprandial 2 hour insulin and HOMA-IR 15 Table 3. Changes in lipid profiles 16 Table 4. Changes in liver enzymes 17

8 < 국문요약 > 지속적근력운동자에서운동량감소가인슐린저항성및당뇨병치료경과에미치는영향 배경 : 최근증가하고있는제 2형당뇨병의병인기전은인슐린저항성과췌장베타세포의인슐린분비장애로알려져있다. 운동을통한인슐린저항성개선에대한연구는지속되어왔으나운동의중단이인슐린저항성및당뇨병경과에미치는영향에대한연구는미비하다. 본연구는과거 2년이상지속적인근력운동을했던환자에서운동의중단이인슐린저항성및당뇨병의치료경과에미치는영향에대해서알아보고자하였다. 대상및방법 : 최근 10년간연세대학교세브란스병원에서제 2형당뇨병을진단받은환자들중 2년이상의지속적인근력운동의과거력이있는환자들을대상으로진단당시와치료 1년및 2년추적관찰기간동안의신체계측및혈청학적검사결과들을나이, 비만도짝짓기를통해선정된대조군의결과와비교, 분석하였다. 결과 : 총 86명의환자를대상으로하였으며, 지속적근력운동의과거력이있는운동군 (N=33) 과운동의과거력이없는 1

9 대조군 (N=53) 을비교한결과, 운동군에서대조군에비해식후 2시간 C-peptide 수치가증가되어있고, 고밀도지단백-콜레스테롤수치가감소되어있는것이외에진단당시다른임상적양상이나혈청학적검사들의유의한차이는없었다. 치료기간에따른당화혈색소의감소와공복시및식후 2시간혈당의감소가대조군에비해운동군에서적게나타났으나, 두군간의통계학적인차이는없었으며공복인슐린및식후 2시간인슐린의변화양상에도두군간유의미한차이는없었다. 그러나인슐린저항성지표인 HOMA-IR의경우대조군의경우추적관찰 2년후감소경향 (3.38 vs. 2.41, P <0.05) 을보여인슐린저항성의개선을보여주고있으나운동군의경우추적관찰 2년후오히려 HOMA-IR 수치의증가 (3.71 vs. 4.66, P <0.05) 를보였고, 2년후운동군에서대조군에비해유의하게 HOMA-IR 수치가높았다. 지방간에대한간접지표로사용된혈청간효소수치의경우, 혈중 ALT 수치가, 대조군에서는치료기간에따라유의하게감소하였으나, 운동군에서는유의하게증가하여 2년후대조군에비해높게나타났다 (54.81±39.0 vs ±17.69, P <0.05). 결론 : 운동의중단은당뇨병의치료경과에있어서혈당강하및인슐린저항성개선에부정적인영향을미치는요소가된다. 따라서대사에미치는운동의효과를유지하기위해서는지속적인운동이필요하며, 지속적인근력운동의과거력이있는당뇨병환자들의 2

10 효과적인치료를위해서는식사, 약물요법뿐만아니라운동 요법이반드시병행되어야할것으로사료된다 핵심되는말 : 인슐린저항성, 제 2 형당뇨, 운동 3

11 지속적근력운동자에서운동량감소가인슐린저항성및당뇨병치료경과에미치는영향 < 지도교수차봉수 > 연세대학교대학원의학과 김경민 Ⅰ. 서론 당뇨병은인구의고령화, 비만, 비활동적생활형태로의변화와연관되어유병률이급격하게증가하고있으며국내에서도향후 2030년경에는 10% 에도달할것으로보고된바있다 1. 이러한당뇨병의증가는당뇨병성콩팥병증, 심근경색, 뇌혈관질환등당뇨병과연관된합병증발생을일으키게되고연관사망률을증가시키게된다. 고령화, 생활습관, 식습관의변화와연관되어증가되고있는당뇨병은제 2형당뇨병으로서이는각장기의인슐린저항성과췌장베타세포의인슐린분비장애에의해서 4

12 발생하는것으로알려져있다. 골격근은인슐린에의해당을이용, 분해시키는중요한장기의하나로서골격근의인슐린저항성이당뇨병발생에큰부분을차지하는것으로생각되고있다. 오랜시간동안운동을통한골격근의인슐린저항성개선에대한연구가많이진행되어왔고운동에의한인슐린저항성과혈당의개선을확인한바있다 2-5. 따라서식사조절과약물치료이외운동요법도당뇨병환자의혈당조절에효과적인치료법으로강조되고있다. 운동에의한인슐린저항성의개선은여러가지기전으로설명되고있다. 그첫째로는, 근육산화효소증가에의한유리지방산의산화증가이다 6, 7. 여러임상실험을통해제 2형당뇨환자나비만환자의경우, 근육내유리지방산의축적이증가되어있음을확인할수있었고운동후유리지방산의산화가빠르게진행됨으로써인슐린저항성개선을확인할수있었다 8, 9. 저항성운동이나유산소운동을지속적으로하는경우, 오히려근육내지방의함량이증가하나이러한증가량보다지방산산화효소의증가가더현저하기때문에인슐린감수성이증가하는것으로보고되었다 10, 11. 두번째기전은근육내 Glucose transporter-4 (GLUT4) 단백질의발현증가로인한근육내인슐린신호체계의활성화이다. 이전의몇몇연구들에서운동후근육의조직검사를통해 GLUT4 단백질의발현이증가되어있음을확인한바있다 12, 13. 5

13 세번째기전으로는운동이하지의혈류량증가를유도하여근육으로전달되는포도당과인슐린의양을증가시킴으로인해인슐린유도당섭취율의증가가나타난다는것이다 12. 그외가능한기전으로 1형우세로의근섬유의구성비율의변화, 근육내모세혈관밀도의증가등이있다 14. 이러한운동에의한인슐린저항성개선의효과는유산소운동에서더욱뚜렷하게나타났으며최근근력운동을대상으로한연구에있어서도유사한결과가보고되었다 15, 16. 그러나대부분의이전연구들은운동을시작함으로인한변화에초점을맞춘것으로운동의중단이가져올수있는변화에대한연구는미비하다. 즉, 운동을통해증가된근육내지방이운동을중단할경우인슐린저항성과당뇨병의발생에미칠영향에대해서는뚜렷하게밝혀진바가없다. 최근한연구에서는근육운동을일정기간지속하게한이후의 GLUT4 단백질발현, 당산화효소수치, 모세혈관밀도, 인슐린, 공복혈당을측정하고이후일정기간운동을중단시킨이후상기인자들의변화를비교한바있다 16. 이연구의결과, GLUT4 단백질발현, 당산화효소수치, 모세혈관밀도, 인슐린, 공복혈당등의인자는운동중단이후에도변화가없었으나인슐린유도당이용률이다시감소됨을확인할수있었고, 따라서운동으로인해증가된인슐린감수성이운동의중단에의해다시감소됨을보고하였다 16. 또한다른연구에서는 6

14 47주간근육운동을통해고밀도지단백-콜레스테롤 (HDLcholesterol), 저밀도지단백-콜레스테롤 (LDL-cholesterol), 인슐린, 인슐린저항성 (Homeostasis model assessment of insulin resistance, HOMR-IR) 등의대사지표들이개선됨을확인한후, 운동을중단시킴으로인해이러한지표들이급격하게악화되는것을보고한바있다 17. 이러한연구의결과를종합해볼때운동의중단은인슐린저항성에영향을미칠것으로생각된다. 따라서본연구에서는근력운동량의감소가인슐린저항성및당뇨병발생과그임상경과에주는영향을확인하고자과거 2년이상의지속적인근력운동의과거력이있는제 2형당뇨병환자들을대상으로당뇨병발병양상과대사지표소견, 추적관찰기간동안의임상양상, 임상병리검사소견알아보고근력운동의과거력이없는대조군과차이점들을비교, 분석하고자하였다. 7

15 Ⅱ. 대상및방법 1. 연구대상 본연구는 1996년 1월부터 2005년 1월까지연세대학교신촌세브란스병원당뇨병센터에내원하여미국당뇨병학회기준에따라제 2형당뇨병으로진단받은남자환자들중과거 2년이상선수생활등록을통한근력운동의과거력이있고 1년이상운동을중단한환자들을대상으로하였다. 이미당뇨병을치료중내원한환자, 제 1형당뇨병을진단받은환자, 대사에영향을미치는약물을복용하고있거나당뇨병이외의내분비질환이있는환자, 만성 B형및 C형간염보균자, 만성신부전환자 ( 혈청 creatinine 수치가 1.5 mg/dl이상 ), 또는악성종양이있는환자는연구대상에서제외되었다. 대조군은나이및비만도짝짓기를통해선정하였다. 2. 연구방법 본연구는후향적비교분석연구 (retrospective, case-control study) 로진행되었다. 선정된환자를대상으로진단당시와추적 8

16 관찰기간 1 년, 2 년째다음의지표를측정하였다. 가. 신체계측및혈압측정 모든대상자는체중과키를측정하였다. 체중과키는신발을벗은상태에서가벼운옷차림으로 0.1kg, 0.1cm 단위까지측정하였고이를통해체질량지수 (body mass index, BMI) 를구하였다. 허리둘레는가쪽엉덩뼈능선 (lateral iliac crest) 과가장아래갈비뼈사이의중간점에서측정하였으며엉덩이둘레는큰돌기 (great trochanter) 가가장돌출된부분에서측정하여허리 / 엉덩이비율 (waist/hip ratio, WHR) 을계산하였다. 고해상도초음파 (SA 9900, Medison, Seoul, Korea) 를사용하여환자를바로눕게한후배꼽위 1cm 위치에서 3.5 MHz probe로내장지방두께 ( 대동맥의 전벽에서복직근내면까지로정의 ) 를측정하였다 18, 19. 혈압은 대상환자가 5 분이상안정을취한상태에서의자에앉아표준화된 수은혈압계를이용하여수축기및확장이혈압을측정하였다. 나. 혈청학적검사 대상환자의혈장에서공복및식후 2시간혈당 (glucose oxidase법 ), 당화혈색소 (HbA1c, high performance liquid chromatography), 공복및식후 2시간인슐린 (RIABEAD II kit, Abbott, Japan), 공복및식후 2시간 C-peptide, Blood urea 9

17 nitrogen, 크레아티닌, 총콜레스테롤, 중성지방 (Triglyceride), 고밀도지단백-콜레스테롤 (HDL-cholesterol), 저밀도지단백- 콜레스테롤 (LDL-cholesterol), aspertate transaminase(ast), alanine transaminase(alt) 수치를측정하였다. 인슐린저항성지표와베타세포기능지표로 HOMA-IR와 HOMA-β (homeostasis model assessment of β cell function) 을사용하였고 HOMA- IR=[ 공복인슐린 (uu/ml)x 공복혈당 (mmol/l)/22.5], HOMA-β=20 x 공복인슐린 (uu/ml)/[ 공복혈당 (mmol/l)-3.5] 으로계산하였다. 인슐린을사용한환자의 HOMA-IR와 HOMA-β수치는제외하였다. 3. 통계분석 모든자료의통계처리는통계프로그램 SPSS 11.0 for Windows package를이용하였으며기술통계값은평균 ± 표준편차 (mean ± SD) 로표시하였으며인슐린, C-peptide, HOMA-IR및 HOMAβ값은중앙값 ( 범위 ) 으로표시하였다. 두군의평균치분석은 Student t-test와 Mann-Whitney test를사용하였고각군에서의치료기간별변화는 paired t-test를사용하였다. 통계결과의유의수준은 P 값을 0.05미만으로하였다. 10

18 Ⅲ. 결과 1. 연구대상자의진단당시의임상적특성 2년이상지속적인근력운동의과거력이있는당뇨병환자 33명이연구에포함되었으며운동의종류로는유도가 9명 (27%) 으로가장많았고그외태권도, 럭비등이있었다. 근력운동의과거력이있는운동군 (N=33) 과근력운동의과거력이없는대조군 (N=53) 의당뇨병진단나이, 가족력유무, 허리 / 엉덩이둘레비및혈압의차이는없었다. 혈청학적검사를비교해볼때, 진단당시당화혈색소는두군에서차이가없었으며, 식후 2시간 C- peptide가운동군에서의미있게높게나타났으나그외공복시혈당, 식후 2시간혈당, 공복시인슐린, 식후 2시간인슐린및공복시 C-peptide 수치는차이가없었다. HOMA-IR의경우, 운동군에서대조군에비해증가되어있었으나통계학적인의미는없었다. 혈청지질은두군에서비교해본결과고밀도지단백- 콜레스테롤이운동군에서유의하게감소되어있었다. 그외총콜레스테롤수치와저밀도지단백-콜레스테롤수치, 중성지방의수치는차이가없었다 (Table 1). 11

19 Table 1. Baseline clinical characteristics and biochemical parameters of subjects untrained trained p-value N Age (years) 42.6± ±11.8 ns Family history of diabetes (%) 28 (52.8%) 14 (43.8%) ns BMI (kg/m2) 28.10± ±3.14 ns WHR 0.95± ±0.42 ns Visceral fat thickness (mm) 65.6± ±19.0 ns Blood pressure Systolic (mmhg) 140.9± ±21.6 ns Diastolic (mmhg) 87.4± ±13.7 ns Serum Glucose and insulin Fasting glucose (mg/dl) ± ±63.3 ns PP 2 hour glucose (mg/dl) ± ±98.37 ns Fasting insulin (uiu/ml) 8.88 (1.70~20.80) 8.41 (2.36~29.48) ns PP 2 hour insulin (uiu/ml) (5.09~224.03) (5.26~202.11) ns Fasting C-peptide (ng/ml) 1.90 (0.81~3.93) 2.13 (1.06~5.04) ns PP 2 hour C-peptide (ng/ml) 4.47 (1.66~11.09) 5.10 (1.43~11.71) 0.03 HOMA-IR 3.38 (0.51~10.45) 3.72 (0.75~11.30) ns HOMA-β (3.44~110.80) (11.45~283.16) ns HbA1c (%) 8.61± ±2.33 ns Liver enzyme AST(IU/L) 28.28± ±11.39 ns ALT(IU/L) 47.04± ±22.04 ns Serum lipids Total cholesterol (mg/dl) ± ±75.57 ns HDL-cholesterol (mg/dl) 42.69± ± LDL-cholesterol (mg/dl) ± ±34.57 ns Triglyceride (mg/dl) (84~632) (76~2302) ns 24hr urine protein (mg) (19.7~999.7) (25~187.0) ns Oral hypoglycemic agent, n (%) Biguanidie 5 (9%) 9 (27%) Biguanide + TZD 24 (45 %) 14 (42%) Biguanide + SU 11 (21%) 2 (6%) Biguanide + TZD + SU 4 (8%) 3 (9%) Others 9 (17%) 5 (15%) N, number of patients; BMI,body mass index; PP,postprandial; HOMA-IR, homeostasis model assessment for insulin resistance; HOMA-β, homeostasis model assessment for β-cell function; TZD, Thiazolidinedione; SU, sulfonylurea; Data are expressed as means ± SD. Insulin, C-peptide, HOMR-IR, HOMR-β, Triglyceride are described as median(minimum~maximun) values 12

20 2. 당뇨병의치료기간에따른혈당강하효과 대조군에서당화혈색소는치료 1년째 17.94±2.53%, 2년째 15.91±3.9% 감소하였고, 운동군에서는각각 12.86±4.1%, 12.12±5.2% 감소하여운동군이대조군에비해서당화혈색소의감소가적었으나통계학적으로의미는없었다 (Figure 1). 공복시혈당및식후 2시간혈당도운동군이대조군에비해서강하효과가적게나타났으나두군간의통계학적인차이는없었다 (Figure 2) year 2 year Figure 1. Mean percent changes of HbA1c from baseline. The percent change of HbA1c in trained group was lower than untrained group, but statistically not significant. Data are expressed as means ± SD. 13

21 Mean % change hanges of fasting glucose Mean % change hanges of PP 2 hour glucose year 2 year year 2 year Figure 2. Mean percent changes of fasting glucose and postprandial 2 hour glucose. The percent change of fasting and postprandial 2 hour glucose in trained group were lower than untrained group, but statistically not significant. Data are expressed as means ± SD. 14

22 3. 당뇨병의치료기간에따른인슐린저항성지표의변화 운동군에서는기저치에비해치료 1년, 2년후공복인슐린과, 식후 2시간인슐린수치가증가하였으며대조군은감소경향을보였으나두군별, 치료기간별통계학적인차이는보이지않았다. HOMA-IR의경우, 대조군의경우기저치에비해 2년후유의하게감소하였으나 (3.38 vs. 2.41, P <0.05), 운동군에있어서는 2년후유의한증가 (3.72 vs. 4.66, P <0.05) 를보였다 (Table 2). 이러한결과기저치의 HOMA-IR값은운동군과대조군의차이가없었으나치료 1년과 2년후에는운동군의 HOMA-IR값이대조군에비해유의한높게나타났다 (Table 2). Table 2. Changes of fasting insulin, PP 2 hour insulin, and HOMA-IR Fasting insulin(uiu/ml) Baseline 1 year 2 year untrained 8.88(1.70~20.80) 8.19(1.32~20.30) 7.03(3.13~13.56) trained 8.41(2.36~29.48) 9.46(4.54~15.70) 14.10(3.88~38.43) PP 2 hour insulin(uiu/ml) untrained 37.64(5.09~224.03) 38.72(9.86~86.11) 33.82(5.02~91.57) trained 44.79(5.26~202.11) 62.38(21.14~185.06) 54.50(17.53~155.62) HOMR-IR untrained 3.38(0.51~10.45) 2.42(0.45~6.82) 2.41(0.85~4.31) trained 3.72(0.75~11.30) 3.23(0.98~5.93)* 4.66(1.28~15.31)*, Data are expressed median(minimum~maximum). PP, postprandial; HOMA-IR, homeostasis model assessment insulin resistance *P< 0.05 versus untrained group P<0.05 versus baseline 15

23 4. 지질대사개선효과 혈청총콜레스테롤 (Total cholesterol) 과저밀도지단백- 콜레스테롤 (LDL-cholesterol), 중성지방 (Triglyceride) 의수치는운동군과대조군에서치료기간에따른유의한변화를보이지않았다. 고밀도지단백-콜레스테롤 (HDL-cholesterol) 은기저치와비교하여 2년후유의한증가를보였으며이러한변화양상은두군별차이는보이지않았다. Table 3. Changes in lipid profiles Baseline 1 year 2 year Total cholesterol untrained ± ± ±32.89 (mg/dl) trained ± ± ±29.03 HDL-cholesterol untrained 42.69± ± ±9.16* (mg/dl) trained 38.71± ± ±7.52* LDL-cholesterol untrained ± ± ±26.28 (mg/dl) trained ± ± ±22.61 Triglyceride untrained 177(64~632) 114(38~735) 217(31~565) (mg/dl) trained 194(107~547) 119(83~682) 206(68~367) Data are expressed means±sd, Triglyceride levels are expressed median(minimum~maximum) HDL, high density lipoprotein; LDL, low density lipoprotein. *P<0.05 versus baseline 16

24 5. 혈청간효소수치의변화 치료기간에따른혈중간효소수치의변화는 Table 4, Figure 3 과같다. 혈중 AST 수치는운동군에서는기저치에비해치료 1년과, 2년후증가되는경향을보이고대조군에서는기저치에비해감소경향을보이나두군에서모두통계학적으로유의한변화는 보이지않았으며두군별차이를나타내지않았다. 혈중 ALT 수치는운동군에서는치료 2 년후통계학적으로유의하게 증가하였으며 (42.30 ± vs ± 39.0, P <0.05), 대조군에서는통계학적으로유의하게감소하여 (47.04 ± vs ± 17.69, P <0.05) 2 년후혈중 ALT 수치는운동군에서 유의하게높게나타났다 (54.81 ± 39.0 vs ± 17.69, P <0.05). Table 4. Changes in liver enzymes Baseline 1 year 2 year AST(IU/L) untrained 28.28± ± ±9.84 trained 27.67± ± ±27.50 ALT(IU/L) untained 47.04± ± ±17.69* trained 42.30± ± ±39.0* Data are expressed means ± SD. AST, aspertate transminase; ALT, alanine transaminase *P<0.05 versus baseline P<0.05 versus untrained groups 17

25 Year * Year Figure 3. Changes in liver enzymes. AST, aspartate transaminase; ALT, alanine transaminase *P <

26 Ⅳ. 고찰 제 2형당뇨병은유전적요인과환경적요인들이복합적으로작용하여생기는대사질환으로근육, 지방, 간등주요장기의인슐린저항성과췌장의인슐린분비능감소가주된병리기전으로알려져있다 20, 21. 따라서당뇨병발생의예방과인슐린저항성의극복을위한연구가활발하게진행되어왔으며운동이이러한결과를가져온다는것을이전의여러연구들을통해확인된바있다 2-4. 그러나운동의중단이가져올수있는인슐린저항성이나대사지표에미치는영향에대한연구는거의없는실정이다. 본연구의목적은지속적인근력운동의과거력이있는환자들중당뇨병을진단받은환자들을대상으로진단당시의임상양상과대사지표들을살펴보고당뇨병치료 1년, 2년후대사지표들의변화양상을확인해보고자하였다. 또한이를운동의과거력이없는대조군의수치와비교해봄으로써, 운동량감소가당뇨병의발생및경과, 대사지표에미치는영향에대해알아보고자진행되었다. 골격근내지방의축적은인슐린저항성의요인으로작용하여당뇨병발생의위험인자로작용함을이전의여러연구들에서이미 밝힌바있다 앞서언급된바와같이운동은인슐린저항성 개선에효과적이다. 그러나지속적인운동을하는경우, 인슐린 19

27 저항성개선과혈당강하효과가나타나나모순적으로근육내 지방의함량은증가된다 8, 14. 그러나운동은골격근내지방의 증가와동시에근육세포의지방산화효소의활성화등을포함한지방산화능력의향상을유발함으로인해인슐린저항성개선을유도하게되는것이다 8, 10, 25, 26. 그러나이와같이향상된대사지표들이지속되는기간에대해서는명확하게알려진바가없으며이전의여러연구들은운동을중단했을경우, 급속도로식후인슐린혈증, 지질대사지표등의악화를가져옴을밝힌바있다 16, 17, 27, 28. 고인슐린혈증과인슐린저항성은제 2형당뇨및몇몇대사질환의특징으로체내지방함량의증가와연관되어있다. 따라서운동으로근육내지방이증가된환자들의경우운동의중단이가져올수있는당대사및지질대사에대한부정적인결과를염려하여야하며이는당뇨병발생이후치료경과에도영향을미칠것으로생각할수있겠다. 본연구에서운동의과거력이없는대조군은인슐린저항성지표인 HOMA-IR이경구혈당강하제를사용하는치료기간에따라감소하는데반해, 운동의과거력이있는군은오히려 HOMA-IR의악화를보이는것을보아근육내지방으로인한인슐린저항성의악화를예상할수있겠다 (Table 2). 또한통계학적으로유의하지는않았으나공복혈당과식후 2시간혈당, 당화혈색소의감소에있어서도운동군에서그개선효과가대조군에비해감소되어있음을확인할수있었다 (Table 2, Figure 20

28 1,2). 운동의중단이인슐린저항성의악화를가져오는병리기전에대해서는뚜렷하게알려진바가없다. 한가지가능성은골격근내 GLUT4 단백질발현의감소이다. 운동은 GLUT4 단백질의발현을증가시켜근육세포내당의섭취율을증가시키게되는데운동의중단이이러한 GLUT4 단백질발현의감소를유발하여근육세포의당섭취효율의감소를유도할것으로생각해볼수있겠으며이전의한실험에서비슷한결과를보고한바있다 29. 그러나이와는반대로운동을중단하였을경우, 인슐린감수성은감소하였으나 GLUT4 단백질의발현에는차이가없었다는다른연구보고도있었다 30. 이러한상반되는결과는운동의종류, 강도및중단시기등의차이에의한것으로생각된다. 따라서운동의중단이 GLUT4 단백질발현에미치는영향을정확하게알아보기위해서는다양한환자군을대상으로하는추가적인연구가필요할것이다. 운동의중단으로인한인슐린저항성유발의다른가능성으로근육내지방축적의증가를생각해볼수있겠다. 운동은근육내지방산화효소활성의증가를유도하며활발한지방산화와분해를유도하는것으로알려져있다 10, 26. 그러나운동을중단했을경우, 근육세포의당과지방산화능력의감소가유발되고따라서근육세포의당이용률이나지방대사율의감소와지방축적이유발되어인슐린저항성의요인으로작용할것으로 21

29 생각되어진다. 그외에도운동의감소로인한에너지소비의감소로인한내장지방의증가를생각해볼수있다. 우리몸에서중요한에너지저장고는근육과지방조직이다. 운동의감소는에너지소비의감소를가져오게되고식후영양분은근육뿐아니라복부지방조직에축적되게된다. 이전의한연구에서운동의중단이허리 / 엉덩이비율의증가를보여복부지방축적을야기함을밝힌 바있다 31. 본연구에서는치료기간별두군의신체계측치의 변화를살펴보지않아이를확인하는데에한계가있으나혈청학적간효소수치의변화를비교하여보았을때, 운동군에서 2년째유의한증가를보였는데, 이러한결과또한복부지방축적에의한지방간의악화등을생각해볼수있을것이다. 본연구에서는과거근력운동을 2년이상지속하였다가최근 1년간운동을중단한환자들을대상으로당대사지표및치료기간에따른인슐린저항성의변화양상을대조군과비교, 분석하였다. 이전의일반인을대상으로한여러연구들에서운동을지속하다가운동을중단했을경우향상된대사지표들의급격한감소를보인다는것은강조한바있다 17, 27, 또한본연구를통해서운동의중단이이러한인슐린저항성의악화뿐만아니라당뇨병발생시, 당뇨치료경과에도부정적인영향을미침을확인할수있었다. 따라서운동을통해증가된인슐린감수성과혈당강하효과, 지질대사개선등을유지하기위해서는지속적인운동이 22

30 필요할것으로생각되며, 운동의과거력이있는당뇨환자의경우에는경구혈당강하제나식사요법뿐아니라, 운동요법을통한근육내지방산화능력의향상및체내인슐린저항성의개선을같이유도하여야혈당강화가효과적으로나타날것으로생각된다. 본연구는소규모환자를대상으로한후향적분석연구로서이를통해운동의중단과인슐린저항성의인과관계를뚜렷하게밝히는것은미흡하리라생각된다. 또한대상환자들의운동의종류와지속, 중단기간의통일성이결여되었고, 신체계측의변화가포함되어있지않다는한계점이있다. 따라서운동의중단이인슐린저항성, 당및지질대사에미치는영향에대한연구를위해서는향후대규모환자를대상으로하는장기간의전향적연구가진행되어야할것으로생각된다. 23

31 Ⅴ. 결론 운동의중단은인슐린저항성을유발하게되며당뇨병치료경과에있어서혈당강하및인슐린저항성개선에부정적인영향을미치는요소가된다. 따라서운동을통한인슐린감수성향상, 당및지질대사의개선을유지하기위해서는지속적인운동의유지가필요하며운동의과거력이있는당뇨병환자들의효과적인치료를위해서는운동요법이병행되어야할것으로생각된다. 24

32 < 참고문헌 > 1. 박이병, 김대중, 김재용, 김화영, 민경완, 박석원, 등. 국내당뇨병역학연구보고서. 대한당뇨병학회 2007: Castaneda C, Layne JE, Munoz-Orians L, Gordon PL, Walsmith J, Foldvari M, et al. A randomized controlled trial of resistance exercise training to improve glycemic control in older adults with type 2 diabetes. Diabetes Care 2002;25(12): Rice B, Hudson R, Janssen I, Ross R. Effects of Aerobic or Resistance Exercise and/or Diet on Glucose Tolerance and Plasma Insulin Levels in Obese Men. Diabetes Care 1999;22: Shaibi GQ, Cruz ML, Ball GD, Weigensberg MJ, Salem GJ, Crespo NC, et al. Effects of resistance training on insulin sensitivity in overweight Latino adolescent males. Med Sci Sports Exerc 2006;38(7): Boulé NG, Weisnagel SJ, Lakka TA, Tremblay A, Bergman RN, Rankinen T, et al. Effects of exercise training on glucose homeostasis: the HERITAGE Family Study. Diabetes Care 2005;28(1): Ryder JW, Chibalin AV, Zierath JR. Intracellular mechanisms underlying increases in glucose uptake in response to insulin or exercise in skeletal muscle. Acta Physiol Scand 2001;171(3): Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance 25

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38 <Abstract> The effect of detraining on insulin resistance and progress of type 2 diabetes mellitus in persistent strength trained athletes Kyoung Min Kim Department of Medicine The Graduate School, Yonsei University (Directed by Professor Bong Soo Cha) Background : The objective of this study was to determine the effects of long-term detraining on insulin resistance and progress of diabetes in athletes who were given persistent strength training previously. Methods : Thirty three newly diagnosed type 2 diabetes mellitus patients with previous persistent strength training and 53 of age- and body mass index- 31

39 matched untrained diabetic subjects were enrolled. Anthropometric parameters and serum metabolic variables were measured and compared at the time of diagnosis, after 1 year and 2 year of treatment with oral hypoglycemic agents. Results : There were no differences between two groups in the clinical characteristics and metabolic parameters at baseline except for the higher postprandial 2 hour C-peptide level and the lower high-density lipoprotein cholesterol in the trained group. The improvement of HbA1c, fasting glucose and postprandial 2 hour glucose levels after 1 and 2 year of treatment were much better in untrained group than trained group, without statistical significance. The level of HOMA-IR was increased after 2 year in the trained group (3.71 vs. 4.66, P <0.05), but was decreased in the untrained group (3.38 vs. 2.41, P <0.05). Therefore after 2 year, the level HOMA-IR was significantly higher in the trained group than untrained group. The untrained group showed significant decrease in the level of liver enzymes, particularly the serum alanine transferase, 2 years after the treatment, however the trained group showed the significant increase in that enzyme. Conclusions : Detraining resulted in insulin resistance and affected unfavorably in type 2 diabetes treatment and progress. Persistently trained subject did not seem to take advantage of their physical activity when they stopped exercise. Accordingly continuing physical exercise is required to 32

40 maintain the favorable metabolic effects of exercise. Moreover, exercise should be combined with the medical therapy for successful treatment of diabetes in trained subjects Key Words : insulin resistance, type 2 diabetes mellitus, exercise 33

DIABETES FACT SHEET IN KOREA 2012 SUMMARY About 3.2 million Korean people (10.1%) aged over 30 years or older had diabetes in 2010. Based on fasting g

DIABETES FACT SHEET IN KOREA 2012 Korean Diabetes Association (KDA) / Korea Centers for Disease Control and Prevention (CDC) DIABETES FACT SHEET IN KOREA 2012 SUMMARY About 3.2 million Korean people (10.1%)