대한내과학회지 : 제 70 권제 4 호 2006 당뇨병성족부병변에서임상경과와동맥경화증지표와의관계 전남대학교의과대학내과학교실 김경민 강세훈 조동혁 강호철 정동진 정민영 =Abstract= Relationship between clinical course and measures of atherosclerosis in diabetic foot Kyoung Min Kim, M.D., Se Hun Kang, M.D., Dong Hyeok Cho, M.D., Ho Cheol Kang, M.D., Dong Jin Chung, M.D. and Min Young Chung, M.D. Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea Background : Although various factors may influence the outcome of diabetic foot ulcers in diabetic subjects, the severity of peripheral vascular disease (PVD) is the main independent risk factor for amputation. The carotid intima-medial thickness (IMT), ankle brachial pressure index (ABPI) and pulse wave velocity (PWV) have been used as noninvasive markers of PVD. The present study aims to examine the association of carotid IMT, ABPI and PWV with the risk of lower extremity amputation in diabetic foot patients. Methods : Total 114 diabetic patients (39 diabetic foot patients and 75 patients who didn't have diabetic foot) were participated for the study. Twenty four of diabetic foot patients underwent lower extremity amputation. Informations about past history, social habit and courses of diabetic foot were collected from the patients by means of a structured interview. We measured carotid IMT, ABPI and PWV. Results : The following characteristics were significantly related to the development of diabetic foot ulcers: male, smoker, alcohol drinker, longer diabetes duration, presence of diabetic chronic complications, lower ABPI (<0.9), increased mean IMT (>0.8 mm), increased PWV. Patients with amputation had lower HDL cholesterol, higher incidence of osteomyelitis and older age, compared with patients without amputation. We observed a significant association between mean carotid IMT and the rate of amputation in diabetic foot patients [odd ratio, 11.42 (95% confidence interval, 1.03~ 127.19)]. Conclusions : This study suggests that measurement of carotid IMT as noninvasive index of atherosclerosis may be a useful indirect method in identifying diabetic foot patients who may have lower extremity amputation.(korean J Med 70:361-370, 2006) Key Words : Amputation, Diabetic foot, Intima-medial thickness 접수 : 2005 년 6 월 15 일 통과 : 2005 년 9 월 2 일 교신저자 : 정민영, 광주시동구학 1 동 8, 전남대학교의과대학내과학교실 (501-757) E-mail : mychung@chonnam.ac.kr - 361 -
-The Korean Journal of Medicine : Vol. 70, No. 4, 2006 - 서론당뇨병성족부병변은당뇨병환자에서비교적흔히볼수있는합병증중의하나로서약 15% 정도가일생동안한차례이상이환되는것으로보고되고있으며, 당뇨병환자의생존기간이연장되면서그유병율도더욱증가되고있는실정이다 1). 김등 2) 은당뇨병성족부병변의발생률이 2.6% 이며매년증가하는추세임을보여주고있다. 또한당뇨병환자가병원에입원하게되는원인의약 20% 를차지할만큼입원기간의증가및경제적인손실의중요한요인이되고있다 3). 당뇨병성족부병변은족부궤양, 봉와직염, 농양또는골수염등의형태로나타나며이들병변중의일부는괴사로진행되거나심한감염증으로인하여족부절단수술이필요한경우로악화되기도한다 3). 미국에서는매년당뇨병성족부병변환자가 50만명에서 1백만명에이르며, 이중약 5만건에서하지절단수술이시행되고있다 4). 또한하지절단수술과관련된직접적인비용만도 11 억불이상이소요되고있는것으로보고되고있다 5). 높은이환율및경제적인비용외에도당뇨병성족부병변이이환된환자는일반당뇨병환자보다사망률이 2배이상더높은것으로보고되고있다 6). 당뇨병성족부병변을야기하는병인으로는동맥경화증으로인한혈관병증및혈액순환장애와당뇨병성신경병증이가장중요한인자로알려져있으며특히동맥경화증으로인한족부혈류장애가당뇨병성족부병변의예후와연관이큰것으로알려져있다 7). 많은연구들에의하면당뇨병성족부병변환자에서말초혈관질환이동반되어있으며 8), 특히혈관조영술상에서하지동맥의협착정도가심할수록 9) 하지절단수술의빈도가증가된다고보고하고있다. 그러나이러한고식적인혈관조영술은말초혈관의상태를정확히반영할수있는반면에침습적이며쉽게시행할수없는단점들이있다. 이에비해발목위팔동맥압지수 (ABPI, ankle brachial pressure index), 맥박파전파속도 (PWV, pulse wave velocity), 경동맥초음파를이용한경동맥내중막두께 (carotid IMT, carotid intima-medial thickness) 측정은비침습적이고전신적인동맥경화증을잘반영할수있는것으로알려져있으며 10-14), 이러한동맥경화증의지표와말초혈관질환과의관련성이여러연구에서보고되고있다 15, 16). 하지만이러한비침습적인검사방법들이당뇨병성족 부병변의임상경과및예후와어떠한관련성을보이는지에대해서는보고가많지않으며검사방법들간에어떠한차이를보이는지에대해서도잘알려져있지않다. 따라서본연구는동맥경화증의정도를나타낼수있는비침습적인검사방법들이당뇨병성족부병변의임상경과와어떠한연관성이있는지를알아보고자하였다. 대상및방법 1. 대상 2004년 3월부터 2004년 9월까지전남대학교병원에입원한당뇨병환자 114명을대상으로하였다. 총 114명의당뇨병환자중 39명이당뇨병성족부병변의과거력이있거나현재이환되어있었으며, 75명은당뇨병성족부병변의병력이없었다. 39명의당뇨병성족부병변대상자중에서 24명이절단수술을시행하였다. 전체대상군의평균연령은 60.2±14.5세, 체질량지수는 23.3±3.6 kg/m 2, 당뇨병의평균유병기간은 14.0±0.9 년이었으며남성이 63.2% 였다. 2. 방법내원당시모든환자들을대상으로과거병력및흡연, 음주등의생활습관에대한문진을하였다. 이학적검사및혈압을측정하였으며, 신체계측을통한체질량지수 (BMI, body mass index) 를구하였다. 혈액학적검사로서는일반적인혈액검사외에 8시간이상금식시킨후총콜레스테롤, 고밀도지단백콜레스테롤, 저밀도지단백콜레스테롤, 중성지방을각각 enzymatic colorimetry, immunoinhibition method, direct selective method, glycerol-phosphate- oxidase method로측정하였으며장비는 AU5400 (Olympus R, Japan) 을이용하였다. 혈청 lipoprotein(a) 농도는 N Latex Lipoprotein(a) Reagent 를이용하여 immunonephelometer assay (Behring R, Germany) 로측정하였다. Apolipoprotein A1, Apolipoprotein B는 nephrometry (nephrometer analyser II, DADE Behring R, Germany) 로측정하였다. 저밀도지단백콜레스테롤이 100 mg/dl 이상이거나고밀도지단백콜레스테롤이 40 mg/dl 이하또는고지혈증에대한약물을투여중인환자들을고지혈증이있는것으로간주하였다. 당화혈색소는 ion exchange liquid chromatography (HLC-723 GHbV, TOSOH R, Japan) 법으로측 - 362 -
-Kyoung Min Kim, et al : Relationship between clinical course and measures of atherosclerosis in diabetic foot - Table 1. Comparison of clinical characteristics between diabetic foot patients with amputation and diabetic foot patients without amputation Age (year) Male (%) Duration of diabetes (year) Body mass index (kg/m 2 ) Alcohol (%) Smoking (%) Hyperlipidemia (%) Hypertension (%) Macrovascular complication (%) Peripheral vascular disease (%) Diabetic nephropathy (%) Diabetic retinopathy (%) Diabetic neuropathy (%) Osteomyelitis (%) UAE (mg/gcr) HbA 1C (%) Total cholesterol (mg/dl) HDL Cholesterol<40 mg/dl (%) LDL Cholesterol (mg/dl) Apo B (mg/dl) Apo A1 (mg/dl) Apo B/Apo A1 Lipoprotein(a) (mg/dl) Homocysteine (μmol/l) ABPI<0.9 (%) PWV (m/sec) Diabetic foot patients with amputation (n=24) 67.5±9.4 * 79.2 19.1±9.6 22.6±3.4 45.8 45.8 95.8 62.5 54.2 50.0 87.0 87.0 100.0 66.7 * 468.5±478.7 9.1±1.7 174.7±47.6 91.7 * 110.8±35.0 95.2±33.0 87.1±25.2 1.1±0.3 35.4±25.4 14.2±6.3 60.0 18.6±4.9 Diabetic foot patients without amputation (n=15) 59.8±8.2 86.7 15.2±7.8 23.7±3.0 73.3 60.0 93.3 66.7 46.7 40.0 71.4 76.9 100.0 28.6 359.4±730.2 8.5±1.7 160.6±52.4 64.3 103.0±46.1 94.9±32.3 91.8±26.8 1.1±0.4 27.5±20.2 9.6±2.3 33.3 17.7±5.5 *p<0.05, Mann-Whitney U test was done. Data are means±sd. ABPI, ankle brachial pressure index; IMT, intima-medial thickness; UAE, urine albumin excretion 정하였다. 당뇨병성신증은미세알부민뇨정량검사를시행하여요알부민배설율이 30 mg/gcr 미만인경우를정상, 요알부민배설율이 30~299 mg/gcr 인경우를미세알부민뇨, 요알부민배설율이 300 mg/gcr 이상이거나 24시간요단백이 500 mg/day 이상인경우를현성단백뇨로구분하였다. 당뇨병성망막증은경험있는안과의사에의한안저검사를통하여정상, 비증식성망막증및증식성망막증으로구분하였다. 당뇨병성신경병증은진동감각역치검사 (VPT, vibration perception threshold) 와심박수변화검사 (BBV, cardiac beat-to-beat variability) 및신경전도검사 (NCV, nerve conduction velocity) 를시행 하여감각신경병증, 자율신경병증및말초신경병증을진단하였다. 대혈관합병증은문진등을통하여협심증, 심근경색증, 뇌혈관질환, 말초혈관질환등의과거력이있거나, 심근관류스캔, 관상동맥조영술, 뇌자기공명영상및말초혈관촬영술등을통하여새로진단된경우로하였다. 말초혈관질환의경우에는과거력이있거나하지혈관조영술상협착소견을보이는경우를말초혈관질환이있은것으로간주하였다. 동맥경화증을반영하는지표로서는발목위팔동맥압지수, 맥박파전파속도, 경동맥내중막두께를기준으로하였다. 발목위팔동맥압지수와맥박파전파속도의측정은자동화된 ABPI/PWV 측정기 (VaSera TM, VS-1000 R, Japan) 를이용하였고, 발목 - 363 -
- 대한내과학회지 : 제 70 권제 4 호통권제 548 호 2006 - Table 2. Association between amputation and IMT in diabetic foot patients (n=26) * Mean IMT>0.8 mm Maximal IMT>1.0 mm Crude Odds Ratio (95% CI) 6.50 (1.09-38.63) 5.83 (0.95-35.71) Adjusted Odds Ratio (95% CI) 11.41 (1.03-127.19) 11.19 (0.88-142.03) * Carotid IMT was measured in 26 diabetic foot patients, 17 with amputation and 9 without amputation. Adjusted for age and HDL cholesterol p<0.05, CI, confidence interval; IMT, intima-medial thickness Table 3. Correlation between IMT and other measures (n=64) Age Maximal IMT Mean IMT 0.55 * (<0.001) 0.57 (<0.001) 0.26 0.31 DM duration (0.04) (0.01) -0.14-0.12 HbA 1C (0.26) (0.33) Homocysteine UAE LDL cholesterol 0.27 (0.09) -0.10 (0.46) 0.03 (0.80) 0.30 (0.06) -0.08 (0.57) -0.01 (0.92) -0.08-0.11 HDL cholesterol (0.54) (0.38) * correlation coefficient (p value) p<0.05, IMT, intima-medial thickness; DM, diabetes mellitus; UAE, urine albumin excretion 위팔동맥압지수는각각우측과좌측의상완과발목부위혈압의비로계산하여그수치가 0.9 미만인경우를이상소견으로간주하였다. 경동맥내중막두께의측정은고해상도 B-모드초음파기기인 LOGIQ7 (GE Medical Systems R, USA) 의 10 MHz 선상탐촉자를이용하였고측정시의오차를줄이기위하여동일한검사자에의하여시행되었다. 환자를앙와위로하고전사위및측위에서초음파를투시하여좌측과우측경동맥의종단면을따라총경동맥이내경동맥과외경동맥으로분리되는분지점의근위부에위치한총경동맥의초음파영상을얻었으며, Pignoli 등의방법 17) 에따라처음반사면의선연으로부터두번째반사면의선연까지의거리를컴퓨터프로그램 (Intimascope, Mediacross R, Japan) 을이용하여원벽에서내중막두께 가최고인지점을측정하여좌우의평균을구하여최대경동맥내중막두께 (maximal carotid IMT) 로하였고이를중심으로근위 10 mm, 원위 10 mm 사이의평균값을구하고좌우의평균값을평균경동맥내중막두께 (mean carotid IMT) 로하였다. 이때내중막두께의측정이예정된부위가석회화되었거나내강내로돌출된병변이면서초음파상이질성을보이는죽전 (plaques) 이있는경우에는죽전이포함되지않은근위부에서측정을시행하였다. 3. 통계처리모든자료는평균값 ± 표준편차및퍼센트로표시하였다. 그룹간평균비교는 Mann-Whitney U test를이용하였고, 그룹간율의비교는카이검정법을이용하였다. - 364 -
- 김경민외 5 인 : 당뇨병성족부병변에서임상경과와동맥경화증지표와의관계 - Table 4. Comparison of clinical characteristics between diabetic patients with diabetic foot and without diabetic foot Diabetic patients with diabetic foot (n=39) Diabetic patients without diabetic foot (n=75) Age (year) Male (%) Duration of diabetes (year) Body mass index (kg/m 2 ) Alcohol (%) Smoking (%) Hyperlipidemia (%) Hypertension (%) Macrovascular complication (%) Peripheral vascular disease (%) Nephropathy (%) Retinopathy (%) Neuropathy (%) UAE (mg/gcr) HbA 1C (%) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL Cholesterol (mg/dl) LDL Cholesterol (mg/dl) ApoB (mg/dl) ApoA1 (mg/dl) ApoB/ApoA1 Lipoprotein(a) (mg/dl) Homocysteine (μmol/l) ABPI<0.9 (%) Maximal PWV (m/sec) Maximal IMT>1.0 mm (%) Mean IMT>0.8 mm (%) 64.6±9.4 82.1 * 17.6±9.1 * 23.0±3.2 56.4 * 51.3 * 94.9 * 64.1 51.3 * 46.2 * 81.1 * 83.3 * 100.0 * 428.0±576.7 * 8.9±1.7 169.6±49.2 164.7±103.9 31.2±11.4 * 107.9±39.0 95.1±32.3 88.8±25.6 * 1.1±0.3 * 32.5±23.7 12.5±5.5 47.4 * 18.1±5.1 * 57.7 69.2 * 57.9±16.0 53.3 12.2±8.6 23.5±3.8 24.3 29.7 78.7 48.0 29.3 5.3 59.5 47.4 70.5 274.5±486.8 9.0±2.5 172.2±58.4 136.8±70.8 43.3±14.9 106.7±52.1 91.0±36.6 117.7±35.7 0.8±0.3 30.7±33.3 11.2±5.7 20.6 15.3±3.3 42.1 42.1 * p<0.05, Mann-Whitney U test was done. Data are means±sd. ABPI, ankle brachial pressure index; IMT, intima-medial thickness; PWV, pulse wave velocity; UAE, urine albumin excretion 당뇨병성족부병변환자에서경동맥내중막두께와하지절단수술과의관련성을보기위하여로지스틱회귀분석을시행하였다. p 값은 0.05 미만일때통계적으로유의하다고판정하였다. 통계처리기법은 SPSS 11.0 for Windows (SPSS R Inc, chicago, IL) 를이용하였다. 결과당뇨병성족부병변의병력이있는환자군 (n=39) 에서각환자별족부병변의평균갯수는 1.8개였고, 절단수술 을시행하였던환자는 24명 (61.5%) 이었다. 절단수술을시행하였던군 (n=24) 과시행하지않은군 (n=15) 사이의임상양상을비교해보면절단수술을시행하였던군에서연령이유의하게높았고, 골수염의유병율이높았으며, 고밀도지단백콜레스테롤이 40 mg/dl 미만인환자의비율이유의하게높았다 ( 표 1). 동맥경화증의지표에대한비교에서는절단수술을시행한군과시행하지않은군사이에발목위팔동맥압지수및맥박파전파속도값의유의한차이는없었다 ( 표 1). 절단수술을시행하였던군 - 365 -
-The Korean Journal of Medicine : Vol. 70, No. 4, 2006 - Table 5. Risk factors of diabetic foot development determined by multiple logistic regression Factors Sex Female Male Macrovascular complication No Yes Smoking No Yes Alcohol No Yes HDL cholesterol 40 mg/dl <40 mg/dl ABPI 0.9 <0.9 Crude Odds Ratio (95% CI) 3.99 (1.57-10.18) * 2.53 (1.13-5.64) * 2.48 (1.11-5.54) * 4.02 (1.76-9.19) * 5.33 (2.09-13.63) * 3.46 (1.16-10.27) * * p<0.01, p<0.05 CI, confidence interval; ABPI, ankle brachial pressure index Adjusted Odds Ratio (95% CI) 2.17 (0.39-11.94) 3.05 (0.80-11.64) 1.02 (0.18-5.53) 4.99 (0.98-25.3) 3.30 (0.89-12.2) 1.60 (0.41-6.19) 이평균경동맥내중막두께가 0.8 mm 이상인비율이유의하게높았고, 절단수술에대한경동맥내중막두께의관련성을보기위해서로지스틱회귀분석을시행한결과평균경동맥내중막두께가절단수술과유의한관계를보여주었으며 [odd ratio, 6.50 (95% confidence interval, 1.09~38.63)], 이를연령및고밀도지단백콜레스테롤농도로보정한이후에도통계적으로유의하였다 [odd ratio, 11.42 (95% confidence interval, 1.03~ 127.19)] ( 표 2). 경동맥내중막두께값과환자의연령및당뇨병의유병기간과유의한상관관계를보여주었으나당화혈색소, 요알부민배설율및고지혈증과는유의한상관관계를보이지않았다 ( 표 3). 또한당뇨병성족부병변의병력이있는당뇨병환자와병력이없는당뇨병환자사이의차이점을비교하였다 ( 표 4). 당뇨병성족부병변의병력이있었던환자에서남성, 흡연자, 알코올섭취자, 고지혈증, 만성당뇨병성합병증, 대혈관합병증, 말초혈관질환, 발목위팔동맥압지수 0.9 미만, 평균경동맥내중막두께 0.8 mm 이상인비율이통계적으로유의하게많았고, 요알부민배설율과맥박파전파속도값이유의하게높았다. 또한고밀도지단 백콜레스테롤, Apo A1 농도가통계적으로유의하게낮았다. 당뇨병성족부병변과관련된위험인자들에대한단순로지스틱회귀분석에서는남성인경우, 대혈관합병증이있는경우, 흡연력이있는경우, 알코올섭취시, 고밀도지단백콜레스테롤이 40 mg/dl 이하인경우, 발목위팔동맥압지수가 0.9 미만인경우에서유의하게당뇨병성족부병변의위험성이증가함을알수있었다. 그러나각각의위험인자들로다중로지스틱회귀분석을시행한결과통계적으로유의한독립적인위험인자는발견되지않았다 ( 표 5). 고찰당뇨병관리방법의개선과더불어당뇨병성혈관합병증같은만성합병증이급성대사성합병증보다당뇨병의이환율과사망률을높이는중요한인자로부각되고있다 18). 이러한만성합병증중에서특히당뇨병성족부병변이최근증가되고있어이로인한막대한시간적, 경제적손실을초래하고있다 19). 일반적으로당뇨병환자들은비당뇨병환자에비하여족부의궤양과괴저가발생하기쉽고, 절단술을받을위 - 366 -
-Kyoung Min Kim, et al : Relationship between clinical course and measures of atherosclerosis in diabetic foot - 험이 70배가더높다고보고되고있다 20). 당뇨병성족부병변은초기에보존적치료, 약물치료, 죽은조직절제술 (debridement) 등을통하여호전될수있으며, 이러한적극적인초기치료를통하여절단수술의빈도를줄일수있다 21). 따라서당뇨병성족부병변의고위험환자를미리예측하여적극적인예방법을시행하고발생초기에당뇨병성족부병변에대한적극적인치료가하지절단을줄이는데가장효과적일것으로생각된다. 당뇨병성족부병변의발병원인으로동맥경화증, 동맥혈관내의칼슘침착, 미세혈관병증등에의한허혈, 통증감각의소실, 발근육의마비와자율신경병증등의신경장애, 감염그리고이들의혼합등을생각할수있다 22). 이처럼다양한요인들이당뇨병성족부병변의발생과관련되어있으며, 이는당뇨병성족부병변이다양한병태생리기전들에의하여발생함을간접적으로시사한다고할수있다. 현재까지당뇨병성족부병변의위험인자에대한수많은보고들이있다. Benotmane 등 23) 은당뇨병성족부병변의발생이남성, 40세이상의연령, 혈관병증및신경병증이있는경우에유의하게많았음을보고하였으며, Bresater 등 24) 은알코올섭취와당뇨병성족부병변의연관성을보고한바있다. 또한 Edward 등 25) 은당뇨병성족부병변의위험인자에대한후향적연구를통하여당뇨병성족부병변을갖는군에서키가크거나, 비만이거나, 당뇨병의유병기간이길거나, 인슐린의사용기간이길거나, 혈당및당화혈색소와혈청크레아티닌농도가높거나, 족부변형이나시력이나쁜경우가많았으나당뇨병성족부병변의발생과환자의연령, 인종, 흡연력과는유의한상관관계가없음을보고하였다. 그리고 5.07 monofilament 검사에의한신경병증, 인슐린의사용, 비만, Charcot 변형, 시력저하등이독립적인위험인자임을보고하였다. Kobayashi 등 26) 은고밀도지단백콜레스테롤감소시에당뇨병성족부병변의발생이증가함을보여주었다. 본연구에서는당뇨병성족부병변을동반한군에서남성과알코올섭취자및흡연력이있는경우가유의하게많았으며, 당뇨병의유병기간도더길었다. 또한당뇨병성족부병변을갖는군에서고밀도지단백콜레스테롤과이를반영하는 Apo A1 농도가유의하게낮았고, Apo B/Apo A1은유의하게높았다. 그러나당화혈색소, 연령및체질량지수와는유의한상관관계가없어상기연구들과는차이를보여주고있다. 그리고각각의위험인자들간의단순로지스틱회귀 분석을통하여남성, 대혈관합병증, 흡연, 알코올섭취, 저고밀도지단백콜레스테롤혈증, 낮은발목위팔동맥압지수가통계적으로유의한위험도의증가를보여주었으나다중로지스틱회귀분석에서는독립적인위험인자를발견할수없었다. 당뇨병성족부병변의발생및치료에영향을주는인자로당뇨병성만성합병증과의연관성을보고한연구들도많다. Murphie 등 27, 28) 은당뇨병성족부병변환자에서소혈관에나타나는여러혈류역학적인이상소견을증명하였으며진행된당뇨병성신증, 망막증및신경병증이있는환자에서족부병변의빈도가증가됨을보고하였다. 특히당뇨병성신경병증과당뇨병성족부병변의관계는그밖의여러연구를통해증명되었다 25, 29). 본연구에서도당뇨병성족부병변이있는환자에서당뇨병성신경병증이동반된경우가 100% 였으며, 당뇨병성족부병변이없는환자에서는당뇨병성신경병증이 70.5% 에서동반되어통계적으로유의한차이를보여주고있다. 당뇨병성신경병증이당뇨병성족부병변의발생에기여하는기전으로는운동신경병증, 자율신경병증, 감각신경병증등이각각모두작용하는것으로알려지고있다. 즉자율신경병증은족부에혈액의저류를증가시키고족부의부종을일으킬수있으며, 운동신경병증은족부근육의위축을일으키고이는족부의변형과관절의운동을감소시키게되며, 결국이러한변화는발바닥의압력이증가되는범위를넓히게된다. 여기에감각신경병증으로인한감각의소실은압력이증가된부분에서잦은손상을초래하고결국당뇨병성족부병변을유발하게된다고설명하고있다 30). 당뇨병성대혈관합병증및이와관련된동맥경화증과당뇨병성족부병변과의연관성이많은연구들에서보고된바있다. Birrer 등 31) 은동맥경화증의진행이심혈관계질환, 뇌경색증등의대혈관합병증을증가시키는것처럼당뇨병성족부병변도동맥경화증과연관성이있음을제시하고있다. 본연구에서는말초혈관질환의과거력이있었거나혈관조영술상말초혈관질환이증명된환자에서그렇지않은환자에비하여당뇨병성족부병변의발생이통계적으로유의하게증가함을보여주었다. 또한동맥경화증의비침습적인지표로널리이용되는여러검사법들이당뇨병성족부병변의발생을예측할수있다는보고들도있다. Jirkovska 등 32) 은동맥경화증의지표중에서특히발목위팔동맥압지수가낮은경 - 367 -
- 대한내과학회지 : 제 70 권제 4 호통권제 548 호 2006 - 우에당뇨병성족부병변의발생이증가함을증명한바있다. 본연구에서는동맥경화증의비침습적인지표들중에서발목위팔동맥압지수, 맥박파전파속도및경동맥내중막두께등이당뇨병성족부병변에미치는영향을조사하였는데, 당뇨병성족부병변이있는군에서발목위팔동맥압지수가통계적으로유의하게낮았고, 맥박파전파속도와평균경동맥내중막두께가증가함을관찰할수있어여러다른연구들과비슷한결과를보여주었다. 이처럼많은인자들이당뇨병성족부병변의발생과연관되어있음을알수있고, 이러한위험인자들의교정을통하여당뇨병성족부병변의발생을줄일수있을것으로판단된다. 족부병변이이미발생된경우에어떠한인자가임상경과에영향을미치는지에대한연구에서당뇨병성신경병증과말초혈관질환이당뇨병성족부병변과이로인한절단수술의중요한위험인자로인식되어왔다 33). Hill 등 34) 은말초혈관질환에의한허혈이당뇨병성족부병변의유발요인이며, 내원기간의단축과하지절단수술을예방하는데있어서말초혈관질환이중요한치료대상임을보고하였다. 최근의보고들에서당뇨병성족부병변의발생에는신경병증의변화가주로관여하나상처치유와관련해서는혈관병증이더중요하다는연구들이있다 35). 또한당뇨병성족부병변의예후에영향을줄수있는검사들에대한연구에서는상처부위에대한혈액공급의장애를대변해줄수있는검사결과가족부병변의상처치유실패와관련이있다고보고된바있다 36). 이처럼당뇨병성말초혈관병증이당뇨병성족부병변의발생과임상경과사이에서중요한역할을하는인자임이밝혀지고있다. 이러한당뇨병성말초혈관병증의발생과연관이있는것으로보고되고있는검사들로는동맥경화증의지표로사용되어지고있는발목위팔동맥압지수, 맥박파전파속도, 경동맥내중막두께등이있다 10-16). 본연구에서는당뇨병성족부병변환자에서평균경동맥내중막두께가증가할수록절단수술을시행한비율이유의하게증가하였으며, 이는연령및고밀도지단백콜레스테롤농도로보정한후에도유의한결과를보여주고있다. 하지만발목위팔동맥압지수는당뇨병성족부병변으로절단수술을시행한군에서절단수술을시행하지않은군보다수치가낮은경향을보이고는있으나통계적유의성은없었다. 맥박파전파속도는당뇨병성족부병변으로절단수술을시행한군에서수치가높은경 향을보이고있으나통계적유의성은없었다. 그외에당뇨병성족부병변으로절단수술을시행한군에서골수염의빈도가높았고연령도더많았으며고밀도지단백콜레스테롤 40 mg/dl 이하인비율이더높은것으로나타났으며, 절단수술을하게되는데있어서골수염의유무가중요하다는일반적인보고들과일치된다. 임상에서당뇨병성족부병변환자를진료할때이환자가과연절단수술을해야하는지, 아니면간단한괴사조직의제거와피부이식만으로완치될수있는지, 또는약물치료등의보존적인요법만으로도호전될수있을지여부를조기에판단하는것은어려우며이에대한지침이필요한실정이다. 본연구의결과에따르면당뇨병성족부병변에서절단수술을시행한군이족부병변의골수염과저고밀도지단백콜레스테롤혈증을더많이갖고있었으며연령도더많고평균경동맥내중막두께값이더높았는데, 당뇨병성족부병변환자가절단수술을시행해야하는지가능성을예측하는데참고할수있을것으로사료된다. 그러나그외의동맥경화증의지표로사용되는발목위팔동맥압지수나맥박파전파속도등의비침습적인검사가당뇨병성족부병변의예후와어떤연관성이있는지에대해서는더많은환자를대상으로한연구가필요하리라사료된다. 요약목적 : 당뇨병성족부병변은장기간의치료를요하게되고, 흔히절단에이르는경우가많아이환기간및신체장애가중요한사회적인문제가되고있다. 당뇨병성족부병변으로인한절단수술은말초혈관질환과연관이있는것으로알려져있고, 발목위팔동맥압지수, 맥박파전파속도, 경동맥내중막두께등이말초혈관질환의비침습적인지표로이용되어지고있다. 이에본연구는동맥경화증의지표가당뇨병성족부병변환자의임상경과와연관성이있는지알아보고자하였다. 방법 : 전남대학교병원에입원한당뇨병환자중 114 명을대상으로하였으며, 그중 39명은당뇨병성족부병변이이환되어있거나족부병변으로치료하였던과거력이있었고, 75명은당뇨병성족부병변의병력이없었다. 39명의당뇨병성족부병변환자중에 24명이절단수술을시행하였다. 모든환자들을대상으로과거력및생활습관에대하여문진하였으며, 당뇨병성족부병변이있었던환자들은족부병변의치료기간및치료방법등에 - 368 -
- 김경민외 5 인 : 당뇨병성족부병변에서임상경과와동맥경화증지표와의관계 - 대하여조사하였다. 동맥경화증의지표로서발목위팔동맥압지수, 맥박파전파속도및경동맥내중막두께를측정하였다. 결과 : 동맥경화증지표와의관련성을보았을때당뇨병성족부병변이있는군에서없는군에비하여발목위팔동맥압지수가 0.9 미만인비율과평균경동맥내중막두께의값이 0.8 mm 이상인비율이유의하게높았으며맥박파전파속도가유의하게높았다. 당뇨병성족부병변의임상경과중절단수술과의연관성을살펴보면평균경동맥내중막두께가절단수술과유의한관련이있었으며 [odd ratio, 6.50 (95% confidence interval, 1.09~ 38.63)], 연령과고밀도지단백콜레스테롤농도로보정한후에도유의하였다 [odd ratio, 11.42 (95% confidence interval, 1.03~127.19)]. 또한절단수술을시행하였던군에서는연령이높거나, 골수염또는저고밀도지단백콜레스테롤혈증 (<40 mg/dl) 을보이는경우가유의하게많았다. 결론 : 비침습적인동맥경화증의지표중의하나인경동맥내중막두께의측정이당뇨병성족부병변환자들에서절단수술의가능성을미리예측해볼수있는간접적인방법들중의하나가될수있을것으로사료된다. 색인단어 : 당뇨병성족부병변, 경동맥내중막두께, 절단 REFERENCES 1) Palumbo PJ, Melton LJ. Peripheral vascular disease and diabetes. In: Diabetes in America. no. 85-1468, Washington, U.S. Govt. Printing Office, NIH publ. 1985 2) 김재만, 김덕윤, 우정택, 김성운, 양인명, 김진우, 김영설, 김광원, 최영길. 당뇨병성족부병변의임상적관찰. 당뇨병 17:387-394, 1993 3) Gibbons GM, Eliopoulos GM. Infection of the diabetic foot. In: Kozak GP, Campbell DR, Frykberg RG, Habershaw GM, eds. Management of diabetic foot problems. p. 121-129, Philadelphia, WB Saunders, 1995 4) Eckman MH, Greenfield S, Mackey WC, Wong JB, Kaplan S, Sullivan L, Dukes K, Pauker SG. Foot infections in diabetic patients: decision and costeffectiveness analyses. JAMA 273:712-720, 1995 5) Levin ME. Preventing amputation in the patient with diabetes. Diabetes Care 18:1383-1394, 1995 6) Boyko EJ, Ahroni JH, Smith DG, Davignon D. Increased mortality associated with diabetic foot ulcer. Diabet Med 13:967-972, 1996 7) American Diabetes Association. Peripheral arterial disease in people with diabetes. Diabetes Care 26:3333-3341, 2003 8) Real Collado JT, Valls M, Basanta Alario ML, Ampudia Blasco FJ, Ascaso Gimilio JF, Carmena Rodriguez R. Factors associated with amputation in diabetic patients with foot ulcer. An Med Interna 18:59-62, 2001 9) Faglia E, Favales F, Quarantiello A, Calia P, Clelia P, Brambilla G, Rampoldi A, Morabito A. Angiographic evaluation of peripheral arterial occlusive disease and its role as a prognostic determinant for major amputation in diabetic subjects with foot ulcers. Diabetes Care 21:625-630, 1998 10) Poli A, Tremoli E, Colombo A, Sirtori M, Pignoli P, Paoletti R. Ultrasonographic measurement of the common carotid artery wall thickness in hypercholesterolemic patients: a new model for the quantitation and follow-up of preclinical atherosclerosis in living human subjects. Atherosclerosis 70:253-261, 1988 11) Yamashina A, Tomiyama H, Takeda K, Tsuda H, Arai T, Hirose K, Koji Y, Hori S, Yamamoto Y. Validity, reproducibility, and clinical significance of noninvasive brachial-ankle pulse wave velocity measurement. Hypertens Res 25:359-364, 2002 12) Norman PE, Eikelboom JW, Hankey GJ. Peripheral arterial disease: prognostic significance and prevention of atherothrombotic complications. Med J Aust 181:150-154, 2004 13) 고영국, 박석원, 김대중, 장혁재, 안철우, 남재현, 송영득, 임승길, 김경래, 이현철, 허갑범. 인슐린비의존형당뇨병환자에서고해상도 B-mode 초음파로측정한경동맥내중막두께와죽상경화증위험인자들과의관계. 당뇨병 23:234-242, 1999 14) 박태선, 백홍선. 당뇨병성대혈관합병증에서경동맥내막 - 중막두께측정의유용성. 당뇨병 23:230-233, 1999 15) Yokoyama H, Shoji T, Kimoto E, Shinohara K, Tanaka S, Koyama H, Emoto M, Nishizawa Y. Pulse wave velocity in lower-limb arteries among diabetic patients with peripheral arterial disease. J Atheroscler Thromb 10:253-258, 2003 16) Poredos P, Golob M, Jensterle M. Interrelationship between peripheral arterial occlusive disease, carotid atherosclerosis and flow mediated dilation of the brachial artery. Int Angiol 22:83-87, 2003 17) Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. - 369 -
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