DOI : 10.4093/kdj.2009.33.5.392 ORIGINAL ARTICLES 제 2 형당뇨병환자에서대사증후군과만성합병증과의관계 고려대학교의과대학내과학교실 1, 한림대학교의과대학내과학교실 2, 연세대학교원주의과대학내과학교실 3 정혜수 1 ㆍ서지아 1 ㆍ김신곤 1 ㆍ김난희 1 ㆍ김두만 2 ㆍ정춘희 3 ㆍ최동섭 1 Relationship Between Metabolic Syndrome and Risk of Chronic Complications in Koreans with Type 2 Diabetes Hye Soo Chung 1, Ji A Seo 1, Sin Gon Kim 1, Nan Hee Kim 1, Doo Man Kim 2, Choon Hee Chung 3, Dong seop Choi 1 1 Department of Internal Medicine, Korea University College of Medicine, 2 Department of Internal Medicine, Hallym University College of Medicine, Seoul, 3 Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea Abstract Background: We examined the relationships between components of metabolic syndrome at the time of diagnosis of type 2 diabetes, and the development of chronic complications in Korean patients with type 2 diabetes. Methods: The medical records of patients with type 2 diabetes who had undergone treatment for at least five years prior were collected from 10 general hospitals in Korea. Among a total of 1,418 patients reviewed for possible inclusion in this study, 603 patients were selected, and the occurrence of complications among these patients was evaluated. Results: Among the 603 patients (male, 253; female, 350), 154 males (60.8%) and 266 females (76.0%) were diagnosed with metabolic syndrome at the time of initial diagnosis of type 2 diabetes. The incidence of chronic complications (average follow-up 15.2 ± 4.9 years) included 60 cases of coronary artery disease (CAD), 57 cases of cerebrovascular accident (CVA), 268 cases of diabetic retinopathy (DR), 254 cases of diabetic nephropathy (DN), and 238 cases of diabetic peripheral neuropathy (DPN). As compared to patients without metabolic syndrome, the adjusted relative risks (95% CI) of incidental diabetic complications in patients with metabolic syndrome were 3.28 (1.40~7.71) for CAD, 2.04 (0.86~4.82) for CVA, 1.53 (1.10~2.14) for DR, 1.90 (1.29~2.80) for DN, and 1.51, (1.06~2.14) for DPN. With the addition of just one constituent of metabolic syndrome, the relative risk of developing CAD, CVD, DR, DN, and DPN increased by 2.08 (95% CI, 1.27~3.40), 1.16 (0.80~1.66), 1.09 (0.93~1.26), 1.29 (1.06~1.57) and 1.06 (0.87~1.26), respectively. Conclusion: Metabolic syndrome in Korean patients with type 2 diabetes increases the risk of developing both macrovascular and microvascular complications. (Korean Diabetes J 33:392-400, 2009) Key words: Diabetes complication, Metabolic syndrome X, Type 2 diabetes mellitus 접수일자 : 2009 년 4 월 6 일, 통과일자 : 2009 년 7 월 23 일교신저자 : 최동섭, 고려대학교의과대학내과학교실, E-mail: cdongs@kumc.or.kr 392
정혜수외 6 인 : 제 2 형당뇨병환자에서대사증후군과만성합병증과의관계 서론대사증후군은인슐린저항성과고혈압, 이상지질혈증을특징으로하고있으며, 대부분과체중이나비만을동반하고있다. 대사증후군은또한심혈관질환의위험인자이며, 모든원인으로인한사망과연관되어있다고보고되었다 1,2). 제2 형당뇨병환자의경우제1형당뇨병과달리대사증후군의유병률이높다고보고되고있으며, 제2형당뇨병환자가대사증후군을동반할때사망률이증가한다고알려져있다 1-3). 또한제2형당뇨병의대혈관및미세혈관합병증과고혈압, 이상지질혈증등의대사증후군의구성요소들과의연관성에대한연구들이발표되어있다 4,5). 제2형당뇨병환자에서만성합병증의유병률은종족간에차이가있으며관련인자에대한보고도다양하다 6-15). 한국인의당뇨병은구미각국의그것에비해합병증의발생양상이다른것으로알려져있어 10-13) 구미지역의연구결과를그대로적용하기어렵다. 중국인제2형당뇨병환자를대상으로한연구에서 75.1% 의환자가대사증후군의진단기준을만족하였고 14), 한국인환자를대상으로한연구에서 60~70% 의환자가대사증후군의진단기준을만족하여많은수에서동반질환을보임에도불구하고 15,16), 한국인에서대사증후군의유무에따른당뇨병성만성합병증의발생에대한보고는적은실정이다. 따라서한국인제2형당뇨병환자를대상으로대사증후군및그구성인자에따른대혈관및미세혈관합병증의발생정도를알아보기위해후향적연구를시행하였다. 족력, 식단관리, 운동, 흡연, 음주, 공복혈당, 식후 2시간혈당, 당화혈색소 (HbA1c), 총콜레스테롤, 중성지방, HDL-콜레스테롤 (high density lipoprotein-cholesterol), 혈당관리및혈관합병증발생여부에대하여구조화된증례기록서로하였다. 2. 대사성증후군의진단 National Cholesterol Education Panel-Adult Treatment Panel (NCEP-ATP) III의대사증후군진단기준은 1) 복부비만 : 남성에서허리둘레 > 102 cm, 여성에서 > 88 cm, 2) 고중성지방혈증 (hypertriglyceridemia): 150 mg/dl, 3) 저 HDL-콜레스테롤혈증 : 남성에서 < 40 mg/dl, 여성에서 < 50 mg/dl, 4) 고혈압 : 130/85 mm Hg 또는고혈압약복용중, 5) 고혈당 : 공복혈당 110 mg/dl 진단중 3가지이상을만족하는경우로정의하였다 17). 본연구에서는대사증후군을진단하기위하여 NCEP-ATP III criteria가사용되었으나, 허리둘레대신 WHO (World Health Organization) 진단기준에포함되어있는체질량지수를포함하였고 18), 기준치는아시아태평양지역에서과체중의기준인 BMI (body mass index) 23 kg/m 2 를이용하였다. 제2형당뇨병환자를대상으로한소그룹연구이기때문에 NCEP-ATP III 의진단기준중고혈당항목은모두만족한다는가정하에다른나머지진단기준중 2가지이상을만족하는경우대사증후군으로진단하였고, 진단시점또한제2형당뇨병이처음진단된때를기준으로하였다. 1. 대상환자 대상및방법 3. 혈관계합병증진단 제2형당뇨병의혈관합병증은대혈관및미세혈관합병증으로나누었으며, 각각의진단은다음과같이하였다. 본연구는 1980년부터 1994년까지한국 10개의종합병원에서새로이당뇨병을진단받고 5년이상추적관리를받은환자 ( 진단당시연령만 30세이상, 75세미만 ) 를대상으로하는후향적연구로진행되었으며전체적으로 1,418명의환자의자료가수집되었다. 그중제1형당뇨병, 유전적결함또는췌장질환, 약물로인한당뇨병환자, 진단당시심혈관질환, 당뇨병만성합병증이있는경우는제외하였고, 당뇨병진단당시대사증후군 4가지요소에대한정보가있는 603명의환자가포함되었다. 자료수집전 IRB 승인과모든환자의동의서를받았으며, 자료수집기간은 2004년 7 월부터 2004년 8월이었다. 자료수집은환자의등록기준과증례기록서작성지침을기준으로, 의무기록과가능한경우회상면담을통해진단당시의체질량지수, 혈압, 과거력, 가 1) 대혈관합병증대혈관합병증으로는관상동맥질환 (coronary artery disease, CAD) 과뇌혈관질환 (cerebrovascular accident, CVA) 을포함하였다. 관상동맥질환은전형적인흉통, 심전도상협심증이나심근경색에합당한변화, 심장효소의의미있는상승중 2가지이상을만족하는경우나혈관조영술검사결과를참고하여진단하였고, 뇌혈관질환은컴퓨터단층좔영등영상검사로확인된경우진단하였다. 별도의검사를실시하지않은경우는없는것으로간주하였다. 2) 미세혈관합병증당뇨병성망막병증 (diabetic retinopathy, DR) 은안과의사에의하여시행한안저검사결과증식성망막증또는비증식 393
성망막증이있는경우로진단하였으며, 당뇨병성신증 (diabetic, nephropathy, DN) 은미세알부민뇨, 단백뇨, 질소혈증을포함하였다. 미세알부빈뇨 (microalbuminuria, MA) 는뇨알부민수치가 30~300 mg/day인경우, 단백뇨는뇨스틱검사가양성 (++ 이상또는 + 가 2회이상 ) 이거나 24시간소변에서뇨알부민수치가 300 mg/day이상, 또는단백질배설이 500 mg/day 이상인경우로정의하였다. 질소혈증은혈중크레아틴수치가 2.0 이상으로정의하였으며, 질소혈증과단백뇨를가지는경우모두를현성당뇨병성신증 (overt nephropathy, ON) 으로분류하였다. 당뇨병성신경병증 (diabetic peripheral neuropathy, DPN) 은치료약제 (tricyclic antidepressant, gabapentin, and other analgesics) 를복용중이며전형적인말초신경병증증상을가진경우와근전도검사결과가양성인경우로정의하였다. 4. 통계분석대사증후군이있는그룹과없는그룹사이의기본적임상적특징비교를위해 t-test 또는 chi-square를시행하였고, 평균값과표준편차를제시하였다. 대사증후군의유무에따라서 또는대사증후군의각각의독립된구성요소에따라생기는당뇨병합병증발생은비례위험분석 (i.e. Cox s proportional hazard model) 을이용하였고대사증후군유무, 나이, BMI, 혈압, 중성지방, 고밀도콜레스테롤, 진단당시 HbA1c, 연구기간동안의평균 HbA1c를설명변수로하였다. 합병증의발생양상을대사증후군의유무에따라살펴본누적위험함수를구하였고, 각예후요인을층화변수로하여살펴본 Log rank test 통계량과그유의성도함께제시하였다. 각범주화된집단간에계층적인경향성이나타나는경우에는 log rank를이용하여이에대한경향성을검정하였다. 최종적결론도출시예상되는결과를귀무가설의채택방향으로대치하였다. 통계분석은 SAS를사용하였고 P 값이 0.05 이하인경우를통계적으로유의하다고정의하였다. 결과 1. 대상군의특성 603명의환자중제2형당뇨병진단당시대사증후군이동반된 420명과대사증후군이동반되지않은 183명으로나 Table 1. Baseline characteristics of study subjects MetS (-) MetS (+) P N (%Male/%Female) 183 (54%/46%) 420 (37%/53%) < 0.01 Age at diagnosis 47.2 ± 9.3 51.1 ± 8.9 < 0.01 Body mass index (kg/m 2 ) Male 21.2 ± 1.8 24.9 ± 2.7 < 0.01 Female 21.0 ± 2.4 26.2 ± 3.3 < 0.01 Systolic BP (mm Hg) 115.5 ± 13.3 138.3 ± 22.3 < 0.01 Diastolic BP (mm Hg) 75.0 ± 8.8 88.4 ± 13.8 < 0.01 Fasting blood glucose (mg/dl) 185.2 ± 75.0 198.1 ± 76.3 0.12 PP2hr glucose (mg/dl) 270.8 ± 120.0 286.7 ± 109.0 0.22 HbA1c (%) 8.8 ± 3.2 9.2 ± 3.1 0.30 Total-cholesterol (mg/dl) 181.1 ± 38.7 212.3 ± 62.8 < 0.01 Triglyceride (mg/dl) 111.0 ± 62.1 223.7 ± 174.8 < 0.01 HDL-cholesterol (mg/dl) 51.6 ± 17.2 41.9 ± 11.9 < 0.01 Smoking (%) Never 64.6 72.5 0.10 Ex 3.5 4.6 Current 31.9 22.9 Alcohol (%) Never 53.5 67.1 < 0.01 Ex 1.4 4.4 Current 45.1 28.5 Physical activity (%) None 31.9 21.5 0.07 1~2 per a week 50.0 57.0 Almost everyday 18.1 21.5 Diet control (%) None 30.8 48.2 < 0.01 Irregularly 34.1 30.8 Regularly 35.1 21.0 BP, blood pressure; HDL, high density lipoprotein; MetS, metabolic syndrome. 394
정혜수외 6 인 : 제 2 형당뇨병환자에서대사증후군과만성합병증과의관계 누었고, 두군의기본특징을 Table 1에정리하였다. 인구학적특징은연령, 공복혈당 (fasting blood sugar, FBS), 비만 (BMI), 대사증후군으로제시하였으며건강행태는흡연, 음주상태, 생리적활성도및식이조절로제시하였다. 실험기간중혈당조절이합병증에미친영향을비교하기위해 1년마다의 HbA1c를평균한값을비교하였으나두군간유의한차이는보이지않았다. 대사증후군을가진환자군에서가지지않은환자군에비해연령이높았고, 체질량지수, 수축기및이완기혈압, 총콜레스테롤, 중성지방이유의하게높았고, HDL-콜레스테롤농도가유의하게낮았다 (Table 1). 본연구대상에서 NCEP-ATP III 기준 ( 허리둘레대신 BMI를진단기준으로사용 ) 에의한제2형당뇨병환자중대사증후군유병률은 69.7% 였다. 평균연령은 49.9 ± 9.1, 평균관찰기간은 15.2 ± 4.9 years이었으며, 대사증후군이있 는환자군과대사증후군이없는환자군의평균관찰기간은의미있는차이를보이지않았다. 자료수집기간 2004년 7월부터 2004년 8월을기준으로하였을때추적관찰소실은대사증후군이있는환자군에서 12.13%, 대사증후군이없는환자군에서 16.92% 였으며 (P-value 0.2795), 그원인으로는단순히외래를방문하지않거나전원, 사망이있었다. 사망은대사증후군이있는환자군에서 2.67% 로저혈당, 폐혈증에의하였으며, 대사증후군이없는환자군에서는 1.6% 로심장마비, 간경변, 급성신경학적이상, 간암, 간성혼수, 당뇨로인한만성합병증에의하였다. 2. 대사증후군과당뇨병성합병증과의관계당뇨병진단당시대사증후군이있는환자군과대사증후군이없는환자군의평균관찰기간 (15.2 ± 4.9 years) 동안 Table 2. Occurence of chronic complications MetS (-) MetS (+) crr 95% C.I. arr 95% C.I. CAD 8.8% 10.8% 3.18 * (1.68~6.01) 3.28 * (1.40~7.71) CVA 10.5% 9.3% 2.00 * (1.08~3.69) 2.04 (0.86~4.82) DR 60.2% 41.0% 1.69 * (1.30~2.20) 1.53 * (1.10~2.14) DN 52.7% 39.3% 1.89 * (1.41~2.54) 1.90 * (1.29~2.80) DN-micro 48.3% 36.9% 1.90 * (1.32~2.73) 2.00 * (1.26~3.16) DN-Overt 30.8% 16.1% 1.35 (0.89~2.05) 1.28 (0.75~2.19) DPN 52.5% 35.3% 1.61 * (1.22~2.14) 1.51 * (1.06~2.14) * P < 0.05. arr, adjusted relative risk (adjusted for age at T2DM diagnosis, sex, smoking, alcohol, physical activity & diet control); CAD, coronary artery disease; crr, crude relative risk; CVA, cerebro-vascular accident; DN, diabetic nephropathy; DPN, diabetic peripheral neuropathy; DR, diabetic retinopathy; MetS, metabolic syndrome; micro, microalbuminuria; overt, overt nephropathy. A B Fig. 1. Estimated cumulative hazard ratio of Macrovascular complications in diabetic patients with and without metabolic syndrome. A. Coronary artery disease (P < 0.01). B. Cerebrovascular accident (P = 0.02). 395
당뇨병성만성합병증의발생률에대하여분석해보았다 (Table 2). 대혈관합병증인관상동맥질환과뇌혈관질환은각각대사증후군이합병된환자군에서통계적으로유의하게발생률이증가되었으나제2형당뇨병진단당시나이, 성별, 담배, 술생리적활성도, 식이요법과연구기간중평균당화혈색소로보정한결과관상동맥질환은통계적으로유의하게발생률이증가하였으나뇌혈관질환의발생률증가에는통계적유의성을보이지않았다. 미세혈관합병증인당뇨병 A B C D E Fig. 2. Estimated cumulative hazard ratio of Microvascular complications in diabetic patients with and without metabolic syndrome. A. Diabetic retinopathy (P < 0.01). B. Diabetic nephropathy (P < 0.01). C. Microalbuminuria (P < 0.01). D. Overt nephropathy (P = 0.15). E. Diabetic neuropathy (P < 0.01). 396
정혜수외 6 인 : 제 2 형당뇨병환자에서대사증후군과만성합병증과의관계 성망막병증, 당뇨병성신증, 당뇨병성신경병증모두대사증후군이합병된환자군에서발생률이증가된것을보였다 Fig. 1A에서대사증후군여부에따른관상동맥질환발병위험을살펴보았다. 관상동맥질환발병위험은제2형당뇨진단이후약 10년이내에는큰차이를보이지않다가그이후꾸준히증가하는추세를나타내고있다. Fig. 1B에서대사증후군여부에따른뇌혈관질환발병위험을살펴보았다. 당뇨병진단이후약 10년부터대사증후군이있는환자군에서뇌혈관질환발병위험이놓은경향을나타내고있지만통계적으로유의한차이는아니었다. Fig. 2에서대사증후군여부에따른미세혈관합병증의발병위험을살펴보았다. 미세혈관합병증인당뇨병성망막병증, 당뇨병성신증, 당뇨병성신경병증모두대사증후군이합병된환자군에서통계적으로유의하게발생위험이증가된것을보였다. 그러나당뇨병성신증을미세알부빈뇨와현성당뇨병성신증으로분류하여발병위험을조사하였을때미세알부빈뇨발병위험증가는통계적유의성을보인반면, 현성당뇨병성신증발병위험증가는통계적유의성이없었다. Table 3에서표시한바와같이대사증후군의각구성요 Table 3. The relative risk for chronic diabetic complications by the presence of each component of metabolic syndrome Obesity Hypertriglyceridemia Low HDLC Hypertension crr arr crr arr crr arr crr arr CAD 2.80 * (1.51~5.20) 2.41 * (1.16~5.01) 2.28 * (1.24~4.19) 2.69 * (1.28~5.67) 2.83 * (1.44~5.57) 3.21 * (1.40~7.34) 1.93 * (1.06~3.51) 1.49 (0.69~3.23) CVA 1.60 (0.89~2.87) 1.96 (0.88~4.39) 1.57 (0.85~2.91) 1.89 (0.89~4.04) 1.30 (0.69~2.46) 0.93 (0.44~1.96) 2.40 * (1.28~4.50) 2.42 * (1.00~5.85) DR 1.54 * (1.18~2.00) 1.43 * (1.04~1.96) 1.44 * (1.10~1.89) 1.39 * (1.01~1.90) 1.62 * (1.20~2.19) 1.39 (0.98~1.97) 1.36 * (1.04~1.78) 1.08 (0.78~1.51) DN 1.63 * (1.21~2.20) 1.48 * (1.03~2.12) 1.60 * (1.17~2.19) 1.60 * (1.11~2.31) 2.25 * (1.58~3.20) 2.07 * (1.37~3.12) 1.47 * (1.09~2.00) 1.22 (0.83~1.81) DN-micro 1.70 * (1.18~2.43) 1.48 (0.96~2.27) 1.47 * (1.02~2.13) 1.59 * (1.04~2.44) 2.01 * (1.33~3.02) 1.85 * (1.15~2.99) 1.42 (0.99~2.05) 1.21 (0.76~1.95) DN-overt 1.31 (0.85~2.03) 1.19 (0.71~1.99) 1.71 * (1.08~2.71) 1.87 * (1.10~3.16) 1.45 (0.85~2.46) 1.47 (0.80~2.70) 1.24 (0.81~1.91) 1.00 (0.58~1.72) DPN 1.45 * (1.10~1.91) 1.44 * (1.03~1.99) 1.21 (0.90~1.62) 1.09 (0.78~1.51) 1.59 * (1.14~2.21) 1.52 * (1.05~2.20) 1.17 (0.88~1.55) 1.01 (0.71~1.43) * P < 0.05. ( ) 95% C.I.. arr, adjusted relative risk (adjusted for age at T2DM diagnosis, sex, smoking, alcohol, physical activity & diet control); CAD, coronary artery disease; crr, crude relative risk; CVA, cerebro-vascular accident; DN, diabetic nephropathy; DPN, diabetic peripheral neuropathy; DR, diabetic retinopathy; HDLC, high density lipoprotein cholesterol; micro, microalbuminuria; overt, overt nephropathy. Table 4. The relative risk of developing complication of diabetes with the addition of one constituent of metabolic syndrome crr 95% C.I. arr 95% C.I. CAD 1.75 * (1.23~2.49) 2.08 * (1.27~3.40) CVA 1.27 (0.97~1.67) 1.16 (0.80~1.66) DR 1.15 * (1.02~1.29) 1.09 (0.93~1.26) DN 1.27 * (1.09~1.48) 1.29 * (1.06~1.57) DN-micro 1.26 * (1.06~1.51) 1.24 (0.97~1.56) DN-Overt 1.18 (0.93~1.49) 1.16 (0.86~1.58) DPN 1.06 (0.93~1.22) 1.06 (0.87~1.26) * P < 0.05. arr, adjusted relative risk (adjusted for age at T2DM diagnosis, sex, smoking, alcohol, physical activity & diet control); CAD, coronary artery disease; crr, crude relative risk; CVA, cerebro-vascular accident; DN, diabetic nephropathy; DPN, diabetic peripheral neuropathy; DR, diabetic retinopathy; HDLC, high density lipoprotein cholesterol; micro, microalbuminuria; overt, overt nephropathy. 397
소에따른당뇨병의만성합병증의발생위험에대하여조사하였다. 우선비만 (BMI 23) 환자군에서관상동맥질환, 당뇨병성망막병증, 당뇨병성신증, 당뇨병성신경병증발병위험이통계적으로유의하게증가하였고비만이없는환자군과비교하여비만이있는환자군에서관상동맥질환이 2.4 배로다른만성합병증들에비해가장발병률이많이증가하는것을관찰할수있다. 고중성지방혈증은관상동맥질환, 당뇨병성망막병증, 당뇨병성신증의발병의위험인자인것을알수있었고낮은 HDL-콜레스테롤은관상동맥질환, 당뇨병성신증, 당뇨병성신경병증발병의위험인자인것을알수있었다. 또고혈압 (BP 130/85) 이있는환자군에서뇌혈관질환이 2.4배 (95% C.I. 1.00~5.85) 증가하는것을볼수있었다. Table 4에서표시한바와같이당뇨병을제외한대사증후군의구성요소개수가증가할수록관상동맥질환과당뇨병성신증의유병률이유의하게증가하였다고찰제2형당뇨병에서는비만, 이상지질혈증, 고혈압등의대사증후군의구성요소가흔히동반되어나타나며이들은널리알려진관상동맥질환의위험인자이다. 본연구에서는한국인제2형당뇨병과동반된대사증후군이관상동맥질환, 당뇨병성망막병증, 당뇨병성신증및당뇨병성신경병증의당뇨병성만성합병증의발병을증가시키는것을볼수있었고특히관상동맥질환의발병률을가장높게증가시켰다. 이결과는이탈리아에서 7,859명의제2형당뇨병환자를대상으로 International Diabetes Federation (IDF) 으로대사증후군을정의하여시행한미세혈관및대혈관합병증에대한연구결과와같은결론을보이고있으며 19), 다른인종을대상으로시행한연구결과와도큰차이가없었다 20-22). 특히대사증후군구성요소중비만과고중성지방혈증과저HDL- 콜레스테롤혈증은관상동맥질환, 당뇨병성신증발병의상대적위험도 (RR) 를, 고혈압은뇌혈관질환발병의상대적위험도를, 비만과고중성지방혈증은당뇨병성망막병증발병의상대적위험도를, 비만과저HDL-콜레스테롤혈증은당뇨병성신경병증발병의상대적위험도를증가시켰다. 또고혈당을제외한대사증후군의구성요소개수가증가할수록관상동맥질환과당뇨병성신증발병률이유의하게증가하는것을볼수있었다 2001년에서 2003월까지서울대학교병원당뇨병클리닉을방문한제2형당뇨병환자 989 명을대상으로시행한연구에서도같은결과를얻었으며, 대사증후군의모든구성요소를다갖는환자는당뇨병만있 는환자에비해관상동맥질환과당뇨병성신증의발병위험도가 5.4배, 6.8배높다고발표해 16) 적극적인혈압과지질조절및비만관리가필요하다고밝혔다. 본연구와이전발표된연구결과를종합하였을때한국인에서제2형당뇨병의만성합병증과이에따른의료비용의증가나국민건강의위험도를대사증후군의구성인자를개선시키려는노력이혈당조절이상중요할수있음을시사한다. 이연구의제한점으로는 603명이라는작은규모의환자가연구에포함되었다는것과후향적코호트연구로생길수있는한계점인선택비뚤림 (selection bias), 회상비뚤림 (recall bias), 결손자료 (missing data) 등을들수있다. 즉, 10개의 3차병원을대상으로연구를하였기때문에당뇨병이상대적으로심한환자를대상으로연구가시행되었을가능성과 10개의다른병원에서자료를모았기때문에각병원간의병력기록차이나측정방법차이에따른오차의가능성이있다. 또환자들의면담을통한회상자료를이용함으로정확하지않은자료가이용되었을가능성, 기초자료를이미작성한의무기록을기준으로분석하였으므로빠진자료등이변수로작용할가능성이있다. 덧붙여이자료를해석함에있어서대사증후군유무를판단할수있는기록이있는사람들만을대상으로했다는것을고려해야한다. 이연구가가지는의의로는첫째, 지금까지의연구들은한병원에국한된연구였으나본연구는 10개의종합병원환자를대상으로시행되었다는점, 둘째한국인연구로는처음시행된합병증관련후향적연구라는점이다. 합병증연구를위해서는비교적긴관찰기간이필요하여시간및비용이많이들기에지금까지이에대한연구가적었다. 이연구는앞으로시행될당뇨병과합병된대사증후군환자의만성합병증에대한연구의기초자료로써기여할것으로생각되며, 앞으로많은전향적연구가필요할것으로생각된다. 요약연구배경 : 제2형당뇨병환자에서만성합병증의유병률은종족간에차이가있는것으로알려져있고한국인에서대사증후군의유무에따른당뇨병성만성합병증의발생에대한보고는적은실정이어서, 한국인제2형당뇨병환자에서대사증후군및그구성인자에따른대혈관및미세혈관합병증의발생정도를조사하였다. 방법 : 이연구는 10개의종합병원에서새로이당뇨병을 398
정혜수외 6 인 : 제 2 형당뇨병환자에서대사증후군과만성합병증과의관계 진단받고 5년이상추적관리를받은환자 ( 진단당시연령만 30세이상, 75세미만 ) 를대상으로후향적연구로진행되었다. 603명의환자가본연구에포함되었고대사증후군진단은 NCEP-ATP III의진단기준은사용하였으며자료는증례기록서작성지침을기준으로의무기록과가능한경우면담을통해수집되었다. 결과 : 당뇨병진단당시대사증후군의유무에따른당뇨병성만성합병증의발생률에대하여분석하였을때대혈관및미세혈관합병증의발생률이증가되는결과를얻어서한국인에서의대사증후군이당뇨병합병증에미치는영향이다른인종과다르지않다는것을보여주었다. 또당뇨병환자가대사증후군의구성인자를많이가질수록관상동맥질환과당뇨병성신증의유병률이유의하게증가되었다. 결론 : 한국인제2형당뇨병환자에서대사증후군이동반되었을때대혈관및미세혈관합병증이증가하였다. 이는당뇨병환자에있어서엄격한혈당조절뿐만아니라대사증후군의구성인자개선이중요하다는것을시사한다. 참고문헌 1. Bonora E, Targher G, Formentini G, Calcaterra F, Lombardi S, Marini F, Zenari L, Saggiani F, Poli M, Perbellini S, Raffaelli A, Gemma L, Santi L, Bonadonna RC, Muggeo M: The metabolic syndrome is an independent predictor of cardiovascular disease in type 2 diabetic subjects: prospective data from the Verona Diabetes complications study. Diabet Med 21:52-8, 2004 2. Ford ES: Risks for all cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence. Diabetes Care 28:1769-78, 2005 3. Alexander CM, Landsman PB, Teutsch SM, Haffner SM: NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years abd older. Diabetes 52:1210-4, 2003 4. Mykkanen L, Kuusisto J, Pyorala K, Laakso M: Cardiovascular disease risk factors as predictors of type 2 diabetes mellitus in elderly subjects. Diabetologia 36:553-9, 1993 5. Haffner SM, Valdez RA, Hazuda HP, Mitchell BD, Morales PA, Stern MP: Prospective analysis of the insulin resistance syndrome(syndrome X). Diabetes 41:715-22, 1992 6. Fujimoto WY, Bergstrom RW, Newell-Morris L, Leonetti DL: Nature and nurture in the etiology of type 2 diabetes mellitus in Japanese Americans. Diabetes Metab Rev 5:707-25, 1989 7. Hamman RF, Franklin GA, Mayer EJ, Marshall SM, Marshall JA, Baxter J, Kahn LB: Microvascular complications of NIDDM in Hispanics and non-hispanic Whites. Diabetes Care 14:655-64, 1991 8. Thompson TJ, Hegazy EM, Sous ES, Badran A, Herman WH: The onset of NIDDM and its relationship to clinical diagnosis in Egyptian adults. Diabet Med 13:337-40, 1996 9. WHO: Prevalence of small vessel and large vessel disease in diabetic patients from 14 centres. The World Health Organization multinational study of vascular disease in diabetics. diabetes drafting group. Diabetologia 28:615-40, 1985 10. Nam JW, Lee SH, Lee HJ, Han JH, Kim JG, Ha SW, Kim BW: The prevalence of chronic complications in non-insulin dependent diabetic patients. J Korean Diabetes Assoc 23:702-15, 1999 11. Ko KS, Oh TG, Kim CH, Park KS, Lee MK, Kim SY, Cho BY, Lee HK, Koh CS, Min HK: A clinical study on the complications of non-insulin-dependent diabetes mellitus in Korea. J Korean Diabetes Assoc 15:257-62, 1991 12. Min HK: The clinical characteristic of diabetes mellitus in Korean. J Korean Diabetes Assoc 16:163-74, 1992 13. Hong YS, Hong LZ, Lee JS, Jung BS, Kim SW, Song CS: The clinical observation of diabetic complication. J Korean Diabetes Assoc 14:85-90, 1990 14. Lee YJ, Tsai JC: ACE gene insertion/deletion polymorphism associated with 1998 World Health Organization definition of metabolic syndrome in Chinese type 2 diabetic patients. Diabetes Care 25:1002-8, 2002 15. Lee SH, Kang ES, Lee KE, Jin HD, Choi SH, Kim DJ, Ahn CW, Cha BS, Lim SK, Lee HC, Huh KB: 399
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