42 Myong Soo Kim and Kyung A Shin. Serum Uric Acid to Creatinine Ratio as a Predictor of Metabolic Syndrome ORIGINAL ARTICLE Korean J Clin Lab Sci. 2019;51(1):42-49 https://doi.org/10.15324/kjcls.2019.51.1.42 pissn 1738-3544 eissn 2288-1662 Serum Uric Acid to Creatinine Ratio as a Predictor of Metabolic Syndrome in Healthy Adults Men Myong Soo Kim 1, Kyung A Shin 2 1 Department of Laboratory Medicine, Samsung Medical Center, Seoul, Korea 2 Department of Clinical Laboratory Science, Shinsung University, Dangjin, Korea 건강한성인남성의대사증후군위험예측인자로서혈청요산 / 크레아티닌비율 김명수 1, 신경아 2 1 삼성서울병원진단검사의학과, 2 신성대학교임상병리과 This study compared the utility of the serum uric acid/creatinine ratio with that of uric acid as a risk predictor of metabolic syndrome. From November 2016 to October 2018, 14,190 adult men under the age of 20 years, who underwent a comprehensive health checkup at a general hospital in their metropolitan area, were included. Metabolic syndrome was assessed according to the American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) criteria. Abdominal obesity was based on the WHO criteria in the Western Pacific region. The serum uric acid/creatinine ratio was found to be higher in the fourth quartile than in the first quartile, with a high incidence of metabolic syndrome and metabolic syndrome components. On the other hand, ROC analysis revealed the serum uric acid/creatinine ratio to be a similar indicator of the metabolic syndrome risk to serum uric acid (AUC, 0.554 vs 0.566). The serum uric acid/creatinine ratio showed lower sensitivity and higher specificity than uric acid. In conclusion, the utility of the serum uric acid/creatinine ratio as an independent indicator to predict the risk of metabolic syndrome is limited, and should be used only as an auxiliary marker. Key words: Creatinine, Metabolic syndrome, Risk factor, Serum uric acid Corresponding author: Kyung A Shin Department of Clinical Laboratory Science, Shinsung University, 1 Daehak-ro, Jeongmi-myeon, Dangjin 31801, Korea Tel: 82-41-350-1408 Fax: 82-41-350-1355 E-mail: mobitz2@hanmail.net ORCID: https://orcid.org/0000-0001-5266-5627 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2019 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: January 2, 2019 Revised 1 st : January 29, 2019 Revised 2 nd : February 12, 2019 Accepted: February 13, 2019 서론대사증후군 (metabolic syndrome, MetS) 은심혈관질환및뇌졸중위험도증가, 심뇌혈관질환과관련된다양한대사이상을의미하며, 대사증후군구성요소에는복부비만, 고중성지방혈증및저고밀도지단백콜레스테롤 (high density lipoprotein, HDL-C) 혈증을포함한이상지질혈증, 혈압상승, 공복혈당장애가포함된다 [1]. National Cholesterol Education Program (NCEP) 의 Adult Treatment Panel (ATP) III, 국제당뇨병연맹 (International Diabetes Federation, IDF) 및세계보건기구 (World Health Organization, WHO) 에서제안한대사증후군의정의에다소차이가있으나, 인슐린저항성과복부비만은대사증후군발병진행의중요한요소로제시된다 [2-4]. 대사증후군은심혈관질환, 제2형당뇨병, 만성콩팥질환의발병위험이높은환자를확인하는데도움이되며, 자율신경계및염증반응, 폐기능과관련된다고보고되고있어임상적으로중요성이강조
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 43 된다 [5-9]. 특히최근대사증후군과만성콩팥질환간의관련성에대한관심이증가하고있다. 당뇨병과고혈압은만성콩팥질환의주요원인이며, 공복혈당장애와혈압상승은대사증후군정의에포함되기때문에대사증후군과만성콩팥질환진행사이에독립적인연관성이보고된다 [10]. 만성콩팥질환의초기단계는전형적인증상이없어진단이어렵기때문에대사증후군의진행을예방하는것이만성콩팥질환및심혈관질환의병인발생과진행을예방하는방법일수있다 [11]. 혈청크레아티닌은사구체여과율 (glomerular filtration rate, GFR) 의변화를발견하기위해일반적으로사용되며, 초기만성콩팥질환을진단하는생리적지표이다 [12]. 또한크레아티닌증가는심혈관질환, 비만및고혈압, 대사증후군위험증가와관련이있다고보고된다 [13, 14]. 유사하게, 혈청요산증가는콩팥기능의감소를나타내는지표로서고혈압및심혈관질환, 대사증후군의위험인자로알려져있다 [15, 16]. 혈청요산은퓨린대사의최종생성물이며, 주로간에서합성되어콩팥을통해소변으로배설된다 [17]. 혈중요산은대사증후군과관련이있는것으로보고되고있다 [16]. 대사증후군에서인슐린저항성은콩팥의요산재흡수를증가시켜혈중요산치상승에기여하고고요산혈증은산화질소의활성을저해하여인슐린저항성을가속화시킨다 [16, 18]. 콩팥을통한혈청요산의제거가콩팥기능에영향을받는다는것을고려하여콩팥기능을반영한혈청요산 / 크레아티닌비율이생성되었다 [19]. Gu 등 [19] 은혈청요산 / 크레아티닌비율이요산단독측정보다만성콩팥질환과밀접한관련이있음을입증하였다. 또한 Al-Daghri 등 [11] 은제2형당뇨환자를대상으로대사증후군위험요인이증가할수록혈청요산 / 크레아티닌비율이증가하며, 혈청요산 / 크레아티닌비율은대사증후군의예후를결정하는데유용하다고보고하였다. 그러나이와같은연구들은특정질환자를대상으로하였으며 [11, 19], 특히국내에서는혈청요산 / 크레아티닌비율과대사증후군과의연관성을확인한연구는제한적이다 [20]. 한국인을대상으로한연구는국민건강영양조사자료를이용하여대사증후군구성요소와혈청요산 / 크레아티닌비율간의상관성을확인한연구가유일하며 [20], 혈청요산 / 크레아티닌비율의임상적유용성에대해서는알려지지않았다. 또한대사증후군은진단기준, 인종, 성별, 연령에따라다양한결과를보이고있어, 국내에서대사증후군예측지표로서혈청요산 / 크레아티닌비율을평가하는것은의미가있다하겠다. 이에본연구에서는건강한성인남성을대상으로수신자조 작특성 (receiver operating characteristic, ROC) 곡선분석을통해대사증후군위험예측인자로서요산과비교하여혈청요산 / 크레아티닌비율의유용성을확인해보고자하였다. 재료및방법 1. 연구대상본연구는 2016년 11월부터 2018년 10월까지수도권소재의일개종합병원에서종합건강검진을받은 20세이상 80세미만의성인남성을대상으로수행되었다. 자기기입식건강설문조사를통해갑상선질환자, Anti-HCV Ab 또는 HBs Ag 양성자를포함한간질환자, 통풍질환자, 콩팥질환자, 뇌졸중및심근경색, 협심증환자와모든측정지표에결측치를포함한대상자를제외한최종연구대상자는 14,190 명이었다. 본연구는수도권소재종합병원생명윤리심의위원회의승인을받아진행하였다 (IRB No: D-2018-012-2468). 2. 연구방법 1) 대사증후군진단기준대사증후군진단기준은 NCEP-ATP III 기준을변형한 American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) 의기준에따라 5가지대사증후군구성요소중 3가지이상해당되는경우대사증후군으로평가하였다. 5가지대사증후군구성요소는공복혈당 100 mg/dl, 중성지방 150 mg/dl, 저밀도콜레스테롤은남성 <40 mg/dl, 수축기혈압 130 mmhg 또는이완기혈압 85 mmhg, 복부비만은 WHO 서태평양지역의기준인허리둘레는남성 >90 cm을적용하였다 [21, 22]. 2) 신체계측및혈액검사신장과체중은직립자세에서체성분분석기 Inbody 720 (Biospace Co., Seoul, Korea) 을활용하여생체임피던스법으로측정하였고, 체질량지수 (body mass index, BMI) 는체중 (kg) 을키 (m 2 ) 로나누어계산하였다. 허리둘레는양발을 25 30 cm으로벌려체중을분산시킨후숨을내쉰상태로늑골하부 (lower border of rib cage) 와장골능상부 (top of iliac crest) 의중간부분을줄자로 0.1 cm까지측정하였다. 수축기혈압과이완기혈압은 5분동안안정상태를유지한후아네로이드혈압계 (Medisave UK Ltd., Weymouth, UK) 로측정하였다. 혈액분석은 8시간이상공복상태에서오전에채혈하여측정하였으며, 혈청총콜레스테롤 (total cholesterol, TC), 중성지방 (trigly-
44 Myong Soo Kim and Kyung A Shin. Serum Uric Acid to Creatinine Ratio as a Predictor of Metabolic Syndrome ceride, TG), HDL-C, 저밀도지단백콜레스테롤 (low density lipoprotein, LDL-C), 공복혈당, 요산, 혈액요소질소 (blood urea nitrogen, BUN), 크레아티닌은 TBA-2000FR NEO 자동생화학분석기 (Toshiba, Tokyo, Japan) 로분석하였다. 또한당화혈색소 (hemoglobin A1c, HbA1c) 는 Variant II (Bio Rad, CA, USA) 로, 인슐린은 Roche Modular Analytics E170 (Roche, Mannheim, Germany) 으로측정하였다. 3. 통계분석이연구의통계처리는 SPSS version 24.0 (SPSS Inc., Chicago, IL, USA) 으로실시하였다. 요산 / 크레아티닌비율의사분위수에따른연구대상자의일반적특징의차이및대사증후군구성요소의개수에따른요산 / 크레아티닌비율의차이는 일원변량분석 (one-way ANOVA) 을통해확인하였으며, 사후검증은 Scheffe 법으로검증하였다. 또한요산 / 크레아티닌비율의사분위수에따른대사증후군및대사증후군구성요소의발병률의차이를비교하고자카이제곱검정 (chi-squared test) 을시행하였다. 요산및요산 / 크레아티닌비율수준에따른대사증후군발병률의차이는연령과 BMI를통제한상태에서로지스틱회귀분석 (logistic regression) 을통해위험비 (odds ratio) 와 95% 신뢰구간 (95% confidence interval) 을구하였다. 요산 / 크레아티닌비율은정규성가정에위배되어로그변환을하였다. 또한요산 / 크레아티닌비율의대사증후군예측력을확인하기위해요산과비교하여요산 / 크레아티닌비율의 ROC 곡선을이용한곡선하면적 (area under curve, AUC) 값을구하였다. 대사증후군을예측하기위한요산 / 크레아티닌비율과요산의최 Table 1. General characteristic of subjects based on uric acid/creatinine ratio quartile Variables 1 st quartile (<4.48) 2 nd quartile (4.49 5.15) 3 rd quartile (5.16 5.88) 4 th quartile (5.89 ) P-value N 2,479 3,208 3,924 4,579 UA/Cr ratio 3.66±0.49 4.59±0.19 a 5.26±0.21 ab 6.43±0.70 abc <0.001 Clinical characteristics Age (years) 49.18±11.84 46.61±10.77 a 44.74±10.30 ab 43.60±10.27 abc <0.001 Height (cm) 170.57±6.49 171.29±6.22 a 171.72±6.23 ab 171.86±6.43 ab <0.001 Weight (kg) 70.14±9.97 71.18±9.33 a 72.74±9.96 ab 74.75±10.86 abc <0.001 BMI (kg/m 2 ) 24.07±2.96 24.25±2.78 24.63±2.86 ab 25.26±3.08 abc <0.001 WC (cm) 82.36±7.76 82.64±7.36 83.65±7.41 ab 85.28±7.59 abc <0.001 SBP (mmhg) 112.49±13.93 111.96±12.82 112.45±12.76 113.43±12.78 abc <0.001 DBP (mmhg) 72.45±9.85 72.45±9.72 72.89±9.83 73.59±10.00 abc <0.001 Lipid profile TC (mg/dl) 189.55±33.69 193.94±33.43 a 195.45±33.17 a 199.26±34.95 abc <0.001 TG (mg/dl) 127.02±75.11 134.11±87.89 a 139.77±83.89 a 166.25±113.39 abc <0.001 HDL-C (mg/dl) 53.66±12.72 52.50±12.01 a 51.94±11.85 a 50.85±11.75 abc <0.001 LDL-C (mg/dl) 116.81±30.44 121.27±29.45 a 123.02±29.90 a 124.97±31.72 abc <0.001 Glycemic profile Glucose (mg/dl) 97.40±29.20 92.70±21.01 a 90.58±16.26 ab 90.92±15.86 ab <0.001 HbA1c (%) 5.88±1.15 5.66±0.78 a 5.58±0.62 ab 5.56±0.54 ab <0.001 Insulin ( U/mL) 4.94±3.16 4.97±3.24 5.09±3.03 5.62±3.45 abc <0.001 Renal profile BUN (mg/dl) 14.67±4.34 14.34±3.54 a 14.12±3.38 a 13.92±3.31 ab <0.001 Creatinine (mg/dl) 1.21±0.22 1.19±0.12 a 1.17±0.11 ab 1.13±0.11 abc <0.001 Uric acid (mg/dl) 4.40±0.80 5.45±0.58 a 6.14±0.62 ab 7.28±0.97 abc <0.001 MetS components (%) MetS 273 (11.0) 297 (9.3) 408 (10.4) 663 (14.5) <0.001 Elevated WC 410 (16.5) 541 (16.9) 802 (20.4) 1,212 (26.5) <0.001 Elevated BP 447 (18.0) 484 (15.1) 643 (16.4) 841 (18.4) 0.001 Reduced HDL-C 273 (11.0) 401 (12.5) 482 (12.3) 714 (15.6) <0.001 Elevated fasting glucose 589 (23.8) 580 (18.1) 608 (15.5) 752 (16.4) <0.001 Elevated TG 701 (28.3) 976 (30.4) 1,349 (34.4) 2,026 (44.2) <0.001 Values are presented as means±standard deviations and number (%). a, significantly different from the 1st quartile; b, significantly different from 2nd quartile; c, significantly different from 3rd quartile. Abbreviations: UA/Cr, uric acid/creatinine; BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; TG, triglyceride; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; HbA1c, hemoglobin A1c; BUN, blood urea nitrogen; MetS, metabolic syndrome.
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 45 적절단값 (optimum cut-off values) 은민감도 (sensitivity) 와특이도 (specificity) 의합이최대가되는지점의값을적정절단값으로선택하였다. 이연구에서모든통계분석의유의수준은 P<0.05 를기준으로설정하였다. 결과 1. 요산 / 크레아티닌비율의사분위수에따른연구대상자의일반적특징요산 / 크레아티닌비율의사분위수에따른대상자의일반적특징은 Table 1과같다. 연령, 신장, 체중은사분위수가증가할수록비례하여증가하였다 ( 각각 P<0.001). BMI와허리둘레, 수축기와이완기혈압은 4사분위수에서가장높은수치를보였다 ( 각각 P<0.001). 혈액분석항목중 TC, TG, LDL-C은 1사분위수보다상위분위수에서높게나타났으며, 4사분위수는 3사분위수보다도높았다 ( 각각 P<0.001). 그러나 HDL-C은 1사분위수보다상위분위수에서낮게나타났고, 4사분위수는 3사분위수보다도낮았다 (P<0.001). 공복혈당과 HbA1c은 1사분위수보다상위분위수에서낮았으며, 3사분위수와 4사분위수는 2 사분위수보다낮았다 (P<0.001). 인슐린은 4사분위수가하위분위수보다높게나타났다 (P<0.001). BUN은 1사분위수보다상위분위수에서낮았으며, 4사분위수는 2사분위수보다낮았다 (P<0.001). 크레아티닌은 1사분위수보다상위분위수에서낮았고 3사분위수와 4사분위수는 2사분위수보다낮았으며, 4 사분위수는 3사분위수보다낮았다 (P<0.001). 요산은 1사분위수보다상위분위수에서높았고 3사분위수와 4사분위수는 2사 분위수보다높았으며, 4사분위수는 3사분위수보다높았다 ( 각각 P<0.001). 대사증후군발생빈도는 4사분위수에서 14.5% 로가장높은빈도를보였으며, 허리둘레증가는사분위수가증가할수록발생빈도가증가하였다 ( 각각 P<0.001). 높은혈압 (P=0.001) 과 HDL-C (P<0.001) 의감소는 4사분위수에서각각 18.4% 와 15.6% 로가장높은발생빈도를보였다. 공복혈당증가는 1사분위수에서 23.8% 로가장높은발생빈도를보였으며, TG 증가는사분위수가증가할수록발생빈도가증가하였다 ( 각각 P<0.001). 2. 대사증후군구성요소의개수에따른요산 / 크레아티닌비율의차이대사증후군구성요소의개수에따른요산 / 크레아티닌비율의차이를확인한결과대사증후군구성요소가없는군보다 1개, 2개, 3개, 4개이상의구성요소를가진군에서요산 / 크레아티닌비율이높았으며, 대사증후군구성요소를 2개, 3개가진군은 1개, 2개의구성요소를가진군보다높게나타났다 (P<0.001) (Figure 1). 3. 요산 / 크레아티닌비율및요산의사분위수에따른대사증후군과의관련성요산 / 크레아티닌비율의사분위수에따른대사증후군발병위험비는보정을하지않은경우 1사분위수를기준으로 2사분위수 (P=0.023) 에서 0.82배 (0.685 0.972) 낮았으며, 4사분위수 (P<0.001) 에서는 1.37배 (1.175 1.586) 높았다. 그러나연령과 BMI를통제한후요산 / 크레아티닌비율은대사증후군발병위험과관련이없었다 (Table 2). 요산의사분위수에따른대사증후군발병위험비는보정을하지않은경우 1사분위수를기준으로 3사분위수 (P=0.016) 에서 1.21배 (1.035 1.411), 4사분위수 (P<0.001) 에서 1.65배 (1.425 1.903) 높게나타났다. 그러나연령과 BMI를통제한후요산은 1사분위수를기준으로 4사분위수 (P=0.036) 에서 1.18배 (1.011 1.407) 대사증후군발병위험이높았다 (Table 2). 4. 대사증후군을예측하기위한요산 / 크레아티닌비율및요산의절단값 Figure 1. The values of uric acid/creatinine ratio according to number of metabolic syndrome components. a, significantly different from the MetS components 0; b, significantly different from MetS components 1; c, significantly different from MetS components 2. Data are mean±sd. MetS components 0: 5.07±1.02, MetS components 1: 5.24±1.09, MetS components 2: 5.32±1.15, MetS components 3: 5.41±1.21, MetS components 4: 5.37±1.27. Abbreviation: MetS, metabolic syndrome. 대사증후군예측을위한요산 / 크레아티닌비율의곡선하면적 (area under the curve, AUC) 값은 0.554이며, 요산의 AUC 값은 0.566이었다 (Table 3, Figure 2). 대사증후군예측을위한요산 / 크레아티닌비율의절단값은 5.75, 민감도는 37.4%, 특이도는 72.0% 로나타났다 (P<0.001). 요산의대사증후군예측을위한절단값은 6.35 mg/dl이며, 민감도는 48.1%, 특이도는
46 Myong Soo Kim and Kyung A Shin. Serum Uric Acid to Creatinine Ratio as a Predictor of Metabolic Syndrome Table 2. Odds ratio for the metabolic syndrome according to the uric acid/creatinine ratio quartile UA/Cr ratio Prevalence of MetS Crude (95% CI) P-value Adjusted (95% CI) P-value 1 st quartile 1 1 2 nd quartile 0.816 (0.685 0.972) 0.023 0.853 (0.703 1.034) 0.106 3 rd quartile 0.951 (0.809 1.118) 0.540 0.948 (0.791 1.135) 0.561 4 th quartile 1.365 (1.175 1.586) <0.001 1.171 (0.986 1.390) 0.071 Uric acid (mg/dl) Prevalence of MetS Crude (95% CI) P-value Adjusted (95% CI) P-value 1 st quartile 1 1 2 nd quartile 0.931 (0.792 1.094) 0.386 0.911 (0.763 1.088) 0.305 3 rd quartile 1.209 (1.035 1.411) 0.016 1.050 (0.883 1.247) 0.583 4 th quartile 1.647 (1.425 1.903) <0.001 1.183 (1.011 1.407) 0.036 Adjusted odds ratios for age, BMI. Abbreviations: MetS, metabolic syndrome; UA/Cr, uric acid/creatinine; CI, confidence interval. Table 3. ROC analysis for uric acid/creatinine ratio and uric acid associated with metabolic syndrome Variables AUC (95% CI) Cutoff value Sensitivity (%) Specificity (%) P-value Uric acid/creatinine ratio 0.554 (0.539 0.570) 5.75 37.4 72.0 <0.001 Uric acid (mg/dl) 0.566 (0.550 0.581) 6.35 48.1 62.6 <0.001 Abbreviations: ROC, receiver operating characteristic; CI, confidence interval. Figure 2. ROC curve of uric acid/creatinine ratio and uric acid for diagnosis of metabolic syndrome. Abbreviations: ROC, receiver operating characteristic; AUC, area under the curve. 62.6% 였다 (P<0.001) (Table 3). 고찰 이연구는건강한성인남성에서혈청요산 / 크레아티닌비율 이대사증후군을예측하는지표로활용될수있는지를평가하고자하였다. 혈청요산 / 크레아티닌비율은 4사분위수가 1사분위수보다대사증후군및대사증후군구성요소의높은발생빈도를보였다. 그러나 ROC 분석결과혈청요산 / 크레아티닌비율은대사증후군위험예측에있어혈청요산치보다더유용한지표는아니었으며 (AUC, 0.554 vs 0.566), 요산치보다낮은민감도와높은특이도를보였다. 이전연구에따르면고요산혈증은높은 BMI, 이상지질혈증및고혈압과관련이있는것으로보고된다 [23, 24]. 인슐린저항성은이러한대사장애의발달과함께고요산혈증을유발하는기전으로의심되지만, 그기전은아직명확하지않다 [11]. 메타분석에의하면혈청요산치가 1 mg/dl 증가할때마다제2형당뇨병의위험이 17% 증가한다고보고되며 [25], 최근에혈중요산치가당뇨환자와당뇨가없는환자모두에서콩팥손상을예측하는지표로제시된다 [26, 27]. 임상시험을통해서혈청요산치를낮추는것이콩팥질환의진행을지연시킬수있으며, 알로푸리놀 (allopurinol) 로통풍치료를받은환자가위약군보다더안정적인콩팥기능을나타낸다고보고된다 [28]. 일부연구에서결과가상충되고있지만혈청요산치는대부분의연구에서콩팥질환을예측하는것으로나타났다 [29, 30]. 이것은혈청요산치와사구체여과율사이의강한상호작용때문으로생각된다 [31].
Korean J Clin Lab Sci. Vol. 51, No. 1, March 2019 47 요산은퓨린대사의최종산물로서주로소변으로제거되며, 콩팥질환에서요산제거장애로혈청요산치가증가하는것은추론가능하다 [32]. 또한크레아티닌증가는심혈관질환및대사증후군위험증가와관련이있다고보고된다 [13, 14]. 이전의연구가대개혈청요산치에초점을맞추었으나, 혈청요산및크레아티닌은대사증후군을예측하는데사용될수있다는제한된증거로인해콩팥기능을고려한혈청요산 / 크레아티닌비율이생성되었다 [19]. 혈청요산 / 크레아티닌비율은제2형당뇨환자에서대사증후군구성요소의수가증가함에따라증가하며, 혈청요산 / 크레아티닌비율은대사증후군및그구성요소와관련이있다고보고된다 [11]. 이연구결과는혈청요산 / 크레아티닌비율의상위사분위수에서대사증후군및허리둘레증가, 높은혈압, HDL-C 감소의발생빈도가높았다. 또한 TG 증가는혈청요산 / 크레아티닌비율의사분위수가증가할수록발생빈도가증가하였다. 이는혈청요산 / 크레아티닌비율과대사증후군간에관련이있으며, 혈청요산 / 크레아티닌비율의상위분위수에서복부비만, 고중성지방혈증, 저 HDL-C 및고혈압발병률이증가한다는연구결과와유사한결과이다 [11, 20]. 이연구에서흥미로운점은혈청요산 / 크레아티닌비율의분위수가증가할수록공복혈당과 HbA1c가감소하였다는것이다. 이러한결과는 Al-Daghri 등 [11] 의연구에서도나타나는데혈청요산 / 크레아티닌비율의상위삼분위수에서공복혈당의감소를보여혈청요산 / 크레아티닌비율과공복혈당간에역상관관계가있음을보고하였다. 이는혈당증가가과여과상태 (hyper filtration state) 를촉진시켜콩팥으로요산배설을증가시키는결과를유발했기때문으로설명되고있으나 [33], 정확한기전을설명하기위해서는이를뒷받침할수있는후속연구가필요하겠다. 또한 Gu 등 [19] 은제2형당뇨병환자에서혈청요산 / 크레아티닌비율은만성콩팥질환발병과연관되어있으며, 만성콩팥질환예측인자로서혈청요산보다효율적인지표라고보고하였다. 그러나이러한혈청요산 / 크레아티닌비율이대사증후군위험을예측하는데사용될수있다는증거는매우제한적이다 [11, 20]. 이연구에서는연령과 BMI를통제한후혈청요산 / 크레아티닌비율은대사증후군발병과관련이없었으나, 요산은 1사분위수보다 4사분위수에서대사증후군발병위험이 1.18배높게나타났다. 또한 ROC 분석결과대사증후군예측을위한혈청요산 / 크레아티닌비율과요산치의 AUC 값은각각 0.554, 0.566 이었으며, 혈청요산 / 크레아티닌비율은요산치보다낮은민감도와높은특이도를보였다. 따라서선행연구에서확인된바와같이제2형당뇨환자에서혈청요산 / 크레아티닌비율은대사증 후군과밀접한관련이있지만, 이연구에서는건강한성인남성을대상으로대사증후군예측인자로서혈청요산 / 크레아티닌비율의효율성은낮은것으로나타났다. 혈청요산 / 크레아티닌비율은콩팥기능을반영한지수로서이는내인성혈청요산치를나타내며, 당뇨병및베타세포기능장애를비롯한대사장애와관련이있다고보고된다 [34]. 대사증후군의정의는개념상의단점에대한몇가지논쟁이있기는하지만심혈관질환위험이높은환자를구별하는데간단하고실용적인도구로널리사용되고있다 [10]. 저자의선행연구를보면대사증후군을예측하는요산 AUC 값은 0.620, 남성은 0.564로나타났으며, 대사증후군을예측하는독립적인지표로서한계가있음을제시하였다 [35]. 이연구결과는대사증후군정의의단점을보완하는지표로서혈청요산 / 크레아티닌비율의유용성을확인한결과건강한성인남성의대사증후군위험을예측하는독립적인지표로사용하는데제한이있음을시사하며, 보조적인표지자로사용하는것이바람직하겠다. 이연구의제한점은횡단면연구라는특성때문에대사증후군의위험과혈청요산 / 크레아티닌비율간의인과관계를추론하는것에한계가있다. 연령, BMI와같은일부혼란변수에대해통제하였지만, 퓨린섭취를고려한식습관, 운동과같은다른요인에대한충분한정보가부족하여이를반영하지못하였다. 또한남성에서고요산혈증및통풍의발생빈도가높다고보고되어본연구는남성을대상으로연구를진행하였으며 [36], 이결과는여성에게적용하는데제한이있다. 결론적으로, 건강한성인남성을대상으로혈청요산 / 크레아티닌비율은 1사분위수보다 4사분위수에서대사증후군및대사증후군구성요소의높은발생빈도를보였으나, 혈청요산 / 크레아티닌비율이대사증후군위험예측에있어혈청요산치보다더유용한지표는아닌것으로나타났다. 대사증후군발병기전과혈청요산 / 크레아티닌간의관계를규명하기위해대상자를성별과연령별로구분하여차이를확인하는연구가필요하겠다. 요약이연구는대사증후군위험예측인자로서요산과비교하여혈청요산 / 크레아티닌비율의유용성을확인하고자하였다. 2016년 11월부터 2018년 10월까지수도권소재의일개종합병원에서종합건강검진을받은 20세이상 80세미만의성인남성 14,190명을대상으로하였다. 대사증후군진단기준은 American Heart Association/National Heart Lung and
48 Myong Soo Kim and Kyung A Shin. Serum Uric Acid to Creatinine Ratio as a Predictor of Metabolic Syndrome Blood Institute (AHA/NHLBI) 의기준에따라 5가지대사증후군구성요소중 3가지이상해당되는경우대사증후군을평가하였으며, 이중복부비만은 WHO 서태평양지역의기준에따랐다. 이연구결과혈청요산 / 크레아티닌비율은 1사분위수보다 4 사분위수의대사증후군및대사증후군구성요소의높은발생빈도를보였다. 그러나 ROC 분석결과혈청요산 / 크레아티닌비율은대사증후군위험예측에있어혈청요산치보다더유용한지표는아니었으며 (AUC, 0.554 vs 0.566), 요산치보다낮은민감도와높은특이도를보였다. 결론적으로혈청요산 / 크레아티닌비율의유용성을확인한결과대사증후군위험을예측하는독립적인지표로사용하는데제한이있으며, 보조적인표지자로사용하는것이바람직하겠다. Acknowledgements: None Conflict of interest: None Author s information (Position): Kim MS 1, M.T.; Shin KA 2, Professor. REFERENCES 1. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, et al. 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