건강증진센터를방문한성인한국남성에서대사증후군관련지표와소변중 ph 의상관관계 The Correlation between Metabolic Syndrome and in Adult Korean Men Who Visited a Health Promotion Center Korean Journal of Urology Vol. 50 No. 7: 694-698, July 2009 DOI: 10.4111/kju.2009.50.7.694 Tae Sung Jung, Won Jae Yang, Yun Seob Song From the Department of Urology, Soonchunhyang University College of Medicine, Seoul, Korea Purpose: Low urinary ph is a risk factor for uric acid stones, and acidic urine has been described as a renal manifestation of the metabolic syndrome. We evaluated the association between metabolic syndrome and urinary ph in adult Korean men who visited a health promotion center. Materials and Methods: From 2004 to 2008, a total of 18,513 adult men who visited our health promotion center were enrolled in this study. The relation between urinary ph and various parameters associated with the metabolic syndrome were evaluated. Results: The average age was 45.6 years (range, 18-95 years), and 4987 men (26.9%) were classified as having the metabolic syndrome. The mean urinary ph of the metabolic syndrome group was 5.91, which was significantly lower than that of the normal group (6.08). In univariate and multivariate analysis, body mass index, serum triglyceride, and blood sugar were negatively correlated with urinary ph (p<0.05). In multivariate logistic regression analysis, obesity (body mass index 25 kg/m 2 ), hypertriglyceridemia ( 150 mg/dl), high fasting glucose ( 110 mg/dl), and low high-density lipoprotein cholesterol (<45 mg/dl) were the significant factors that predicted low urinary ph ( 5.5). Conclusions: Metabolic syndrome was related to lower urinary ph in ostensively healthy adult Korean men. Further studies are needed to elucidate the exact mechanism responsible for the lower urinary ph in individuals with the metabolic syndrome. (Korean J Urol 2009;50:694-698) Key Words: Metabolic syndrome X, Obesity, Urinalysis 순천향대학교의과대학비뇨기과학교실 정태성ㆍ양원재ㆍ송윤섭 Received:April 24, 2009 Accepted:June 3, 2009 Correspondence to: Won Jae Yang Department of Urology, Soonchunhyang University College of Medicine, Desagwangil 22, Hannam-dong, Yongsan-gu, Seoul 140-210, Korea TEL: 02-709-9378 FAX: 02-709-9554 E-mail: wonjya@hosp.sch.ac.kr C The Korean Urological Association, 2009 서론요석은흔한비뇨기과질환중의하나로식생활의서구화로인한과체중, 고혈당, 고지혈증과관련하여증가추세에있다. 1 요석의원인과발생기전에관해서는많은연구가있었지만아직도그기전이명확하게밝혀지지않은상태다. 소변중 ph 5.5 이하에서는소변에포함된요산중해리되지않은형태의요산이증가하여요산석의형성이증가하며, 2 요산결정의이질성핵화 (heterogenous nucleation) 에의해살산칼슘석의형성이촉진된다. 이와같은기전으로 소변의산성화가일어나는모든질환에서요석이잘발생한다. 3 대사증후군은 1988년 Reaven 4 이처음으로기술하였으며, 이는지질대사이상, 고혈압, 비만과내당능장애등 2형당뇨병, 관상동맥질환위험요인들이서로군집을이루는현상을한가지질환군으로개념화시킨것이다. 최근한국에서도식이와생활방식의서구화가급속도로진행되면서대사증후군으로인한관상동맥질환및그위험인자의유병률이빠른속도로증가하고있다. 5,6 대사증후군은당뇨및인슐린저항성과관련이있고이에의해소변중의암모늄이온이감소되면서요석의위험인자인소변의산성화를일 694
Tae Sung Jung, et al:the Correlation between Metabolic Syndrome and 695 으키는것으로알려져있지만, 7 한국인을대상으로한연구는없다. 이에저자들은본원건강증진센터를방문한성인한국남성을대상으로대사증후군관련지표와소변중 ph 사이에어떠한상관성이있는지를알아보았다. 1. 연구대상 대상및방법 2004년 1월부터 2008년 6월까지본원건강증진센터를방문하여일반건강검진을시행받은외형적으로건강한 18 세이상의한국남성을대상으로하였다. 2. 평가항목및진단기준 혈압, 체질량지수 (body mass index; BMI), 중성지방, 공복혈당, 고밀도지단백-콜레스테롤 (high-density lipoprotein cholesterol; HDL-C) 등대사증후군의여러지표와소변중 ph와의관계에대해조사하였다. 신장과체중은가벼운복장에서신발을신지않은상태에서측정하였으며혈압은최소 5분간의충분한휴식후전자식혈압계로수축기와이완기혈압을측정하였다. BMI는신장 (height; H) 과체중 (weight; W) 을공식 (BMI=W/H 2 ) 에대입하여산출하였고, 방문자들의혈액샘플은전날자정부터최소 8시간이상금식하도록한후에채취하였으며, 이를이용하여요산, 공복혈당, 중성지방, HDL-C를 enzymatic colorimetric assay로측정하였다. Table 1. Baseline characteristics of the study population by the presence of the metabolic syndrome Variables Absent Present Total No. of patients 13,526 4,987 18,513 (%) (73.1%) (26.9%) (100%) Age (years) 45.3±8.8 6.7±8.5 45.7±8.7 Height (cm) 171.0±5.7 170.8±5.8 170.9±5.8 Weight (kg) 69.3±8.3 77.5±9.2 71.5±9.3 BMI (kg/m 2 ) 23.7±2.3 26.5±2.3 24.5±2.6 Systolic BP (mmhg) 120.1±12.8 131.1±12.9 123.1±13.7 Diastolic BP (mmhg) 78.3±10.3 87.0±10.0 80.7±10.9 Triglyceride (mg/dl) 128.8±70.2 233.5±132.3 157.0±102.4 HDL-C (mg/dl) 52.9±10.5 43.9±8.3 50.5±10.7 Fasting glucose (mg/dl) 96.1±14.9 109.6±28.0 99.7±20.2 Uric acid (mg/dl) 6.05±1.18 6.56±1.36 6.18±1.25 lipoprotein-cholesterol 대사증후군의진단은가장최근에발표된 National Cholesterol Education Program Adult Treatment Panel III (NCEPATP III) 의정의에따라다음의 5가지기준중 3가지이상을만족하는경우로하였다. 8 5가지기준은 1) 고혈당 ( 공복시혈당이 110 mg/dl 이상 ), 2) 고혈압 ( 수축기혈압이 130 mmhg 이상혹은이완기혈압이 85 mmhg 이상 ), 3) 고중성지방혈증 (150 mg/dl 이상 ), 4) 저HDL-C (45 mg/dl 미만 ), 5) 비만 ( 허리둘레가 90 cm 이상이거나 BMI가 25 kg/m 2 이상 ) 으로본연구에서는 BMI가허리둘레와높은상관관계를보이는만족할만한대체자이기때문에, 9 측정의편의를위하여허리둘레대신 BMI를이용하였다. 이중비만에대한항목에서 BMI는아시아-태평양비만기준 (<18.5: 저체중, 18.5-22.9: 정상, 23-24.9: 과체중, 25 kg/m 2 : 비만 ) 에따라분류하였다. 10,11 3. 통계학적분석 대사증후군의유무및보유위험인자각각에따른소변중 ph의차이에대한분석을시행하였다. 또한 BMI에따른소변중 ph의차이에대한분석을시행하였다. 통계분석은 Window R 용 SPSS 14.0 KO을이용하여각각의측정값에대해 chi-square test, 상관분석, 독립표본 Student's t-test, 다중회귀분석, 다변량로지스틱회귀분석을시행하였고, p값이 0.05 미만인경우통계학적으로유의한것으로간주하였다. 결 총 18,513명이분석에포함되었고평균연령은 45.7세 (18-95) 였다 (Table 1). Fig. 1. The prevalence of the metabolic syndrome by number of components. 과
696 Korean Journal of Urology vol. 50, 694-698, July 2009 1. 대사증후군의비율전체연구대상 18,513명에서대사증후군의위험인자를 3개이상가진자는 4,987명 (26.9%) 이었다 (Fig. 1). 대사증후군의위험인자별로비만은 7,432명 (40.2%), 고혈압은 7,584명 (40.9%), 고중성지방은 7,510명 (40.6%), 저HDL-C는 6,517명 (35.2%), 내당능장애는 2,718명 (14.7%) 의유병률을보였다. 2. 대사증후군의위험인자와소변중 ph의관계대사증후군환자의소변중 ph의평균치는 (5.96±8.8) 정상군 (6.07±0.8) 에비해의미있게낮았다 (p<0.001). 이변량분석에서소변중 ph는체중, BMI, 중성지방, 공복시혈당과음의상관관계를보였으며수축기 / 이완기혈압및 HDL-C와는양의상관관계를보였다 (Table 2). 이에대한다변량분석에서비만, 고중성지방혈증, 고혈당과음의상 관관계를나타냈으며, 높은이완기혈압과는양의상관관계를나타냈다 (Table 3). 3. BMI 분류에따른소변중 ph의차이아시아-태평양비만기준에따라따라 BMI를나누었을때정상, 과체중, 비만에해당하는자는각각 5,393명 (29.1%), 5,688명 (30.7%), 7,432명 (40.2%) 이었으며저체중인자는없었다. 정상과과체중군사이에서소변중 ph의차이는없었으나 (p=0.053), 비만군은정상, 과체중군에비해의미있게소변중 ph가낮았다 (p<0.001, p<0.001). 4. 요산석의위험인자인소변중 ph 5.5 이하와대사증후군의관계 4,987명의대사증후군환자중 2,049명 (41.1%) 의소변중 ph가 5.5 이하였으며이는정상군에서의비율 (35.8%) 과차이가있었다 (p<0.001) (Table 4). 다변량분석결과대사증 Table 2. Correlation between urinary ph and components of the metabolic syndrome Variables r a Age (years) 0.014 0.066 Height (cm) 0.006 0.433 Weight (kg) 0.045 <0.001 BMI (kg/m 2 ) 0.050 <0.001 Systolic BP (mmhg) 0.016 0.029 Diastolic BP (mmhg) 0.015 0.042 Triglyceride (mg/dl) 0.071 <0.001 HDL-C (mg/dl) 0.042 <0.001 Fasting glucose (mg/dl) 0.068 <0.001 lipoprotein-cholesterol, a : Pearson s correlation coefficient Table 3. Multivariate linear regression model between urinary ph and components of the metabolic syndrome Variables Coefficient BMI 0.046±0.014 <0.001 Systolic BP 0.030±0.018 0.103 Diastolic BP 0.040±0.018 0.026 Triglyceride 0.102±0.014 <0.001 HDL-C 0.026±0.014 0.072 Fasting glucose 0.155±0.019 <0.001 lipoprotein-cholesterol Table 4. Correlation between low urinary ph ( 5.5) and components of the metabolic syndrome a 5.5 >5.5 BMI <25 kg/m 2 4,010 7,164 <0.000 25 kg/m 2 2,879 4,460 Systolic BP <130 mmhg 4,826 8,074 0.395 130 mmhg 2,063 3,550 Diastolic BP <85 mmhg 4,518 7,524 0.238 85 mmhg 2,371 4,100 Triglyceride <150 mg/dl 3,849 7,154 <0.000 150 mg/dl 3,040 4,470 HDL-C 45 mg/dl 4,326 7,670 <0.000 <45 mg/dl 2,563 3,954 Fasting glucose <110 mg/dl 5,690 10,105 <0.000 110 mg/dl 1,199 1,519 lipoprotein-cholesterol, a : chi-square test Table 5. Multivariate logistic regression analysis between low urinary ph ( 5.5) and components of the metabolic syndrome OR (95% CI) Obesity (BMI<, 25 kg/m 2 ) 1.120 (1.042-1.203) 0.002 Triglyceride (<, 150 mg/dl) 1.223 (1.138-1.316) <0.001 HDL-C (<, 45 mg/dl) 1.090 (1.017-1.169) 0.015 Fasting glucose (<, 110 mg/dl) 1.379 (1.260-1.510) <0.001 OR: odds ratio, CI: confidence interval, BMI: body mass index, HDL-C: high density lipoprotein-cholesterol
Tae Sung Jung, et al:the Correlation between Metabolic Syndrome and 697 후군요소중비만 (BMI 25 kg/m 2 ), 고중성지방혈증 ( 150 mg/dl), 고혈당 ( 110 mg/dl), 저HDL-C (<45 mg/dl) 가소변중 ph 5.5 이하를예측할수있는인자였다 (Table 5). 대사증후군환자의혈중요산의평균치는 (6.56±1.36) 정상군 (6.05±1.18) 에비해의미있게높았다 (p<0.001). 고찰식생활의서구화에의해한국에서도비만인구가급증하고있다. 비만은자체로서질병으로인식되고있어이와연관된대사증후군에대한연구가활발히이루어지고있다. 대사증후군은우리몸에서다양한생리적인변화를일으킨다. Abate 등 7 은대사증후군은콩팥기능에영향을미쳐소변의산성화를일으킬수있다고보고하였다. 대사증후군환자에서소변의산성화가발생하는기전은명확하게밝혀지지않았지만대사증후군및비만환자에서흔하게나타나는인슐린저항성과연관이있을것으로여겨지고있다. 4 소변의산성화는산의배출및완충제의장애에의해발생한다. 암모늄 (NH 3) 은중요한소변의완충제로서, 12 콩팥에서의암모늄생성및배설에의해소변의산-염기환경이조절된다. 인슐린은콩팥에서 glutamine으로부터의암모늄생성을촉진한다. 또한근위세뇨관에서 Na + /H + 교환기를자극하여 H + 의배설을촉진하며배설된 H + 은소변에서암모늄과결합하여암모늄이온 (NH + 4 ) 이된다. 하지만, 인슐린저항성이있으면이러한과정에장해가생겨소변에서가장강력한완충제로서의역할을하는암모늄생성이저하되어이에따라소변의산성화가촉진된다는것이현재까지의유력한가설이다. 2 요석의형성기전에대해서는많은학설이보고되었으나명확하게규명되지않았으며여러인자들이복합적으로작용하는것으로알려져있다. 요산석은칼슘석에이어두번째로많은요석으로그발생은소변의산성도와밀접한관련이있다. 요산은약한유기산이며비수용성퓨린계대사의산물로서, 소변에서의 pka는 5.35로 ph 5.35에서소변에포함된모든요산중반은해리되지않은형태의요산으로, 나머지반은 1가의음이온으로존재한다. 13 Coe 3 의보고에의하면요산은소변의 ph가 6.5일경우 ph 5.0에서보다 11 배정도의용해도를보인다고하였다. 소변의산성화가진행되어용해되지않은요산이증가하면요산석의발생이촉진된다. 또한소변이산성화된상태에서용해되지않은요산이증가하면 monosodium urate가결정성물질이되고그위에칼슘성분의결정성침착이이루어지면서결정이성장하는중가현상 (epitaxy) 이발생하며, monosodium urate 자체가여러억제인자와결합함으로써이질성핵화 (heterogenous nucleation) 를유도하여옥살산칼슘석을발생시킬수도있다. 14 따라서소변의산성화는요산석뿐아니라옥살산칼슘석의발생에도많은영향을끼친다. 본연구는대사증후군관련지표와소변중 ph의관계에대해분석하였으며, 다변량분석에서소변중 ph는비만, 고중성지방혈증, 고혈당과음의상관관계를나타냈으나높은이완기혈압과는양의상관관계를나타냈다. Maalouf 등 15 은요석의과거력, 콩팥부전이없는 148명의자원자들에서 24시간채집된소변을이용하여, 대사증후군관련지표들과소변중 ph의관계에대해규명하였다. 대사증후군각인자중혈당, 수축기혈압, 혈중중성지방혈증은소변중 ph와는음의상관관계, 혈중 HDL-C와는양의상관관계가있다고보고하였다. 이는본연구결과와비슷하나본연구에서는소변중 ph와특히이완기혈압이다변량분석에서양의상관관계를나타냈다. 이러한차이가생긴원인은확실치않다. 아마도지역이나인종의차이, 대상자숫자, 소변채취등연구방법상에서의차이등에그이유가있을것으로추측할뿐이다. ph 5.5 이하의산성소변은원인이없는요산석의가장중요한위험인자이다. 2 하지만소변중 ph 5.5 이하와대사증후군과의관계에대한연구는보고되지않았다. 본연구에서는대사증후군에서요산석의위험인자인소변중 ph 5.5 이하인경우가정상군에비해의미있게높았으며, 다변량분석결과비만, 고중성지방혈증, 고혈당, 저HDL-C가소변중 ph 5.5 이하를예측할수있는인자로밝혀졌다. 이처럼비만등각대사증후군의위험인자는소변의산성화에관여하여요산석이나고요산뇨증옥살산칼슘석등산성소변에서많이발생하는요석의형성에영향을줄것으로여겨지므로대사증후군위험인자의조절은요산석등발생의예방에유용할것이라생각한다. 본연구에서는건강증진센터를방문한사람을대상으로했기때문에과거요석발생등의자세한문진을시행하지않아실제로대사증후군에서요석이더많이발생했는지여부는알수없었지만, 최근연구에서당뇨를앓는요석환자의 33.9% 가요산석인반면, 당뇨가없는요석환자의 6.2% 만이요산석이라는사실이보고되어대사증후군 ( 당뇨 ) 의낮은요중 ph가요석형성기전에실제로영향을미치는것으로여겨진다. 16,17 물론이의직접적인기전과연관성은추가적인연구를통해밝혀져야할것이다. 결론본연구는한국성인남성에서대사증후군과소변중 ph 의관계를분석하였으며대사증후군의소변중 ph가정상
698 Korean Journal of Urology vol. 50, 694-698, July 2009 군에비해더낮다는것이확인되었다. 대사증후군관련지표중비만, 고중성지방혈증, 고혈당, 저HDL-C가요산석형성의위험인자인소변중 ph 5.5 이하를예측할수있는의미있는인자로밝혀졌다. 이후대사증후군혹은비만환자에서이러한현상의정확한기전과실제로요석의발생에미치는영향에대한추가적인연구가필요할것으로생각한다. REFERENCES 1. Borghi L, Schianchi T, Meschi T, Guerra A, Allegri F, Maggiore U, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med 2002;346:77-84 2. Maalouf NM, Cameron MA, Moe OW, Sakhaee K. Novel insights into the pathogenesis of uric acid nephrolithiasis. Curr Opin Nephrol Hypertens 2004;13:181-9 3. Coe FL. Uric acid and calcium oxalate nephrolithiasis. Kidney Int 1983;24:392-403 4. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37:1595-607 5. Eckel RH, Grundy SM, Zimmet PZ. The metabolic syndrome. Lancet 2005;365:1415-28 6. Wilson PW, D Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998;97:1837-47 7. Abate N, Chandalia M, Cabo-Chan AV Jr, Moe OW, Sakhaee K. The metabolic syndrome and uric acid nephrolithiasis: novel features of renal manifestation of insulin resistance. Kidney Int 2004;65:386-92 8. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. Executive summary of the third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA 2001;285:2486-97 9. Ford ES, Mokdad AH, Giles WH. Trends in waist circumference among US adults. Obes Res 2003;11:1223-31 10. Oh SW, Yoon YS, Shin SA. Effects of excess weight on cancer incidences depending on cancer sites and histologic findings among men: Korea National Health Insurance Corporation Study. J Clin Oncol 2005;23:4742-54 11. WHO Expert Consultation. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet 2004;363:157-63 12. DuBose TD Jr, Good DW, Hamm LL, Wall SM. Ammonium transport in the kidney: New physiological concepts and their clinical implications. J Am Soc Nephrol 1991;1:1193-203 13. Wasko R, Frankenfield BA. Allopurinol dissolution of renal uric acid calculi. JAMA 1968;205:801 14. Stoller ML. Gout and stones or stones and gout? J Urol 1995;154:1670 15. Maalouf NM, Cameron MA, Moe OW, Adams-Huet B, Sakhaee K. Low urine ph: a novel feature of the metabolic syndrome. Clin J Am Soc Nephrol 2007;2:883-8 16. Daudon M, Lacour B, Jungers P. High prevalence of uric acid calculi in diabetic stone formers. Nephrol Dial Transplant 2005;20:468-9 17. Pak CY, Sakhaee K, Moe O, Preminger GM, Poindexter JR, Peterson RD, et al. Biochemical profile of stone-forming patients with diabetes mellitus. Urology 2003;61:523-7