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1 대한내과학회지 : 제 73 권제 6 호 2007 제 2 형당뇨병환자에서초음파측정내장지방지표와심혈관계위험인자와의관계 전남대학교의과대학내과학교실 정귀홍 김성균 정진욱 조동혁 정동진 정민영 =Abstract= Association between ultrasonographic visceral fat indices and cardiovascular risk factors in type 2 diabetic patients Gwi Hong Jeong, M.D., Sung Kyun Kim, M.D., Jin Ook Chung, M.D., Dong Hyeok Cho, 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 : Visceral obesity is known as an independent risk factor of cardiovascular disease and metabolic syndrome. The objective of this study was to evaluate the association of ultrasonographic-determined visceral fat thickness and other parameters of obesity, metabolic syndrome, and risk factors of cardiovascular disease in type 2 diabetes. Methods : A total of 191 type 2 diabetic patients (101 men and 90 women) participated in this study. Anthropometric, clinical, and laboratory data including the body mass index, waist circumference, blood pressure and lipid profiles were measured. Insulin resistance was calculated by using the homeostasis model assessment-insulin resistance (HOMA-IR). The visceral fat thickness was measured by abdominal ultrasonography at 1 cm above the umbilicus. Results : The visceral fat thickness was positively correlated with the body mass index (p<0.001), waist circumference (p<0.001), fat mass (p<0.001), fat distribution (p<0.001), and HOMA-IR (p<0.05), whereas it was negatively correlated with thehdl-cholesterol level (p<0.05). The visceral fat thickness was better correlated with the presence of metabolic syndrome than with the subcutaneous fat thickness. The highest tertile of visceral fat thickness had a higher odds ratio for hypertension (OR=4.02, 95% CI 1.08~14.98), dyslipidemia (OR=9.64, 95% CI 1.08~85.37), and metabolic syndrome (OR=11.35, 95% CI 1.34~96.00) than did those in the lowest tertile, after adjustment for age, sex, and body mass index. Conclusions : The results of our study show that the measurement of abdominal visceral fat thickness using abdominal ultrasonography can be used as a reliable method to identify the risk for metabolic syndrome and cardiovascular disease in type 2 diabetic patients. (Korean J Med 73: , 2007) Key Words : Type 2 diabetes mellitus, Ultrasonography, Visceral fat, Cardiovascular disease Received : Accepted : Correspondence to : Min Young Chung, M.D., Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju , Korea MYChung@jnu.ac.kr

2 -Gwi Hong Jeong, et al : Association between ultrasonographic visceral fat indices and cardiovascular risk factors - 서론 대상및방법 비만은제2형당뇨병, 고혈압, 고지혈증, 고인슐린혈증및동맥경화증등의대사질환과밀접한관계가있으며 1), 이로인하여관상동맥질환같은심혈관계질환의위험도를증가시키는것으로알려져있다 2). 전신적인지방의양뿐만아니라체내지방의국소적인분포도매우중요하며 3), 복강내에지방이축적되는내장비만이특히대사증후군등심혈관계질환의위험도를증가시키는것으로보고되고있다 4, 5). 일반적으로비만도측정은신장과체중을이용한비만도및체질량지수 (body mass index, BMI) 와같은신체계측학적방법이널리이용되며, 복부비만을측정하기위한방법으로는허리둘레및허리엉덩이둘레비와같은신체계측학적방법 5) 과이중에너지방사선흡수법 (dual-energy X-ray absorptiometry, DXA) 6) 및컴퓨터단층촬영 (computed tomography, CT) 등이이용되고있다. 이중에서컴퓨터단층촬영은복부의내장지방과피하지방을정확하게구분할수있고, 재현성이있어서내장지방측정의표준적인방법으로알려져있으나 2), 방사선에노출되는등의제한점을가지고있다. 따라서 1990년대이후로초음파 (ultrasonography, US) 를이용한내장지방의측정이더간단하고경제적이며비침습적인방법으로제시되고있으며 7), 컴퓨터단층촬영을이용하여측정한내장지방과도높은상관관계를보임이여러연구에서밝혀진바있다 8). 초음파측정내장지방은심혈관계질환의위험도와도유의한관계가있음이보고되고있다 9). 국내의연구에따르면김등 10) 은초음파측정내장지방두께가컴퓨터단층촬영으로측정한내장지방의지표와유의한관계가있음을증명하였으며, 황등 11) 은컴퓨터단층촬영으로측정한복부내장지방면적이 10 cm 2 씩증가할때마다대사증후군의위험도가 1.14배 (95% CI; 1.03~1.27) 씩증가함을보고하였다. 그러나초음파측정내장지방두께와심혈관계질환의위험인자와의관계에대한연구는많지않으며, 특히제2형당뇨병환자를대상으로초음파를이용한내장지방의측정이심혈관계위험도를평가할수있는지에대한연구는거의없는실정이다. 따라서본연구는제2형당뇨병환자에서초음파측정내장지방두께와다른비만측정법들과의관련성을알아보고초음파를통하여평가한내장비만이심혈관계위험인자와어떠한연관성이있는지살펴보고자하였다. 1. 대상 2005년 9월부터 2006년 8월까지전남대학교병원에내원한제2형당뇨병환자 191명을대상으로하였으며남성이 101명, 여성이 90명이었다. 제1형당뇨병환자는제외하였으며, 장기간침상안정중이거나복수가있는경우, 20세미만과 85세이상, 전이성암, 만성간질환이나간비대및비장비대가있는경우, 최근 3개월동안 3 kg 이상의체중감소가있는경우, 임신및수술등으로측정부위에이상소견이있는환자는연구대상에서제외하였다. 2. 방법문진을통하여흡연력, 고혈압, 고지혈증등의과거력및약물력등을조사하였다. 협심증이나심근경색증과같은심혈관계질환, 뇌졸중과같은뇌혈관질환및말초혈관질환의과거력을조사하였다. 15분이상휴식을취한상태에서수축기및이완기혈압을측정하였다. 발목위팔동맥압지수 (ankle brachial pressure index, ABPI) 는자동화된 ABPI 측정기 (VaSera TM, VS-1000, Japan) 를이용하여각각우측과좌측의상완과발목부위혈압의비로계산하여그수치가 0.9 미만인경우를이상소견으로판단하였다. 비만도측정을위하여신체계측학적방법으로신장, 체중및허리둘레를측정하였고, 이를통하여체질량지수 (body mass index=kg/m 2, BMI) 를계산하였다. 허리둘레는직립자세에서늑골최하연과골반장골능사이의중간부위를호기끝에서측정하였다. 생체전기임피던스법을이용한체지방측정기 (Inbody 3.0, Biospace Co. Korea) 를이용하여체지방량 (fat mass, kg), 체지방률 (percent body fat, %) 그리고복부지방률 (fat distribution) 을측정하였다. 혈액학적검사로는 8시간이상공복후채혈하여총콜레스테롤 (enzymatic colorimetry, AU5400, Olympus, Japan), 중성지방 (glycerol-phosphate-oxidase method, AU5400, Olympus, Japan), 고밀도지단백콜레스테롤 (immunoinhibition method, AU5400, Olympus, Japan), 저밀도지단백콜레스테롤 (direct selective method, AU5400, Olympus, Japan) 을측정하였으며아포지단백 A1, 아포지단백 B (nephrometer analyser II, DADE Behring, Germany) 및 lipoprotein(a) 의농도 (N latex lipoprotein

3 - 대한내과학회지 : 제 73 권제 6 호통권제 568 호 (a) reagent) 를측정하였다. 인슐린저항성은 Homeostasis model for insulin resistance (HOMA-IR) 방법을통하여측정하였으며, 공복포도당농도 (mmol/l) 공복인슐린농도 (µu/ml)/22.5로계산하였다. 대사증후군의유무를판단하기위하여 2001년에개정된제3차콜레스테롤관리지침 (the third national cholesterol education program expert panel on detection, evaluation, and treatment of high blood cholesterol in adult, NCEP- ATP III) 에따라각각고혈압 ( 수축기혈압 130 mmhg, 이완기혈압 85 mmhg), 내당능장애 ( 공복혈당 110 mg/dl), 고중성지방혈증 ( 150 mg/dl), 저-HDL- 콜레스테롤혈증 ( 남 : <40 mg/dl, 여 : <50 mg/dl), 허리둘레 ( 남 : 90 cm, 여자 : 80 cm, 아시아-태평양기준 ) 의총다섯가지중세가지이상에해당될때대사증후군을갖고있는것으로정의하였다 12). 고혈압및고지혈증약제를복용중인경우에는과거의검사결과를기준으로하여각각고혈압과고지혈증을동반하고있는것으로판단하였다. 당뇨병성만성미세혈관합병증은망막증에대한안저검사, 신증에대한뇨알부민배설률 (urine albumin excretion, UAE) 측정, 신경병증에대한진동감각역치검사 (vibration perception threshold), 심박수변화검사 (cardiac beat-to-beat variability, BBV) 및신경전도검사 (nerve conduction velocity) 로확인하였다. 대혈관합병증은과거력을갖고있는경우에나증상이있어관상동맥조영술, 뇌컴퓨터단층촬영이나자기공명영상촬영, 말초혈관조영술등을시행하여이상소견이있는경우로판단하였다. 초음파를이용한내장지방의측정은고해상도초음파기기 (LOGIQ7, GE Medical Systems, USA) 를이용하여 Fernando F. Ribeiro-Filho 등의방법 13) 으로시행하였다. 방법은동일한검사자가환자를눕힌상태에서 3.5 MHz 탐침으로호기말에백선을따라서배꼽상방 1 cm 부위에서피하지방두께와내장지방두께를측정하였다. 초음파로측정한피하지방두께 (ultrasonographic measured subcutaneous fat thickness, USFT) 는피부와복부기립근의바깥쪽사이의길이로정하였으며, 내장지방두께 (ultrasonographic measured visceral fat thickness, UVFT) 는같은부위에서복부기립근의안쪽면부터대동맥의전벽까지의길이로정하였다 13) ( 그림 1). 복막전둘레 (preperitoneal circumference, PC) 는허리둘레-(2π USFT) 로계산하였다 15). 모든초음파측정은한사람의숙련된검사자가시행하였으며, 검사당 2회씩측정하여 Figure 1. The visceral fat thickness indices measured by ultrasonography. Ultrasonographic imaging at 1 cm above the umbilicus. Ultrasonographically measured subcutaneous fat thickness was defined as the distance between the skin and external face of the rectus abdominis muscle, and visceral fat thickness was defined as the distance between the internal face of the same muscle and the anterior wall of the aorta. Ao; Aorta, USFT, ultrasonographically measured subcutaneous fat thickness, UVFT, ultrasonographically measured visceral fat thickness 그평균값을수치로정하였다. 3. 통계처리 통계분석은 SPSS for windows를이용하였다 (version 12.0, SPSS Inc, Chicago). 초음파측정내장지방두께와다른연속변수들과상관분석을이용하였다. 초음파측정내장비만두께는기준치 (cut-off value) 를정하기위하여 ROC 곡선을이용하여계산하였다 ( 그림 3). 심혈관계질환의위험인자와초음파측정내장지방두께와의관계를확인하기위하여교차분석및회귀분석을시행하였다. 결과는 p 값이 0.05 미만일때통계적으로유의하다고판정하였다. 결과 1. 연구대상자의일반적인특성 ( 표 1) 연구대상자의평균연령은 62.3±10.6 세 (36 세 -83 세 ) 이

4 - 정귀홍외 5 인 : 제 2 형당뇨병환자에서초음파측정내장비만과심혈관계위험 - Table 1. Clinical characteristics of the subjects Male (n=101) Female (n=90) Total (n=191) Age (years) BMI (kg/m 2 ) Waist circumference (cm) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) ApoA1 (mg/dl) ApoB (mg/dl) Lp(a) (mg/dl) HbA1C (%) UAE (mg/gcr) Fasting glucose (mg/dl) Fasting insulin (µu/ml) Fasting glucose/fasting insulin HOMA-IR Fat mass (Kg) Percent body fat (%) Fat distribution USFT (mm) UVFT (mm) UVFT/USFT PC (cm) 62.5± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±12.3 ** 118.3± ±28.4 * 101.5± ±29.2 * 8.5± ± ± ± ± ± ±5.7 * 38.2± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ±6.9 HOMA-IR, homeostasis model assessment-insulin resistance PC, preperitoneal circumference = waist circumference-(2π USFT) UAE, urine albumin excretion USFT, ultrasonographically measured subcutaneous fat thickness UVFT, ultrasonographically measured visceral fat thickness * p<0.05 vs. male ** p<0.001 vs. male 며, 제2형당뇨병의평균유병기간은 10.3±9.3년 (1개월 -35년) 이었다. 대상군을남녀로구분한경우허리둘레는남성이 90.6±7.3 cm, 여성이 90.6±7.5 cm으로성별에따른유의한차이는보이지않았다. 대상군의연령이나체질량지수에서도성별에따른유의한차이는없었다. 체지방측정기를이용하여측정한체지방량은여성이유의하게더많았으나, 초음파측정내장지방지표들에있어서성별에따른차이는보이지않았다. 2. 초음파측정내장지방두께와다른비만지표와의상관관계 ( 표 2, 그림 2) 초음파측정내장비만지표들과신체계측학적방법이나체지방측정기를이용하여측정한다른비만지표들과 의상관관계를보았을때초음파측정내장지방두께는체질량지수 (r=0.444), 허리둘레 (r=0.466), 체지방량 (r=0.477), 복부지방률 (r=0.274) 과유의한양의상관관계를나타내었다. 복막전둘레도체질량지수 (r=0.564), 허리둘레 (r=0.939), 체지방량 (r=0.570), 복부지방률 (r=0.453) 과유의한상관관계를보였으며, 특히초음파측정내장지방두께보다도더좋은상관관계가관찰되었다. 초음파측정피하지방두께도비만지표들과유의한상관관계를관찰할수있었으나, 내장지방과피하지방의두께비는신체계측학적방법이나체지방측정기를이용하여측정한지표와유의한상관관계를보이지않았다

5 -The Korean Journal of Medicine : Vol. 73, No. 6, Table 2. Correlation between ultrasonographic visceral fat indices, anthropometric data, and clinical data USFT (mm) UVFT (mm) UVFT/USFT PC (cm) BMI (kg/m 2 ) WC (cm) Fat mass (Kg) Percent body fat (%) Fat distribution ** ** ** ** ** ** ** ** * ** ** ** ** BMI, body mass index PC, preperitoneal circumference = waist circumference-(2π USFT) USFT, ultrasonographically measured subcutaneous fat thickness UVFT, ultrasonographically measured visceral fat thickness WC, waist circumference. * p<0.05 ** p<0.001 r=.477, p<0.001 r=.274, p<0.001 r=.444, p<0.001 r=.466, p<0.001 Figure 2. Correlation between ultrasonographically measured visceral fat thickness and other obesity indices. Visceral fat thickness measured by ultrasonography was correlated with fat mass, fat distribution, body mass index, and waist circumference. BMI, body mass index; UVFT, ultrasonographically measured visceral fat thickness

6 -Gwi Hong Jeong, et al : Association between ultrasonographic visceral fat indices and cardiovascular risk factors - Table 3. Correlation between the ultrasonographic visceral fat thickness indices, waist circumference, lipid profiles, and insulin resistance USFT (mm) UVFT (mm) UVFT /USFT PC (cm) WC (cm) Total-cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) * LDL-cholesterol (mg/dl) ApoA1 (mg/dl) ApoB (mg/dl) Lp(a) (mg/dl) Fasting insulin (µu/ml) Fasting glucose/insulin * * * * * HOMA-IR * * * * HOMA-IR, homeostasis model assessment-insulin resistance PC, preperitoneal circumference = waist circumference-(2π USFT) USFT, ultrasonographically measured subcutaneous fat thickness UVFT, ultrasonographically measured visceral fat thickness WC, waist circumference * p< 초음파측정내장지방두께와심혈관계위험인자와의상관관계 ( 표 3) 초음파측정내장지방두께는공복인슐린농도 (r=0.266), 공복혈당 / 공복인슐린비 (r=-0.323), HOMA-IR (r=0.286) 와유의한상관관계를보였으며, 복막전둘레는 HOMA-IR (r=0.242) 에서유의한상관관계가관찰되었다. 허리둘레의경우공복혈당 / 공복인슐린비 (r=0.306) 및 HOMA-IR (r=0.299) 와유의한상관관계를보였다. 초음파측정내장지방지표들과혈중지질과의상관관계를비교하기위하여대상군중고지혈증치료제를사용하지않은환자들 ( 총 89명 ) 만을대상으로분석하였을때초음파측정내장지방두께는고밀도지단백콜레스테롤 (r=-0.240) 과유의한음의상관관계를보였다. 4. 대사증후군의유무에따른초음파측정내장지방두께의비교 ( 표 4) 전체대상환자들을 NECP-ATP III 지침에따른대사증후군의유무에따라두군으로나누었으며, 대사증후군을갖고있는환자들은총 148명이었다. 대사증후군을갖고있는군은갖고있지않은군에비하여체질량지수, 허리둘레, 체지방측정기를이용하여측정한체지방량, 중성지방, 아포지단백 B가유의하게높았으며, 고밀도지단 백콜레스테롤과공복포도당 / 공복인슐린비는유의하게낮았다. HOMA-IR 은대사증후군을갖고있는군에서높았으나통계학적으로유의하지않았다. 초음파측정내장지방두께와복막전둘레는대사증후군을갖고있는군에서유의하게높았으며, 피하지방두께는양군간에유의한차이를보이지않았다. 5. 초음파측정내장지방두께에따른비만군과비비만군의비교 ( 표 5, 그림 3) 초음파측정내장지방두께와허리둘레에따른복부비만의유무와의관계를 ROC 곡선을통하여분석하여초음파측정내장지방두께가 44.5 mm 이상인경우를비만군으로정하였다 ( 그림 3). 초음파측정내장지방두께에따른비만군과비비만군을비교하였을때, 비만군이체질량지수및허리둘레가유의하게높았으며, 혈액검사중에서중성지방, 공복포도당 / 공복인슐린비및 HOMA-IR 수치가유의하게높았다. 6. 초음파측정내장지방두께에따른비만군에서심혈관계위험인자및대사증후군의위험도 ( 표 6) 초음파측정내장지방두께가 44.5 mm 이상인비만군이비비만군에비하여이상지혈증 (OR=2.45, p=0.030) 및대사증후군 (OR=2.66, p=0.011) 의위험도가유의하게증

7 - 대한내과학회지 : 제 73 권제 6 호통권제 568 호 Table 4. Comparison between the clinical characteristics of the metabolic syndrome and non-metabolic syndrome group Non-metabolic syndrome group (n=38) Age (years) 63.5±10.7 BMI (kg/m 2 ) 23.3±2.9 Waist circumference (cm) 85.5±5.4 Total cholesterol (mg/dl) 165.6±39.9 Triglyceride (mg/dl) 95.4±32.0 HDL-cholesterol (mg/dl) 50.5±14.2 LDL-cholesterol (mg/dl) 108.4±38.2 ApoA1 (mg/dl) 129.5±34.3 ApoB (mg/dl) 86.5±28.2 Lp(a) (mg/dl) 40.0±48.2 Free fatty acid (µeq/l) 666.0±348.3 HbA1C (%) 8.5±2.2 UAE (mg/gcr) 144.9±358.8 Fasting glucose/fasting insulin 35.4±41.9 HOMA-IR 3.1±2.2 Fat mass (kg) 15.8±5.3 Percent body fat (%) 50.6±76.3 USFT (mm) 16.0±4.4 UVFT (mm) 44.9±11.8 PC (cm) 75.3±4.8 BMI, body mass indexhoma-ir, homeostasis model assessment-insulin resistance PC, preperitoneal circumference = waist circumference-(2π X USFT) UAE, urine albumin excretion USFT, ultrasonographically measured subcutaneous fat thickness UVFT, ultrasonographically measured visceral fat thickness * p<0.05 vs. non-metabolic syndrome group ** p<0.001 vs. non-metabolic syndrome group metabolic syndrome group (n=148) 620± ±3.3 * 92.0±7.3 ** 180.6± ±90.8 ** 40.9±11.4 ** 118.2± ± ±34.5 ** 35.7± ± ± ± ±29.0 * 8.2± ±5.7 * 31.9± ± ±16.7 * 81.2±6.8 ** 가하였으며, 복막전둘레 75.3 cm을기준으로비만군을구분한경우에도이상지혈증 (OR=2.43, p=0.049) 및대사증후군 (OR=7.89, p<0.001) 의위험도가유의하게증가하였다. 7. 초음파측정내장지방두께및복막전둘레에따라삼분위로구분하여심혈관계질환위험인자와의위험도비교 ( 표 7) 초음파측정내장지방두께에따라삼분위로구분하였을때상위삼분위군은하위삼분위군에비하여이상지혈증 (OR=5.00, 95% CI; 1.07~23.19) 과대사증후군 (16.08, 95% CI; 2.06~125.26) 의위험도가증가하였으며, 나이, 성별및체질량지수로보정한후에는이상지혈증 (OR=9.64, 95% CI; 1.08~85.37), 대사증후군 (OR=11.35, 95% CI; 1.34~96.00), 고혈압 (OR=4.02, 95% CI; 1.08~14.98) 의위 험도가증가하였다. 고찰내장비만은심혈관계질환의위험인자이며이환률과사망률을증가시키는독립적인위험인자로도잘알려져있으며 1), 인슐린저항성, 제2형당뇨병, 고혈압, 이상지혈증, 여성에서의고안드로겐혈증외다양한질환들과도연관되어있다 14). 복부내장지방은복부피하지방에비하여대사증후군의인자들과관련성이더높은것으로보고되고있으며 15), 이러한특징은지방조직의분포부위에따라대사적특징이다르기때문으로알려져있다. 내장지방조직은피하지방조직에비하여기초지방분해율이더높은것으로보고되었으며 16), 이로인하여내장지방이증가하는경우에는간문맥으로유리지방산, 사이토카인 (cyto

8 - 정귀홍외 5 인 : 제 2 형당뇨병환자에서초음파측정내장비만과심혈관계위험 - Table 5. Comparison of clinical characteristics between obese and non-obese group by ultrasonographically measured visceral fat thickness Non-obese Group (n=69) Age (years) 64.0±9.2 BMI (kg/m 2 ) 23.0±3.0 Waist circumference (cm) 87.0±5.7 Total cholesterol (mg/dl) 171.1±51.0 Triglyceride (mg/dl) 136.0±84.8 HDL-cholesterol (mg/dl) 44.6±14.1 LDL-cholesterol (mg/dl) 111.6±44.8 Apo A1 (mg/dl) 128.5±29.0 Apo B (mg/dl) 96.3±35.2 Lp(a) (mg/dl) 28.3±28.1 Free fatty acid (µeq/l) 635.6±302.7 HbA1c (%) 8.5±2.3 UAE (mg/gcr) 242.7±385.0 Fasting glucose/fasting insulin 34.5±46.4 HOMA-IR 3.4±2.4 Fat mass (Kg) 16.6±4.2 Percent body fat (%) 31.2±24.6 according to UVFT, obese 44.5 mm BMI, body mass index HOMA-IR, homeostasis model assessment-insulin resistance PC, preperitoneal circumference = waist circumference-(2π X USFT) UAE, urine albumin excretion USFT, ultrasonographically measured subcutaneous fat thickness UVFT, ultrasonographically measured visceral fat thickness * p<0.05 vs. non-obese syndrome group ** p<0.001 vs. non-obese syndrome group Obese Group (n=122) 61.0± ±3.1 ** 92.6±7.6 ** 181.4± ±87.6* 41.7± ± ± ± ± ± ± ± ±18.0 * 9.0±14.6 * 20.0±6.1 * 36.9±46.4 kines), 혈관활성펩티드 (vasoactive peptide) 등의분비가증가되어간에서인슐린대사및작용을변화시켜해로운작용을유발함으로서 14), 대사증후군의병태생리에중요한역할을하는것으로알려져있다 17). 내장비만을진단하는방법으로는허리둘레, 허리엉덩이둘레비, 배의정중단면길이측정등의간단하고비침습적인신체계측학적방법이쉽게이용되고있다 5). 신체계측학적방법중에서허리둘레는허리엉덩이둘레비보다쉽게측정이가능하면서도보다민감하고내장지방및심혈관계질환의위험도를잘반영해주는지표로널리인정받고있다. Seidell 등 5) 은허리둘레가체질량지수보다고혈압, 고중성지방혈증및저-고밀도콜레스테롤혈증과높은관련성을보이며, 허리엉덩이둘레비에비해서도심혈관계질환의위험인자와더좋은상관관계가있음을보고하였다. Pouliot 등 18) 도허리둘레가허리엉덩이둘레비 에비하여내장지방의축적정도를더정확하게반영할수있으며, 공복및식후혈청인슐린농도의증가와더높은상관관계를보임을증명하였다. 그리고허리둘레가 100 cm를초과하는경우에는잠재적으로동맥경화증을일으킬수있는대사이상과연관되어있음을보고하였다 18). 그러나허리둘레와심혈관계위험의연관은항상정확하지는않아서, Grundy 등은허리둘레가큰사람이항상인슐린저항성이높지는않다고하였으며, 그이유로유전적문제나측정방법의문제등을제시하였다 19). 또한허리둘레가심혈관계질환의위험과항상연관되지못하는이유는허리둘레가내장지방뿐만아니라피하지방과도높은상관관계를가지고있기때문으로생각되고있다 20). 복부의피하지방을제외한내장지방만을직접측정하는방법들로현재까지여러가지측정법이제시되고있으며, 그중에서컴퓨터단층촬영을이용하여측정한내장지방

9 -The Korean Journal of Medicine : Vol. 73, No. 6, <visceral fat thickness> sensitivity: 76% specificity: 54% <preperitoneal circumference> sensitivity: 87% specificity: 56% Figure 3. Receiver operating characteristic (ROC) analyses of ultrasonographic measured visceral fat thickness and preperitoneal circumference as a predictor of the presence or absence of abdominal obesity. The higher the area under the curve, i.e., the greater the curvature away from the 50% line, the greater the predictive power. A visceral fat thickness of 44.5 mm and preperitoneal circumference of 75.3 cm were chosen as the discriminator values to predict the presence of abdominal obesity. The area under the ROC curve was in visceral fat thickness and in the preperitoneal circumference. Table 6. Cardiovascular risk factors related with ultrasonographically measured visceral obesity Hypertension Dyslipidemia Macrovascular complications Insulin resistance Metabolic syndrome UVFT obesity PC obesity OR (range) p value OR (range) p value 1.48 (.76~2.89) (.99~4.64) (1.07~5.63) (.98~5.99) (.65~2.07) (.40~1.65) (.55~3.00) (.84~6.26) (1.23~5.76) (3.29~18.93) UVFT obesity means UVFT 44.5 mm PC obesity means PC 75.3 cm OR, odd ratio USFT, ultrasonographically measured subcutaneous fat thickness UVFT, ultrasonographically measured visceral fat thickness 면적이비교적정확히내장지방을정량화할수있는표준방법으로알려져있다 21). 현재까지많은연구들에서컴퓨터단층촬영을이용한내장지방면적이심혈관계위험인자와유의한상관관계가있음이보고되고있다. Fujioka 등 4) 은배꼽위치에서컴퓨터단층촬영을이용하여측정한내장지방과피하지방의면적비가혈당, 중성지방, 총콜레스테롤농도와높은상관관계가있음을증명하였으며, Matsuzawa 등 22) 은컴퓨터단층촬영으로측정한내장지방면적과피하지방면적비가 0.4 이상일때내당능장애와지질대사이상이증가하였으며심혈관계질환의유병률이 증가함을보여주었다. 따라서일본비만학회에서는비만과관련되어심혈관계질환등의합병증이증가하는기준으로컴퓨터단층촬영을이용하여측정한내장지방면적 100 cm 2 이상을제시하였다 23). 우리나라에서는황등 11) 이컴퓨터단층촬영으로측정한내장지방면적이 120 cm 2 이상인경우에대사증후군의위험도가급격히증가함을보고하여비슷한결과를보여주었다. 그러나컴퓨터단층촬영을통한내장지방면적측정은비교적고가이며, 일반적인중소병원에서는쉽게이용하기어렵고, 방사선에노출된다는점등으로인하여임상적으로쉽게이용하기어려

10 -Gwi Hong Jeong, et al : Association between ultrasonographic visceral fat indices and cardiovascular risk factors - Table 7. Cardiovascular risk factors related with the tertile of ultrasonographic measured visceral fat thickness Unadjusted Adjusted Low tertile Middle tertile High tertile Low tertile Middle tertile High tertile hypertension (0.58, 2.47) 2.69 (0.92, 7.89) (0.60, 2.92) 4.02 * (1.08, 14.98) dyslipidemia (0.85, 4.92) 5.00 * (1.07, 23.19) (0.85, 5.90) 9.64 * (1.08, 85.37) macrovascular complications (0.80, 2.90) 1.09 (0.49, 2.40) (0.88, 3.73) 1.37 (0.52, 3.60) insulin resistance (0.42, 2.67) 2.76 (0.80, 9.51) (0.36, 2.94) 2.30 (0.47, 11.19) metabolic syndrome (0.85, 3.84) * (2.06, ) (0.71, 3.91) * (1.34, 96.00) * p<0.05; significantly different from the low tertile (logistic regression analysis) Adjusted for age, sex and body mass index 운단점을가지고있다. 이러한컴퓨터단층촬영의제한점으로인하여복강내내장지방을직접적으로평가하는비침습적인방법들이제시되고있으며, 특히초음파를이용한내장비만측정법이 1990년대이후로널리연구되고있다 24-26). Tornaghi 등은초음파로측정한내장지방두께가일반적인신체계측학적방법들보다컴퓨터단층촬영으로측정한내장지방면적과더좋은유의한상관관계 (r= ) 를보임을보고하였으며 7), Riberio-Filho 등 8) 도초음파를이용하여배꼽 1 cm 상방에서측정한내장지방두께가컴퓨터단층촬영으로측정한내장지방과유의한상관관계 (r=0.67, p<0.0001) 가있음을증명하였다. 그리고 Hirooka 등 27) 은초음파를이용하여복부기립근과비장정맥사이의거리, 배꼽높이에서의복부근육과대동맥사이의거리및신장뒷면의지방두께등다양한방법을통하여계산한내장지방의양이컴퓨터단층촬영으로측정한지방의양과매우높은상관관계 (r=0.86, p<0.0001) 가있음을제시하였으며, Koda 등 28) 도초음파를이용하여내장지방두께와피하지방두께를측정하는방법이컴퓨터단층촬영및자기공명영상촬영으로측정한내장지방의양과유의한상관관계가있음을보고하여초음파를이용한내장지방의측정이컴퓨터단층촬영을이용한내장지방측정의좋은대안으로제시하고있다. 초음파측정내장지방두께와다른신체계측학적방법들과의상관관계에대한연구들도많으며 Meriño-Ibarra 등은초음파측정내장지방두께와복막전둘레가체질량지수및허리둘레와유의한상관관계가있었다고보고하였고 16), 우리나라에서는 Kim 등 29) 이초음파측정내장지방두께가허리둘레및체질량지수와유의한관련성이있음을보고한바있다. 본연구에서도초음파측정내장지방두께및복막전둘레가체질량지수및허리둘레와유의한상관관계가있음을확인할수있어다른연구들과비슷한결과를보여주었다. 내장지방은이상지혈증과관련이있음은널리알려져있으며초음파측정내장지방두께와혈청지질농도와의상관관계를보고한논문들도있다. Kim 등 29) 은초음파측정내장지방두께가남자에서혈청고밀도지단백콜레스테롤및중성지방농도와유의한상관관계가있었으며여자에서는중성지방농도와유의한상관관계가있음을보여주었다. 그리고 Meriño-Ibarra 등 16) 은초음파측정복막전둘레가허리둘레에비하여중성지방및아포지단백 A1 농도를보다잘예측할수있다고보고하였다. 본연구에서는초음파측정내장지방두께가다른지질농도에비하여혈청고밀도지단백콜레스테롤과유의한음의상관관계가있음을보여주었으며, 이는다른연구와비슷한결과로내장지방이지질대사이상중에서특히고밀도지

11 - 대한내과학회지 : 제 73 권제 6 호통권제 568 호 단백콜레스테롤과관련성이높음을암시해주는결과라고할수있겠다. 한편본연구에서허리둘레는지질대사이상과상관관계를보이지않았으나초음파로측정한내장지방의두께는이상지혈증과더좋은상관관계를보임으로서허리둘레보다더좋은지표가될수있는가능성을보여주었다. 내장지방의증가가인슐린저항성및고인슐린혈증을유발할수있음은많은연구들에서밝혀져있다. Ribero- Filho 등 30) 은내장지방이비만과인슐린저항성을연결하는중요한인자라고주장하였고, Taniguchi 등 31) 은비만하지않은제2형당뇨병환자에서 HOMA-IR 이컴퓨터단층촬영으로측정한내장지방과유의한양의상관관계 (r=0.408, p=0.001) 가있음을보고하였으며, Meriño-Ibarra 등 16) 도초음파측정내장지방지표들중복막전둘레가허리둘레에비하여 HOMA-IR 을보다잘예측할수있는지표임을보여주었다. 따라서 Suzuki 등 25) 은내장지방이인슐린저항성의주요인자이며복부초음파를통한내장지방측정이내장비만을평가하는쉽고믿을수있는방법임을제시하였다. 본연구에서는초음파측정내장지방두께가공복인슐린, 공복혈당 / 공복인슐린농도비및 HOMA-IR 과유의한양의상관관계를보였고, 복막전둘레도 HOMA-IR 과유의한상관관계를보였다. 초음파측정내장지방두께가복막전둘레보다인슐린저항성과약간더좋은상관관계가있음을관찰할수있어 Meriño- Ibarra 등 16) 과비슷한결과를보여주었다. 본연구에서허리둘레는공복포도당 / 공복인슐린농도비및 HOMA-IR 과유의한상관관계가있었다. HOMA-IR 의경우본연구에서는초음파로측정한복막전둘레가허리둘레보다더큰상관관계를보였던 Meriño-Ibarra의결과와일치하지않았으나 16), 더많은환자를대상으로연구가필요하리라생각되었다. 내장지방이심혈관계질환의위험인자로알려져있어초음파측정내장지방두께가심혈관계질환의위험도과연관되어있음을보고한연구들도있다. Leite 등 9) 은초음파측정내장지방두께가심혈관계질환의독립적인위험인자라고하였으며, Kim 등 29) 도제2형당뇨병환자에서초음파측정내장지방이심혈관계위험인자와연관되어있음을보고하였다. 초음파로측정한내장비만의기준값에대한연구는아직부족한실정이다. Kim 등 29) 은 ROC 곡선을통하여남자 47.6 mm ( 민감도 71%, 특이도 74%), 여자 35.5 mm ( 민감도 69%, 특이도 78%) 를기준값으로정하였으나, 이값을심혈관질환의위험도를예측할수있는기준으로제시하지는못하였다. 본연구에서는 ROC 곡선을통한분석을이용하여초음파측정내장지방두께 44.5 mm를기준으로비만군을결정하였으며, 비만군에서이상지혈증의위험도가 2.45배, 대사증후군의위험도가 2.66배정도증가하였다. 복막전둘레 75.3 cm를기준으로한비만군에서는이상지혈증의위험도가 2.43배, 대사증후군의위험도가 7.89배정도증가함을보여주었다. 이는대사증후군의위험도를예측하는지표로서복막전둘레가내장지방두께보다보다좋은지표가될수있음을제시한다고할수있으며, 이상지혈증의예측인자로는두가지지표가비슷함을보여주었다. 따라서초음파측정내장지방두께및복막전둘레는대사증후군의좋은예측인자이며심혈관계질환의예측및심혈관계위험인자의하나로서이용될수있을것으로판단된다. 그러나향후기준값에대한더많은데이터를바탕으로한연구가필요하리라사료된다. 초음파를통한내장지방의측정에대해서는많은연구자들이여러가지방법들을제시하고있다. Stolk 등 24) 은누운자세에서측정한복막에서척주의전면까지의거리를내장지방의지표로제시하였고, Hirooka 등 27) 은배꼽위치에서복부기립근의안쪽면에서부터대동맥의후벽사이의거리를지표로제시하였으며그외에우측신장주위지방층의두께등여러다른지표를측정하고, 이를계산식을이용하여내장지방의양을추정해내는방법을사용하기도하였다. 그이외에도내장지방의지표로서여러방법들이보고되었으나이러한측정방법들간의차이와표준화의부족으로인하여연구자와논문들간에통일성을이루지못하고있어향후표준화가필요한실정이며많은피험자를대상을하여내장비만의지표로삼을수있는기준의제시가필요하다고하겠다. 그리고본연구는단면적인연구로향후에초음파측정내장지방두께및복막전둘레가대사증후군이나심혈관계질환의유병률및사망률에어떠한영향을미치는지에대한전향적인연구도필요하겠다. 결론적으로제2형당뇨병환자에서초음파측정내장지방두께및복막전둘레는내장비만의유의한지표가될수있으며심혈관계질환및대사증후군의위험인자중의하나로제시할수있겠다. 그러나향후에초음파측정내장지방지표에대한표준화및기준의제시가필요하며

12 - 정귀홍외 5 인 : 제 2 형당뇨병환자에서초음파측정내장비만과심혈관계위험 - 심혈관계질환의유병률및사망률에미치는영향에대한전향적인연구가필요할것으로사료된다. 요약 목적 : 비만특히내장비만은일반인과제2형당뇨병에서모두심혈관계질환의독립적인위험인자로알려져있다. 비만을측정하는방법은다양하며그중에서특히내장지방의양을측정할수있는방법으로는허리둘레, 컴퓨터단층촬영, 이중에너지방사선흡수법및초음파측정법등이있다. 본연구에서는제2형당뇨병환자에서초음파측정내장지방지표와다른비만지표와의상관관계및대사증후군을비롯한심혈관계질환의위험인자와의관계를알아보고자하였다. 방법 : 전남대학교병원에제2형당뇨병으로내원한환자 191명 ( 남자 101명, 여자 90명 ) 을대상으로하여심혈관계질환등의과거력을문진하였고, 체질량지수, 허리둘레및혈압을계측하였다. 공복혈액검사를통하여지질대사이상과인슐린저항성정도를측정하였고, 당뇨병성미세혈관합병증과대혈관합병증여부를검사하였다. 생체전기임피던스법을이용한체지방측정기를이용하여체지방량, 체지방률및복부지방률을측정하였다. 초음파검사를통하여복부백선을따라배꼽 1 cm 상방에서내장지방및피하지방두께를측정하였다. 결과 : 초음파측정내장지방두께는체질량지수 (r=0.444, p<0.001), 허리둘레 (r=0.466, p<0.001), 체지방량 (r=0.477, p<0.001), 복부지방율 (r=0.274, p<0.001) 과유의한상관관계가있었으며, HDL-콜레스테롤 (r=-0.240, p<0.05) 과공복인슐린 (r=0.266, p<0.05), 공복혈당 / 공복인슐린비 (r=-0.323, p<0.05), HOMA-IR (r=0.286, p<0.05) 과유의한상관관계를보였다. 대상군중에서대사증후군을가진환자들이없는환자들보다초음파측정내장지방두께가더증가하였으며, 내장지방두께에따라대상환자들을삼분위로구분하였을때연령, 성별및체질량지수로보정한후에도하위삼분위군보다상위삼분위군에서고혈압 (OR=4.02, 95% CI; 1.08~14.98), 고지혈증 (OR=9.64, 95% CI; 1.08~85.37), 대사증후군 (11.35, 95% CI; 1.34~96.00) 의위험도가증가하였다. 결론 : 제2형당뇨병환자에서초음파를이용하여측정한내장지방은내장비만의유의한지표가될수있으며대사증후군을비롯한심혈관계질환의위험인자중하나로제시될수있을것으로사료된다. 중심단어 : 제2형당뇨병, 초음파, 내장지방, 심혈관계질환 REFERENCES 1) Bray GA. Overweight is risking fate: definition, classification, prevalence, and risks. Ann N Y Acad Sci 499:14-28, ) Larsson B, Svardsudd K, Welin L, Wilhelmsen L, Bjorntorp P, Tibblin G. Abdominal adipose tissue distribution, obesity, and risk of cardiovascular disease and death: 13-year follow-up of participants in the study of men born in Br Med J 288: , ) DeFronzo RA, Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: , ) Fujioka S, Matsuzawa Y, Tokunaga K, Tauri S. Contribution of intra-abdominal fat accumulation to the impairment of glucose and lipid metabolism in human obesity. Metabolism 36:54-59, ) Seidell JC, Cigolini M, Charzewska J, Ellsinger BM, Deslypere JP, Cruz A. Fat distribution in European men: a comparison of anthropometric measurements in relation to cardiovascular risk factors. Int J Obes Relat Metab Disord 16:17-22, ) Bertin E, Marcus C, Ruiz JC, Eschard JP, Leutenegger M. Measurement of visceral adipose tissue by DXA combined with anthropometry in obese humans. Int J Obes Relat Metab Disord 24: , ) Tornaghi G, Raiteri R, Pozzato C, Rispoli A, Bramani M, Cipolat M, Craveri A. Anthropometric or ultrasonic measurements in assessment of visceral fat?: a comparative study. Int J Obes Relat Metab Disord 18: , ) Ribeiro-Filho FF, Faria AN, Kohlmann O Jr, Ajzen S, Ribeiro AB, Zanella MT, Ferreira SR. Ultrasonography for the evaluation of visceral fat and cardiovascular risk. Hypertension 38: , ) Leite CC, Wajchenberg BL, Radominski R, Matsuda D, Cerri GG, Halpern A. Intra-abdominal thickness by ultrasonography to predict risk factors for cardiovascular disease and its correlation with anthropometric measurements. Metabolism 51: , ) 김수경, 김세화, 이유미, 최성희, 조유리, 안철우, 차봉수, 임승길, 김경래, 이현철, 허갑범. 컴퓨터단층촬영으로측정한복강내지방조직길이와내장지방면적, 내장지방 / 피하지방면적비및내장지방 / 골격근면적비와의비교. 대한내과학회지 64:49-59,

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