222 ISSN 1738-3544 Correlation of Hemoglobin and RBC count with Adiponectin Level Moon-Jung Shim Department of Clinical Laboratory Science, Ansan University, Ansan, Gyeonggi-do, 426-701, Korea Adiponectin is secreted specifically by adipose tissue and regulates lipid and glucose metabolism. In addition, adiponectin has been found to inhibit inflammatory process and possibly atherogenesis. This study was done to compare hematological parameters, serum lipids with serum adiponectin level according to body mass index (BMI) and gender in eighty eight Korean adults aged 40 to 68. In this study, the association between serum adiponectin and other variables including RBC counts, hemoglobin, hematocrit and albumin were investigated. RBC, hemoglobin status, was inversely associated with serum adiponectin levels in normal adult women. Adiponectin levels were significantly lower in men than women (p<0.01). In men, serum adiponectin levels were negatively correlated with body mass index (BMI) (p<0.05). However, no correlations were found in women. These results might imply that the regulation of key adipokines such as adiponectin might be a strategy for the prevention or treatment of obesityassociated diseases. Key words : Adiponectin, Hemoglobin, RBC, BMI, Obesity 서론 비만의원인이되는지방세포는중성지방을합성하여저 장하고있다가필요시다른조직이나기관에공급하는수동 적인에너지저장고의기능뿐아니라최근에내분비기관 으로서각종단백질호르몬들을분비하여지방대사와당대 사를포함한체내에너지대사를조절하는데중요한역할 을하는것으로알려져있다 (Funahashi 등, 1999). 지방세포 에서생성, 분비되어다양한신호전달에관여하는물질인 아디포사이토카인 (adipocytokine) 중에서아디포넥틴은지 방세포에서만유도되는특이적인호르몬이고혈중에풍부 Corresponding auther: Moon-Jung, Shim, Department of Clinical Laboratory Science, Ansan University, Ansan, Gyeonggi-do, 426-701, Korea Tel : +82-31-400-6938, 010-6202-7020 Fax : +82-31-400-6933 E-mail : mjshim@ansan.ac.kr Received : 19 November 2012 Return for modification : 5 December 2012 Accepted : 14 December 2012 하게존재한다. 최근연구에서아디포넥틴의 mrna는골수, 조골세포, 태아조직, 근육세포, 심근세포, 타액선상피에서도발현되는것으로조사되었다 (Pineiro 등, 2005). 최근지방조직은에너지저장장소의역할뿐아니라여러단백질들, 즉종양괴사인자 (tumor necrosis factor-a), plasminogen inhibitor-1, 렙틴, 레지스틴, 아디포넥틴등을분비하여에너지대사, 혈관긴장도, 인슐린저항성등에중요한역할을하는것으로알려지고있으며 (Hotamisligil 등, 1993), 비만환자와당뇨병환자에서아디포넥틴의혈중농도가감소되어있음이보고되었다 (Hotta 등, 2000) 비만시지방세포의과도한증가는유전자발현과신호전달시스템의변화를가져와아디포카인의분비이상을초래하고이로인하여제2형당뇨병이나인슐린저항성, 심혈관계질환등과같은질환의발병에중요한역할을하는것으로알려져있다 (Kumada 등 2003). 아디포카인은비만으로동반되는인슐린저항성및이와관련된대사이상들을악화시키거나지방산의산화와당대사등생체내에너지대사에도주요한역할을한다 (Kim 등, 2005). 아디포넥틴은성인의지방세포에서가장많이분비되는 222
사이토카인의하나로단백질호르몬이며, 남자에비해여자에서혈중아디포넥틴의농도가유의하게높은것으로알려져있다 (Corbetta 등, 2005). 또한아디포넥틴은비만한사람에게서농도가감소되어있으며, 아디포넥틴의농도감소는제2형당뇨병이나인슐린저항성, 심혈관계질환과연관성이있는것으로보고되고있다 (Matsuzawa 등, 2004). 그리고혈색소가증가함에따라인슐린저항성을동반한다는논문이보고된바있으나, 아직한국에서는혈색소와아디포넥틴과의관계에대한연구가없어, 본연구에서아디포넥틴과비만, 적혈구수, 혈색소등과같은혈액학적인자들과의상관관계를알아보고자하였다. 재료및방법 1. 연구대상 2009년 10월 1일부터 2010년 2월 28일까지, 서울소재 1 개종합병원의건강증진센터에 40세이상의성인중고혈압이나고지혈증또는당뇨병으로치료중인환자, 백혈구 11,000 10 3 /μl이넘거나, 혈청페리틴 200μg/l가넘는경우, 급성감염성질환자, 고감도 C-반응단백이 10 mg/l를초과하는경우, SGOT나 SGPT가 35 U/l를넘거나급성간질환자를제외한 40~65세남성 23명과 40~68세여성 65명을대상으로하였다. 2. 연구방법 1) 문진및신체계측설문지를통하여연령, 성별, 과거력및복용약물등을조사하였고, 신장및체중을킬로그램과센티미터단위로각각소수점한자리까지측정하였다. 체질량지수 (body mass index) 는체중 (kg)/ 키 (m) 2 으로계산하였다. 2) 혈액검사 8시간이상금식후혈액을채취하여공복혈당, 총콜레스테롤, 고밀도지단백 (HDL), 중성지방을측정하였으며저밀도지단백 (LDL) 은 Friedewald equation에의해총콜레스테롤-고밀도지단백 (HDL)-중성지방/5로계산되었으며, 공복혈당, 총콜레스테롤, 중성지방, 고밀도콜레스테롤과 hs-crp는 ADIVA 1650 chemistry (Siemens, Tarrytown, NY, USA) 로측정하였다. 저밀도콜레스테롤은 Friedewald s formula로계산하였고, 중성지방이 400 mg/dl가넘는경우는제외하였다. 공복인슐린농도는전기화학발색면역검사법 (Roche, Indianapolis, IN, USA) 으로검사하였다. 인슐린저항성지표로는 HOMA-IR(Homeostasis model for insulin resistance) 로 fasting glucose(mmol /l) fasting insulin(mu/ml)/22.519로계산하였다. CBC 검사는 ADIVA 120 cell count(siemens, Tarrytown, NY, USA) 로측정하였으며, 아디포넥틴 (Interassay CV : 4.63%. Intra-assay CV : 2.72%) 은 ELISA 방법을이용하여측정하였다 (AdipoGen, Seoul, Korea). 3. 통계분석모든자료의통계처리는 SPSS Window 10.0 package를이용하였으며, 기술통계값은평균과표준편차로표현하였다. 남녀자료는 t-test를이용하여비교하였고, BMI 2군, 아디포텍틴 3군간의비교는 ANOVA test를이용하였다. 아디포넥틴, 혈색소, BMI, 인슐린저항성지표및당, 지질농도의관계는 Pearson 상관관계분석을시행하였다. p-value가 0.05 미만인경우를통계적으로유의한차이가있는것으로간주하였다. 결과 1. 연구대상자의일반적인특성연구대상자의평균연령은남성이 54.0±7.6세, 여성이 55.0±6.4세이며, 체질량지수는남성이 25.2±2.8 kg/m 2, 여성이 24.0±2.6 kg/m 2 이었다. 혈액학적지표로는적혈구수가남녀 4.8±0.4 10 6 /μl, 4.4±0.3 10 6 /μl, 혈색소는 14.8±1.0 g/dl, 13.3±1.0 g/dl, 헤마토크릿은 42.7±2.9%, 38.7±2.8% 로나타났다. 생화학적지표로는콜레스테롤이 198.0±37.3 mg/dl, 199.1±31.0 mg/dl, 중성지방은 136.2±78.3 mg/dl, 122.0±110.5 mg/dl, 고밀도지단백콜레스테롤은 50.2±9.7 mg/dl, 56.1±10.8 mg/dl, 저밀도지단백콜레스테롤은 120.5±38.5 mg/dl, 118.0±30.7 mg/dl로나타 Correlation of Hemoglobin with Adiponectin Level 223
났으며, 아디포넥틴은 4.6±2.0μg/ml, 8.9±4.6μg/ml 이었다. 남녀간비교에서는적혈구수, 혈색소, 헤마토크릿, 이완기혈압, 백혈구수, 고밀도지단백콜레스테롤, 아디포넥틴에서유의한차이를보였다 (Table 1). 2. 아디포넥틴농도와비교인자들과의상관관계아디포넥틴과여러인자들간의상관관계를살펴보고자 88명의대상자를아디포넥틴농도에따라삼분위로나누었다. 각군의아디포넥틴농도는첫번째분위 3.5±1.0μg/ ml, 두번째분위 6.8±0.9μg/ml, 세번째분위 12.9±3.5μg/ ml 로조사되었다. 이에따라각인자들의수치를본결과 적혈구수, 혈색소, 헤마토크릿, 알부민, 중성지방에서통계적으로유의한결과를보였다 (Table 2). BMI와의관계에서는아디포넥틴농도가높은세번째분위에서농도가낮은첫번째분위와비교하여낮게나타났으나통계적으로유의하지는않았다. 하지만 BMI 23 kg/m 2 을기준으로정상체중군과과체중군, 비만군을두그룹으로나누어아디포넥틴농도와의상관관계를본결과 BMI 23 kg/m 2 이상군에서는 7.2 ± 4.2μg/ml로 23 kg/m 2 미만군인 9.5 ± 4.8μg/ml와비교해서유의하게낮게나타났다 (Table 3). 이외에도혈압, 혈당, 고밀도지단백콜레스테롤, 백혈구수치와상관관계를보였다. 이를통해아디포넥틴농도는 BMI가높아질수 Table 1. General characteristics in study population Variables Male (N=23) Female (N=65) p Age (years) 54.0 ± 7.6 55.0 ± 6.4 0.525 BMIa (kg/m 2 ) 25.2 ± 2.8 24.0 ± 2.6 0.085 RBC count ( 10 6 /μl) 4.8 ± 0.4 4.4 ± 0.3 0.000** Hb (g/dl) 14.8 ± 1.0 13.3 ± 1.0 0.000** Hct (%) 42.7 ± 2.9 38.7 ± 2.8 0.000** SBPb ( mmhg) 136.8 ± 20.0 131.3 ± 19.0 0.243 DBPc ( mmhg) 85.0 ± 13.5 77.6 ± 12.4 0.019* Cholesterol (mg/dl) 198.0 ± 37.3 199.1 ± 31.0 0.888 Triglyceride (mg/dl) 136.2 ± 78.3 122.0 ± 110.5 0.573 HDL-cholesterol (mg/dl) 50.2 ± 9.7 56.1 ± 10.8 0.023* LDL-cholesterol (mg/dl) 120.5 ± 38.5 118.0 ± 30.7 0.800 Albumin (g/dl) 4.3 ± 0.3 4.2 ± 0.2 0.075 Fasting glucose (mg/dl) 95.0 ± 9.7 92.1 ± 10.5 0.248 Fasting insulin (μiu/ml) 13.8 ± 29.7 7.8 ± 15.8 0.357 HOMA-IR d 3.3 ± 7.2 1.8 ± 3.6 0.339 WBC ( 10 3 /μl) 6.5 ± 1.5 5.7 ± 1.4 0.038* Hs-CRP (mg/dl) 0.2 ± 0.4 0.2 ± 0.6 0.112 PLT ( 10 3 /μl) 247.4 ± 57.3 239.8 ± 56.7 0.586 adiponectin (μg/ml) 4.6 ± 2.0 8.9 ± 4.6 0.000** a body mass index, b systolic blood pressure, c diastolic blood pressure, d homeostasis model assessment of insulin resistance. 224 Correlation of Hemoglobin with Adiponectin Level
Table 2. Tertile according to adiponectin levels Variables Q1 (N=29) Q2 (N=29) Q3 (N=30) P adiponectin (μg/ml) 3.5 ± 1.0 6.8 ± 0.9 12.9 ± 3.5 0.000 BMI (kg/m 2 ) 24.3 ± 2.7 25.0 ± 3.0 23.7 ± 2.3 0.228 RBC count ( 10 6 /μl) 4.6 ± 0.4 4.4 ± 0.4 4.3 ± 0.3 0.002** Hb (g/dl) 14.4 ± 1.0 13.6 ± 1.0 13.1 ± 1.1 0.000** Hct (%) 41.6 ± 2.7 39.5 ± 3.4 38.3 ± 3.2 0.000** SBP ( mmhg) 132.3 ± 16.6 130.2 ± 19.8 135.7 ± 21.6 0.542 DBP ( mmhg) 77.5 ± 14.0 80.3 ± 11.3 80.8 ± 13.7 0.574 Fasting glucose (mg/dl) 94.2 ± 9.5 90.8 ± 11.1 93.5 ± 10.4 0.426 Insulin (μiu/ml) 10.9 ± 23.2 9.9 ± 22.6 5.5 ± 3.4 0.711 HOMA-IR 2.5 ± 5.3 2.3 ± 5.5 1.3 ± 0.8 0.717 Albumin (g/dl) 4.3 ± 0.3 4.2 ± 0.2 4.1 ± 0.2 0.046* Total cholesterol (mg/dl) 203.5 ± 34.3 197.5 ± 34.4 195.5 ± 29.4 0.625 Triglyceride (mg/dl) 163.6 ± 160.8 112.2 ± 54.3 101.6 ± 36.7 0.047* HDL-cholesterol (mg/dl) 53.1 ± 11.9 54.7 ± 10.2 55.9 ± 10.4 0.604 LDL-cholesterol (mg/dl) 117.7 ± 38.1 120.4 ± 31.5 117.9 ± 29.0 0.943 PLT ( 10 3 /μl) 237.6 ± 62.9 256.9 ± 47.9 231.4 ± 56.7 0.200 WBC ( 10 3 /μl) 6.2 ± 1.4 6.0 ± 1.4 5.6 ± 1.4 0.205 Hs-CRP (mg/dl) 0.1 ± 0.2 0.4 ± 0.9 0.1 ± 0.1 0.185 록감소함을알수있었다. 그리고, 아디포넥틴과관련된인자들을살펴보기위해상관분석을실시한결과아디포넥틴과통계적유의성을보이는인자는적혈구수 (p<0.01), 혈색소 (p<0.01), 헤마토크릿 (p<0.01), 알부민 (p<0.05) 으로나타났으며, 아디포넥틴과는모두음의상관관계를보였다. 성별에따라서도아디포넥틴농도는남성에서유의하게여성군에비해감소되어나타났다 (Table 4). 앞의결과에서아디포넥틴과관련된인자들의상관분석결과적혈구관련인자들과의관련성이나타나적혈구는특성상남녀간의차이를보이는인자이므로성별에따라아디포넥틴과의상관관계를살펴보았다. 그결과남성의경우 BMI와의상관관계를보였으며, 여성의경우앞의결과와일 치하는결과를보였다 (Table 5). 고찰 비만은인슐린저항성과관련이있으며, 제2형당뇨병및심혈관질환의중요한병인중의하나이다. 지방조직에서분비되는물질중지방산과 TNF-a는인슐린신호전달을방해하여인슐린저항성을유발하고, plasminogen inhibitor-1과 interleukin-6 등또한인슐린저항성을증가시켜당뇨병및심혈관질환을유발하는것으로알려져있다 (Hotamisligil 등, 1993). 아디포넥틴은지방세포에서유래되는단백질임에도불 Correlation of Hemoglobin with Adiponectin Level 225
Table 3. Comparison of measured variables according to BMI 구하고비만에서혈중아디포넥틴이감소하는이유는되먹 이기전으로설명되고있으며, 실제로비만모델쥐인 ob/ob mice 나비만한사람에서아디포넥틴 mrna 의발현감소가 관찰되었다 (Hu 등, 1996). Motoshima 등 (2002) 의연구에 서비만도가높은사람일수록내장지방세포에서아디포넥 틴분비가감소됨을증명하였다. 본연구결과비만군에서 아디포넥틴의농도가유의적으로낮은것으로나타나유사 한결과를보였다. 아디포넥틴과비만이갖는음의상관관 계는피하지방보다는내장지방과더명확한데, 아직기전에 대해밝혀지지는않았지만한가지가능한설명은아디포넥 틴유전자의프로모터를강력히억제할수있는 TNF-a 의 발현이내장지방이축적할수록증가한다는것이다 (Maeda 등, 2001). Variables <23(N=24) =23 (N=64) P adiponectin (μg/ml) 9.5 ± 4.8 7.2 ± 4.2 0.032* RBC count ( 10 6 /μl) 4.4 ± 0.3 4.5 ± 0.4 0.148 Hb (g/dl) 13.4 ± 1.3 13.8 ± 1.1 0.189 Hct (%) 39.5 ± 3.6 39.9 ± 3.3 0.639 SBP ( mm Hg) 123.6 ± 19.1 136.2 ± 18.4 0.006** DBP ( mm Hg) 73.5 ± 12.7 81.8 ± 12.5 0.007** Fasting glucose (mg/dl) 87.7 ± 9.2 94.8 ± 10.1 0.003** Insulin (µiu/ml) 4.2 ± 1.7 11.5 ± 23.4 0.196 HOMA-IR 0.9 ± 0.4 2.7 ± 5.5 0.184 Albumin (g/dl) 4.1 ± 0.2 4.2 ± 0.2 0.104 Total cholesterol (mg/dl) 196.1 ± 33.1 199.8 ± 32.5 0.641 Triglyceride (mg/dl) 134.2 ± 162.5 122.6 ± 69.3 0.642 HDL-cholesterol (mg/dl) 60.3 ± 12.6 52.4 ± 9.3 0.002** LDL-cholesterol (mg/dl) 109.0 ± 35.6 122.3 ± 31.1 0.090 PLT ( 10 3 /μl) 244.0 ± 57.4 241.0 ± 57.4 0.823 WBC ( 10 3 /μl) 5.4 ± 1.2 6.1 ± 1.5 0.026* Hs-CRP (mg/dl) 0.0 ± 0.0 0.2 ± 0.6 0.168 Table 4. Correlations between adiponectin and measured variables Variables adiponectin Age (years) 0.107 0.323 gender 0.423 0.000** Adiposity index BMI (kg/m 2 ) -0.098 0.363 Blood pressure ( mm Hg) Systolic 0.051 0.639 Diastolic 0.057 0.597 RBC parameter RBC count ( 10 6 /μl) -0.434 0.000** Hb (g/dl) -0.490 0.000** Hct (%) -0.460 0.000** WBC count ( 10 3 /μl) -0.142 0.191 PLT count ( 10 3 /μl) -0.071 0.508 Lipid profile Total cholesterol (mg/dl) -0.164 0.127 Triglyceride (mg/dl) -0.201 0.062 HDL-cholesterol (mg/dl) 0.061 0.576 Albumin (g/dl) Hs-CRP (mg/dl) 또한, 본연구에서남녀에따른혈중아디포넥틴농도를 비교하였을때남성에게유의하게감소되어있었다. 아디포 넥틴농도에대한성호르몬의영향을보면, 본연구결과와 같이남성에서여성에비해아디포넥틴농도가감소되어있 고, 여성의경우폐경전후아디포넥틴농도의차이가없음 을보고한연구가있다. 따라서성별에따른아디포넥틴농 도의차이는안드로젠이아디포넥틴의감소를유발하기때 문인것으로생각된다 (Nishizawa 등, 2002). 최근미국과중국성인을대상으로한연구에서저장 철농도와대사증후군과의밀접한관련성이제시되었으며 (Jehn 등, 2004; Sun 등, 2008), 일본의연구에의하면, 혈색 R -0.262-0.003 P 0.015* 0.978 Coefficients (r) and P-values were calculated by the Pearson correlation model. 226 Correlation of Hemoglobin with Adiponectin Level
Table 5. Correlations between adiponectin and measured variables according to gender Variables Male (N=23) Female (N=65) R P R P Age (years) -0.209 0.338 0.144 0.251 Adiposity index BMI (kg/m 2 ) 0.426 0.043* -0.095 0.454 Blood pressure ( mm Hg) Systolic 0.203 0.352 0.109 0.390 Diastolic 0.166 0.450 0.200 0.110 RBC parameter RBC count ( 10 6 /μl) -0.234 0.283-0.327 0.008** Hb (g/dl) -0.335 0.118-0.352 0.004** 에서는베타세포의손상으로인슐린합성과분비가저해되고간에서는인슐린추출저하및당신생합성억제저하가발생하여포도당의분포조절을방해하여인슐린저항을증가시킨다는보고가있다 (Andrews 등, 1999). 본연구에서는정상성인에서아디포넥틴과관련된인자들간의상관성을본결과남성에서유의하게감소되었으며, 적혈수수, 혈색소, 헤마토크릿과의음의상관관계를보였고 (p<0.01), 남성의경우 BMI와통계적으로유의한음의상관관계를보였다 (p<0.05). 본연구를통해체지방질량지수가높고, 적혈구관련인자가높은군에서아디포넥틴농도가감소함을확인하였으며, 앞으로연관성이높은대사증후군과심혈관계질환등과연계해보다광범위한연구가필요하리라사료된다. Hct (%) -0.294 0.173-0.323 0.009** WBC count ( 10 3 /μl) 0.060 0.790-0.007 0.581 PLT count ( 10 3 /μl) -0.406 0.055-0.001 0.991 Lipid profile Total cholesterol (mg/dl) -0.257 0.236-0.192 0.126 Triglyceride (mg/dl) -0.019 0.933-0.214 0.089 HDL-cholesterol (mg/dl) 0.243 0.263-0.087 0.493 LDL-cholesterol (mg/dl) -0.303 0.160-0.038 0.765 Albumin (g/dl) -0.008 0.971-0.259 0.039* Hs-CRP (mg/dl) 0.249 0.334-0.021 0.885 소량이혈청아디포넥틴농도와관련이있다고보고되었다 (Kawamoto 등, 2010). 이는본연구결과에서나타난혈색 소, 적혈구수, 헤마토크릿과아디포넥틴농도와의음의상 관관계와일치하는결과를보였다. 혈색소는철대사와관 련되어있고, 메트혈색소는 LDL에헴을전달함으로써산화 적활동을하고있다 (Grinshtein 등, 2003). 당뇨전단계에 서는증가된혈색소를가진사람인경우혈압이높고, 염증 과관련된사이토카인인 CD40L 수치가증가된것을알수 있었다 (Kutlu 등, 2009). 더불어과도한철이간, 근육, 췌장 에축적되면서기관에특이적인산화손상을유발하여췌장 참고문헌 1. Andrews NC. Disorders of iron metabolism. N Engl J Med. 1999, 341(26):1986-1995. 2. Corbetta S, Bulfamante G, Cortelazzi D, Barresi V, Cetin I, Mantovani G, Bondioni S, Beck-Peccoz P, Spada A. Adiponectin expression in human fetal tissues during mid- and late gestation. J Clin Endocrinol Metab. 2005, 90(4):2397-2402. 3. Funahashi T, Nakamura T, Shimomura I, Maeda N, Kuriyama H, Takahashi M, Arita Y, kihara S, Matsuzawa Y. Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Inter Med. 1999, 38(2):202-206. 4. Grinshtein N, Bamm VV, Tsemakhovich VA, Shaklai N. Mechanism of low-density lipoprotein oxidation by hemoglobinderived iron. Biochemistry. 2003, 42:6977-6985. 5. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-a: direct role in obesity-linked insulin resistance. Science. 1993, 259:87-91. 6. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol. 2000, 20:1595-1599. 7. Hu E, Liang P, Spiegelman BM. AdipoQ is a novel adiposespecific gene dysregulated in obesity. J Biol Chem. 1996, 271:10697-10702. Correlation of Hemoglobin with Adiponectin Level 227
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