untitled

Size: px

Start display at page:

Download "untitled"

준 탁
6 years ago
Views:

1 대한소아소화기영양학회지 : 제 14 권제 4 호 영양 한국청소년의 HOMA-IR 과대사위험요소와의연관성 인제대학교의과대학상계백병원소아청소년과학교실 서유진ㆍ이선근ㆍ김신혜ㆍ박미정 HOMA-IR and Its Association with Metabolic Risk Factors among Korean Adolescents Eugene Seo, M.D., Sun Geun Lee, M.D., Shin Hye Kim, M.D. and Mi Jung Park, M.D., Ph.D. Department of Pediatrics, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea Purpose: This study was performed to evaluate the distribution of homeostasis model assessment of insulin resistance (HOMA-IR), a surrogate marker of insulin resistance, and its association with metabolic risk factors among Korean adolescents. Methods: This study was based on data from Korean National Health and Nutrition Examination Survey (KNHANES) Data from 2,035 adolescents (1,053 boys, 982 girls; aged years) were analyzed. We classified all subjects into four groups, based on the quartiles of HOMA-IR, and the highest quartile group was defined as the group with insulin resistance. We performed multivariate logistic regression analysis to determine the independent risk factors for insulin resistance. Results: The highest quartile values of HOMA-IR representing insulin resistance were 3.4 for boys and 3.6 for girls. Mean body mass index, waist circumference, systolic blood pressure, serum triglyceride, alanine aminotransferase (ALT), fasting glucose and insulin increased, whereas HDL cholesterol decreased with increased HOMA-IR. We found HOMA-IR has significant positive correlation with waist circumference, triglyceride, ALT level and systolic/diastolic blood pressure, while it has negative correlation with HDL-cholesterol level (p<0.005). Independent predictors (odds ratio) for insulin resistance were elevated ALT (3.53 for boys; 4.04 for girls), central obesity (3.01 for boys; 3.20 for girls), and hypertriglyceridemia (3.03 for boys; 1.94 for girls). Conclusion: Metabolic risk factors were strongly associated with insulin resistance, defined as highest quartile values of HOMA-IR ( 3.4 for boys and 3.6 for girls). These values could be useful as a marker of insulin resistance and metabolic risk in Korean adolescents. (Korean J Pediatr Gastroenterol Nutr 2011; 14: ) Key Words: Adolescent, Insulin resistance, Metabolic profile, Metabolic syndrome 접수 :2011 년 9 월 21 일, 수정 :2011 년 11 월 1 일, 승인 :2011 년 11 월 2 일책임저자 : 박미정, , 서울시노원구상계 7 동 761-1, 인제대학교의과대학상계백병원소아청소년과학교실 Tel: , Fax: , PMJ@paik.ac.kr 376

2 서유진외 :HOMA-IR and Metabolic Risk Factors among Korean Adolescents ㆍ 377 서 론 대상및방법 전세계적으로소아청소년의비만은증가하고있는추세이며국내에서도식습관의서구화, 사회경제적발달과함께소아비만유병률은급속히증가하여 1980 년대초 2% 였던우리나라의소아비만유병률이 2005 년에는 9.7% 에이르렀다 1 3). 비만으로인해발생되는인슐린저항성은인슐린이정상적으로분비됨에도불구하고생리학적인작용이현저히감소된상태로서내당능장애, 이상지질혈증, 고혈압및심혈관질환을초래할수있다 4). 특히인슐린저항성을기전으로복부비만, 고혈당, 고혈압, 이상지질혈증등의심혈관질환위험요인이군집을이루어발생되는경우를대사증후군이라하며 5), 국내소아에서도이에대한연구가활발히진행되고있다 1,6,7). 비만청소년에서인슐린저항성여부를검사하는것은당뇨병및심혈관계질환발생의예방과조기진단및치료를위해매우중요하다 8). 현재까지인슐린저항성또는인슐린민감도를측정할수있는가장정확하고표준적인검사법에는정상혈당클램프검사 (hyperinsulinemic euglycemic glucose clamp test), 경구당부하검사 (oral glucose tolerance test, OGTT) 등이있으나잦은채혈및침습적인검사법으로인해소아에서의인슐린저항성및분비능력평가에는제한적이다 9). 한편, homeostasis model assessment of insulin resistance (HOMA-IR) 은인구집단을대상으로한인슐린저항성의선별검사로사용되는검사로서 10), 공복인슐린 (fasting insulin level), 공복혈당 / 인슐린비 (fasting glucose/ insulin ratio, FGIR), 인슐린지수 (quantitative insulin sensitivity check index, QUICKI) 등의다른지표자들보다정확하게인슐린저항성을측정하는유용한검사임이밝혀졌다 11). 그러나현재까지한국소아청소년에서인슐린저항성의진단에도움이되는 HOMA-IR의절단치 (cutoff value) 에대한연구는없었다. 이에본연구에서는한국청소년에서인슐린저항성의지표로서활용할수있는 HOMA-IR 절단치를제시하고, 인슐린저항성과대사위험인자들과의연관성을분석하고자하였다. 1. 대상본연구는보건복지부산하질병관리본부에서시행한 년국민건강영양조사의원시자료를이용하여분석하였다. 조사에참여한 10 18세연령의소아청소년 2,665명중혈액검사를시행하지않은 366 명, B형간염표면항원양성인 12명, 공복혈당이 126 mg/dl 이상으로당뇨병이의심되는 3명, 간질병력이있는 5명, 공복시간이 10시간미만인 244명을제외한총 2,035명 ( 남 1,053명, 여 982명 ) 을대상자로선정하여최종분석을시행하였다. 이들중의사로부터당뇨병을진단받은대상자는없었다. 2. 신체검진과생화학지수측정검진조사는사전에교육을받은검진조사팀에의해수행되었으며, 검진조사원이신체계측을, 보건소간호사가혈압측정을, 보건소임상병리사가혈액채취를수행하였다. 신장과체중은 Seca 225 (Seca Deutchland, Hamburg, Germany) 신장측정기와 GL (CASKOREA, Seoul, Korea) 체중측정기로측정하였다. 혈압측정시측정방법과커프크기선정은미국심장협회 (American Heart Association) 에서제시한기준을따랐으며혈압계는 Baumanometer의수은혈압계 (Baumanometer R, WA Baum Co., Inc., Copiague, New York, NY, USA) 를사용하여 5분이상휴식후 2회에걸쳐측정하였다. 고혈압기왕력이없으면서, 최종혈압이수축기혈압 140 mmhg, 이완기혈압 90 mmhg 이상인대상자는다른날혈압을재측정하였다. 허리둘레는줄자가수평면을이루게하여, 가볍게숨을내쉰상태에서마지막늑골의하단부와장골능선상단부의중간부위를맨살위에서측정하였다. 비만하여가장좁은부분을가려내기힘든경우에는늑골과장골능선사이에서가장작은둘레를측정하였다. 체질량지수 (body mass index, BMI) 는체중 (kg)/[ 신장 (m)] 2 으로구하였다. HOMA-IR은공복인슐린농도 (mu/l) 공복혈당농도 (mmol/l)/22.5로계산하였다 10). 채혈은아침공복상태에서이루어졌으며혈액은검체처리후냉장보관하였으며, 검체는당일중앙검사기관으로우송하여 24시간이내에검사를진행하였다. 공복

3 378 ㆍ대한소아소화기영양학회지 : 제 14 권제 4 호 2011 혈당, 총콜레스테롤, 중성지방, HDL-콜레스테롤농도는 Hitachi Automatic Analyzer 7600 (Hitachi, Tokyo, Japan) 을사용하여각각 Pureauto S GLU, Pureauto SCHO-N, Pureauto S TG-N, CHOLESTEST N HDL을이용한 enzymaticcolorimeter method 방법으로, 혈청 aspartate aminotransferase (AST) 및 alanine aminotransferase (ALT) 농도는 Puereauto S ALT, Puerauto S ALT를이용한 UN method로분석하였다. 공복인슐린농도는 1,470 Wizard gamma-counter (PerkinElmer, Turku, Finland) 를사용하여 immunoradiometric assay (Biosource, Nivelles, Belgium) 방법으로측정하였다. 각조사항목별방법은국민건강영양조사제4기진행보고서를참고하여기술하였다 12). 3. 진단기준대상청소년을 HOMA-IR 사분위수에따라네군으로나누어 HOMA-IR의가장높은사분위수에해당하는수치를인슐린저항성의지표로정하였다. 인슐린저항성의독립적인위험인자를분석하기위해, 복부비만, 고중성지방혈증, 고혈압, 저 HDL-콜레스테롤혈증, 높은 ALT를대사위험요인으로선정하였다. 소아청소년비만의정의는 2007년소아청소년표준성장도표를참조값으로이용하여성별연령별체질 량지수 95백분위수이상을비만으로, 성별연령별체질량지수 85백분위수이상에서 95백분위수미만을과체중으로정의하였다 13). 복부비만은성별과연령에따른참고치의 90백분위수이상일경우로정하였다 14) 년국제당뇨병연맹 (International Diabetes Federation) 14) 과미국콜레스테롤교육프로그램 (National Cholesterol Education Program Adult Treatment Panel III) 15) 에서제시한소아청소년의대사증후군진단기준에따라공복혈당의증가는 100 mg/dl 14), 고혈압은수축기혈압또는이완기혈압이각성별에서의 90백분위수 14), 고중성지방혈증은 110 mg/dl 15), 저HDL-콜레스테롤혈증은 <40 mg/dl 15) 로정하였다. 높은 ALT의기준은최근발표된한국성인의혈청 ALT 정상상한치에대한연구결과에근거하여남아에서 32 IU/L 이상, 여아에서 24 IU/L 이상으로하였다 16). 4. 통계처리통계처리는 SPSS 프로그램 version 17.0 (SPSS Inc., Chicago, IL, USA) 을이용하였고 p값이 0.05 미만일때통계적으로유의하다고판정하였다. 변수의값들은평균 ± 표준오차 (mean±se) 또는백분율 (%) 로나타내었고 HOMA-IR의사분위수에따른네군에서의대사위험 Table 1. General Characteristics of the Subjects Boys (N=1,053) Girls (N=982) p-value Age (years) Weight (kg) Body mass index (kg/m 2 ) Normal/overweight/obese (%) Waist circumference (cm) Systolic blood pressure (mmhg) Diastolic blood pressure (mmhg) Total cholesterol (mg/d) Triglyceride (mg/dl) HDL* cholesterol (mg/dl) Fasting blood sugar (mg/dl) Fasting insulin (μiu/ml) Serum AST (IU/L) Serum ALT (IU/L) HOMA-IR 13.9± ± ± /11/ ± ± ± ± ± ± ± ± ± ± ± ± ± ± /11.7/ ± ± ± ± ± ± ± ± ± ± ± Data are expressed as Mean±SE for continuous variables and percentage (%) for categorical variables. Obesity level was determined according to the gender and age-specific BMI percentile; normal (BMI<85 percentile), overweight (BMI 85 percentile and <95 percentile) and obese (BMI 95 percentile). *HDL: high density lipoprotein, AST: serum aspartate aminotransferase, ALT: serum alanine aminotransferase, HOMA-IR: homeostasis model assessment of insulin resistance.

4 서유진외 :HOMA-IR and Metabolic Risk Factors among Korean Adolescents ㆍ 379 요소의차이는분산분석 (ANOVA) 과 χ 2 검정을사용하여분석하였다. HOMA-IR과대사위험요소의연관성은연령을보정한후편상관관계분석 (Partial correlation analysis) 으로유의성을판정하였다. 각대사위험요인이인슐린저항성에미치는독립적인위험도를분석하기위해연령을보정한후다변량로지스틱회귀분석을사용하였다. 본연구의결과는가중치를적용한가중표본평균또는분율이며표본추출률과응답률을반영하였다. 결과 1. 일반적특징비만및과체중청소년의비율은남녀간에차이가없었다. 수축기 / 이완기혈압, 공복혈당, 혈청 AST/ALT 농도는남아에서여아보다유의하게높았고, 총콜레스테롤및 HDL-콜레스테롤은여아에서남아보다유의하게높았다 (p). 공복인슐린과중성지방의평균값은성별에따른차이를보이지않았으며, HOMA-IR 의평균값도남아 2.9±0.5, 여아 3.0±0.5로남녀간에유의한차이를보이지않았다 (Table 1). 2. HOMA-IR 사분위수에따른대사위험요소의차이대상자를 HOMA-IR 사분위수에따라네군으로나누어각군의대사위험요소를제시하였다 (Table 2). 가장높은사분위수에해당하는 HOMA-IR의절단치는남아는 3.4, 여아는 3.6이었다. HOMA-IR의사분위수가증가함에따라비만및과체중대상자의비율이유의하게증가하였으며평균체질량지수, 허리둘레도함께증가하였다. 또한가장높은 HOMA-IR 사분위수에해당하는군이다른군들에비해수축기혈압, 중성지방, 공복혈당및인슐린농도, ALT 농도가통계적으로유의하게높았고, HDL-콜레스테롤농도는유의하게낮았다 (p<0.001, Table 2). 3. HOMA-IR과대사위험요소와의연관성 HOMA-IR과대사위험요소와의편상관관계분석결과를제시하였다 (Table 3). 복부둘레, 공복혈당, 중성지방및 ALT 농도, 수축기 / 이완기혈압은 HOMA-IR과 Table 2. Metabolic Risk Factors Stratified by HOMA-IR Quartiles Boys Girls Quartile Quartile Quartile Quartile1 <2.0, HOMA-IR* p-value Quartile Quartile Quartile Quartile 1 <2.1 p-value ± ± ± ± ± ± ± ± ± ± ± ± ±0.7 60/21.3/ ± ± ± ± ± ± ± ± ± ± ± ± ± /12.2/ ± ± ± ± ± ± ± ± ± ± ± ± ±0.3 80/9.1/ ± ± ± ± ± ± ± ± ± ± ± ± ± /4.4/ ± ± ± ± ± ± ± ± ± ± ± ± ± /26.6/ ± ± ± ± ± ± ± ± ± ± ± ± ± /14.1/ ± ± ± ± ± ± ± ± ± ± ± ± ± /6.4/ ± ± ± ± ± ± ± ± ± ± ± ± ± /3.2/0.8 N HOMA-IR* Age (years) Body mass index (kg/m 2 ) Waist circumference (cm) Systolic BP (mmhg) Diastolic BP (mmhg) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL cholesterol (mg/dl) Fasting blood sugar (mg/dl) Fasting insulin (μiu/ml) AST (IU/L) ALT (IU/L) Nomal/overweight/obese (%) Data are shown as means±se. The subjects were stratified into four groups according to HOMA-IR quartiles. Obesity level was determined according to gender and age-specific BMI percentile; normal (BMI<85 percentile), overweight (BMI 85 percentile and <95 percentile) and obese (BMI 95 percentile). *HOMA-IR: homeostasis model assessment of insulin resistance, BP: blood pressure, HDL: high density lipoprotein, AST: aspartate aminotransferase, ALT: alanine aminotransferase.

5 380 ㆍ대한소아소화기영양학회지 : 제 14 권제 4 호 2011 유의한양의상관관계를보였으며 (p<0.005), HDL-콜레스테롤은 HOMA-IR과유의한음의상관관계를보였다 (p<0.005, Table 3). 4. 대사위험요인이인슐린저항성에미치는위험도각대사위험요인의인슐린저항성에대한위험도를분석한결과, 높은 ALT가인슐린저항성의위험도를가장높게상승시키는인자였으며 ( 남아 3.53배 [95% 신뢰구간 : ], 여아 4.04배 [ ]), 복부비만 ( 남아 3.01배 [ ], 여아 3.20배 [ ]), 고중성지질혈증 [ 남아 3.03배 ( ), 여아 1.94배 ( )] 의순으로인슐린저항성의위험도를높이는것으로나타났다 (Table 4). 고찰 HOMA-IR은공복인슐린과공복혈당을이용하여인슐린저항성을간편하게계산할수있는실용적인표지자로인구집단을대상으로한대규모연구에서사용되고있다 10,16). 청소년집단에서 HOMA-IR의평균및분포를조사한대규모연구는미국국민건강영양조사자료를분석한 Lee 등 17) 의연구가유일하다. 본연구의결과, 우리나라청소년의평균 HOMA-IR은남아는 2.9, 여아는 3.0으로, 미국청소년의평균 HOMA-IR값 ( 남 2.84, 여 2.91) 과비슷한수준이었다 17). 본연구에서는평균 HOMA-IR값이남녀간차이가없었다. 미국청소년에서는평균 HOMA-IR이여아에서남아보다유의하게높았으나연령별분석에서는 12 Table 3. Age-adjusted Correlations between Homeostasis Model Assessment of Insulin Resistance and Metabolic Risk Factors Boys Girls Beta p-value Beta p-value Waist circumference (cm) Triglyceride (mg/dl) Serum ALT* (IU/L) Systolic blood pressure (mmhg) Diastolic blood pressure (mmhg) HDL cholesterol (mg/dl) Correlation coefficients were calculated using partial correlation analysis. *ALT: alanine aminotransferase, HDL: high density lipoprotein. Table 4. Age-adjusted Odds Ratios (95% Confidence Intervals) for Insulin Resistance by Multivariate Logistic Regression Elevated serum ALT Central obesity Hypertriglyceridemia Low HDL cholesterol Hypertension Boys OR* (95% CI ) p-value OR (95% CI) p value Girls Subjects with a homeostasis model assessment of insulin resistance (HOMA-IR) level greater than the highest quartile ( 3.4 for boys and 3.6 for girls) were defined as insulin resistant. Elevated fasting glucose: Fasting glucose 100 mg/dl, Elevated ALT: ALT 32 IU/L for boys, ALT 24 IU/L for girls. Central obesity: Waist circumference 90 percentile of sex and age specific reference, Hypertriglyceridemia: TG 110 mg/dl. Low HDL: HDL<40 mg/dl, Hypertension: systolic BP or diastolic BP 90 percentile of sex, age and height specific reference. *OR: odds ratio, CI: confidence interval, ALT: alanine aminotransferase, HDL: high density lipoprotein.

6 서유진외 :HOMA-IR and Metabolic Risk Factors among Korean Adolescents ㆍ 세에서는여아가남아보다높고, 14 15세에서는남아가여아보다높은것으로나타나성별에따른 HOMA-IR값의차이는연령또는사춘기단계에영향을받는것으로해석된다 17). 사춘기에는성장호르몬, 성호르몬, insulin-like growth factor 1 분비가증가하고체지방량이증가하므로인슐린민감도는낮아지고인슐린분비는증가하여일시적인인슐린저항성이나타날수있다 18). 여러횡종단적연구들에서사춘기가시작하는 Tanner 2단계에서인슐린저항성이증가하여사춘기의마지막단계인 Tanner 5단계에서사춘기이전수준으로낮아짐이밝혀졌다 19 21). 사춘기단계에따라남녀별인슐린저항성을측정한한연구에서사춘기 Tanner 4 단계에서만여아가남아보다인슐린저항성이높아진다고하였다 19). Hirschler 등 21) 은인슐린저항성이체지방률과사춘기단계에영향을받고성별에는유의한영향을받지않으며, 사춘기연령인여아의평균 HOMA-IR이남아보다높은것은여아에서사춘기가남아보다빠르기때문인것으로해석하였다. 청소년기에발생하는생리적인슐린저항성은췌장의베타세포에지속적인자극을가함으로써당뇨병및대사증후군의발현을촉진시키는역할을할수있다 18). 소아청소년기에대사증후군이있거나복부비만이있었던경우에성인기에대사증후군, 당뇨병또는심혈관질환의위험이높기때문에 18) 청소년에서인슐린저항성의병적인상태를찾아내고교정하기위한기준치를찾기위한연구가시도되고있다. 당뇨병이없는인구집단에서인슐린저항성으로정의되는 HOMA-IR의절단치는 75백분위수, 90백분위수, 95백분위수, 상위 2.5백분위수등연구자마다다양한기준이제시되고있다 17,22). 미국소아청소년을대상으로한대규모종단적연구에따르면, 연구첫해에공복인슐린농도가가장높은사분위수에해당하는고인슐린혈증을보인대상자의 40% 는 8년후에도지속적인고인슐린혈증을보인다고하였으며 23) European Group for the Study of Insulin Resistance (EGIR) 에서는당뇨병이없는인구집단에서인슐린저항성의지표또는공복인슐린농도가상위 25백분위수에속할때인슐린저항성이있는것으로정의할것을제안하였다 24). 이를근거로본연구에서는 HOMA-IR값이가장높은사분위수에해당하는군을인슐린저항성이있는군으로정의하였다. 본연구결과, 우리나라청소년의가장높은사분위수에해당하는 HOMA-IR값은남아 3.4, 여아 3.6 이상으로, 이는미국청소년집단을대상으로분석한 HOMA-IR의가장높은사분위수인 ) 보다다소높은수치였다. 또한우리나라성인인구집단에서분석된 HOMA-IR의가장높은사분위수에해당하는수치인남 2.11, 여 ), 또는 ) 이상과미국성인인구집단에서의 HOMA-IR 절단치인 ) 또는 ) 이상보다본연구대상인한국청소년의 HOMA-IR 절단치가더높았다. 인슐린저항성으로인해포도당합성억제가불완전해지면간의포도당합성이식후에도지속되어고혈당의원인이된다 29). 한편고인슐린혈증은간에서초저밀도지단백 (very-low-density lipoprotein, VLDL) 의합성을증가시킴으로써중성지방을증가시키며, 말초지방조직내 lipoprotein lipase의인슐린에대한저항성도중성지방의증가에기여한다 30). 또한인슐린저항성이생기면 HDL-콜레스테롤의합성이증가함에도불구하고 apolipoprotein A1/HDL 콜레스테롤의분해속도가더월등히증가하여저HDL-콜레스테롤혈증을유발하게된다 31). 본연구의결과, 가장높은 HOMA-IR 사분위수에해당하는군이다른군들에비해허리둘레, 혈압, 중성지방, 공복혈당이유의하게높고, HDL-콜레스테롤농도는유의하게낮았다. 또한 HOMA-IR은연령을보정한후에도복부둘레, 수축기 / 이완기혈압, 공복혈당, 중성지방, HDL-콜레스테롤등대사위험요소들과유의한상관관계를보였다. 이것은비만아동 32,33) 이나건강한성인 17,34) 을대상으로분석한연구들과동일한결과였다. 회귀분석결과, 대사증후군의요소중복부비만, 고중성지방혈증만이인슐린저항성의독립적인위험요인이었으며, 고혈압과저HDL-콜레스테롤은유의한위험요인이아니었는데, 이는성인을대상으로한연구들 34,35) 에서대사증후군의다섯가지요소들모두유의한인슐린저항성의위험요인으로나타난것과대조적인결과이다. Amiel 등 36) 의연구에서도본연구결과와같이사춘기청소년의고혈압은개별적인자로서는인슐린저항성과연관성이없는것으로분석되었다. 청소년기에는성인과달리고혈압의유병률이낮고, 인슐린저항성이있는청소년이라하더라도지속적인고혈압을보이는경우는흔하지않으며, 고혈압을일으키는기전이다양한요소의영향을받으므로 37) 인슐린저

7 382 ㆍ대한소아소화기영양학회지 : 제 14 권제 4 호 2011 항성이고혈압의주요인자로작용하지않기때문인것으로생각된다. 저HDL-콜레스테롤혈증은성인을대상으로한연구에서도인슐린저항성에대한교차비 (odds ratio) 가높지않았는데 34,35), 이는 HDL-콜레스테롤이중성지방과의상관성이매우높아, 중성지방을포함하는다변량회귀분석에서통계적유의성을잃기때문인것으로분석된다. 성인과소아에서만성적인 ALT 상승의가장흔한원인은비알코올지방간질환으로알려져있으며 ALT 농도는비알코올지방간질환에대한유의한예측인자로여겨지고있다 38). 2002년 Vozarova 등은 ALT 상승이간내인슐린감수성의감소와관련이있다고하였으며 39), 2005년 Hanley 등은 ALT 상승이대사증후군발생의유용한예측인자임을밝혔는데 40), 이후우리나라성인연구 16) 에서 40 IU/L 미만의경한 ALT 상승도대사증후군의예측인자임이보고되었다. 본연구에서는정상범위로알려져있는경미한 ALT 상승이다른대사위험요인들과독립적으로인슐린저항성의유의한위험인자임을확인할수있었으며, 그위험도는복부비만과고중성지방혈증보다더높았다. 향후소아에서높은 ALT 와제2형당뇨병및심혈관질환발생과의연관성을밝히는종적연구가필요할것으로보인다. 본연구의제한점은첫째, 2년간의국민건강영양조사자료를바탕으로분석한단면적연구로서, 인과관계를추론할수없고, 둘째, 사춘기단계가변수에포함되지않아사춘기단계를보정하는대신연령을보정하여인슐린저항성과각대사위험요인의연관성및위험도를분석하여향후사춘기연령에따른추가연구가필요할것으로보인다. 그럼에도불구하고본연구는인슐린저항성에대한진단기준이필요성이증대되는현시점에서건강한한국청소년을대상으로 HOMA-IR의분포와대사위험요소들과의연관성을연구한최초의대표성이있는자료를대상으로한연구로서의의가있다. 결론적으로정상한국청소년에서 HOMA-IR값은인슐린저항성및대사위험도를평가하는데유용한지표로사용될수있으며, 절단치설정을위해추후연구가필요할것으로생각된다. 요약목적 : 식습관의서구화, 사회경제적발달과함께소아청소년인구의비만이급격히증가함에따라인슐린저항성과내당능장애도증가하는것으로보고되고있다. 본연구에서는한국청소년에서의인슐린저항성의지표인 HOMA-IR (Homeostasis model assessment for insulin resistance) 과대사위험요소와의연관성에대하여알아보고자하였다. 방법 : 년국민건강영양조사에참여한만 10 19세청소년총 2,035명 ( 남 1,053명, 여 982명 ) 을대상으로하였다. 대사위험요소인허리둘레, 체질량지수, 수축기이완기혈압, 공복혈당, 공복인슐린농도, 혈청ㆍ지질농도, 혈청 alanine aminotransferase (ALT) 를분석에사용하였다. 대상청소년을 HOMA-IR의사분위수에따라네군으로나누어각군별대사위험요소를비교하였다 HOMA-IR이가장높은사분위수에해당하는대상군을인슐린저항성이있는군으로정의하여, 인슐린저항성에대한각대사위험요인들의위험도를측정하였다. 결과 : 인슐린저항성에해당하는 HOMA-IR은남자 3.4, 여자 3.6 이상이었다. 남녀모두에서 HOMA-IR의사분위수가증가함에따라체질량지수, 허리둘레, 수축기혈압, 중성지방, 공복혈당, 공복혈중인슐린농도, ALT, 비만도가증가하였고 HDL-콜레스테롤은감소하였다. 복부둘레, 공복혈당, 중성지방, ALT, 혈압은 HOMA-IR과양의상관관계를보였고 HDL-콜레스테롤은음의상관관계를보였다. 다변량로지스틱회귀분석에의한인슐린저항성에대한위험도는높은 ALT는남아 3.53배 ( ), 여아 4.04배 ( ), 복부비만은남아 3.04배 ( ), 여아 3.20배 ( ), 중성지방은남아 3.03배 ( ), 여아 1.94배 ( ) 였다. 결론 : 건강한한국청소년에서가장높은사분위수에해당하는 HOMA-IR값은남자 3.4, 여자 3.6 이상이며, 이는인슐린저항성및대사위험도를평가하는데유용한지표로사용될수있을것이다.

8 서유진외 :HOMA-IR and Metabolic Risk Factors among Korean Adolescents ㆍ 383 참고문헌 1) Chu MA, Choe BH. Obesity and metabolic syndrome among children and adolescents in Korea. J Korean Med Assoc 2010;53: ) Oh K, Jang MJ, Lee NY, Moon JS, Lee CG, Yoo MH, et al. Prevalence and trends in obesity among Korean children and adolescents in 1997 and Korean J Pediatr 2008;51: ) Park MJ, Boston BA, Oh M, Jee SH. Prevalence and trends of metabolic syndrome among Korean adolescents: from the Korean NHANES survey, J Pediatr 2009;155: ) Groop L. Orho-Melander M. The dysmetabolic syndrome. J Intern Med 2001;250: ) Reaven GM. Banting Lecture Role of insulin resistance in human disease. Diabetes 1988;37: ) Park MJ. Epidemiology of the metabolic syndrome among Korean children and adolescents. Korean J Pediatr 2008;51: ) Song Y, Park MJ, Paik HY, Joung H. Secular trends in dietary patterns and obesity-related risk factors in Korean adolescents aged years. Int J Obes 2010;34: ) Long SD, O Brien K, MacDonald KG, Leggett-Frazier N, Swanson MS, Pories WJ, et al. Weight loss in severely obese subjects prevents the progression of impaired glucose tolerance to type II diabetes. A longitudinal interventional study. Diabetes Care 1994;17: ) Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981;68: ) Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28: ) Kenskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005;115: ) Lee JK, Kim YT. Korean National Health and Nutrition Examination Survey (KNHANES) IV progress report. Chungbuk, Korea: Korea centers for disease control and prevention; Available at [accessed on 20 Feb 2011]. 13) Moon JS, Lee SY, Nam CM, Choi JM, Choe BK, Seo JW, et al Korean National Growth Charts: review of developmental process and an outlook. Korean J Pediatr 2008;51: ) Zimmet P, Alberti KG, Kaufman F, Tajima N, Silink M, Arslanian S, et al. IDF Consensus Group. The metabolic syndrome in children and adolescents - an IDF consensus report. Pediatr Diabetes 2007;8: ) Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH. Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, Arch Pediatr Adolesc Med 2003;15: ) Kang HS, Um SH, Seo YS, An H, Lee KG, Jin J, et al. Healthy range for serum ALT and the clinical significance of unhealthy normal ALT levels in the Korean population. J Gastroenterol Hepatol 2011;26: ) McAuley KA, Williams SM, Mann JI, Walker RJ, Lewis-Barned NJ, Temp Duncan AW. Diagnosing insulin resistance in the general population. Diabetes Care 2001; 24: ) Goran MI, Ball GD, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 2003;88: ) Moran A, Jacobs DR, Steinberger J, Hong CP, Prineas R, Luepker R, et al. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 1999;48: ) Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes 2001;50: ) Hirschler V, Maccallini G, Karam C, Gonzalez C, Aranda C. Are girls more insulin-resistant than boys? Clin Biochem 2009;42: ) Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG. Prevalence and determinants of insulin resistance among U.S. adolescents: a population based study. Diabetes Care 2006;29: ) Bao W, Srinivasan SR, Berenson GS. Persistent elevation of plasma insulin levels is associated with increased cardiovascular risk in children and young adults. The Bogalusa Heart Study. Circulation 1996;93: ) Balkau B, Charles MA. Comment on the provisional report from the WHO consultation. European Group for the Study of Insulin Resistance (EGIR). Diabet Med 1999;16: ) Kang HT, Yoon JH, Kim JY, Ahn SK, Linton JA, Koh SB, et al. The association between the ratio of triglyceride

9 384 ㆍ대한소아소화기영양학회지 : 제 14 권제 4 호 2011 to HDL-C and insulin resistance according to waist circumference in a rural Korean population. Nutr Metab Cardiovasc Dis 2011 Jul 14. [Epub ahead of print] 26) Kim CS, Lim S, Rosenson RS. Hyperinsulinemia and homeostasis model assessment of insulin resistance as predictors of hypertension: a 5-year follow-up study of Korean sample. Am J Hypertens 2011;24: ) Ausk KJ, Boyko EJ, Ioannou GN. Insulin resistance predicts mortality in nondiabetic individuals in the U.S. Diabetes Care 2010;33: ) Pande RL, Perlstein TS, Beckman JA, Creager MA. Association of insulin resistance and inflammation with peripheral arterial disease: the National Health and Nutrition Examination Survey, 1999 to Circulation 2008;118: ) Cha BS. Pathophysiology of insulin resistence. In: Cho HK, editor. Metabolic syndrome nd ed. Seoul: Jin publishing Co, 2009: ) Sadur CN, Yost TJ, Eckel RH. Insulin responsiveness of adipose tissue lipoprotein lipase is delayed but preserved in obesity. J Clin Endocrinol Metab 1984;59: ) Golay A, Zech L, Shi MZ, Chiou YA, Reaven GM, Chen YD. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using titrated HDL. J Clin Endocrinol Metab 1987;65: ) Byun SH, Jeon JD, Kim HS, Kim SY. A study of serum adiponectin and insulin resistance in children and adolescents. J Korean Soc Pediatr Endocrinol 2007;12: ) Ahn JG, Kim JM, Shin JH. Factors related to complications of childhood obesity. J Korean Soc Pediatr Endocrinol 2006;11: ) Lee SH, Choi SH, Kim HJ, Chung YS, Lee KW, Lee HC, et al. Cutoff values of surrogate measures of insulin resistance for metabolic syndrome in Korean non-diabetic Adults. J Korean Med Sci 2006;21: ) Choi HJ, Yun KE. Predictors of insulin resistance in postmenopausal women. J Korean Soc Menopause 2010; 16: ) Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 1986;315: ) Steinberger J, Daniels SR. Obesity, insulin resistance, diabetes, and cardiovascular risk in children: an American Heart Association scientific statement from the Atherosclerosis, Hypertension, and Obesity in the Young Committee (Council on Cardiovascular Disease in the Young) and the Diabetes Committee (Council on Nutrition, Physical Activity, and Metabolism). Circulation 2003;107: ) Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol 2003;98: ) Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, et al. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 2002;51: ) Hanley AJ, Williams K, Festa A, Wagenknecht LE, D'Agostino RB Jr, Haffner SM. Liver markers and development of the metabolic syndrome: the insulin resistance atherosclerosis study. Diabetes 2005;54:

DIABETES FACT SHEET IN KOREA 2012 SUMMARY About 3.2 million Korean people (10.1%) aged over 30 years or older had diabetes in 2010. Based on fasting g

DIABETES FACT SHEET IN KOREA 2012 Korean Diabetes Association (KDA) / Korea Centers for Disease Control and Prevention (CDC) DIABETES FACT SHEET IN KOREA 2012 SUMMARY About 3.2 million Korean people (10.1%)