12_( ) _장경순,임현술.hwp

DOI : 10.4093/kdj.2009.33.6.537 ORIGINAL ARTICLES 지역사회주민에서당뇨병실태및관련요인이심박동수변이에미치는영향 동국대학교의과대학예방의학교실 장경순 이관 임현술 The Status of Diabetes Mellitus and Effects of Related Factors on Heart Rate Variability in a Community Kyeong-Soon Chang, Kwan Lee, Hyun-Sul Lim Department of Preventive Medicine, Dongguk University College of Medicine, Gyeongju, Korea Abstract Background: This study was performed to examine the status of diabetes mellitus (DM) in the community and effects of related factors on heart rate variability (HRV). Methods: The author conducted HRV testing, a questionnaire survey, and blood chemistry analysis for fasting blood sugar (FBS) and HbA1c levels in 855 patients in a community over a period of 10 days, from August 14 to 25, 2006. The subjects were divided into a DM group and normal group by our study criteria. Results: The proportion of DM was 12.6% and increased with old age. The mean measures of HRV (SDNN, Tp, Vlf, Lf, Hf, Lf/Hf) in the DM group were 22.7 (1.6) msec, 364.9 (2.7) msec 2, 174.1 (3.0) msec 2, 88.1 (3.2) msec 2, 55.3 (3.2) msec 2, and 1.6 (2.6), respectively, while those in the normal group were 32.2 (1.6) msec, 676.6 (2.8) msec 2, 295.7 (3.1) msec 2, 169.2 (3.4) msec 2, 117.2 (3.2) msec 2, and 1.4 (2.6), respectively. All parameters except for Lf/Hf were significantly lower in the DM group than in the normal group (P < 0.01). The Spearman's correlation coefficients between HRV and FBS or HbA1c were SDNN -0.222/-0.244 (P < 0.01), Tp -0.211/-0.212 (P < 0.01), Vlf -0.149/-0.132 (P < 0.01), Lf -0.188/-0.235 (P < 0.01), Hf -0.207/-0.204 (P < 0.01), and Lf/Hf (P > 0.05), respectively. Conclusion: This study shows that the DM group had a reduced HRV and increased pulse rate in comparison with the normal group. According to our results, the HRV test may be used accessorily for the early detection of cardiovascular autonomic neuropathy (CAN) and its related factors, as well as to prevent CAN. (Korean Diabetes J 33:537-546, 2009) Key words: Diabetes mellitus, Diabetic neuropathies, Heart rate, Risk factors 서론당뇨병은우리나라사망원인에서암, 뇌혈관질환, 심장질환에이어 5번째를차지하고있으며 1), 30세이상성인에서 2001년 8.6%, 2005년 9.2%, 2007년 9.5% 로증가하는양상을보이고있는질병이다 2). 이러한당뇨병의증가는단순히 당뇨병환자의수적인증가에그치지않고당뇨병에병발하는각종당뇨병성합병증발생의증가를의미한다 3). 특히당뇨병은심혈관및뇌혈관질환의중요한위험인자로알려져있으며, 실제당뇨병환자의사망요인역시심혈관질환이나뇌혈관질환이상당부분을차지하고있다 4,5). 그러나당뇨병은조기에진단하여적절한치료와관리만이루어진다 접수일자 : 2009 년 7 월 16 일, 통과일자 : 2009 년 10 월 23 일교신저자 : 임현술, 동국대학교의과대학예방의학교실, E-mail: wisewine@dongguk.ac.kr 537

면합병증과사망률을감소시킬수있는질병으로적절한당뇨병관리가당뇨병의합병증을감소시키고, 생존율을향상시킬수있다 6-8). 당뇨병에의한대표적합병증의하나인자율신경병증은위장관계, 비뇨기계, 심혈관계등의다양한장기에서발생할수있으며, 그유병률은보고자마다다르지만일반적으로전체환자의 20~40% 를차지하고있다 9). 그러나증상이뚜렷하지않고진단이어렵다는이유로별로주목받지못하였지만 4,5), 그중에서사망의직접인원인의하나로알려진체위성저혈압에의한실신, 안정시빈맥, 무통성심근경색증, 급사등의심혈관계자율신경병증 (cardiovascular autonomic neuropathy, CAN) 은다른형태의당뇨병성자율신경병증 (diabetic autonomic neuropathy, DAN) 과는달리심박동수변이 (heart rate variability, HRV) 를분석함으로써평가할수있으며, 심혈관계질환의발생을줄일수있는유용한도구로사용하기위한노력이진행되어왔다 10,11). 국내에서도심전도상의 QTc 간격의분포나심박수의변화를통한 DAN의분석 12,13), 24시간홀터를이용한심박수변화율분석을통한당뇨병의진행정도, 미세혈관합병증과의상관성을밝혀내는연구 14) 등이진행된상황이다. 이연구는당뇨병과 CAN의관련성을파악하기위해지역사회일반인구를대상으로당뇨병실태및관련위험요인이 HRV에미치는영향을파악하고자시행하였다. 용하여 standard deviation of normal to normal intervals, in milliseconds (SDNN) 을산출하였다. 주파수범주에서는일반적으로혈압과심박동에대하여세가지주기성분으로정의된다. 첫째는 0.15 Hz에서 0.4 Hz사이의호흡활동과관련이있는 Hf 성분, 둘째혈압조절메커니즘과관련이있는 0.1 Hz를중심으로하는 Lf 성분, 셋째로체온조절, 혈관운동, 다양한심폐메카니즘과관련이있는 0.04 Hz 이하의 Vlf 성분으로정의되지만주파수대역의정의에있어다소차이가있다 15). 그러나본연구에서는일반적으로는 Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology 16) 에서정의하는성분을중심으로산출한바, 주파수범주에서는전체강도 Tp (total power, 1.15 10-5 ~0.40 Hz), 교감및부교감신경계를대표하는극저주파수영역 Vlf (very low frequency power, 0.003~0.04 Hz), 교감신경계를대표하는저주파수영역 Lf (low frequency power, 0.04~0.15 Hz), 부교감신경계를대표하는고주파수영역 Hf (high frequency power, 0.15~0.40 Hz), 그리고교감신경과부교감신경사이의평형정도를반영하는고주파수영역에대한저주파수영역의비 (Lf/Hf) 등을산출하였다. SDNN은심박동의변이도를나타내는지표로이는각 대상및방법 1. 대상 2006년 8월 14일부터 25일까지휴일을제외하고 10일간실시한포항시남구주민에대한건강검진에자발적으로참여한지역주민 1,015명중만 20세미만의어린이와청소년을제외한 855명을연구대상으로하였다 (Fig. 1). 연구계획은동국대학교경주병원임상시험심사위원회로부터승인 (2006년 7월 26일 ) 을받았으며, 모든대상자에게사전동의서를받은후연구를수행하였다. 2. 방법 1) HRV 검사 HRV 검사는 SA-3000P (Cardio-Peri; Medicore, Seoul, Korea) 를이용하였고, 측정방법은검사대상자가의자에앉은후좌 우측손목과좌측발목부분에전극을부착시켜안정상태를확인한뒤 5분간측정하였다. 측정결과는시간범주와주파수범주로나누어분석하였다. 시간범주를이 Fig. 1. The flow chart of this study. 538

장경순외 2 인 : 지역사회주민에서당뇨병실태및관련요인이심박동수변이에미치는영향 각의 normal to normal (NN) interval이평균과얼마나많은차이를나타내는가를의미하는데, SDNN이큰경우에는심박동의변동신호가그만큼불규칙하다는것을의미하며, 반대로 SDNN이작은경우는심박동의변동신호가그만큼단조롭다는것을의미하는것이다. 특히 SDNN 지표는심혈관계의안정도와더불어자율신경계의신체에대한제어능력에관한정보를제공하는강력한지표로사용된다 15-17). 기위해서당뇨병군에대한정의를하였다. 이연구에서최종적인변수로이용할당뇨병군에대한정의에앞서당뇨병군은첫째, 설문조사결과당뇨병으로진단받고현재약물을복용하고있는자, 둘째, 공복혈당검사에서 1997년미국당뇨병학회에서제시된당뇨병진단기준 19,20) 인 126 mg/dl 이상인자, 셋째, 당화혈색소치가 7.0% 이상인자 21,22) 중에한가지이상을만족하는경우로하였다. 2) 이학적검사및생화학적검사사전에안내문을통하여검진시공복상태를유지하도록하였고, 혈압, 체질량지수, 혈당, 당화혈색소치, 총콜레스테롤을측정하였다. 혈압은자동혈압계 (FT-500R plus; Jawon medical Co., Kyoungsan, Korea) 를이용하여앉은상태에서 5분간안정을취한후 2회측정하여평균값을이용하였다. 체질량지수 (body mass index, BMI) 는키와몸무게를측정하여체중 (kg) 을키의제곱 (m 2 ) 으로나눈값으로정의하였다. 혈당은 glucose oxidase법 (HITACHI 747~200; Hitachi Co., Tokyo, Japan) 을이용하여측정하였고, 당화혈색소 (HbA1c) 치는고성능액체크로마토그래피 (HPLC) 를이용한 VARIANT II (Bio-Rad Inc, Hercules, CA, USA) 를이용하여측정하였다. 3) 설문조사설문지는연구진이직접개발 18) 하였으며, 조사는사전에잘교육된의과대학학생들이시행하였으며, 사전에설문지를나누어준경우에는기재누락에대한점검을실시하였다. 설문은성별, 나이, 흡연여부및흡연량, 음주여부및음주량, 당뇨병약물복용여부, 약물복용기간, 평소규칙적운동여부및운동량, 평소육체적활동량등의항목으로구성하였다. 흡연의정의는지금까지총 400개비이상의흡연을하였고, 현재에도흡연을하고있는경우로정의하였고, 음주는원래부터음주를하지않은경우는제외하고, 현재에도한달에 1회이상음주를하고있는경우로정의하였다. 운동의정의는 몸에땀이날정도의규칙적운동 ' 으로하였고, 운동량은주 1~2회, 주 3~4회, 주 5~6회, 매일등으로분류하였다. 육체적활동량은 힘쓰는육체적노동 ' 으로정의하였고, 예시로 무거운짐운반, 짐싣고내리기, 땅파기, 모내기, 김매기, 기타힘이많이드는육체노동 ' 등을제시하였다. 4) 환례정의이연구에서당뇨병군과정상군의 HRV의차이를관찰하 5) 통계방법종속변수로이용된심박동변이의요소인평균심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf의분포가모두우측으로편위된형태를보이고있기때문에자료의요약에대해서는기하평균 ( 기하표준편차 ) 의형태로제시하였다. 모든자료는엑셀에전산입력하였고, 자료는한글 SPSS 14.0 for Windows (SPSS Inc., Chicago, IL, USA) 를이용하여통계분석하였다. 당뇨병과관련된생활습관 ( 흡연, 음주, 운동, 신체활동등 ), 당뇨병여부, 성별등과같은범주용자료에따른 HRV 요소의차이는 Mann-Whitney U 검정을실시하였고, 연령, 콜레스테롤, BMI, 혈압, 혈당, 당화혈색소등의비범주형자료와 HRV의관련성은 Spearman's correlation 검정을실시하였다. 또한범주형자료간의유의성은 Chi-square 검정과 Chi-square for trend 검정을실시하여, P < 0.05를유의하다고판단하였다. 이를통하여 HRV의각요소와관련이있는유의한변수를독립변수로이용하여, 단계별변수선택방법으로 HRV의각요소 (SDNN, Tp, Vlf, Lf, Hf, Lf/Hf) 를종속변수로하는선형회귀분석을실시하였다. 결과 1. 일반적특성조사대상자의성별은여자가 550명 (64.3%) 으로많았고, 연령별로는 50대가 36.8% 로가장많았다. 대상자의흡연율은 14.0%, 음주율 38.9%, 운동실천율 41.5%, 신체활동자분율 38.1% 이었다. 2. 당뇨병조사총 855명을대상으로공복혈당, 당화혈색소치, 설문조사등의기준을이용하여당뇨병분율을산출하였다. 조사대상자의당뇨병분율은 12.6% 이고, 남자가 13.8% 로여자보다높았으며, 연령이증가함에따라당뇨병분율이유의하게증가하였다 (P < 0.01). 539

3. HRV 조사 1) 당뇨병군과정상군의비교당뇨병군과정상군의나이, 총콜레스테롤, 체질량지수, 수축기혈압, 확장기혈압, 공복혈당, 당화혈색소치의차이를조사하였다. 평균나이는당뇨병군에서 58.4 ± 7.9세로정상군의 51.7 ± 12.4세보다유의하게높았고 (P < 0.01), 총콜레스테롤은차이가없었다. BMI는당뇨병군에서 24.6 ± 2.9 kg/m 2 로정상군의 23.9 ± 2.8 kg/m 2 보다유의하게높았다 (P < 0.05). 수축기혈압은당뇨병군에서 121.7 ± 16.8 mm Hg로정상군의 117.0 ± 16.2 mm Hg보다유의하게높았고 (P < 0.01), 공복혈당과당화혈색소치는각각당뇨병군에서 146.7 ± 48.4 mg/dl, 6.6 ± 1.3% 로, 정상군의 96.2 ± 10.6 mg/dl, 5.3 ± 0.4% 보다유의하게높았다 (P < 0.01, Table 1). 당뇨병군과정상군의심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf 등의차이는심박동수와 Lf/Hf를제외하고는모두당뇨병군에서정상군보다유의하게낮았다 (P < 0.01, Table 2). 2) 관련인자에따른비교성별, 흡연, 음주, 규칙적운동, 육체적활동여부에따른심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf 등의차이를조사하였다 (Table 3). 심박동수와 Hf를제외하고는모두여자에서남자보다유의하게낮았다 (P < 0.01). 흡연유무에따른심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf 등의차이를조사하였다. Lf/Hf (P < 0.01) 를제외하고는모두유의하지않았다. 음주여부에따른심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf 등의차이를조사하였다. 심박동수를제외하고는모두비음주자가음주자보다유의하게낮았다 (P < 0.01). 규칙적운동여부에따른심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf 등의차이를조사하였다. 심박동수 (P < 0.01) 를제외하고는모두유의하지않았다. 육체적활동여부에따른심박동수, SDNN, Tp, Vlf, Lf, Hf, Lf/Hf 등의차이를조사하였다. 심박동수, Lf/Hf를제외하고는모두육체적활동을하지않는군에서육체적활동을하는군보다유의하게낮았다 (P < 0.01). 비범주형자료인연령, 콜레스테롤, 체질량지수, 수축기 / 확장기혈압, 공복혈당, 당화혈색소치등과 HRV의각요소 Table 1. The comparisons of the factors related to diabetes mellitus between the DM group and normal group Factors DM group (n = 108) Normal group (n = 747) Age (yr) 58.4 ± 7.9 * 51.7 ± 12.4 Total cholesterol (mg/dl) 191.9 ± 35.2 190.8 ± 34.6 BMI (kg/m 2 ) 24.6 ± 2.9 23.9 ± 2.8 Systolic blood pressure (mm Hg) 121.7 ± 16.8 * 117.0 ± 16.2 Diastolic blood pressure (mm Hg) 72.7 ± 9.8 72.5 ± 10.6 Fasting blood glucose (mg/dl) 146.7 ± 48.4 * 96.2 ± 10.6 HbA1c (%) 6.6 ± 1.3 * 5.3 ± 0.4 All values are mean ± standard deviation * P < 0.01 by Student's t test P < 0.05 by Student's t test. DM, diabetes mellitus. Table 2. The comparisons of the variables related to heart rate variability between the DM group and normal group Variables DM group Normal group Pulse rate 71.8 (1.1) * 68.2 (1.2) SDNN (msec) 22.7 (1.6) * 32.2 (1.6) Tp (msec 2 ) 364.9 (2.7) * 676.6 (2.8) Vlf (msec 2 ) 174.1 (3.0) * 295.7 (3.1) Lf (msec 2 ) 88.1 (3.2) * 169.2 (3.4) Hf (msec 2 ) 55.3 (3.2) * 117.2 (3.2) Lf/Hf (msec 2 ) 1.6 (2.6) 1.4 (2.6) All values are geometric mean (geometric standard deviation). * P < 0.01 by Mann-Whitney U test. DM, diabetes mellitus; Hf, high frequency power; Lf, low frequency power; SDNN, standard deviation of normal to normal intervals; Tp, total power; Vlf, very low frequency power. 540

장경순외 2 인 : 지역사회주민에서당뇨병실태및관련요인이심박동수변이에미치는영향 Table 3. The comparisons of the variables related to heart rate variability by gender Variables Pulse rate SDNN Tp Vlf Lf Hf Lf/Hf (msec) (msec 2 ) (msec 2 ) (msec 2 ) (msec 2 ) (msec 2 ) Gender Male 68.5 (1.2) 32.5 (1.7) * 719.1 (3.1) * 317.5 (3.4) * 198.2 (3.6) * 108.2 (3.4) 1.8 (2.5) * (n = 305) Female 68.7 (1.1) 29.9 (1.6) 579.4 (2.7) 256.1 (3.0) 136.4 (3.3) 105.7 (3.2) 1.3 (2.6) (n = 550) Smoking Yes 69.7 (1.2) 29.9 (1.7) 635.0 (3.0) 289.5 (3.4) 169.8 (3.5) 94.4 (3.2) 1.8 (2.3) * (n = 120) No 68.5 (1.2) 31.0 (1.6) 624.3 (2.8) 274.5 (3.1) 153.6 (3.5) 108.7 (3.3) 1.4 (2.6) (n = 735) Drinking Yes 68.8 (1.1) 33.1 (1.6) * 737.7 (2.8) * 316.0 (3.1) * 202.0 (3.4) * 120.5 (3.2) * 1.7 (2.5) * (n = 333) No 68.5 (1.2) 29.5 (1.6) 563.5 (2.8) 253.9 (3.1) 132.0 (3.4) 98.5 (3.3) 1.3 (2.6) (n = 522) Regular Yes 67.2 (1.2) * 31.5 (1.6) 643.5 (2.9) 283.6 (3.4) 160.5 (3.5) 110.1 (3.2) 1.5 (2.6) exercise (n = 354) No 69.7 (1.2) 30.5 (1.6) 616.1 (2.8) 272.8 (3.0) 153.1 (3.4) 104.6 (3.4) 1.5 (2.6) (n = 498) Physical Yes 67.4 (1.2) * 32.9 (1.6) * 717.6 (2.6) * 316.1 (2.9) * 180.0 (3.3) * 118.2 (3.1) 1.5 (2.7) activities (n = 319) No (n = 519) 69.4 (1.2) 29.6 (1.6) 574.4 (2.9) 254.1 (3.2) 141.7 (3.5) 100.1 (3.3) 1.4 (2.5) All values are geometric mean (geometric standard deviation). * P < 0.01 by Mann-Whitney U test, P < 0.05 by Mann-Whitney U test. Hf, high frequency power; Lf, low frequency power; SDNN, standard deviation of normal to normal intervals; Tp, total power; Vlf, very low frequency power. Table 4. Correlations between contents related to heart rate variability and factors related to diabetes mellitus SDNN Tp Vlf Lf Hf Lf/Hf Pulse rate -0.335 * -0.281 * -0.232 * -0.151 * -0.356 * 0.241 * Age -0.414 * -0.393 * -0.252 * -0.459-0.397 * -0.113 * Total cholesterol -0.044-0.033-0.028-0.051-0.029-0.038 BMI -0.084-0.071-0.083-0.071-0.054-0.007 Systolic BP -0.088 * -0.050-0.027-0.059-0.056-0.008 Diastolic BP -0.075-0.040-0.030-0.025-0.063 0.039 FBS -0.222 * -0.211 * -0.149 * -0.188 * -0.207 * 0.000 HbA1c -0.244 * -0.212 * -0.132 * -0.235 * -0.204 * -0.064 * P < 0.01 by Spearman's correlation test, P < 0.05 by Spearman's correlation test. BMI, body mass index; BP, blood pressure; FBS, fasting blood sugar; Hf, high frequency power; Lf, low frequency power; SDNN, standard deviation of normal to normal intervals; Tp, total power; Vlf, very low frequency power. 간상관관계는 Table 4와같다. 3) 다변량분석결과단변량분석에서 HRV의각요소와유의하였던변수를독립변수로하는다변량분석을실시하였다 (Table 5). 선형 회귀분석을이용한다변량분석결과 SDNN, Tp, Vlf, Lf의경우연령, 심박동수, 당뇨병군일수록감소하고, 남자의경우증가하였다. 또한 Hf의경우연령, 심박동수, 당뇨병군일수록감소하였고, Lf/Hf의경우에는연령이증가할수록감소하였고, 심박동수와음주자에서증가하였다. 541

Table 5. The results of multiple regression using the contents related to heart rate variability and its related factors Models Variables Adjusted R 2 β 95% CI for β Lower limit Upper limit P-value ln (SDNN) Constant 0.335 9.793 8.988 10.597 0.000 Age -0.016-0.018-0.014 0.000 Ln (PR) -1.309-1.494-1.124 0.000 DM (yes) -0.175-0.258-0.092 0.000 Gender (male) 0.062 0.007 0.118 0.028 ln (Tp) Constant 0.280 18.364 16.557 20.170 0.000 Age -0.034-0.039-0.029 0.000 ln (PR) -2.407-2.823-1.992 0.000 DM (yes) -0.265-0.450-0.079 0.005 Gender (male) 0.177 0.052 0.302 0.005 ln (Vlf) Constant 0.154 16.128 13.981 18.276 0.000 ln (PR) -2.193-2.687-1.700 0.000 Age -0.024-0.030-0.018 0.000 Gender (male) 0.185 0.037 0.333 0.014 DM (yes) -0.258-0.478-0.037 0.022 ln (Lf) Constant 0.282 15.344 13.192 17.496 0.000 Age -0.047-0.053-0.041 0.000 ln (PR) -1.872-2.367-1.378 0.000 Gender (male) 0.334 0.185 0.482 0.000 DM (yes) -0.239-0.460-0.017 0.034 ln (Hf) Constant 0.333 21.026 19.041 23.012 0.000 Age -0.040-0.046-0.035 0.000 ln (PR) -3.362-3.819-2.905 0.000 DM (yes) -0.302-0.506-0.097 0.004 ln (Lf/Hf) Constant 0.069-5.657-7.501-3.813 0.000 ln (PR) 1.479 1.054 1.903 0.000 Drinking (yes) 0.185 0.055 0.314 0.005 Age -0.005-0.011 0.000 0.040 CI, confidence interval; Hf, high frequency power; Lf, low frequency power; SDNN, standard deviation of normal to normal intervals; Tp, total power; Vlf, very low frequency power. 고찰본연구에서사용된당뇨병진단기준은당화혈색소가 7.0% 이상이거나, 당뇨병진단을받고투약중인자, 또는공복혈당이 126 mg/dl 이상인자로하였다. 본연구의기준에의하면당뇨병분율은 12.6% 로 2007년국민건강영양조사 2) 의 9.5% 보다높았다. 남자가여자보다높고, 연령이증가하면서증가하는사실은기존연구결과의경향과유사하였으나, 높은당뇨병분율은연구대상자의연령이평균적으로높아과다측정이되었을가능성이있다. 또한공복혈당을진단기준으로하였기때문에지역사회의건강검진특성상완벽한공복이유지되지않은상태에서검진을할경우이분율은과다측정의결과일가능성도있다 23). 당뇨병군과정상군의일반적특성의비교에서당화혈색소치가당 뇨병군에서 6.6% 로, 일반적인당뇨병환자의기준또는조절의지표로통용되는 7.0% 이상은아니었지만, 정상범위인 4.0~6.0% 는초과하고있었다 22). 당뇨병환자의 1/6 정도가자율신경계의이상을동반하고있으며, DAN은일반적으로말기합병증으로, 자율신경계의이상이사망률에영향을미치는중요한요인이다 24). 자율신경병증이동반된당뇨병환자는그렇지않은당뇨병환자에비해 10년동안 5배이상의사망률을나타낸다 25). 당뇨병환자에서전체적인 HRV의감소의소견이보이며, 이는심장의부교감신경이감소되고, 교감신경이증가한결과로알려져있다. 당뇨병환자에서자율신경계의이상은점진적으로발생하기때문에조기에자율신경계이상유무를판단하는것은당뇨병환자에서장기간치료전략에중요한문제일수있다 24). 특히증가된심박동수와감소된 HRV는건강한성인에서무증상염증반응과관련이깊으며이러한 542

장경순외 2 인 : 지역사회주민에서당뇨병실태및관련요인이심박동수변이에미치는영향 기전으로사망률의증가를초래한다고보고한바있다 26). 이와관련하여당뇨병진단후 5~8년후의경동맥동맥경화증의진행과정도를예측할수있는데, 특히감소된 Lf는이러한환자에서동맥경화의진행을의미한다 27). 유병기간이 10년이상인당뇨병환자에서 DAN의분율이높은데, 이런사실은효과적인혈당조절을통한예방의중요성을시사하고있다 24). 본연구에서는당뇨병의유병기간에따른 HRV 의관련성은관찰되지않았다. 이는본연구가당뇨병환자를대상으로하는연구이기보다지역사회에서당뇨병을일정기준으로판단하고, 이에따른 HRV의차이를관찰하고자하는것이기때문에, 유병기간에따른 HRV의관련성을파악하기위해서는당뇨병유병기간을알수있는환자의수가 40명으로적었기때문으로생각한다. 특히고혈압같은다른질환과동반될경우 HRV의유의한차이를예측할수있으나본연구에서는당뇨병약단독투약군과고혈압약과의병행투여군간의유의한 HRV는관찰되지않았다. 우리나라에서임상적으로당뇨병관련연구를제외하면 HRV에관한연구는교대근무근로자에서 24시간생체주기의변화를심박동변이를통하여파악한연구이외에는거의없지만 28), 외국에서는이미 1996년유럽심장학회와북미심조율전기생리학회에서 HRV의측정방법, 생리적해석, 그리고임상적사용에대한표준이제정된바있다 16). 고전적으로자율신경병증을진단하기위해 1970년대부터사용된발살바법 (Valsalva Maneuver), 심호흡및기립시의심박동의변화, 기립시및지속적인악력 (handgrip) 에대한혈압의변화등의 5가지방법은일반심전도로할수있다는장점이있었지만, 재현성이높지않고시행과정이복잡하며피검사자의협조가어려운점 29), 번거롭고수동적계산이필요하기때문에최근에는객관성과편리성등을고려하여심혈관검사만전문적으로검사하는장비와컴퓨터분석프로그램을이용하고있다 9,30,31). 또한 DAN 중 CAN에대하여 HRV 검사는당뇨병환자의선별검사로적당하며, 실제미국당뇨병학회에서는제2형당뇨병환자의진단당시및운동처방시이검사를시행하도록권고하고있다 11). 결국이러한 HRV 검사의장점과유용성에도불구하고기존에시행되었던자율신경병증을진단하는여러도구들을평가절하될수는없다고생각한다. 보완적으로고전적으로사용하고있는방법들을같이사용한다면검사의신뢰성과정확성을높일수있을것이다. 자율신경계의기능을결정하는가장중요한인자로는연령, 당뇨병유무, 고혈압약제의사용이며 32), HRV를결정하는인자로는연령과심박동수로알려져있다 33). 이연구에 서는고혈압약제, 특히 β-차단제를비롯한약제의종류에대해서는조사하지못하였으나, 고혈압유무에따른 HRV 의유의한차이는관찰할수없었다. 이연구의결과에서도 HRV에영향을미치는요소는연령, 성별, 당뇨병유무, 심박동수등으로조사되었다. 흡연의경우 HRV 중 Hf를감소시키는것으로보고 34) 되고있지만, 이연구의단변량분석에서흡연유무에따른 HRV의유의한차이는 Lf/Hf 이외에는관찰되지않았다. 음주의경우중등도의알콜섭취자가비섭취자에비해저녁과밤동안의 Hf의유의한감소가있다는보고 35) 와적절한와인섭취는 HRV의증가를가져온다는상반된보고가있다 36). 이연구에서이러한상반된결과는단면연구의한계로서당뇨병및고혈압, 심혈관계질환을앓고있는환자는금연과금주를실천하는경우가많고, 건강한사람들이흡연과음주를하기때문에발생하는선택생존의가능성을배제하기어렵다. 지속적인운동은자율신경기능을호전시키는효과를가지기때문에 HRV에도영향을줄것으로생각된다. 그러나 5개월간의유산소운동을시킨후고강도의운동을수행한군에서만이심박동수의감소가있었고, 저강도운동군에서는의미있는변화가없었으며, HRV는의미있게변하지않았음을보고하면서, 5개월동안의운동도 HRV에영향을주기에는짧은기간이라고보고한바있다 37). 이연구에서도일반인구에서규칙적인운동여부에따른 HRV의차이는심박동수가낮아지는것을제외하고는다른요소의차이를관찰할수없었다. 대신에육체적활동있는경우는없는경우에비해심박동수의감소와 HRV의유의한증가를관찰하였다. 한편자율신경계의조절이상은당뇨병의발생에중요한역할을수행한다. Carnethon 등은감소된 HRV와증가된심박동수는당뇨병으로의발전이가능하다고보고하였다 38). 증가된교감신경은혈중카테콜라민분비를촉진하고, 이는인슐린저항을증가시키는유리지방산의증가를초래한다 39). 이연구의자료로도 HRV와당뇨병과의관련성에대해서 HRV를통하여당뇨병을일부예측할수는있지만, 현실적으로당뇨병의진단은혈당과당화혈색소를통해서진단되는신뢰할수있는명확한기준이있기때문에 HRV를당뇨병의진단도구로사용하기는어렵다. 이연구를통하여당뇨병환자군에서정상군에비해 SDNN, Tp, Vlf, Lf, Hf 등의 HRV 수치가유의하게낮음을확인할수있었다. 이러한사실은당뇨병환자군에서 CAN이발생할확률이높다는점을시사하는소견이다. 그 543

러나 HRV의가장민감한지표인 SDNN과 Tp를성, 연령, 심박동수, 당뇨병유무등을통해예측할경우그설명력은각각 33.5%, 28.0% 로서 HRV의경우당뇨병, 심박동수, 성, 연령뿐만아니라다른요인에의한영향도많다는점을시사하고있다. 그렇지만이연구에서는당뇨병에의한자율신경병증에대한정확한진단이없었기때문에 HRV 검사를통하여 CAN 여부를밝히지못하였다. 다만이연구와문헌고찰을통하여당뇨병환자군에서 CAN의발생확률이높다는사실과 HRV의차이를통하여앞으로당뇨병의합병증인 CAN 을조기에진단하는데활용하는연구가보다활발히진행되길바라며, CAN을조기에발견함으로써당뇨병과그합병증을보다효율적으로관리하는계기가마련되기를바란다. 요약연구배경 : 당뇨병에의한대표적합병증의하나인자율신경병증은전체환자의 20~40% 를차지하고있으나증상이뚜렷하지않고, 진단이어렵다는이유로별로주목받지못하였다. 이연구는당뇨병과심혈관계자율신경병증의관련성을파악하기위해지역사회일반인구를대상으로당뇨병실태및관련위험요인이 HRV에미치는영향을파악하고자시행하였다. 방법 : 경상북도포항시남구지역주민 855명을편의추출하였으며, 이들을대상으로 2006년 8월 14일부터 8월 25 일까지설문조사, 혈압, 체질량지수등의이학적검사, 공복혈당, 콜레스테롤, 당화혈색소등의생화학적검사및심박동변이검사를실시하였다. 결과 : 조사대상자 855명중공복시혈당, 설문조사, 당화혈색소를기준에부합하는대상자는 108명으로당뇨병분율은 12.6% 이었다. 당뇨병군에서 HRV 요소 (SDNN, Tp, Vlf, Lf, Hf, Lf/Hf) 의기하평균 ( 기하표준편차 ) 은각각 22.7 (1.6) msec, 364.9 (2.7) msec 2, 174.1 (3.0) msec 2, 88.1 (3.2) msec 2, 55.3 (3.2) msec 2, 1.6 (2.6) 이었고, 정상군에서는각각 32.2 (1.6) msec, 676.6 (2.8) msec 2, 295.7 (3.1) msec 2, 169.2 (3.4) msec 2, 117.2 (3.2) msec 2, 1.4 (2.6) 로 Lf/Hf 이외에는 HRV 요소모두통계적으로당뇨병군에서유의하게낮았다 (P < 0.01). 각 HRV 요소와공복혈당및당화혈색소와의상관계수 (r) 는 SDNN이각각 -0.222/-0.244 (P < 0.01), Tp -0.211/-0.212 (P < 0.01), Vlf -0.149/-0.132 (P < 0.01), Lf -0.188/-0.235 (P < 0.01), Hf -0.207/-0.204 (P < 0.01), Lf/Hf (P < 0.05) 등이었다. 단변량분석에서 HRV의각요소와유의하였던변수를독립변수로하는선형회귀분석을이용한다변량분석결과 SDNN과 Tp는모두연령, 심박동수, 당뇨병유무, 성별이유효한변수로작용하였고, 설명력은각각 33.5%, 28.0% 이었다. 결론 : HRV의차이를통하여앞으로당뇨병의합병증인심혈관계자율신경병증을조기에진단하는데활용하는연구가보다활발히진행되길바라며, 심혈관계자율신경병증을조기에발견함으로써궁극적으로당뇨병과그합병증을보다효율적으로관리하는계기가마련되기를바란다. 참고문헌 1. Korea National Statistical Office: 2007 annual report on the cause of death statistics. Daejeon, Korea National Statistical Office, 2008 2. Ministry for Health, Welfare and Family Affairs; Korea Centers for Disease Control and Prevention: The 4th national health and nutrition examination survey. Seoul, Korea Centers for Disease Control and Prevention, 2009 3. Ko SH, Kwon HS, Lee JM, Kim SR, Cho JH, Yoo KD, Park YM, Lee WC, Song KH, Yoon KH, Cha BY, Son HY, Ahn YB: Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus. J Korean Diabetes Assoc 30:226-35, 2006 4. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 339:229-34, 1998 5. Wheeler SG, Ahroni JH, Boyko EJ: Prospective study of autonomic neuropathy as a predictor of mortality in patients with diabetes. Diabetes Res Clin Pract 8:131-8, 2002 6. The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329:977-86, 1993 7. Nicolucci A, Cavaliere D, Scorpiglione N, Carinci F, Capani F, Tognoni G, Benedetti MM: A comprehensive 544

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