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1 ORIGINAL ARTICLE Korean J Clin Lab Sci. 2018;50(3): pissn eissn Korean J Clin Lab Sci. Vol. 50, No. 3, September Correlation between Serum Osteocalcin and Hemoglobin A1c in Gwangju General Hospital Patients Yo-Han Seo 1, Hee-Young Shin 2 1 Department of Laboratory Medicine, Gwangju Veterans Hospital, Gwangju, Korea 2 Department of Biomedical Science, Chonnam National University Medical School, Gwangju, Korea 광주소재한종합병원을방문한성인에서혈중 Osteocalcin 과 HbA1c 의상관관계 서요한 1, 신희영 2 1 광주보훈병원진단검사의학과, 2 전남대학교의과대학의생명과학교실 Recently, there have been many studies on the relationship between the bone metabolism and the mechanism of diabetes. In those studies, it was shown that osteocalcin can be involved in the treatment of type 2 diabetes. Therefore, this study examined the correlation between osteocalcin and HbA1c. From January 1, 2015 to December 31, 2016, a total of 714 adults aged 40 years or older (70.8±10.4 years, 452 males), in whom both osteocalcin and HbA1c checked in a general hospital in Gwangju, were enrolled in the study. The serum calcium, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, and 25-(OH) vitamin D were measured and basic information, such as the height and weight, were recorded. There was a weak negative correlation (r= 0.183, P<0.001) between the osteocalcin and HbA1c levels in diabetic patients but a negative correlation (r= 0.251, P<0.001) when adjusted by all other study variables. The present study showed that there was a negative correlation between the osteocalcin and HbA1c levels in diabetic patients. The relationship between the bone metabolism and the incidence of diabetes mellitus should be studied based on the influence of biological mechanisms and associated factors of bone and glucose metabolism. Key words: Bone, Diabetes mellitus, Hemoglobin A1c, Osteocalcin Corresponding author: Hee-Young Shin Department of Biomedical Science, Chonnam National University Medical School, 322 Seoyang-ro, Hwasun-eup, Hwasun-gun, Jeonnam 58128, Korea Tel: Fax: hyshin@jnu.ac.kr This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright 2018 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: May 19, 2018 Revised 1 st : July 25, 2018 Revised 2 nd : August 10, 2018 Accepted: August 13, 2018 서론전세계적으로당뇨병환자가기하급수적으로증가하고있는추세에서당뇨병전단계에있는사람들의 5 10% 가당뇨병으로악화되므로당뇨병전단계상태를조기발견하고관리하는것이필요하다 [1]. 이때식전혈당이나식후 2시간후혈당을측정하는것보다식사여부와상관없이측정가능한 HbA1c가당뇨병의지표로유용하게사용될수있으며, 미국당뇨병학회에 서는당뇨병의진단기준으로 HbA1c 6.5% 를추가한바있다 [2, 3]. 콜롬비아의과대학연구팀은정상적인골격이재생되는동안오래된뼈의파괴 ( 골흡수 ) 가혈액에서정상혈당수준을유지하는데필요하다는것을보여줌으로써, 골격이혈당조절에서중요한역할을한다는것을발견했다. 뼈흡수는새로운뼈를만들기위해일어나는과정이지만, 이흡수과정이인슐린의분비를촉진하여몸전체에서세포의당흡수를개선시키는작용

2 314 Yo-Han Seo and Hee-Young Shin. Correlation between Serum Osteocalcin and Hemoglobin A1c 을한다는것을발견했다. Osteocalcin 은췌장에서인슐린의생성을작동시키고다른세포의당흡수능력을증진시키는데, 이들과정모두 2형당뇨병에서는손상되어있다. 인슐린은뼈흡수를촉진하고, 이것은 osteocalcin 의활성을촉진하여결국인슐린의합성과분비를촉진하게된다. 이로인해, 당뇨병이 osteocalcin 의수준을증가시킴에의해치료될수있다는것을제안한다. 이연구는 osteocalcin 이당뇨발병에연관되어있고, 뼈가 2형당뇨병의새로운표적이될수있으며, 적정수준의 osteocalcin 을유지하는것이 2형당뇨병을위한치료법이될수있다는것을보인다 [4]. 최근제 2형당뇨병에서 osteocalcin 과당대사의관계에대한연구가이루어지고있다 [5]. Osteocalcin 이체질량지수를비롯한에너지대사및인슐린저항성과관련이있다는연구들이다양한분석방법으로진행되고있다 [6]. 해외에서는여러가지당대사에관련된지표와함께 osteocalcin 의상관성연구가성별, 부족등다양하게세분화된그룹으로많이진행되고있지만, 국내에서는다양한사례를찾아보기힘든실정이다 [7]. 그리하여, 본연구에서는당뇨병의유무에따라나이, 성별, 체질량지수등의기본정보와칼슘, 25-수산화비타민D, 카르복시말단펩티드와같은골대사관련요인그리고총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤과같은지질대사관련요인들을보정하여 HbA1c 와 osteocalcin 의상관관계를알아보고자하였다. 대상및방법 1. 연구대상본연구는광주보훈병원임상시험심사위원회 (Institutional Review Board, IRB) 의승인 ( 인간 차-1호 ) 을받아전산실에의뢰하여이미기록된환자들의 2차자료를수집하였다. 2015년 1월 1일부터 2016년 12월 31일까지광주소재한종합병원수진자중 osteocalcin 과 HbA1c를비롯하여칼슘, 카르복시말단펩티드 (C-terminal cross linking telopeptide of type 1 collagen), 총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤, 25-수산화비타민D 를동일한날모두측정하고키, 몸무게, 나이, 성별, 상병전체의기본정보가기록되어있는 40세이상의성인 809명을대상자로선별하였다. 그중, 환자등록번호가중복된데이터와상병상태를알수없는수진자 95명을제외하여총 714명을연구대상자로최종선정하였다. 2. 연구방법 Osteocalcin 은방사면역측정법 (radioimmunoassay) 을이용하여측정 (Packard Cobra Gamma Counter Series, GMI Inc., MN, USA) 하였다. HbA1c는고성능액체크로마토그래피법 (high performance liquid chromatography, HPLC) 에기초한자동당화혈색소분석기 (G8 HPLC Analyzer, Tosoh Inc., CA, USA) 를이용해측정하였다. 칼슘, 총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤은분광광도법 (spectrophotometry) 을이용하여측정 (AU5800, Beckman Coulter Inc., CA, USA) 하였고, 25-수산화비타민D 는화학발광면역측정법 (chemiluminescent immunoassay, CLIA) 을이용하여측정 (Architect i2000sr, Abbott Inc., IL, USA) 하였으며, 카르복시말단펩티드는전자화학발광면역분석법 (electro-chemiluminescence immunoassay, ECLIA) 을이용하여측정 (cobas E 602, Roche Ltd., BS, Switzerland) 하였다. 체질량지수는몸무게 (kg) 를키 (m) 의제곱으로나누어구하였고, 당뇨유무에대해서는기재되어있는상병코드를기준으로분류하여당뇨환자군과비당뇨환자군으로나누었다. 대부분연구대상자들로선정된환자들의검사결과는근골격계질환으로내원하여수술을앞두고시행한수술전검사이다. 따라서, 당뇨병에대한진료가이루어지지않았을가능성을염두에두고비당뇨환자군에서 HbA1c 수치가 6.5% 이상인집단은당뇨환자군으로포함시켰다. 또한, 지금까지성인당뇨조절관련요인은주로성인의전연령층을대상으로연구되어왔으나, 최근당뇨의유병률이 40세이상에서유의한증가율을보이고있는것을참고하여대상자를 40세이상으로한정하였다 [8]. 3. 통계분석의료정보시스템에서얻은데이터는 SPSS statistics 20(SPSS Inc., Chicago, IL, USA) 프로그램을이용하여통계분석하였다. 각변수들은 Kolmogorov-Smirnov 검정을통해정규분포에따르는것을확인하였다. 모든분석은당뇨환자군과비당뇨환자군으로나누어분석하였으며, 두군의기본특성은독립표본 t 검정 (Independent two-sample t-test) 또는카이제곱검정 (Chi-square test) 으로비교하였다. Osteocalcin 과다른요인들과의상관관계및 HbA1c와다른요인들과의상관관계는피어슨의상관계수 (Pearson's correlation coefficient) 로분석하였고, 유의미한상관관계를보이는요인들은성별로분류하여 HbA1c 를종속변수로두고단계선택다중회귀분석 (Stepwise multiple regression analysis) 을시행하였다. Osteocalcin과

3 Korean J Clin Lab Sci. Vol. 50, No. 3, September HbA1c의상관관계는칼슘, 카르복시말단펩티드, 총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤, 25-수산화비타민D, 체질량지수, 나이, 성별총 10개의요인을보정하여편상관분석법 (partial-correlation analysis) 으로측정하였다. 통계적유의수준은 P<0.05로설정하였다. 결과 1. 연구대상자의기본특성비교연구대상자는총 714명으로평균연령은 70.8±10.4세였고, 성별은남자 (63.3%) 가여자 (36.7%) 보다많았다. 두군의골대사지표중 osteocalcin 만이유의한차이가없었고 (P=0.477), 지질대사지표중중성지방만이유의한차이를보였다 (P<0.001)(Table 1). 2. 각요인들과의상관관계당뇨환자군에서 osteocalcin 과 HbA1c는약한음의상관관계 (r= 0.183, P<0.001) 가있음을보였고, 비당뇨환자군에서는유의한상관관계를보이지않았다. Osteocalcin 은당뇨환자군에서카르복시말단펩티드 (r=0.473, P<0.001), 총콜레스테롤 (r=0.276, P<0.001), 고밀도지질단백콜레스테롤 (r=0.147, P=0.005), 저밀도지질단백콜레스테롤 (r=0.272, P<0.001) 및비당뇨환자군에서카르복시말단펩티드 (r=0.473, P<0.001) 와양의상관관계를보였다 (Table 2). HbA1c는당뇨환자군에서나이 (r=0.118, P=0.023), 비당뇨환자군에서중성지방 (r=0.148, P=0.006) 과양의상관관계를 보였다. 또한, 당뇨환자군에서 osteocalcin(r= 0.183, P< 0.001), 25-수산화비타민D (r= 0.137, P=0.008), 중성지방 (r= 0.110, P=0.033) 및비당뇨환자군에서카르복시말단펩티드 (r= 0.208, P<0.001), 고밀도지질단백콜레스테롤 (r= 0.154, P=0.004) 과음의상관관계를보였다 (Table 3). 3. Osteocalcin 과 HbA1c 의편상관관계 나이, 성별, 체질량지수, 칼슘, 25-수산화비타민D, 카르복시말단펩티드, 총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤총 10개의요인을보정하였을때, osteocalcin 과 HbA1c가당뇨환자에서약한음의상관관계 (r= 0.251, P<0.001) 를보였다. 비당뇨환자에서의상관관계값 (r=0.033, P=0.547) 은유의하지않았다. 당뇨환자에서 Table 2. Correlation between osteocalcin and other study variables in diabetic and non-diabetic patients r(p) Variables Diabetic patients Non-Diabetic patients Age (0.411) (0.832) Body mass index (0.542) (0.244) HbA1c (<0.001) (0.160) CTx (<0.001) (<0.001) Calcium (0.245) (0.538) 25-(OH) Vitamin D (0.183) (0.418) Total cholesterol (<0.001) (0.491) Triglyceride (0.142) (0.452) HDL-Cholesterol (0.005) (0.152) LDL-Cholesterol (<0.001) (0.570) P-values are calculated by Pearson s correlation analysis. r, Pearson s correlation coefficient. Table 1. Comparison of general characteristics of study subjects (Mean±SD) Variables Total patients (N=714) Diabetic patients (N=371) Non-Diabetic patients (N=343) P Age (year) 70.8± ± ±11.9 <0.001 Sex-male/female (%) 452/262 (63.3/36.7) 255/116 (68.7/31.3) 197/146 (57.4/42.6) Body mass index ( kg /m 2 ) 23.6± ± ±3.5 <0.001 Height (cm) 161.1± ± ± Weight (kg) 63.5± ± ±12.2 <0.001 CTx (ng/dl) 0.377± ± ±0.317 <0.001 Osteocalcin (ng/dl) 6.4± ± ± HbA1c (%) 6.2± ± ±0.4 <0.001 Calcium (mg/dl) 8.7± ± ±0.5 < (OH) Vitamin D (ng/dl) 17.7± ± ± Total Cholesterol (mg/dl) 165.5± ± ± Triglyceride (mg/dl) 138.4± ± ±63.2 <0.001 HDL-Cholesterol (mg/dl) 44.5± ± ± LDL-Cholesterol (mg/dl) 95.2± ± ± P-values are calculated by independent samples t-test or chi-square test. Abbreviations: HDL-Cholesterol, high density lipoprotein cholesterol; LDL-Cholesterol, low density lipoprotein cholesterol; CTx, C-terminal cross linking telopeptide of type 1 collagen; HbA1c, hemoglobin A1c.

4 316 Yo-Han Seo and Hee-Young Shin. Correlation between Serum Osteocalcin and Hemoglobin A1c Table 3. Correlation between HbA1c and other study variables in diabetic and non-diabetic patients r(p) Variables Diabetic patients Non-Diabetic patients Age (0.023) (0.778) Body mass index (0.272) (0.145) Osteocalcin (<0.001) (0.160) CTx (0.076) (<0.001) Calcium (0.082) (0.174) 25-(OH) Vitamin D (0.008) (0.334) Total cholesterol (0.819) (0.470) Triglyceride (0.033) (0.006) HDL-Cholesterol (0.151) (0.004) LDL-Cholesterol (0.404) (0.194) P-values are calculated by Pearson s correlation analysis. r, Pearson s correlation coefficient. Table 4. The partial correlations between osteocalcin and HbA1c Division r P-value Diabetic patients Total <0.001 Male <0.001 Female Non-Diabetic patients Total Male Female P-values are calculated by partial-correlation analysis adjusting for age, sex, Body Mass Index, calcium, 25-(OH) vitamin D, CTx, total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol r, partial-correlation coefficient. 남성 (r= 0.258, P<0.001) 이여성 (r= 0.243, P=0.012) 보다좀더유의한상관관계를보였다 (Table 4). 4. HbA1c 를종속변수로한다중회귀분석 HbA1c를종속변수로한상관분석에서유의한상관관계를보였던나이, osteocalcin, 카르복시말단펩티드, 25-수산화비타민D, 중성지방, 고밀도지질단백콜레스테롤총 6개의요인을독립변수로설정하고 HbA1c를종속변수로하여단계선택다중회귀분석을시행하였을때, 남성집단에서는중성지방 (R 2 =0.060, =0.181, P<0.001) 과 osteocalcin (R 2 =0.060, =-0.171, P<0.001) 이유의한결과를나타내었다. 여성집단에서는중성지방 (R 2 =0.051, =0.226, P<0.001) 만이유의한결과를나타내었다 (Table 5). 고찰 Osteocalcin 과 HbA1c 는당뇨환자군에서약한음의상관관 Table 5. Multiple regression analysis for HbA1c by gender Division Variables R 2 P-value Male Triglyceride <0.001 Osteocalcin <0.001 Female Triglyceride <0.001 P-values are calculated by Stepwise multiple regression analysis. R 2, Coefficient of determination;, Standardized coefficient. 계 (r= 0.183, P<0.001) 가있었고, 비당뇨환자군에서는유의한상관관계가없었다. 나이, 성별, 체질량지수, 칼슘, 25-수산화비타민D, 카르복시말단펩티드, 총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤총 10 개의요인을보정한 osteocalcin 과 HbA1c의편상관분석에서도당뇨환자군에서는여전히약한음의상관관계 (r= 0.270, P< 0.001) 가있음을보여줌으로써선행연구들에서제시된골대사와당대사의관련성을보여주었지만, 비당뇨환자군에서상관관계는유의하지않았다 [7, 9]. 이는당뇨환자군이비당뇨환자군에비해동반질환이많으며, 골절의비교위험도가상승한연구에서처럼골대사와당대사의관계는비당뇨환자군보다당뇨환자군에서더뚜렷한상관관계가있음을나타낸다 [10]. 대상자수를늘리고환자의정확한상병정보를확보하여분석한다면비당뇨환자군에서 osteocalcin 과 HbA1c의상관관계에대한비교적신뢰도가높은결과를확인할수있을것으로사료된다. Osteocalcin 과다른요인들의상관관계중당뇨환자군에서총콜레스테롤 (r=0.276, P<0.001), 고밀도지질단백콜레스테롤 (r=0.147, P=0.005), 저밀도지질단백콜레스테롤 (r=0.272, P<0.001) 이유의한양의상관관계를나타냈다. 이는 osteocalcin 이지질대사에관여한다는연구를뒷받침한다 [11]. HbA1c와다른요인들의상관관계중비당뇨환자군에서만유의한상관관계를나타내는인자는카르복시말단펩티드 (r= 0.208, P< 0.001) 였다. 이는정상포도당내성 (normal glucose tolerance, NGT) 을가진사람에서카르복시말단펩티드가독립적으로 HbA1c와관련이있다는것을뒷받침한다 [12]. 상관분석과는다르게추가적으로실시한 HbA1c를종속변수로둔단계선택다중회귀분석에서 osteocalcin 은남성집단에서만 osteocalcin 이유의한결과를나타내었으며, 중성지방은남녀집단모두에서유의한결과를나타내었다 [13]. 결과에제시하진않았지만 25-수산화비타민D는당뇨환자군과비당뇨환자군모두에서총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤과유의한상관관계가없었다. 이는제2형당뇨병환자에서생화학적지표중총콜

5 Korean J Clin Lab Sci. Vol. 50, No. 3, September 레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤등은혈청 25-수산화비타민D 농도에유의한영향을미치지못하는것으로나타난선행연구를뒷받침해준다 [9]. 한편으로는, 25-수산화비타민D 결핍이총콜레스테롤수준상승과연관이있음을관찰한연구도있어혈중 25-수산화비타민D의농도와지질대사와의상관관계에대한연구들은아직일관된결과를보이지않고있다 [14-16]. 25-수산화비타민 D는골대사와관련된역할이외에당뇨병과고혈압의유병에도영향을미치는것으로나타나고있으며, 한국성인의혈중비타민D의농도가낮은실정에비추어볼때, 비타민D 부족이영향을미칠수있는질환등에관련된폭넓은연구의필요성이높다고판단된다 [9, 17]. 선행연구에서제1형당뇨병에서 osteocalcin 과카르복시말단펩티드가낮은것으로밝혀졌고, 본연구에서도카르복시말단펩티드와 osteocalcin 의비교적높은상관성을볼때카르복시말단펩티드또한당뇨병과관련하여많은연구가이루어져야한다 [18]. 그외, 대한비만학회의 비만진료지침 2018 에따르면체질량지수는 25 kg /m 2 이상인경우성인비만으로진단되며, kg /m 2 는 비만전단계, kg /m 2 까지 1단계비만, kg /m 2 까지 2단계비만, 그리고 35 kg /m 2 이상부터는 3단계비만 으로진단되는데, 당뇨환자군의평균체질량지수 (24.2±3.3) 는 비만전단계 를보였다 [19]. 체질량지수는비만도를보여주는것으로당뇨의주요위험인자로분류되어왔지만, 본연구에서당뇨의지표중하나로선택된 HbA1c와체질량지수사이에유의한상관관계는없었다 [20]. 또한, 당뇨병환자의골밀도에대한문헌중선별된대표적인 65편결과의메타분석에서는제2형당뇨병에서체질량지수가골밀도의가장중요한결정인자로관찰되었지만, 본연구에서체질량지수와골질을평가하는대표적인표지자로선정된 osteocalcin 의상관관계는유의하지않았다 [1]. 하지만, osteocalcin 과체질량지수의상관관계를알아보는연구에서단순상관분석으로는유의한관계를보이지않았으나다중회귀분석으로분석한결과음의상관관계를보인것을볼때, 혼란요인들을보정하지않은본연구의결과들로상관관계를단언하는것은무리가있다 [6]. 현재사용되는당뇨진단기준에는표준검사법인경구당부하검사, 공복혈당, HbA1c 세가지다. 서로다른혈당대사의상태를반영하기때문에당뇨확진에는모두시행하나, 대규모선별검사에서경구당부하검사는시행의불편함으로인해활용하기에어려움이있다 [21]. 그리하여, HbA1c를당뇨를나타내는지표중하나로선정하였다. Osteocalcin 과 HbA1c 외요인들의선정배경은다음과같다. Osteocalcin 과함께골대사를나타내는대표적인요인중골흡수의특이적표지자인카르복시말단펩티드를비롯한칼슘, 25-수산화비타민D를선택하였다 [22]. 골격성장및유지, 칼슘의항상성유지에필수적인호르몬이고, 골다공증의예방과치료뿐만아니라골격계이외의조직에서도중요한역할을하는비타민D의영양상태는간에서수산화를거친 25-수산화비타민D의혈중농도로평가할수있다. 비타민D는세포증식및세포분화의조절, 면역기능조절, 항암작용등의기능도있음이보고되었고, 당뇨병, 비만및대사증후군과의관련성도있음이보고된바있어그임상적가치에대해서관심이커지고있다 [23, 24]. Osteocalcin 은포도당대사뿐만아니라지질대사와도밀접하게관련이있으므로총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤총 4개의요인을선택하였다 [11]. Osteocalcin 의생성및활성을각각촉진하고억제하는것에는두가지호르몬이관여한다. 그중한가지는인슐린이다. 골흡수자극에반응한 osteocalcin 은골질에서방출되어탈카르복실화를통해활성화된다. 골아세포 (osteoblast) 에서의인슐린전달신호는골세포 (osteocyte) 에의한활성으로 osteocalcin 생성을촉진시키고췌장베타세포의분비를촉진시킨다. 이사이클을억제조절해주는것이바로지방세포유래호르몬인렙틴이다. 렙틴은교감신경에미치는영향을통해 osteocalcin 생성을억제할수있다 [25]. 이런기전들이밝혀지고있는추세와함께동물실험에서는매일 osteocalcin 을주사하여인슐린감수성과포도당내성을부분적으로회복한사례가있다 [26]. 따라서, osteocalcin 은뼈와췌장및지방조직과같은에너지항상성의조절과보다고전적으로연관된기관사이의복잡한신호전달네트워크의일부이므로, 뼈도내분비기관으로서의연구가필요하다. 이연구의제한점은다음과같다. 첫째, 두군을나눈기준을상병코드에의존했기때문에당뇨환자군에서합병증의빈도와관련있는당뇨병이환기간을알수없었다 [27]. 연구대상자 714명가운데정형외과수진자가 701명이었다. 이들은골격계관련수술을위한수술전검사를한환자들이었기때문에정상포도당내성에대한검사는이루어지지않았다. 둘째, 당뇨병을비롯한골다공증관련약의복용여부확인이불가했다. 미국당뇨병학회에서제시한근거에따라 HbA1c 수치 (6.5% 이상 ) 로비당뇨환자군에서일부대상자들을당뇨환자군으로포함시켰으나실제당뇨병이환자가잠복해있을가능성은여전히있다. 셋째, 측정한요인중카르복시말단펩티드는오전 5시에최소치

6 318 Yo-Han Seo and Hee-Young Shin. Correlation between Serum Osteocalcin and Hemoglobin A1c 를갖고오후 2시에최대치를갖는일내변동성이있다고알려져있으나측정시간이동일하지않았다 [28]. 넷째, 성별과연령의차이를고려하지않고분석하였다. 대상자의선정에있어서위와같은현실적인제한점들이있었지만, 본연구는골대사를나타내는물질중하나인 osteocalcin 과당뇨병을대표하는지표중하나인 HbA1c의상관관계에서혼란요인들을보정한결과가유의했다는것을확인하는데에의의가있다고본다. 골대사와당뇨병을일으키는기전에관련된연구들과제 1형당뇨병환자에서 osteocalcin 과 HbA1c의상관관계에관한연구, osteocalcin 과당대사및지질대사의관계에서유전인자를염두에두고종족을기준으로연구대상자를선정한연구등많은연구들이이루어지고있다 [7, 29]. 이러한연구추세와각요인들간의상관관계를볼때향후어떤부분에초점을맞추어연구가이루어져야하는지에대한의견들을고려하여다양한요인들과의연관성에대한많은연구가진행되어야한다. 요약최근골대사와당뇨병발생기전의관계에대해많은연구가진행되고있으며, osteocalcin 이제 2형당뇨병을위한치료법에관련될수있다는것이밝혀지고있다. 따라서본연구는 osteocalcin과 HbA1c의상관관계를알아보고자한다 년 1월 1일부터 2016년 12월 31일까지광주소재한종합병원수진자중 osteocalcin 과 HbA1c 를비롯하여칼슘, 카르복시말단펩티드, 총콜레스테롤, 중성지방, 고밀도지질단백콜레스테롤, 저밀도지질단백콜레스테롤, 25-수산화비타민D, 키, 몸무게를측정한 40세이상의성인총 714명 (70.8±10.4세) 을연구대상자로최종선정하였다. 성별은남자 (452명, 63.3%) 가여자 (262명, 36.7%) 보다많았다. 당뇨환자군에서 osteocalcin과 HbA1c는약한음의상관관계 (r= 0.183, P<0.001) 가있었고, 다른요인들을모두보정했을때에도여전히음의상관관계 (r= 0.251, P<0.001) 가있었다. 본연구는당뇨환자에서의 osteocalcin 과 HbA1c가음의상관관계가있음을보여주었다. 골대사와당대사의생물학적기전및관련요인들이미치는영향을바탕으로골대사와당뇨병발생의상호관계에대한연구가지속되어야한다. Acknowledgements: None Conflict of interest: None REFERENCES 1.Oh KW. Diabetes and osteoporosis. Korean Diabetes J. 2009;33: Han AL, Shin SR, Park SH, Lee JM. Association of hemoglobin A1c with visceral fat measured by computed tomography in nondiabetic adults. J Agric Med Community Health. 2012; 37: Lee YS, Moon SS. The use of HbA1c for diagnosis of Type 2 diabetes in Korea. Korean J Med. 2011;80: Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell. 2010;142: doi.org/ /j.cell Wang Q, Zhang B, Xu Y, Xu H, Zhang N. The relationship between serum osteocalcin concentration and glucose metabolism in patients with Type 2 diabetes mellitus. Int J Endocrinol. 2013; Kim KJ, Kim KK, Hwang IC, Lee KS, Suh HS. The relation of plasma osteocalcin and BMI in subjects who visited a health promotion center of a general hospital. Korean J Obes. 2011; 20: Chen Y, Zhao Q, Du G, Xu Y. Association between serum osteocalcin and glucose/lipid metabolism in Chinese Han and Uygur populations with Type 2 diabetes mellitus in Xinjiang: two cross-sectional studies. Lipids Health Dis. 2017;16: Korean Diabetes Association. Korean diabetes fact sheet 2015 [Internet] Seoul: Korean Diabetes Association; 2015 [cited 2018 Aug 8]. Available from: &page=1&number=215&mode=view&order=&sort= &keyfield=&key=. 9. Bao YQ, Zhou M, Zhou J, Lu W, Gao YC, Pan XP, et al. Relationship between serum osteocalcin and glycaemic variability in Type 2 diabetes. Clin Exp Pharmacol Physiol. 2011; 38: Lipscombe LL, Jamal SA, Booth GL, Hawker GA. The risk of hip fractures in older individuals with diabetes: a population-based study. Diabetes Care. 2007;30: dc Zhou M, Ma X, Li H, Pan X, Tang J, Gao Y, et al. Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals. Eur J Endocrinol. 2009;161: Xuan Y, Sun LH, Liu DM, Zhao L, Tao B, Wang WQ, et al. Positive association between serum levels of bone resorption marker CTX and HbA1c in women with normal glucose tolerance. J Clin Endocrinol Metab. 2015;100: /jc Urano T, Shiraki M, Kuroda T, Tanaka S, Urano F, Uenishi K, et al. Low serum osteocalcin concentration is associated with incident type 2 diabetes mellitus in Japanese women. J Bone Miner Metab. 2017;36: Parfitt AM, Gallagher J, Heaney RP, Johnston C, Neer R,

7 Korean J Clin Lab Sci. Vol. 50, No. 3, September Whedon GD. Vitamin D and bone health in the elderly. Am J Clin Nutr. 1982;36: Auwerx J, Bouillon R, Kesteloot H. Relation between 25-hydroxyvitamin D3, apolipoprotein A-1 and high density lipoprotein cholesterol. Arterioscler Thromb. 1992;12: Chiu KC, Chu A, Go VL, Saad MF. Hypovitaminosis D is associated with insulin resistance and beta cell dysfuntion. Am J Clin Nutr. 2004;79: Kim MY, Kim MJ, Ly SY. Vitamin D intake, serum 25OHD, and bone mineral density of Korean adults: based on the Korea National Health and Nutrition Examination Survey (KNHANES, 2011). J Nutr Health. 2016;49: jnh Starup-Linde J. Diabetes, biochemical markers of bone turnover, diabetes control, and bone. Front Endocrinol (Lausanne). 2013;4: Treatment Guidelines Commission of The Korean Society for The Study of Obesity. Obesity treatment guidelines 2018 [Internet]. Seoul: The Korean Society for The Study of Obesity; 2018 [cited 2018 Aug 8]. Available from: or.kr/html/user/core/view/reaction/main/kosso/inc/data/ type02.pdf. 20. Tentolouris N, Andrianakos A, Karanikolas G, Karamitsos D, Trontzas P, Krachtis P, et al. Type 2 diabetes mellitus is associated with obesity, smoking and low socioeconomic status in large and representative samples of rural, urban, and suburban adult Greek populations. Hormones (Athens). 2012;11: Kwon SY, Na YA. The cutoff value of HbA1c in predicting diabetes and impaired fasting glucose. Korean J Clin Lab Sci. 2017;49: Chubb SA. Measurement of C-terminal telopeptide of type I collagen (CTX) in serum. Clin Biochem. 2012;45: Chung YS, Yoo BW, Oh JE, Lee DC, Lee HS, Cho CY. The relationship between vitamin D levels and chronic diseases. Korean J Clin Geriatr. 2010;11: Holick MF. Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am J Clin Nutr. 2004;79: Ducy P. The role of osteocalcin in the endocrine cross-talk between bone remodelling and energy metabolism. Diabetologia. 2011;54: Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G. Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone. 2012;50: Kim DW, Kim DH. Hemoglobin Alc levels according to duration and complications of diabetes mellitus. The DongGuk Journal of Medicine. 1999;6: Qvist P, Christgau S, Pedersen BJ, Schlemmer A, Christiansen C. Circadian variation in the serum concentration of C-terminal telopeptide of type I collagen (serum CTx): effects of gender, age, menopausal status, posture, daylight, serum cortisol, and fasting. Bone. 2002;31: Maddaloni E, D Onofrio L, Lauria A, Maurizi AR, Strollo R, Palermo A, et al. Osteocalcin levels are inversely associated with Hba1c and BMI in adult subjects with long-standing type 1 diabetes. J Endocrinol Invest. 2014;37:

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%)