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1 312 Pil Seung Kwon and Insoo Rheem. Assessment of Blood Glucose Distribution and Glycemic Control Indicators ORIGINAL ARTICLE Korean J Clin Lab Sci. 2016;48(4): pissn eissn The Assessment of Blood Glucose Distribution according to the Fasting State and Glycemic Control Indicators for Diabetes Screening Pil Seung Kwon 1, Insoo Rheem 2 1 Department of Clinical Laboratory Science, Wonkwang Health Science University, lksan 54538, Korea 2 Department of Laboratory Medicine, Dankook University Hospital, Cheonan 31116, Korea 금식여부에따른혈당치분포와당뇨병선별을위한혈당조절지표의평가 권필승 1, 임인수 2 1 원광보건대학교임상병리과, 2 단국대학교병원진단검사의학과 This study analyzed the distribution of the blood glucose level according to the fasting status. Moreover, a relationship was analyzed between fasting blood glucose level and glycemic control indicators. A total of 707 outpatients, who visited Dankook University Hospital, were included and classified into either the fasting group and the non-fasting group. The mean blood glucose level of each group was calculated and analyzed by sex, age, and clinic. In addition, blood glucose, HbA1c, fructosamine, and 1,5-AG were measured in 153 fasting health check-up patients, and the correlation between the blood glucose level and glycemic control indicators was evaluated. Blood glucose averages between the two groups (non-fasting vs. fasting mg/dl) were different (p<0.05); and the mean difference was lower in women (4.8 mg/dl) than in men (12.2 mg/dl). A significant difference of the median glucose values among the age groups was only observed in the non-fasting group (Kruskal-Wallis test, p<0.01), and not in the fasting group. A 1,5-Anhydroglucitol was estimated to be significantly correlated with the fast blood glucose level in the range of the criteria of impaired fasting glucose (IFG). We presented an assessment of the distribution of blood glucose level in accordance with the fasting status among outpatients, and estimated that 1,5-anhydroglucitol was well correlated with the fasting blood glucose than fructosamine and HbA1c, through the analysis of results of health screening subjects. It is suggested that the use of glycemic indicators that reflect short-term blood glucose control can be used together with the blood glucose measurement in the screening of diabetes mellitus. Key words: Fasting glucose, 1,5-Anhydroglucitol, Glycemic control indicators, Diabetes mellitus Corresponding author: Insoo Rheem Department of Laboratory Medicine, Dankook University Hospital, 201 Manghyang-ro, Dongnam-gu, Cheonan 31116, Korea Tel: Fax: insoo@dankook.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 2016 The Korean Society for Clinical Laboratory Science. All rights reserved. Received: October 22, 2016 Revised 1 st : October 28, 2016 Revised 2 nd : November 1, 2016 Revised 3 rd : November 2, 2016 Accepted: November 2, 2016 서론 20 세기들어와인류는획기적인과학기술의발달과더불어의 학은많은발전을이루었다. 우리나라는그동안경제발전과건강보험제도를통해의료수준의개선이이루어졌고이에따라평균수명이증가해왔다. 유엔의 2008년세계인구현황보고서에따르

2 Korean J Clin Lab Sci. Vol. 48, No. 4, December 면 년한국인의평균수명은 79.4세이었고 OECD 자료에의하면 2013년 81.9세로 11위이다. 이와같은평균수명의증가로사람들은질병의예방특히만성질환의예방에관심이증가하고있다. 당뇨병은고혈압과더불어대표적인만성질환으로다양한혈관및장기에합병증을유발하여예방과적절한치료가중요한질환이다. 고령화시대에서삶의질은중요하며, 이를위한노력의하나로서당뇨병은조기진단은매우필요하다. 당뇨병은인슐린이결핍된종류인제1형과인슐린의저항성, 분비결손이특징인제2 형으로분류된다. 전당뇨병은아직당뇨병의임상증상을나타내지는않으나혈당수준이정상보다증가되어있는상태로내당능장애 (impaired glucose tolerance, IGT) 와공복시포도당장애 (impaired fasting glucose, IFG) 로구분된다 [1-3]. 1997년미국당뇨병학회 (American Diabetes Association, ADA) 는공복시포도당장애선별기준을당뇨병진단에추가하였다 [4]. 당뇨병진단을위한선별검사는혈당농도의측정과일정한기간동안의혈당조절을의미하는혈당조절지표검사로구분된다. 당뇨병진단을위한혈당검사는공복혈당, 임의혈당검사와포도당부하검사 (oral glucose tolerance test, OGTT) 등이있으며혈당조절지표검사에는당화혈색소 (glycated hemoglobin, HbA1c), 프록토사민 (fructosamine), 당화알부민 (glycated albumin) 과 1,5-anhydroglucitol (1,5-AG) 이있다. 당화혈색소는 2, 3개월의혈당조절을반영하며프록토사민과 1,5-AG 는그보다짧은 2, 3주와 1 3 일의혈당조절의결과를반영한다 [5-7]. 당화알부민과 1,5-AG 는식후혈당또는고혈당을더크게반영하는혈당변동성 (glucose fluctuations) 지표로서사용될수있으며, 1,5-AG 는다른혈당조절지표보다단기간의변동성을알수있는혈당변동성지표로서보고되고있다 [7]. 본연구는금식을하지않고내원한환자에대해당뇨병선별이필요한경우에대한대처방법의일환으로시작되었고혈당조절지표의활용을함께분석하였다. 임의혈당과공복혈당의분포차이를비교평가하였고혈당검사와함께시행시추가정보를줄수있는, 단기혈당조절능력을잘반영하는혈당조절지표를선별하였다. 재료및방법 1. 연구대상본연구는외래환자를대상으로금식여부에따른혈당치분포의차이를분석하였고, 건강검진대상자의금식검체에대해혈당과혈당조절지표검사들을시행하여공복혈당과의상관성을평가하였다. 1) 금식여부에따른혈당치분포의평가단국대학교병원에외래진료를목적으로내원하여채혈실을방문한환자중금식여부가확인된 707명을대상으로혈당검사를시행하여금식군과비금식군으로나누어혈당치의차이를비교하였고성별, 연령별, 그리고내과 (internal medicine) 와비내과 (non-internal medicine) 로임상과별차이를평가하였다. 2) 혈당조절지표와공복혈당의상관성분석혈당조절지표와공복혈당의상관성분석은건강검진을목적으로단국대학교병원산업의학과에내원한금식상태의 153명을대상으로혈당, 1,5-AG, 프록토사민과당화혈색소를측정하였다. 2. 검체분석외래환자 707명의혈당검사는환자의전완정맥 (antebrachial vein) 에서검체를채혈하여응고가완료된후, 원심분리한혈청을자동임상화학장비 (747 Automatic Analyzer, Hitachi, Tokyo, Japan) 로표준포도당산화법에의하여측정하였다. 건강검진대상자검체들은혈중포도당농도는 Hexokinase 법, 프록토사민은비색법 (colorimetric assay), 1,5-AG 는효소법의 Lana TM (Japan Chemistry Medicine, Tokyo, Japan) 시약을이용하여 Modular analytics (Roche Diagnostics GmbH, Mannheim, Germany) 로측정하였다. 당화혈색소는 Variant II turbo (Bio-Rad, Hercules, CA, USA) 의 HPLC법으로측정하였다. 3. 평가방법 1) 금식여부에따른혈당치분포의평가외래환자의혈당치분석은금식군과비금식군에서각각평균과중앙값그리고 95% 신뢰구간의혈당치평균구간을추정하였고성별, 연령별및임상과별로그차이를비교하였다. 금식여부에따른혈당치차이의유의성검증은당뇨병환자로추정되는극외치들을포함한분석이므로, 윌콕슨순위합검증 (Wilcoxon rank sum test) 방법으로 5% 유의수준의단측검정을적용하여중앙값차이여부를평가하였다. 그리고연령대에따른중앙값의변화를평가하기위하여비금식군계열과금식군계열각각에서크루스칼왈리스검정 (Kruskal-Wallis test) 을시행하였다. 2) 혈당조절지표와공복혈당의상관성분석당뇨병의혈당진단기준치초과 (>125 mg/dl) 구간, ADA 의공복시포도당장애의선별범위 ( mg/dl) 구간과그이하의정상치구간으로조작적으로정의하여분석하였고혈당및혈당조절지표간상관성은켄달의일치도검정으로평가하였다. 그리고

3 314 Pil Seung Kwon and Insoo Rheem. Assessment of Blood Glucose Distribution and Glycemic Control Indicators 각 혈당조절지표의 평균치 차이를 공복 시 포도당 장애 선별 구간 결 과 과 정상 참고치 내 100 mg/dl 이하 구간에서 비교 평가하였다. 혈 당조절지표의 참고범위는 각각 당화혈색소 %, 프록토사 1. 금식여부에 따른 혈당치의 차이 분석 민 umol/l, 그리고 1,5-AG 14 mg/ml 이상으로, 혈당 금식 여부에 따른 성별, 연령별 및 과별 혈당치 분포는 그림과 같 치의 각 범위 구간에서 혈당조절지표의 양성 결과의 사례 건수를 다(Figs. 1 3). 외래 환자 707명 전체의 혈당의 평균 mg/dl, 산출하는데 적용하였다. 통계 분석 및 유의성 평가는 SAS 9.2 (SAS 중앙값 mg/dl 이었고 비금식 군 혈당 평균은 mg/dl Institute Inc., Cary, NC, USA)를 사용하였다. (중앙값 mg/dl), 금식 군은 mg/dl (중앙값 98.0 mg/dl)로서 유의한 차이가 있었고(Wilcoxon rank sum test, p 0.05) 남자와 여자 그리고 내과와 비내과에서도 비금식 군과 금 Fig. 1. Distribution of glucose level of outpatients on the fasting status by gender. Abbreviation: Q1, the first quartile (25th percentile); Q2, the second quartile (median); Q3, the third quartile (75th percentile). Fig. 2. Distribution of glucose level of outpatients on the fasting status by clinics. Abbreviation: See Fig. 1.

4 Korean J Clin Lab Sci. Vol. 48, No. 4, December Fig. 3. Distribution of glucose level of outpatients on the fasting status by ages. There was a significant difference in the median glucose values among the age groups only in the non-fasting group (Kruskal-Wallis test, p 0.01) and not in the fasting group (p=0.39). *Non-fasting state, Fasting-state. Abbreviation: See Fig. 1. Table 1. Statistics of blood glucose level distribution for outpatients according to the fasting status Category All Sex Male Female Clinic IM Non-IM Fasting status No. of patients Median Mean (95% CI) Mean difference Min Max N* ( ) ( ) N N ( ) ( ) ( ) ( ) N N ( ) ( ) ( ) ( ) *Non-fasting state, Fasting state. was calculated by Wilcoxon rank sum test. Abbreviation: CI, confidence interval; IM, internal medicine; Non-IM, non-internal medicine. 식 군은 유의한 차이가 있었다(Table 1). 평균치 차이는 여자에서 연령대 별 중앙값의 차이가 있는지를 크루스칼 왈리스 검정 4.8 mg/dl로서 남자보다 적었다. 연령군별에 따른 외래 환자의 금 (Kruskal-Wallis test)로 검정한 결과는 비금식 군에서만 연령대 별 식여부에 따른 혈당치의 차이는 Table 2와 같다. 비금식 군과 금식 유의한 차이가 있었고(p 0.01) 금식 군에서는 유의하지 않았다 군 간 혈당치의 차이는 20대까지는 적다고 할 수 있었으나 30대 이 (p=0.39) (Fig. 3). 따라서 금식 여부에 따른 혈당 중앙값의 차이는 후에는 비교적 큰 차이를 보였다. 윌콕슨 순위합 검정에서 20대까 연령이 증가함에 따라 비금식 군의 평균 혈당치가 높아지는 것에 지 금식에 따른 혈당치의 유의한 차이가 없는 것으로 평가되었으나 영향을 받는 것으로 평가하였다. (p 0.05) 사례 건수가 적었다(Table 2, Fig. 3) 세 연령대 의 금식 여부에 따른 평균치 차이 평가에서 p=0.07의 검정 결과는 2. 혈당조절지표와 공복 혈당의 상관성 평가 이 연령대에서 특이적인 양상을 나타냈다기보다는 연구 대상자 수 Table 3은 각 혈당치 구간에 대한 혈당조절지표들의 양성과 음 가 충분하지 못한 경우 표본집단에 따라 통계적 유의성이 달라질 성의 결과치 분포이다. 당뇨병 기준인 126 mg/dl 이상 구간에서는 수 있는 경우로 분석하였다. 모든 지표는 2건의 동일한 사례(145 mg/dl; 389 mg/dl)에서 양

5 316 Pil Seung Kwon and Insoo Rheem. Assessment of Blood Glucose Distribution and Glycemic Control Indicators Table 2. Statistics of blood glucose level distribution for outpatients according to the fasting status by age group Age group Fasting status No. of patients Median Mean (95% CI) Mean difference Min Max 0 9 N* ( ) ( ) N ( ) ( ) N ( ) ( ) N ( ) < ( ) N ( ) ( ) N ( ) < ( ) N ( ) < ( ) *Non-fasting state, Fasting state. was calculated by Wilcoxon rank sum test. Abbreviation: CI, confidence interval. Table 3. Distribution on the results of fasting glucose and glycemic control indicators by the ranges for health check-up subjects Glucose range (mg/dl) Test item 1,5-AG (mg/ml) Fructosamine (umol/l) HbA1c (%) 14 >14 > >6 6 No. by range Positive Negative Positive Negative Positive Negative < > Total 성결과를보였다. 100 mg/dl 이하구간에서 1,5-AG의양성결과치 3 사례의혈당치는 70, 74, 98 mg/dl이었다. 프록토사민은혈당 100 mg/dl 이하구간에서 14건의양성사례를보여주었고공복시포도당장애선별구간 ( mg/dl) 에서는양성사례가없었다. 혈당치 100 mg/dl 이하, 공복시포도당장애선별기준구간 ( mg/dl) 및 126 mg/dl 이상의각구간의공복혈당과각혈당조절지표의기본통계치와분포양상을상자수염그림 (box whisker plot) 으로도식하였다 (Fig. 4). 100 mg/dl 이하구간과공복시포도당장애선별기준구간을대상으로각혈당조절지표결과치를 t-test로검정한결과 1,5-AG 만이의미있는평균치의차이를보였다 (p<0.05) (Table 4). 또한켄달타우일치도검정결과는혈당전체범위에서혈당대 1,5-AG (Kendall s tau= , p=0.0030) 와프록토사민대당화혈색소 (tau=0.1338, p=0.0192) 가의미있는상관성이있었다 (Table 5). 구간별로는혈당치 100 mg/dl 이하구간에서프록토사민대당화혈색소 (tau=0.1405, p=0.0214), 혈당치 mg/dl 구간에서는혈당대 1,5-AG (tau= , p=0.0635), 프록토사민대 1,5-AG (tau=0.3828, p=0.0475) 의상관성이있었다 (Table 6). 따라서평균치분석과상관성검정결과로서공복시포도당장애선별구간에서는혈당조절표지종목들중 1,5-AG 가공복혈당과가장상관성이있는것으로평가하였다. 고찰당뇨병진단을위한혈당기준은당뇨병질환의조기선별의필요성이높아짐에따라그기준이엄격해져왔으며일정기간의혈당치조절을추적하는방법으로혈당조절지표들이활발하게사용되고있다. 2010년 ADA기준은당화혈색소기준 (HbA1c 6.5% 이상 ) 이추가되어혈당조절지표는당뇨병의경과및치료관찰과더불어진단에서도중요한의미를갖게되었다 [8]. 혈당조절지표중가장널리이용되는당화혈색소는 Hb A1의 80% 를차지하는주요분획으로이루어져있어적혈구질환및혈색소이상, 그리고투석환자에서는혈당조절의정확한반영이되지않는다 [9]. 프록토사민, 당화알부민, 1,5-AG 는이와같은당화혈색소검사의적용이불완전한경우에이용될수있다. 당화알부민과 1,5-AG 는혈당변동

6 Korean J Clin Lab Sci. Vol. 48, No. 4, December Fig. 4. Distribution of the level of the fasting blood glucose and the glycemic indicators for health check-up subjects. The average values of 1,5-AG between the ranges of glucose level mg/dl and 100 mg/dl or less were significantly different (p 0.05). Table 4. Independent samples t-test of glycemic indicators according to blood glucose range for health check-up subjects 100 (n=134) Glucose range (mg/dl) Test item 1,5-AG (ug/ml) Fructosamine (umol/l) HbA1c (%) (n=15) Mean SD Mean SD t value * *p Table 5. Correlation between fasting blood glucose and glycemic control indicators for 153 health check-up subjects Glucose tau Glucose 1,5-AG Fructose HbA1c 1 1,5-AG Fructose HbA1c tau tau tau ** * *p 0.05, **p Abbreviation: tau, Kendall rank correlation coefficient. 성을 잘 반영하는 지표로 알려져 있다[7]. 당화혈색소는 2, 3개월의 여 단기적 및 장기적으로 혈당량 조절에 대한 판정이나 당뇨와 관 평균혈당을 반영하는 중기 혈당조절지표로서 사용되고 있으며 련된 합병증 예방을 위한 추적에 유효하다고 보고되고 있다[5,13-16]. [10-12], 1,5-AG는 혈당의 대사상태의 변화에 더 민감하게 반응하 프록토사민은 평균 혈당 또는 식전 혈당을 더 반영한다고 하였고

7 318 Pil Seung Kwon and Insoo Rheem. Assessment of Blood Glucose Distribution and Glycemic Control Indicators Table 6. Correlation between fasting blood glucose and glycemic control indicators on the blood glucose range for health check-up subjects Test Item 1,5-AG Fructose HbA1c Glucose range (mg/dl) No. of Results tau tau tau Overall ** < * > *p<0.05, **p<0.01. Abbreviation: tau, Kendall rank correlation coefficient. [5,17], 프록토사민과당화혈색소는혈당변동성에대한상관성이낮은것으로알려져있다. 1,5-AG 는식후혈당이나높은농도의혈당변화에대한반응성이높고결과치변동폭이넓어치료경과추적시유용하다고보고되었다 [5,7,18-21]. Frattali 등은 1,5-AG 가당뇨병진단목적으로사용될수있다는의견을제시하였고 [22], amanouchi 등은당뇨병검출에있어당화혈색소, 프록토사민보다효과적이라고보고하였으며 [15], Kim 등은 1,5-AG 가경증및중등도당뇨병환자에서공복혈당과당화혈색소는상관관계가있다고보고하였다 [12]. 본연구에서도 1,5-AG 는 100 mg/dl 이하구간의평균치 30.8 ug/ml에서공복시포도당장애의선별혈당구간 ( mg/dl) 의 25.0 ug/ml로감소하여 (p<0.05) 연구대상의혈당조절지표중공복혈당치를가장잘반영하는종목으로 1,5-AG 가평가되었다. 프록토사민은혈당농도 100 mg/dl이하에 14건의양성결과사례를보여주었는데, 문헌보고에따르면프록토사민은혈장내다른물질에따라농도가변화할수있는것으로도알려져있어 [23], 저농도혈당구간에서이러한영향을받았을가능성이추정되었다. 내당능장애는혈당조절능력을평가하는전당뇨병선별기준이지만공복혈당이충분히낮은경우라면경구포도당부하검사를위한임상적판단이어려울수있다. 1,5-AG 는식후혈당이나당부하후혈당치와상관성이있는것으로보고되고있다 [5,7,24,25]. 따라서본연구결과에서 100 mg/dl 이하구간의 1,5-AG 양성결과 3 사례 (70, 74, 98 mg/dl) 는내당능장애선별이필요할수있을것으로사료되었다. 혈당과혈당조절지표의상관성분석을위해시행한, 전체구간에대한켄달타우일치도검정결과에서프록토사민및당화혈색소의상관성이유의하지않게평가된것은연구대상이건강검진대상자로참고치상한 (125 mg/dl) 을벗어나는결과치사례가 4건으로높은농도의결과치들이제외되었기때문으로생각되었다. 검사를위한금식기준은통상 8시간으로알려져있다 [26]. 본연구에서금식여부는채혈환자에게구두질문을통해확인하였으므로금식기준이명확하게적용되지는못하였지만금식에따른혈당 치차이의대체적인경향을파악을하는데도움이되고자하였다. 본연구에서 10대이후연령대가증가함에따라중앙값과 75% 백분위수가높아지는것이추정되어크루스칼왈리스검정을시행한결과비금식군에서만유의한차이가있는것으로평가되었다. 10 대미만연령대가 10대보다중앙값이높게산출 (106.5 vs. 103 mg/dl) 된것은영아기의혈당조절의불완전성에따른것으로추정되며 [27,28], 또한각연령대별의금식군연구대상자수가충분하지못하여추가연구가필요할것으로생각되었다. 저자들은금식여부에따른혈당치분포를파악하기위한연구방법으로평균치또는중앙값의대표값을비교평가하였지만성별, 임상과, 연령대및금식여부에관계없이당뇨병환자가해당군에포함되면변동성요인이될수있기때문에군간대표값차이의근본이유는연령대증가에따라비금식상태에서혈당치가높아지는것에기인한것으로추정되었다. 저자들은금식여부에따른혈당치분포와연령대에따른혈당치변화의통계적인특성을파악하여당뇨병선별진단에추가적인정보를제공하고자하였다. 질환의선별에는개인의개별적특질이중요하므로이를감안한임상적판단이이루어져야하겠다. 당뇨병합병증이나심혈관질환의발생에식후고혈당이실제적인영향을줄수있는것으로알려져, 식후고혈당변화를잘반영하는당화알부민이나 1,5-AG 에대한관심이최근높아지고있다 [5,7,29]. 당뇨병진단검사로서 1,5-AG 검사의우선적인이용에는다양한의견이있지만 [15,22,24], 당뇨병및전당뇨병선별시예민도와특이도를높이는차원에서혈당조절지표를병행사용하는필요성에대한여러보고들이있었다 [23,30,31]. 저자들은당뇨병선별검사로서단기혈당조절능력이나혈당변동성을잘반영하는혈당조절지표의활용이유용할것으로생각하였다. 본연구에서비교분석한혈당조절지표중 1,5-AG 가공복시포도당장애구간에서공복혈당치와유의한상관성이있는것으로평가하였다.

8 Korean J Clin Lab Sci. Vol. 48, No. 4, December 요약 본연구는금식여부에따른혈당치분포차이를분석하였고공복혈당치와혈당조절지표인당화혈색소, 프록토사민, 1,5-AG 의상관성을분석하여전당뇨병선별에필요한추가정보를제공하고자하였다. 단국대학교병원에내원한 707명의외래환자를금식군과비금식군으로나누어혈당검사를시행한후각군의혈당치평균을산출하고성별, 연령별및임상과별결과치분포를분석을하였다. 또한건강검진을목적으로내원한금식상태의 153명에대해혈당치와당화혈색소, 프록토사민, 1,5-AG 을측정하여혈당치와혈당조절지표의상관성을평가하였다. 비금식군의혈당평균치는 mg/dl, 금식군은 mg/dl로서유의한차이가있었고 (p<0.05) 평균치차이는여자가 4.8 mg/dl로서남자의 12.2 mg/dl보다적었다. 연령대에따른중앙값의차이는비금식군에서만유의한차이가있었고 (Kruskal-Wallis test, p<0.01) 금식군에서는유의하지않았다. 공복시포도당장애선별구간에서혈당농도와상관성이높은검사종목은 1,5-AG 로평가되었다. 저자들은금식여부에따른혈당치분포의차이를외래환자를대상으로분석하였으며, 건강검진대상자의결과치분석을통해 1,5-AG 가프록토사민, 당화혈색소보다공복혈당치와유의한상관성이있는것으로평가하였다. 당뇨병선별시혈당측정과함께단기혈당조절능력을반영하는지표가활용될수있을것으로사료된다. Acknowledgements: None Funding: None Conflict of interest: None References 1. World Health Organization. Definition, diagnosis, and classification of diabetes mellitus and its complications: Report of a WHO Consultation. Part 1. Diagnosis and classification of diabetes mellitus. Geneva: World Health Organization; Harris MI, Eastman RC, Cowie CC, Flegal KM, Eberhardt MS. Comparison of diabetes diagnostic categories in the U.S. population according to 1997 American Diabetes Association and World Health Organization diagnostic criteria. Diabetes Care. 1997;20: Gabir MM, Hanson RL, Dabelea D, Imperatore G, Roumain J, Bennett PH, et al. The 1997 American Diabetes Association and 1999 World Health Organization criteria for hyperglycemia in the diagnosis and prediction of diabetes. Diabetes Care. 2000; 23: Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. 1997;20: Dungan KM. 1,5-anhydroglucitol (Glyco-Mark TM ) as a marker of short-term glycemic control and glycemic excursions. Expert Rev Mol Diagn. 2008;8(1): Kim CB. A determination of serum fructosamine in relation to blood glucose and glycosylated hemoglobin in diabetes mellitus. Korean Journal of Medical Technologists. 1989;21: Kim WJ, Park C. Review of the potential glycemic markers glycated albumin and 1,5-anhydroglucitol. J Korean Diabetes. 2012;13: Aldasouqi SA, Gossain VV. Update on diabetes diagnosis: A historical review of the dilemma of the diagnostic utility of glycohemoglobin A1c and a proposal for a combined glucose-a1c Diagnostic Method. Ann Saudi Med. 2012;32(3): Sofronescu AG, Williams LM, Andrews DM, Zhu. Unexpected hemoglobin A1c results. Clin Chem. 2011;57(2): Hom FG, Ettinger B, Lin MJ. Comparison of serum fructosamine vs glycohemoglobin as measures of glycemic control in a large diabetic population. Acta Diabetol. 1998;35: Tahara, Shima K. Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level. Diabetes Care. 1995;18: Kim WJ, Park C, Lee KB, Park SE, Rhee EJ, Lee W, et al. Serum 1,5-anhydroglucitol concentrations are a reliable index of glycemic control in type 2 diabetes with mild or moderate renal dysfunction. Diabetes Care. 2012;35: Dworacka M, Winiarska H. The application of plasma 1,5-anhydro-D-glucitol for monitoring type 2 diabetic patients. Dis Markers. 2005;21: SKim MJ, Jung HS, Hwang-Bo, Cho SW, Jang HC, Kim S, et al. Evaluation of 1,5-anhydroglucitol as a marker for glycemic variability in patients with type 2 diabetes mellitus. Acta Diabetol. 2013;50: amanouchi T, Akanuma, Toyota T, Kuzuya T, Kawai T, Kawazu S, et al. Comparison of 1,5-Anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus. Diabetes. 1991; 40: amanouchi T, Ogata N, Tagaya T, Kawasaki T, Sekino N, Funato H, et al. Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycaemic control. Lancet. 1996;347: Watanabe M, Kokubo, Higashiyama A, Ono, Miyamoto, Okamura T. Serum 1,5-anhydro-D-glucitol levels predict firstever cardiovascular disease: an 11-year population-based cohort study in Japan, the Suita study. Atherosclerosis. 2011; 216(2): Dabrowska AM, Tarach JS, Kurowska M. 1,5-Anhydroglucitol (1,5-AG) and Its usefulness in clinical practice. Medical and Biological Sciences. 2012;26(3): amanouchi T, Ogata N, Tagaya T, Kawasaki T, Sekino N, Funato H, et al. Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycaemic control. Lancet. 1996:347; Suwa T, Ohta A, Matsui T, Koganei R, Kato H, Kawata T, et al. Relationship between clinical markers of glycemia and glucose excursion evaluated by continuous glucose monitoring (CGM). Endocr J. 2010;57: Ryu JR, Ahn JS, Park J, Nam HC, Kim CS. Comparison of

9 320 Pil Seung Kwon and Insoo Rheem. Assessment of Blood Glucose Distribution and Glycemic Control Indicators 1,5-anhydroglucitol and HbA1c as clinical marker of glycemic control in type II diabetes mellitus patients. Korean J Clin Lab Sci. 2002;34: Frattali AL, Wolf BA. 1,5-anhydroglucitol: a novel serum marker for screening and monitoring diabetes mellitus? Clin Chem. 1994; 40: Armbruster DA. Fructosamine: structure, analysis, and clinical usefulness. Clin Chem. 1987;33: Gerstein HC. Fasting versus postload glucose Levels: Why the controversy? Diabetes Care. 2001;24: Robertson DA, Alberti KG, Dowse GK, Zimmet P, Tuomilehto J, Gareeboo H. Is serum anhydroglucitol an alternative to the oral glucose tolerance test for diabetes screening? The Mauritius Noncommunicable Diseases Study Group. Diabet Med. 1993; 10: Sacks DB, Bruns DE, Goldstein DE, Maclaren NK, McDonald JM, Parrott M. Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus. Clin Chem. 2002;48: Kweon S, Han J, Kim DC, Song HS. Effect of preoperative fasting time on blood glucose concentrations in children. Korean J Anesthesiol. 2000;39(4): Kim E. Glucose metabolism and evaluation of hypoglycemia in neonate. Korean J Pediatr. 2007;50: amanouchi T, Inoue T, Ogata E, Kashiwabara A, Ogata N, Sekino N, et al. Post-load glucose measurements in oral glucose tolerance tests correlate well with 1,5-anhydroglucitol, an indicator of overall glycaemic state, in subjects with impaired glucose tolerance. Clin Sci. 2001;101: Parappil A, Doi SA, Al-Shoumer KA. Diagnostic criteria for diabetes revisited: making use of combined criteria. BMC Endocr Disord. 2002;2(1): Kim KW, Kim L, Kim SH, Kim, Cho IJ. Comparison of hemoglobin A1c and fasting blood glucose for diagnosis of diabetes in Korea. Korean J Fam Pract. 2016;6(5):

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