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1 전남의대학술지제 45 권제 3 호 Chonnam Medical Journal Vol. 45, No. 3, pp DOI: /cmj 당뇨병성위마비의예측인자와위배출신티그래피의연관성 전남대학교의과대학내과학교실 이경주ㆍ유경호ㆍ정진욱ㆍ조동혁ㆍ정동진ㆍ정민영 * Correlation between Predictors for Diabetic Gastroparesis and Gastric Emptying Scintigraphy Kyung-Ju Lee, Kyoung-Ho Ryu, Jin-Ook Chung, Dong-Hyeok Cho, Dong-Jin Chung and Min-Young Chung* Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea The objective of this study was to evaluate the prevalence of gastroparesis in diabetic patients with severe upper gastrointestinal symptoms and to examine the predictors of diabetic gastroparesis to improve the efficiency of gastric emptying scintigraphy. Gastric emptying of a solid meal (scintigraphy) was measured in 40 patients with diabetes (10 type 1 and 30 type 2) who had severe upper abdominal symptoms. All patients were evaluated for anthropometry, lipid profiles, glycated hemoglobin, cardiac autonomic neuropathy, and other chronic diabetic complications. Of the 40 patients who underwent scintigraphy, the gastric emptying of solids was delayed in 16 (40%) patients, and 24 (60%) patients had cardiac autonomic neuropathy. The BBV cardiac beat-to-beat variability test score correlated positively with the gastric emptying time [OR=6.78 ( ), p=0.018]. The deep breathing test (abnormal E/I ratio), one of the BBV tests, correlated positively with the gastric emptying rate of solids [OR=7.00 ( ), p=0.025]. However, delayed gastric emptying was not related to the type or duration of diabetes, abdominal symptoms, glycated hemoglobin, body mass index, lipid profiles, or other chronic diabetic complications. Our results suggest that the BBV test, especially the abnormal deep breathing test, is associated with an increased risk of diabetic gastroparesis in diabetic patients with gastrointestinal symptoms. Key Words: Autonomic nervous system deseases; Diabetic neuropathies; Gastroparesis; Gastric emptying 서 당뇨병성위마비는당뇨병환자들의 30 40% 정도에서발생되는비교적흔한합병증으로무증상인경우도있으나 게재결정 : 2009 년 11 월 25 일 * 교신저자 : 정민영, , 전남대학교의과대학내과학교실, Phone: , FAX: , mychung@chonnam.ac.kr 론 오심, 구토및복부팽만감등다양한증상을보일수도있으며증상이심한경우에는식후저혈당을비롯하여혈당조절에어려움을초래할수있다. 1-5 당뇨병성위마비의표준적인진단법은위배출신티그래피 (gastric emptying scintigraphy) 검사를이용하여위배출시간을측정하는방법으로주로상부위장관증상을호소하는당뇨병환자에서당뇨병성위마비의여부를진단하기위 175

2 176 전남의대학술지제 45 권제 3 호 2009 해시행되고있다. 6 그러나많은연구들은상부위장관증상과당뇨병성위마비사이에관련성이낮음을보고하고있다. 2-4 Tomi 등 7 은당뇨병환자를대상으로상부위장관증상의유무에따라위배출시간을측정하였고증상의유무에관계없이 41.1% 에서위배출시간의지연을보였으며위배출시간과상부위장관증상과의관련성이낮다고하였고, Punkkinen 등 8 도상부위장관증상을가진환자들을대상으로위배출시간을측정하여증상과당뇨병성위마비의관련성이낮음을보고하였다. 그외에도많은연구들이비슷한결과를보고하고있어이로인하여상부위장관증상을호소하는모든당뇨병환자에서위배출신티그래피검사를시행해야하는지에대한의문이제기되고있다. 그리고이러한관점에서상부위장관증상을동반한당뇨병환자가당뇨병성위마비에이환되어있는지여부를예측할수있는임상적인인자들에대한연구들이보고된바있다. Koch와 Uwaifo 9 는혈당조절상태에따른위배출시간의변화를보고하였고, Darwiche 등 10 은자율신경병증과위마비의관련성을보고하였다. 그러나아직까지당뇨병환자에서위배출시간의지연과관련성을보이는인자들에대해서는논란이있으며이에대한연구가더필요한실정이다. 본연구에서는상부위장관증상을호소하는당뇨병환자들을대상으로상부위장관증상과위배출지연과의관계를살펴보고위배출신티그래피의효율적사용을위한당뇨병성위마비와관련된예측인자를조사하고자하였다. 대상및방법 1. 대상 2004년 3월부터 2008년 9월까지입원이필요한심한상부위장관증상으로전남대학교병원에내원하였던 307명의당뇨병환자들을대상으로후향적으로조사하였다. 대상당뇨병환자중위장또는대장내시경검사상이상소견이있거나다른위장관질환으로진단받았거나위장관증상과유사한증상을유발할수있는순환기계질환등을동반하고있었던 242명의환자를제외하고위배출신티그래피검사를시행하였던환자는총 65명이었다. 이중에서내원시에요독증상이있었거나최근에신기능의급격한악화를보였던환자또는신경정신계약물을복용하고있는환자들을제외한 40명의환자를대상으로하였다. 2. 방법문진을통하여당뇨병의병형과유병기간, 흡연력, 고혈압, 고지혈증등의과거력및약물력등을조사하였다. 15분이상휴식을취한상태에서수축기및이완기혈압을측정하였고, 비만도측정을위하여신체계측학적방법으로신장및체중을측정하였으며, 이를통하여체질량지수 (body mass index, BMI) 를계산하였다. 혈액학적검사로는 8시간공복후채혈하여총콜레스테롤 (enzymatic colorimetry, AU5400, Olympus, Japan), 중성지방 (glycerol-phosphate-oxidase method, AU5400, Olympus, Japan), 고밀도지단백콜레스테롤 (immunoinhibition method, AU5400, Olympus, Japan), 저밀도지단백콜레스테롤 (direct selective method, AU5400, Olympus, Japan) 을측정하였으며혈당조절의지표로당화혈색소를측정하였다. 또한당뇨병증신증에대한뇨알부민배설률 (urine albumin excretion, UAE) 과 BUN (blood urea nitrogen), 크레아티닌을측정하였다. 고형상위배출신티그래피 (solid phase gastric emptying scintigraphy) 검사는 15분간격으로 120분까지위에남아있는음식물의양을측정하여음식물섭취직후위의최대음식물양에대한비인위잔류율 (FR: fraction of mealretention in the stomach) 을계산함으로써위배출지연정도를측정하였다. 99m Tc-DTPA 18.5 MBq이들어있는고형식을먹인후 120분까지앙와위에서전면상을촬영하였고영상획득은 SPECT 스캐너를이용하였다. 국내 18개대학에서정상위배출시간을측정하기위해시행한연구에서정상위배출시간은평균 T 1/2 86.2±30분으로보고된바있어본연구에서는위배출시간 T 1/2 >90분을비정상으로정의하였다. 6 자율신경기능검사는 Monitor one ndx (QMed, Inc. Eatontown, NJ) 기계를이용하여심박수의변화를측정하는 BBV (cardiac beat-to-beat variability) 검사로평가하였고, 검사시행전에항우울제, 카페인, 흡연, 항히스타민제, 베타차단제등자율신경기능검사에영향을줄수있는약제를 48시간전부터중단하였다. BBV 검사항목으로는호기와흡기시 (deep breathing test, E/I 비 ), 발살바수기시 (valsalva maneuver test), 체위변화시 (postural test, 30:15 비 ) 심박동수의변화를측정하였다. E/I 비는앉은자세에서흡기와호기시심박수의변화와비율을보는검사로분당 6 회의속도로깊게숨을쉬면서호기시가장긴 R-R 간격의

3 이경주외 5 인 : Diabetic Gastroparesis and Gastric Emptying Scintigraphy 177 평균값을흡기시가장짧은 R-R 간격의평균값으로나눈수치로정의하였다. 발살바수기시에는앉아서 mouthpiece 로공기를불면서 15초정도 40 mmhg 압력을유지하면서 R-R 간격을측정하였고총 3회를시행하였으며수기시행후최대 R-R 간격과수기시행중최소 R-R 간격을비교하여 1.1 이하시비정상으로정의하였다. 체위변화검사는누웠다가앉으면서시행하는검사로정상적으로누운자세에서일어나면사람의심박동은 15회빨라지고후에 30회느려지므로 30회시기의 R-R 간격과 15회시 R-R 간격을비교하여 1.0 이하인경우를비정상으로하였다 각각의세가지항목에대하여정상은 0점, 경계형은 1점, 비정상은 2점으로계산하였고자율신경병증은세가지항목의점수를모두합산하여 3점이상인경우로정의하였다. 그리고개별적으로세가지검사와위마비의연관성을평가한경우에는경계형을비정상으로정의하였다. 3. 분석방법모든자료는평균값 ± 표준편차및퍼센트로표시하였다. 통계학적유의성검증은 SPSS (Statistical Package for Social Science, Version 15.0, Chicago, U.S.A) 를사용하여연속변수의평균치비교는독립표본 t검정, 비연속적변수는교차분석을시행하였고, p값이 0.05 미만이면통계적으로유의한것으로평가하였다. 위마비의위험인자분석을위해서는로지스틱회귀분석을시행하였고, 단변량분석에서 p<0.05인경우다변량분석을시행하였다. 결과 1. 연구대상자의일반적인특성연구대상자의평균연령은 52.5±16.8세, 당뇨병의평균유병기간은.3±8.0년이었다. 당뇨병의병형은제2형당뇨병환자가 30명으로 75.0% 를차지하고있었고전체대상자중에인슐린치료를하고있는환자가 65.3% 포함되어있었다. 체질량지수는 22.08±2.86 kg/m 2 ( 전체환자중 6명이체질량지수 25.0 kg/m 2 이상 ) 으로비교적비만을보인환자는적었고평균당화혈색소는 8.49±2.75% 이었다. 혈중지질농도에대한검사에서총콜레스테롤 ±43.39 mg/dl, 중성지방 ±80.01 mg/dl, 저밀도지단백콜레스테롤 0.65±63.70 mg/dl, 고밀도지단백콜레스테롤 52.52± mg/dl을보였다 (Table 1). Table 1. Clinical characteristics of subjects Characteristics n=40 Age (years) Sex (M/F) Duration of diabetes (years) Type of diabetes (Type 1/Type 2) Current Treatment method (Insulin/OHA only) Current smoking (n) Body mass index (kg/m 2 ) HbA 1C (%) Total cholesterol (mg/dl) Triglyceride (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) UAE (mg/gcr) Blood urea nitrogen (mg/dl) Creatinine (mg/dl) 52.5± /26.3±8.0 10/30 26/ ± ± ± ± ± ± ± ± ±0.84 Values are mean±sd. OHA, oral hypoglycemic agents; HDL, high density lipoprotein; LDL, low density lipoprotein; UAE, urinary albumin excretion. 2. 위배출시간과임상적인요인들과의상관관계 당뇨병성위마비에영향을줄수있는여러임상적인요인들과고형상위배출신티그래피검사상위배출시간과의상관관계를보았을때 BUN (r=0.347) 이통계적으로유의한상관관계를보였으며, 당뇨병의유병기간, 체질량지수, 당화혈색소, 콜레스테롤농도, 크레아티닌, 뇨알부민배설률등은유의한상관관계를보이지않았다 (Fig. 1). 3. 위배출시간의지연유무에따른심혈관계자율신경병증의비교 전체 40명의모든환자들에서위배출신티그래피검사를시행하였고위배출시간에따라 T 1/2 이 90분이상을보이는환자들을위배출시간이지연된군 (n=16) 으로, T 1/2 이 90 분미만인환자들을위배출시간이정상인군 (n=24) 으로나누어심혈관계자율신경검사의결과를비교하였다. 위배출시간이지연된군에서 BBV 검사결과상비정상이 81% 로정상인군에서 45% 에비하여높게관찰되었다 (p= 0.02). 그러나심혈관계자율신경검사에포함된 3가지검사를각각따로비교하였을때위배출시간이지연된군에서 deep breathing test에서비정상인결과가통계적으로유의하게더많이관찰되었으나 (p=0.04), valsalva maneuver test (p=0.71) 와 postural test (p=0.74) 상에서는유의한차이가관찰되지않았다 (Table 2).

4 178 전남의대학술지제 45 권제 3 호 2009 Fig. 1. Correlation between clinical parameters and gastric emptying time. Table 2. Correlation between cardiovascular reflex tests and gastric emptying time Deep breathing test Valsalva test Posture test BBV test (n=27) (n=) (n=30) (n=10) (n=15) (n=25) (n=24) (n=16) Delayed group* (n=16) 14 (35.0%) 2 (5.0%) 3 (7.5%) 7 (17.5%) 9 (22.5%) 3 (7.5%) group (n=24) 11 (27.5%) 17 (42.5%) 7 (17.5%) 8 (20.0%) 16 (40.0%) 11 (27.5%) p value *Group with patients presenting delayed gastric emptying time of solids; Group with patients presenting normal gastric emptying time of solids; BBV: cardiac beat-to-beat variability; Total score of >3 was taken to indicate autonomic neuropathy. 4. 위배출시간의지연유무에따른임상적인특징의비교위배출시간이정상인군 (n=24) 과지연된군 (n=16) 으로나누어기타임상적특징들을비교하였으나, 두군사이에당뇨병의병형및유병기간과치료방법에있어서의유의한차이는보이지않았으며, 체질량지수, 당화혈색소, 총콜레스테롤, 중성지방, 저밀도지단백콜레스테롤및고밀도지단백콜레스테롤에있어서도유의한차이가없었다. 당뇨병성신경병증을제외한만성합병증의유무를두군간에비교하였을때당뇨병성신증에대한검사상 BUN, 크레아티닌및뇨알부민배설율에있어서유의한차이를보이지않았고, 당뇨병성망막증의유병률에도유의한차이를보이지않았다 (Table 3). 5. 심혈관계자율신경병증의유무에따른위배출시간지연의위험도비교 BBV 검사와그에포함되어있는 deep breathing test에대하여환자의연령, 당뇨병의병형및유병기간, 흡연력, 당화혈색소, 체질량지수, 혈청지질농도를보정하여다중회귀분

5 이경주외 5 인 : Diabetic Gastroparesis and Gastric Emptying Scintigraphy 179 Table 3. Comparison of clinical characteristics between groups with and without diabetic gastroparesis Variables Sex (Men/Women) Type of diabetes (Type 1/Type 2) Current Smoker Insulin Treatment Age (years) BMI (Kg/m 2 ) Duration of diabetes (years) HbA 1C (%) Total cholesterol (mg/dl) HDL-cholesterol (mg/dl) LDL-cholesterol (mg/dl) Triglyceride (mg/dl) UAE (mg/gcr) BUN (mg/dl) Creatinine (mg/dl) Delayed group* (n=16) 4/12 6/10 (81.3%) 11 (68.8%) 48.6± ±3.27.1± ± ± ± ± ± ± ± ±0.01 group (n=24) 10/14 4/20 21 (87.5%) 15 (62.5%) 55.2± ±2.59.4± ± ± ± ± ± ± ± ±0.14 p value * Group with patients presenting delayed gastric emptying time of solids; Group with patients presenting normal gastric emptying time of solids; BMI, body mass index; HDL, high density lipoprotein; LDL, low density lipoprotein; UAE, urinary albumin excretion; BUN, blood urea nitrogen. 석을시행하였다. 위배출시간을지연시키는인자로는 BBV 검사 (OR=6.73, 95% CI; 1.53~30.04) 와 deep breathing test (OR=7.00, 95% CI; 1.27~38.35) 의위험도가통계적으로유의하게높은것으로나타났다 (Table 4). 고 당뇨병환자들이흔히경험하는상부위장관증상은연하곤란, 위역류로인한흉통에서오심, 구토, 복부팽만감까지다양하다. 원인으로는일반적으로당뇨병성위마비를위심하는경우가많으나, 현재까지상부위장관증상과당뇨병성위마비와의관련성에대해서많은연구들이보고되었고대부분의연구들에서증상과위마비간에연관성이낮은것으로나타났다. 본연구에서는입원치료를받아야할정도로상부위장관증상의정도가심한당뇨병환자들이대상이었음에도불구하고위마비진단의표준적인검사인위배출신티그래피검사상 16명 (40.0%) 의환자에서만이위배출시간의지연을보여일반적인당뇨병환자에서보이는위마비의 찰 Table 4. Predictors for delayed gastric emptying time Predictors Cardiac autonomic neuropathy (BBV test) Deep breathing test (E/I ratio test) Gastric emptying time OR (range) 6.78 ( ) 7.00 ( ) p value Multiple regression analysis, p <0.05. Model includes age, smoking habit, type and duration of diabetes, body mass index, urinary albumin excretion, blood urea nitrogen, LDL-cholesterol, and HDLcholesterol. 이환율과비슷한결과를보였다. 따라서이는상부위장관증상의유무뿐만아니라상부위장관증상의중증도도당뇨병성위마비와의관련성이낮음을보여주는결과라고할수있다. 위배출신티그래피검사는위배출시간을측정하여위마비를진단하는표준적인검사로고형식 (solid) 과유동식 (liquid) 검사로나누어져있다. 당뇨병환자에서는유동식검사에서정상적인위배출시간을보이더라도고형식검사에서는위배출시간이지연되는경우도있고, 그반대의경우도가능하다. 그러나위마비를진단하는데있어서일반적으로고형식위배출신티그래피검사가민감도에있어더우수함이알려져있어당뇨병성위마비의진단에일반적으로가장널리이용되고있다. 6 Jones 등 15 은자율신경검사와고형식및유동식위배출신티그래피검사의관련성을연구하여자율신경병증이유동식보다는고형식의위배출상태를민감하게반영하는검사임을보고한바있다. 이에따라본연구에서도검사의효율성을고려하여고형식위배출신티그래피검사를이용하였다. 그러나상부위장관증상과당뇨병성위마비와의연관성이낮은것으로알려져있고위장관증상을호소하는당뇨병환자에서증상의원인이당뇨병성위마비외에도소화성궤양, 역류성식도염에서부터위장관증상을유발하는약물의복용, 순환기계질환, 또는신경정신과적문제에이르기까지다양할수있으므로당뇨병성위마비의진단을위하여조기에위배출신티그래피검사를시행하는것은검사의효율성에있어서적절하지않을수있다. 이에대하여본연구에서는위장관증상을호소하는당뇨병환자에서위장및대장내시경검사의시행과약물및신경정신과적문제에대한조사등위장관증상을유발할수있는다른원인들이먼저배제된경우에상부위장관증상이당뇨병성위마비임을나타낼수있는예측인자들이어떠한것들이있는지알아봄으로써위배출신티그래피검

6 180 전남의대학술지제 45 권제 3 호 2009 사의효율성을높이는데도움을얻고자하였다. 당뇨병성위마비에영향을미치는인자들에대한많은연구들이보고되어있으며, 연구된인자들로는환자의연령, 성별, 당뇨병의병형및유병기간, 흡연력, 체질량지수, 당뇨병성자율신경병증을포함한당뇨병성만성합병증에대한검사등이있다. 그중에서도특히혈당조절상태나자율신경병증과당뇨병성위마비와의관련성에대한연구가많이시행되었다. 9-11,15-21 본연구에서환자의성별, 연령, 당뇨병의병형및유병기간은당뇨병성위마비와유의한관련성을보이지않았다. Camilleri 20 는장기간의유병기간을가진당뇨병환자들이최근에진단받은당뇨병환자들과비교하여위마비의이환율이높음을제시하였으나본연구에서는대상환자들의당뇨병유병기간이평균.3년이었고당뇨병성위마비의유무에따라유병기간에유의한차이를보이지않았다. 이는대상이되는환자의숫자가비교적적었고대부분당뇨병의유병기간이긴환자들이많았음이제한점으로작용할수있다. 당뇨병에서혈당의상승은위배출을지연시키고, 혈당의감소는위배출을촉진시키는것으로알려져있고혈액내의급격한혈당변화가위배출시간에영향을미친다는연구결과들이있다 Lydon 등 11 은당화혈색소가위배출시간과유의한관련성이없다고주장하였으며 Schvarcz 등 21 은제1형당뇨병환자에서인슐린주입후유발된저혈당은위배출시간을감소시킨다는결과를보고하였다. 본연구에서는혈당조절지표인당화혈색소를측정하여혈당조절정도와당뇨병성위배출사이의관련성을조사하였으나유의하지않았으며이는당화혈색소가급성적인혈당변화보다는비교적만성적인혈당조절을의미하는지표임을고려할때본연구가주로만성적인위장관증상이아닌급성위장관증상을호소하여내원한환자들을대상으로하였기때문일것으로생각된다. 당뇨병성위마비는자율신경병증과밀접한관련이있음이밝혀져있으며자율신경병증이위마비의중요한병태생리로잘알려지고있다. 20 장관신경계장애, 자가면역 ( 가스트린, 위벽세포항체 ) 반응등도당뇨병성위마비와관련되어있음이보고되고있으나아직이에대해서는정확히알려져있지못하다. 22 또한상부위장관의자율신경계장애는자가미주신경절단 (autovagotomy) 에의한것으로설명되기도하지만위배출시간의지연을보이는당뇨병환자에서미주신경의형태학적인이상이없다는연구가보고되기도하여이에대해서도아직정확히밝혀져있지않다. 23 자율신경병증을객관적으로평가할수있는방법은다양하며그중에서특히심혈관계자율신경기능검사가널리이용된다. 11 심혈관계자율신경기능검사는일반적으로심박동수의변이성과혈압의변동을통하여평가할수있고, 그결과를해석하는방법은연구자들마다조금씩차이를보인다. 10,11,14,22 여러검사항목에서하나라도비정상이나오는경우에자율신경병증이있는것으로판단하거나, deep breathing test (E/I ratio) 검사만을시행하여이상이있는경우에자율신경병증이있음을진단한연구도있었으나일반적으로각각의검사항목결과를점수화한후합산하여자율신경병증이있음을진단하는방법이많은연구들에서가장널리이용되었다. 본연구에서도이방법에따라자율신경병증을진단하였고당뇨병성자율신경병증이당뇨병성위마비의유의한예측인자라는결과를보였다. 그러나 deep breathing test, valsalva maneuver test, postural test 등 3가지항목들에있어서검사항목들간에자율신경병증에대한진단적인차이가많음을고려하여각각의검사항목들과당뇨병성위마비와의연관성을평가하였고, 이중에서특히 deep breathing test가다른검사항목들에비하여유의한연관성을보여주었다. Deep breathing test는자율신경계중에서특히부교감신경기능을보다민감하게평가하는검사로알려져있고, 당뇨병성위마비의병태생리가부교감신경중의하나인미주신경의자가절단 (autovagotomy) 으로설명되어지고있음을고려할때, 부교감신경을민감하게측정할수있는 deep breathing test가위마비와특히연관성이높은결과를설명해줄수있는병태생리적기전으로판단된다. 12,20 본연구는심한위장관증상을호소하는입원환자들만을대상으로후향적인연구를시행하였고추후에환자들에대한추적관찰이이루어지지않은점이제한점이될수있으며일반적으로외래에서가장흔히접하는경증또는증등도의위장관증상을호소하는당뇨병환자들에게본연구의결과를그대로적용할수있을지에대해서는향후에추가적인연구가필요할것으로판단된다. 그리고허혈성심질환의증상이위장관증상과유사하게나타날수있음이여러연구들에서보고된바있다. 24,25 따라서위장관증상으로위배출신티그래피검사를시행하여정상으로결과가나오더라도추후에위장관증상과유사한증상을보일수있는허혈성심질환등의다른질환들에대한추가적인확인이필요할것으로판단된다. 본연구에서도위배출신티그래피검사에서정상으로보였던 24명의환자들중 3명에서내원당시에심전도나심장초음파검사에서는이상이없었으나경과

7 이경주외 5 인 : Diabetic Gastroparesis and Gastric Emptying Scintigraphy 181 관찰중에협심증등이동반된것으로확인된바있어내원초기에나타났던위장관증상이허혈성심질환에의한것이었을가능성을배제할수없었다. 결론적으로심한상부위장관증상을가진당뇨병환자에서심장자율신경계검사, 특히심호흡시심박수의변화 (E/I 비 ) 에이상을보이는경우에는당뇨병성위마비의위험도가증가하므로위배출신티그래피검사와같은적극적인검사가필요할것으로사료된다. References 1. Horowitz M, Maddox AF, Wishart JM, Harding PE, Chatterton BE, Shearman DJ. Relationships between oesophageal transit and solid and liquid gastric emptying in diabetes mellitus. Eur J Nucl Med 1991;18: Keshavarzian A, Iber FL, Vaeth J. Gastric emptying in patients with insulin-requiring diabetes mellitus. Am J Gastroenterol 1987;82: Wegener M, Börsch G, Schaffstein J, Luerweg C, Leverkus F. Gastrointestinal transit disorders in patients with insulin-treated diabetes mellitus. Dig Dis 1990;8: Annese V, Bassotti G, Caruso N, De Cosmo S, Gabbrielli A, Modoni S, et al. Gastrointestinal motor dysfunction, symptoms and neuropathy in non insulin-dependent (type 2) diabetes mellitus. J Cli Gastroenterol 1999;29: Jones KL, Horowitz M, Wishart MJ, Maddox AF, Harding PE, Chatterton BE. Relationship between gastric emptying, intragastric meal distribution and blood glucose concentrations in diabetes mellitus. J Nucl Med 1995;36: Yoon MK, Hwang KH, Choe WS, Lee BI, Lee JS. Reducing the scan time in gastric emptying scintigraphy by using mathematical models. Korean J Nucl Med 2005;39: Tomi S, Plazińska M, Zagórowicz E, Ziólkowski B, Muszynski J. Gastric emptying disorders in diabetes mellitus. Pol Arch Med Wewn 2002;108: Punkkinen J, Färkkilä M, Mätzke S, Korppi-Tommola T, Sane T, Piirilä P, et al. Upper abdominal symptoms in patients with type 1 diabetes: unrelated to impairment in gastric emptying caused by autonomic neuropathy. Diabet Med 2008;25: Koch CA, Uwaifo GI. Are gastrointestinal symptoms related to diabetes mellitus and glycemic control? Eur J Gastroenterol Hepatol 2008;20: Darwiche G, Almér LO, Björgell O, Cederholm C, Nilsson P. Delayed gastric emptying rate in type 1 diabetics with cardiac autonomic neuropathy. J Diabetes Complications 2001;15: Lydon A, Murray C, Cooke T, Duggan PF, O'Halloran D, Shorten GD. Evaluation of standard haemodynamic tests of autonomic function and HbA1C as predictors of delayed gastric emptying in patients with type 1 diabetes mellitus. Eur J Anaethesiol 2000;17: Agelink MW, Malessa R, Baumann B, Majewski T, Akila F, Zeit T, et al. Standardized tests of heart rate variability: normal ranges obtained from 309 healthy humans, and effects of age, gender and heart rate. Clin Auton Res 2001;11: Bannister R. Autonomic failure. Textbook of Clinical Disorders of The Autonomic Nervous System. 4th Oxford. Oxford University Press. 1999; Ko SH, Kwon HS, Lee JM, Kim SR, Cho JH, Yoo KD, et al. Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus. J Korean Diabetes Assoc 2006;30: Jones KL, Russo A, Stevens JE, Wishart JM, Berry MK, Horowitz M. Predictors of delayed gastric emptying in diabetes. Diabetes care 2001;24: Buysschaert M, Moulart M, Urbain JL, Pauwels S, de Roy L, Ketelslegers JM, et al. Impaired gastric emptying in diabetic patients with cardiac autonomic neuropathy. Diabetes Care 1987;10: Fraser RJ, Horowitz M, Maddox AF, Harding PE, Chatterton BE, Dent J. Hyperglycaemia slows gastric emptying in type 1 (insulin dependent) diabetes mellitus. Diabetologia 1990;33: Samsom M, Akkermans LM, Jebbink RJ, van Isselt H, van Berge-Henegouwen GP, Smout AJ. Gastrointestinal motor mechanisms in hyperglycemia induced delayed gastric emptying in type 1 diabetes mellitus. Gut 1997;40: Schvarcz E, Palmér M, Aman J, Horowitz M, Stridsberg M, Berne C. Physiological hyperglycaemia slows gastric emptying in normal subjects and patients with insulin dependent diabetes mellitus. Gastroenterology 1997;1: Camilleri M. Clinical practice. Diabetic gastroparesis. N Engl J Med 2007;356: Schvarcz E, Palmér M, Aman J, Lindkvist B, Beckman KW. Hypoglycaemia increases the gastric emptying rate in patients with type 1 diabetes mellitus. Diabet Med 1993;10: De Block CE, De Leeuw IH, Pelckmans PA, Callens D, Máday E, Van Gaal LF. Delayed gastric emptying and gastric autoimmunity in type 1 diabetes. Diabetes Care 2002;25: Yoshida MM, Schuffler MD, Sumi SM. There are no morphological abnormalities of the gastric wall or abdominal vagus in patients with diabetic gastroparesis. Gastroenterology 1988;94: DeVon HA, Ryan CJ, Ochs AL, Shapiro M. Symptoms across the continuum of acute coronary syndromes: differences between women and men. Am J Crit Care 2008;17: Zhang QT, Hu DY, Yang JG, Zhang SY, Zhang XQ, Liu SS. Public knowledge of heart attack symptoms in Beijing residents. Chin Med J (Engl) 2007;120:

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%)