대한안과학회지 2017 년제 58 권제 9 호 J Korean Ophthalmol Soc 2017;58(9):1050-1057 ISSN 0378-6471 (Print) ISSN 2092-9374 (Online) https://doi.org/10.3341/jkos.2017.58.9.1050 Original Article 안저검사에서이상이발견되어당뇨병을새롭게진단받은환자의임상분석 Clinical Analysis of Newly Diagnosed Diabetes Mellitus Patients by Abnormal Fundus Examination 최화수 김성진 박종석 Hwa Su Choi, MD, Sung Jin Kim, MD, Jong Seok Park, MD, PhD 을지대학교의과대학을지병원안과 Department of Ophthalmology, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, Korea Purpose: To investigate the clinical analysis of newly diagnosed diabetes mellitus (NDM) patients with abnormal fundus examination at the first visit. Methods: This retrospective study utilized the first visit medical records of 15 patients (30 eyes) who were diagnosed with NDM from February 2011 to October 2016. Results: Patients were divided into 3 groups: 1) diabetic retinopathy group including proliferative diabetic retinopathy (PDR) (3) and severe non-proliferative diabetic retinopathy (NPDR) (1); 2) retinal vascular disease group including central retinal vein occlusion (CRVO) (1), branch retinal vein occlusion (1), vitreous hemorrhage with CRVO (1) and macular edema (1); and 3) other retinal disease group including vitreous hemorrhage due to choroidal neovascular rupture (1), exudative age-related macular degeneration (3), central serous chorioretinopathy (2), and macular hole (1). All 3 PDR patients had latent autoimmune diabetes in adults (type 1.5 diabetes). The remaining 12 patients had type 2 diabetes. Three patients showed mild NPDR in the opposite eye and the other 9 patients did not have diabetic retinopathy in the opposite eye. Onset age, HbA1C and proteinuria were significantly different between the diabetic retinopathy group and the other retinal disease group (p = 0.006, p = 0.012 and p = 0.006, Mann-Whitney test). Conclusions: In patients with various retinal diseases, early detection of NDM could be achieved by performing fundoscopic imaging and systemic examination as well as basic ophthalmologic examination. In addition, patients with diabetic retinopathy should be treated promptly through ophthalmology and internal medicine consultation. For the retinal vascular disease and other retinal disease groups, not only treatment for ophthalmic diseases, but also education about diabetes treatment are important. J Korean Ophthalmol Soc 2017;58(9):1050-1057 Keywords: Diabetic retinopathy, HbA1C, Latent autoimmune diabetes in adults, Newly diagnosed diabetes mellitus Received: 2017. 6. 29. Revised: 2017. 8. 18. Accepted: 2017. 9. 5. Address reprint requests to Jong Seok Park, MD, PhD Department of Ophthalmology, Nowon Eulji Medical Center, Eulji University, #68 Hangeulbiseok-ro, Nowon-gu, Seoul 01830, Korea Tel: 82-2-970-8269, Fax: 82-2-970-8272 E-mail: pjs4106@eulji.ac.kr * Conflicts of Interest: The authors have no conflicts to disclose. 당뇨병환자는진단당시에다뇨, 다갈, 체중감소, 생식기의가려움, 구내염및시력장애등고혈당에의한증상들을보인다. 1 이러한증상들은당뇨병을진단하는데중요한역할을하고있으며, 증상이없는경우가 31.2%, 증상을보이는경우는 69.8% 정도로알려져있다. 증상이있는환자들에서그빈도를보면, 다갈 (63.7%), 피로감 (61.0%), 다뇨 (53.9%), 체중감소 (34.8%), 시력장애 (24.9%) 등으로보고 c2017 The Korean Ophthalmological Society This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. 1050
- 최화수외 : 안저검사로진단한당뇨환자의임상분석 - 하였다. 1,2 새롭게진단된당뇨병 (newly diagnosed diabetes mellitus, NDM) 은혈당이당뇨병의진단기준에해당하나아직당뇨병으로진단받지않은환자에서처음으로당뇨병을새로진단한경우를말하며, 이환자들에서안과안저검사상당뇨망막병증의유병률은 10-20% 정도로알려져있다. 3-5 이러한 NDM 환자에게서당뇨망막병증이발생하는데영향을주는요인들로는나이, 당화혈색소 (HbA1C), 높은공복혈당, 중성지방및저밀도지단백콜레스테롤의증가, 고혈압등이연관이있는것으로보고되고있다. 3,6-8 또한당뇨병이망막중심정맥폐쇄나망막분지정맥폐쇄와같은망막혈관질환들의발병에영향을주는것으로알려져있다. 9,10 당뇨망막병증과더불어당뇨병은그유무에따라환자의치료계획및치료효과가판이하게달라질수있다. 하지만당뇨병의과거력을인지하지못하고있는환자가시력장애를주소로안과에초진하였을때, 특징적인당뇨망막병증의소견을보이지않는다면기본적인안과검사만으로당뇨병의유무를알아차리기란쉽지않은일이다. 이에저자들은당뇨병의과거력이없는망막초진환자에서전신검사 ( 혈당, HbA1C, 요검사등 ) 및형광안저혈관조영술을포함한안과적검사들을시행하였고당뇨병의진단기준에따라 NDM으로진단받은 15명의환자들의임상양상을분석하였다. 대상과방법 2011년 2월부터 2016년 10월까지본원에망막질환으로처음방문한환자중병력청취에서당뇨병의과거력이없었으나전신검사 ( 혈당, HbA1C, 요검사등 ) 및형광안저혈관조영술을통해 NDM을발견한환자 15명의 30안을대상으로하였다. HbA1C의영향을가늠하고자, HbA1C가진단기준으로포함되게된 2011년도이후를대상범위로하였고이들의의무기록을후향적으로조사하였다. 본연구는본원의학연구심의위원회 (Instituitional Review Board, IRB) 의승인을받고, 연구관련심의규정및지침에따라진행되었다. 2011년도대한당뇨병학회의당뇨병진료지침에따른당뇨병의진단기준은 1) HbA1C가 6.5% 이상또는 2) 8시간이상공복혈장혈당 126 mg/dl 이상또는 3) 75 g 경구포도당부하검사후 2시간혈장혈당 200 mg/dl 이상또는 4) 당뇨병의전형적인증상 ( 다뇨, 다음, 설명되지않는체중감소 ) 과임의혈장혈당 200 mg/dl 이상으로정의하고있으며이에해당할경우 NDM으로진단하였다. 혈액검사에는혈당, HbA1C 외에총콜레스테롤, 저밀도 지단백콜레스테롤, 중성지방, 크레아티닌, 사구체여과율 (glomerular filtration rate, GFR) 등을포함하였으며요검사를통하여요단백등의수치를측정하였다. 초진시나이, 성별, 고혈압유무, 안과적주증상을문진하였고최대교정시력과안압측정, 세극등현미경검사, 안저사진, 빛간섭단층촬영 (Spectralis OCT; Heidelberg Engineering, Heidelberg, Germany) 등의기본적인검사에더불어형광안저혈관조영술 (HRA2; Heidelberg Engineering, Heidelberg, Germany) 을시행하였다. 당뇨망막병증그룹과망막혈관질환그룹에서는모든환자에서전신검사, 안과기본적인검사및형광안저혈관조영술을시행하였다. 기타망막질환그룹에서삼출성나이관련황반변성및특발성황반원공은노인에서빈도가증가하므로기본적으로모든환자에서혈당, HbA1C, 요검사, 지질검사등을하였으며중심장액맥락망막병환자는비교적젊은나이에발생하지만간기능과고지혈증, 혈당등을보기위하여가능한모든환자에서시행하였다. 형광안저혈관조영술은나이관련황반변성과중심장액맥락망막병환자에서모두시행하였고, 특발성황반원공환자에서는연성드루젠이동반된일부환자에서형광안저혈관조영술을시행하였다. 환자는안저소견에따라망막질환의진단을당뇨망막병증, 망막혈관질환, 기타망막질환의세그룹으로나누었으며, 또한나누어진그룹에맞는세부진단명을기술하였다. 그룹별환자의임상적특성과혈액검사등을분석하고비교하였으며전신질환인당뇨병의특성을고려하여반대눈의안저소견또한확인하였고그양상을확인하였다. 자료의분석은 SPSS 20.0 for Windows (IBM Corp., Armonk, NY, USA) 를사용하였으며, 당뇨망막병증, 망막혈관질환, 기타망막질환세그룹을비교분석하였다. 적은표본수로비모수적검정법인 Kruskal-Wallis 검정을시행하여나이, 성별, 혈당, HbA1c, 고혈압등의상관관계를먼저분석하였다. 사후검정으로 Mann-Whitney 검정을시행하여상관관계가있는변수를각그룹간에비교분석하였고, Bonferroni s method로제1종오류를보정하여 0.05/3=0.0167의유의수준을적용하였다. 결과 본원에서망막질환으로초진하여 NDM으로진단된환자 15명의 30안의내원당시연령분포를살펴보면평균연령은 58.3 ± 15.9세이며, 남자의평균연령은 62.6 ± 14.2세, 여자의평균연령은 51.8 ± 17.4세로남자에서더연령이높았다. 대상자 15명중남자가 9명 (60.0%), 여자는 6명 (40.0%) 이었다. 과거력을청취하였을때 15명의환자에서모두당 1051
- 대한안과학회지 2017 년제 58 권제 9 호 - Table 1. Clinical features and characteristics of newly diagnosed diabetes mellitus patients, classified into 3 groups Groups Patient No. Onset age Sex HTN Diagnosis Type of DM Diabetic retinopathy 1 39 F No PDR Type 1.5 (LADA) 2 38 M No PDR Type 1.5 (LADA) 3 31 F No PDR Type 1.5 (LADA) 4 51 M No Severe NPDR Type 2 Retinal vascular disease 5 46 F Yes CRVO Type 2 6 72 M Yes Mild NPDR, BRVO Type 2 7 84 M No Vitreous hemorrhage with CRVO Type 2 8 52 F No Mild NPDR, Macular edema Type 2 Other retinal disease 9 53 M Yes Vitreous hemorrhage with CNV rupture Type 2 10 70 M Yes Wet AMD Type 2 11 78 M No Wet AMD Type 2 12 79 F Yes Wet AMD Type 2 13 51 M Yes CSC Type 2 14 62 M No CSC Type 2 15 64 F Yes Idiopathic MH stage II Type 2 HTN = hypertension; DM = diabetes mellitus; F = female; M = male; PDR = proliferative diabetic retinopathy; LADA = latent autoimmune diabetes in adults; NPDR = non-proliferative diabetic retinopathy; CRVO = central retinal vein occlusion; BRVO = branch retinal vein occlusion; CNV = choroidal neovascularization; AMD = age-related macular degeneration; CSC = central serous chorioretinopathy; MH = macular hole. A B Figure 1. Fundus photography of a patient who was diagnosed with proliferative diabetic retinopathy and latent autoimmune diabetes in adult. A 39-year-old female patient (Patient No.1) presented with decreased visual acuity in the right eye. (A) The patient underwent pars plana vitrectomy due to vitreous hemorrhage and subhyaloid hemorrhage in the right eye. (B) Neovascularization (at the disc and elsewhere) and hard exudate were observed in the opposite eye. 뇨병을인지하지못하고있었으며이중 7명 (46.6%) 은고혈압을앓고있었고환자의대부분은시력저하 (11명, 73.3%) 를호소하였으며변시증을보이는환자가 2명, 기타증상을호소하는환자가 2명이었다. 전체환자중 2명은개인의원에서망막의이상소견으로의뢰되었다. 15명의환자들은각각당뇨망막병증, 망막혈관질환, 기타망막질환을가진군의세부류로나누었다. 당뇨망막병증그룹에는증식당뇨망막병증이 3명, 심한비증식당뇨망막병증이 1명이있었다. 망막혈관질환그룹에는망막중심정맥폐쇄 1명, 망막분지정맥폐쇄 1명, 유리체출혈이동반된망막중심정맥폐쇄 1명, 황반부종 1명이있었다. 기타망 막질환그룹에는맥락막신생혈관파열에의한유리체출혈 1명, 삼출성나이관련황반변성 3명, 중심장액맥락망막병증 2명, 특발성황반원공 1명이있었다 (Table 1). 당뇨망막병증그룹의증식당뇨망막병증으로내원한 3명의환자들은안저검사에서유리체하및유리체의출혈, 시신경및망막의신생혈관증식, 망막견인의소견과더불어형광안저혈관조영술에서혈관성형광유출등증식당뇨망막병증을강력하게의심할수있는소견 (Fig. 1) 을보였다. 심한비증식당뇨망막병증환자에서도안저검사에서저명한당뇨망막병증의소견이있었으나형광안저혈관조영술에서는증식당뇨망막병증을시사하는소견은보이지않았다. 당 1052
- 최화수외 : 안저검사로진단한당뇨환자의임상분석 - A B Figure 2. A case of central retinal vein occlusion (CRVO) in the right eye (Patient No. 5). Fundus photography and fluorescein angiography of a 46-year-old woman who presented with decreased visual acuity in the right eye. (A) In the fundus photograph, the right eye showed diffuse flame-shaped retinal hemorrhages and cotton wool patches of CRVO. And there was one flame-shaped retinal hemorrhage (black arrow) with cotton wool patch in the left eye and no microaneurysms. (B) However, two microaneurysms (white arrow) are observed in the left eye in the fluorescein angiography. 뇨망막병증그룹은기타망막질환그룹과비교하였을때나이, HbA1C, 단백뇨모두유의한차이를보였으나, 망막혈관질환그룹과는차이를보이지않았다 (p=0.006, p=0.012, p=0.006, Mann-Whitney test). 증식당뇨망막병증환자는 30대의상대적으로젊은연령대로보아 1형당뇨병을의심하였고내인성인슐린의분비능을반영하는 C-peptide를추가로검사하였다. 그결과 3 명의환자모두정상보다낮은 C-peptide 수치를보여인슐린의존성당뇨병 (insulin-dependent diabetes mellitus) 에해당되는것을알수있었다. 특히 1.5형당뇨병으로도불리는 latent autoimmune diabetes in adults (LADA) 인것을알수 있었으며, 나머지 12명의환자들은모두 2형당뇨병에해당하였다 (Table 1). 망막혈관질환그룹 4명은망막중심정맥폐쇄 (2명), 망막분지정맥폐쇄 (1명), 황반부종 (1명) 의세가지질환을확인하였으며망막분지정맥폐쇄와황반부종환자는같은눈에가벼운비증식당뇨망막병증이동반되어있었다. 반대눈을조사하였을때는전체 4명의환자중 3명의환자에게서안저검사및형광안저혈관조영술상미세동맥류, 망막반점출혈의가벼운비증식당뇨망막병증소견을보였다 (Fig. 2). 기타망막질환그룹 7명의환자에서는안저검사및형광안저혈관조영술에서양안모두당뇨망막병증이없는것으 1053
- 대한안과학회지 2017 년제 58 권제 9 호 - Table 2. Comparison of diagnosis between both eyes Group Patient No. Diagnosis Diagnosis of opposite eye Diabetic retinopathy 1 PDR PDR 2 PDR PDR 3 PDR PDR 4 Severe NPDR Old RRD Retinal vascular disease 5 CRVO Mild NPDR 6 Mild NPDR, BRVO Mild NPDR 7 Vitreous hemorrhage with CRVO No DR, RPE atrophy 8 Mild NPDR, Macular edema Mild NPDR Other retinal disease 9 Vitreous hemorrhage with CNV rupture No DR 10 Wet AMD No DR, Dry AMD 11 Wet AMD No DR, RPE atrophy 12 Wet AMD No DR 13 CSC No DR 14 CSC No DR 15 Idiopathic MH stage II No DR PDR = proliferative diabetic retinopathy; NPDR = non-proliferative diabetic retinopathy; RRD = rhegmatogenous retinal detachment; CRVO = central retinal vein occlusion; BRVO = branch retinal vein occlusion; DR = diabetic retinopathy; RPE = retinal pigment epithelium; CNV = choroidal neovascularization; AMD = age-related macular degeneration; CSC = central serous chorioretinopathy; MH = macular hole. Table 3. Diabetic status, lipid profile and renal function test results of the patients Patient No. Plasma glucose (mg/dl) HbA1C (%) Total cholesterol (mg/dl) LDL cholesterol (mg/dl) TG (mg/dl) Cr (mg/dl) GFR (ml/min/1.73 m 2 ) Proteinuria of initial visit 1 251 12.5 335 207 255 0.7 99.7 3+ 2 146 9.1 187 134 94 0.8 78.9 1+ 3 137 11.9 154 82 169 0.7 103.9 1+ 4 205 10.7 220 110 166 0.9 94.7 2+ 5 131 6.7 230 157 123 0.9 71.8 0 6 118 7.0 215 132 111 1.1 70 0 7 165 * 6.0 146 71 81 2.4 27.7 0 8 128 6.5 197 112 137 0.8 80.2 0 9 229 10.5 181 107 198 1 83.2 0 10 135 6.7 198 131 105 0.9 89.3 0 11 134 6.6 176 103 126 1.1 69.1 0 12 165 6.6 145 70 152 0.8 74.6 0 13 143 6.7 158 73 218 1.1 75.1 0 14 93 6.5 196 136 157 1.1 73.7 0 15 205 5.9 171 79 48 0.8 77.1 0 HbA1C = hemoglobin A1C; LDL = low density lipoprotein; TG = triglyceride; Cr = creatinine; GFR = glomerular filtration rate. * It was measured in the fasting state; Although HbA1C did not meet the standard of 5.9%, random glucose measured as 205 mg/dl and diagnosed as newly diagnosed diabetes mellitus. 로확인되었고 (Table 2), 망막혈관질환과기타망막질환그룹모두혈액검사및요검사상에서는두드러지는이상소견은보이지않았으나기존에신부전을진단받은한명의환자에서크레아티닌및 GFR의이상을확인할수있었다 (Table 3). LADA이며증식당뇨망막병증으로진단된환자 3명과유리체출혈이동반되었던망막중심정맥폐쇄, 맥락막신생혈관파열환자는모두유리체절제술을시행하였으며나머지환자들은진단에적합한약물적치료를시행하였고내분비내과와 의협의진료를통하여당뇨병치료또한함께진행하였다. 고찰 망막질환환자들에있어당뇨병의유무는매우중요할것이며특히망막혈관질환들에서의영향은더크다. 하지만급성으로발병하는 1형당뇨병이나임신성당뇨병과달리 2형당뇨병은수년간증상이나타나지않는경우가많아많은환자들이본인이당뇨병을갖고있는지모르는경 1054
- 최화수외 : 안저검사로진단한당뇨환자의임상분석 - 우가많으며내분비내과에서는이를발견하기위해많은노력을기울이고있다. 11 또한증상이나타난다하더라도시력장애는약 24.9% 로당뇨병에서주증상이아니기때문에안과에서숨겨진당뇨병을알아차리고검사하는것을생각하기는쉽지않다. 2 그러나안과적으로당뇨병및당뇨망막병증의유무를감별하는것은망막질환의치료및경과에있어매우중요하며, 형광안저혈관조영술을같이시행한다면좀더정확성을높일수있다. 또한전신검사를통해당뇨병을조기에발견하고망막질환과더불어함께치료할수있다면더큰치료효과를기대할수있을것이다. 안과에망막질환으로초진한환자중 NDM으로진단된환자들을당뇨망막병증그룹, 망막혈관질환그룹, 기타망막질환그룹으로구분할수있었다. 당뇨망막병증그룹중증식성당뇨망막병증을보인환자 3명은 LADA에해당하는것을알수있었는데, LADA란 glutamic acid decarboxylase (GAD) 항체를포함한 circulating islet antibody 를갖고있는환자들로, 1형당뇨병에비하여비교적연령이높은성인에서발병하는양상을보이고, 많은환자들이비만하지않은모습과초기에인슐린치료가필요하지않는점을특징으로하는 2형당뇨병의모습도갖고있어 1.5 형당뇨병으로도불리는질환이다. 12-14 아직진단기준은확립되어있지않아 20-30대의성인에서발병, 초기에인슐린치료가필요하지않은점, GAD 항체의유무가진단기준으로이용되고있다. 또한췌장의 β cell이천천히파괴되기때문에내인성인슐린의분비능을반영하는 C-peptide가정상보다미만이긴하나어느정도의수치를보이는것이진단에도움이될수있다. 본연구에서 LADA 환자 3명은수치가 0.3-0.4 ng/ml로본원의정상범위기준인 0.5-4.0 ng/ml 보다떨어져있으나췌장의기능이어느정도있는것을알수있었다. 12,14,15 또한당뇨망막병증그룹이기타망막질환그룹에비하여의미있게연령이낮은것으로확인되었는데 (p=0.006, Mann-Whitney test), 이는발병연령이낮은 LADA 환자가당뇨망막병증그룹의대부분을차지하고있기때문으로보인다. LADA 환자에서당뇨망막병증의유병률은아직자세히알려져있지않다. Arikan et al 16 은 GAD 항체를가진터키환자들에게서당뇨망막병증및신장병증을가진환자가많았다고보고하고있으나 Myhill et al 17 은당뇨망막병증의유병률은유의한차이를보이지않았다. 또한한국인에서는제1형당뇨병, 제2형당뇨병, LADA의세환자군의합병증으로당뇨망막병증을비교하였을때세군간의유의한차이를확인할수없었다. 14 본연구에서세명의 LADA 환자는내분비내과와의협의진료를통해모두심한형태의 LADA에해당함을알수있었고, 안과초진시이미합병 증으로증식당뇨망막병증을갖고있었다. 세명의환자모두안과적증상외에타증상이없었으며시력저하나비문증같은안과적증상이주증상으로발생하여내원하였고, 병이일정수준이상진행하기전까지는증상이적은당뇨망막병증의특성때문에내원당시 LADA 및당뇨망막병증이이미악화된상태였던것으로생각된다. 18 망막혈관질환그룹에서 4명중 3명의환자의반대눈에서가벼운당뇨망막병증을확인할수있었고이를통하여당뇨병이망막혈관질환들의발병에영향을주었음을생각해볼수있었다. 9,10 아직고혈당이망막의미세혈관에영향을주는기전에대해서는명확하지않으나여러연구를통해작용기전들이제시되고있으며이들의상관관계가유의함을밝히고있다. 19 5번환자 (Fig. 2) 는우안의망막중심정맥폐쇄로내원하였는데좌안에서 7시방향에망막동맥을따라불꽃모양출혈과면화반이관찰되었다. 이러한소견만본다면고혈압망막병증을의심할수도있을것이다. 하지만형광안저혈관조영술을시행한결과에서좌안 5시방향의후극부와적도부사이에미세동맥류 2개가있는것을발견하였고가벼운비증식당뇨망막병증이동반된것을알수있었다. 이처럼안저검사만시행할경우미세동맥류를발견하여가벼운비증식당뇨망막병증을진단하기란쉽지않으며, 환자에게서보인망막반점출혈을고혈압망막병증으로오진하거나무관심으로인하여당뇨망막병증을놓칠수도있다. 20 이때형광안저혈관조영술을시행한다면안저검사로발견하지못한미세동맥류를발견함으로써다른망막질환에숨겨져있는당뇨망막병증을발견하는데도움이될수있고이는환자의예후와치료적효과에있어중대한분기점이될수있다. 기타망막질환그룹은모두 7명이었으며, 이환자들에서진단된망막질환들이모두당뇨병과관련이있음을알수있었다. 삼출성나이관련황반변성, 중심장액맥락망막병증, 특발성황반원공모두당뇨병이하나의전신적인위험인자로보고된적이있으며, 21-23 맥락막신생혈관파열환자도삼출성나이관련황반변성과비슷한기전및위험요인이작용한것으로생각된다. LADA인증식당뇨망막병증을갖고있는 3명의환자들은내원당시이미다른환자들보다더높은 HbA1C의수치 (11.2 ± 1.8%) 를보였고단백뇨가동반된것을알수있었다. 연구에따르면높은 HbA1C와단백뇨가당뇨망막병증의발생에기여한다는보고가있으며특히단백뇨를보일경우증식당뇨망막병증을갖고있을확률이높다고보고하고있다. 24,25 본연구에도 HbA1C와단백뇨가당뇨망막병증그룹과기타망막질환그룹간에유의한차이 (p=0.012, p=0.006, Mann-Whitney test) 를보여기존의보고를한번더입증할 1055
- 대한안과학회지 2017 년제 58 권제 9 호 - 수있었다. 반면고혈당과혈중지질농도의이상이당뇨망막병증의발생, 당뇨황반부종등과연관이있는것으로알려져있으나연구에서는유의한차이를보이지않았다 (plasma glucose; p=0.163, total cholesterol; p=0.321, low density lipoprotein cholesterol; p=0.363, triglyceride; p=0.279, Kruskal-Wallis test). 6 고혈압은당뇨망막병증환자에서그조절여부에따라합병증의발생빈도가달라지며, 미세동맥류및면화반등의악화에기여할수있고환자의시력예후에도영향을준다는보고가있다 26,27 연구대상인 15명의환자중 7명에서과거력상고혈압을갖고있거나현재혈압약을복용하고있었다. 하지만고혈압의과거력을가진환자수가전체환자수의많은비중을차지함에도불구하고고혈압이각그룹간에미치는영향에는유의한차이가없었다 (p=0.087, Kruskal-Wallis test). 이번연구를통해 NDM을발견하고분석한것과마찬가지로, 혈압측정을통하여안과초진환자에서고혈압을발견하고고혈압과망막질환의연관성을분석해보는것또한앞으로해볼만한과제로생각한다. 본연구는무작위대조군연구가아닌제한된환자군을대상으로소규모단면조사연구를시행한점이제한점으로볼수있다. 이에질환의그룹이아닌다양한망막질환과 NDM의유의한관계나유병률등에대해서는알수없었다. 또한표본수가적어서 HbA1C, 고혈압, 중성지방등의요인들과각질환그룹과의관계에대해서비모수적검정을사용하였기에상대적으로검정력이약한것이제한점이되겠다. 마지막으로혈광안저혈관조영술의시행이숨겨진당뇨망막병증을찾을수있는중요한검사로제시되고있으나현실적으로모든망막질환환자에게서형광안저혈관조영술을시행할수없는점이실제임상에서의한계점이되겠다. 이연구의의의로는대한당뇨병학회의기준에따라 2011년이후의환자들을대상으로 HbA1C를조사한점에의미가있는것으로본다. 또한 HbA1C를기본적인전신검사에포함함으로써망막혈관질환그룹과기타망막질환그룹총 11명중 8명이임의혈장혈당상에서는정상혹은당뇨병의증단계였으나 HbA1C 검사상에서모두 6.5% 이상으로확인되었고 NDM으로확진할수있었다. 임의혈장혈당만으로는당뇨의유무를판별하기어려운환자들에게있어 HbA1C가 NDM으로진단할수있는중요한인자임을알수있었으며당뇨망막병증에서 HbA1C의중요성을다시확인할수있었다. 또한나이관련황반변성, 특발성황반원공이나중심장액맥락망막병환자와같이 NDM을생각보다다양한망막질환환자에게서진단할수있었으며, 이는많은안과진료환자들에게숨겨진당뇨병이있을가능성 을보여주고있다. 다양한망막질환으로안과에서초진한환자를대상으로전신적검사를하여 NDM을조기에발견할수있었고, 기본적인안과적검사와더불어시행한형광안저혈관조영술이당뇨망막병증의발견에도움이되었다. 또한내과의사와의협의진료를통하여이미발병한당뇨망막병증환자는신속히안과및내과적으로치료하고, 망막혈관질환환자의경우망막혈관질환의치료뿐아니라당뇨병치료의중요성을교육하여야한다. 기타망막질환환자는지속적인경과관찰을통하여향후발생할수도있는당뇨망막병증을조기에발견하는데도움을줄수있다. REFERENCES 1) Drivsholm T, de Fine Olivarius N, Nielsen AB, Siersma V. Symptoms, signs and complications in newly diagnosed type 2 diabetic patients, and their relationship to glycaemia, blood pressure and weight. Diabetologia 2005;48:210-4. 2) Colagiuri S, Cull CA, Holman RR; UKPDS Group. Are lower fasting plasma glucose levels at diagnosis of type 2 diabetes associated with improved outcomes?: U.K. prospective diabetes study 61. Diabetes Care 2002;25:1410-7. 3) Wahab S, Mahmood N, Shaikh Z, Kazmi WH. Frequency of retinopathy in newly diagnosed type 2 diabetes patients. J Pak Med Assoc 2008;58:557-61. 4) Harris MI, Klein R, Welborn TA, Knuiman MW. Onset of NIDDM occurs at least 4 7 yr before clinical diagnosis. Diabetes Care 1992;15:815-9. 5) Abdollahi A, Malekmadani MH, Mansoori MR, et al. Prevalence of diabetic retinopathy in patients with newly diagnosed type II diabetes mellitus. Acta Med Iran 2006;44:415-9. 6) Yau JW, Rogers SL, Kawasaki R, et al. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care 2012;35: 556-64. 7) Tapp RJ, Shaw JE, Harper CA, et al. The prevalence of and factors associated with diabetic retinopathy in the Australian population. Diabetes Care 2003;26:1731-7. 8) Klein R, Klein BE, Moss SE, Linton KL. The Beaver Dam Eye Study: retinopathy in adults with newly discovered and previously diagnosed diabetes mellitus. Ophthalmology 1992;99:58-62. 9) Klein R, Klein BE, Moss SE, Meuer SM. The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study. Trans Am Ophthalmol Soc 2000;98:133-41; discussion 141-3. 10) Hayreh SS, Podhajsky PA, Zimmerman MB. Retinal artery occlusion: associated systemic and ophthalmic abnormalities. Ophthalmology 2009;116:1928-36. 11) American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2004;27 Suppl 1:S11-4. 12) Tuomi T, Santoro N, Caprio S, et al. The many faces of diabetes: a disease with increasing heterogeneity. Lancet 2014;383:1084-94. 13) Juneja R, Hirsch IB, Naik RG, et al. Islet cell antibodies and glutamic acid decarboxylase antibodies, but not the clinical phenotype, help to identify type 1(1/2) diabetes in patients presenting with type 2 diabetes. Metabolism 2001;50:1008-13. 1056
- 최화수외 : 안저검사로진단한당뇨환자의임상분석 - 14) Roh MO, Jung CH, Kim BY, et al. The prevalence and characteristics of latent autoimmune diabetes in adults (LADA) and its relation with chronic complications in a clinical department of a university hospital in Korea. Acta Diabetol 2013;50:129-34. 15) Stenström G, Gottsäter A, Bakhtadze E, et al. Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment. 2005;54 Suppl 2:S68-72. 16) Arikan E, Sabuncu T, Ozer EM, Hatemi H. The clinical characteristics of latent autoimmune diabetes in adults and its relation with chronic complications in metabolically poor controlled Turkish patients with Type 2 diabetes mellitus. J Diabetes Complications 2005;19:254-8. 17) Myhill P, Davis WA, Bruce DG, et al. Chronic complications and mortality in community-based patients with latent autoimmune diabetes in adults: the Fremantle Diabetes Study. Diabet Med 2008;25:1245-50. 18) Fong DS, Aiello L, Gardner TW, et al. Retinopathy in diabetes. Diabetes Care 2004;27 Suppl 1:S84-7. 19) Chistiakov DA. Diabetic retinopathy: pathogenic mechanisms and current treatments. Diabetes Metab Syndr 2011;5:165-72. 20) Harding SP, Broadbent DM, Neoh C, et al. Sensitivity and specificity of photography and direct ophthalmoscopy in screening for sight threatening eye disease: the Liverpool Diabetic Eye Study. BMJ 1995;311:1131-5. 21) Haimovici R, Koh S, Gagnon DR, et al. Risk factors for central serous chorioretinopathy: a case control study. Ophthalmology 2004;111:244-9. 22) Clemons TE, Milton RC, Klein R, et al. Risk factors for the incidence of Advanced Age-Related Macular Degeneration in the Age-Related Eye Disease Study (AREDS): AREDS report no. 19. Ophthalmology 2005;112:533-9. 23) Evans JR, Schwartz SD, McHugh JD, et al. Systemic risk factors for idiopathic macular holes: a case-control study. Eye (Lond) 1998;12 (Pt 2):256-9. 24) Mogensen CE, Chachati A, Christensen CK, et al. Microalbuminuria: an early marker of renal involvement in diabetes. Uremia Invest 1985-1986;9:85-95. 25) Cruickshanks KJ, Ritter LL, Klein R, Moss SE. The association of microalbuminuria with diabetic retinopathy. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Ophthalmology 1993;100:862-7. 26) Matthews DR, Stratton IM, Aldington SJ, et al. Risks of progression of retinopathy and vision loss related to tight blood pressure control in type 2 diabetes mellitus: UKPDS 69. Arch Ophthalmol 2004;122:1631-40. 27) Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ 1998;317:703-13. = 국문초록 = 안저검사에서이상이발견되어당뇨병을새롭게진단받은환자의임상분석 목적 : 안과에초진하여시행한안저검사에서이상이발견되어새롭게진단받은당뇨병 (newly diagnosed diabetes mellitus, NDM) 환자의임상양상에대하여분석하고자하였다. 대상과방법 : 2011 년 2 월부터 2016 년 10 월까지과거력상당뇨병이없었으며망막질환으로안과에서초진하여발견한 NDM 환자 15 명의 30 안을대상으로의무기록을후향적으로조사하였다. 당뇨병의기준으로는임의혈당이 200 mg/dl 이상이거나공복혈당이 126 mg/dl 이상, 또는당화혈색소 (HbA1C) 가 6.5% 이상인환자를 NDM 으로진단하였다. 초진시나이, 성별, 과거력, 증상, 세극등현미경검사, 안저사진, 빛간섭단층촬영등의기본적인검사에더불어형광안저혈관조영술과전신검사로써 HbA1C 를포함한혈액검사와요검사를시행하였으며당뇨망막병증, 망막혈관질환, 기타망막질환의세그룹으로나누어분석하였다. 결과 : 당뇨망막병증그룹에는증식당뇨망막병증 3 명, 심한비증식당뇨망막병증 1 명이포함되었고망막혈관질환그룹에는망막중심정맥폐쇄 1 명, 망막분지정맥폐쇄 1 명, 유리체출혈을동반한망막중심정맥폐쇄 1 명, 황반부종 1 명이포함되었으며, 기타망막질환그룹에는맥락막신생혈관파열에의한유리체출혈 1 명, 삼출성나이관련황반변성 3 명, 중심장액맥락망막병 2 명, 특발성황반원공 1 명이포함되었다. 증식당뇨망막병증 3 명의환자는모두양안에서증식당뇨망막병증이있었고 latent autoimmune diabetes in adults (LADA) 였다. 나머지 12 명은 2 형당뇨병환자였으며, 이들을분석한결과 3 명 ( 망막중심정맥폐쇄 1 명, 망막분지정맥폐쇄 1 명, 황반부종 1 명 ) 이반대눈에가벼운비증식당뇨망막병증이있었고, 9 명의환자들은반대눈에당뇨망막병증이없었다. 환자의나이, HbA1C, 단백뇨는당뇨망막병증그룹이기타망막질환그룹에비하여유의한차이를보였다 (p=0.006, p=0.012, p=0.006, Mann-Whitney test). 결론 : 다양한망막질환으로안과에초진한환자에서기본적인안과적검사뿐만아니라형광안저혈관조영술및전신적검사를하여 NDM 을조기에발견할수있었다. 또한내과의사와의협의진료를통하여이미발병한당뇨망막병증환자는신속히안과및내과적으로치료하고, 망막혈관질환환자에서는안과질환의치료뿐아니라당뇨병치료의중요성을교육시키고, 그이외의망막질환환자에서는지속적인경과관찰을통하여향후발생할수도있는당뇨망막병증을조기에발견하는데도움을줄수있다. < 대한안과학회지 2017;58(9):1050-1057> 1057