Focused Issue J Korean Diabetes 2015;16: Vol.16, No.2, 2015 ISSN 제 1 형당뇨병환자의진단및혈당조절목표 김재현

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1 J Korean Diabetes 2015;16: Vol.16, No.2, 2015 ISSN 김재현인제대학교일산백병원소아청소년과 Diagnosis and Glycemic Control of Type 1 Diabetes Jae Hyun Kim Department of Pediatrics, Inje University Ilsan Paik Hospital, Goyang, Korea Abstract Type 1 diabetes mellitus (T1DM) is characterized by an immune-mediated beta-cell destruction that causes lifelong insulin dependency. Diagnosis of diabetes is based on fasting glucose, 2-h plasma glucose value after a 75-g oral glucose tolerance test, or hemoglobin A1c (HbA1c) levels. Differentiation between type 1 and 2 diabetes is important for both education and treatment. Diabetes-associated autoantibodies, c-peptide and clinical characteristics should be considered to confirm the diagnosis of T1DM. A single HbA1c target of < 7.5% across all pediatric age groups is recommended. In nonpregnant adults, a reasonable HbA1c goal is < 7.0% to reduce the incidence of microvascular complications of T1DM. Glycemic targets should be individualized according to lifestyle, psychosocial and medical circumstances. Keywords: Diagnosis, Glycemic target, Type 1 diabetes 서론 제1형당뇨병은자가면역기전에의해췌장의베타세포가파괴되어, 이에따른인슐린결핍에의해발생하는질환이다. 전체당뇨병환자중 5~10% 정도를차지하는것으로알려져있으며, 소아에서더많이발생한다 [1]. 이유는명 확하지않으나, 소아청소년연령에서는전세계적으로연간 3% 정도의발생률의증가를보이고있다 [2]. 제1형당뇨병발생률의증가와함께유병률도증가하고있다. 그이유로는성인에서제1형당뇨병환자가증가하고, 소아청소년연령에진단받은환자들의수명이길어졌기때문이다. 우리나라에서도소아청소년연령에서제1형당뇨병의발생이증 Corresponding author: Jae Hyun Kim Department of Pediatrics, Inje University Ilsan Paik Hospital, 170 Juhwa-ro, Ilsanseo-gu, Goyang , Korea, pedendo@paik.ac.kr Received: Apr. 27, 2015; Accepted: May. 6, 2015 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 c 2015 Korean Diabetes Association The Journal of Korean Diabetes 101

2 가하는것으로보인다 [3]. 이렇게증가하고있는제1형당뇨병환자의관리를위해서는당뇨병을정확하게진단하는것이중요하다. 소아청소년의경우제1형당뇨병의진행이빠른경우가많고진단당시전형적인증상이있는경우가많기때문에발병부터진단까지소요되는시간이길지않을수있으나, 성인의경우에는소아청소년보다는진행이늦은경우가많다고알려져있다 [4]. 당뇨병으로진단된후에는혈당조절을잘하는것이당뇨병으로인한미세혈관 / 대혈관합병증예방에중요하다. 따라서본논문에서는제1형당뇨병의진단과혈당조절목표에대하서살펴보고자한다. 본론 1. 당뇨병의진단이전에는당뇨병의진단을위한검사방법으로공복혈당과 75 g 경구당부하검사 2시간후의혈당이사용되었다. 1997년에당뇨병의진단기준을재개정할때, 당뇨병성망박병증의유무와혈당과의관련성을중심으로기준을정하였고, 이러한결과로장기간지속되는식후 2시간혈당이 200 mg/dl일경우에당뇨병으로진단을하는것이타당하 다고결정하였다 [5]. 이수치는당뇨병망막병증의유병률을증가시키는변곡점에해당하며, 공복혈당및경구당부하검사당화혈색소와유의한관련이있다. 당화혈색소를사용하는방법은공복혈당을진단기준으로사용하는것보다몇가지장점이있는데, 검사를위한금식이필요없고, 검사전의안정성도좋은것으로보이며, 스트레스나질병에의한일중, 일간의변동도심하지않은편이다. 하지만이러한장점에도불구하고, 혈색소증이나특정빈혈이있는경우에는당화혈색소의결과가실제혈당수준과는다를수있으므로판정에주의하여야한다. 당화혈색소는 The National Glycohemoglobin Standardization Program에서공인된방법으로시행하고표준화되어야한다. 현재까지당화혈색소에의한당뇨병의진단은성인에한정된것으로, 소아청소년연령에서진단기준으로당화혈색소 6.5% 를사용할수있을지는아직불명확상태로추가적인연구가필요하다 [6]. 공복혈당, 2시간혈당및당화혈색소에의한당뇨병의진단이 100% 의일치를보이는것은아니다. 미국의 National Health and Nutrition Examination Survey 자료에의하면당뇨병으로진단받지않은사람들에대한스크리닝검사에서당화혈색소가 6.5% 이상을기준으로했을때에는공복혈당이 126 mg/dl 이상을기준으로했을때보다 1/3 정도적 Table 1. Criteria for the diagnosis of diabetes A1C 6.5%. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. a OR FPG 126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h. a OR 2-h PG 200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. a OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose 200 mg/dl (11.1 mmol/l). NGAP, The National Glycohemoglobin Standardization Program; DCCT, Diabetes Control and Complications Trial; FPG, fasting plasma glucose; PG, plasma glucose; OGTT, oral glucose tolerance test. a In the absence of unequivocal hyperglycemia, results should be confirmed by repeat testing. Adapted from Korean Diabetes Association: Treatment guideline for diabetes. 5th ed. Seoul: Gold s Planning and Development; p5-9 [7]. 102

3 김재현 게당뇨병으로진단되었다. 하지만, 성인에서많은수의환자들이당뇨병으로진단받지못하고있는상태에서당화혈색소의민감도가낮은것이검사의편의성을생각할때실제로는진단받는환자의수를늘릴수는있을것으로보인다. 당뇨병의진단기준을종합하면 Table 1과같다 [7]. 2. 제1형당뇨병과제2형당뇨병의구분당뇨병으로진단하는기준은제1형과제2형이동일하다. 제1형당뇨병과제2형당뇨병을구별하는것은임상적으로중요한데, 그이유는치료계획수립과당뇨병교육을위한접근방법에차이가있기때문이다 [8]. 하지만, 제1형당뇨병은소아청소년이나성인모두에서발현양상이매우다양하다. 소아청소년연령에서는급성으로심한증상을동반하는경우가흔하지만성인의경우에는더서서히진행하는양상을보인다. 초기증상이제2형당뇨병과구분이되지않는경우도많이있어제1형과제2형당뇨병을구분하는것은쉽지않은일이다. 제1형과제2형당뇨병을구별하는데도움을주는것은임상적인양상, 췌도자가항체, 가족력등이있다. 일반적으로마른체형의사람이전형적인증상을보이면서당뇨병의가족력이없는경우에는 1형당뇨병을더시사한다. 반대로과체중이상의사람이대사증후군이동반되면서당뇨병의가족력이있을경우에는 2형당뇨병을더시사한다. 하지 만, 최근들어비만이증가하는것과 2형당뇨병환자일부에서당뇨병케톤산증이발생하는것이제1형과제2형당뇨병의구별을어렵게한다 [9,10]. 또한췌도와관련된자가항체를측정하는것이 1형당뇨병을진단하는데중요한방법이될수있다. Glutamic acid decarboxylase 항체, protein tyrosine phosphatase 항체, 인슐린자가항체 (insulin autoantibodies), zinc transporter protein 8 항체가존재한다면제1형당뇨병으로진단하는데도움을준다 [11]. 제1형당뇨병으로진단된환자의 85-90% 에서위의항체중한가지이상이진단시에발현하는것으로보고되고있다 [12]. 하지만, 아시아인들의경우제1형당뇨병환자에서자가항체양성률이낮은것으로알려져있어주의가필요하다 [13,14]. 제2형당뇨병의임상양상을보이는환자들에게서자가항체양성인경우도 < 20% 로보고되고있다 [15]. 또한 2형당뇨병의경우에도또한공복시 c-peptide 농도가제1형당뇨병과 2형당뇨병을구별하는데사용될수있다 [16]. 하지만소아청소년연령에서는 c-peptide 농도는제1형과제2형당뇨병의경우진단후첫 1년후에는상당히겹치기때문에급성기에는추천되지않는다. 진단된연령과무관하게 c-peptide가진단후 40년이후에도발견되었다는보고도있다 [17]. 따라서 1형당뇨병의진단은당뇨병의진단기준을만족하면서, 임상양상과자가항체양성, c-peptide 감소등의소견등을종합해서고려해야한다 (Table 2). Table 2. Clinical characteristics of type 1 and type 2 diabetes Characteristic Type 1 diabetes Type 2 diabetes Age of onset Mostly children, adolescents and young adults Mostly middle and old age Clinical presentation Most often acute, rapid with typical symptoms (polyuria, polydipsia, weight loss, fatigue) Usually gradual with no frequently complaints Autoantibodies associated Approximately 85~90% at onset < 20% with diabetes Ketosis Common Uncommon Obesity Population frequency Increased frequency Acanthosis nigricans No Yes Parent with diabetes 2~4% Approximately 80% 103

4 3. 제1형당뇨병의혈당조절목표고혈당은당뇨병을진단하는기준이되며, 당뇨병의합병증의발생과도직접적으로관련되어있다. 따라서혈당을조절하는것이당뇨병관리에가장기본이된다. 모든연령에서혈당조절목표를설정하는데에는생활습관, 정신사회적, 의학적인상황들이고려되어야한다. 기존에는소아청소년연령에서혈당조절목표는연령별로차이가있어서, 당화혈색소기준으로 6세미만에서는 < 8.5%, 6~12세에는 < 8.0%, 13~19세에는 < 7.5% 였다. 이러한목표는당화혈색소를낮게유지하는것이반복적인저혈당의빈도를증가시키는것과관련이있다는연구에서유래되었다 [18,19]. 반복적인심한저혈당이소아청소년에서신경인지기능의장애와관련이있을것이라는보고가있었다 [20]. 하지만최근들어서저혈당과신경인지기능저하와관련이없다는연구가발표되고 [21,22], 사춘기전에혈당을잘조절하는것이미래의미세혈관또는대혈관합병증을감소시킬것이라고생각되며, 고혈당과혈당의변화가심한것이단기간의신경인지기능과중추신경계에부정적인영향을끼친다는연구결과가발표되었다 [23,24]. 또한, 최근의연구에의하면인슐린펌프나다회주사법등을이용한인슐린집중치료를할경우에도과거와같이저혈당의위험을높이지않는다는보고도있다 [25,26]. 이러한결과들을바탕으로 The International Society for Pediatric and Adolescent Diabetes에서소아청소년연령에서혈당조절목표를당화혈색소 < 7.5% 로권고하였고, 이후 American Diabetes Association도같은기준으로혈당조절목표를결정하였다 [4,27]. 또한혈장포도당농도는식전에 90~130 mg/dl, 자기전및새벽에는 90~150 mg/dl 로유지하는것이추천된다. 하지만중요한것은소아청소년연령에서심한저혈당과고혈당의위험을최소화하고정상적인성장과발달을유지할수있는수준에서, 개인의상황에맞게혈당조절목표를설정해야한다는점이다. 성인의경우에는당화혈색소를 7% 미만으로낮추는것이미세혈관합병증을감소시키는데도움이되고, 장기적 인대혈관합병증의감소와도관련이있어, 임신하지않은성인의혈당조절목표로당화혈색소 7% 미만이추천된다 [18,28]. 식전혈당은 80~130 mg/ml, 식후최고혈당은 < 180 mg/dl를유지하는것이추천된다. 심한저혈당이나인슐린치료의다른부작용이없는경우에는더낮은당화혈색소목표를고려해볼수있다 [29]. 여기에는진단받은지얼마안되는경우나, 기대여명이긴경우, 저혈당인지를잘할때와심각한심혈관질환이없는경우가해당된다. 당화혈색소목표를약간높게설정하는경우는심한저혈당이있거나, hypoglycemia unawareness, 기대여명이길지않을때, 진행된혈관합병증이있을때, 또는광범위한동반질환이있을때이다. 모든연령에서혈당조절은당화혈색소뿐만아니라자가혈당측정을통해서도시행해야한다. 또한식전혈당이목표범위이지만당화혈색소가목표에비해서높은경우에는식후 2시간혈당을측정해보아야한다. 결론 1형당뇨병을진단하기위해서는당뇨병의진단기준에부합해야하며, 이것은공복혈당, 당부하검사후혈당, 당화혈색소등의기준에의한다. 당뇨병으로진단된후 1형과 2형을구별하는것은임상양상과자가항체양성여부, c-peptide 농도등을종합해서고려해야한다. 당뇨병에서혈당을조절하는것은합병증예방을위해서매우중요한데, 성인의경우에는당화혈색소 < 7.0%, 소아청소년의경우에는 < 7.5% 가추천된다. 모든연령에서혈당조절목표를설정하는데에는생활습관, 정신사회적, 의학적인상황들이고려되어야한다. REFERENCES 1. DIAMOND Project Group. Incidence and trends of childhood Type 1 diabetes worldwide Diabet Med 2006;23:

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A 617 Special Issue Diabetic Retinopathy Won Ki Lee, M.D. Department of Ophthalmology The Catholic University of Korea College of Medicine Kangnam St. Mary s Hospital E mail : wklee@catholic.ac.kr Abstract R