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1 J Korean Diabetes 2016;17:30-34 Vol.17, No.1, 2016 ISSN 한승진아주대학교의과대학내분비대사내과학교실 Treatment Strategy to Prevent Hypoglycemia Seung Jin Han Department of Endocrinology and Metabolism, Ajou University School of Medicine, Suwon, Korea Abstract Hypoglycemia is the limiting factor in the glycemic management of diabetes. It causes recurrent morbidity in patients with diabetes and is sometimes fatal. For most people with diabetes who are at risk for hypoglycemia, health care providers should focus on the risk factors of hypoglycemia and more actively seek a solution to the problem in order to prevent the development of severe hypoglycemia. The glycemic goals should be individualized in patients with diabetes in order to minimize the risk of iatrogenic hypoglycemia. In addition, appropriate drug selection, structured patient education, and short-term avoidance of hypoglycemia will reduce the incidence of hypoglycemia. Patient education needs to cover a broad range of information on hypoglycemia and practical training in order to prevent and manage hypoglycemia. Keywords: Diabetes mellitus, Hypoglycemia, Risk management 서론 저혈당은당뇨병환자를치료하는과정에서빈번하게관찰되는급성합병증으로적절하게대처되지않을경우심각한위험을초래하게된다. 또한저혈당의경험은환자들에 게혈당관리를어렵게해서고혈당과악순환을이루며궁극적으로적절한혈당관리를방해하는요소가된다. 저혈당발생빈도는제1형당뇨병과유병기간이긴제2형당뇨병환자에서높게나타난다. 제1형당뇨병환자에서중증저혈당의발생률은 100인 / 년을기준으로 115~320회이고제 Corresponding author: Seung Jin Han Department of Endocrinology and Metabolism, Ajou University School of Medicine, 164 WorldCup-ro, Yeongtong-gu, Suwon 16499, Korea, hsj@ajou.ac.kr Received: Jan. 31, 2016; Accepted: Feb. 3, 2016 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 2016 Korean Diabetes Association 30 The Journal of Korean Diabetes

2 한승진 2형당뇨병환자에서는 35~70회이다 [1,2]. 그러나제2형당뇨병환자의수가훨씬많고, 인슐린투여하는경우가많아서실제임상에서는제2형당뇨병환자에서의저혈당소견을흔히보게된다. 따라서당뇨병환자에서저혈당발생의위험요소를살펴보고저혈당발생을막을수있는구체적인치료전략을살펴보고자한다. 본론 1. 저혈당의위험요인저혈당은절대적또는상대적인인슐린의과다와이에따라저혈당발생을막으려는생리적인, 행동적인길항작용이원활하지않을때발생한다. 임상에서는인슐린과다로만발생하는저혈당은드물고저혈당에방어하는길항작용의장애가주요한원인이된다. 저혈당시첫번째방어기전은인슐린분비의감소이고두번째는글루카곤의증가이다 [3]. 세번째방어기전은교감신경에의한에피네프린증가인데인슐린과글루카곤의반응이감소된환자에서는이반응또한약화되어서저혈당에대한길항작용이나타나지않게된다. 이는저혈당관련자율신경장애의주요한요인이며수면이나운동중교감신경부신반응감소, 과거발생한저혈당에의한내성등으로발생한다 [4,5]. 1) 저혈당관련자율신경장애의위험요인 [6] 절대적인인슐린결핍증 중증저혈당및무증상저혈당의과거력 최근에발생한저혈당에대한내성 운동이나수면중교감신경부신반응감소 과도한혈당조절 2) 인슐린과다를초래하는위험요인 [4] 인슐린이나인슐린분비촉진제의과다한투여또는투여시간이나종류가잘못된경우 포도당섭취감소 : 긴공복, 식사를거르는경우 인슐린의존성포도당소모증가 : 운동중또는운동직후 인슐린에대한민감도증가 : 운동후수시간, 야간, 혈당조절이잘될때, 체중감량 내부에서포도당생성감소 : 음주 인슐린제거율감소 : 신부전 2. 저혈당방지를위한전략당뇨병초기의엄격한혈당관리효과가당뇨병의합병증발생을감소시키는것으로알려져있다. 그러나엄격한혈당관리는저혈당발생의위험을높이므로저혈당이자주오는환자, 기대수명이짧은경우, 고령이나소아, 다른질환이나합병증이동반된환자의혈당조절목표에대하여는약물의용량조절이나치료약제의조절등이필요하며혈당조절목표를덜엄격하게설정해야한다 [7,8]. 1) 환자와보호자교육환자와함께거주하는가족들에게저혈당의증상을빠르게인지하도록교육해야하고저혈당발생시대처할수있도록교육을시켜야한다. 저혈당의자율신경증상은발한, 떨림, 공복감, 불안등이며신경학적증상은집중력저하, 쇠약감, 무기력, 시력저하, 운동실조및의식저하등이있다. 그러나환자마다느끼는저혈당의증상이다르고같은환자의경우에도때에따라다른증상으로나타나므로초기대응이어려울수있다 [9]. 또한음주, 피로, 베타차단제의복용, 수면중일때는저혈당을조기에발견을방해하는요인으로작용할수있다. 특히인슐린이나인슐린분비촉진제를투여받고있거나저혈당무감지증 (hypoglycemia unawareness) 이있는환자에서는매진료시마다저혈당경험여부를물어보고저혈당예방법및치료법에대한교육을해야한다 [10]. 당뇨병환자에게저혈당이반복될때저혈당무감지증이발생할수있으므로반복적인저혈당이발생하지않도록예 31

3 방하는것이중요함을인지시키는것이필요하겠다 [11,12]. 2) 저혈당예방을위한식사교육적절한칼로리의규칙적인식사를하도록하고초속효성인슐린사용시식사시간에맞추어서적절한시간에인슐린을투여하도록교육한다. 또한갑작스런저혈당발생에대처하게위해서혈당을빠르게올릴수있는포도당이함유된음식을항상소지하도록교육한다. 취침전간식섭취는야간저혈당방지를위한오래된대응방법이나현재까지는이에대한효과가입증되지않았으므로여러다른저혈당예방방법과함께환자의특성에맞추어서사용해볼수있겠다 [13,14]. 3) 운동유발저혈당방지운동시근육에서포도당소모를증가시키므로당뇨병환자는운동시작전혈당이정상또는다소높더라고운동에의한저혈당이발생할수있다. 특히운동시간이길고, 갑자기운동강도가셀때, 식사량이적절하게공급되지않을때증가한다. 따라서운동전과후에자가혈당측정해서운동전후혈당이 140 mg/dl 미만이면약간의음식을더섭취하도록하고인슐린투여량을줄이도록한다. 4) 약물치료조정저혈당발생이불규칙한식사나과도한운동, 음주와같은원인없이자주발생하는경우는현재사용중인당뇨병약제의용량이과도할가능성을시사한다. 기저인슐린으로 neutral protamine Hagedorn 보다글라진이나디터미어를사용하고식후혈당조절을위해서 regular insulin보다는초속효성인슐린을사용하는경우저혈당발생을줄일수있다. 설폰요소제를사용하는경우에다른경구혈당강하제보다저혈당발생위험이높으므로저혈당이자주발생시저혈당발생이상대적으로낮은약제로대체하는것이필요하다. 5) 혈당모니터링식사전, 취짐전, 그리고저혈당증상발현시자가혈당측정을해서확인즉시환자스스로저혈당에대한대처행동을하도록한다. 최근에사용되기시작하는지속혈당감시 (continuous glucose monitoring) 는지속적혈당측정혈당치를 5분간격으로실시간으로측정하고혈당추세에대한정보를제공해주므로저혈당무감지증이있거나잦은저혈당을겪는환자들에게유용할수있다 [15]. 3. 저혈당의치료저혈당의치료목표는즉각적으로낮은혈당을감지하고치료하여이로인한증상및손상을최소화하는것이다. 혈당은빠르게상승시킬수있는포도당또는포도당이함유된 15~20 g의탄수화물을섭취하도록한다. 포도당섭취후저혈당증상이소실되더라도인슐린이나인슐린분비촉진제를사용한경우약물의작용이남아있어서저혈당이반복될수있으므로자가혈당측정을통해서확인하고간식이나식사를해서저혈당재발을막아야한다. 환자가의식이혼미해서포도당섭취를할수없는없는중증저혈당발생시에대비해서환자의가족이나동료가저혈당상황을인지하고치료할수있도록교육해야한다. 이경우응급실을빨리내원하거나정맥주사가가능하면포도당 20~50 ml를 1~3분에거쳐서투여하고, 글루카곤키트가준비되어있는경우라면글루카곤을주사하도록한다. 결론 저혈당은당뇨병환자의치료에있어서고혈당와악순환을이루며당뇨병환자의삶에심각한위험을초래할뿐만아니라적절한혈당관리를방해하는요인이다. 당뇨병환자진료시환자마다저혈당관련자율신경장애나인슐린과다를초래하는저혈당발생의위험요인이있는지확인하여저혈당발생의위험이높은환자에서는목표혈당을높게설정하는것이필요하다. 또한저혈당예방과대처에대해 32

4 한승진 서보다적극적으로환자와보호자교육을하는것이중요하다. REFERENCES 1. UK Hypoglycaemia Study Group. Risk of hypoglycaemia in types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia 2007;50: Donnelly LA, Morris AD, Frier BM, Ellis JD, Donnan PT, Durrant R, Band MM, Reekie G, Leese GP; DARTS/ MEMO Collaboration. Frequency and predictors of hypoglycaemia in type 1 and insulin-treated type 2 diabetes: a population-based study. Diabet Med 2005;22: Gerich JE, Langlois M, Noacco C, Karam JH, Forsham PH. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science 1973;182: Cryer PE. The barrier of hypoglycemia in diabetes. Diabetes 2008;57: Dagogo-Jack SE, Craft S, Cryer PE. Hypoglycemiaassociated autonomic failure in insulin-dependent diabetes mellitus. Recent antecedent hypoglycemia reduces autonomic responses to, symptoms of, and defense against subsequent hypoglycemia. J Clin Invest 1993;91: Segel SA, Paramore DS, Cryer PE. Hypoglycemiaassociated autonomic failure in advanced type 2 diabetes. Diabetes 2002;51: Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R; American Diabetes Association; Endocrine Society. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. J Clin Endocrinol Metab 2013;98: Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A, Wender R, Matthews DR. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015;38: Towler DA, Havlin CE, Craft S, Cryer P. Mechanism of awareness of hypoglycemia. Perception of neurogenic (predominantly cholinergic) rather than neuroglycopenic symptoms. Diabetes 1993;42: Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J, Vigersky R. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care 2013;36: Fanelli CG, Epifano L, Rambotti AM, Pampanelli S, Di Vincenzo A, Modarelli F, Lepore M, Annibale B, Ciofetta M, Bottini P, et al. Meticulous prevention of hypoglycemia normalizes the glycemic thresholds and magnitude of most of neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with short-term IDDM. Diabetes 1993;42: Fanelli C, Pampanelli S, Epifano L, Rambotti AM, Di Vincenzo A, Modarelli F, Ciofetta M, Lepore M, Annibale B, Torlone E, et al. Long-term recovery from unawareness, deficient counterregulation and lack of cognitive dysfunction during hypoglycaemia, following institution of rational, intensive insulin therapy in IDDM. Diabetologia 1994;37: Kalergis M, Schiffrin A, Gougeon R, Jones PJ, Yale JF. Impact of bedtime snack composition on prevention of nocturnal hypoglycemia in adults with type 1 diabetes undergoing intensive insulin management using lispro 33

5 insulin before meals: a randomized, placebo-controlled, crossover trial. Diabetes Care 2003;26: Raju B, Arbelaez AM, Breckenridge SM, Cryer PE. Nocturnal hypoglycemia in type 1 diabetes: an assessment of preventive bedtime treatments. J Clin Endocrinol Metab 2006;91: Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Study Group, Tamborlane WV, Beck RW, Bode BW, Buckingham B, Chase HP, Clemons R, Fiallo-Scharer R, Fox LA, Gilliam LK, Hirsch IB, Huang ES, Kollman C, Kowalski AJ, Laffel L, Lawrence JM, Lee J, Mauras N, O'Grady M, Ruedy KJ, Tansey M, Tsalikian E, Weinzimer S, Wilson DM, Wolpert H, Wysocki T, Xing D. Continuous glucose monitoring and intensive treatment of type 1 diabetes. N Engl J Med 2008;359:

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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