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1 당뇨병약물치료시식사고려사항 서울대학교병원급식영양과주달래 Nutritional Considerations for Diabetic Patients on Diabetes Medication Dal LaeJu Department of Food Service and Nutrition Care, Seoul National University Hospital, Seoul, Korea Abstract Individuals who have diabetes should receive individualized medical nutrition therapy (MNT) based on an assessment of the individual's current eating patterns, preferences, and metabolic goals. The dietician should be able to coordinate food choices with the type of diabetes medicine being taken. Knowledge of the actions, side effects, and contraindication of diabetes medicine can help the dietician coordinate appropriate MNT and physical activity, to assist the individual with diabetes to achieve optimal glycemic control without unwanted effects. Carbohydrate consistency is important for diabetic patients on oral diabetes medications. The primary side effects with initial treatment of biguanides, α-glucosidase inhibitors, and incretin mimetics include gastrointestinal discomfort, which can be minimized by taking the medication with food, starting at a low dosage, and increasing the dosage slowly. Common side effects from use of insulin and insulin secretagogues (sulfonylureas and meglitinides) are hypoglycemia and weight gain. Consistent meal times and carbohydrate consistency are important to reduce risk of hypoglycemia. Energy restriction, reduced fat intake, regular physical activity, and avoidance of frequent hypoglycemia can be beneficial in preventing or limiting weight gain. The insulin regimen should be fitted to the meal plan and adjusted over time based on the results of blood glucose monitoring. (J Korean Diabetes 2014;15:35-40) 35 Keywords: Diabetes mellitus, Medicine, Nutrition therapy 서론 당뇨병환자의합병증을예방하기위해서는무엇보다도혈당을철저하게조절해야하며, 당뇨병관리에있어서개별환자들에게맞는혈당치료목표와관리방법을선택하는것이중요하다 [1]. 철저한혈당조절을위해서는당뇨병진단초기부터적극적인생활습관개선및약물치료가권장되며 [1,2], 혈당조절을위해경구혈당강하제나인슐린등당뇨병약제를사용하는경우식사와의조화및상호작용에대해서도고려해야한다 [3]. 성공적인임상영양치료를위해서는개개인의식 욕, 기호도, 평소의식습관이나활동량뿐만아니라사용약물의특성을고려한개별화된식사계획이필요하다. 약물의특성과식사계획이잘맞지않는경우에는저혈당이나공복감, 체중증가등의문제가발생할수있으므로당뇨병교육영양사는경구혈당강하제의종류와각약제의작용기전과부작용, 인슐린의종류와작용시간, 인슐린 regimen 에대해잘이해하고이를영양치료시적용할수있어야한다. 이에영양치료의목표를설정하거나식사를계획할때당뇨병약물치료와관련하여영양적으로고려해야할사항들에대해살펴보고자한다. 교신저자 : 주달래, 서울시종로구대학로 101 서울대학교병원급식영양과, jurea@snuh.org

2 본론 1. 경구혈당강하제사용시영양적고려사항 경구혈당강하제는그작용기전에따라크게설폰요소계, 메글리티나이드계, 비구아나이드계, 알파글루코시데이제억제제, 티아졸리딘디온계, DPP-4 억제제, GLP-1 analogues 로나눌수있다 [2]. 이러한약제들은제 2 형당뇨병환자나인슐린을생성할수있는능력이어느정도남아있는이차성당뇨병환자를치료하는데단독요법으로사용하거나서로다른약제또는인슐린과복합요법으로사용할수있다 [4]. 경구혈당강하제를사용할경우가능하면매일매일의탄수화물섭취량 을일정하게유지하는것이혈당조절에유리하며 [5], 이들약제의특징과약제사용에따른영양적고려사항은다음과같다 (Table 1). 1) 설폰요소계 (sulonylureas) 설폰요소계는췌장의베타세포에서인슐린분비를자극함으로써혈당을떨어뜨리는작용을하기때문에베타세포의인슐린분비능이남아있는제 2 형당뇨병환자에게적용되는약제이다. 일반적으로아침식전에복용하며, 식사시간이지연되면저혈당이발생할수있기때문에식사를거르지않는것이중요하다. 특히노인과간이나신장기능이감소된경우설폰요소계의대사능력이감소되어저혈당의위험이더높으며, 식사가 Table 1. Nutritional implications related to oral glucose-lowering agents [2-5,10] 36 Medication class Potential for weight gain Potential for hypoglycemia Gastrointestinal side effects Nutritional implications Sulfonylureas Yes Yes No Carbohydrate intake should be consistent day-to-day at meals Energy restriction, reduced fat intake, and regular physical activity can be beneficial in preventing or limiting weight gain. Meglitinides Yes Yes No Best if carbohydrate intake is consistent day-to-day at meals and snacks, but the medication can be adjusted for the amount of carbohydrate to be consumed. If meal is omitted, the corresponding dose should be omitted to prevent hypoglycemia. Energy restriction, reduced fat intake, and regular physical activity can be beneficial in preventing or limiting weight gain. Biguanides No No Yes Best if carbohydrate intake is consistent day-to-day at meals Not for use in people who consume alcohol daily. Gradually titrate to minimize gastrointestinal side effects when initiating use. Taken with food to reduce gastrointestinal upset Potential to decrease vitamin B12 and folate absorption. Alpha glucosidase inhibitors No No Yes Best if carbohydrate intake is consistent day-to-day at meals Gradually titrate to minimize gastrointestinal side effects when initiating use. If hypoglycemia occurs in combination therapy, it should be treated with glucose. Thiazolidinediones Yes No No Best if carbohydrate intake is consistent day-to-day at meals Energy restriction, reduced fat intake, and regular physical activity can be beneficial in preventing or limiting weight gain. DPP-4 inhibitors No No Yes Best if carbohydrate intake is consistent day-to-day at meals and snacks, Gradually titrate to minimize gastrointestinal side effects when initiating use GLP-1 analogues Decreased No Yes Gradually titrate to minimize gastrointestinal side effects when initiating use DPP-4, dipeptidyl peptidase-4 ; GLP-1, glucagon like peptide-1.

3 당뇨병약물치료시식사고려사항 불규칙하거나탄수화물섭취가일정하지않을때, 또과도한운동시저혈당의위험이높다 [5]. 설폰요소계복용시 2~5 kg 정도의체중증가가보고되는데 [6] 이는인슐린분비의증가에의해이차적으로나타나기도하지만, 빈번한저혈당발생과저혈당의과도한치료과정과관련이있을수도있다 [5]. 따라서체중증가를예방하기위해서는열량제한및지방섭취조절, 규칙적인운동, 저혈당의예방및적절한치료가중요하다. 2) 메글리티나이드계 (meglitinides) 비설폰요소계이면서인슐린분비를촉진시키는약제로반감기가매우짧고흡수가빨라제 2 형당뇨병환자에있어식후혈당개선에유용하다 [4,5]. 약효가빠르기때문에식사 15 분전에복용해야하며, 만약식사를거르게되거나식사량이 240 kcal 미만으로적은경우저혈당예방을위해약제도복용하지않아야한다. 설폰요소계와마찬가지로인슐린분비증가에의해체중증가가문제가될수있으므로주의해야한다 [5]. 3) 비구아나이드계 (biguanides) 메트포르민은간에서당생성을억제시켜혈당을낮추는약제로, 심한인슐린저항성과이상지질혈증을보이는비만한제 2 형당뇨병환자의초기단독요법으로적합한약제이다 [4]. 식욕감소, 구역, 구토, 복통, 소화장애, 복부팽만감, 설사등의위장장애가발생할수있어식사직전또는식사와함께복용하고적은용량부터시작하여점진적으로약물용량을늘리는것을권장한다 [5]. (glucose tablets) 와같은단순당을섭취하여야한다 [3,7]. 5) 티아졸리딘디온계열약제티아졸리딘디온은 peroxisome proliferatoractivated receptor-γ (PPAR-γ) 수용체에대한강한선택성을갖고있는촉진제로말초의인슐린저항성을개선시키는약제이다 [4]. 부종과체중증가의부작용이있다. 인슐린을함께사용할경우체중증가가더많이발생하며, 약물용량이증가할수록체중증가가더큰것으로알려져있다 [5]. 열량제한및지방섭취조절, 규칙적인운동을통해체중이증가되지않도록주의해야한다. 6) DPP-4 억제제 (dipeptidyl peptidase-4 inhibitors) 인크레틴은경구음식물섭취후소장에서분비되는호르몬으로포도당의존적으로인슐린분비를증가시키고, 글루카곤농도는감소시켜포도당항상성을유지하는데중요한역할을한다. 체내에는 GLP-1 (glucagon like peptide-1) 과 GIP (glucose-dependent insulinotropic polypeptide) 의두가지인크레틴호르몬이존재하지만, 분비 1~2 분만에 DPP-4 에의하여빠른속도로비활성화된다. DPP-4 억제제는이러한인크레틴에대한분해효소의작용을억제하여인크레틴에의한인슐린의분비증가효과를극대화함으로써, 식후고혈당을효과적으로조절하는약제이다 [7]. 음식물복용과관계없이투약이가능하다. 저혈당발생이적으며체중에있어서도중립적인영향을나타낸다 [4]. 37 4) 알파글루코시데이즈억제제 (α-glucosidase inhibitors) 알파글루코시데이제억제제는소장세포막에존재하는알파글루코시데이제를억제하여장내에서포도당과같은단당류의생성을지연시켜식후혈당상승을억제하고, 식후인슐린분비반응을감소시킨다 [4]. 알파글루코시데이제억제제를사용할경우소장에서탄수화물의흡수가불완전함에따라대장에서탄수화물의추가적인분해로인하여지방산, 이산화탄소및수소가스가발생되고이에따라설사혹은복부팽만감등의소화기계부작용이약 30% 정도에서보고된다 [7]. 적은용량부터시작하고점진적으로약물용량을증가시키면부작용을최소화할수있으며 [5] 소화기계부작용에따라탄수화물의양을조정하는것이필요하다 [8]. 알파글루코시데이제억제제사용자체가저혈당을유발하지는않으나설폰요소계또는인슐린과병용할경우저혈당이발생할수있으며, 이경우에는반드시포도당정제 7) GLP-1 유사체 (GLP-1 analogues) GLP-1 유사체는사람의주요인크레틴인 GPL-1 이 DPP-4 에의해분해되는것을막기위한치료제이다. 평균 0.78~3.95 kg 정도의체중감소가관찰되며, 흔한부작용은상부위장관계증상 ( 구역, 구토, 포만감및드물게설사 ) 이있다 [9]. 적은용량부터시작하고, 점진적으로약물용량을증가시키면부작용을최소화할수있다 [5]. 2. 인슐린치료시영양적고려사항 1) 인슐린 regimen 에따른식사배분 (Table 2) 개개인의식욕, 기호도, 평소의식사습관이나활동량등에기초하여식사를계획하고, 이에맞추어인슐린치료를조정한다. 정해진용량의인슐린용량을사용하는경우에는매일매일의당질섭취량을일정하게유지하는것이좋으며, 투여한인슐린의작용시간에맞추어

4 Table 2. Nutritional implications related to insulin regimens [2-5,10] Insulin regimen Fixed insulin regimen - constant dose of basal insulin, may be combined with standard mealtime dose of rapid- or short-acting insulin. - premixed insulin may be used. Flexible insulin regimen - basal insulin(intermediate -acting or long acting) given once or twice daily in addition to bolus insulin (rapid- or short-acting insulin). - insulin pumps Nutritional implications related to insulin regimen Keep meal times consistent. Eat similar amounts of carbohydrates each day to match the set doses of insulin. Insulin doses need to be taken at consistent times every day. If short-acting insulin is combined with intermediate-acting insulin, snacks are helpful. Do not skip meals to reduce risk of hypoglycemia. It is helpful to exercise at consistent times. Take mealtime insulin before eating. If larger snacks (> 15 g carbohydrate) are eaten, an extra bolus of insulin can be injected pre snack. Mealtime insulin dose can be changed based on insulin-to-carbohydrate ratio and correction factor. Insulin can be adjusted to accommodate varying exercise times and amounts of exercise. 38 적절한간식을배분하는것이필요하다. 아침과저녁식사전에혼합된인슐린을투여하는혼합분할요법 (split-mixed insulin regimen) 의경우중간형과속효성인슐린주사최고작용시간에일어날수있는저혈당을예방하기위하여오전, 오후, 자기전간식을배분하여섭취하도록한다. 인슐린집중치료시속효성인슐린 (regular insulin) 을사용하는경우저혈당예방을위해간식섭취가필요할수도있으나초속효성인슐린 (rapid insulin) 의경우최고작용시간이짧아간식을생략하는것이좋다. 초속효성인슐린을사용할경우에는한끼식사량을충분히하면서식사에포함된당질량에맞도록인슐린용량을조절하는것이좋다 [11]. The Diabetes Control and Complications Trial (DCCT) 에서는음식섭취에따라인슐린용량을조절한군의당화혈색소가인슐린용량을조절하지않은군보다 0.5% 더낮게보고되었다 [12]. 적극적인슐린요법 ( 다회인슐린주사요법또는인슐린펌프 ) 을사용하는경우에는식사횟수나식사량, 운동량에대하여유연하게조절할수있고, 음식과간식의당질량에따라필요한식전인슐린의양을결정함으로써혈당목표에도달할수있다 [11]. 이를위해서는고급당질계산법 (advanced carbohydrate counting) 을이용한식사계획에대한교육이필요하다. 고급당질계산법은명절이나외식, 모임등평소와다른식사상황에서개별적인슐린대당질비 (insulin-to-carbohydrate ratio) 를이용하여실제섭취한당질의양에맞는적절한양의인슐린용량을조정하여혈당을조절하는방법이다. 또한고혈당발생시인슐린감수성지수 (insulin sensitivity factor) 를이용하여고혈당을교정하는방법도교육내용에포함된다 [11,13]. 2) 인슐린주사시간과식사시간초속효성인슐린은식사시에바로투여하거나식사 시작몇분내에투여하는것이좋다. 반면속효성인슐린의경우흡수되어작용하는데 30 분정도의시간이필요하므로식사 30 분전에투여해야한다. 하지만속효성주사투여후 30 분을기다리지못하고식사를하는경우식후혈당조절이어렵게되어인슐린사용량이늘어날수있다. 따라서제 1 형당뇨병, 인슐린을필요로하는제 2 형당뇨병환자는인슐린과식사의시간을잘맞추어인슐린과량사용으로인한체중증가를예방하여야한다 [5]. 속효성인슐린투여후식사시작할때까지기다릴수없을때에는당질이함유되지않은음식이나샐러드등을먼저섭취하면식후고혈당을막는데도움이된다. 식사를빨리끝내야한다면당질음식은나중에따로먹을수있도록준비하는것도한가지방법이될수있다 [10]. 반면중간형인슐린과작용시간이겹치거나인슐린펌프사용시기초주입량이많은경우, 또는활동량이나운동량이증가한경우에는인슐린투여후식사를기다리는동안저혈당이발생하는경우가있다. 이때에는인슐린주사시간과식사시간의간격을줄여야한다 [11]. 이러한경우들은현재의인슐린 regimen 과혈당측정결과에대한자료를모아개별적인치료지침을만들어야한다. 중국음식, 튀김류, 멕시칸음식, 피자, 육류위주의외식과같이고단백질 / 고지방식을섭취할경우는식사속의당질이혈당으로전환되는것이지연되어혈당의 peak time 이달라질수있으므로상황에따라인슐린주사시간이나방법을조절할필요가있다. 초속효성인슐린을사용하는경우라면인슐린을식사후에투여하거나식사전과후에나누어투여할수있다. 인슐린펌프사용시에는 bolus 인슐린주입방법을 Square Wave 또는 Dual Wave 방법으로선택하는것이좋다 [14]. 위의효과를평가하기위해자가혈당측정을시행하여관리하여야한다.

5 당뇨병약물치료시식사고려사항 3) 인슐린사용에따른부작용예방을위한식사시주의사항인슐린치료의가장큰부작용은저혈당이다. 대부분의저혈당의원인은약물이나인슐린의과다사용, 부적절한자가관리행위, 알코올, 기타약제사용등과관련되는경우가많으므로원인제거를위한식사계획및실천이중요하다 [11]. 저혈당이발생하면신속하게대처하고, 적절한양의당질을섭취하여과도한치료를최소화시켜야한다. 저혈당의정도및증상은개인에따라차이가있으므로개별화된치료지침을마련하는것이필요하다. 일반적인저혈당치료지침은혈당이 70 mg/dl 미만일때단순당질 g 을섭취하고 분뒤혈당을재측정하여계속낮으면추가로당질을섭취하는것이다 [4]. 저혈당의정도가심할수록당질필요량이증가하며, 보통 5 g 의포도당은혈당을약 15 mg/dl 정도증가시킨다. 신속한혈당회복을위해흡수가빠른단순당 ( 가장좋은것은포도당 ) 을섭취하도록하고, 과도한저혈당치료는이후고혈당을유발할수있으므로주의하도록한다. 저혈당의정확한원인을파악하여저혈당의재발을막도록한다. 만약이때체중감소에관심이적은환자는열량을추가로섭취하고, 체중조절이필요한경우에는인슐린의양을줄이는방향으로식사계획을수정한다. 알코올섭취가문제가된경우에는알코올섭취의문제, 올바른음주요령, 저혈당대비에대한교육을실시하여야한다 [11]. 인슐린을사용하면일반적으로체중이 2~3 kg 증가하며엄격한조절에서는 5 kg 이상증가할수있는데이는주로첫 1 년에발생한다. 이러한체중증가는인슐린투여후소변으로당배출이줄어들고, 조직의분해가줄어들며, 간헐적인저혈당에의한공복감으로음식섭취량이늘어나고, 인슐린의지방합성작용이증가하는기전으로알려져있다 [4]. 인슐린사용으로인한체중증가의문제를예방하기위해서는열량과지방의과잉섭취에주의해야하며, 저혈당으로인한과도한간식섭취를줄이기위해서는규칙적인식사와사전에계획된운동, 저혈당에대한교육이중요하다. 3. 식사, 운동, 약물의조화 한의학적제한사항이있는지, 운동을왜하는지, 기대하는효과는무엇인지에대한내용을사전에파악해야한다. 만약체중감량이목적이면고열량간식을추가하는것보다저열량간식을섭취하거나인슐린용량을줄이는것이좋다. 운동시간식섭취를고려할때에는운동의종류, 강도, 지속시간, 운동전혈당, 식사 / 간식시간, 인슐린의작용시간, 인슐린주사부위, 컨디션, 운동과관련된과거경험, 탈수의위험등을고려하여야한다 [11]. 혈당을모니터할때에는먼저식사계획에비추어식사시간과양이적절했는지, 운동및활동량이어떠했는지, 혈당에영향을미치는신체요인 ( 스트레스, 감기ㆍ몸살, 생리등 ) 이있었는지를파악하도록한다. 특별한문제가없었음에도혈당이조절되지않을경우에는약물처방의변경및인슐린 regimen 과용량조절을고려해야한다. 약물요법을시작하거나약물용량의변화가필요한경우이것이식사요법의실패로인한것이아니고영양, 운동, 약물요법의복합치료로바뀌는자연스러운치료과정임을이해시켜야한다. 결론 당뇨병교육영양사는환자의상태나동반질환, 처방약물, 합병증진행정도, 평소섭취량및식습관, 사회경제적상황, 당뇨병에대한적응능력, 환자의기호도등을고려하여개별화된영양치료계획을수립하여야한다. 경구혈당강하제또는인슐린을사용하는당뇨병환자의경우약제에대한올바른이해를토대로식사 / 운동 / 약물의조화에대해세밀하게신경을써야할것이다. 인슐린또는인슐린분비촉진혈당강하제를사용하는경우저혈당또는체중증가와같은부작용이생기지않도록사전에식사계획을세우고교육을통해저혈당을예방하고혈당검사결과를토대로융통성있는당뇨관리능력을향상시킬수있도록끊임없이훈련시키는것이중요하다. 이러한개별화된영양치료는실현가능한합리적인치료를가능하게하여대사조절향상에기여할수있으며 삶의질 향상측면에서도매우중요한역할을한다. 39 육체적활동과운동은강도, 지속시간등에따라차이가있으나혈당을감소시키며운동의효과는운동후 24 시간까지작용한다. 만약계획된운동이라면사전에약물사용을줄이거나식사량을조절하여야한다. 경구혈당강하제를사용하거나인슐린치료시비계획적인운동을할경우운동강도와운동전혈당수준에따라음식섭취를조정해야한다. 이를위해서는운동에대 참고문헌 1. American Diabetes Association. Standards of medical care in diabetes Diabetes Care 2014;37 Suppl 1:S Korean Diabetes Association. Treatment guideline for diabetes. 4th ed. Seoul: Gold Planning and Development; p64-80.

6 40 3. Evert AB, Boucher JL, Cypress M, Dunbar SA, Franz MJ, Mayer-Davis EJ, Neumiller JJ, Nwankwo R, Verdi CL, Urbanski P, Yancy WS Jr. Nutrition therapy recommendations for the management of adults with diabetes. Diabetes Care 2013;36: Korean Diabetes Association Education Committee. The guide for diabetes education. 3rd ed. Seoul: Gold Planning and Development; p American Dietetic Association. American Dietetic Association guide to diabetes medical nutrition therapy and education. Chicago: American Dietetic Association; p Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA 2002;287: Yoo HJ. Pharmacotherapy for postprandial hyperglycemia in type 2 diabetes. J Korean Diabetes 2012;13: Franz MJ, Reader D, Monk A. Implementing group and individual medical nutrition therapy for diabetes. American Diabetes Association. Alexandria: American Dietetic Association; p Chun HJ, Kwon HS. Clinical efficacy of glucagon like peptide-1 (GLP-1) analogues. J Korean Diabetes 2013;14: Warshaw HS, Bolderman KM. Practical carbohydrate counting: A how-to-teach guide for health professionals. 2nd ed. Alexandria: American Diabetes Association; p51-68, American Diabetes Association. Intensive Diabetes Management. 3rd Ed. Alexandria: American Dietetic Association; p Anderson EJ, Richardson M, Castle G, Cercone S, Delahanty L, Lyon R, Mueller D, Snetselaar L. Nutrition interventions for intensive therapy in the Diabetes Control and Complications Trial. The DCCT Research Group. J Am Diet Assoc 1993;93: Warshaw HS, Kulkarni K. Complete guide to carb counting. Alexandria: American Diabetes Association; p Bolderman KM. Putting your patients on the pump. Alexandria: American Dietetic Association; p47-52.

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ

Pharmacotherapeutics Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee Univ Application of New Pathogenesis on the Drug Treatment of Diabetes Young Seol Kim, M.D. Department of Endocrinology Kyung Hee University College of Medicine & Hospital E mail : ycell2@yahoo.co.kr Abstract