J Korean Diabetes 2017;18:229-238 Vol.18, No.4, 2017 ISSN 2233-7431 이민진, 김상수부산대학교의과대학부산대학교병원내분비대사내과 Management of Obesity in Patients with Diabetes Mellitus Min Jin Lee, Sang Soo Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea Abstract Both obesity and diabetes impose not only individual health problems, but also large socioeconomic burdens worldwide. Obesity is a major cause of insulin resistance and diabetes and is closely linked to a series of microvascular and macrovascular complications that ultimately lead to increased morbidity and mortality. According to recent national survey data in Korea, obesity affects about 50% of adults with type 2 diabetes mellitus. Given the evidence that anti-obesity management has been beneficial in the treatment for patients with type 2 diabetes mellitus and obesity, providers should establish a strategy for weight loss for optimal, comprehensive patient management. Lifestyle intervention including diet and exercise is the cornerstone of prevention and management for obesity and type 2 diabetes mellitus. Antiobesity drugs should be provided to those who do not respond appropriately to lifestyle intervention. Emerging data support the superiority of metabolic surgery over lifestyle or medical management for the management of type 2 diabetes associated with severe obesity. This article concisely reviews the current recommendation for lifestyle intervention including diet and exercise and pharmacological and surgical methods for obesity management in type 2 diabetic patients. Keywords: Bariatric surgery, Diabetes mellitus, Diet therapy, Exercise, Obesity Corresponding author: Sang Soo Kim Division of Endocrinology and Metabolism, Department of Internal Medicine, Pusan National University Hospital, Pusan National University School of Medicine, 179 Gudeok-ro, Seo-gu, Busan 49241, Korea, E-mail: drsskim7@gmail.com Received: Oct. 18, 2017; Accepted: Oct. 19, 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/bync/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Copyright c 2017 Korean Diabetes Association The Journal of Korean Diabetes 229
서론 국내비만의유병률은점차증가하고있으며, 최근국내의조사에따르면 2015년에는 32.4% 에달하는것으로보고하고있다 [1]. 또한국내제2형당뇨병환자에서절반이비만한것으로알려져있어 [2], 당뇨병환자에게서비만관리는보다중요할것으로여겨진다. 제2형당뇨병에서비만이동반되었을때, 당뇨병관련미세혈관합병증과대혈관합병증의유병률이증가하고나아가사망률또한증가함으로써, 질환의부담을배가시켜준다 [3]. 반면, 비만을관리하였을때당뇨병전단계또는제2형당뇨병으로의진행을막아줄뿐아니라, 당뇨병환자의관리에있어서도다른여러이점을제공해줄수있다 [4-6]. 과체중또는비만한제2형당뇨병환자가중등도로지속적인체중감량을하였을때, 혈당조절이양호해지고당뇨병약제의사용정도를줄여줄수있다 [6]. 체중감소를통한혈당개선효과는, 비만과동반한인슐린저항성으로인해가역적인베타세포기능부전및인슐린분비능감소를일으키는제2형당뇨병발생의초기단계에제공하였을때보다저명한것으로알려져있다 [7]. 그러나실제임상진료에서환자와임상의사들은당뇨병과비만을동시에바라보고관리하기보다는혈당조절그자체에만보다집중하는경향이있다. 제2형당뇨병환자의포괄적이고최적의치료법을제공해주기위해당뇨병에동반한비만을관리하는것이매우중요한요소임에틀림없을것이다. 본원고에서는제2형당뇨병환자에게서포괄적이고최적의관리를제공하기위한비만관리법을식이및운동을통한생활요법, 약물요법및수술적치료법등으로나누어살펴보고자한다. 식이요법 과체중또는비만한사람에서체중감량은제2형당뇨병의발생을예방할뿐만아니라, 당뇨병의조절과관리에있어서도효과적인방법으로알려져있다. 체중감량을위한생활습관중재는운동요법, 행동교정과함께식이요법이중 추적인역할을하고있다. 비만한당뇨병환자에서이상적인체중감량은체중의 7% 이상감량이며, 체중의 5% 감량은혈당을개선시키고, 체중의 5% 이상감량은혈당뿐만아니라, 지질과혈압을개선시키는것으로알려져있다 [4]. 미국당뇨병학회에따르면체중감량을위해서는하루총칼로리섭취에서 500~750 kcal/d를줄여야하고, 개인의체중과활동량에따라차이가있겠지만, 체중감량을위해서는여성에있어서는 1,200~1,500 kcal/d, 남성에있어서는 1,500~1,800 kcal/d 정도의칼로리섭취를권하고있다 [4]. 과체중또는비만한제2형당뇨병환자들을대상으로생활습관중재를통한체중감량이심혈관질환의위험과사망률에미치는영향을알아보기위한대규모의연구 (Look Action for Health in Diabetes [AHEAD] Trial) 가있었다 [8-10]. 체중감량을위한집중적생활습관중재 (intensive lifestyle intervention) 는식이와운동요법을함께하였기때문에식이요법단독의효과는알수없지만, 그내용을살펴보면하루총칼로리섭취를 1,200~1,800 kcal ( 체중이 140 kg 미만일때 1,200~1,500kcal/d, 140 kg 이상일때 1,500~1,800 kcal/d, 지방은총칼로리의 30% 미만, 포화지방은 10% 미만 ) 로제한하고, 일주일동안최소 175분이상중증도의육체적인활동을통해최소한 7% 이상의체중감량을목표로하였다. 약 10년정도의관찰에서비록집중적생활습관중재그룹에서심혈관질환과사망을유의하게감소시키지는못했지만, 집중적인생활습관중재그룹에서평균적으로체중의 4.7% 정도감량이있었고, 이그룹의약 50% 에서는체중의 5% 이상감소, 27% 에서는체중의 10% 이상감소가관찰되었다. 뿐만아니라집중적생활습관중재그룹에서평균당화혈색소가감소하였고, 항당뇨병약물또는항고혈압, 항고지혈증약물의필요성또한감소하였다. Look AHEAD 연구 1년째에체중, 당화혈색소, 혈압, 지질등의지표가가장큰차이를보였고시간이지날수록그차이가줄어듦을보여주었는데, 이는요요현상과관련이있고, 심혈관질환과사망률의감소를증명하지못한주요원인으로생각된다. 영양소의종류와양에따라식이의구성은다양할수있 230
이민진외 는데, 하루총칼로리섭취를동일하게제한한다면유사한체중감량과혈당조절에기여할수있다 [11,12]. 한메타연구는 6개월이상의연구를시행한무작위대조연구 20개를포함해서총 3,073명의제2형당뇨병환자를분석하였다 [13]. 저탄수화물식단, 채식식단, 저당질식단, 고섬유질식단, 지중해식식단, 그리고고단백식단을대조군 ( 저지방식단, 저단백식단, 고당질식단 ) 과비교하였다. 체중감량은저탄수화물식단 ( 0.69 kg, P = 0.21) 과지중해식식단 ( 1.84 kg, P < 0.001) 에서크게나타났고, 당화혈색소의감소는저탄수화물식단 ( 0.12%, P = 0.04), 저당질식단 ( 0.14%, P = 0.008), 지중해식식단 ( 0.47%, P < 0.001), 그리고고단백식단 ( 0.28%, P < 0.001) 에서크게나타났다. 하지만다양한식단의효과를비교하기위한연구는제한적이며, 이는식단의정의가일관적이지않고, 적은연구대상, 그리고탈락자의높은비율등으로인한것이다. 초저열량식 (very low calorie diet) 은하루에 800 kcal 이하로극심하게열량을제한하는것인데, 이를 3개월동안하였을때체중의 10~15% 정도감량이나타났다 [14,15]. 초저열량식은의학적감시와생활습관개선을위한중재가강도높게이루어질수있는상황에서만제한적으로사용되어야하고, 초저열량식을중단하였을때체중의증가가대조군에비해더심하게나타났기때문에장기간유지프로그램의뒷받침이필요하다. 현재의추세는저탄수화물식단, 저당질식단, 지중해식식단, 그리고초저열량식을선호하고있지만, 당뇨병환자에서비만관리를위한최적의식단은아직연구가더필요하다. 비만한당뇨병환자의체중감량을위해서는하루총섭취칼로리를제한하는것이중요하며, 환자의기호와건강상태를고려해서장기간잘실천할수있는식단을선택하는것이중요하다. 운동요법 제2형당뇨병의예방과관리를위한생활습관중재에서운동은앞서소개한식이요법과함께중추적인역할을한다. 규칙적인운동은혈당조절을향상시키고, 심혈관질환의 위험을감소시키며체중감소에기여한다. 제2형당뇨병환자를대상으로운동에의한당화혈색소와체질량지수의변화를살펴본메타분석에서운동군에서체중감소와무관하게당화혈색소가의미있게감소함을보여주었는데, 이는운동자체의혈당감소효과를보여준것이다 [16]. 유산소운동, 저항성운동, 그리고복합운동모두인슐린작용의개선에효과적이며, 장기간의운동은골격근, 지방, 간, 췌장기능에있어서혈당조절에유리한방향으로기능을개선한다고알려져있다 [17]. 미국당뇨병학회는제2형당뇨병환자에게최대심박수의 50~70% 인중등도강도이상의유산소운동을일주일에적어도 150분이상 ( 최대심박수의 70% 이상인고강도유산소운동일경우에는일주일에적어도 75 분이상 ), 3일이상해야하고연속해서 2일이상쉬지않도록하고, 금기사항이없다면저항성운동도일주일에 2회이상시행하도록권고하고있다 [18]. 과체중또는비만한성인들을대상으로체중감량을위한다양한운동프로그램들이제시되고있다. 미국과유럽의체중감량을위한상업적운동프로그램을메타연구한결과를살펴보면, Weight Watchers 프로그램을 12개월시행하였을때대조군보다적어도 2.6% 이상의체중감량을보여주었고, Jenny Craig 프로그램은대조군보다 4.9% 이상의체중감량, Nutrisystem 프로그램은 3개월에비교하였고대조군보다 3.8% 이상의체중감량을보여주었다 [19]. 이연구들은비록당뇨병환자만을대상으로한연구는아니지만, 비만한성인들을대상으로정형화된운동프로그램의체중감량효과를비교할수있었다는점에서의의가있다. Foster 등 [20] 은비만한제2형당뇨병환자에서 Nutrisystem 프로그램을 3개월동안하였을때체중감량뿐만아니라, 혈당개선측면에서도긍정적인결과를보여주었다. 과체중또는비만한제2형당뇨병환자에서운동요법단독으로체중감량의목표를달성하기는어렵다. 미국당뇨병학회에서제시한제2형에따르면, 체중의 5% 이상감량을위해서식이, 운동, 행동교정을포함한생활습관중재를적극적으로해야하는데, 하 www.diabetes.or.kr 231
루총에너지에서 500~750 kcal를줄여야한다고설명하고있다 [4]. 과체중또는비만한제2형당뇨병환자에서집중적인생활습관중재를통해서단기간의체중감량에성공하였다면, 1년이상의장기간체중감량을유지하기위해서는포괄적인관리가필요하다. 이는지속적으로체중을감시하고, 식이섭취칼로리를제한하고, 주 200~300분의높은강도의운동을필요로한다 [4]. 비만한당뇨병환자에서체중감량의목표를이루기위해서는더많은시간의운동 (200~300 min/wk) 을요구하고있지만, 운동요법은운동으로인한위험성 ( 발의상처, 심혈관질환, 망막출혈이나망막박리등 ) 을피하면서운동으로인한대사적이득은최대화할수있는적절한강도와양으로이루어져야한다. 할것을권고하고있다 [4,21]. 다만이런약물치료는저칼로리식이와육체적활동을포함한생활양식의변화를보조하고지속적으로유지할수있도록도와줌으로써체중감소효과를최대화할수있음을주지해야한다. 임신중이거나계획하고여성에서는금기이다. 약물치료첫 3개월동안매달효과와안전성에대한평가를해야한다. 만약치료 3개월후에도 5% 미만의체중감소효과를보이거나약제관련부작용을보인다면, 약제복용을중단하거나다른약제로변경할것을고려해야한다 [4]. 미국식품의약국 (U.S. Food and Drug Administration) 에서사용을승인한항비만약제들로주로제2형당뇨병환자에서의사용과관련해요약하고자한다. 항비만약물요법 1. Orlistat 제2형당뇨병환자에게서보다포괄적이고최적의치료를제공하기위해혈당조절그자체뿐아니라비만을동시에관리하는매우중요하다. 우선항당뇨병약제를선택함에있어, 체중관리가동시에필요로하는경우체중관리에보다이점을줄수있는약제를선택에앞서고려할필요가있다. 체중감소와연관있는항당뇨병약제들로는메트포르민, 알파 -글리코시다제억제제, sodium glucose cotransporter-2 억제제, glucagon-like peptide-1 (GLP-1) 작용제, 아밀린등은체중감소와연관이있는약제이며, 인슐린분비촉진제, 티아졸리디네디온, 인슐린등은체중증가와연관이있는약제로분류할수있다. 반면, dipeptidyl peptidase-4 억제제는체중증감소와무관한것으로알려져있다. 또한체중증가를유발할수있는다른약제를환자들이동시에투여받고있다면이를최소화하거나다른약제로의대체할수있는지고민해야한다. 체중증가를유발할수있는약제로는비정형항정신병제, 항우울제, 스테로이드, 경구피임제, 항전간제, 항히스타민제및항콜린약등이있다 [4]. 체질량지수가 27 kg/m 2 이상인제2형당뇨병환자는식이, 운동요법과더불어체중감소를위한약물치료를시도 Orlistat (Xenical; Roche, Basel, Switzerland) 은미국식품의약국에서체중조절을위해장기간사용할수있도록허가받은약이다. Pancreatic lipase 를억제해장으로부터지방흡수의 30% 를감소시켜준다. 우선비만환자에게서 orlistat은 4년간의치료기간동안제2형당뇨병의발생률을 37.3% 감소시켜주었다 [22]. 체중감소와독립적으로저밀도지단백콜레스테롤을감소시켜주었다. 반면지용성비타민 (A, D, E, K) 의혈중농도가낮아지기때문에, orlistat 복용하기 2시간전후에이런지용성비타민을보충할필요가있다. 2. Phentermine/topiramate extended-release Phentermine은교감신경작용약으로일차적으로식욕을감소시켜주고미국식품의약국에서는단기복용 (12주까지) 을허용하고있다. Phentermine은 28주동안위약대비 3.8 kg (phentermine군, 5.3 kg; 위약군, 1.5 kg) 의체중감소를보였으나 [23], 1년이상의임상연구는없어장기간사용에따른심혈관계안정성이확보되어있지않다. 주요부작용으로어지러움, 구갈, 수면장애, 변비및심박수증가 232
이민진외 등이있다. 이약제는심혈관질환, 울혈성심부전, 조절되지않는고혈압및뇌졸중이있는경우금기이다. 저위험에서중등도심혈관질환위험도를가진비만한제2형당뇨병환자에게서체중조절과대사조절을이루기위해, 생활요법과동시에시작해체중감소치료시작시점에시동을걸어주는역할을할수있을것이다. Topiramate는간질치료및편두통예방에사용되는신경치료제이다. Phentermine 과 topiramate는기전적으로시너지효과와부작용감소를통해각각처방하였을때보다더효과적으로체중감소를보여준다. 한연구에서 phentermine 15 mg과 topiramide 92 mg 을 56주사용하였을때, 9.8% 의체중감소 ( 위약군, 1.2%) 를보였다 [24]. 이연구에서제2형당뇨병환자에서는당화혈색소감소효과를, 당뇨병전단계에서는당뇨병으로의진행률을감소시켜주었다. 흔한부작용은구갈, 이상감각및변비이다. 뇌졸중, 조절되지않는고혈압, 관상동맥질환, 녹재장, 갑상산기능항진증및임신은금기이다. Topiramide는요로결석의발생과연관이있기때문에이에대한주의를기울일필요가있다. 3. Bupropion/naltrexone Bupropion은도파민과노르에피네프린의재흡수를억제하여작용하는반면, naltrexine은 opioid 수용체에작용을통해식욕을억제하고에너지대사를높여주는것으로알려져있다. 두가지약물을함께사용했을때상승효과를기대할수있으며 [24], 미국식품의약국에서도이복합제의사용을최근승인하였다. 과체중또는비만한제2형당뇨병환자를대상으로 bupropion/naltrexone 복합제를 56주투여하였을때, 체중을 5.0% 감소시켜줌과동시에 ( 위약군, 1.8%), 당화혈색소를 0.6% 감소시켜주었다 [24]. 흔한부작용으로오심, 변비, 두통, 구토및현훈등이있다 [25]. 4. 로카세린 (lorcaserin) 로카세린은시상하부의세로토닌수용체 5-HT 2c 수용체 에선택적으로작용하여식욕을억제하는것으로알려져있다. 비선택적으로 5-HT 2A, 5-HT 2B 수용체에작용하는약제들이심장판막질환발생의연관성으로시장에서철수된반면, 5-HT 2c 수용체에보다선택적으로작용한다고알려져있다 [26]. 비만한제2형당뇨병환자에서로카세린 10 mg 을하루두번 1년간복용하였을때, 체중을 4.5% 감소시켜주었고 ( 위약군, 1.5%), 당화혈색소를 1.0%, 공복혈당을 28.4 mg/dl 감소시켜주었다 [27]. 두통이가장흔한부작용이며, 오심, 피로감등이보고되고있으나, 판막질환의발생과악화에는영향이없는것으로알려져있다. 5. 리라글루타이드 (liraglutide) 리라글루타이드는 GLP-1 수용체작용제로서, 당뇨병환자에게서혈당조절뿐아니라, 최근미국식품의약국으로부터체중조절을위한약제로의승인을받았다. 제2형당뇨병환자에게서리라글루타이드 1.2 mg과 1.8 mg으로 2.5 kg과 4 kg의체중감소와함께, 당화혈색소를 0.48% 와 1.84% 감소시켜주었다 [28]. 비만치료목적으로써는하루 3 mg을 1회투여하도록하고있다. Satiety and Clinical Adiposity Liraglutide Evidence in non diabetic and diabetic individuals (SCALE) Diabetes 연구에서 56주동안리라글루타이드 3.0 mg은 6.0% 의체중감소와 ( 위약군, 2.0%) 더불어당화혈색소를 1.3% 감소시켜주었다 [29]. 또한최근리라글루타이드는심혈관계질환위험성이높은환자에게서주요심혈관질환의발생을유의하게줄여준바있다 [30]. 따라서이를근거로비만하고심혈관질환을동반한고위험군제2형당뇨병환자에게리라글루타이드는좋은선택약제가될수있겠다. 수술적치료 ( 대사수술, METABOLIC SURGERY) 베리아트릭수술 (bariatric surgery) 은일차적으로고도비만환자에게서체중감소를위한대체치료중하나로시 www.diabetes.or.kr 233
행되어왔다. 하지만당뇨병환자에서수술이후체중감소에앞서혈당개선효과를보이며, 또한단순히위장관의배열순서만재배치하더라도혈당조절에직접적인영향미치는연구결과들이이런위장관수술이제2형당뇨병치료를위한좋은치료법이될수있음을시사해주었다 [31]. 이런의미에서대사수술은일차적으로제2형당뇨병및그와연관된대사장애를치료하기위해시행된베리아트릭수술을말한다. 많은무작위대조연구를포함한연구들에서비만한제2형당뇨병환자에서혈당조절과심혈관질환위험인자를감소시키는데대사수술이생활요법개선및약물치료에비해우월함을보여주고있다 [32]. 비록무작위대조연구가아니지만, 여러관찰연구들에서당뇨병관련미세혈관합병증및대혈관합병증이개선시켜주고나아가사망률을감소시켜줌을보여주고있다 [33,34]. 여러연구에서수술후 30~63% 의당뇨병관해를보인다고보고하고있다 [32]. 시간이지남에따라점차재발하는비율이증가하지만, 수술을시행받은대부분의환자들은재발여부에관계없이좋은혈당개선효과를보여주고있다 [35,36]. 젊은나이, 짧은당뇨병유병기간, 인슐린비사용등이높은당뇨병관해율과낮은재발률과연관이있는것으로보고하고있다 [37]. 수술도중사망률과이환율은담낭절제술과충수절제술과같은저위험의복부수술과유사한것으로알려져있다 [33]. 드물지만심근경색및폐색전증같은심폐합병증이수술도중발생하는사망의 70% 를차지하는주요사망원인이다. 문합부위의누출, 장폐색, 변연궤양등이수술후발생할수있다. 대사수술에따른수술합병증이발생할위험인자는높은체질량지수, 나이, 동반한이환질환, 흡연및재수술등이있다 [38]. 수술후발생하는영양결핍은위우회술과담췌류전환술에서보다흔하고위소매절제술과위밴드술에서는보다드물게발생한다. 수술후흔한영양결핍으로는비타민 A, B 12, D, 아연, 철분, 페리틴, 셀레늄과엽산등이있다 [39]. 따라서수술전에이런결핍이있는지미리확인하고동반한결핍은교정할것을권고할수있겠다. 수술후철분과비타민 B 12 의흡수저하로인해경미 한빈혈이흔히발생한다. 영양결핍은적절한비타민, 철분및칼슘보충제등으로예방하고교정할수있다 [40]. 골밀도의감소도대사수술후발생하는것으로알려져있다 [41]. 체중감소로인한기계적인중력부하의감소와칼슘과비타민 D 등의미세영양소의흡수저하, 신경호르몬의변화등이골밀도저하의원인으로여겨진다. 하지만수술후발생하는골밀도저하가부하감소에따른골격의기능적적응에따른것인지, 골다공증성골절이얼마나증가하는지등에대해서는아직잘알려져있지않다. 단백질의결핍이또한종종발생할수있다. 수술후경구단백질보충제 ( 하루 80~100 g) 를먹기를권장하고, 영양과관련한합병증을평생모니터링할것을권장한다 [42]. 한편, 신장결석, 알코올중독, 우울증및자살의증가들도뚜렷하지않으나우려되는합병증으로생각되기때문에, 임상의사들은이에대해주의를기울일필요가있다 [43]. 제2형당뇨병환자에서관리하는데있어, 대사수술에대한국제적인의견일치는아직없는상태이다. 전세계 50개이상의당뇨병또는의학관련단체에의해추천된 2nd Diabetes Surgery Summit (DSS-II) Consensus Conference에서제2형당뇨병에서대사수술에대한권고문을발표한바있다 [10]. 이권고사항에따르면, 혈당조절상태와상관없이 Class III ( 체질량지수 40 kg/m 2 ) 와생활요법및최적의내과적치료에도혈당조절이불량한 Class II ( 체질량지수 35.0~39.9 kg/m 2 ) 에해당하는제2형당뇨병환자의치료를위해대사수술을권고해야만한다고합의하고있다. 또한경구및주사제치료로혈당조절이불량한체질량지수가 30.0에서 34.9 kg/m 2 인제2형당뇨병환자에서도수술을고려할수있다고하고있다. 아시아인들에게는체질량지수기준을 2.5 kg/m 2 를차감하여고려하도록하고있다. 결론 비만과제2형당뇨병은우리나라를포함한전세계적으로심각한사회경제적문제를야기하고있는대표적질환이다. 234
이민진외 제2형당뇨병환자에동반된비만은혈압조절뿐아니라당뇨병합병증관련한높은이환율과사망률과연관이있기때문에, 당뇨병관리에서있어혈당조절상태와더불어체중조절에세심한관심을기울일필요가있다. 식이와운동요법은제2형당뇨병과함께비만을관리하는데중추적인역할을하는것은분명한사실이다. 생활요법만으로충분한체중감량효과를보이지못하는경우허가를받은항비만약물치료와대사수술등을포함한적극적인관리를통해환자들의삶의질을개선시키고자노력을기울여야할것이다. REFERENCES 1. Kim YH, Han K, Son JW, Lee SS, Oh SW, Kwon HS, Shin SA, Kim YY, Lee WY, Yoo SJ; Taskforce Team of the Obesity Fact Sheet of the Korean Society for the Study of Obesity. Data analytic process of a nationwide population-based study on obesity using the national health information database presented by the national health insurance service 2006-2015. J Obes Metab Syndr 2017;26:23-7. 2. Noh J, Han KD, Ko SH, Ko KS, Park CY. Trends in the pervasiveness of type 2 diabetes, impaired fasting glucose and co-morbidities during an 8-year-follow-up of nationwide Korean population. Sci Rep 2017;7:46656. 3. Oldridge NB, Stump TE, Nothwehr FK, Clark DO. Prevalence and outcomes of comorbid metabolic and cardiovascular conditions in middle- and older-age adults. J Clin Epidemiol 2001;54:928-34. 4. American Diabetes Association. 7. Obesity management for the treatment of type 2 diabetes. Diabetes Care 2017;40(Suppl 1):S57-63. 5. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403. 6. Pastors JG, Warshaw H, Daly A, Franz M, Kulkarni K. The evidence for the effectiveness of medical nutrition therapy in diabetes management. Diabetes Care 2002;25:608-13. 7. Rothberg AE, McEwen LN, Kraftson AT, Fowler CE, Herman WH. Very-low-energy diet for type 2 diabetes: an underutilized therapy? J Diabetes Complications 2014;28:506-10. 8. Look AHEAD Research Group, Wing RR, Bolin P, Brancati FL, Bray GA, Clark JM, Coday M, Crow RS, Curtis JM, Egan CM, Espeland MA, Evans M, Foreyt JP, Ghazarian S, Gregg EW, Harrison B, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jakicic JM, Jeffery RW, Johnson KC, Kahn SE, Kitabchi AE, Knowler WC, Lewis CE, Maschak-Carey BJ, Montez MG, Murillo A, Nathan DM, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Reboussin D, Regensteiner JG, Rickman AD, Ryan DH, Safford M, Wadden TA, Wagenknecht LE, West DS, Williamson DF, Yanovski SZ. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. N Engl J Med 2013;369:145-54. 9. Look AHEAD Research Group. Eight-year weight losses with an intensive lifestyle intervention: the look AHEAD study. Obesity (Silver Spring) 2014;22:5-13. 10. Look AHEAD Research Group, Gregg EW, Jakicic JM, Blackburn G, Bloomquist P, Bray GA, Clark JM, Coday M, Curtis JM, Egan C, Evans M, Foreyt J, Foster G, Hazuda HP, Hill JO, Horton ES, Hubbard VS, Jeffery RW, Johnson KC, Kitabchi AE, Knowler WC, Kriska A, Lang W, Lewis CE, Montez MG, Nathan DM, Neiberg RH, Patricio J, Peters A, Pi-Sunyer X, Pownall H, Redmon B, Regensteiner J, Rejeski J, Ribisl PM, Safford M, Stewart K, Trence D, Wadden TA, Wing RR, Yanovski SZ. Association of the magnitude of weight loss and www.diabetes.or.kr 235
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