Metastatic gastric carcinoma in a 19-year-old man.

Ku, Yun Hyi,Lee, Keun-Wook,Kim, Jee Hyun,Ko, Hyoungsuk,Lee, Hye Seung,Choe, Gheeyoung,Kim, Young Hoon Grune Stratton ; American Society of Clinical Onco 2007 Journal of clinical oncology Vol.25 No.31

제2형 당뇨병환자에서 유산소 운동 강도에 따른 인슐린저항성의 변화

구윤희 ( Yun Hyi Ku ),구보경 ( Bo Kyung Koo ),안희정 ( Hee Jung Ahn ),정지연 ( Ji Yun Jeong ),석희금 ( Hee Geum Seok ),김호철 ( Ho Chul Kim ),한경아 ( Kyung Ah Han ),민경완 ( Kyung Wan Min ) 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.5

연구배경: 운동은 주로 동맥경화증 및 인슐린저항성으로부터 보호하는 작용을 통해 사망률을 감소시키는 데에 도움이 되는 것으로 알려져 있다. 이번 연구에서는 제2형 당뇨병환자에서 어떤 강도의 운동이 염증을 완화하고, 내피 세포 기능을 개선시키며 인슐린저항성을 호전시키는 데에 더욱 도움이 되는지 알아보고자 하였다. 방법: 총 59명의 비만한 여성 2형 당뇨병환자가 대조군(CG, N=18), 중강도 운동군(MEG, N=17), 고강도 운동군(VEG, N=14)으로 randomly 배정되어, 가속계로 모니터하며 12주간 운동 요법을 시행하였다. 연구시작시점, 12주 운동 종료 시점, 연구시작으로부터 1년 시점에 체중, 전산화 단층 촬영을 이용하여 복부지방, 피하지방, 내장지방을 측정하였으며, 혈장 hs-CRP, IL-6, 인슐린감수성을 측정하였다. 결과: 평균 연령은 54±7세, 체질량지수는 26.9±2.5 kg/m2이었다. 운동 요법 동안 두 운동군은 운동 칼로리로 각각 488.6±111.9 kcal/day, 518.8±104.1 kcal/day를 사용하였다. 체질량지수, 복부지방, 피하지방은 두 운동군에서(ΔBMI: -1.1±0.7, -0.8±0.5, ΔTF: -4,647±3,613 mm2, -2,577±2,872 mm2, ΔSF: -2,057±2,021 mm2, -1,141±1,825 mm2, respectively) 대조군에 비해 유의하게 감소하였으나(P<0.01), hs-CRP, IL-6 및 FMD는 변화 없었다. 인슐린감수성은 고강도 운동군에서만 감소하였으며, 내장지방은 중강도 운동군에서만 감소하였다. 1년 추적관찰 결과, 이러한 차이는 모두 소실되는 경향을 보였다. 결론: 제2형 당뇨병환자에서 체중 및 체지방 감소를 동반한 고강도 운동은 3개월간의 intervention을 통해 전신 염증수치나 내피 세포 기능의 변화 없이 인슐린감수성 개선 효과를 나타냈다. Background: Exercise offers protection against atherosclerosis and insulin resistance. We evaluated the benefits of exercise at different levels of intensity for ameliorating inflammation, endothelial dysfunction, and insulin resistance in a sample of type 2 diabetic subjects. Methods: Fifty-nine overweight women with type 2 diabetes were randomly assigned to control (CG, N=18), moderate-intensity exercise (MEG, N=17), and vigorous-intensity exercise (VEG, N=14) groups. Patients in the two experimental groups completed a 12-week exercise program, with their exercise activities monitored by accelerometers. We assessed the patients` body weights, total abdominal fat (TF), subcutaneous fat (SF) and visceral fat (VF) via computed tomography, measurements of plasma levels of hs-C-reactive protein (hs-CRP) and interleukin-6 (IL-6), assessment of endothelial function by brachial artery flow-mediated dilation (FMD), and evaluation of insulin sensitivity by insulin tolerance tests, at baseline, at the end of the 12-week interventions, and one year after initiation of the study. Results: At baseline, the average age of all subjects was 54±7 years, and average body mass index (BMI) was 26.9±2.5 kg/m2. During the intervention, patients in the MEG and VEG groups expended comparable amounts of activity-related calories (488.6±111.9 kcal/day, 518.8±104.1 kcal/day, respectively). Although BMI, TF, and SF decreased similarly in the MEG and VEG groups (ΔBMI: -1.1±0.7, -0.8±0.5, ΔTF: -4,647±3,613 mm2, -2,577±2,872 mm2, ΔSF: -2,057±2,021 mm2, -1,141±1,825 mm2, respectively), compared to control (P<0.01), hs-CRP, IL-6, and FMD remained constant in both exercise groups even after completion of the 12-week exercise intervention. Insulin sensitivity improved only in patients subjected to vigorous exercise (VEG). Visceral fat loss was observed only in patients subjected to moderate exercise (MEG). At one-year follow up, these values had all returned to baseline. Conclusion: Exercise vigorous enough to result in significant weight and fat reduction did not ameliorate inflammation and endothelial dysfunction as measured at the end of a 12-week exercise intervention, nor did it result in sustained improvements in insulin sensitivity in type 2 diabetic subjects. (Korean Diabetes J 33:401-411, 2009)

저자회신 : 제2형 당뇨병환자에서 유산소 운동 강도에 따른 인슐린저항성의 변화(Korean Diabetes J 33:(5)401-411, 2009)

구윤희 ( Yun Hyi Ku ),구보경 ( Bo Kyung Koo ),민경완 ( Kyung Wan Min ) 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.6

원저 : Adipose Differentiation-Related Protein (ADRP)이 골격근의 포도당 수송에 미치는 영향

구윤희 ( Yun Hyi Ku ),김민 ( Min Kim ),김세나 ( Se Na Kim ),박호선 ( Ho Seon Park ),김한종 ( Han Jong Kim ),이인규 ( In Kyu Lee ),신동훈 ( Dong Hoon Shin ),정성수 ( Sung Soo Chung ),박상규 ( Sang Gyu Park ),조영민 ( Young Min Cho 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.3

연구배경: 골격근은 양적으로 인슐린저항성의 가장 중요한 조직이다. 최근의 연구결과들은 골격근 내의 지질 축적에 따라 인슐린저항성이 증가하는 것을 보여주고 있다. 이에 따라 골격근의 지질수송, 저장 및 대사에 관여하는 단백질들이 인슐린작용에 미치는 영향에 대한 관심도 증가되고 있다. Adipose differentiation-related protein (ADRP)는 lipid droplet의 표면에 존재하는 단백질의 하나로 peroxisome proliferator activated receptor γ (PPARγ)에 의해 조절되며 인슐린저항성과 관련이 있을 것으로 주목 받고 있으나 골격근에서 ADRP가 포도당 대사에 대해 어떤 역할을 하는지는 잘 알려져 있지 않다. 방법: db/db 마우스의 골격근에서 ADRP의 발현을 조사하고 PPARγ agonist투여 후의 ADRP의 발현의 변화를 비교하였다. 또한, 사람의 골격근 세포를 배양하여 PPARγ agonist 혹은 고지방배지를 처리하였을 때 ADRP의 발현을 조사하고, siRNA를 이용하여 ADRP를 knockdown 혹은 아데노바이러스를 이용하여 과발현 시킨 후 포도당 수송의 변화를 측정하였다. 결과: db/db 마우스는 정상 대조군에 비해 골격근에서 ADRP의 발현이 증가되어 있었으며, PPARγ agonist를 처리하면 더욱 증가하는 경향을 보였다. 또한 사람의 근육세포에서도 PPARγ agonist 혹은 고지방배지 처리에 의해 ADRP의 발현이 증가함을 확인하였다. ADRP를 knockdown 시키면 기저 및 인슐린 자극에 의한 포도당 수송이 유의하게 감소하였으며, 과발현 시키면 유의하게 증가하였다. 결론: ADRP는 고지방에 노출된 경우 혹은 PPARγ agonist에 의해 골격근에서 발현이 증가되며, 증가된 ADRP는 골격근으로의 포도당 수송능을 증가시키는 효과를 보였다. 이는 골격근에서 PPARγ 활성화가 직접적으로 인슐린감수성을 개선시키는 한 가지 기전으로 생각되며, 또한 세포 내 지방 축적 시 인슐린저항성을 유도하는데, 이때 ADRP가 세포 내 지방으로부터 보호하는 역할을 하는 것으로 생각된다. Background: Skeletal muscle is the most important tissue contributing to insulin resistance. Several studies have shown that accumulation of intramyocellular lipid is associated with the development of insulin resistance. Thus, proteins involved in lipid transport, storage and metabolism might also be involved in insulin action in skeletal muscle. Adipose differentiation-related protein (ADRP), which is localized at the surface of lipid droplets, is known to be regulated by peroxisome proliferator activated receptor γ (PPARγ). However, it is not known whether ADRP plays a role in regulating glucose uptake and insulin action in skeletal muscle. Methods: ADRP expression in skeletal muscle was measured by RT-PCR and western blot in db/db mice with and without PPARγ agonist. The effect of PPARγ agonist or high lipid concentration (0.4% intralipos) on ADRP expression was also obtained in cultured human skeletal muscle cells. Glucose uptake was measured when ADRP was down-regulated with siRNA or when ADRP was overexpressed with adenovirus. Results: ADRP expression increased in the skeletal muscle of db/db mice in comparison with normal controls and tended to increase with the treatment of PPARγ agonist. In cultured human skeletal muscle cells, the treatment of PPARγ agonist or high lipid concentration increased ADRP expression. siADRP treatment decreased both basal and insulin-stimulated glucose uptake whereas ADRP overexpression increased glucose uptake in cultured human skeletal muscle cells. Conclusion: ADRP expression in skeletal muscle is increased by PPARγ agonist or exposure to high lipid concentration. In these conditions, increased ADRP contributed to increase glucose uptake. These results suggest that insulin-sensitizing effects of PPARγ are at least partially achieved by the increase of ADRP expression, and ADRP has a protective effect against intramyocellular lipid-induced insulin resistance. (Korean Diabetes J 33:206-214, 2009)

SGLT2 억제제와 케톤산증: 발생기전과 대처

구윤희 ( Yun Hyi Ku ) 대한내과학회 2017 대한내과학회지 Vol.92 No.5

Sodium-glucose cotransporter 2 inhibitors are antidiabetic drugs that increase urinary glucose excretion by inhibiting proximal tubular reabsorption of glucose in the kidney. Some sodium-glucose cotransporter 2 inhibitors have been shown to afford effective glycemic control and to decrease the risks of major adverse cardiovascular events. However, these drugs may increase the risk of diabetic ketoacidosis. This is a rare complication that occurs in less than 0.1% of treated patients with type 2 diabetes. The condition may be euglycemic, and is triggered by controllable precipitating factors such as surgery, infection, and insulin reduction or omission. It is important to understand individual patient profiles and to prevent diabetic ketoacidosis by appropriate prescribing, by withholding sodium-glucose cotransporter 2 inhibitors when indicated, and by counseling patients on sick day management. (Korean J Med 2017;92:443-449)

제2형 당뇨병환자에서 나이에 따른 최대근력의 변화

권휘련 ( Hwi Ryun Kwon ),구윤희 ( Yun Hyi Ku ),안희정 ( Hee Jung Ahn ),정지연 ( Ji Yun Jeong ),류상열 ( Sang Ryol Ryu ),구보경 ( Bo Kyung Koo ),한경아 ( Kyung Ah Han ),민경완 ( Kyung Wan Min ) 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.5

연구배경: 당뇨병환자에서 유산소 운동만으로는 근력 향상의 효과를 기대하기는 어렵다. 저항운동으로 근력 운동을 병행했을 때 근질량, 근력 및 인슐린감수성이 향상된다. 그러나 우리나라 당뇨병환자에서 저항운동의 기준이 되는 최대근력에 대한 자료가 없는 실정이다. 본 연구에서는 제 2형 당뇨병환자에서 운동 강도와 부하의 척도가 되는 최대근력의 기준 자료를 마련하고, 연령에 따라 최대근력이 어떻게 변화하는지 알아보고자 하였다. 방법: 제2형 당뇨병환자 총 266명(남: 95, 여: 171)이 연구에 참여하였다. 근력의 척도로 최대근력(1RM; KEISER, Fresno, CA, USA)을 측정하였고, 최대근력 측정을 위해 상체는 체스트 프레스(chest press), 하체는 레그 프레스(leg press)를 이용하였다. 결과: 상·하지 최대근력은 연령이 증가할수록 유의하게 감소하였다. 상지 최대근력: (남) r=-0.454, P<0.001, (여) r=-0.480, P<0.001; 하지 최대근력: (남) r=-0.569, P<0.001, (여) r=-0.452, P<0.001. 남자의 최대근력은 나이가 증가하면서 감소하는 경향을 보였지만 통계학적으로 유의한 감소는 70대부터 관찰되었고 여자는 50대부터 지속적으로 유의하게 감소하였다. 결론: 제2형 당뇨병환자에서 남·녀 모두 최대근력은 연령이 증가함에 따라 감소하는 경향을 보였다. 특히, 50대 이후부터 저항운동이 도움이 될 것으로 사료된다. Background: It is difficult to improve muscle strength with only aerobic exercise training in type 2 diabetes patients. Resistance training is effective for improving muscle mass, muscle strength and insulin sensitivity. One repetition maxima (1RM), or the maximum amount of weight a subject can lift in a single repetition, may be a useful unit for evaluating the results of resistance training in type 2 diabetic patients. This study was aimed to assess baseline values for 1RM in a sample of Korean type 2 diabetes mellitus patients that are scaled for intensity and load of exercise, and to assess the relationship of 1RM to age. Methods: A total of 266 (male: 95, female: 171) Korean patients with type 2 diabetes mellitus were included in the study sample. Maximal muscle strength was assessed by measuring 1RM for each subject (KEISER, Fresno, CA, USA). Two different exercises were used to measure 1RM: the chest press for the upper extremities, and the leg press for the lower extremities. Results: Both upper and lower values of 1RM decreased with age in men and women; upper 1RM: r=-0.454, P<0.001 in men, r=-0.480, P<0.001 in women, lower 1RM: r=-0.569, P<0.001 in men, and r=-0.452, P<0.001 in women. Values of 1RM significantly decreased in men only after the age of 70. In women, values of 1RM continuously decreased after the age of 60. Conclusion: The maximal muscle strength of individuals with type 2 diabetes decreases with age. We believe that resistance training is especially beneficial for type 2 diabetes mellitus patients after the sixth decade of life. (Korean Diabetes J 33:412-420, 2009)

증례 : 후신경모세포종에 합병된 이소성 부신피질자극 호르몬 증후군 1예

구보경 ( Bo Kyung Koo ),구윤희 ( Yun Hyi Ku ),김진택 ( Jin Taek Kim ),김홍일 ( Hong Il Kim ),이유진 ( You Jin Lee ),조영민 ( Young Min Cho ),김성연 ( Seong Yeon Kim ) 대한내과학회 2006 대한내과학회지 Vol.71 No.3

요약하면 본 증례는 후신경모세포종에 병발한 이소성 ACTH 증후군에 대한 보고로서 국내에서는 첫 보고이다. 고 코르티솔 혈증에 의한 면역 기능 약화로 주폐포자충 폐렴 및 거대세포바이러스 폐렴에 이환되었으며 부신의 스테로이드 합성 억제 및 TMP/SMX 투약 후 회복되었다. 이소성 ACTH 증후군에서 원인 질환의 조속한 치료와 더불어 내인성 코르티솔 과잉 상태의 해결이 필요함을 시사하는 증례이다. We here present the case of a 37-year-old woman who suffered from adrenocorticotrophic hormone (ACTH)-dependent Cushing`s syndrome due to an olfactory neuroblastoma. The patient`s clinical course was complicated by co-infection with cytomegalovirus and Pneumocystis jirovechi, which improved with appropriate antimicrobial therapy and suppression of endogenous steroidogenesis with ketoconazole and octreotide. Radiation to the mass in the nasal cavity resulted in reduction of tumor size and remission of the Cushing`s syndrome. This is the first report of the ectopic ACTH syndrome resulting from olfactory neuroblastoma in Korea.(Korean J Med 71:309-315, 2006)

Original Article : The Effects of Resistance Training on Muscle and Body Fat Mass and Muscle Strength in Type 2 Diabetic Women

( Hwi Ryun Kwon ),( Kyung Ah Han ),( Yun Hyi Ku ),( Hee Jung Ahn ),( Bo Kyung Koo ),( Ho Chul Kim ),( Kyung Wan Min ) 대한당뇨병학회 2010 Diabetes and Metabolism Journal Vol.34 No.2

Background: Our goal was to investigate the effects of low intensity resistance training on body fat, muscle mass and strength, cardiovascular fitness, and insulin sensitivity in type 2 diabetes. Methods: Twenty-eight overweight women with type 2 diabetes were randomly assigned to a resistance training group (RG, n=13) or a control group (CG,n=15). RG performed resistance training using elastic bands, of which strength was equal to 40 to 50% of one repetition maximum (1RM), for three days per week. Each exercise consisted of three sets for 60 minutes. We assessed abdominal fat using computed tomography, muscle mass using dual-energy X-ray absorptiometry, and muscle strength using Keiser`s chest and leg press. Insulin sensitivity was measured using the insulin tolerance test, and aerobic capacity was expressed as oxygen uptake at the anaerobic threshold (AT-VO2) before and after the 12-week exercise program. Results: The age of participants was 56.4±7.1 years, duration of diabetes was 5.9±5.5 years, and BMI was 27.4±2.5 kg/m2 , without significant differences between two groups. During intervention, a greater increase in muscle mass and greater decreases in both total fat mass and abdominal fat were observed in RG compared to those of CG (P=0.015, P=0.011, P=0.010, respectively). Increase in 1RM of upper and lower extremities was observed in the RG (P=0.004, P=0.040, respectively), without changes in AT-VO2 and insulin resistance in either group. Conclusion: In conclusion, the low intensity resistance training was effective in increasing muscle mass and strength and reducing total fat mass without change of insulin sensitivity in type 2 diabetic patients.

Poster Session : PS 1311 ; Endocrinology : Brown Tumor Regression in the Patient with Parathy-roid Carcinoma Induced Primary Hyperparathyroidism

( Gil Tae Lee ),( Eun Kyoung Kim ),( Il Han Lim ),( Guk Haeng Lee ),( Yun Hyi Ku ) 대한내과학회 2014 대한내과학회 추계학술대회 Vol.2014 No.1

Primary hyperparathyroidism is a generalized disorder of calcium, phosphate, and bone metabolism due to an increased secretion of parathyroid hormone(PTH). Because of an extensive bone resorption is occasionally accompanied, it is able to be mistaken for bone metastases of solid tumors or multiple myeloma. We report the case of a 29-year-old woman who presented with back and pelvic pain and extensive bone lesions in radiologic imaging studies. 18F-fiuorodeoxyglucose positron emission tomography/ computed tomography (18FDG-PET/CT) showed multiple osteolytic lesions on mandible, C-T-L-S spines, both scapula, both clavicles, both humeri, right radius, both ulna, multiple metacapal bones, both ribs, both pelvic bones and both femora. Biopsies of the right iliac bone and bone marrow were identified with brown tumors associated with primary hyperparathyroidism. Thyroid ultrasonogram revealed 5cm sized cystic mass in the left portion of anterior neck, 99mTc MIBI scan showed faint delayed uptake of left thyroid area, and plasma intact-PTH was 1155.4 pg/mL, which were suggestive of hyperparathyroidism derived from left parathyroid lesion. Resection of the left upper parathyroid mass was performed, and pathological diagnosis con-firmed parathyroid carcinoma. Eight months later, 18FDG-PET/CT showed no abnormal . ndings in systemic skeleton any longer. In addition, severe osteoporosis was dramatically improved in 8 months (Z-score of lumbar spines: -4.4 to -1.3, Z-score of femur neck:-4.4 and -3.8 to normal) and alkaline phosphatase measured more than 10 times above reference range at diagnosis was decreased to normal. It is suggested that hyperparathyroidism should be considered for differential diagnosis of multiple osteolytic bone lesions and that severe bone lesions of hyperparathyroidism are able to be fully recovered by proper management.

제2형 당뇨병환자에서 최대근력과 유산소 운동능력 및 비만도의 관련성

권휘련 ( Hwi Ryun Kwon ),한경아 ( Kyung Ah Han ),구윤희 ( Yun Hyi Ku ),안희정 ( Hee Jung Ahn ),구보경 ( Bo Kyung Koo ),민경완 ( Kyung Wan Min ) 대한당뇨병학회 2009 Diabetes and Metabolism Journal Vol.33 No.6

연구배경: 당뇨병환자에서 유산소 운동과 근력 운동을 병행하면 심폐기능 향상, 복부지방 감소, 혈당 강하, 인슐린감수성 증가 등의 이점이 있다. 복합 운동을 시행할 때 유산소 운동능력 및 최대근력이 운동 강도 설정의 기본이 된다. 본 연구에서는 당뇨병환자에서 최대근력과 유산소 운동능력 및 비만도와의 상관성을 알아보고자 하였다. 방법: 총 177명(남: 85, 여: 92)의 당화혈색소 10% 이하의 제2형 당뇨병환자를 대상으로 하였다. 상체는 chest press, 하체는 leg press로 최대근력(Keiser)을 측정하였고, VO2max (ER900; Jager)를 이용하여 유산소 운동 능력을, 체성분분석(Inbody 3.0)을 통해 근육량을 측정하였다. 결과: 제2형 당뇨병환자에서 최대근력과 최대산소섭취량은 유의한 상관관계가 없었다(남자: 상·하지 각각 P=0.122, P=0.138, 여자: 상·하지 각각 P=0.952, P=0.570). 최대근력과 근육량과 유의한 상관관계가 있었다(남자: 상지 r=0.493, P<0.001, 하지 r=0.437 P<0.001; 여자: 상지 r=0.315, P=0.002, 하지 r=0.307, P=0.003). 체질량지수와 근육량은 유의한 상관관계가 있었다. 그러나 체질량지수 25 kg/m2 이상인 비만인 환자의 경우 남자는 근육량과 체질량지수가 유의한 상관관계에 있었으나(r=0.374, P=0.032) 여자는 유의한 상관성이 없었다(r=0.249, P=0.169). 결론: 우리나라 제2형 당뇨병환자의 경우 일반인에 비해 저항운동이 더욱 필요하며, 특히 비만한 여자 환자들은 근육량을 늘리기 위한 복합운동이 필수적이라 하겠다. Background: Combination fitness regimens (including aerobic and resistance exercises) are effective for improving cardio-respiratory fitness, reducing visceral fat and increasing insulin sensitivity in diabetic patients. The combination exercise intensity that a patient is capable of is limited by his or her aerobic capacity and one repetition maximum (1RM). We investigated the relationships between 1RM, aerobic exercise capacity and body mass index in patients with type 2 diabetes. Methods: A total of 177 (men: 85, women: 92) diabetic subjects with HbA1c≤10% were enrolled. Muscle strength and 1RM were assessed bychest press (upper body) and leg press (lower body). We assessed aerobic capacity by VO2max and muscle mass by bioimpedance analysis. Results: There was no correlation between 1RM and VO2max in type 2 diabetic patients (upper: P=0.122, lower: P=0.138 for men, and upper: P=0.952, lower: P=0.570 for women). However, 1RM was significantly correlated with muscle mass both in men and women (upper: r=0.493, P<0.001, r=0.315, P=0.002 lower: r=0.437 P<0.001, r=0.307, P=0.003, respectively). There was also a significant correlation between 1RM and BMI. In obese male subjects with BMI≥25 kg/m2, we observed a significant correlation between muscle mass and BMI (r=0.374, P=0.032), but this correlation was not observed in women. Conclusion: Clinicians treating Korean type 2 diabetic subjects should recommend resistance exercise to their patients. In particular, obese women with diabetes may receive greater benefits by increasing muscle mass through resistance exercises. (Korean Diabetes J 33:511-517, 2009)