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PubMed | Eli Lilly and Company, Peking University and Eulji Hospital
Type: | Journal: Diabetes, metabolic syndrome and obesity : targets and therapy | Year: 2016

The objective of this study was to explore the efficacy and safety of insulin lispro mix 25 (25% insulin lispro and 75% insulin lispro protamine suspension [LM25]) or insulin glargine plus insulin lispro (G+L) in insulin-nave patients with type 2 diabetes from different racial/ethnic groups.Three subgroups from the PARADIGM study were analyzed post hoc: non-Asian (n=130), Asian Indian (n=106), and East Asian (n=89).All subgroups recorded glycated hemoglobin (HbA1c) reductions: non-Asian (LM25, -2.07%; G+L, -2.05%), Asian Indian (LM25, -1.75%; G+L, -1.60%), and East Asian (LM25, -2.03%; G+L, -1.76%); end point HbA1c values were higher in Asian Indians and East Asians than in non-Asians. Fewer Asian Indians (LM25, 43.2%; G+L, 29.2%) and East Asians (LM25, 37.5%; G+L, 36.1%) reached HbA1c <7% versus non-Asians (LM25, 51.7%; G+L, 48.1%); differences were not significant (P=0.12 and P=0.06, respectively). The mean total daily insulin dose (U/kg) for non-Asians was 0.67 (LM25) and 0.61 (G+L), for Asian Indians was 0.91 (LM25) and 0.90 (G+L), and for East Asians was 0.53 (LM25) and 0.59 (G+L). The ratio of mealtime to total insulin dose in the G+L arm for non-Asians was 0.190.23, for Asian Indians was 0.330.25, and for East Asians was 0.340.27. Overall incidence (%) of hypoglycemia in non-Asians was 94.1 (LM25) and 91.8 (G+L), in Asian Indians was 90.4 (LM25) and 88.5 (G+L), and in East Asians was 69.8 (LM25) and 77.3 (G+L).Asian Indians showed least improvement in glycemic HbA1c reduction despite greater insulin use. East Asians and non-Asians achieved similar HbA1c reduction in the LM25 arm with a lower rate of hypoglycemia. Asians required more mealtime insulin coverage than non-Asians. This study added important insight into the effect of ethnicity on insulin treatment outcomes in patients with type 2 diabetes.


Choi K.M.,Korea University | Yannakoulia M.,Beth Israel Deaconess Medical Center | Yannakoulia M.,Harokopio University | Park M.S.,Korea University | And 11 more authors.
American Journal of Clinical Nutrition | Year: 2011

Background: Adipocyte fatty acid-binding protein (A-FABP), retinol-binding protein 4 (RBP4), and adiponectin have been associated with insulin resistance and the metabolic syndrome in adults. Objective: We evaluated the association of A-FABP, RBP4, and adiponectin with the metabolic syndrome in Korean boys. Design: In this prospective cohort study, 159 boys participated in a school-based health examination and were followed up after 3 y. The metabolic syndrome in children was defined by using the pediatric adaptation of the National Cholesterol Education Program criteria. Results: Compared with normal-weight participants, overweight children had significantly higher A-FABP (23.6 ± 8.2 compared with 12.8 ± 5.1 μg/L, P < 0.001) and RBP4 (69.3 ± 17.1 compared with 59.7 ± 15.3 μg/mL, P = 0.001) concentrations and significantly lower adiponectin concentrations (11.5 ± 5.4 compared with 18.1 ± 8.4 μg/mL, P < 0.001). Baseline A-FABP concentrations were significantly higher in children who developed the metabolic syndrome than in those who did not, whereas adiponectin concentrations were significantly lower. Baseline RBP4 concentrations were not significantly different between the 2 groups. Multiple logistic regression analysis showed that only A-FABP was an independent predictor of the development of the metabolic syndrome after adjustment for Tanner stage, insulin resistance, body mass index, sleep duration, and physical activity (odds ratio: 17.3; 95% CI: 1.25, 239.76; highest compared with lowest tertile), whereas the significant association between adiponectin and the metabolic syndrome observed by using bivariate analysis reflects, in part, an underlying association with obesity. Conclusion: A-FABP predicts the development of the metabolic syndrome independently of pubertal status, adiposity, and insulin resistance in Korean boys. © 2011 American Society for Nutrition.


Koo B.K.,Seoul National University | Han K.A.,Eulji University | Ahn H.J.,Eulji Hospital | Jung J.Y.,Eulji Hospital | And 2 more authors.
Diabetic Medicine | Year: 2010

Aims We examined the effects of physical activity with or without dietary restriction for 3 months on regional fat and insulin sensitivity and compared the effect of total energy expenditure from all levels of physical activity with that of physical activity energy expenditure from moderate-to-vigorous exercise in obese women with Type 2 diabetes. Methods In this randomized, controlled trial, we assessed change of body weight, abdominal visceral fat area, subcutaneous fat area and insulin sensitivity, expressed as KITT, and monitored total energy expenditure and physical activity energy expenditure using an accelerometer during a 12-week intervention in four groups: control, diet, exercise and diet plus exercise. Results The mean body mass index was 28.0 ± 2.7 kg/m2 and the mean duration of diabetes was 8 ± 6 years. Both the diet and diet plus exercise groups showed significant body weight loss compared with the control group (P < 0.05). However, the visceral fat area was reduced only in the diet and exercise group (P = 0.017) and the subcutaneous fat area was reduced only in the diet group (P = 0.009). Mean energy intake was an independent determinant of the change in subcutaneous fat area (P = 0.020) and mean total anergy expenditure was an independent determinant of visceral fat area (P = 0.002). Insulin sensitivity K ITT was associated with physical activity energy expenditure (P = 0.006), energy intake (P = 0.047) and the change in fructosamine level (P = 0.016) but not with changes in body weight, subcutaneous fat area, visceral fat area or adipokine level. Conclusions Exercise had an additive effect to dietary restriction on visceral fat reduction. Visceral fat area was associated with total energy expenditure, but insulin sensitivity was associated with physical activity energy expenditure. © 2010 Diabetes UK.


Ku Y.H.,Eulji University | Han K.A.,Eulji University | Ahn H.,Eulji Hospital | Kwon H.,Eulji Hospital | And 3 more authors.
Journal of International Medical Research | Year: 2010

Lipid accumulation in muscle is associated with diminished insulin sensitivity. It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 (RBP4), which is linked to adipose tissue and insulin sensitivity in diabetics. Forty-four women with type 2 diabetes were randomly assigned to three groups for a period of 12 weeks: control (asked to maintain a sedentary lifestyle); resistance exercise (elastic band exercise at moderate intensity five times per week); and aerobic exercise (walking for 60 min at moderate intensity five times per week). Subcutaneous (SCAT), subfascial (SFAT) and intramuscular (IMAT) adipose tissues at mid-thigh level were assessed using computed tomography, and RBP4 level and insulin sensitivity (fractional disappearance rate of insulin, kITT) were assessed before and after intervention. Changes in SCAT, SFAT, IMAT, RBP4 and kITT were similar among the three groups. Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups, but RBP4 decreased significantly only with resistance exercise. Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity. © 2010 Field House Publishing LLP.


Choi K.M.,Korea University | Han K.A.,Eulji University | Ahn H.J.,Eulji Hospital | Lee S.Y.,Korea University | And 9 more authors.
Clinical Endocrinology | Year: 2013

Objectives The liver-secreted protein fetuin-A is associated with insulin resistance, metabolic syndrome, type 2 diabetes and atherosclerosis. We examined the effect of caloric restriction (CR) on fetuin-A levels and concomitant changes in hepatic steatosis and cardiovascular risk factors in rats and humans. Design and Subjects We performed a randomized, controlled clinical trial to examine circulating fetuin-A levels and cardiovascular risk parameters including visceral fat area (VFA), atherogenic lipid profile, inflammatory markers, adipokines levels and brachial artery endothelial function in 76 overweight women with type 2 diabetes before and after 12 weeks of CR. In addition, the effects of CR on hepatic steatosis and fetuin-A mRNA expression were evaluated in Otuska Long Evans Tokushima Fatty (OLETF) rats, an animal model of obesity and type 2 diabetes. Results Circulating fetuin-A levels were significantly decreased after 12 weeks of CR and were accompanied by improvements in VFA, blood pressure, glucose, lipid profiles and liver function. The CR group also showed a significant decrease in apolipoprotein B, leptin and insulin resistance compared to those in the control group, although endothelial function was not different. Multiple regression analysis showed that the changes in fetuin-A levels were independently associated with CR and changes in hsCRP and adiponectin (R2 = 0·156). Moreover, CR significantly reduced hepatic steatosis and fetuin-A expression, as well as weight, glucose, total cholesterol and triglyceride levels, in OLETF rats. Conclusion Caloric restriction significantly reduced the hepatic expression of fetuin-A and its circulating levels and improved several cardiovascular risk factors in obese rats and humans with type 2 diabetes. © 2012 John Wiley & Sons Ltd.


Choi K.M.,Korea University | Han K.A.,Eulji Hospital | Ahn H.J.,Eulji Hospital | Hwang S.Y.,Korea University | And 7 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Low levels of soluble receptor for advanced glycation end-products (sRAGE) have been linked to systemic inflammation and vascular complications in patients with type 2 diabetes mellitus (T2DM). Objective: We examined the effects of exercise on sRAGE and its association with diverse cardiometabolic risk factors and indicators of atherosclerosis in patients with T2DM. Design, Setting, and Participants: Seventy-five patients withT2DM were randomized into a control group and an aerobic exercise group (60 min at moderate intensity, five times/wk for 12 wk). Main Outcome Measures: We evaluated sRAGE, energy expenditure, dietary energy intake, cardiorespiratory fitness, inflammatory markers, visceral fat area, pulse-wave velocity, and flowmediated dilatation. Results: Baseline sRAGE concentrations were independently associated with age, glycated hemoglobin, glucose, triglyceride, and high-density lipoprotein cholesterol levels (R2 = 0.244). After 12 wk of exercise training, the exercisegroupshowedsignificantly decreasedbodyweight, waist circumference, blood pressure, glycated hemoglobin, apolipoprotein B, and free fatty acid levels. Concurrently, cardiorespiratory fitness assessed by oxygen uptake at anaerobic threshold was improved, and body fat percentage and visceral fat area were significantly decreased in the exercise group, although pulsewave velocity and flow-mediated dilatation were not changed. Furthermore, sRAGE levels were increased and high-sensitivity C-reactive protein levels were decreased in the exercise group but not in the control group. Percent change of sRAGE level was negatively correlated with that of high-sensitivity C-reactive protein during the study period (r =-0.27; P = 0.019). Conclusions: Aerobic exercise increases sRAGE levels along with improvement of various cardiometabolic risk factors in patients with T2DM. Copyright © 2012 by The Endocrine Society.


Lee S.H.,Korea University | Kim S.M.,Korea University | Park H.S.,University of Ulsan | Choi K.M.,Korea University | And 3 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2013

Background and Aim: Evidence of the relationship between serum vitamin D levels and cardiovascular risk factors in children is limited. We investigated the associations between serum vitamin D levels (25-hydroxyvitamin D [25(OH)D]) and obesity and metabolic syndrome and its components in Korean children. Methods and Results: We recruited 1660, nine-year-old, Korean children (904 boys and 756 girls) who voluntarily participated in this study while being examined during school-based health examinations. We measured anthropometric variables (height and weight), metabolic parameters (blood pressure, fasting plasma glucose, triglyceride, and HDL cholesterol levels) and serum vitamin D levels. We analyzed the data using multivariate logistic regression models. Mean 25(OH)D levels were lower in children defined as obese or abdominally obese (P < 0.001). When serum levels of 25(OH)D were divided into quartiles, BMI, waist circumference, and triglyceride levels were lower, and HDL cholesterol levels were higher, as vitamin D levels increased. Using children from the highest quartile of 25(OH)D levels as a referent, the adjusted ORs (95% CI) for obesity in those in the third, second, and lowest quartiles of 25(OH)D levels were 1.55 (1.01-2.40), 1.87 (1.22-2.85), and 2.59 (1.71-3.90), respectively (P for trend <0.001). For abdominal obesity the ORs (CI) were 2.08 (1.20-3.60), 2.32 (1.36-3.95), and 2.96 (1.75-5.00) (P for trend<0.001), and for metabolic syndrome they were 2.60 (1.08-6.30), 4.00 (1.73-9.26), and 4.25 (1.84-9.85), respectively (P for trend <0.05). Conclusions: We found low vitamin D levels in Korean children to be associated with obesity and metabolic syndrome. Insufficient serum vitamin D levels in children may be a risk factor of obesity and metabolic syndrome. © 2012 Elsevier B.V.


PubMed | Bristol Myers Squibb, Astrazeneca, Shenyang University and Eulji Hospital
Type: Journal Article | Journal: Journal of diabetes | Year: 2015

Dapagliflozin, a highly selective sodium-glucose cotransporter 2 inhibitor, reduces hyperglycemia, body weight, and blood pressure in patients with type 2 diabetes (T2D).This randomized double-blind placebo-controlled parallel-group 24-week study assessed the efficacy, safety, and tolerability of dapagliflozin added to metformin in Asian patients with inadequately controlled T2D (HbA1c 7.5%-10.5%). Patients were randomized to receive placebo (n=145) or dapagliflozin 5 (n=147) or 10mg (n=152).Most participants were Chinese (86.0%), with a mean age of 53.8years and mean T2D duration of 4.9years; 92.1% completed the study. Adjusted mean HbA1c changes from baseline at Week 24 (primary endpoint) were -0.23%, -0.82%, and -0.85% in the placebo, dapagliflozin 5 and 10mg groups, respectively, resulting in dapagliflozin 5 and 10mg versus placebo differences of -0.59% and -0.62%, respectively (both P<0.0001). Dapagliflozin 5 and 10mg differences versus placebo were, respectively: -1.2 and -1.5mmol/L for fasting plasma glucose; -1.1 and -1.8kg for weight; and -2.3 and -2.7mmol/L for 2-h postprandial glucose (all P<0.0001). In the placebo, dapagliflozin 5 and 10mg groups, respectively: adverse events (AEs) occurred in 52.4%, 52.4%, and 55.3% of patients; serious AEs occurred in 4.1%, 2.0%, and 2.0%; urinary tract infections occurred in 4.8%, 4.1%, and 6.6%; and genital infections occurred in 0%, 2.0%, and 1.3%. No AEs of pyelonephritis or renal failure occurred.Dapagliflozin 5 or 10mg as add-on to metformin was well tolerated in Asian patients with T2D and significantly improved glycemic control with the additional benefit of weight reduction.


Mo J.-H.,Dankook University | Kim J.-S.,Eulji Hospital | Lee J.-W.,Dankook University | Chung P.-S.,Dankook University | Chung Y.-J.,Dankook University
Clinical and Experimental Otorhinolaryngology | Year: 2013

Objectives. Cartilage reshaping by laser irradiation is used to correct septal and auricular cartilage deformities. Chondrocyte viability following laser irradiation and reshaping has been well established. However, the regeneration process of chondrocyte after laser irradiation has not been revealed yet. The aims of this study were to determine the mechanism of cartilaginous thermal injury and the regenerative process of damaged cartilage following laser irradiation. Methods. Laser irradiation was performed on human septal cartilage and rabbit auricular cartilage using a 1,460-nm diode laser. We observed change in the shape of cartilage and evaluated the extent of cartilage injury using live/dead cell assay via confocal microscopy. Hoechst and propidium iodide (PI) staining was used to evaluate the mechanism of chondrocyte injury after laser irradiation. To evaluate the regeneration of cartilage, laser irradiated cartilages were reimplanted into a subperichondrial pocket and were harvested at 1, 2, and 4 weeks after reimplantation for viability assessment and histologic examination. Results. Laser irradiation using a 1,460-nm diode laser produced a marked shape change in both human septal and rabbit auricular cartilages. Thermal damage on cartilage was correlated with the exposure time and the laser power. Hoechst and PI staining showed that chondrocyte death by laser irradiation was due to mainly necrosis, rather than apoptosis. In lower power treatment group (0.3 W and 0.5 W), all the chondrocytes regenerated within 4 weeks, however, in 1 W treatment group, chondrocytes could not regenerate until 4 weeks. Conclusion. Reshaping of cartilage using 1,460 nm diode laser was attained concurrently with the thermal injury to the chondrocytes. The extent of thermal damage on chondrocytes was dependent on the exposure time and the laser power and the damaged chondrocytes irradiated with lower level of laser power could be regenerated after reimplantation into subperichondrial pocket. © 2013 by Korean Society of Otorhinolaryngology-Head and Neck Surgery.


Shim S.J.,Eulji Hospital | Cha J.,Yonsei University | Koom W.S.,Yonsei University | Kim G.E.,Yonsei University | And 3 more authors.
Radiation Oncology | Year: 2010

Background: The aim of this study was to assess the results of curative surgery with and without radiotherapy in patients with T1-2N0-1oral tongue squamous cell carcinoma (OSCC) and to evaluate survival and prognostic factors.Methods: Retrospective analysis of 86 patients with T1-2N0-1OSCC who received surgery between January 2000 and December 2006. Fourteen patients (16.3%) received postoperative radiotherapy (PORT). Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were analyzed.Results: The median follow-up was 45 months. The five-year overall survival (OS) and disease-free survival (DFS) rates were 80.8% and 80.2%, respectively. Higher tumor grade and invasion depth ≥ 0.5 cm were the significant prognostic factors affecting five-year OS and DFS (OS rate; 65% vs. 91%, p = 0.001 for grade; 66% vs. 92%, p = 0.01 for invasion depth: DFS rate; 69% vs. 88%, p = 0.005 for grade; 66% vs. 92%, p = 0.013 for invasion depth). In the risk group, there was no local failure in patients with postoperative radiotherapy.Conclusions: In T1-2N0-1OSCC, factors that affected prognosis after primary surgery were higher tumor grade and deep invasion depth over 0.5 cm. Postoperative radiotherapy should be considered in early oral tongue cancer patients with these high-risk pathologic features. © 2010 Shim et al; licensee BioMed Central Ltd.

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