• Title/Summary/Keyword: crossover design

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Bioequivalence of EtodolTM Tablet to KuhnillodineTM Tablet (Micronized Etodolac 200 mg) (건일로딘 정(미결정에토돌락 200 mg)에 대한 에토돌 정의 생물학적동등성)

  • Lee, Jung-Ae;Lee, Yun-Young;Cho, Tae-Seob;Park, Young-Joon;Moon, Byoung-Seok;Kim, Ho-Hyun;Lee, Ye-Rie;Lee, Hee-Joo;Lee, Kyung-Ryul
    • Journal of Pharmaceutical Investigation
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    • v.34 no.4
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    • pp.319-325
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    • 2004
  • A bioequivalence of $Etodol^{TM}$ tablets (Yuhan corporation) and $Kuhnillodine^{TM}$ tablets (Kuhnil Pharm. Co., Ltd.) was evaluated according to the guideline of Korea Food and Drug Administration (KFDA). Single 200 mg dose of etodolac of each medicine was administered orally to 24 healthy male volunteers. This study was performed in a $2{\times}2$ crossover design. Concentrations of etodolac in human plasma were monitored by a high-performance liquid chromatography. $AUC_t$ (the area under the plasma concentration-time curve from time zero to 24 hr) was calculated by the linear trapezoidal rule method. $C_{max}$ (maximum plasma drug concentration) and $T_{max}$ (time to reach $C_{max}$) were compiled from the plasma concentration-time data. Analysis of variance was performed using logarithmically transformed $AUC_t$ and $C_{max}$. No significant sequence effect was found for all of the bioavailability parameters. The 90% confidence intervals of the $AUC_t$ ratio and the $C_{max}$ ratio for $Etodol^{TM}/Kuhnillodine^{TM}$ were 1.01-1.10 and 0.87-1.06, respectively. This study demonstrated a bioequivalence of $Etodol^{TM}$ and $Kuhnillodine^{TM}$ with respect to the rate and extent of absorption.

Bioequivalency and Pharmacokinetics of Two Clarithromycin Tablets (Clarithromycin 정제의 생물학적 동등성 및 약물동태)

  • Kang, Won Ku;Park, Sun Young;Park, Yong Soon;Woo, Jong Su;Choi, Kyung Eob;Kwon, Kwang Il
    • Korean Journal of Clinical Pharmacy
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    • v.9 no.1
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    • pp.49-54
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    • 1999
  • This study was carried out to compare the bioavailability of Hanmi clarithromycin (250 mg/tablet) with that of $Klaricid^{(R)}$ The bioavailability was examined on 20 volunteers who received a single dose (500 mg) of each drug in the fasting state in a randomized balanced 2-way crossover design. After dosing, blood samples were collected for a period of 12 hours. Plasma samples were analyzed for clarithromycin and roxithromycin(internal standard) by HPLC/Coulometric BCD. The pharmaco-kinetic parameters ($AUC_{0-l2hr}$, Cmax, Tmax, $AUC_{inf}$, Ka, Kel, $t_{1/2}$, Vd/F and Cl/F) were calculated from the plasma clarithromycin concentration-time data of each volunteer. The computer program 'WinNonlin' was used for compartmental analysis. One compartment model with first-order input, from order output with lag time, weighting factor $l/y^2$ was chosen as the appropriate pharmacokinetic model. The major pharmacokinetic parameters ($AUC_{0-l2hr},\;AUC_{inf}$, Cmax and Tmax) of Hanmi clarithromycin were $10.7\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;12.7\pm0.7\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.7\pm0.1\;{\mu}g/ml\;and\;2.0\pm0.2\;hr$, respectively, and those of $Klaricid^{(R)}\;were\;9.8\pm0.5\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;11.7\pm0.6\;{\mu}g{\cdot}hr{\cdot}ml^{-1},\;1.6\pm0.1\;{\mu}g/ml\;and\;2.1\pm0.1\;hr$, respectively. The differences in mean values of $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax between two products were $9.88\%,\;8.94%\;and\;6.59\%$, respectively. The least significant differences at $\alpha=0.05$ for $AUC_{0-l2hr},\;AUC_{inf}$ and Cmax were $16.08\%,\;17.81\%\;and\;18.94\%$, respectively. Though the plasma clarithromycin concentrations of Hanmi clarithromycin were higher than those of $Klaricid^{(R)}$ at all observed times, the bioavailability of Hanmi clarithromycin appeared to be bioequivalent with that of $Klaricid^{(R)}$. The Ka, Kel, $t_{1/2}$, Vd/F and Cl/F of the Hanmi clarithromycin were $2.69\pm0.53\;hr^{-1},\;0.18\pm0.01 hr^{-1},\;3.9\;hr,\;248.8\pm11.4\;L\;and\;43.7\pm2.6\;L/hr$, respectively, and those of $Klaricid^{(R)} were 2.19\pm0.51\;hr^{-1},\;0.18\pm0.02\;hr^{-1},\;3.7\;hr,\;266.7\pm22.4\;L\;and\;45.3\pm2.8L/hr$, respectively. There were no statistically significant differences between two drugs in all pharmacokinetic parameters.

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The Effects of Active Movement Myofascial Decompression Therapy and Static Myofascial Decompression Therapy on Range of Motion, Muscle Strength, Functional Movement in Young Adults. (젊은 성인에서 능동 움직임을 결합한 근막감압치료 적용과 정적 적용이 관절가동범위, 근력, 기능적 움직임에 미치는 영향)

  • Lee, Jee-Hyun;Kim, Tae-Hyeon;Kang, Si-Yun;Kum, Do-Gun;Lee, Sung-Yeon;Do, Kwang-Sun;Kim, Chang-Sook;Bae, Ju-Han;Park, Jun-Hyuck;Kim, Jae-Eun
    • Journal of The Korean Society of Integrative Medicine
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    • v.9 no.3
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    • pp.165-173
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    • 2021
  • Purpose : Myofascial decompression is frequently mentioned as a method applied to cupping. The purpose of this study is to evaluate and compare active range of motion (AROM), muscle strength, and functional movement by applying myofascial decompression to the hamstrings. Methods : This study evaluated AROM, muscle strength, and functional movement by applying active movement myofascial decompression and static myofascial decompression to the dominant leg, respectively, in a crossover design conducted with normal adults (n=21) in their average 20s enrolled at G University in G city, Gyeongsangbuk-do. Active movement myofascial decompression was implemented for five minutes at a rate of 100 bpm to make the beats in flexion and extension respectively. Static myofascial decompression was only performed for five minutes while at rest. All of these interventions were performed at a cupping depth of two mm. After a one-week washout period, static was applied again to compare the same dependent variables. Results : Regarding AROM and muscle strength, both groups showed significant differences in the before and after results (p<.05). However, in the Functional Reach Aspect and Single Leg Hop test, the active movement myofascial decompression group showed better results. There was no statistical difference between the Active movement myofascial decompression group and Static myofascial decompression group in any dependent variable (p<.05). Conclusion : As a result of this experiment, both active movement myofascial decompression and static myofascial decompression had a positive effect on dependent variable. Therefore this study is meaningful in that it is easier and simpler to see the effect on flexibility, muscle strength, and functional movement just by implementing movement myofascial decompression.

Ginsenoside Rg1 supplementation clears senescence-associated β-galactosidase in exercising human skeletal muscle

  • Wu, Jinfu;Saovieng, Suchada;Cheng, I-Shiung;Liu, Tiemin;Hong, Shangyu;Lin, Chang-Yu;Su, I-Chen;Huang, Chih-Yang;Kuo, Chia-Hua
    • Journal of Ginseng Research
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    • v.43 no.4
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    • pp.580-588
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    • 2019
  • Background: Ginsenoside Rg1 has been shown to clear senescence-associated beta-galactosidase (SA-${\beta}$-gal) in cultured cells. It remains unknown whether Rg1 can influence SA-${\beta}$-gal in exercising human skeletal muscle. Methods: To examine SA-${\beta}$-gal change, 12 young men (age $21{\pm}0.2years$) were enrolled in a randomized double-blind placebo controlled crossover study, under two occasions: placebo (PLA) and Rg1 (5 mg) supplementations 1 h prior to a high-intensity cycling (70% $VO_{2max}$). Muscle samples were collected by multiple biopsies before and after cycling exercise (0 h and 3 h). To avoid potential effect of muscle biopsy on performance assessment, cycling time to exhaustion test (80% $VO_{2max}$) was conducted on another 12 participants (age $23{\pm}0.5years$) with the same experimental design. Results: No changes of SA-${\beta}$-gal were observed after cycling in the PLA trial. On the contrary, nine of the 12 participants showed complete elimination of SA-${\beta}$-gal in exercised muscle after cycling in the Rg1 trial (p < 0.05). Increases in apoptotic DNA fragmentation (PLA: +87% vs. Rg1: +133%, p < 0.05) and $CD68^+$ (PLA:+78% vs. Rg1:+121%, p = 0.17) occurred immediately after cycling in both trials. During the 3-h recovery, reverses in apoptotic nuclei content (PLA:+5% vs. Rg1 -32%, p < 0.01) and increases in inducible nitrate oxide synthase and interleukin 6 mRNA levels of exercised muscle were observed only in the Rg1 trial (p < 0.01). Conclusion: Rg1 supplementation effectively eliminates senescent cells in exercising human skeletal muscle and improves high-intensity endurance performance.

Ruminal pH pattern, fermentation characteristics and related bacteria in response to dietary live yeast (Saccharomyces cerevisiae) supplementation in beef cattle

  • Zhang, Xiangfei;Dong, Xianwen;Wanapat, Metha;Shah, Ali Mujtaba;Luo, Xiaolin;Peng, Quanhui;Kang, Kun;Hu, Rui;Guan, Jiuqiang;Wang, Zhisheng
    • Animal Bioscience
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    • v.35 no.2
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    • pp.184-195
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    • 2022
  • Objective: In this study we aimed to evaluate the effect of dietary live yeast supplementation on ruminal pH pattern, fermentation characteristics and associated bacteria in beef cattle. Methods: This work comprised of in vitro and in vivo experiments. In vitro fermentation was conducted by incubating 0%, 0.05%, 0.075%, 0.1%, 0.125%, and 0.15% active dried yeast (Saccharomyces cerevisiae, ADY) with total mixed ration substrate to determine its dose effect. According to in vitro results, 0.1% ADY inclusion level was assigned in in vivo study for continuously monitoring ruminal fermentation characteristics and microbes. Six ruminally cannulated steers were randomly assigned to 2 treatments (Control and ADY supplementation) as two-period crossover design (30-day). Blood samples were harvested before-feeding and rumen fluid was sampled at 0, 3, 6, 9, and 12 h post-feeding on 30 d. Results: After 24 h in vitro fermentation, pH and gas production were increased at 0.1% ADY where ammonia nitrogen and microbial crude protein also displayed lowest and peak values, respectively. Acetate, butyrate and total volatile fatty acids concentrations heightened with increasing ADY doses and plateaued at high levels, while acetate to propionate ratio was decreased accordingly. In in vivo study, ruminal pH was increased with ADY supplementation that also elevated acetate and propionate. Conversely, ADY reduced lactate level by dampening Streptococcus bovis and inducing greater Selenomonas ruminantium and Megasphaera elsdenii populations involved in lactate utilization. The serum urea nitrogen decreased, whereas glucose, albumin and total protein concentrations were increased with ADY supplementation. Conclusion: The results demonstrated dietary ADY improved ruminal fermentation dose-dependently. The ruminal lactate reduction through modification of lactate metabolic bacteria could be an important reason for rumen pH stabilization induced by ADY. ADY supplementation offered a complementary probiotics strategy in improving gluconeogenesis and nitrogen metabolism of beef cattle, potentially resulted from optimized rumen pH and fermentation.

Effect of Bi-/Unilateral Masticatory Training on Memory and Concentration - Assessor-blind, Cross-over, Randomized Controlled Clinical Trial

  • Bae, Jun-hyeong;Kim, Hyungsuk;Kang, Do Young;Kim, Hyeji;Kim, Jongyeon;Kim, Koh-Woon;Cho, Jae-Heung;Song, Mi-yeon;Chung, Won-Seok
    • The Journal of Korean Medicine
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    • v.43 no.2
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    • pp.61-74
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    • 2022
  • Objectives: This study aimed to explore the short-term effects of bilateral masticatory training using an intraoral device on memory and concentration, which is an advanced form of Gochi, compared to the unilateral form with gum. Methods: Thirty young healthy participants (age, 16-30 years) were screened and randomly assigned to one of two sequences in a crossover design. The participants assigned to sequence A (n=15) performed bilateral mastication using an intraoral device with a total of 300 taps, followed by unilateral mastication using gum with the same number of repetitions and frequency, separated by a 7-day washout period. A reverse order was used for sequence B. The primary and secondary outcomes were the digit span test result and the symbol digit modality test and the word list recall results, respectively, which were conducted before and after each intervention. Results: Symbol digit modality test scores increased by 12.03±8.33 with bilateral mastication, which was significantly higher than that obtained with chewing gum (5.17 points;95% confidence interval: 0.99, 9.34; p<0.05). Changes in the digit span test and word list recall scores were not significantly different between the two groups. In the digit span test forward, symbol digit modality test, and word list recall test, bilateral mastication was not inferior to unilateral mastication in improving memory and concentration. Conclusions: Bilateral masticatory exercises using an intraoral device are not inferior to unilateral mastication with gum for improving memory in healthy young individuals. Further research is needed to determine the efficacy of bilateral masticatory training on cognitive function.

MRI Evaluation of Suspected Pathologic Fracture at the Extremities from Metastasis: Diagnostic Value of Added Diffusion-Weighted Imaging

  • Sun-Young Park;Min Hee Lee;Ji Young Jeon;Hye Won Chung;Sang Hoon Lee;Myung Jin Shin
    • Korean Journal of Radiology
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    • v.20 no.5
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    • pp.812-822
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    • 2019
  • Objective: To assess the diagnostic value of combining diffusion-weighted imaging (DWI) with conventional magnetic resonance imaging (MRI) for differentiating between pathologic and traumatic fractures at extremities from metastasis. Materials and Methods: Institutional Review Board approved this retrospective study and informed consent was waived. This study included 49 patients each with pathologic and traumatic fractures at extremities. The patients underwent conventional MRI combined with DWI. For qualitative analysis, two radiologists (R1 and R2) independently reviewed three imaging sets with a crossover design using a 5-point scale and a 3-scale confidence level: DWI plus non-enhanced MRI (NEMR; DW set), NEMR plus contrast-enhanced fat-saturated T1-weighted imaging (CEFST1; CE set), and DWI plus NEMR plus CEFST1 (combined set). McNemar's test was used to compare the diagnostic performances among three sets and perform subgroup analyses (single vs. multiple bone abnormality, absence/presence of extra-osseous mass, and bone enhancement at fracture margin). Results: Compared to the CE set, the combined set showed improved diagnostic accuracy (R1, 84.7 vs. 95.9%; R2, 91.8 vs. 95.9%, p < 0.05) and specificity (R1, 71.4% vs. 93.9%, p < 0.005; R2, 85.7% vs. 98%, p = 0.07), with no difference in sensitivities (p > 0.05). In cases of absent extra-osseous soft tissue mass and present fracture site enhancement, the combined set showed improved accuracy (R1, 82.9-84.4% vs. 95.6-96.3%, p < 0.05; R2, 90.2-91.1% vs. 95.1-95.6%, p < 0.05) and specificity (R1, 68.3-72.9% vs. 92.7-95.8%, p < 0.005; R2, 83.0-85.4% vs. 97.6-98.0%, p = 0.07). Conclusion: Combining DWI with conventional MRI improved the diagnostic accuracy and specificity while retaining sensitivity for differentiating between pathologic and traumatic fractures from metastasis at extremities.

Effects of Cardiotonic Pills® on Cerebrovascular CO2 Reactivity and Erythrocyte Deformability in Normal Subjects: A Pilot Study

  • Sang-Kwan Moon;Han-Gyul Lee;Seungwon Kwon;Seung-Yeon Cho;Seong-Uk Park;Woo-Sang Jung;Jung-Mi Park;Chang-Nam Ko;Ki-Ho Cho
    • The Journal of Korean Medicine
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    • v.44 no.4
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    • pp.87-103
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    • 2023
  • Backgrounds and objectives: Cardiotonic Pills® (CP) are used for vascular diseases such as coronary diseases, atherosclerosis, and cerebral infarction. This study aimed to determine the transient effects of CP on cerebrovascular CO2 reactivity (CVR) and erythrocyte deformability in normal subjects. Methods: This study had a crossover design and included 10 participants who were randomly allocated to 2 groups. The experimental group was given CP with water, while the control group was given only water. CVR was measured by hyperventilation-induced CVR of the middle cerebral artery (MCA) using transcranial Doppler (TCD). Erythrocyte deformability was measured using a Rheoscan-D microfluidic ektacytometer. All measurements were performed prior to and 1, 2, and 3 hours after CP or water administration. Blood pressure and heart rate were also measured before and after administration. Results: CP significantly improved CVR 3 hours after administration in the experimental group compared to the control group (p = 0.042). The corrected blood flow velocity at partial pressure of end-tidal carbon dioxide (PETCO2) = 40mmHg (CV40) was also significantly improved 2 and 3 hours after administration in the CP group compared to the control group (p = 0.036 and p = 0.021, respectively). CP significantly improved erythrocyte deformability 3 hours after administration in the experimental group compared to the control group (p = 0.027). Mean heart rate and mean blood pressure showed no change. Conclusions: This study demonstrated that CP increases CVR and erythrocyte deformability. These results suggested that CP improves cerebral microcirculation which provide evidence for the future use of CP for prevention of ischemic stroke and neurodegenerative diseases.

Optimization of Support Vector Machines for Financial Forecasting (재무예측을 위한 Support Vector Machine의 최적화)

  • Kim, Kyoung-Jae;Ahn, Hyun-Chul
    • Journal of Intelligence and Information Systems
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    • v.17 no.4
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    • pp.241-254
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    • 2011
  • Financial time-series forecasting is one of the most important issues because it is essential for the risk management of financial institutions. Therefore, researchers have tried to forecast financial time-series using various data mining techniques such as regression, artificial neural networks, decision trees, k-nearest neighbor etc. Recently, support vector machines (SVMs) are popularly applied to this research area because they have advantages that they don't require huge training data and have low possibility of overfitting. However, a user must determine several design factors by heuristics in order to use SVM. For example, the selection of appropriate kernel function and its parameters and proper feature subset selection are major design factors of SVM. Other than these factors, the proper selection of instance subset may also improve the forecasting performance of SVM by eliminating irrelevant and distorting training instances. Nonetheless, there have been few studies that have applied instance selection to SVM, especially in the domain of stock market prediction. Instance selection tries to choose proper instance subsets from original training data. It may be considered as a method of knowledge refinement and it maintains the instance-base. This study proposes the novel instance selection algorithm for SVMs. The proposed technique in this study uses genetic algorithm (GA) to optimize instance selection process with parameter optimization simultaneously. We call the model as ISVM (SVM with Instance selection) in this study. Experiments on stock market data are implemented using ISVM. In this study, the GA searches for optimal or near-optimal values of kernel parameters and relevant instances for SVMs. This study needs two sets of parameters in chromosomes in GA setting : The codes for kernel parameters and for instance selection. For the controlling parameters of the GA search, the population size is set at 50 organisms and the value of the crossover rate is set at 0.7 while the mutation rate is 0.1. As the stopping condition, 50 generations are permitted. The application data used in this study consists of technical indicators and the direction of change in the daily Korea stock price index (KOSPI). The total number of samples is 2218 trading days. We separate the whole data into three subsets as training, test, hold-out data set. The number of data in each subset is 1056, 581, 581 respectively. This study compares ISVM to several comparative models including logistic regression (logit), backpropagation neural networks (ANN), nearest neighbor (1-NN), conventional SVM (SVM) and SVM with the optimized parameters (PSVM). In especial, PSVM uses optimized kernel parameters by the genetic algorithm. The experimental results show that ISVM outperforms 1-NN by 15.32%, ANN by 6.89%, Logit and SVM by 5.34%, and PSVM by 4.82% for the holdout data. For ISVM, only 556 data from 1056 original training data are used to produce the result. In addition, the two-sample test for proportions is used to examine whether ISVM significantly outperforms other comparative models. The results indicate that ISVM outperforms ANN and 1-NN at the 1% statistical significance level. In addition, ISVM performs better than Logit, SVM and PSVM at the 5% statistical significance level.

Effects of a low glycemic load diet on body weight loss in overweight or obese young adults (식단의 당부하량에 따른 20대 성인의 체중 감량 효과 연구)

  • Park, Mi Hyeon;Nam, Kisun;Chung, Sang-Jin
    • Journal of Nutrition and Health
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    • v.53 no.5
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    • pp.464-475
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    • 2020
  • Purpose: This study compared the effects of a high glycemic load (high GL) diet and low glycemic load (low GL) diet on the body weight, body fat, blood pressure, and blood lipid indicators. Methods: Twenty-one young adults aged between 21 and 28 years who were overweighted or obese (body mass index [BMI] between 23 and 33.5 kg/㎡) before the study and after calorie reduction diets with either low GL or high GL for 2 weeks each were examined. The study was a randomized crossover design with a 2-week washout period between the 2 types of diet. The order of the low GL and high GL diet periods was randomized. The body weight, body fat, blood pressure, levels of blood lipids, fasting glucose, insulin, homeostatic model assessment (HOMA) insulin, C-peptide, and HOMA C-peptide were measured at the baseline, as well as 2, 4, and 6 weeks after starting the experiment. Results: When subjects were on the low GL diet, they lost more weight than those eating the high GL diet (mean ± SD, -2.77 ± 1.09 vs. -1.56 ± 0.78 kg; p < 0.001); there were greater decreases in body fat mass (-1.62 ± 1.19 vs. -0.88 ± 0.91 kg; p = 0.024) and BMI (-0.95 ± 0.32 vs. -0.56 ± 1.08 kg/㎡; p < 0.001). On the other hand, there were no significant differences in changes in biochemical parameters, such as blood lipids and fasting glucose levels, and blood pressure. The body weight, body fat mass, BMI, percent body fat, blood pressure, cholesterol (total, low-density lipoprotein, and high-density lipoprotein), fasting glucose, C-peptide, HOMA-insulin resistance-C-peptide levels were decreased significantly at 6 weeks. Conclusion: The low GL diet may be more effective in losing body weight, body fat mass, and BMI than the high GL diet for 2 weeks in healthy young overweight or obese adults.