1.Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun LEE ; Seung Hee YU ; Sung Rae KIM ; Kyu Jeung AHN ; Kee-Ho SONG ; In-Kyu LEE ; Ho-Sang SHON ; In Joo KIM ; Soo LIM ; Doo-Man KIM ; Choon Hee CHUNG ; Won-Young LEE ; Soon Hee LEE ; Dong Joon KIM ; Sung-Rae CHO ; Chang Hee JUNG ; Hyun Jeong JEON ; Seung-Hwan LEE ; Keun-Young PARK ; Sang Youl RHEE ; Sin Gon KIM ; Seok O PARK ; Dae Jung KIM ; Byung Joon KIM ; Sang Ah LEE ; Yong-Hyun KIM ; Kyung-Soo KIM ; Ji A SEO ; Il Seong NAM-GOONG ; Chang Won LEE ; Duk Kyu KIM ; Sang Wook KIM ; Chung Gu CHO ; Jung Han KIM ; Yeo-Joo KIM ; Jae-Myung YOO ; Kyung Wan MIN ; Moon-Kyu LEE
Diabetes & Metabolism Journal 2024;48(4):730-739
Background:
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods:
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results:
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.
2.IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway
Young-Ju KANG ; Hee Jun CHO ; Yunhee LEE ; Arum PARK ; Mi Jeong KIM ; In Cheul JEUNG ; Yong-Wook JUNG ; Haiyoung JUNG ; Inpyo CHOI ; Hee Gu LEE ; Suk Ran YOON
Immune Network 2023;23(2):e14-
Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.
3.The association between dietary pattern and depression in middle-aged Korean adults
Seon Joo PARK ; Myung Sunny KIM ; Hae Jeung LEE
Nutrition Research and Practice 2019;13(4):316-322
BACKGROUND/OBJECTIVES: The association between dietary patterns and depression has been reported but the results have been inconsistent. This study was conducted to investigate the association between dietary patterns and depression in middle-aged Korean adults. SUBJECTS/METHODS: The participants were selected from a community-based cohort, a subset of the Korean Genome and Epidemiology Study. Depression was assessed using the Korean version of the Beck Depression Inventory (BDI) and those with a BDI score ≥ 16 were defined as having depression. The subjects' food intakes over the year preceding the survey were estimated by using a validated semi-quantitative food frequency questionnaire. Dietary patterns were identified by using factor analysis. Multiple logistic regression was used to assess the association of dietary pattern with depression. RESULTS: Among 3,388 participants, 448 (13.2%) were identified as having depression. We identified two major dietary patterns: ‘Healthy’ dietary pattern was characterized by high intakes of vegetables, soybeans, mushroom, seaweeds, white fish, shellfish and fruits and a low intake of white rice. ‘Unhealthy’ dietary pattern was characterized by high intakes of white rice, meats, ramen, noodles, bread and coffee and a low intake of rice with other grains. Compared with subjects in the lowest quartiles, those in the highest quartiles of the healthy dietary pattern had a significantly lower odds ratio (OR = 0.59, 95% CI: 0.42–0.82, P for trend = 0.0037) after adjusting for potential confounders. In contrast, the unhealthy dietary pattern was negatively associated with depression (OR = 1.65, 95% CI: 1.19–2.28, P for trend = 0.0021). CONCLUSION: This results suggest that a healthy dietary pattern (rich in vegetables, soybeans, mushroom, seaweeds, white fish, shellfish, and fruits) is associated with low risk of depression. Whereas an unhealthy dietary pattern (rich in white rice, meats, ramen, noodles, bread, and coffee) is associated with a high risk of depression in middle-aged Korean adults.
Adult
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Agaricales
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Bread
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Coffee
;
Cohort Studies
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Depression
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Epidemiology
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Factor Analysis, Statistical
;
Fruit
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Genome
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Humans
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Logistic Models
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Meat
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Odds Ratio
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Shellfish
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Soybeans
;
Vegetables
4.Anti-diabetic effects of blue honeyberry on high-fed-diet-induced type II diabetic mouse
Anshul SHARMA ; Joo Wan KIM ; Sae Kwang KU ; Jae Suk CHOI ; Hae Jeung LEE
Nutrition Research and Practice 2019;13(5):367-376
BACKGROUND/OBJECTIVE: The blue honeysuckle berry (Lonicera caerulea var. edulis L.) is a small deciduous shrub belonging to the Caprifoliaceae family that is native to Russia, China, Japan, and Korea. The berry of this shrub is edible, sweet and juicy and is commonly known as the blue honeyberry (BHB). This study examined the anti-diabetic potential of BHB on high-fat-diet-induced mild diabetic mice. The hypoglycemic, and nephroprotective effects of the 12-week oral administration of blue honeyberry extract were analyzed. MATERIALS/METHODS: The hypoglycemic effects were based on the observed changes in insulin, blood glucose, and glycated hemoglobin (HbA1c). Furthermore, the changes in the weight of the pancreas, including its histopathology and immunohistochemical investigation were also performed. Moreover, the nephroprotective effects were analyzed by observing the changes in kidney weight, its histopathology, blood urea nitrogen (BUN), and serum creatinine levels. RESULTS: The results showed that the high-fat diet (HFD)-induced control mice showed a noticeable increase in blood glucose, insulin, HbA1c, BUN, and creatinine levels. Furthermore, growth was observed in lipid droplet deposition related to the degenerative lesions in the vacuolated renal tubules with the evident enlargement and hyperplasia of the pancreatic islets. In addition, in the endocrine pancreas, there was an increase in the insulin-and glucagon-producing cells, as well as in the insulin/glucagon cell ratios. On the other hand, compared to the HFD-treated mice group, all these diabetic and related complications were ameliorated significantly in a dose-dependent manner after 84 days of the continuous oral administration of BHBe at 400, 200 and 100 mg/kg, and a dramatic resettlement in the hepatic glucose-regulating enzyme activities was observed. CONCLUSIONS: By assessing the key parameters for T2DM, the present study showed that the BHBe could act as a potential herbal agent to cure diabetes (type II) and associated ailments in HFD-induced mice.
5.The development of food image detection and recognition model of Korean food for mobile dietary management
Seon Joo PARK ; Akmaljon PALVANOV ; Chang Ho LEE ; Nanoom JEONG ; Young Im CHO ; Hae Jeung LEE
Nutrition Research and Practice 2019;13(6):521-528
BACKGROUND/OBJECTIVES: The aim of this study was to develop Korean food image detection and recognition model for use in mobile devices for accurate estimation of dietary intake. SUBJECTS/METHODS: We collected food images by taking pictures or by searching web images and built an image dataset for use in training a complex recognition model for Korean food. Augmentation techniques were performed in order to increase the dataset size. The dataset for training contained more than 92,000 images categorized into 23 groups of Korean food. All images were down-sampled to a fixed resolution of 150 × 150 and then randomly divided into training and testing groups at a ratio of 3:1, resulting in 69,000 training images and 23,000 test images. We used a Deep Convolutional Neural Network (DCNN) for the complex recognition model and compared the results with those of other networks: AlexNet, GoogLeNet, Very Deep Convolutional Neural Network, VGG and ResNet, for large-scale image recognition. RESULTS: Our complex food recognition model, K-foodNet, had higher test accuracy (91.3%) and faster recognition time (0.4 ms) than those of the other networks. CONCLUSION: The results showed that K-foodNet achieved better performance in detecting and recognizing Korean food compared to other state-of-the-art models.
Dataset
6.High dairy products intake reduces osteoporosis risk in Korean postmenopausal women: A 4 year follow-up study.
Seon Joo PARK ; Ji Hye JUNG ; Myung Sunny KIM ; Hae Jeung LEE
Nutrition Research and Practice 2018;12(5):436-442
BACKGROUND/OBJECTIVES: The aim of this study was to identify the effect of dairy products, milk and yogurt on osteoporosis incidence among Korean postmenopausal women using prospective cohort data. MATERIALS/METHODS: Between 2001 and 2003, 10,038 participants were recruited in rural and urban areas for a baseline examination of a community-based cohort study. Of those, 1,573 postmenopausal women (aged 40–69 years at baseline) were eligible for the present study. Intakes of dairy products, milk, and yogurt were assessed using a validated semi-quantitative food frequency questionnaire. The speed of sound at the radius and tibia were measured using a quantitative ultrasound device and osteoporosis was defined based on the WHO criteria (T-score ≤−2.5). RESULTS: During the 4-years follow-up study, the cumulative incidence of osteoporosis was 18.4% (273 cases) in the radius and 33.6% (407 cases) in the tibia. The subjects with higher frequency of dairy product consumption showed a decreased risk of radius osteoporosis after adjusting for potential confounders [hazard ratio (HR) = 0.51, 95% confidence interval (CI): 0.33–0.80 for >1 time/day vs. non consumer; P for trend = 0.0027]. Similarly, high frequency of milk and yogurt consumption had a protective effect on radius osteoporosis risk [milk: HR = 0.60, 95% CI: 0.42–0.87 for >5–6 times/week vs. non consumer (P for trend = 0.0130), yogurt: HR = 0.51, 95% CI: 0.30–0.85 for > 5–6 times/week vs. non consumer (P for trend = 0.0167)]. However, high dairy products consumption was not related with tibia osteoporosis. CONCLUSIONS: This study suggests that daily intake of dairy products could potentially reduce radius osteoporosis incidence among Korean postmenopausal women.
Cohort Studies
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Dairy Products*
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Female
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Follow-Up Studies*
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Humans
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Incidence
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Korea
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Milk
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Osteoporosis*
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Postmenopause
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Prospective Studies
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Radius
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Tibia
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Ultrasonography
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Yogurt
7.Evaluation of in vitro anti-oxidant and anti-inflammatory activities of Korean and Chinese Lonicera caerulea.
You Suk LEE ; Il Je CHO ; Joo Wan KIM ; Sun Kyoung LEE ; Sae Kwang KU ; Hae Jeung LEE
Nutrition Research and Practice 2018;12(6):486-493
BACKGROUND/OBJECTIVES: The honeysuckle berry (HB) contains ascorbic acid and phenolic components, especially anthocyanins, flavonoids, and low-molecular-weight phenolic acids. In order to examine the potential of HB as a hepatoprotective medicinal food, we evaluated the in vitro anti-oxidant and anti-inflammatory activities of Korean HB (HBK) and Chinese HB (HBC). MATERIALS/METHODS: Antioxidant and anti-inflammatory effects of the extracts were examined in HepG2 and RAW 264.7 cells, respectively. The anti-oxidant capacity was determined by DPPH, SOD, CAT, and ARE luciferase activities. The production of nitric oxide (NO) as an inflammatory marker was also evaluated. The Nrf2-mediated mRNA levels of heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone] 1 (Nqo1), and glutamate-cysteine ligase catalytic subunit (Gclc) were measured. The concentrations of HB extracts used were 3, 10, 30, 100, and 300 µg/mL. RESULTS: The radical scavenging activity of all HB extracts increased in a concentration-dependent manner (P < 0.01 or P < 0.05). SOD (P < 0.05) and CAT (P < 0.01) activities were increased by treatment with 300 µg/mL of each HB extract, when compared to those in the control. NO production was observed in cells pretreated with 100 or 300 µg/mL of HBC and HBK (P < 0.01). Treatment with 300 µg/mL of HBC significantly increased Nqo1 (P < 0.01) and Gclc (P < 0.05) mRNA levels compared to those in the control. Treatment with 300 µg/mL of HBK (P < 0.05) and HBC (P < 0.01) also significantly increased the HO-1 mRNA level compared to that in the control. CONCLUSIONS: Thus, the Korean and Chinese HBs were found to possess favorable in vitro anti-oxidant and anti-inflammatory activities. Nrf2 and its related anti-oxidant genes were associated with both anti-oxidant and anti-inflammatory activities in HB-treated cells. Further studies are needed to confirm these in vivo effects.
Animals
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Anthocyanins
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Ascorbic Acid
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Asian Continental Ancestry Group*
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Catalytic Domain
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Cats
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Flavonoids
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Fruit
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Glutamate-Cysteine Ligase
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Heme Oxygenase-1
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Humans
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In Vitro Techniques*
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Lonicera*
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Luciferases
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Nitric Oxide
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Oxidoreductases
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Phenol
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RAW 264.7 Cells
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RNA, Messenger
8.Preoperative Templating in PACS for Total Hip Replacement.
Myoung Soo KIM ; Moo Chul JEONG ; Nam Gu JI ; Jung Sub LEE ; Jeung Il KIM ; Kuen Tak SUH
The Journal of the Korean Orthopaedic Association 2011;46(6):472-477
PURPOSE: The objective of our study was to compare preoperative "Monitor Templating" with postoperative results for total hip replacement and to investigate the accuracy of "Monitor Templating" that was carried out by monitoring with picture archiving communication system (PACS). MATERIALS AND METHODS: Forty five patients underwent primary cementless total hip replacements. For setting parameters, we located the 10cm rod placed in the medial thigh on anteroposterior view of both hips and in the anterior thigh on Lowenstein lateral view. We measured implant sizes and the predictive value of corrective change in leg length and horizontal offset, by using radiographs magnified 120% of the anteroposterior views of both hips and Lowenstein lateral view of PACS on 27 inch monitor. We examined the correlation between preoperative monitor templating and the actual implant size, postoperative leg length and horizontal offset difference. RESULTS: The preoperative monitor templating showed a high rate of coincidence with the actual implant size, the postoperative leg length, and the horizontal offset difference. The averages in accurate prediction were 98% in the acetabular cup, 98% in the femoral stem, 97% in the postoperative actual difference of leg length, and 97% in the horizontal offset. With regard to leg length discrepancy, the sick limb was on average 4.7 mm shorter and 0.5 mm longer postoperatively than the contralateral limb. The average ratio of horizontal offset of the sick limb to the contralateral limb was 94.6% preoperatively and increased to 97.8% postoperatively. CONCLUSION: Preoperative "Monitor Templating" using PACS images on 26 inch monitor is an easy and effective method for predicting implant size, correcting leg length discrepancy and restoring horizontal offset.
Arthroplasty, Replacement, Hip
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Extremities
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Hip
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Humans
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Leg
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Organothiophosphorus Compounds
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Thigh
9.Dietary source of vitamin B12 intake and vitamin B12 status in female elderly Koreans aged 85 and older living in rural area.
Chung Shil KWAK ; Mee Sook LEE ; Hae Jeung LEE ; Jin Yong WHANG ; Sang Chul PARK
Nutrition Research and Practice 2010;4(3):229-234
Recently, we found and analyzed vitamin B12 in some Korean traditional plant foods which had not reported, yet. This study was to investigate vitamin B12 intake and its dietary sources and the vitamin B12 status in the very old elderly Koreans. We measured serum vitamin B12 level and estimated the amounts of vitamin B12 intake from different dietary sources in female elderly Koreans aged 85 and over who had consumed a relatively low animal traditional diet for the whole life. The average age of the subjects (n = 127) was 98.0 years (85-108 years). The assessment on energy and nutrient intake involved a one-day 24-hour recall, and serum vitamin B12 concentration was measured by radioimmunoassay. Overall diet pattern was not different between the 85-99 yr-old group and centenarians, except centenarians were taking more dairy product. The average ratio of plant food to animal food consumption was 87.5:12.5 in weight. The average vitamin B12 intake of our subjects was 3.2 microg/day, and 52.7% of subjects consumed under estimated average requirement, 2.0 microg/day. On dietary source, 67.3% of dietary vitamin B12 was from meat, eggs and fishes and 30.6% was from plant foods, such as soybean-fermented foods, seaweeds, and kimchi. The average serum vitamin B12 concentration was 450.5 pg/mL, and low serum vitamin B12 (< 200 pg/mL) was found in 9.6% of subjects. Dietary vitamin B12 intake was significantly lower in subjects with low serum vitamin B12 (0.79 microg/day) than those with normal serum vitamin B12 (3.47 microg/day). There were no significant difference in vitamin B12 intake and its dietary sources and serum vitamin B12 level between the 85-99 yr-old group and centenarians. In conclusion, several plant-origin foods including seaweed, soybean-fermented foods, and kimchi, may contribute significantly to good vitamin B12 status in very old elderly Koreans.
Aged
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Aged, 80 and over
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Animals
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Dairy Products
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Diet
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Eggs
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Female
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Fishes
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Humans
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Meat
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Ovum
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Plants
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Radioimmunoassay
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Seaweed
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Vitamin B 12
;
Vitamins
10.Red beet (Beta vulgaris L.) leaf supplementation improves antioxidant status in C57BL/6J mice fed high fat high cholesterol diet.
Jeung Hee LEE ; Chan Wook SON ; Mi Yeon KIM ; Min Hee KIM ; Hye Ran KIM ; Eun Shil KWAK ; Sena KIM ; Mee Ree KIM
Nutrition Research and Practice 2009;3(2):114-121
The effect of diet supplemented with red beet (Beta vulgaris L.) leaf on antioxidant status of plasma and tissue was investigated in C57BL/6J mice. The mice were randomly divided into two groups after one-week acclimation, and fed a high fat (20%) and high cholesterol (1%) diet without (control group) or with 8% freeze-dried red beet leaf (RBL group) for 4 weeks. In RBL mice, lipid peroxidation determined as 2-thiobarbituric acid-reactive substances (TBARS value) was significantly reduced in the plasma and selected organs (liver, heart, and kidney). Levels of antioxidants (glutathione and beta-carotene) and the activities of antioxidant enzyme (glutathione peroxidase) in plasma and liver were considerably increased, suggesting that antioxidant defenses were improved by RBL diet. Comet parameters such as tail DNA (%), tail extent moment, olive tail moment and tail length were significantly reduced by 25.1%, 49.4%, 35.4%, and 23.7%, respectively, in plasma lymphocyte DNA of RBL mice compared with control mice, and indicated the increased resistance of lymphocyte DNA to oxidative damage. In addition, the RBL diet controlled body weight together with a significant reduction of fat pad (retroperitoneal, epididymal, inguinal fat, and total fat). Therefore, the present study suggested that the supplementation of 8% red beet leaf in high fat high cholesterol diet could prevent lipid peroxidation and improve antioxidant defense system in the plasma and tissue of C57BL/6J mice.
Acclimatization
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Adipose Tissue
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Animals
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Antioxidants
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Beta vulgaris
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Body Weight
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Cholesterol
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Diet
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DNA
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Heart
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Lipid Peroxidation
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Liver
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Lymphocytes
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Mice
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Olea
;
Plasma

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