Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
Comparative Efficacy of Rosuvastatin Monotherapy and Rosuvastatin/Ezetimibe Combination Therapy on Insulin Sensitivity and Vascular Inflammatory Response in Patients with Type 2 Diabetes Mellitus: Ji Hye Han, Kyong Hye Joung, Jun Choul Lee, Ok Soon Kim, Sorim Choung, Ji Min Kim, Yea Eun Kang, Hyon-Seung Yi, Ju Hee Lee, Bon Jeong Ku, Hyun Jin Kim; Diabetes Metab J. 2024;48(1):112-121. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0402

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Background
Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM.
Methods
A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment.
Results
The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups.
Conclusion
Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Citations

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Combining Ezetimibe and Rosuvastatin: Impacts on Insulin Sensitivity and Vascular Inflammation in Patients with Type 2 Diabetes Mellitus
Eun Roh
Diabetes & Metabolism Journal.2024; 48(1): 55. CrossRef
Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
Il Rae Park, Jun Sung Moon
Diabetes & Metabolism Journal.2024; 48(3): 387. CrossRef
A Comparison of Rosuvastatin Monotherapy and Rosuvastatin Plus Ezetimibe Combination Therapy in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials
Samuel K Dadzie, Godfrey Tabowei, Mandeep Kaur, Saeed Ahmed, Aayushi Thakur, Khaldoun Khreis, Monika Bai, Adil Amin
Cureus.2024;[Epub] CrossRef
The Pleiotropic Effects of Lipid-Modifying Interventions: Exploring Traditional and Emerging Hypolipidemic Therapies
Dimitris Kounatidis, Nikolaos Tentolouris, Natalia G. Vallianou, Iordanis Mourouzis, Irene Karampela, Theodora Stratigou, Eleni Rebelos, Marina Kouveletsou, Vasileios Stamatopoulos, Eleni Tsaroucha, Maria Dalamaga
Metabolites.2024; 14(7): 388. CrossRef

Clinical Diabetes & Therapeutics
Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea: Yu Mi Kang, Chang Hee Jung, Seung-Hwan Lee, Sang-Wook Kim, Kee-Ho Song, Sin Gon Kim, Jae Hyeon Kim, Young Min Cho, Tae Sun Park, Bon Jeong Ku, Gwanpyo Koh, Dol Mi Kim, Byung-Wan Lee, Joong-Yeol Park; Diabetes Metab J. 2019;43(4):432-446. Published online June 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0092

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Background

We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM).

Methods

This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia.

Results

The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011).

Conclusion

The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.

Citations

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Glycaemic control with add‐on thiazolidinedione or a sodium‐glucose co‐transporter‐2 inhibitor in patients with type 2 diabetes after the failure of an oral triple antidiabetic regimen: A 24‐week, randomized controlled trial
Jaehyun Bae, Ji Hye Huh, Minyoung Lee, Yong‐Ho Lee, Byung‐Wan Lee
Diabetes, Obesity and Metabolism.2021; 23(2): 609. CrossRef
Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease
Kyung-Soo Kim, Byung-Wan Lee
Clinical and Molecular Hepatology.2020; 26(4): 430. CrossRef

Others
Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance: Yea Eun Kang, Ji Min Kim, Hyon-Seung Yi, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2019;43(3):368-376. Published online October 23, 2018; DOI: https://doi.org/10.4093/dmj.2018.0066

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Background

Recent in vivo studies indicated that R-spondin 1 (RSPO1) regulates food intake and increases insulin secretion, but its role in humans remains unknown. This study investigated the association between serum levels of RSPO1 and diverse metabolic parameters in humans.

Methods

The study population consisted of 43 subjects with newly diagnosed diabetes mellitus, and 79 non-diabetic participants. Serum levels of RSPO1 were measured using the enzyme-linked immunosorbent assay. The relationships between circulating RSPO1 and diverse metabolic parameters were analyzed.

Results

Circulating RSPO1 levels increased to a greater extent in the obese group than in the lean group. Moreover, serum levels of RSPO1 were higher in the insulin-resistant group than in the insulin-sensitive group. Serum levels of RSPO1 were significantly correlated with a range of metabolic parameters including body mass index, fasting C-peptide, homeostasis model assessment of insulin resistance index, and lipid profile. Moreover, levels were significantly associated with insulin resistance and obesity in non-diabetic subjects.

Conclusion

This study demonstrated the association between serum levels of RSPO1 and a range of metabolic parameters in humans. Serum levels of RSPO1 are significantly related to obesity and insulin resistance, although the precise mechanisms remain unknown.

Citations

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Systems genetics analysis of human body fat distribution genes identifies adipocyte processes
Jordan N Reed, Jiansheng Huang, Yong Li, Lijiang Ma, Dhanush Banka, Martin Wabitsch, Tianfang Wang, Wen Ding, Johan LM Björkegren, Mete Civelek
Life Science Alliance.2024; 7(7): e202402603. CrossRef
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Ningning Zhang, Mingyang Yuan, Jiqiu Wang
Endocrine Reviews.2023; 44(4): 647. CrossRef
R-Spondin1 and tumor necrosis factor-alpha in infertile women with polycystic ovary syndrome: relationships with insulin resistance and other parameters
Tuğba GÜRBÜZ, Oya GÖKMEN, Asena AYAR MADENLİ, Berna DİLBAZ
Journal of Health Sciences and Medicine.2023; 6(2): 449. CrossRef
An early prediction model for type 2 diabetes mellitus based on genetic variants and nongenetic risk factors in a Han Chinese cohort
Jinjin Li, Qun Ye, Hongxiao Jiao, Wanyao Wang, Kai Zhang, Chen Chen, Yuan Zhang, Shuzhi Feng, Ximo Wang, Yubao Chen, Huailin Gao, Fengjiang Wei, Wei-Dong Li
Frontiers in Endocrinology.2023;[Epub] CrossRef
Emerging Therapeutic Strategies for Attenuating Tubular EMT and Kidney Fibrosis by Targeting Wnt/β-Catenin Signaling
Lichao Hu, Mengyuan Ding, Weichun He
Frontiers in Pharmacology.2022;[Epub] CrossRef
Does Serum R-Spondin-1 Play a Role in PCOS Pathophysiology?
Osman BAŞPINAR, Yasin ŞİMŞEK, Derya KOÇER, Oğuzhan Sıtkı DİZDAR, Hatice KAYIŞ TOPALOĞLU
Genel Tıp Dergisi.2022; 32(5): 490. CrossRef
Silencing of RSPO1 mitigates obesity-related renal fibrosis in mice by deactivating Wnt/β-catenin pathway
Xuesong Su, Guangyu Zhou, Mi Tian, Si Wu, Yanqiu Wang
Experimental Cell Research.2021; 405(2): 112713. CrossRef
Exosome miR‐27a‐3p secreted from adipocytes targets ICOS to promote antitumor immunity in lung adenocarcinoma
Xuehan Fan, Jingya Wang, Tingting Qin, Yujia Zhang, Wenting Liu, Kaiting Jiang, Dingzhi Huang
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Integrative Analyses of Genes Associated with Subcutaneous Insulin Resistance
Manoj Kumar Pujar, Basavaraj Vastrad, Chanabasayya Vastrad
Biomolecules.2019; 9(2): 37. CrossRef

Brief Report

Others
Serum Soluble Epidermal Growth Factor Receptor Level Increase in Patients Newly Diagnosed with Type 2 Diabetes Mellitus: Ji Min Kim, Sorim Choung, Kyong Hye Joung, Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2018;42(4):343-347. Published online May 2, 2018; DOI: https://doi.org/10.4093/dmj.2017.0082

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We analyzed circulating soluble epidermal growth factor receptor (sEGFR) levels in humans. Serum sEGFR levels were higher in subjects with newly diagnosed type 2 diabetes mellitus compared with controls. Serum sEGFR was positively correlated with glycosylated hemoglobin and serum glucose and negatively correlated with serum insulin and C-peptide levels.

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Increased serum extrachromosomal circular DNA SORBS1circle level is associated with insulin resistance in patients with newly diagnosed type 2 diabetes mellitus
Xiang Kong, Shu-jun Wan, Tian-bing Chen, Lan Jiang, Yu-jie Xing, Ya-ping Bai, Qiang Hua, Xin-ming Yao, Yong-li Zhao, Hong-mei Zhang, De-guo Wang, Qing Su, Kun Lv
Cellular & Molecular Biology Letters.2024;[Epub] CrossRef
A Pilot Genome-Wide Association Study Identifies Novel Markers of Metabolic Syndrome in Patients with Psoriasis
Seung-Min Oh, Su-Kang Kim, Hye-Jin Ahn, Ki-Heon Jeong
Annals of Dermatology.2023; 35(4): 285. CrossRef
Effect of cholesterol-lowering agents on soluble epidermal growth factor receptor level in type 2 diabetes and hypercholesterolemia
Jun Choul Lee, Kyong Hye Joung, Ji Min Kim, Seon Mee Kang, Hyun Jin Kim, Bon Jeong Ku
Medicine.2022; 101(34): e30287. CrossRef
Soluble EGFR, a hepatokine, and adipsin, an adipokine, are biomarkers correlated with distinct aspects of insulin resistance in type 2 diabetes subjects
Mayu Kyohara, Jun Shirakawa, Tomoko Okuyama, Yu Togashi, Ryota Inoue, Jinghe Li, Daisuke Miyashita, Yasuo Terauchi
Diabetology & Metabolic Syndrome.2020;[Epub] CrossRef
Epidermal growth factor protects against myocardial ischaemia reperfusion injury through activating Nrf2 signalling pathway
Jun Ma, Ge Jin
Free Radical Research.2019; 53(3): 313. CrossRef

Original Articles

Others
Clinical Implications of Using Post-Challenge Plasma Glucose Levels for Early Diagnosis of Type 2 Diabetes Mellitus in Older Individuals: Kyong Hye Joung, Sang Hyun Ju, Ji Min Kim, Sorim Choung, Jae Min Lee, Kang Seo Park, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2018;42(2):147-154. Published online February 13, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.147

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Background

The aim of this study was to explore the differences in the clinical characteristics and diagnostic rates of diabetes mellitus (DM) according to various criteria in different age groups and to evaluate the efficacy of each criterion for screening older patients.

Methods

We studied 515 patients and measured the fasting plasma glucose level (FPG), 2-hour plasma glucose level after the 75 g oral glucose tolerance test (2-hour postload glucose [2-h PG]), and glycosylated hemoglobin (HbA1c) for re-evaluation of hyperglycemia without a history of diabetes. Patients with newly diagnosed DM were grouped by age as younger (<65 years) or older (≥65 years).

Results

Older patients had significantly lower HbA1c, FPG, and 2-h PG levels and a higher homeostatic level of pancreatic β-cell function compared with younger patients (P<0.001). The older group had the lowest diagnostic rate when using the FPG level (45.5%) and the highest diagnostic rate when using the 2-h PG level (84.6%). These results were mostly due to the higher frequency of isolated post-challenge hyperglycemia in the older patients than in the younger group (28.8% vs. 9.2%). The use of both the FPG and HbA1c levels significantly enhanced the low diagnostic power when employing only the FPG levels in the older group (71.2% vs. 45.5%).

Conclusion

In the older patients, the 2-h PG level was the most accurate diagnostic criterion. When we consider the costs and convenience, a combination of the FPG and HbA1c criteria may be recommended as a screening test for DM in older people.

Citations

Citations to this article as recorded by

International Diabetes Federation Position Statement on the 1-hour post-load plasma glucose for the diagnosis of intermediate hyperglycaemia and type 2 diabetes
Michael Bergman, Melania Manco, Ilhan Satman, Juliana Chan, Maria Inês Schmidt, Giorgio Sesti, Teresa Vanessa Fiorentino, Muhammad Abdul-Ghani, Ram Jagannathan, Pramod Kumar Thyparambil Aravindakshan, Rafael Gabriel, Viswanathan Mohan, Martin Buysschaert,
Diabetes Research and Clinical Practice.2024; 209: 111589. CrossRef
Development and validation of a machine learning‐based model to predict isolated post‐challenge hyperglycemia in middle‐aged and elder adults: Analysis from a multicentric study
Rui Hou, Jingtao Dou, Lijuan Wu, Xiaoyu Zhang, Changwei Li, Weiqing Wang, Zhengnan Gao, Xulei Tang, Li Yan, Qin Wan, Zuojie Luo, Guijun Qin, Lulu Chen, Jianguang Ji, Yan He, Wei Wang, Yiming Mu, Deqiang Zheng
Diabetes/Metabolism Research and Reviews.2024;[Epub] CrossRef
A unified technique for entropy enhancement based diabetic retinopathy detection using hybrid neural network
Fatima, Muhammad Imran, Anayat Ullah, Muhammad Arif, Rida Noor
Computers in Biology and Medicine.2022; 145: 105424. CrossRef
In-silico identification of peroxisome proliferator-activated receptor (PPAR)α/γ agonists from Ligand Expo Components database
Xiao-Yan Feng, Ting-Ting Ding, Ya-Ya Liu, Wei-Ren Xu, Xian-Chao Cheng
Journal of Biomolecular Structure and Dynamics.2021; 39(5): 1853. CrossRef

Others
Addition of Ipragliflozin to Metformin Treatment in Korean Patients with Type 2 Diabetes Mellitus: Subgroup Analysis of a Phase 3 Trial: Kyung-Wan Min, Bon Jeong Ku, Ji-Hyun Lee, Min-Seon Kim, Kyu-Jeung Ahn, Moon-Kyu Lee, Satoshi Kokubo, Satoshi Yoshida, Hyun-Ji Cho, Bong-Soo Cha; Diabetes Metab J. 2017;41(2):135-145. Published online January 11, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.2.135

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Background

This is a subgroup analysis of Korean patients from a phase 3 clinical trial investigating the efficacy and safety of ipragliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin.

Methods

This multicenter, placebo-controlled, double-blind, parallel-group study was carried out between November 2011 and January 2013. Patients entered a 2-week placebo pretreatment period, followed by a 24-week treatment period with either ipragliflozin (50 mg/day) or placebo, while continuing metformin. Efficacy outcomes (glycosylated hemoglobin [HbA1c], fasting plasma glucose [FPG], and body weight) and safety outcomes (treatment-emergent adverse events [TEAEs]) were measured and compared between the two treatment groups for patients enrolled in all 18 study sites in Korea.

Results

Eighty-two Korean patients received ipragliflozin (n=43) or placebo (n=39) during the study period. Mean changes in HbA1c levels from baseline to the end of treatment were –0.97% in the ipragliflozin group and –0.31% in the placebo group, with an adjusted between-group difference of –0.60% (P<0.001). Compared to placebo, FPG and body weight also decreased significantly (both P<0.001) from baseline after treatment in the ipragliflozin group, with between-group differences of –21.4 mg/dL and –1.53 kg, respectively. Decreased weight was the most common TEAE in the ipragliflozin group (7.0%); there were no reports of genital and urinary tract infection.

Conclusion

Ipragliflozin treatment in addition to metformin led to significant improvement in glycemic outcomes and reduction in body weight in Korean patients with type 2 diabetes mellitus, compared with metformin treatment alone; the safety profile was comparable in both groups.

Citations

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Effects of sodium-glucose cotransporter 2 inhibitors on bone metabolism in patients with type 2 diabetes mellitus: a systematic review and meta-analysis
Jing Wang, Xin Li, Yang Li, Chen Lei
BMC Endocrine Disorders.2024;[Epub] CrossRef
Effect of ipragliflozin on liver enzymes in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials
Rizwana Parveen, Shadan Hussain, Sparsh Saini, Parvej Khan, Nilanjan Saha, Nidhi
Expert Opinion on Pharmacotherapy.2024; 25(7): 925. CrossRef
Add-on therapy with dapagliflozin in routine outpatient care of type 2 diabetes patients from Turkey: a retrospective cohort study on HbA1c, body weight, and blood pressure outcomes
Derun Taner Ertugrul, Erdal Kan, Cigdem Bahadir Tura, Haci Bayram Tugtekin, Hayati Ayakta, Mehmet Celebioglu, Ceren Yılmaz, Onur Utebay, Ilhan Yetkin, Eren Gurkan, Kerem Sezer, Ramazan Gen, Suleyman Ozcaylak, Yildiz Okuturlar, Mehmet Coskun, Nilgun Govec
International Journal of Diabetes in Developing Countries.2022; 42(1): 147. CrossRef
SGLT2 Inhibitors as Add-On Therapy to Metformin for People with Type 2 Diabetes: A Review of Placebo-Controlled Trials in Asian versus Non-Asian Patients

André J Scheen
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2020; Volume 13: 2765. CrossRef
Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial
Eugene Han, Yong-ho Lee, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha
Journal of Clinical Medicine.2020; 9(1): 259. CrossRef
Safety of Ipragliflozin in Patients with Type 2 Diabetes Mellitus: Pooled Analysis of Phase II/III/IV Clinical Trials
Atsunori Kashiwagi, Marina V. Shestakova, Yuichiro Ito, Masahiro Noguchi, Wim Wilpshaar, Satoshi Yoshida, John P. H. Wilding
Diabetes Therapy.2019; 10(6): 2201. CrossRef
Mechanistic effects of SGLT2 inhibition on blood pressure in diabetes
Habib Yaribeygi, Stephen L. Atkin, Amirhossein Sahebkar
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2019; 13(2): 1679. CrossRef
Ipragliflozin as an add-on therapy in type 2 diabetes mellitus patients: An evidence-based pharmacoeconomics evaluation
Hongmei Wang, Gaoqiong Yao, Xi Chen, Jing Ouyang, Jiadan Yang
Diabetes Research and Clinical Practice.2019; 157: 107867. CrossRef
Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea
Eugene Han, Ari Kim, Sung Jae Lee, Je-Yon Kim, Jae Hyeon Kim, Woo Je Lee, Byung-Wan Lee
Diabetes Therapy.2018; 9(4): 1689. CrossRef
A phase 3 randomized placebo-controlled trial to assess the efficacy and safety of ipragliflozin as an add-on therapy to metformin in Russian patients with inadequately controlled type 2 diabetes mellitus
Marina V. Shestakova, John P.H. Wilding, Wim Wilpshaar, Reiner Tretter, Valeria L. Orlova, Andrey F. Verbovoy
Diabetes Research and Clinical Practice.2018; 146: 240. CrossRef
Efficacy and safety of ipragliflozin as an add‐on therapy to sitagliptin and metformin in Korean patients with inadequately controlled type 2 diabetes mellitus: A randomized controlled trial
Kyung‐Ah Han, Suk Chon, Choon Hee Chung, Soo Lim, Kwan‐Woo Lee, SeiHyun Baik, Chang Hee Jung, Dong‐Sun Kim, Kyong Soo Park, Kun‐Ho Yoon, In‐Kyu Lee, Bong‐Soo Cha, Taishi Sakatani, Sumi Park, Moon‐Kyu Lee
Diabetes, Obesity and Metabolism.2018; 20(10): 2408. CrossRef
Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
Diabetes & Metabolism Journal.2017; 41(5): 337. CrossRef
Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association
Seung-Hyun Ko, Kyu-Yeon Hur, Sang Youl Rhee, Nan-Hee Kim, Min Kyong Moon, Seok-O Park, Byung-Wan Lee, Hyun Jin Kim, Kyung Mook Choi, Jin Hwa Kim
The Korean Journal of Internal Medicine.2017; 32(6): 947. CrossRef
Combination therapy of oral hypoglycemic agents in patients with type 2 diabetes mellitus
Min Kyong Moon, Kyu Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
The Korean Journal of Internal Medicine.2017; 32(6): 974. CrossRef
Combination Therapy of Oral Hypoglycemic Agents in Patients with Type 2 Diabetes Mellitus
Min Kyong Moon, Kyu-Yeon Hur, Seung-Hyun Ko, Seok-O Park, Byung-Wan Lee, Jin Hwa Kim, Sang Youl Rhee, Hyun Jin Kim, Kyung Mook Choi, Nan-Hee Kim
Diabetes & Metabolism Journal.2017; 41(5): 357. CrossRef

Others
Effect of Atorvastatin on Growth Differentiation Factor-15 in Patients with Type 2 Diabetes Mellitus and Dyslipidemia: Ji Min Kim, Min Kyung Back, Hyon-Seung Yi, Kyong Hye Joung, Hyun Jin Kim, Bon Jeong Ku; Diabetes Metab J. 2016;40(1):70-78. Published online February 19, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.1.70

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Background

Elevated serum levels of growth differentiation factor-15 (GDF-15) are associated with type 2 diabetes. Therefore, the effects of atorvastatin on metabolic parameters and GDF-15 levels in patients with type 2 diabetes and dyslipidemia were evaluated.

Methods

In this prospective randomized trial from February 2013 to March 2014, 50 consecutive type 2 diabetic patients with a low density lipoprotein cholesterol (LDL-C) levels ≥100 mg/dL were enrolled. The patients were divided into two groups based on the amount of atorvastatin prescribed, 10 mg/day (n=23) or 40 mg/day (n=27). The effect of atorvastatin on metabolic parameters, including lipid profiles and GDF-15 levels, at baseline and after 8 weeks of treatment were compared.

Results

The baseline metabolic parameters and GDF-15 levels were not significantly different between the two groups. After 8 weeks of treatment, the total cholesterol (TC) and LDL-C levels were significantly decreased in both groups. The mean changes in TC and LDL-C levels were more significant in the 40 mg atorvastatin group. The GDF-15 level was decreased in the 10 mg atorvastatin group, from 1,460.6±874.8 to 1,451.0±770.8 pg/mL, and was increased in the 40 mg atorvastatin group, from 1,271.6±801.0 to 1,341.4±855.2 pg/mL. However, the change in the GDF-15 level was not statistically significant in the 10 or 40 mg atorvastatin group (P=0.665 and P=0.745, respectively).

Conclusion

The GDF-15 levels were not significantly changed after an 8-week treatment with atorvastatin in type 2 diabetic patients.

Citations

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The relationship of Growth differentiation factor-15 with renal damage and dyslipidemia in non-albuminuric and albuminuric Type-2 Diabetes Mellitus
Hasan Esat Yücel, Bilal İlanbey
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Alexander Hodkinson, Dialechti Tsimpida, Evangelos Kontopantelis, Martin K Rutter, Mamas A Mamas, Maria Panagioti
BMJ.2022; : e067731. CrossRef
The Cytokine Growth Differentiation Factor-15 and Skeletal Muscle Health: Portrait of an Emerging Widely Applicable Disease Biomarker
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Atherosclerosis.2019; 281: 128. CrossRef

Response

Response: GDF15 Is a Novel Biomarker for Impaired Fasting Glucose (Diabetes Metab J 2014;38:472-9): Jun Hwa Hong, Bon Jeong Ku, Minho Shong; Diabetes Metab J. 2015;39(1):84-86. Published online February 16, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.1.84

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Original Article

GDF15 Is a Novel Biomarker for Impaired Fasting Glucose: Jun Hwa Hong, Hyo Kyun Chung, Hye Yoon Park, Kyong-Hye Joung, Ju Hee Lee, Jin Gyu Jung, Koon Soon Kim, Hyun Jin Kim, Bon Jeong Ku, Minho Shong; Diabetes Metab J. 2014;38(6):472-479. Published online December 15, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.6.472

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Background

Growth differentiation factor-15 (GDF15) is a protein that belongs to the transforming growth factor β superfamily. An elevated serum level of GDF15 was found to be associated with type 2 diabetes mellitus (T2DM). T2DM is an inflammatory disease that progresses from normal glucose tolerance (NGT) to impaired fasting glucose (IFG). Hence, we aimed to validate the relationship between GDF15 and IFG.

Methods

The participants were divided into the following three groups: NGT (n=137), IFG (n=29), and T2DM (n=75). The controls and T2DM outpatients visited the hospital for routine health check-ups. We used fasting blood glucose to detect IFG in nondiabetic patients. We checked the body mass index (BMI), C-reactive protein level, metabolic parameters, and fasting serum GDF15 level.

Results

Age, BMI, triglyceride, insulin, glucose, homeostatic model assessment-insulin resistance (HOMA-IR), and GDF15 levels were elevated in the IFG and T2DM groups compared to the NGT group. In the correlation analysis between metabolic parameters and GDF15, age and HOMA-IR had a significant positive correlation with GDF15 levels. GDF15 significantly discriminated between IFG and NGT, independent of age, BMI, and HOMA-IR. The serum levels of GDF15 were more elevated in men than in women. As a biomarker for IFG based on the receiver operating characteristic curve analysis, the cutoff value of GDF15 was 510 pg/mL in males and 400 pg/mL in females.

Conclusion

GDF15 had a positive correlation with IR independent of age and BMI, and the serum level of GDF15 was increased in the IFG and T2DM groups. GDF15 may be a novel biomarker for detecting IFG in nondiabetic patients.

Citations

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Response

Bone Mineral Density in Prediabetic Men (Korean Diabetes J 2010;34:294-302): Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku; Korean Diabetes J. 2010;34(6):386-387. Published online December 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.6.386

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Original Articles

Bone Mineral Density in Prediabetic Men: Ju Hee Lee, Yun Hyeong Lee, Kyoung Hye Jung, Min Kyeong Kim, Hye Won Jang, Tae Kyun Kim, Hyun Jin Kim, Young Suk Jo, Minho Shong, Tae Yong Lee, Bon Jeong Ku; Korean Diabetes J. 2010;34(5):294-302. Published online October 31, 2010; DOI: https://doi.org/10.4093/kdj.2010.34.5.294

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Background

There are many studies regarding the effects of insulin on bone metabolism and changes in bone mineral density (BMD) in the setting of diabetes. The effect of prediabetes on BMD is not known.

Methods

A total of 802 men participated in the Korea Rural Genomic Cohort Study (in Geumsan County). According to the results of an oral glucose tolerance test, subjects were classified into normal, prediabetic, and diabetic categories. One hundred twenty-four subjects diagnosed with type 2 diabetes were excluded, leaving 678 subjects for the study inclusion. BMD was estimated with a quantitative ultrasonometer.

Results

The average BMD T scores of normal and prediabetic subjects were -1.34 ± 1.42 and -1.33 ± 1.30, respectively; there was no significant difference in the BMD T scores between these groups. The BMD T score was inversely associated with age and positively correlated with body weight, body mass index, total cholesterol, low density lipoprotein cholesterol, and HbA1c. On multiple linear regression analysis, low density lipoprotein cholesterol was the only statistically significant variable for prediabetes (β = 0.007, P = 0.005). On the stepwise regression analysis, age (β = -0.026, P < 0.001), the body mass index (β = 0.079, P < 0.001), and low density lipoprotein cholesterol (β = 0.004, P = 0.016) were significant variables for prediabetes.

Conclusions

There was no significant difference in the BMD T score between the normal and prediabetic subjects. Further studies are needed regarding the association of fracture risk and changes in BMD with the development of overt diabetes.

Citations

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Response: Bone Mineral Density in Prediabetic Men (Korean Diabetes J 2010;34:294-302)
Ju Hee Lee, Hyun Jin Kim, Bon Jeong Ku
Korean Diabetes Journal.2010; 34(6): 386. CrossRef
Letter: Bone Mineral Density in Prediabetic Men (Korean Diabetes J 2010;34:294-302)
Chul-Hee Kim
Korean Diabetes Journal.2010; 34(6): 384. CrossRef

The Effects of D-Chiro-Inositol on Glucose Metabolism in 3T3-L1 Cells.: Kang Seo Park, Jae Min Lee, Bon Jeong Ku, Young Suk Jo, Seong Kyu Lee, Kyung Wan Min, Kyung Ah Han, Hyo Jeong Kim, Hyun Jin Kim; Korean Diabetes J. 2008;32(3):196-203. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.196

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BACKGROUND
The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.

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Seung-Min Seo, Yeon-Shin Jeong, Dhakal Krisna Hari, Dong-Hyun Shin, In-Jung Lee, Eun-Sook Park, Jeong-Dong Lee, Young-Hyun Hwang
Korean Journal of Crop Science.2011; 56(1): 50. CrossRef

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The Plasma Adiponectin Levels in Patients with Newly Diagnosed Type 2 Diabetes.: Ihn Suk Lee, Bon Jeong Ku, Young Kun Kim; Korean Diabetes J. 2008;32(2):173-174. Published online April 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.2.173

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Original Articles

The Plasma Adiponectin Levels in Patients with Newly Diagnosed Type 2 Diabetes.: Ihn Suk Lee, Yun Jeung Kim, Jong Im Kim, Jea Hyung Park, Bon Jeong Ku, Kang Seo Park, Tae Yong Lee, Young Kun Kim; Korean Diabetes J. 2007;31(6):507-516. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.507

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Abstract PDF: BACKGROUND
Adiponectin is secreted from adipose tissue and plays an important role in the regulation of glycemia and insulin resistance. In this study, the relationship between adiponectin and the adiposity, body composition, insulin sensitivity, lipid profile were respectively examined in newly diagnosed type 2 diabetes. METHODS: Total 1993 were participated in the Korea Rural Genomic Cohort Study (Geumsan County). After a 12-hour overnight fast, all subjects underwent 75-g oral glucose tolerance test. 105 of those were studied as newly diagnosed type 2 diabetes. The body composition was analyzed by means of bioelectric impedance analysis and the insulin sensitivity was estimated by fasting insulin, HOMA-IR and QUICKI method, respectively. RESULTS: Adiponectin positively correlated with high-density lipoprotein cholesterol (r = 0.246, P < 0.05). Adiponectin inversely associated with waist circumference (r = - 0.408, P < 0.01), triglyceride (r = -0.274, P < 0.05), ferritin (r = -0.260, P < 0.05), visceral fat (r = -0.248, P < 0.05), high sensitivity C-reactive protein (r = -0.228, P < 0.05) and body mass index (r = -0.225, P < 0.05). In multiple linear regression, waist circumference and high-density lipoprotein cholesterol were analyzed as independent variables of serum adiponectin. CONCLUSION: Adiponectin concentrations were closely related to waist circumference in newly diagnosed type 2 diabetes.

Change of Cardiac Function and NT-proBNP According to Degree of Albuminuria in Type 2 Diabetic Patients.: Bon Jeong Ku, Jeong Hee Kim, Jin Ok Jeong, Eun Seok Jeon, Dong Hyun Seo, Jae Min Lee, Si Wan Choi, In Whan Seong, Young Kun Kim; Korean Diabetes J. 2004;28(1):28-35. Published online February 1, 2004

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Abstract PDF: BACKGROUND
The prevalence of diabetes mellitus has increased recently. The morbidity and mortality of diabetic patients are mainly caused by chronic complications, especially cardiovascular events. N-terminal proB-type natriuretic peptide(NT-proBNP) is a neurohormone that is secreted from ventricular myocardium due to myocardial dilatation or pressure overload. NT-proBNP has prognostic value, and reflects cardiac function in patients with myocardial infarction or heart failure. This study was performed to evaluate functional changes of the heart, according to the degree of albuminuria and the prognostic value of NT-proBNP in type 2 diabetic patients. METHODS: 57 patients with type 2 diabetes were divided into three groups according to their degree of albuminuria, these being normal(below 30mg/day), microalbuminuria(30 between 300mg/day) and overt proteinuria(over 300mg/ day). The clinical parameters in each of the patients were evaluated, echocardiography performed and the levels of NT-proBNP checked, and compared between the three groups. RESULTS: Of the 57 patients with type 2 diabetes the male:female ratio of 32:25, with mean age, duration of diabetes and BMI of 55.8+/-10.1 and 11.3+/-8.2 years, and 23.2+/-4.0kg/m2, respectively. Twenty-eight patients showed normal(49.1%), 15 microalbuminuria(26.3%) and 14 overt proteinuria(24.6%). The age, BMI, diastolic BP and glycosylated hemoglobin showed no significant difference between the three groups. The duration of diagnosed diabetes was significantly longer, the systolic blood pressure and serum creatinine levels significantly higher and the serum hemoglobin significantly lower (p<0.05) in the overt proteinuria compared to the normal group. The duration of diabetes was significantly longer and serum creatinine levels significantly higher in the overt proteinuria than the microalbuminuria group(p<0.05). The echocardiographic data showed no difference among the groups. The NT-proBNP levels also showed no significant difference, but tended to be elevated toward albuminuria. CONCLUSION: The cardiac function and NT-proBNP levels showed no significant difference between each of the albuminuric groups. This study suggests that the degree of albuminuria is not a predictive factor for changes of the cardiac function and NT-proBNP levels

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