Diabetes & Metabolism Journal

Original Articles

Drug/Regimen
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 Metab J. 2024;48(4):730-739. Published online May 20, 2024; DOI: https://doi.org/10.4093/dmj.2023.0077

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Abstract PDF Supplementary Material PubReader ePub: 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.

Basic Research
DWN12088, A Prolyl-tRNA Synthetase Inhibitor, Alleviates Hepatic Injury in Nonalcoholic Steatohepatitis: Dong-Keon Lee, Su Ho Jo, Eun Soo Lee, Kyung Bong Ha, Na Won Park, Deok-Hoon Kong, Sang-In Park, Joon Seok Park, Choon Hee Chung; Diabetes Metab J. 2024;48(1):97-111. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2022.0367

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Abstract PDF Supplementary Material PubReader ePub: Background
Nonalcoholic steatohepatitis (NASH) is a liver disease caused by obesity that leads to hepatic lipoapoptosis, resulting in fibrosis and cirrhosis. However, the mechanism underlying NASH is largely unknown, and there is currently no effective therapeutic agent against it. DWN12088, an agent used for treating idiopathic pulmonary fibrosis, is a selective prolyl-tRNA synthetase (PRS) inhibitor that suppresses the synthesis of collagen. However, the mechanism underlying the hepatoprotective effect of DWN12088 is not clear. Therefore, we investigated the role of DWN12088 in NASH progression.
Methods
Mice were fed a chow diet or methionine-choline deficient (MCD)-diet, which was administered with DWN12088 or saline by oral gavage for 6 weeks. The effects of DWN12088 on NASH were evaluated by pathophysiological examinations, such as real-time quantitative reverse transcription polymerase chain reaction, immunoblotting, biochemical analysis, and immunohistochemistry. Molecular and cellular mechanisms of hepatic injury were assessed by in vitro cell culture.
Results
DWN12088 attenuated palmitic acid (PA)-induced lipid accumulation and lipoapoptosis by downregulating the Rho-kinase (ROCK)/AMP-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and protein kinase R-like endoplasmic reticulum kinase (PERK)/α subunit of eukaryotic initiation factor 2 (eIF2α)/activating transcription factor 4 (ATF4)/C/EBP-homologous protein (CHOP) signaling cascades. PA increased but DWN12088 inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 (Ser536, Ser276) and the expression of proinflammatory genes. Moreover, the DWN12088 inhibited transforming growth factor β (TGFβ)-induced pro-fibrotic gene expression by suppressing TGFβ receptor 1 (TGFβR1)/Smad2/3 and TGFβR1/glutamyl-prolyl-tRNA synthetase (EPRS)/signal transducer and activator of transcription 6 (STAT6) axis signaling. In the case of MCD-diet-induced NASH, DWN12088 reduced hepatic steatosis, inflammation, and lipoapoptosis and prevented the progression of fibrosis.
Conclusion
Our findings provide new insights about DWN12088, namely that it plays an important role in the overall improvement of NASH. Hence, DWN12088 shows great potential to be developed as a new integrated therapeutic agent for NASH.

Drug Regimen
Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension: Jun Sung Moon, Il Rae Park, Hae Jin Kim, Choon Hee Chung, Kyu Chang Won, Kyung Ah Han, Cheol-Young Park, Jong Chul Won, Dong Jun Kim, Gwan Pyo Koh, Eun Sook Kim, Jae Myung Yu, Eun-Gyoung Hong, Chang Beom Lee, Kun-Ho Yoon; Diabetes Metab J. 2023;47(6):808-817. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0387

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Background
This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination.
Methods
In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998).
Results
Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group.
Conclusion
Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Citations

Citations to this article as recorded by

Efficacy and safety of dapagliflozin add‐on to evogliptin plus metformin therapy in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled study
In‐Kyung Jeong, Kyung Mook Choi, Kyung Ah Han, Kyoung‐Ah Kim, In Joo Kim, Seung Jin Han, Won Young Lee, Soon Jib Yoo
Diabetes, Obesity and Metabolism.2024;[Epub] CrossRef

Basic Research
Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis: Kyung Bong Ha, Eun Soo Lee, Na Won Park, Su Ho Jo, Soyeon Shim, Dae-Kee Kim, Chan Mug Ahn, Choon Hee Chung; Diabetes Metab J. 2023;47(4):500-513. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0110

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Background
Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.
Methods
Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.
Results
TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.
Conclusion
Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

Citations

Citations to this article as recorded by

Molecular Pathways Governing the Termination of Liver Regeneration
Lianne R. de Haan, Rowan F. van Golen, Michal Heger, Martin Michel
Pharmacological Reviews.2024; 76(3): 500. CrossRef
Nicotinate-curcumin improves NASH by inhibiting the AKR1B10/ACCα-mediated triglyceride synthesis
Xiu-lian Lin, Ya-ling Zeng, Jie Ning, Zhe Cao, Lan-lan Bu, Wen-Jing Liao, Zhi-min Zhang, Tan-jun Zhao, Rong-geng Fu, Xue-Feng Yang, Yong-zhen Gong, Li-Mei Lin, De-liang Cao, Cai-ping Zhang, Duan-fang Liao, Ya-Mei Li, Jian-Guo Zeng
Lipids in Health and Disease.2024;[Epub] CrossRef
The pivotal role of dysregulated autophagy in the progression of non-alcoholic fatty liver disease
Qiaohui Shen, Ming Yang, Song Wang, Xingyu Chen, Sulan Chen, Rui Zhang, Zhuang Xiong, Yan Leng
Frontiers in Endocrinology.2024;[Epub] CrossRef

Drug/Regimen
A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus: Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Young Min, Sungrae Kim; Diabetes Metab J. 2022;46(6):855-865. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0264

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Background
Thiazolidinediones (TZDs) have been associated with various safety concerns including weight gain, bladder cancer, and congestive heart failure (CHF). This study evaluated the efficacy and safety of lobeglitazone, a novel TZD in patients with type 2 diabetes mellitus (T2DM) in real practice.
Methods
In this non-interventional, multi-center, retrospective, and observational study conducted at 15 tertiary or secondary referral hospitals in Korea, a total of 2,228 patients with T2DM who received lobeglitazone 0.5 mg for more than 1 year were enrolled.
Results
Overall adverse events (AEs) occurred in 381 patients (17.10%) including edema in 1.97% (n=44). Cerebrovascular and cardiovascular diseases were identified in 0.81% (n=18) and 0.81% (n=18), respectively. One case of CHF was reported as an AE. Edema occurred in 1.97% (n=44) of patients. Hypoglycemia occurred in 2.47% (n=55) of patients. Fracture occurred in 1.17% (n=26) of all patients. Lobeglitazone significantly decreased HbA1c level, resulting in a mean treatment difference of -1.05%± 1.35% (P<0.001), and decreased total cholesterol, triglyceride, and low-density lipoprotein cholesterol. However, it increased high-density lipoprotein cholesterol, regardless of statin administration. The patients who received lobeglitazone 0.5 mg showed an apparent reduction in glycosylated hemoglobin (HbA1c) from baseline during the first 6 months of treatment. The HbA1c levels remained stable between months 6 and 42.
Conclusion
Lobeglitazone has long-term safety profile, good glycemic-lowering effect and long-term durability of glycemic control in real-world clinical settings.

Citations

Citations to this article as recorded by

Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef
Lobeglitazone

Reactions Weekly.2023; 1948(1): 262. CrossRef
Lobeglitazone, a novel thiazolidinedione, for secondary prevention in patients with ischemic stroke: a nationwide nested case-control study
Joonsang Yoo, Jimin Jeon, Minyoul Baik, Jinkwon Kim
Cardiovascular Diabetology.2023;[Epub] CrossRef
Lobeglitazone and Its Therapeutic Benefits: A Review
Balamurugan M, Sarumathy S, Robinson R
Cureus.2023;[Epub] CrossRef
Oldies but Goodies: Thiazolidinedione as an Insulin Sensitizer with Cardioprotection
Eun-Hee Cho
Diabetes & Metabolism Journal.2022; 46(6): 827. CrossRef

Clinical Diabetes & Therapeutics
Effects of Lobeglitazone, a Novel Thiazolidinedione, on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus over 52 Weeks: Soo Lim, Kyoung Min Kim, Sin Gon Kim, Doo Man Kim, Jeong-Taek Woo, Choon Hee Chung, Kyung Soo Ko, Jeong Hyun Park, Yongsoo Park, Sang Jin Kim, Hak Chul Jang, Dong Seop Choi; Diabetes Metab J. 2017;41(5):377-385. Published online October 24, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.5.377

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Background

The aim of this multicenter, randomized, double-blind study was to examine the effect of lobeglitazone, a novel thiazolidinedione, on the changes in bone mineral density (BMD) in patients with type 2 diabetes mellitus.

Methods

A 24-week, double-blinded phase was followed by a 28-week, open-label phase, in which the placebo group also started to receive lobeglitazone. A total of 170 patients aged 34 to 76 years were randomly assigned in a 2:1 ratio to receive lobeglitazone 0.5 mg or a matching placebo orally, once daily. BMD was assessed using dual-energy X-ray absorptiometry at week 24 and at the end of the study (week 52).

Results

During the double-blinded phase, the femur neck BMD showed decreasing patterns in both groups, without statistical significance (−0.85%±0.36% and −0.78%±0.46% in the lobeglitazone and placebo groups, respectively). The treatment difference between the groups was 0.07%, which was also not statistically significant. Further, minimal, nonsignificant decreases were observed in both groups in the total hip BMD compared to values at baseline, and these differences also did not significantly differ between the groups. During the open-label phase, the BMD was further decreased, but not significantly, by −0.32% at the femur neck and by −0.60% at the total hip in the lobeglitazone group, and these changes did not significantly differ compared with the original placebo group switched to lobeglitazone.

Conclusion

Our results indicate that treatment with lobeglitazone 0.5 mg over 52 weeks showed no detrimental effect on the BMD compared to the placebo.

Citations

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Medication-induced Fractures: Screening and Treatment Strategies
Laraib Javed, Aemen Khakwani, Uzair Khan, Mary Beth Humphrey
The American Journal of the Medical Sciences.2024;[Epub] CrossRef
Efficacy and safety of novel thiazolidinedione lobeglitazone for managing type-2 diabetes a meta-analysis
Deep Dutta, Saptarshi Bhattacharya, Manoj Kumar, Priyankar K. Datta, Ritin Mohindra, Meha Sharma
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102697. CrossRef
Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis
Shashank R. Joshi, Saibal Das, Suja Xaviar, Shambo Samrat Samajdar, Indranil Saha, Sougata Sarkar, Shatavisa Mukherjee, Santanu Kumar Tripathi, Jyotirmoy Pal, Nandini Chatterjee
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(1): 102703. CrossRef
The benefits of adipocyte metabolism in bone health and regeneration
Lisa-Marie Burkhardt, Christian H. Bucher, Julia Löffler, Charlotte Rinne, Georg N. Duda, Sven Geissler, Tim J. Schulz, Katharina Schmidt-Bleek
Frontiers in Cell and Developmental Biology.2023;[Epub] CrossRef
Will lobeglitazone rival pioglitazone? A systematic review and critical appraisal
Kalyan Kumar Gangopadhyay, Awadhesh Kumar Singh
Diabetes & Metabolic Syndrome: Clinical Research & Reviews.2023; 17(4): 102747. CrossRef
Comparison of therapeutic efficacy and safety of sitagliptin, dapagliflozin, or lobeglitazone adjunct therapy in patients with type 2 diabetes mellitus inadequately controlled on sulfonylurea and metformin: Third agent study
Jun Hwa Hong, Jun Sung Moon, Kayeon Seong, Soo Lim
Diabetes Research and Clinical Practice.2023; 203: 110872. CrossRef
Bone Mineral Density Evaluation Among Type 2 Diabetic Patients in Rural Haryana, India: An Analytical Cross-Sectional Study
Nitish Khandelwal, Surbhi Rajauria, Siddhesh Pandurang Kanjalkar, Omkar Shivaji Chavanke, Sanjay Rai
Cureus.2023;[Epub] CrossRef
Lobeglitazone and Its Therapeutic Benefits: A Review
Balamurugan M, Sarumathy S, Robinson R
Cureus.2023;[Epub] CrossRef
A double‐blind, Randomized controlled trial on glucose‐lowering EFfects and safety of adding 0.25 or 0.5 mg lobeglitazone in type 2 diabetes patients with INadequate control on metformin and dipeptidyl peptidase‐4 inhibitor therapy: REFIND study
Soree Ryang, Sang Soo Kim, Ji Cheol Bae, Ji Min Han, Su Kyoung Kwon, Young Il Kim, Il Seong Nam‐Goong, Eun Sook Kim, Mi‐kyung Kim, Chang Won Lee, Soyeon Yoo, Gwanpyo Koh, Min Jeong Kwon, Jeong Hyun Park, In Joo Kim
Diabetes, Obesity and Metabolism.2022; 24(9): 1800. CrossRef
A Real-World Study of Long-Term Safety and Efficacy of Lobeglitazone in Korean Patients with Type 2 Diabetes Mellitus
Bo-Yeon Kim, Hyuk-Sang Kwon, Suk Kyeong Kim, Jung-Hyun Noh, Cheol-Young Park, Hyeong-Kyu Park, Kee-Ho Song, Jong Chul Won, Jae Myung Yu, Mi Young Lee, Jae Hyuk Lee, Soo Lim, Sung Wan Chun, In-Kyung Jeong, Choon Hee Chung, Seung Jin Han, Hee-Seok Kim, Ju-Y
Diabetes & Metabolism Journal.2022; 46(6): 855. CrossRef
Comparative Efficacy of Lobeglitazone Versus Pioglitazone on Albuminuria in Patients with Type 2 Diabetes Mellitus
Kyung-Soo Kim, Sangmo Hong, Hong-Yup Ahn, Cheol-Young Park
Diabetes Therapy.2021; 12(1): 171. CrossRef
Lobeglitazone: A Novel Thiazolidinedione for the Management of Type 2 Diabetes Mellitus
Jaehyun Bae, Taegyun Park, Hyeyoung Kim, Minyoung Lee, Bong-Soo Cha
Diabetes & Metabolism Journal.2021; 45(3): 326. CrossRef
Effect of lobeglitazone on motor function in rat model of Parkinson’s disease with diabetes co-morbidity
Kambiz Hassanzadeh, Arman Rahimmi, Mohammad Raman Moloudi, Rita Maccarone, Massimo Corbo, Esmael Izadpanah, Marco Feligioni
Brain Research Bulletin.2021; 173: 184. CrossRef
Recent Perspective on Thiazolidinedione
Won Jun Kim
The Journal of Korean Diabetes.2021; 22(2): 97. CrossRef
Use of in vitro bone models to screen for altered bone metabolism, osteopathies, and fracture healing: challenges of complex models
Sabrina Ehnert, Helen Rinderknecht, Romina H. Aspera-Werz, Victor Häussling, Andreas K. Nussler
Archives of Toxicology.2020; 94(12): 3937. CrossRef
Update on: effects of anti-diabetic drugs on bone metabolism
Guillaume Mabilleau, Béatrice Bouvard
Expert Review of Endocrinology & Metabolism.2020; 15(6): 415. CrossRef
The use of metformin, insulin, sulphonylureas, and thiazolidinediones and the risk of fracture: Systematic review and meta‐analysis of observational studies
Khemayanto Hidayat, Xuan Du, Meng‐Jiao Wu, Bi‐Min Shi
Obesity Reviews.2019; 20(10): 1494. CrossRef
Diabetes pharmacotherapy and effects on the musculoskeletal system
Evangelia Kalaitzoglou, John L. Fowlkes, Iuliana Popescu, Kathryn M. Thrailkill
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Morin Exerts Anti‐Arthritic Effects by Attenuating Synovial Angiogenesis via Activation of Peroxisome Proliferator Activated Receptor‐γ
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The effects of diabetes therapy on bone: A clinical perspective
Karim G. Kheniser, Carmen M. Polanco Santos, Sangeeta R. Kashyap
Journal of Diabetes and its Complications.2018; 32(7): 713. CrossRef
Changes in the Bone Mineral Density of Femur Neck and Total Hip Over a 52-Week Treatment with Lobeglitazone
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Diabetes & Metabolism Journal.2017; 41(5): 374. CrossRef

Obesity and Metabolic Syndrome
Relationship between Regional Body Fat Distribution and Diabetes Mellitus: 2008 to 2010 Korean National Health and Nutrition Examination Surveys: Soo In Choi, Dawn Chung, Jung Soo Lim, Mi Young Lee, Jang Yel Shin, Choon Hee Chung, Ji Hye Huh; Diabetes Metab J. 2017;41(1):51-59. Published online December 21, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.51

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Background

The aim of this study was to investigate the association between regional body fat distribution, especially leg fat mass, and the prevalence of diabetes mellitus (DM) in adult populations.

Methods

A total of 3,181 men and 3,827 postmenopausal women aged 50 years or older were analyzed based on Korea National Health and Nutrition Examination Surveys (2008 to 2010). Body compositions including muscle mass and regional fat mass were measured using dual-energy X-ray absorptiometry.

Results

The odds ratios (ORs) for DM was higher with increasing truncal fat mass and arm fat mass, while it was lower with increasing leg fat mass. In a partial correlation analysis adjusted for age, leg fat mass was negatively associated with glycosylated hemoglobin in both sexes and fasting glucose in women. Leg fat mass was positively correlated with appendicular skeletal muscle mass and homeostasis model assessment of β cell. In addition, after adjusting for confounding factors, the OR for DM decreased gradually with increasing leg fat mass quartiles in both genders. When we subdivided the participants into four groups based on the median values of leg fat mass and leg muscle mass, higher leg fat mass significantly lowered the risk of DM even though they have smaller leg muscle mass in both genders (P<0.001).

Conclusion

The relationship between fat mass and the prevalence of DM is different according to regional body fat distribution. Higher leg fat mass was associated with a lower risk of DM in Korean populations. Maintaining leg fat mass may be important in preventing impaired glucose tolerance.

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Mahdi Vajdi, Mahsa khajeh, Ehsan Safaei, Seyedehelham Moeinolsadat, Samin Mousavi, Hooria Seyedhosseini-Ghaheh, Mahdieh Abbasalizad-Farhangi, Gholamreza Askari
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Feray Çağiran Yilmaz, Aysun Atilgan, Günay Saka
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Dan-dan Li, Yang Yang, Zi-yi Gao, Li-hua Zhao, Xue Yang, Feng Xu, Chao Yu, Xiu-lin Zhang, Xue-qin Wang, Li-hua Wang, Jian-bin Su
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Impaired Lung Function and Lung Cancer Incidence: A Nationwide Population-Based Cohort Study
Hye Seon Kang, Yong-Moon Park, Seung-Hyun Ko, Seung Hoon Kim, Shin Young Kim, Chi Hong Kim, Kyungdo Han, Sung Kyoung Kim
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Su Nam Lee, Seung-Hyun Ko, Sung-Ho Her, Kyungdo Han, Donggyu Moon, Sung Kyoung Kim, Ki-Dong Yoo, Yu-Bae Ahn
Scientific Reports.2022;[Epub] CrossRef
Is imaging-based muscle quantity associated with risk of diabetes? A meta-analysis of cohort studies
Shanhu Qiu, Xue Cai, Yang Yuan, Bo Xie, Zilin Sun, Tongzhi Wu
Diabetes Research and Clinical Practice.2022; 189: 109939. CrossRef
Research Progress of Body Composition Changes in Type 2 Diabetes Patients
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Advances in Clinical Medicine.2022; 12(08): 7181. CrossRef
Associations of eating speed with fat distribution and body shape vary in different age groups and obesity status
Saili Ni, Menghan Jia, Xuemiao Wang, Yun Hong, Xueyin Zhao, Liang Zhang, Yuan Ru, Fei Yang, Shankuan Zhu
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Review

Diabetes Epidemics in Korea: Reappraise Nationwide Survey of Diabetes "Diabetes in Korea 2007": Ie Byung Park, Jaiyong Kim, Dae Jung Kim, Choon Hee Chung, Jee-Young Oh, Seok Won Park, Juneyoung Lee, Kyung Mook Choi, Kyung Wan Min, Jeong Hyun Park, Hyun Shik Son, Chul Woo Ahn, Hwayoung Kim, Sunhee Lee, Im Bong Lee, Injeoung Choi, Sei Hyun Baik; Diabetes Metab J. 2013;37(4):233-239. Published online August 14, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.4.233

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There are many studies on the prevalence, clinical characteristics, and economic burden of diabetes across the past four decades in Korea. Nonetheless, there is a dearth of nationwide study regarding diabetes encompassing all age group. Eight years ago, the Committee on the Epidemiology of Diabetes Mellitus of Korean Diabetes Association collaborated with Health Insurance Review & Assessment Service to evaluate the status of diabetes care and characteristics in diabetic patients in Korea. In 2007, the collaborative task force team published a comprehensive survey titled "Diabetes in Korea 2007." In this review, we reappraise the diabetic epidemics from the joint report and suggest further studies that are needed to be investigated in the future.

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Original Articles

Role of HbA1c in the Screening of Diabetes Mellitus in a Korean Rural Community: Jae Hyun Kim, Gun Woo Kim, Mi Young Lee, Jang Yel Shin, Young Goo Shin, Sang Baek Koh, Choon Hee Chung; Diabetes Metab J. 2012;36(1):37-42. Published online February 17, 2012; DOI: https://doi.org/10.4093/dmj.2012.36.1.37

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Abstract PDF PubReader

Background

Recently, the measurement of glycated hemoglobin (HbA1c) was recommended as an alternative to fasting plasma glucose or oral glucose tolerance tests for diagnosing diabetes mellitus (DM). In this study, we analyzed HbA1c levels for diabetes mellitus screening in a Korean rural population.

Methods

We analyzed data from 10,111 subjects from a Korean Rural Genomic Cohort study and generated a receiver operating characteristic curve to determine an appropriate HbA1c cutoff value for diabetes.

Results

The mean age of the subjects was 56.3±8.1 years. Fasting plasma glucose and 2-hour plasma glucose after 75 g oral glucose tolerance tests were 97.5±25.6 and 138.3±67.1 mg/dL, respectively. The mean HbA1c level of the subjects was 5.7±0.9%. There were 8,809 non-DM patients (87.1%) and 1,302 DM patients (12.9%). A positive relationship between HbA1c and plasma glucose levels and between HbA1c and 2-hour plasma glucose levels after oral glucose tolerance tests was found in a scatter plot of the data. Using Youden's index, the proper cutoff level of HbA1c for diabetes mellitus screening was 5.95% (sensitivity, 77%; specificity, 89.4%).

Conclusion

Our results suggest that the optimal HbA1c level for DM screening is 5.95%.

Citations

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Effects of Spironolactone and Losartan on Diabetic Nephropathy in a Type 2 Diabetic Rat Model: Mi Young Lee, Myoung Sook Shim, Bo Hwan Kim, Soon Won Hong, Ran Choi, Eun Young Lee, Soo Min Nam, Gun Woo Kim, Jang Yel Shin, Young Goo Shin, Choon Hee Chung; Diabetes Metab J. 2011;35(2):130-137. Published online April 30, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.2.130

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Background

While there is an evidence that the anti-inflammatory properties of spironolactone can attenuate proteinuria in type 2 diabetes, its effects on vascular endothelial growth factor (VEGF) expression in diabetic nephropathy have not been clearly defined. In this study, we examined the effects of spironolactone, losartan, and a combination of these two drugs on albuminuria, renal VEGF expression, and inflammatory and oxidative stress markers in a type 2 diabetic rat model.

Methods

Thirty-three Otsuka-Long-Evans-Tokushima-Fatty (OLETF) rats were divided into four groups and treated with different medication regimens from weeks 25 to 50; OLETF diabetic controls (n=5), spironolactone-treated (n=10), losartan-treated (n=9), and combination of spironolactone- and losartan-treated (n=9).

Results

At week 50, the albumin-to-creatinine ratio was significantly decreased in the losartan and combination groups compared to the control OLETF group. No decrease was detected in the spironolactone group. There was a significant reduction in renal VEGF, transforming growth factor (TGF)-β, and type IV collagen mRNA levels in the spironolactone- and combination regimen-treated groups. Twenty-four hour urine monocyte chemotactic protein-1 levels were comparable in all four groups but did show a decreasing trend in the losartan and combination regimen groups. Twenty-four hour urine malondialdehyde levels were significantly decreased in the spironolactone- and combination regimen-treated groups.

Conclusion

These results suggest that losartan alone and a combined regimen of spironolactone and losartan could ameliorate albuninuria by reducing renal VEGF expression. Also, simultaneous treatment with spironolactone and losartan may have protective effects against diabetic nephropathy by decreasing TGF-β and type IV collagen expression and by reducing oxidative stress in a type 2 diabetic rat model.

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Relationship Between Metabolic Syndrome and Risk of Chronic Complications in Koreans with Type 2 Diabetes.: Hye Soo Chung, Ji A Seo, Sin Gon Kim, Nan Hee Kim, Doo Man Kim, Choon Hee Chung, Dong seop Choi; Korean Diabetes J. 2009;33(5):392-400. Published online October 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.5.392

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BACKGROUND
We examined the relationships between components of metabolic syndrome at the time of diagnosis of type 2 diabetes, and the development of chronic complications in Korean patients with type 2 diabetes. METHODS: The medical records of patients with type 2 diabetes who had undergone treatment for at least five years prior were collected from 10 general hospitals in Korea. Among a total of 1,418 patients reviewed for possible inclusion in this study, 603 patients were selected, and the occurrence of complications among these patients was evaluated. RESULTS: Among the 603 patients (male, 253; female, 350), 154 males (60.8%) and 266 females (76.0%) were diagnosed with metabolic syndrome at the time of initial diagnosis of type 2 diabetes. The incidence of chronic complications (average follow-up 15.2 +/- 4.9 years) included 60 cases of coronary artery disease (CAD), 57 cases of cerebrovascular accident (CVA), 268 cases of diabetic retinopathy (DR), 254 cases of diabetic nephropathy (DN), and 238 cases of diabetic peripheral neuropathy (DPN). As compared to patients without metabolic syndrome, the adjusted relative risks (95% CI) of incidental diabetic complications in patients with metabolic syndrome were 3.28 (1.40~7.71) for CAD, 2.04 (0.86~4.82) for CVA, 1.53 (1.10~2.14) for DR, 1.90 (1.29~2.80) for DN, and 1.51, (1.06~2.14) for DPN. With the addition of just one constituent of metabolic syndrome, the relative risk of developing CAD, CVD, DR, DN, and DPN increased by 2.08 (95% CI, 1.27~3.40), 1.16 (0.80~1.66), 1.09 (0.93~1.26), 1.29 (1.06~1.57) and 1.06 (0.87~1.26), respectively. CONCLUSION: Metabolic syndrome in Korean patients with type 2 diabetes increases the risk of developing both macrovascular and microvascular complications.

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Diabetes & Metabolism Journal.2012; 36(5): 357. CrossRef

A Nationwide Survey about the Current Status of Glycemic Control and Complications in Diabetic Patients in 2006: The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus.: Soo Lim, Dae Jung Kim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee; Korean Diabetes J. 2009;33(1):48-57. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.48

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BACKGROUND
The Committee of the Korean Diabetes Association on the Epidemiology of Diabetes Mellitus performed a nationwide survey about the current status of glycemic control and diabetic complications in 2006. METHODS: The current study included 5,652 diabetic patients recruited from the rosters of endocrinology clinics of 13 tertiary hospitals in Korea. Age, gender, height, weight, waist circumference and blood pressure were investigated by standard method. Fasting and postprandial 2 hour glucose, glycosylated hemoglobin (HbA1c), lipid profiles, fasting insulin and c-peptide levels were measured. Microvascular (microalbuminuria, retinopathy and neuropathy) and macrovascular (coronary artery disease [CAD], cerebrovascular disease [CVD] and peripheral artery disease [PAD]) complications were reviewed in their medical records. RESULTS: Mean age of total subjects was 58.7 (+/- 11.6) years and duration of diabetes was 8.8 (0~50) years. Mean fasting and postprandial 2 hour glucose levels were 145.9 +/- 55.0 and 208.0 +/- 84.4 mg/dL, respectively. Their mean HbA1c was 7.9 +/- 1.9%: the percentage of patients within target goal of glycemic control (< 7% of HbA1c) was 36.7%. In this study, 30.3%, 38.3% and 44.6% of patients was found to have microalbuminuria, retinopathy and nephropathy, respectively. Prevalence of CAD, CVD and PAD was 8.7%, 6.7% and 3.0%, respectively. Diabetic complications were closely related with age, duration of diabetes and glycemic control, and this relationship was stronger in microvascular complications than macrovascular ones. CONCLUSION: Only about one third of patients with diabetes was found to reach target glycemic control in tertiary hospitals of Korea. More tight control is needed to reduce deleterious complications of diabetes in Korea.

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Prevalence of the Metabolic Syndrome in Type 2 Diabetic Patients.: Tae Ho Kim, Dae Jung Kim, Soo Lim, In Kyung Jeong, Hyun Shik Son, Choon Hee Chung, Gwanpyo Koh, Dae Ho Lee, Kyu Chang Won, Jeong Hyun Park, Tae Sun Park, Jihyun Ahn, Jaetaek Kim, Keun Gyu Park, Seung Hyun Ko, Yu Bae Ahn, Inkyu Lee; Korean Diabetes J. 2009;33(1):40-47. Published online February 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.1.40

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Abstract PDF

BACKGROUND
The aim of this study was to analyze the prevalence of metabolic syndrome in Korean type 2 diabetic patients. METHODS: A total of 4,240 diabetic patients (male 2,033, female 2,207; mean age 58.7 +/- 11.3 years; DM duration 8.9 +/- 7.6 years) were selected from the data of endocrine clinics of 13 university hospitals in 2006. Metabolic syndrome was defined using the criteria of the American Heart Association/National Heart Lung and Blood Institute and the criteria of waist circumference from the Korean Society for the Study of Obesity. RESULTS: The prevalence of metabolic syndrome was 77.9% (76.7% of males, 78.9% of females). The average number of the components of metabolic syndrome was 2.4 +/- 1.1. Abdominal obesity was seen in 56.8% of the patients, hypertriglyceridemia in 42.0%, low HDL cholesterol in 65.1%, and high blood pressure in 74.9%. Abdominal obesity and high blood pressure were much more prevalent among females than males, and low HDL cholesterol was much more prevalent among males than females. The prevalence of metabolic syndrome was not different according to the duration of diabetes. Metabolic syndrome was strongly related with obesity (odds ratio, 6.3) and increased age (odds ratio in the over 70 group, 3.4). CONCLUSION: The prevalence of metabolic syndrome was 77.9% in Korean type 2 diabetic patients. Its prevalence was greater in obese patients and in those over 40 years of age.

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Relationship between Menopausal Status and Metabolic Syndrome Components in Korean Women.: Jang Hyun Koh, Mi Young Lee, Soo Min Nam, Joong Kyung Sung, Pil Moon Jung, Jin Kyu Noh, Jang Yel Shin, Young Goo Shin, Choon Hee Chung; Korean Diabetes J. 2008;32(3):243-251. Published online June 1, 2008; DOI: https://doi.org/10.4093/kdj.2008.32.3.243

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Abstract PDF

BACKGROUND
Postmenopausal status is associated with a 60% increased risk for metabolic syndrome. It is thought to be associated with decreased estrogens and increased abdominal obesity in postmenopausal women with metabolic syndrome. The purpose of this study was to investigate the association between metabolic syndrome components and menopausal status. METHODS: A total of 1,926 women were studied and divided into three groups according to their menstrual stage (premenopausal, perimenopausal or postmenopausal). The presence of metabolic syndrome was assessed using the National Cholesterol Education Program's (NCEP) Adult Treatment Panel III criteria. RESULTS: The prevalence of metabolic syndrome was 7.1% in premenopause, 9.8% in perimenopause, and 24.2% in postmenopause. The strong correlation was noted between the metabolic syndrome score and waist circumference in postmenopause (r = 0.56, P < 0.01) and perimenopause (r = 0.60, P < 0.01). Along the menopausal transition, the risk of metabolic syndrome increased with high triglyceride after the age-adjusted (odds ratio (OR) 1.517 [95% confidence interval (CI) 1.014~2.269] in perimenopausal women and OR 1.573 [95% CI 1.025~2.414] in postmenopausal women). In addition, the prevalence of metabolic syndromeincreased in accordance with elevated alanine aminotransferase (ALT) and gamma-glutamyl transpeptidase (GGT) levels. CONCLUSION: Triglyceride and waist circumference were important metabolic syndrome components, though ALT and GGT may also be related for predicting metabolic syndrome during the transition to menopause.

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Review

The Role of Glomerular Podocytes in Diabetic Nephropathy.: Eun Young Lee, Choon Hee Chung; Korean Diabetes J. 2007;31(6):451-454. Published online November 1, 2007; DOI: https://doi.org/10.4093/jkda.2007.31.6.451

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Diabetic nephropathy is the most common cause of end-stage renal disease and accounts for significant morbidity and mortality among individuals with diabetes mellitus. Therefore, the clarification of the pathogenesis of diabetic nephropathy is an urgent issue. Podocytes cover the outer layer of the glomerulus and maintain its integrity so that fluid and toxins exit in urine, but cells and important proteins are kept in the blood stream. Diabetes mellitus alters this structure, it becomes scarred and then the ability of the kidney to clear toxins is lost. Recent evidence shows that early in diabetes the podocyte number is reduced, areas of the glomerular basement membrane are denuded, and podocyte number predicts long-term urinary albumin excretion in the patients with diabetes and microalbuminuria. These results suggest that podocytes play a critical role in the early stage of diabetic nephropathy. It is the purpose of this article to review the pathogenetic role of podocytes in diabetic nephropathy.

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