Diabetes & Metabolism Journal

Volume 43(5); October 2019

Reviews

Pathophysiology
Regulation of Systemic Glucose Homeostasis by T Helper Type 2 Cytokines: Yea Eun Kang, Hyun Jin Kim, Minho Shong; Diabetes Metab J. 2019;43(5):549-559. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0157

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Obesity results in an inflammatory microenvironment in adipose tissue, leading to the deterioration of tissue protective mechanisms. Although recent studies suggested the importance of type 2 immunity in an anti-inflammatory microenvironment in adipose tissue, the regulatory effects of T helper 2 (Th2) cytokines on systemic metabolic regulation are not fully understood. Recently, we identified the roles of the Th2 cytokine (interleukin 4 [IL-4] and IL-13)-induced adipokine, growth differentiation factor 15 (GDF15), in adipose tissue in regulating systemic glucose metabolism via signal transducer and activator of transcription 6 (STAT6) activation. Moreover, we showed that mitochondrial oxidative phosphorylation is required to maintain these macrophage-regulating autocrine and paracrine signaling pathways via Th2 cytokine-induced secretion of GDF15. In this review, we discuss how the type 2 immune response and Th2 cytokines regulate metabolism in adipose tissue. Specifically, we review the systemic regulatory roles of Th2 cytokines in metabolic disease and the role of mitochondria in maintenance of type 2 responses in adipose tissue homeostasis.

Citations

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A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome
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Biomedicines.2023; 11(9): 2558. CrossRef
Gdf15 deletion exacerbates acute lung injuries induced by intratracheal inoculation of aerosolized ricin in mice
Mengyun Deng, Duo Su, Nan Xiao, Zhipeng Zhang, Yifeng Wang, Fuliang Zong, Sha Li, Jinglin Wang, Dongsheng Zhou, Yuee Zhao, Huiying Yang
Toxicology.2022; 469: 153135. CrossRef
Role of PPAR Receptor and Ligands in the Pathogenesis and Therapy of Hematologic Malignancies
Jian Wu, Min Zhang, Allison Faircloth
Hemato.2022; 3(3): 422. CrossRef
Macrophage and Adipocyte Mitochondrial Dysfunction in Obesity-Induced Metabolic Diseases
Liwen Wang, Jie Hu, Haiyan Zhou
The World Journal of Men's Health.2021; 39(4): 606. CrossRef
Th2 Cytokines Increase the Expression of Fibroblast Growth Factor 21 in the Liver
Seul-Gi Kang, Seong-Eun Lee, Min-Jeong Choi, Joon-Young Chang, Jung-Tae Kim, Ben-Yuan Zhang, Yea-Eun Kang, Ju-Hee Lee, Hyon-Seung Yi, Minho Shong
Cells.2021; 10(6): 1298. CrossRef
Growth/Differentiation Factor-15 (GDF-15): From Biomarker to Novel Targetable Immune Checkpoint
Jörg Wischhusen, Ignacio Melero, Wolf Herman Fridman
Frontiers in Immunology.2020;[Epub] CrossRef
Transcriptional, Epigenetic and Metabolic Programming of Tumor-Associated Macrophages
Irina Larionova, Elena Kazakova, Marina Patysheva, Julia Kzhyshkowska
Cancers.2020; 12(6): 1411. CrossRef

Obesity and Metabolic Syndrome
Contributing Factors to Diabetic Brain Injury and Cognitive Decline: Nirmal Verma, Florin Despa; Diabetes Metab J. 2019;43(5):560-567. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0153

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The link of diabetes with co-occurring disorders in the brain involves complex and multifactorial pathways. Genetically engineered rodents that express familial Alzheimer's disease-associated mutant forms of amyloid precursor protein and presenilin 1 (PSEN1) genes provided invaluable insights into the mechanisms and consequences of amyloid deposition in the brain. Adding diabetes factors (obesity, insulin impairment) to these animal models to predict success in translation to clinic have proven useful at some extent only. Here, we focus on contributing factors to diabetic brain injury with the aim of identifying appropriate animal models that can be used to mechanistically dissect the pathophysiology of diabetes-associated cognitive dysfunction and how diabetes medications may influence the development and progression of cognitive decline in humans with diabetes.

Citations

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The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia
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New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer’s disease
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Molecular and Cellular Biochemistry.2023; 478(12): 2739. CrossRef
Nicotinamide Prevents Diabetic Brain Inflammation via NAD+-Dependent Deacetylation Mechanisms
Jeimy Katherine Torres-Méndez, Julia Niño-Narvión, Patricia Martinez-Santos, Elena María Goretti Diarte-Añazco, Karen Alejandra Méndez-Lara, Tania Vázquez del Olmo, Noemi Rotllan, Maria Teresa Julián, Núria Alonso, Didac Mauricio, Mercedes Camacho, Juan P
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Ipriflavone as a non‐steroidal glucocorticoid receptor antagonist ameliorates diabetic cognitive impairment in mice
Ruifang Nie, Jian Lu, Rui Xu, Juanzhen Yang, Xingyi Shen, Xingnan Ouyang, Danyang Zhu, Yujie Huang, Tong Zhao, Xuejian Zhao, Yin Lu, Minyi Qian, Jiaying Wang, Xu Shen
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Effects of linagliptin vs glimepiride on cognitive performance in type 2 diabetes: results of the randomised double-blind, active-controlled CAROLINA-COGNITION study
Geert Jan Biessels, Chloë Verhagen, Jolien Janssen, Esther van den Berg, Gudrun Wallenstein, Bernard Zinman, Mark A. Espeland, Odd Erik Johansen
Diabetologia.2021; 64(6): 1235. CrossRef
The Association Between Second-Line Oral Antihyperglycemic Medication on Types of Dementia in Type 2 Diabetes: A Nationwide Real-World Longitudinal Study
Won Jun Kim, Jung Hyun Noh, Kyungdo Han, Cheol-Young Park
Journal of Alzheimer's Disease.2021; 81(3): 1263. CrossRef
The role of traditional Chinese medicine in the treatment of cognitive dysfunction in type 2 diabetes
Jinni Meng, Yafei Zhu, Huixia Ma, Xiaobo Wang, Qipeng Zhao
Journal of Ethnopharmacology.2021; 280: 114464. CrossRef
Letter: Hypoglycemia and Dementia Risk in Older Patients with Type 2 Diabetes Mellitus: A Propensity-Score Matched Analysis of a Population-Based Cohort Study (Diabetes Metab J 2020;44:125–33)
Jin Hwa Kim
Diabetes & Metabolism Journal.2020; 44(2): 356. CrossRef
Diabetes and dementia – the two faces of Janus
Athanasia Papazafiropoulou, Chris Koros, Andreas Melidonis , Stavros Antonopoulos
Archives of Medical Science – Atherosclerotic Diseases.2020; 5(1): 186. CrossRef

Others
Mitochondrial Toxins and Healthy Lifestyle Meet at the Crossroad of Hormesis: Yu-Mi Lee, Duk-Hee Lee; Diabetes Metab J. 2019;43(5):568-577. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0143

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Mitochondrial function is crucial for the maintenance of cellular homeostasis under physiological and stress conditions. Thus, chronic exposure to environmental chemicals that affect mitochondrial function can have harmful effects on humans. We argue that the concept of hormesis should be revisited to explain the non-linear responses to mitochondrial toxins at a low-dose range and develop practical methods to protect humans from the negative effects of mitochondrial toxins. Of the most concern to humans are lipophilic chemical mixtures and heavy metals, owing to their physical properties. Even though these chemicals tend to demonstrate no safe level in humans, a non-linear dose-response has been also observed. Stress response activation, i.e., hormesis, can explain this non-linearity. Recently, hormesis has reemerged as a unifying concept because diverse stressors can induce similar stress responses. Besides potentially harmful environmental chemicals, healthy lifestyle interventions such as exercise, calorie restriction (especially glucose), cognitive stimulation, and phytochemical intake also activate stress responses. This conceptual link can lead to the development of practical methods that counterbalance the harm of mitochondrial toxins. Unlike chemical hormesis with its safety issues, the activation of stress responses via lifestyle modification can be safely used to combat the negative effects of mitochondrial toxins.

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Polyethylene terephthalate (PET) micro- and nanoplastic particles affect the mitochondrial efficiency of human brain vascular pericytes without inducing oxidative stress
Sean M. Gettings, William Timbury, Anna Dmochowska, Riddhi Sharma, Rebecca McGonigle, Lewis E. MacKenzie, Guillaume Miquelard-Garnier, Nora Bourbia
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Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?
Duk‐Hee Lee, In‐Kyu Lee
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Hormetic Effects of Cerium, Lanthanum and Their Combination at Sub-micromolar Concentrations in Sea Urchin Sperm
Giovanni Pagano, Antonios Apostolos Brouziotis, Daniel Lyons, Ivana Čarapar, Rahime Oral, Serkan Tez, Philippe J. Thomas, Franca Tommasi, Giovanni Libralato, Marco Guida, Marco Trifuoggi
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Mitochondria: It is all about energy
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Type 2 Diabetes Induced by Changes in Proteomic Profiling of Zebrafish Chronically Exposed to a Mixture of Organochlorine Pesticides at Low Concentrations
Yan Gao, Hyojin Lee, Sangkyu Lee, Ki-Tae Kim
International Journal of Environmental Research and Public Health.2022; 19(9): 4991. CrossRef
Effect of Low-Dose Persistent Organic Pollutants on Mitochondrial Function: Human and in Vitro Evidence
Se-A Kim, Hoyul Lee, Sung-Mi Park, Mi-Jin Kim, Yu-Mi Lee, Young-Ran Yoon, Hyun-Kyung Lee, Hyo-Bang Moon, In-Kyu Lee, Duk-Hee Lee
Diabetes & Metabolism Journal.2022; 46(4): 592. CrossRef
Can Environmental Pollutants Be a Factor Linking Obesity and COVID-19?
Duk-Hee Lee
Journal of Korean Medical Science.2021;[Epub] CrossRef
Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study
Yu‐Mi Lee, Sun‐Hee Park, Duk‐Hee Lee
Alzheimer's & Dementia.2020; 16(4): 696. CrossRef
Lipophilic Environmental Chemical Mixtures Released During Weight‐Loss: The Need to Consider Dynamics
Duk‐Hee Lee, David R Jacobs, Lars Lind, P. Monica Lind
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Environmental toxicology and ecotoxicology: How clean is clean? Rethinking dose-response analysis
Evgenios Agathokleous, Edward J. Calabrese
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Editorial

Clinical Diabetes & Therapeutics
An Age of Sodium-Glucose Cotransporter-2 Inhibitor Priority: Are We Ready?: Ji A Seo; Diabetes Metab J. 2019;43(5):578-581. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0173

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Original Articles

Clinical Diabetes & Therapeutics
Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus: You-Cheol Hwang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung; Diabetes Metab J. 2019;43(5):582-589. Published online January 16, 2019; DOI: https://doi.org/10.4093/dmj.2018.0124

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Background

The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy.

Methods

This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks.

Results

After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation.

Conclusion

A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Citations

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Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review
Yura Kang, Jung Mi Park, Sang-Hak Lee
Yonsei Medical Journal.2024; 65(1): 19. CrossRef
Combination Therapy of Ezetimibe and Rosuvastatin for Dyslipidemia: Current Insights
Maya R Chilbert, Dylan VanDuyn, Sara Salah, Collin M Clark, Qing Ma
Drug Design, Development and Therapy.2022; Volume 16: 2177. CrossRef
Ezetimibe and diabetes mellitus:a new strategy for lowering cholesterol
V.A. Serhiyenko, A.A. Serhiyenko
INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2022; 18(5): 302. CrossRef
The Effect of Rosuvastatin on Plasma/Serum Levels of High-Sensitivity C-Reactive Protein, Interleukin-6, and D-Dimer in People Living with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis
Akililu Alemu Ashuro, Yin-Guang Fan, Yuan-Sheng Fu, Dong-Sheng Di, Napoleon Bellua Sam, Hai-Feng Pan, Dong-Qing Ye
AIDS Research and Human Retroviruses.2021; 37(11): 821. CrossRef
Comparison of the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy and Rosuvastatin Monotherapy on Lipoprotein in Patients With Type 2 Diabetes: Multicenter Randomized Controlled Study
Jiwoo Lee, You-Cheol Hwang, Woo Je Lee, Jong Chul Won, Kee-Ho Song, Cheol-Young Park, Kyu Jeung Ahn, Joong-Yeol Park
Diabetes Therapy.2020; 11(4): 859. CrossRef
Comparison of Renal Effects of Ezetimibe–Statin Combination versus Statin Monotherapy: A Propensity-Score-Matched Analysis
Jaehyun Bae, Namki Hong, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee
Journal of Clinical Medicine.2020; 9(3): 798. CrossRef
Combined use of rosuvastatin and ezetimibe improves hepatic steatosis in patients with dyslipidemia
Won Dong Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
European Journal of Gastroenterology & Hepatology.2020; 32(12): 1538. CrossRef
Influence of rosuvastatin dose on total fatty acids and free fatty acids in plasma
Cristian I. Ciucanu, Sonia Olariu, Daliborca C. Vlad, Victor Dumitraşcu
Medicine.2020; 99(48): e23356. CrossRef
The effect of switching from statin-monotherapy to statin/ezetimibe combination therapy on lipid profiles in patients with type 2 diabetes and dyslipidemia: a multicenter open-label study (EUCLID)
Mitsuhide Takeshita, Atsushi Tanaka, Atsushi Kawaguchi, Keiko Sato, Shigeru Toyoda, Teruo Inoue, Koichi Node
Vascular Failure.2020; 4(1): 22. CrossRef
Response: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019;43:582–9)
You-Cheol Hwang
Diabetes & Metabolism Journal.2019; 43(6): 915. CrossRef
Letter: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2019;43:582–9)
Tae Seo Sohn
Diabetes & Metabolism Journal.2019; 43(6): 909. CrossRef
Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes
Amélie I. S. Sobczak, Claudia A. Blindauer, Alan J. Stewart
Nutrients.2019; 11(9): 2022. CrossRef

Clinical Diabetes & Therapeutics
Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors in Korean Patients with Type 2 Diabetes Mellitus in Real-World Clinical Practice: A Ram Hong, Bo Kyung Koo, Sang Wan Kim, Ka Hee Yi, Min Kyong Moon; Diabetes Metab J. 2019;43(5):590-606. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2018.0134

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Background

This study aimed to evaluate the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in Korean patients who had inadequately controlled type 2 diabetes mellitus (T2DM) in real-world clinical practice.

Methods

We included 410 patients who started SGLT2 inhibitors (empagliflozin or dapagliflozin) as add-on therapy or switch therapy between February 2015 and June 2017. The primary efficacy endpoint was a change in glycosylated hemoglobin (HbA1c) from baseline to week 12. The secondary endpoints were patients achieving HbA1c <7.0% and changes in the fasting plasma glucose (FPG), lipid profiles, body weight, and blood pressure (BP).

Results

The mean HbA1c at baseline was 8.5% (8.6% in the add-on group and 8.4% in the switch group). At week 12, the mean adjusted HbA1c decreased by −0.68% in the overall patients (P<0.001), by −0.94% in the add-on group, and by −0.42% in the switch group. Significant reductions in FPG were also observed both in the add-on group and switch group (−30.3 and −19.8 mg/dL, respectively). Serum triglyceride (−16.5 mg/dL), body weight (−2.1 kg), systolic BP (−4.7 mm Hg), and diastolic BP (−1.3 mm Hg) were significantly improved in the overall patients. Approximately 18.3% of the patients achieved HbA1c <7.0% at week 12. A low incidence of hypoglycemia and genital tract infection was observed (6.3% and 2.2%, respectively).

Conclusion

SGLT2 inhibitors can be a suitable option as either add-on or switch therapy for Korean patients with inadequately controlled T2DM.

Citations

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Yesol Hong, Yoomin Jeon, Yoona Choi, Tae Kyu Chung, Howard Lee
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Real-world assessment of effectiveness and safety profile of remogliflozin etabonate in management of type 2 diabetes mellitus
Bipin Sethi, Subhankar Chowdhury, Supratik Bhattacharya, Sagar Katare, Sachin Suryawanshi, Hanmant Barkate
International Journal of Diabetes in Developing Countries.2023; 43(2): 214. CrossRef
Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study
Hyeong Kyu Park, Kyoung‐Ah Kim, Kyung‐Wan Min, Tae‐Seo Sohn, In Kyung Jeong, Chul Woo Ahn, Nan‐Hee Kim, Ie Byung Park, Ho Chan Cho, Choon Hee Chung, Sung Hee Choi, Kang Seo Park, Seoung‐Oh Yang, Kwan Woo Lee
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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 Extensio
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Diabetes & Metabolism Journal.2023; 47(6): 808. CrossRef
Real-world Data of Glycemic Control in a Suburban Population in Northern India during the COVID-19 Pandemic
Jaydip V. Revale, Preeti J. Revale
International Journal of Diabetes and Technology.2023; 2(2): 60. CrossRef
Sodium glucose co-transporter-2 inhibitor, Empagliflozin, is associated with significant reduction in weight, body mass index, fasting glucose, and A1c levels in Type 2 diabetic patients with established coronary heart disease: the SUPER GATE study
Satilmis Bilgin, Ozge Kurtkulagi, Tuba Taslamacioglu Duman, Burcin Meryem Atak Tel, Gizem Kahveci, Murat Kiran, Eray Erge, Gulali Aktas
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Five comparative cohorts to assess the risk of genital tract infections associated with sodium‐glucose cotransporter‐2 inhibitors initiation in type 2 diabetes mellitus
Wajd Alkabbani, Arsène Zongo, Jasjeet K. Minhas‐Sandhu, Dean T. Eurich, Baiju R. Shah, Mhd. Wasem Alsabbagh, John‐Michael Gamble
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Effect of Dapagliflozin in Combination with Lobeglitazone and Metformin in Korean Patients with Type 2 Diabetes in Real-World Clinical Practice
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Using real-world data for supporting regulatory decision making: Comparison of cardiovascular and safety outcomes of an empagliflozin randomized clinical trial versus real-world data
Ha Young Jang, In-Wha Kim, Jung Mi Oh
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Study comparing the efficacy and renal safety for patients with diabetes switching from dapagliflozin to empagliflozin
Ai-Yu Yang, Hung-Chun Chen
International Journal of Clinical Pharmacy.2021; 43(4): 1015. CrossRef
Empagliflozin Regulates the AdipoR1/p-AMPK/p-ACC Pathway to Alleviate Lipid Deposition in Diabetic Nephropathy
Zhiqin Zhang, Lihua Ni, Lian Zhang, Dongqing Zha, Chun Hu, Lingli Zhang, Huiling Feng, Xiaobao Wei, Xiaoyan Wu
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 227. CrossRef
Efficacy and Safety of Luseogliflozin in Patients with Type 2 Diabetes Complicated by Hepatic Dysfunction: A Single-Site, Single-Arm, Open-Label, Exploratory Trial
Hiroaki Seino
Diabetes Therapy.2021; 12(3): 863. CrossRef
Sodium–Glucose Cotransporter 2 Inhibitors and Risk of Retinal Vein Occlusion Among Patients With Type 2 Diabetes: A Propensity Score–Matched Cohort Study
Min-Kyung Lee, Bongsung Kim, Kyungdo Han, Jae-Hyuk Lee, Minhee Kim, Mee Kyoung Kim, Ki-Hyun Baek, Ki-Ho Song, Hyuk-Sang Kwon, Young-Jung Roh
Diabetes Care.2021; 44(10): 2419. CrossRef
Sodium-Glucose Cotransporter-2 Inhibitors Improve Cardiovascular Dysfunction in Type 2 Diabetic East Asians
Muhammad Afzal, Fahad Al-Abbasi, Muhammad Nadeem, Sultan Alshehri, Mohammed Ghoneim, Syed Imam, Waleed Almalki, Imran Kazmi
Metabolites.2021; 11(11): 794. CrossRef
Sodium-Glucose Cotransporter-2 Inhibitor for Renal Function Preservation in Patients with Type 2 Diabetes Mellitus: A Korean Diabetes Association and Korean Society of Nephrology Consensus Statement
Tae Jung Oh, Ju-Young Moon, Kyu Yeon Hur, Seung Hyun Ko, Hyun Jung Kim, Taehee Kim, Dong Won Lee, Min Kyong Moon
Diabetes & Metabolism Journal.2020; 44(4): 489. CrossRef
Sodium-glucose cotransporter-2 inhibitor for renal function preservation in patients with type 2 diabetes mellitus: A Korean Diabetes Association and Korean Society of Nephrology consensus statement
Tae Jung Oh, Ju-Young Moon, Kyu Yeon Hur, Seung Hyun Ko, Hyun Jung Kim, Taehee Kim, Dong Won Lee, Min Kyong Moon
Kidney Research and Clinical Practice.2020; 39(3): 269. CrossRef
Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan
Jung-Fu Chen, Yun-Shing Peng, Chung-Sen Chen, Chin-Hsiao Tseng, Pei-Chi Chen, Ting-I Lee, Yung-Chuan Lu, Yi-Sun Yang, Ching-Ling Lin, Yi-Jen Hung, Szu-Ta Chen, Chieh-Hsiang Lu, Chwen-Yi Yang, Ching-Chu Chen, Chun-Chuan Lee, Pi-Jung Hsiao, Ju-Ying Jiang, S
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Long-Term Effectiveness and Safety of SGLT-2 Inhibitors in an Italian Cohort of Patients with Type 2 Diabetes Mellitus
Maria Mirabelli, Eusebio Chiefari, Patrizia Caroleo, Raffaella Vero, Francesco Saverio Brunetti, Domenica Maria Corigliano, Biagio Arcidiacono, Daniela Patrizia Foti, Luigi Puccio, Antonio Brunetti
Journal of Diabetes Research.2019; 2019: 1. CrossRef
An Age of Sodium-Glucose Cotransporter-2 Inhibitor Priority: Are We Ready?
Ji A Seo
Diabetes & Metabolism Journal.2019; 43(5): 578. CrossRef

Clinical Diabetes & Therapeutics
Progression to Gestational Diabetes Mellitus in Pregnant Women with One Abnormal Value in Repeated Oral Glucose Tolerance Tests: Sunyoung Kang, Min Hyoung Kim, Moon Young Kim, Joon-Seok Hong, Soo Heon Kwak, Sung Hee Choi, Soo Lim, Kyong Soo Park, Hak C. Jang; Diabetes Metab J. 2019;43(5):607-614. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2018.0159

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Background

Women with one abnormal value (OAV) in a 100 g oral glucose tolerance test (OGTT) during pregnancy are reported to have an increased risk of adverse pregnancy outcomes. However, there is limited data about whether women with OAV will progress to gestational diabetes mellitus (GDM) when the OGTT is repeated.

Methods

To identify clinical and metabolic predictors for GDM in women with OAV, we conducted a retrospective study and identified women with OAV in the OGTT done at 24 to 30 weeks gestational age (GA) and repeated the second OGTT between 32 and 34 weeks of GA.

Results

Among 137 women with OAV in the initial OGTT, 58 (42.3%) had normal, 40 (29.2%) had OAV and 39 (28.5%) had GDM in the second OGTT. Maternal age, prepregnancy body mass index, weight gain from prepregnancy to the second OGTT, GA at the time of the OGTT, and parity were similar among normal, OAV, and GDM groups. Plasma glucose levels in screening tests were different (151.8±15.7, 155.8±14.6, 162.5±20.3 mg/dL, P<0.05), but fasting, 1-, 2-, and 3-hour glucose levels in the initial OGTT were not. Compared to women with screen negative, women with untreated OAV had a higher frequency of macrosomia.

Conclusion

We demonstrated that women with OAV in the initial OGTT significantly progressed to GDM in the second OGTT. Clinical parameters predicting progression to GDM were not found. Repeating the OGTT in women with OAV in the initial test may be helpful to detect GDM progression.

Citations

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Maternal and fetal outcomes of pregnancies associated with single versus double abnormal values in 100 gr glucose tolerance test
Mohammadali Shahriari, Ali Shahriari, Maryam Khooshideh, Anahita Dehghaninezhad, Arezoo Maleki-Hajiagha, Rana Karimi
Journal of Diabetes & Metabolic Disorders.2023; 22(2): 1347. CrossRef
One abnormal value or vomiting after oral glucose tolerance test in pregnancy: incidence and impact on maternal-fetal outcomes
Humberto Navarro-Martinez, Juana-Antonia Flores-Le Roux, Gemma Llauradó, Lucia Gortazar, Antonio Payà, Laura Mañé, Juan Pedro-Botet, David Benaiges
Gynecological Endocrinology.2023;[Epub] CrossRef
Analysis of the gut microflora in women with gestational diabetes mellitus
Xuping Wang, Bingfeng Bian, Fuman Du, Chaofeng Xiang, Yu Liu, Na Li, Binhong Duan
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The association between gestational impaired glucose tolerance and hyperglycemic markers: A prospective study
Ohad Gluck, Hadas Ganer Herman, Nataly Fainstein, Neri Katz, Jacob Bar, Michal Kovo
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Association of abnormal-glucose tolerance during pregnancy with exposure to PM2.5 components and sources
Dejian Mai, Chengfang Xu, Weiwei Lin, Dingli Yue, Shaojie Fu, Jianqing Lin, Luan Yuan, Yan Zhao, Yuhong Zhai, Huiying Mai, Xiaoling Zeng, Tingwu Jiang, Xuejiao Li, Jiajia Dai, Boning You, Qin Xiao, Qing Wei, Qiansheng Hu
Environmental Pollution.2022; 292: 118468. CrossRef
Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus
So-Yeon Kim, Young Shin Song, Soo-Kyung Kim, Yong-Wook Cho, Kyung-Soo Kim
Diabetes & Metabolism Journal.2022; 46(1): 140. CrossRef
The Clinical Characteristics of Gestational Diabetes Mellitus in Korea: A National Health Information Database Study
Kyung-Soo Kim, Sangmo Hong, Kyungdo Han, Cheol-Young Park
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Tae Jung Oh, Hak Chul Jang
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Azar Pirdehghan, Mohammad Eslahchi, Farzaneh Esna-Ashari, Shiva Borzouei
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Epidemiology
Association between Change in Alcohol Consumption and Metabolic Syndrome: Analysis from the Health Examinees Study: Seulggie Choi, Kyuwoong Kim, Jong-Koo Lee, Ji-Yeob Choi, Aesun Shin, Sue Kyung Park, Daehee Kang, Sang Min Park; Diabetes Metab J. 2019;43(5):615-626. Published online April 23, 2019; DOI: https://doi.org/10.4093/dmj.2018.0128

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Background

The association between change in alcohol intake and metabolic syndrome is unclear.

Methods

This retrospective cohort consisted of 41,368 males and females from the Health Examinees-GEM study. Participants were divided into non-drinkers (0.0 g/day), light drinkers (male: 0.1 to 19.9 g/day; female: 0.1 to 9.9 g/day), moderate drinkers (male: 20.0 to 39.9 g/day; female: 10.0 to 19.9 g/day), and heavy drinkers (male: ≥40.0 g/day; female: ≥20.0 g/day) for each of the initial and follow-up health examinations. Logistic regression analysis was used to determine the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for developing metabolic syndrome according to the change in alcohol consumption between the initial and follow-up health examinations. Adjusted mean values for the change in waist circumference, fasting serum glucose (FSG), blood pressure, triglycerides, and high density lipoprotein cholesterol (HDL-C) levels were determined according to the change in alcohol consumption by linear regression analysis.

Results

Compared to persistent light drinkers, those who increased alcohol intake to heavy levels had elevated risk of metabolic syndrome (aOR, 1.45; 95% CI, 1.09 to 1.92). In contrast, heavy drinkers who became light drinkers had reduced risk of metabolic syndrome (aOR, 0.61; 95% CI, 0.44 to 0.84) compared to persistent heavy drinkers. Increased alcohol consumption was associated with elevated adjusted mean values for waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels (all P<0.05). Reduction in alcohol intake was associated with decreased waist circumference, FSG, blood pressure, triglycerides, and HDL-C levels among initial heavy drinkers (all P<0.05).

Conclusion

Heavy drinkers who reduce alcohol consumption could benefit from reduced risk of metabolic syndrome.

Citations

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Inverse association between type 2 diabetes and hepatocellular carcinoma in East Asian populations
Jinlong Huo, Yaxuan Xu, Xingqi Chen, Jie Yu, Lijin Zhao
Frontiers in Endocrinology.2024;[Epub] CrossRef
Regulation Mechanism and Potential Value of Active Substances in Spices in Alcohol–Liver–Intestine Axis Health
Jianyu Huang, Tao Huang, Jinjun Li
International Journal of Molecular Sciences.2024; 25(7): 3728. CrossRef
Impact of green space and built environment on metabolic syndrome: A systematic review with meta-analysis
Muhammad Mainuddin Patwary, Mohammad Javad Zare Sakhvidi, Sadia Ashraf, Payam Dadvand, Matthew H.E.M. Browning, Md Ashraful Alam, Michelle L. Bell, Peter James, Thomas Astell-Burt
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Causal effects of sleep traits on metabolic syndrome and its components: a Mendelian randomization study
Yongli Yang, Long Wen, Xuezhong Shi, Chaojun Yang, Jingwen Fan, Yi Zhang, Guibin Shen, Huiping Zhou, Xiaocan Jia
Sleep and Breathing.2024;[Epub] CrossRef
Use of biochemical markers for diabetes prevention in the new decade
Marie Chan Sun, Marie A. S. Landinaff, Ruben Thoplan
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Alcohol consumption and metabolic syndrome: Clinical and epidemiological impact on liver disease
Fredrik Åberg, Christopher D. Byrne, Carlos J. Pirola, Ville Männistö, Silvia Sookoian
Journal of Hepatology.2023; 78(1): 191. CrossRef
Serum Nutritional Biomarkers and All-Cause and Cause-Specific Mortality in U.S. Adults with Metabolic Syndrome: The Results from National Health and Nutrition Examination Survey 2001–2006
Xinwei Peng, Jingjing Zhu, Henry S. Lynn, Xi Zhang
Nutrients.2023; 15(3): 553. CrossRef
Evaluation and Treatment of Obesity and Its Comorbidities: 2022 Update of Clinical Practice Guidelines for Obesity by the Korean Society for the Study of Obesity
Kyoung-Kon Kim, Ji-Hee Haam, Bom Taeck Kim, Eun Mi Kim, Jung Hwan Park, Sang Youl Rhee, Eonju Jeon, Eungu Kang, Ga Eun Nam, Hye Yeon Koo, Jeong-Hyun Lim, Jo-Eun Jeong, Jong-Hee Kim, Jong Won Kim, Jung Ha Park, Jun Hwa Hong, Sang Eok Lee, Se Hee Min, Seung
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Association between alcohol consumption and risk of hyperuricaemia among adults: a large cross-sectional study in Chongqing, China
Siyu Chen, Rui Ding, Xiaojun Tang, Liling Chen, Qinwen Luo, Meng Xiao, Xianbin Ding, Bin Peng
BMJ Open.2023; 13(12): e074697. CrossRef
Lifestyle Factors Associated with Metabolic Syndrome in Urban Cambodia
Miharu Tamaoki, Ikumi Honda, Keisuke Nakanishi, Maki Nakajima, Sophathya Cheam, Manabu Okawada, Hisataka Sakakibara
International Journal of Environmental Research and Public Health.2022; 19(17): 10481. CrossRef
Gender Differences of Health Behaviors in the Risk of Metabolic Syndrome for Middle-Aged Adults: A National Cross-Sectional Study in South Korea
Jaehee Yoon, Jeewuan Kim, Heesook Son
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Association between alcohol consumption and metabolic syndrome among Chinese adults
Yi Lin, Yan-Yan Ying, Si-Xuan Li, Si-Jia Wang, Qing-Hai Gong, Hui Li
Public Health Nutrition.2021; 24(14): 4582. CrossRef
Triglyceride-rich lipoprotein and LDL particle subfractions and their association with incident type 2 diabetes: the PREVEND study
Sara Sokooti, Jose L. Flores-Guerrero, Hiddo J. L. Heerspink, Margery A. Connelly, Stephan J. L. Bakker, Robin P. F. Dullaart
Cardiovascular Diabetology.2021;[Epub] CrossRef

Epidemiology
Longitudinal Changes of Body Composition Phenotypes and Their Association with Incident Type 2 Diabetes Mellitus during a 5-Year Follow-up in Koreans: Hong-Kyu Kim, Min Jung Lee, Eun-Hee Kim, Sung-Jin Bae, Jaewon Choe, Chul-Hee Kim, Joong-Yeol Park; Diabetes Metab J. 2019;43(5):627-639. Published online April 19, 2019; DOI: https://doi.org/10.4093/dmj.2018.0141

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Background

To elucidate longitudinal changes of complex body composition phenotypes and their association with incident type 2 diabetes mellitus.

Methods

A total of 17,280 (mean age, 48.1±8.2 years) Korean adults who underwent medical check-ups were included. The mean follow-up duration was 5.5±0.5 years. Body compositions were assessed using a bioelectrical impedance analysis. Four body composition phenotypes were defined using the median of appendicular skeletal muscle mass (ASM) index and fat mass index: low muscle/low fat (LM/LF); high muscle (HM)/LF; LM/high fat (HF); and HM/HF groups.

Results

Of the individuals in the LM/LF or HM/HF groups, over 60% remained in the same group, and over 30% were moved to the LM/HF group. Most of the LM/HF group remained in this group. In the baseline HM/LF group, approximately 30% stayed in the group, and the remaining individuals transitioned to the three other groups in similar proportions. Incident diabetes was significantly lower in participants who remained in the HM/LF group than those who transitioned to the LM/LF or LM/HF group from the baseline HM/LF group in men. ASM index was significantly associated with a decreased risk for incident diabetes in men regardless of obesity status (adjusted odds ratio [OR], 0.71 per kg/m²; 95% confidence interval [CI], 0.52 to 0.97 in non-obese) (adjusted OR, 0.87; 95% CI, 0.77 to 0.98 in obese) after adjusting for other strong risk factors (e.g., baseline glycosylated hemoglobin and homeostasis model assessment of insulin resistance).

Conclusion

Maintenance of ASM may be protective against the development of type 2 diabetes mellitus in men, regardless of obesity status.

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More appendicular lean mass relative to body mass index is associated with lower incident diabetes in middle-aged adults in the CARDIA study
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Association between hypertension and myosteatosis evaluated by abdominal computed tomography
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Clinical and Molecular Hepatology.2023; 29(4): 987. CrossRef
Association between type 2 diabetes and skeletal muscle quality assessed by abdominal computed tomography scan
Eun Hee Kim, Hong‐Kyu Kim, Min Jung Lee, Sung‐Jin Bae, Kyung Won Kim, Jaewon Choe
Diabetes/Metabolism Research and Reviews.2022;[Epub] CrossRef
Association between fat mass index, fat‐free mass index and hemoglobin A1c in a Japanese population: The Tohoku Medical Megabank Community‐based Cohort Study
Masato Takase, Tomohiro Nakamura, Takumi Hirata, Naho Tsuchiya, Mana Kogure, Fumi Itabashi, Naoki Nakaya, Yohei Hamanaka, Junichi Sugawara, Kichiya Suzuki, Nobuo Fuse, Akira Uruno, Eiichi N Kodama, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hoz
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Jee Hee Yoo, Sung Woon Park, Ji Eun Jun, Sang‐Man Jin, Kyu Yeon Hur, Moon‐Kyu Lee, Mira Kang, Gyuri Kim, Jae Hyeon Kim
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Eun Hee Kim, Kyung Won Kim, Yongbin Shin, Jiwoo Lee, Yousun Ko, Ye-Jee Kim, Min Jung Lee, Sung-Jin Bae, Sung Won Park, Jaewon Choe, Hong-Kyu Kim, Anne Newman
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Ailsa A. Welch, Richard P. G. Hayhoe, Donnie Cameron
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Jung A Kim, Da Hye Kim, Seon Mee Kim, Yong Gyu Park, Nan Hee Kim, Sei Hyun Baik, Kyung Mook Choi, Kyungdo Han, Hye Jin Yoo
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Complications
Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study: Yoo-Ri Chung, Kyoung Hwa Ha, Hyeon Chang Kim, Sang Jun Park, Kihwang Lee, Dae Jung Kim; Diabetes Metab J. 2019;43(5):640-648. Published online February 20, 2019; DOI: https://doi.org/10.4093/dmj.2018.0137

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Background

To investigate the effects of dipeptidyl peptidase-4 inhibitor (DPP4i) as add-on medications to metformin on progression of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus, compared with sulfonylurea (SU) or thiazolidinedione (TZD).

Methods

We identified 4,447 patients with DPP4i, 6,136 with SU, and 617 with TZD in addition to metformin therapy from the database of Korean National Health Insurance Service between January 2013 and December 2015. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for DR progression. The progression of DR was defined by the procedure code of panretinal photocoagulation, intravitreal injection or vitrectomy; or the addition of diagnostic code of vitreous hemorrhage, retinal detachment, or neovascular glaucoma.

Results

The age and sex-adjusted HR of DR progression was 0.74 for DPP4i add-on group compared with SU add-on group (95% confidence interval [CI], 0.62 to 0.89). This lower risk of DR progression remained significant after additional adjustments for comorbidities, duration of metformin therapy, intravitreal injections and calendar index year (HR, 0.80; 95% CI, 0.66 to 0.97).

Conclusion

This population-based cohort study showed that the use of DPP4i as add-on therapy to metformin did not increase the risk of DR progression compared to SU.

Citations

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Effects of newer-generation anti-diabetics on diabetic retinopathy: a critical review
Dimitrios P. Ntentakis, Victor San Martin Carvalho Correa, Anastasia Maria Ntentaki, Eleni Delavogia, Toshio Narimatsu, Nikolaos E. Efstathiou, Demetrios G. Vavvas
Graefe's Archive for Clinical and Experimental Ophthalmology.2024; 262(3): 717. CrossRef
Incretin‐based drugs and the risk of diabetic retinopathy among individuals with type 2 diabetes: A systematic review and meta‐analysis of observational studies
Samuel Igweokpala, Naheemot Olaoluwa Sule, Antonios Douros, Oriana H. Y. Yu, Kristian B. Filion
Diabetes, Obesity and Metabolism.2024; 26(2): 721. CrossRef
Weight loss, bariatric surgery, and novel antidiabetic drugs effects on diabetic retinopathy: a review
Alejandro M. Perez, Emily Neag, Jayanth Sridhar, Basil K. Williams
Current Opinion in Ophthalmology.2024; 35(3): 192. CrossRef
Role of Systemic Factors in Improving the Prognosis of Diabetic Retinal Disease and Predicting Response to Diabetic Retinopathy Treatment
Joe Mellor, Anita Jeyam, Joline W.J. Beulens, Sanjeeb Bhandari, Geoffrey Broadhead, Emily Chew, Ward Fickweiler, Amber van der Heijden, Daniel Gordin, Rafael Simó, Janet Snell-Bergeon, Anniina Tynjälä, Helen Colhoun
Ophthalmology Science.2024; 4(4): 100494. CrossRef
Novel Antidiabetic Drugs and the Risk of Diabetic Retinopathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Artur Małyszczak, Joanna Przeździecka-Dołyk, Urszula Szydełko-Paśko, Marta Misiuk-Hojło
Journal of Clinical Medicine.2024; 13(6): 1797. CrossRef
Prognostic factors for the development and progression of proliferative diabetic retinopathy in people with diabetic retinopathy
Jennifer Perais, Ridhi Agarwal, Jennifer R Evans, Emma Loveman, Jill L Colquitt, David Owens, Ruth E Hogg, John G Lawrenson, Yemisi Takwoingi, Noemi Lois
Cochrane Database of Systematic Reviews.2023;[Epub] CrossRef
Rapid Reduction of HbA1c and Early Worsening of Diabetic Retinopathy: A Real-world Population-Based Study in Subjects With Type 2 Diabetes
Rafael Simó, Josep Franch-Nadal, Bogdan Vlacho, Jordi Real, Ester Amado, Juana Flores, Manel Mata-Cases, Emilio Ortega, Mercedes Rigla, Joan-Anton Vallés, Cristina Hernández, Didac Mauricio
Diabetes Care.2023; 46(9): 1633. CrossRef
Minimum Effective Dose of DPP-4 Inhibitors for Treating Early Stages of Diabetic Retinopathy in an Experimental Model
Patricia Bogdanov, Hugo Ramos, Marta Valeri, Anna Deàs-Just, Jordi Huerta, Rafael Simó, Cristina Hernández
Biomedicines.2022; 10(2): 465. CrossRef
Glucagon-Like Peptide 1 Receptor Agonists – Potential Game Changers in the Treatment of Glaucoma?
Zaynab Ahmad Mouhammad, Rupali Vohra, Anna Horwitz, Anna-Sophie Thein, Jens Rovelt, Barbara Cvenkel, Pete A. Williams, Augusto Azuara-Blanco, Miriam Kolko
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Transcriptomic Analysis Reveals That Retinal Neuromodulation Is a Relevant Mechanism in the Neuroprotective Effect of Sitagliptin in an Experimental Model of Diabetic Retinopathy
Hugo Ramos, Patricia Bogdanov, Rafael Simó, Anna Deàs-Just, Cristina Hernández
International Journal of Molecular Sciences.2022; 24(1): 571. CrossRef
The Safety of Pharmacological and Surgical Treatment of Diabetes in Patients with Diabetic Retinopathy—A Review
Wojciech Matuszewski, Angelika Baranowska-Jurkun, Magdalena Maria Stefanowicz-Rutkowska, Katarzyna Gontarz-Nowak, Ewa Gątarska, Elżbieta Bandurska-Stankiewicz
Journal of Clinical Medicine.2021; 10(4): 705. CrossRef
Effects of Fibrates on Risk of Development of Diabetic Retinopathy in Japanese Working Age Patients with Type 2 Diabetes and Dyslipidemia: a Retrospective Cohort Study
Hayato Akimoto, Yasuo Takahashi, Satoshi Asai
YAKUGAKU ZASSHI.2021; 141(5): 761. CrossRef
Association between Add-On Dipeptidyl Peptidase-4 Inhibitor Therapy and Diabetic Retinopathy Progression
Eugene Yu-Chuan Kang, Chunya Kang, Wei-Chi Wu, Chi-Chin Sun, Kuan-Jen Chen, Chi-Chun Lai, Tien-Hsing Chen, Yih-Shiou Hwang
Journal of Clinical Medicine.2021; 10(13): 2871. CrossRef
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Nidhi Raval, Akshant Kumawat, Dnyaneshwar Kalyane, Kiran Kalia, Rakesh K. Tekade
Drug Discovery Today.2020; 25(5): 862. CrossRef
Letter: Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study (Diabetes Metab J 2019;43:640–8)
Jun Sung Moon
Diabetes & Metabolism Journal.2019; 43(6): 911. CrossRef
Response: Dipeptidyl Peptidase-4 Inhibitors versus Other Antidiabetic Drugs Added to Metformin Monotherapy in Diabetic Retinopathy Progression: A Real World-Based Cohort Study (Diabetes Metab J 2019;43:640–8)
Yoo-Ri Chung, Kyoung Hwa Ha, Kihwang Lee, Dae Jung Kim
Diabetes & Metabolism Journal.2019; 43(6): 917. CrossRef

Pathophysiology
Essential Role of Protein Arginine Methyltransferase 1 in Pancreas Development by Regulating Protein Stability of Neurogenin 3: Kanghoon Lee, Hyunki Kim, Joonyub Lee, Chang-Myung Oh, Heein Song, Hyeongseok Kim, Seung-Hoi Koo, Junguee Lee, Ajin Lim, Hail Kim; Diabetes Metab J. 2019;43(5):649-658. Published online April 8, 2019; DOI: https://doi.org/10.4093/dmj.2018.0232

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Background

Protein arginine methyltransferase 1 (PRMT1) is a major enzyme responsible for the formation of methylarginine in mammalian cells. Recent studies have revealed that PRMT1 plays important roles in the development of various tissues. However, its role in pancreas development has not yet been elucidated.

Methods

Pancreatic progenitor cell-specific Prmt1 knock-out (Prmt1 PKO) mice were generated and characterized for their metabolic and histological phenotypes and their levels of Neurog3 gene expression and neurogenin 3 (NGN3) protein expression. Protein degradation assays were performed in mPAC cells.

Results

Prmt1 PKO mice showed growth retardation and a severely diabetic phenotype. The pancreatic size and β-cell mass were significantly reduced in Prmt1 PKO mice. Proliferation of progenitor cells during the secondary transition was decreased and endocrine cell differentiation was impaired. These defects in pancreas development could be attributed to the sustained expression of NGN3 in progenitor cells. Protein degradation assays in mPAC cells revealed that PRMT1 was required for the rapid degradation of NGN3.

Conclusion

PRMT1 critically contributes to pancreas development by destabilizing the NGN3 protein.

Citations

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Arginine 65 methylation of Neurogenin 3 by PRMT1 is required for pancreatic endocrine development of hESCs
Gahyang Cho, Kwangbeom Hyun, Jieun Choi, Eunji Shin, Bumsoo Kim, Hail Kim, Jaehoon Kim, Yong-Mahn Han
Experimental & Molecular Medicine.2023; 55(7): 1506. CrossRef
Protein arginine methyltransferase 1 in the generation of immune megakaryocytes: A perspective review
Xinyang Zhao, Zechen Chong, Yabing Chen, X. Long Zheng, Qian-Fei Wang, Yueying Li
Journal of Biological Chemistry.2022; 298(11): 102517. CrossRef
Arginine 65 Methylation of Neurogenin 3 by PRMT1 Is Required for Pancreatic Endocrine Development of hESCs
Gahyang Cho, Kwangbeom Hyun, Jieun Choi, Eun Ji Shin, Bumsoo Kim, Hail Kim, Jaehoon Kim, Yong-Mahn Han
SSRN Electronic Journal .2022;[Epub] CrossRef
Protein Arginine Methyltransferase 1 Is Essential for the Meiosis of Male Germ Cells
Sahar Waseem, Sudeep Kumar, Kanghoon Lee, Byoung-Ha Yoon, Mirang Kim, Hail Kim, Keesook Lee
International Journal of Molecular Sciences.2021; 22(15): 7951. CrossRef
Proteome-Wide Alterations of Asymmetric Arginine Dimethylation Associated With Pancreatic Ductal Adenocarcinoma Pathogenesis
Meijin Wei, Chaochao Tan, Zhouqin Tang, Yingying Lian, Ying Huang, Yi Chen, Congwei Chen, Wen Zhou, Tao Cai, Jiliang Hu
Frontiers in Cell and Developmental Biology.2020;[Epub] CrossRef

Pathophysiology
Low-Frequency Intermittent Hypoxia Suppresses Subcutaneous Adipogenesis and Induces Macrophage Polarization in Lean Mice: Yan Wang, Mary Yuk Kwan Lee, Judith Choi Wo Mak, Mary Sau Man Ip; Diabetes Metab J. 2019;43(5):659-674. Published online April 23, 2019; DOI: https://doi.org/10.4093/dmj.2018.0196

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Background

The relationship between obstructive sleep apnoea (OSA) and metabolic disorders is complex and highly associated. The impairment of adipogenic capacity in pre-adipocytes may promote adipocyte hypertrophy and increase the risk of further metabolic dysfunction. We hypothesize that intermittent hypoxia (IH), as a pathophysiologic feature of OSA, may regulate adipogenesis by promoting macrophage polarization.

Methods

Male C57BL/6N mice were exposed to either IH (240 seconds of 10% O₂ followed by 120 seconds of 21% O₂, i.e., 10 cycles/hour) or intermittent normoxia (IN) for 6 weeks. Stromal-vascular fractions derived from subcutaneous (SUB-SVF) and visceral (VIS-SVF) adipose tissues were cultured and differentiated. Conditioned media from cultured RAW 264.7 macrophages after air (Raw) or IH exposure (Raw-IH) were incubated with SUB-SVF during adipogenic differentiation.

Results

Adipogenic differentiation of SUB-SVF but not VIS-SVF from IH-exposed mice was significantly downregulated in comparison with that derived from IN-exposed mice. IH-exposed mice compared to IN-exposed mice showed induction of hypertrophic adipocytes and increased preferential infiltration of M1 macrophages in subcutaneous adipose tissue (SAT) compared to visceral adipose tissue. Complementary in vitro analysis demonstrated that Raw-IH media significantly enhanced inhibition of adipogenesis of SUB-SVF compared to Raw media, in agreement with corresponding gene expression levels of differentiation-associated markers and adipogenic transcription factors.

Conclusion

Low frequency IH exposure impaired adipogenesis of SAT in lean mice, and macrophage polarization may be a potential mechanism for the impaired adipogenesis.

Citations

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Melatonin attenuates chronic intermittent hypoxia-induced intestinal barrier dysfunction in mice
Xinyi Li, Fan Wang, Zhenfei Gao, Weijun Huang, Xiaoman Zhang, Feng Liu, Hongliang Yi, Jian Guan, Xiaolin Wu, Huajun Xu, Shankai Yin
Microbiological Research.2023; 276: 127480. CrossRef
Clinical outcomes and plaque characteristics in patients with coronary artery disease and concomitant sleep-disordered breathing treated by continuous positive airway pressure
Kazuhiro Fujiyoshi, Taiki Tojo, Yoshiyasu Minami, Kohki Ishida, Miwa Ishida, Ken-ichiro Wakabayashi, Takayuki Inomata, Junya Ako
Sleep Medicine.2023; 101: 543. CrossRef
Potential Pathophysiological Pathways in the Complex Relationships between OSA and Cancer
Manuel Sánchez-de-la-Torre, Carolina Cubillos, Olivia J. Veatch, Francisco Garcia-Rio, David Gozal, Miguel Angel Martinez-Garcia
Cancers.2023; 15(4): 1061. CrossRef
Effects of Chronic Intermittent Hypoxia and Chronic Sleep Fragmentation on Gut Microbiome, Serum Metabolome, Liver and Adipose Tissue Morphology
Fan Wang, Juanjuan Zou, Huajun Xu, Weijun Huang, Xiaoman Zhang, Zhicheng Wei, Xinyi Li, Yupu Liu, Jianyin Zou, Feng Liu, Huaming Zhu, Hongliang Yi, Jian Guan, Shankai Yin
Frontiers in Endocrinology.2022;[Epub] CrossRef
C‐X3‐C motif chemokine ligand 1/receptor 1 regulates the M1 polarization and chemotaxis of macrophages after hypoxia/reoxygenation injury
Shuiming Guo, Lei Dong, Junhua Li, Yuetao Chen, Ying Yao, Rui Zeng, Nelli Shushakova, Hermann Haller, Gang Xu, Song Rong
Chronic Diseases and Translational Medicine.2021; 7(4): 254. CrossRef

Obesity and Metabolic Syndrome
The Association between Z-Score of Log-Transformed A Body Shape Index and Cardiovascular Disease in Korea: Wankyo Chung, Jung Hwan Park, Hye Soo Chung, Jae Myung Yu, Shinje Moon, Dong Sun Kim; Diabetes Metab J. 2019;43(5):675-682. Published online April 26, 2019; DOI: https://doi.org/10.4093/dmj.2018.0169

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Abstract PDF Supplementary Material PubReader

Background

In order to overcome the limitations of body mass index (BMI) and waist circumference (WC), the z-score of the log-transformed A Body Shape Index (LBSIZ) has recently been introduced. In this study, we analyzed the relationship between the LBSIZ and cardiovascular disease (CVD) in a Korean representative sample.

Methods

Data were collected from the Korea National Health and Nutrition Examination VI to V. The association between CVD and obesity indices was analyzed using a receiver operating characteristic curve. The cut-off value for the LBSIZ was estimated using the Youden index, and the odds ratio (OR) for CVD was determined via multivariate logistic regression analysis. ORs according to the LBSIZ value were analyzed using restricted cubic spline regression plots.

Results

A total of 31,227 Korean healthy adults were analyzed. Area under the curve (AUC) of LBSIZ against CVD was 0.686 (95% confidence interval [CI], 0.671 to 0.702), which was significantly higher than the AUC of BMI (0.583; 95% CI, 0.567 to 0.599) or WC (0.646; 95% CI, 0.631 to 0.661) (P<0.001). Similar results were observed for stroke and coronary artery diseases. The cut-off value for the LBSIZ was 0.35 (sensitivity, 64.5%; specificity, 64%; OR, 1.29, 95% CI, 1.12 to 1.49). Under restricted cubic spline regression, LBSIZ demonstrated that OR started to increase past the median value.

Conclusion

The findings of this study suggest that the LBSIZ might be more strongly associated with CVD risks compared to BMI or WC. These outcomes would be helpful for CVD risk assessment in clinical settings, especially the cut-off value of the LBSIZ suggested in this study.

Citations

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Body Shape Index and Cardiovascular Risk in Individuals With Obesity
Nazlı Hacıağaoğlu, Can Öner, Hüseyin Çetin, Engin Ersin Şimşek
Cureus.2022;[Epub] CrossRef
Association between body shape index and risk of mortality in the United States
Heysoo Lee, Hye Soo Chung, Yoon Jung Kim, Min Kyu Choi, Yong Kyun Roh, Wankyo Chung, Jae Myung Yu, Chang-Myung Oh, Shinje Moon
Scientific Reports.2022;[Epub] CrossRef
Utility of the Z-score of log-transformed A Body Shape Index (LBSIZ) in the assessment for sarcopenic obesity and cardiovascular disease risk in the United States
Wankyo Chung, Jung Hwan Park, Hye Soo Chung, Jae Myung Yu, Dong Sun Kim, Shinje Moon
Scientific Reports.2019;[Epub] CrossRef

Obesity and Metabolic Syndrome
PF-04620110, a Potent Antidiabetic Agent, Suppresses Fatty Acid-Induced NLRP3 Inflammasome Activation in Macrophages: Seung Il Jo, Jung Hwan Bae, Seong Jin Kim, Jong Min Lee, Ji Hun Jeong, Jong-Seok Moon; Diabetes Metab J. 2019;43(5):683-699. Published online October 24, 2019; DOI: https://doi.org/10.4093/dmj.2019.0112

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Abstract PDF Supplementary Material PubReader

Background

Chronic inflammation has been linked to insulin resistance and type 2 diabetes mellitus (T2DM). High-fat diet (HFD)-derived fatty acid is associated with the activation of chronic inflammation in T2DM. PF-04620110, which is currently in phase 1 clinical trials as a selective acyl-CoA:diacylglycerol acyltransferase-1 (DGAT1) inhibitor, is a potent anti-diabetic agent that may be important for the regulation of chronic inflammation in T2DM. However, the mechanisms by which PF-04620110 regulates fatty acid-induced chronic inflammation remain unclear.

Methods

PF-04620110 was used in vitro and in vivo. DGAT1-targeting gRNAs were used for deletion of mouse DGAT1 via CRISPR ribonucleoprotein (RNP) system. The activation of NLRP3 inflammasome was measured by immunoblot or cytokine analysis in vitro and in vivo.

Results

Here we show that PF-04620110 suppressed fatty acid-induced nucleotide-binding domain, leucine-rich-repeat-containing receptor (NLR), pyrin-domain-containing 3 (NLRP3) inflammasome activation in macrophages. In contrast, PF-04620110 did not change the activation of the NLR family, CARD-domain-containing 4 (NLRC4), or the absent in melanoma 2 (AIM2) inflammasomes. Moreover, PF-04620110 inhibited K⁺ efflux and the NLRP3 inflammasome complex formation, which are required for NLRP3 inflammasome activation. PF-04620110 reduced the production of interleukin 1β (IL-1β) and IL-18 and blood glucose levels in the plasma of mice fed HFD. Furthermore, genetic inhibition of DGAT1 suppressed fatty acid-induced NLRP3 inflammasome activation.

Conclusion

Our results suggest that PF-04620110 suppresses fatty acid-induced NLRP3 inflammasome activation.

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Maria Hernandez-Corbacho, Daniel Canals
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Genetics
Severity of Nonalcoholic Fatty Liver Disease in Type 2 Diabetes Mellitus: Relationship between Nongenetic Factors and PNPLA3/HSD17B13 Polymorphisms: Mattia Bellan, Cosimo Colletta, Matteo Nazzareno Barbaglia, Livia Salmi, Roberto Clerici, Venkata Ramana Mallela, Luigi Mario Castello, Giuseppe Saglietti, Gian Piero Carnevale Schianca, Rosalba Minisini, Mario Pirisi; Diabetes Metab J. 2019;43(5):700-710. Published online July 29, 2019; DOI: https://doi.org/10.4093/dmj.2018.0201

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Background

The prevalence of nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM) is high, though its severity is often underestimated. Our aim is to provide an estimate of the prevalence of severe NAFLD in T2DM and identify its major predictors.

Methods

T2DM patients (n=328) not previously known to have NAFLD underwent clinical assessment, transient elastography with measure of liver stiffness (LS) and controlled attenuation parameter (CAP), and genotyping for patatin like phospholipase domain containing 3 (PNPLA3) and 17β-hydroxysteroid-dehydrogenase type 13 (HSD17B13).

Results

Median LS was 6.1 kPa (4.9 to 8.6). More than one-fourth patients had advanced liver disease, defined as LS ≥7.9 kPa (n=94/238, 29%), and had a higher body mass index (BMI) than those with a LS <7.9 kPa. Carriage of the G allele in the PNPLA3 gene was associated with higher LS, being 5.9 kPa (4.7 to 7.7) in C/C homozygotes, 6.1 kPa (5.2 to 8.7) in C/G heterozygotes, and 6.8 kPa (5.8 to 9.2) in G/G homozygotes (P=0.01). This trend was absent in patients with ≥1 mutated HSD17B13 allele. In a multiple linear regression model, BMI and PNPLA3 genotype predicted LS, while age, gender, disease duration, and glycosylated hemoglobin did not fit into the model. None of these variables was confirmed to be predictive among carriers of at least one HSD17B13 mutated allele. There was no association between CAP and polymorphisms of PNPLA3 or HSD17B13.

Conclusion

Advanced NAFLD is common among T2DM patients. LS is predicted by both BMI and PNPLA3 polymorphism, the effect of the latter being modulated by mutated HSD17B13.

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