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Volume 43(5); October 2019
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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
  • 6,853 View
  • 94 Download
  • 10 Web of Science
  • 10 Crossref
AbstractAbstract PDFPubReader   

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

Citations to this article as recorded by  
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    David Bradley, Tuo Deng, Dharti Shantaram, Willa A. Hsueh
    Annual Review of Physiology.2024; 86(1): 199.     CrossRef
  • Growth and differentiation factor-15: A link between inflammaging and cardiovascular disease
    Balázs Bence Nyárády, Loretta Zsuzsa Kiss, Zsolt Bagyura, Béla Merkely, Edit Dósa, Orsolya Láng, László Kőhidai, Éva Pállinger
    Biomedicine & Pharmacotherapy.2024; 174: 116475.     CrossRef
  • Evaluation of Mitochondrial Function in Blood Samples Shows Distinct Patterns in Subjects with Thyroid Carcinoma from Those with Hyperplasia
    Julia Bernal-Tirapo, María Teresa Bayo Jiménez, Pedro Yuste-García, Isabel Cordova, Ana Peñas, Francisco-Javier García-Borda, Cesar Quintela, Ignacio Prieto, Cristina Sánchez-Ramos, Eduardo Ferrero-Herrero, María Monsalve
    International Journal of Molecular Sciences.2023; 24(7): 6453.     CrossRef
  • A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome
    Ronit Vogt Sionov, Ronit Ahdut-HaCohen
    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
  • 5,155 View
  • 99 Download
  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   

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

Citations to this article as recorded by  
  • The association between renal accumulation of pancreatic amyloid-forming amylin and renal hypoxia
    Nirmal Verma, Florin Despa
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • New insights toward molecular and nanotechnological approaches to antidiabetic agents for Alzheimer’s disease
    Sweta Priyadarshini Pradhan, Pratap Kumar Sahu, Anindita Behera
    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
    Nutrients.2023; 15(14): 3083.     CrossRef
  • 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
    Aging Cell.2022;[Epub]     CrossRef
  • 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
  • 6,037 View
  • 94 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   

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.

Citations

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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
    NanoImpact.2024; 34: 100508.     CrossRef
  • Rules of Heliogeomagnetics Diversely Coordinating Biological Rhythms and Promoting Human Health
    Kuniaki Otsuka, Germaine Cornelissen, Andi Weydahl, Denis Gubin, Larry A. Beaty, Masatoshi Murase
    Applied Sciences.2023; 13(2): 951.     CrossRef
  • Can lipophilic pollutants in adipose tissue explain weight change‐related risk in type 2 diabetes mellitus?
    Duk‐Hee Lee, In‐Kyu Lee
    Journal of Diabetes Investigation.2023; 14(4): 528.     CrossRef
  • 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
    Amaloha Casanova, Anne Wevers, Santiago Navarro-Ledesma, Leo Pruimboom
    Frontiers in Physiology.2023;[Epub]     CrossRef
  • 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
    BioEssays.2020;[Epub]     CrossRef
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    Evgenios Agathokleous, Edward J. Calabrese
    Science of The Total Environment.2020; 746: 138769.     CrossRef
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
  • 3,190 View
  • 35 Download
PDFPubReader   
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
  • 6,856 View
  • 191 Download
  • 14 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   
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

Citations to this article as recorded by  
  • 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
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    Maya R Chilbert, Dylan VanDuyn, Sara Salah, Collin M Clark, Qing Ma
    Drug Design, Development and Therapy.2022; Volume 16: 2177.     CrossRef
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    V.A. Serhiyenko, A.A. Serhiyenko
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    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
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    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
  • 6,902 View
  • 112 Download
  • 19 Web of Science
  • 20 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
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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  • 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
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    Muhammad Afzal, Fahad Al-Abbasi, Muhammad Nadeem, Sultan Alshehri, Mohammed Ghoneim, Syed Imam, Waleed Almalki, Imran Kazmi
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  • 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
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    PeerJ.2020; 8: e9998.     CrossRef
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    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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AbstractAbstract PDFPubReader   
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
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    Humberto Navarro-Martinez, Juana-Antonia Flores-Le Roux, Gemma Llauradó, Lucia Gortazar, Antonio Payà, Laura Mañé, Juan Pedro-Botet, David Benaiges
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    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
    Journal of Family Medicine and Primary Care.2020; 9(2): 1048.     CrossRef
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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AbstractAbstract PDFSupplementary MaterialPubReader   
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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    Jianyu Huang, Tao Huang, Jinjun Li
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    Marie Chan Sun, Marie A. S. Landinaff, Ruben Thoplan
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    Siyu Chen, Rui Ding, Xiaojun Tang, Liling Chen, Qinwen Luo, Meng Xiao, Xianbin Ding, Bin Peng
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    Miharu Tamaoki, Ikumi Honda, Keisuke Nakanishi, Maki Nakajima, Sophathya Cheam, Manabu Okawada, Hisataka Sakakibara
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    Jaehee Yoon, Jeewuan Kim, Heesook Son
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    Yi Lin, Yan-Yan Ying, Si-Xuan Li, Si-Jia Wang, Qing-Hai Gong, Hui Li
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    Sara Sokooti, Jose L. Flores-Guerrero, Hiddo J. L. Heerspink, Margery A. Connelly, Stephan J. L. Bakker, Robin P. F. Dullaart
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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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AbstractAbstract PDFSupplementary MaterialPubReader   
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.

Citations

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    Hye Ah Lee, Hyesook Park
    Diabetes, Obesity and Metabolism.2024; 26(2): 431.     CrossRef
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    Xinchao Du, Zhiwei Yao, Dongwei Wang, Xinwei Dong, Juncai Bai, Yingchun Gu, Yaohua Yu, Weifeng Zhang, Qingxia Qi, Shengyuan Gu, Bo Hu
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    Han Na Jung, Yun Kyung Cho, Hwi Seung Kim, Eun Hee Kim, Min Jung Lee, Joong-Yeol Park, Woo Je Lee, Hong-Kyu Kim, Chang Hee Jung
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    Melanie S. Haines, Aaron Leong, Bianca C. Porneala, Victor W. Zhong, Cora E. Lewis, Pamela J. Schreiner, Karen K. Miller, James B. Meigs, Mercedes R. Carnethon
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    Hong-Kyu Kim, Sung-Jin Bae, Min Jung Lee, Eun Hee Kim, Hana Park, Hwi Seung Kim, Yun Kyung Cho, Chang Hee Jung, Woo Je Lee, Jaewon Choe
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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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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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AbstractAbstract PDFSupplementary MaterialPubReader   
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
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    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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    Wojciech Matuszewski, Angelika Baranowska-Jurkun, Magdalena Maria Stefanowicz-Rutkowska, Katarzyna Gontarz-Nowak, Ewa Gątarska, Elżbieta Bandurska-Stankiewicz
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    Eugene Yu-Chuan Kang, Chunya Kang, Wei-Chi Wu, Chi-Chin Sun, Kuan-Jen Chen, Chi-Chun Lai, Tien-Hsing Chen, Yih-Shiou Hwang
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  • 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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AbstractAbstract PDFPubReader   
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

Citations to this article as recorded by  
  • Role of protein arginine methyltransferase 1 in obesity‐related metabolic disorders: Research progress and implications
    Xiaolei Xuan, Yongjiao Zhang, Yufan Song, Bingyang Zhang, Junjun Liu, Dong Liu, Sumei Lu
    Diabetes, Obesity and Metabolism.2024;[Epub]     CrossRef
  • 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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AbstractAbstract PDFSupplementary MaterialPubReader   
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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  • Obstructive sleep apnea hypopnea syndrome and vascular lesions: An update on what we currently know
    Zhenyu Mao, Pengdou Zheng, Xiaoyan Zhu, Lingling Wang, Fengqin Zhang, Huiguo Liu, Hai Li, Ling Zhou, Wei Liu
    Sleep Medicine.2024; 119: 296.     CrossRef
  • 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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AbstractAbstract PDFSupplementary MaterialPubReader   
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

Citations to this article as recorded by  
  • 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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AbstractAbstract PDFSupplementary MaterialPubReader   
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.

Citations

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  • Drug Targeting of Acyltransferases in the Triacylglyceride and 1-O-AcylCeramide Biosynthetic Pathways
    Maria Hernandez-Corbacho, Daniel Canals
    Molecular Pharmacology.2024; 105(3): 166.     CrossRef
  • Possible therapeutic targets for NLRP3 inflammasome-induced breast cancer
    Xixi Wang, Junyi Lin, Zhe Wang, Zhi Li, Minghua Wang
    Discover Oncology.2023;[Epub]     CrossRef
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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AbstractAbstract PDFPubReader   
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.

Citations

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Diabetes Metab J : Diabetes & Metabolism Journal