Endocrinology and Metabolism

Review Articles

Diabetes, Obesity and Metabolism
Renal Protection of Mineralocorticoid Receptor Antagonist, Finerenone, in Diabetic Kidney Disease: Dong-Lim Kim, Seung-Eun Lee, Nan Hee Kim; Endocrinol Metab. 2023;38(1):43-55. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2022.1629

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Chronic kidney disease (CKD) is the most common cause of end-stage renal disease in patients with type 2 diabetes mellitus (T2DM). CKD increases the risk of cardiovascular diseases; therefore, its prevention and treatment are important. The prevention of diabetic kidney disease (DKD) can be achieved through intensive glycemic control and blood pressure management. Additionally, DKD treatment aims to reduce albuminuria and improve kidney function. In patients with T2DM, renin-angiotensin-aldosterone system inhibitors, sodium glucose cotransporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists can delay the progression of DKD. Hence, there is a need for novel treatments that can effectively suppress DKD progression. Finerenone is a first-in-class nonsteroidal mineralocorticoid receptor antagonist with clinically proven efficacy in improving albuminuria, estimated glomerular filtration rate, and risk of cardiovascular events in early and advanced DKD. Therefore, finerenone is a promising treatment option to delay DKD progression. This article reviews the mechanism of renal effects and major clinical outcomes of finerenone in DKD.

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Neue Antihypertensiva im Renin-Angiotensin-Aldosteron-System
Markus van der Giet
CardioVasc.2024; 24(1): 33. CrossRef
Chicoric acid advanced PAQR3 ubiquitination to ameliorate ferroptosis in diabetes nephropathy through the relieving of the interaction between PAQR3 and P110α pathway
Weiwei Zhang, Yong Liu, Jiajun Zhou, Teng Qiu, Haitang Xie, Zhichen Pu
Clinical and Experimental Hypertension.2024;[Epub] CrossRef
Endothelial CXCR2 deficiency attenuates renal inflammation and glycocalyx shedding through NF-κB signaling in diabetic kidney disease
Siyuan Cui, Xin Chen, Jiayu Li, Wei Wang, Deqi Meng, Shenglong Zhu, Shiwei Shen
Cell Communication and Signaling.2024;[Epub] CrossRef
Molecular Targets of Novel Therapeutics for Diabetic Kidney Disease: A New Era of Nephroprotection
Alessio Mazzieri, Francesca Porcellati, Francesca Timio, Gianpaolo Reboldi
International Journal of Molecular Sciences.2024; 25(7): 3969. CrossRef
Epigenetic modification in diabetic kidney disease
Zhe Liu, Jiahui Liu, Wanning Wang, Xingna An, Ling Luo, Dehai Yu, Weixia Sun
Frontiers in Endocrinology.2023;[Epub] CrossRef
Novel Approaches in Chronic Renal Failure without Renal Replacement Therapy: A Review
Sandra Martínez-Hernández, Martín Muñoz-Ortega, Manuel Ávila-Blanco, Mariana Medina-Pizaño, Javier Ventura-Juárez
Biomedicines.2023; 11(10): 2828. CrossRef
Finerenone and other future therapeutic options for Alport syndrome
Helen Pearce, Holly Mabillard
Journal of Rare Diseases.2023;[Epub] CrossRef

Diabetes, Obesity and Metabolism
Extra-Glycemic Effects of Anti-Diabetic Medications: Two Birds with One Stone?: Eun-Jung Rhee; Endocrinol Metab. 2022;37(3):415-429. Published online June 29, 2022; DOI: https://doi.org/10.3803/EnM.2022.304

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The world is suffering from a rapid increase in the number of people with diabetes due to the increased prevalence of obesity and lengthened life span. Since the development of insulin thanks to the efforts of Prof. Banting and Dr. Best in 1922, for which they won the Nobel Prize, remarkable developments in anti-diabetic medications have dramatically lengthened the lifespan of patients with diabetes. However, the control rate of hyperglycemia in patients with diabetes remains unsatisfactory, since glycemic control requires both medication and lifestyle modifications to slow the deterioration of pancreatic beta-cell function and prevent diabetic complications. From the initial “triumvirate” to the “ominous octet,” and now the “egregious eleven,” the number of organs recognized as being involved in hyperglycemia and diabetes has increased with the development of anti-diabetic medications. Recent unexpected results from outcome trials of anti-diabetic medications have enabled anti-diabetic medications to be indicated for the prevention of chronic kidney disease and heart failure, even in patients without diabetes. In this review, I would like to summarize the extra-glycemic effects of anti-diabetic medications.

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Association between underweight and risk of heart failure in diabetes patients
Tae Kyung Yoo, Kyung‐Do Han, Eun‐Jung Rhee, Won‐Young Lee
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Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification
Jinmi Lee, Seok-Woo Hong, Min-Jeong Kim, Sun Joon Moon, Hyemi Kwon, Se Eun Park, Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2024; 48(1): 83. CrossRef
To do one and to get more: Part I. Diabetes and bone
Wen-Ling Lee, Peng-Hui Wang, Szu-Ting Yang, Chia-Hao Liu, Wen-Hsun Chang, Fa-Kung Lee
Journal of the Chinese Medical Association.2022; 85(10): 965. CrossRef

Original Articles

Diabetes, Obesity and Metabolism
Short-Chain Fatty Acids Attenuate Renal Fibrosis and Enhance Autophagy of Renal Tubular Cells in Diabetic Mice Through the HDAC2/ULK1 Axis: Xiaoying Ma, Qiong Wang; Endocrinol Metab. 2022;37(3):432-443. Published online May 16, 2022; DOI: https://doi.org/10.3803/EnM.2021.1336

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Background
This study investigated the effect of short-chain fatty acids (SCFAs) on diabetes in a mouse model.
Methods
Autophagy in Akita mice and streptozocin (STZ)-induced diabetic C57BL/6 mice was determined by Western blots and immunohistochemistry (IHC). Western blots, IHC, hematoxylin and eosin staining, Masson staining, periodic acid-Schiff staining, and picrosirius red staining were conducted to detect whether autophagy and renal function improved in Akita mice and STZ-induced diabetic C57BL/6 mice after treatment of SCFAs. Western blots, IHC, and chromatin immunoprecipitation were performed to determine whether SCFAs affected diabetic mice via the histone deacetylase (HDAC2)/unc-51 like autophagy activating kinase 1 (ULK1) axis. Diabetic mice with kidney-specific knockout of HDAC2 were constructed, and IHC, Masson staining, and Western blots were carried out to detect whether the deletion of endogenous HDAC2 contributed to the improvement of autophagy and renal fibrosis in diabetic mice.
Results
Reduced autophagy and severe fibrosis were observed in Akita mice and STZ-induced diabetic C57BL/6 mice. Increased autophagy and reduced renal cell fibrosis were found in SCFA-treated Akita diabetic mice and STZ-induced diabetic C57BL/6 mice. Diabetic mice treated with SCFAs had lower HDAC2 expression and more enriched binding of ULK1 promoter sequences to H3K27Ac. Endogenous knockout of HDAC2 caused enhanced autophagy and decreased renal fibrosis in diabetic mice treated with SCFAs.
Conclusion
SCFAs enhanced autophagy of renal tubular cells and attenuated renal fibrosis in diabetic mice through the HDAC2/ULK1 axis.

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NSD1 supports cell growth and regulates autophagy in HPV-negative head and neck squamous cell carcinoma
Iuliia Topchu, Igor Bychkov, Demirkan Gursel, Petr Makhov, Yanis Boumber
Cell Death Discovery.2024;[Epub] CrossRef
Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes: A cross-sectional study
Xin-Hua Jia, Sheng-Yan Wang, Ai-Qin Sun
World Journal of Diabetes.2024; 15(3): 475. CrossRef
Epigenetic and post-translational modifications in autophagy: biological functions and therapeutic targets
Feng Shu, Han Xiao, Qiu-Nuo Li, Xiao-Shuai Ren, Zhi-Gang Liu, Bo-Wen Hu, Hong-Sheng Wang, Hao Wang, Guan-Min Jiang
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
Mechanisms of Blood–Brain Barrier Protection by Microbiota-Derived Short-Chain Fatty Acids
Ekaterina Fock, Rimma Parnova
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The Role of Histone Modifications in the Pathogenesis of Diabetic Kidney Disease
Christodoula Kourtidou, Konstantinos Tziomalos
International Journal of Molecular Sciences.2023; 24(6): 6007. CrossRef
Mechanism of histone deacetylase HDAC2 in FOXO3-mediated trophoblast pyroptosis in preeclampsia
Jia Liu, Weihui Yang
Functional & Integrative Genomics.2023;[Epub] CrossRef
Macrophage polarization induces endothelium-to-myofibroblast transition in chronic allograft dysfunction
Zeping Gui, Xiang Zhang, Qianguang Han, Zhou Hang, Ruoyun Tan, Min Gu, Zijie Wang
Renal Failure.2023;[Epub] CrossRef
Periodic acid–Schiff staining in oral exfoliative cytology of diabetic patients: The odyssey for noninvasive screening – A systematic review and meta-analysis
KYesoda Aniyan, KrithikaChandrasekar Lakshmi, Anuradha Ganesan
Dental Research Journal.2023; 20(1): 73. CrossRef
Luteolin alleviates renal ischemia-reperfusion injury in streptozotocin induced diabetic rats by inhibiting metalloenzymes expression
Rakesh B. Daude, Jigna S. Shah
Current Issues in Pharmacy and Medical Sciences.2023; 36(4): 199. CrossRef
Molecular mechanisms of histone deacetylases and inhibitors in renal fibrosis progression
Jiayu Wang, Jiaxing Li, Xin Zhang, Min Zhang, Xiaopeng Hu, Hang Yin
Frontiers in Molecular Biosciences.2022;[Epub] CrossRef
Sacubitril/Valsartan contributes to improving the diabetic kidney disease and regulating the gut microbiota in mice
Peipei Wang, Ruixue Guo, Xiwen Bai, Wen Cui, Yiding Zhang, Huangmin Li, Jin Shang, Zhanzheng Zhao
Frontiers in Endocrinology.2022;[Epub] CrossRef
Recent advances and potentiality of postbiotics in the food industry: Composition, inactivation methods, current applications in metabolic syndrome, and future trends
Yujie Zhong, Tao Wang, Ruilin Luo, Jiayu Liu, Ruyi Jin, Xiaoli Peng
Critical Reviews in Food Science and Nutrition.2022; : 1. CrossRef

Calcium & Bone Metabolism Big Data Articles (National Health Insurance Service Database)
Hip Fracture Risk According to Diabetic Kidney Disease Phenotype in a Korean Population: Seung Eun Lee, Juhwan Yoo, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi; Endocrinol Metab. 2022;37(1):148-158. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1315

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Background
Diabetic kidney disease (DKD) is associated with an elevated risk of fractures. However, little is known about the association between proteinuric or non-proteinuric DKD and the risk of hip fracture. Thus, we investigated the incidence of hip fractures among Korean adults with type 2 diabetes mellitus (T2DM) stratified by DKD phenotype.
Methods
In this retrospective cohort study using the Korean National Health Insurance Service database, patients with T2DM who received at least one general health checkup between 2009 and 2012 were followed until the date of hip fracture, death, or December 31, 2018. We classified the DKD phenotype by proteinuria and estimated glomerular filtration rate (eGFR), as follows: no DKD (PU⁻GFR⁻), proteinuric DKD with normal eGFR (PU⁺GFR⁻), non-proteinuric DKD with reduced eGFR (PU⁻GFR⁺), and proteinuric DKD with reduced eGFR (PU⁺GFR⁺)
Results
The cumulative incidence of hip fractures was highest in the PU⁺GFR⁺ group, followed by the PU⁻GFR⁺ group and the PU⁺GFR⁻ group. After adjustment for confounding factors, the hazard ratio (HR) for hip fracture was still highest in the PU⁺GFR⁺ group. However, the PU⁺GFR⁻ group had a higher HR for hip fracture than the PU⁻GFR⁺ group (PU⁺GFR⁺ : HR, 1.69; 95% confidence interval [CI], 1.57 to 1.81; PU⁺GFR⁻ : HR, 1.37; 95% CI, 1.30 to 1.46; PU⁻GFR⁺ : HR, 1.20; 95% CI, 1.16 to 1.24 using the PU⁻GFR⁻ group as the reference category).
Conclusion
The present study demonstrated that DKD was significantly associated with a higher risk of hip fracture, with proteinuria as a major determinant.

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Proteinuria screening and risk of bone fracture: a retrospective cohort study using a nationwide population-based database
Akira Okada, Akira Honda, Hideaki Watanabe, Yusuke Sasabuchi, Shotaro Aso, Kayo Ikeda Kurakawa, Masaomi Nangaku, Toshimasa Yamauchi, Hideo Yasunaga, Hirotaka Chikuda, Takashi Kadowaki, Satoko Yamaguchi
Clinical Kidney Journal.2024;[Epub] CrossRef
Fracture risks associated with sodium-glucose cotransporter-2 inhibitors in type 2 diabetes patients across eGFR and albuminuria categories: A population-based study in Hong Kong
David Tak Wai Lui, Tingting Wu, Eric Ho Man Tang, Ivan Chi Ho Au, Chi Ho Lee, Yu Cho Woo, Kathryn Choon Beng Tan, Carlos King Ho Wong
Diabetes Research and Clinical Practice.2023; 197: 110576. CrossRef
Diagnose und Management der Osteoporose bei Diabetes mellitus (Update 2023)
Christian Muschitz, Alexandra Kautzky-Willer, Yvonne Winhofer, Martina Rauner, Judith Haschka, Daniel Cejka, Robert Wakolbinger-Habel, Peter Pietschmann
Wiener klinische Wochenschrift.2023; 135(S1): 207. CrossRef
Association between exercise and risk of fractures in new-onset type 2 diabetes: a retrospective cohort study
Seung Eun Lee, Juhwan Yoo, Bong-Seong Kim, Kyoung-Ah Kim, Kyungdo Han, Han Seok Choi
Archives of Osteoporosis.2023;[Epub] CrossRef
Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea
Seung Eun Lee, Juhwan Yoo, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim
Diabetes & Metabolism Journal.2023; 47(4): 523. CrossRef

Diabetes, Obesity and Metabolism
EW-7197 Attenuates the Progression of Diabetic Nephropathy in db/db Mice through Suppression of Fibrogenesis and Inflammation: Kyung Bong Ha, Weerapon Sangartit, Ah Reum Jeong, Eun Soo Lee, Hong Min Kim, Soyeon Shim, Upa Kukongviriyapan, Dae-Kee Kim, Eun Young Lee, Choon Hee Chung; Endocrinol Metab. 2022;37(1):96-111. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1305

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Background
Diabetic nephropathy (DN) is characterized by albuminuria and accumulation of extracellular matrix (ECM) in kidney. Transforming growth factor-β (TGF-β) plays a central role in promoting ECM accumulation. We aimed to examine the effects of EW-7197, an inhibitor of TGF-β type 1 receptor kinase (ALK5), in retarding the progression of DN, both in vivo, using a diabetic mouse model (db/db mice), and in vitro, in podocytes and mesangial cells.
Methods
In vivo study: 8-week-old db/db mice were orally administered EW-7197 at a dose of 5 or 20 mg/kg/day for 10 weeks. Metabolic parameters and renal function were monitored. Glomerular histomorphology and renal protein expression were evaluated by histochemical staining and Western blot analyses, respectively. In vitro study: DN was induced by high glucose (30 mM) in podocytes and TGF-β (2 ng/mL) in mesangial cells. Cells were treated with EW-7197 (500 nM) for 24 hours and the mechanism associated with the attenuation of DN was investigated.
Results
Enhanced albuminuria and glomerular morphohistological changes were observed in db/db compared to that of the nondiabetic (db/m) mice. These alterations were associated with the activation of the TGF-β signaling pathway. Treatment with EW-7197 significantly inhibited TGF-β signaling, inflammation, apoptosis, reactive oxygen species, and endoplasmic reticulum stress in diabetic mice and renal cells.
Conclusion
EW-7197 exhibits renoprotective effect in DN. EW-7197 alleviates renal fibrosis and inflammation in diabetes by inhibiting downstream TGF-β signaling, thereby retarding the progression of DN. Our study supports EW-7197 as a therapeutically beneficial compound to treat DN.

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TGF-β signaling in health, disease, and therapeutics
Ziqin Deng, Tao Fan, Chu Xiao, He Tian, Yujia Zheng, Chunxiang Li, Jie He
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Oxidative stress and inflammation in diabetic nephropathy: role of polyphenols
Qi Jin, Tongtong Liu, Yuan Qiao, Donghai Liu, Liping Yang, Huimin Mao, Fang Ma, Yuyang Wang, Liang Peng, Yongli Zhan
Frontiers in Immunology.2023;[Epub] CrossRef
Beneficial Effects of a Curcumin Derivative and Transforming Growth Factor-β Receptor I Inhibitor Combination on Nonalcoholic Steatohepatitis
Kyung Bong Ha, Eun Soo Lee, Na Won Park, Su Ho Jo, Soyeon Shim, Dae-Kee Kim, Chan Mug Ahn, Choon Hee Chung
Diabetes & Metabolism Journal.2023; 47(4): 500. CrossRef

Diabetes, Obesity and Metabolism
Tetrahydrocurcumin Ameliorates Kidney Injury and High Systolic Blood Pressure in High-Fat Diet-Induced Type 2 Diabetic Mice: Weerapon Sangartit, Kyung Bong Ha, Eun Soo Lee, Hong Min Kim, Upa Kukongviriyapan, Eun Young Lee, Choon Hee Chung; Endocrinol Metab. 2021;36(4):810-822. Published online August 27, 2021; DOI: https://doi.org/10.3803/EnM.2021.988

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Background
Activation of the intrarenal renin-angiotensin system (RAS) is implicated in the pathogenesis of kidney injury and hypertension. We aimed to investigate the protective effect of tetrahydrocurcumin (THU) on intrarenal RAS expression, kidney injury, and systolic blood pressure (SBP) in high-fat diet (HFD)-induced type 2 diabetic mice.
Methods
Eight-week-old male mice were fed a regular diet (RD) or HFD for 12 weeks, and THU (50 or 100 mg/kg/day) was intragastrically administered with HFD. Physiological and metabolic changes were monitored and the expression of RAS components and markers of kidney injury were assessed.
Results
HFD-fed mice exhibited hyperglycemia, insulin resistance, and dyslipidemia compared to those in the RD group (P<0.05). Kidney injury in these mice was indicated by an increase in the ratio of albumin to creatinine, glomerular hypertrophy, and the effacement of podocyte foot processes. Expression of intrarenal angiotensin-converting enzyme, angiotensin II type I receptor, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-4, and monocyte chemoattractant protein-1 was also markedly increased in HFD-fed mice. HFD-fed mice exhibited elevated SBP that was accompanied by an increase in the wall thickness and vascular cross-sectional area (P<0.05), 12 weeks post-HFD consumption. Treatment with THU (100 mg/kg/day) suppressed intrarenal RAS activation, improved insulin sensitivity, and reduced SBP, thus, attenuating kidney injury in these mice.
Conclusion
THU alleviated kidney injury in mice with HFD-induced type 2 diabetes, possibly by blunting the activation of the intrarenal RAS/nicotinamide adenine dinucleotide phosphate oxidase IV (NOX4)/monocyte chemoattractant protein 1 (MCP-1) axis and by lowering the high SBP.

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The Development of Dyslipidemia in Chronic Kidney Disease and Associated Cardiovascular Damage, and the Protective Effects of Curcuminoids
Zeltzin Alejandra Ceja-Galicia, Ana Karina Aranda-Rivera, Isabel Amador-Martínez, Omar Emiliano Aparicio-Trejo, Edilia Tapia, Joyce Trujillo, Victoria Ramírez, José Pedraza-Chaverri
Foods.2023; 12(5): 921. CrossRef
Translation Animal Models of Diabetic Kidney Disease: Biochemical and Histological Phenotypes, Advantages and Limitations
Wenting Luo, Shiyun Tang, Xiang Xiao, Simin Luo, Zixuan Yang, Wei Huang, Songqi Tang
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 1297. CrossRef
Curcumin ameliorates focal segmental glomerulosclerosis by inhibiting apoptosis and oxidative stress in podocytes
Hui Zhang, Qing-Qing Dong, Hua-Pan Shu, Yu-Chi Tu, Qian-Qian Liao, Li-Jun Yao
Archives of Biochemistry and Biophysics.2023; 746: 109728. CrossRef
An examination of the protective effects and molecular mechanisms of curcumin, a polyphenol curcuminoid in diabetic nephropathy
Xiaoyu Zhu, Xingli Xu, Chigang Du, Yanping Su, Lixue Yin, Xiaoqiu Tan, Hui Liu, Yiru Wang, Lei Xu, Xinghua Xu
Biomedicine & Pharmacotherapy.2022; 153: 113438. CrossRef
An integrated bioinformatics analysis and experimental study identified key biomarkers CD300A or CXCL1, pathways and immune infiltration in diabetic nephropathy mice
WEI LIANG, QIANG LUO, ZONGWEI ZHANG, KEJU YANG, ANKANG YANG, QINGJIA CHI, HUAN HU
BIOCELL.2022; 46(8): 1989. CrossRef

Review Article

Diabetes
Cardiorenal Protection in Diabetic Kidney Disease: Jason F. Lee, Ecaterina Berzan, Vikas S. Sridhar, Ayodele Odutayo, David Z.I. Cherney; Endocrinol Metab. 2021;36(2):256-269. Published online April 19, 2021; DOI: https://doi.org/10.3803/EnM.2021.987

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Over the last 5 years there have been many new developments in the management of diabetic kidney disease. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT2) inhibitors were initially used for glycemic control, but more recent studies have now shown that their benefits extend to cardiovascular and kidney outcomes. The recent addition of data on the novel mineralocorticoid receptor antagonist (MRA) gives us another approach to further decrease the residual risk of diabetic kidney disease progression. In this review we describe the mechanism of action, key studies, and possible adverse effects related to these three classes of medications. The management of type 2 diabetes now includes an increasing number of medications for the management of comorbidities in a patient population at significant risk of cardiovascular disease and progression of chronic kidney disease. It is from this perspective that we seek to outline the rationale for the sequential and/or combined use of SGLT2 inhibitors, GLP-1 RA and MRAs in patients with type 2 diabetes for heart and kidney protection.

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Relative and Absolute Risks of Adverse Events with Real-World Use of SGLT2 Inhibitors in CKD
Ayodele Odutayo, Adeera Levin
Clinical Journal of the American Society of Nephrology.2023; 18(5): 557. CrossRef
Renal Protection of Mineralocorticoid Receptor Antagonist, Finerenone, in Diabetic Kidney Disease
Dong-Lim Kim, Seung-Eun Lee, Nan Hee Kim
Endocrinology and Metabolism.2023; 38(1): 43. CrossRef
Intrarenal Mechanisms of Sodium-Glucose Cotransporter-2 Inhibitors on Tubuloglomerular Feedback and Natriuresis
Eun Sil Koh, Gheun-Ho Kim, Sungjin Chung
Endocrinology and Metabolism.2023; 38(4): 359. CrossRef
SGLT2 and DPP4 inhibitors improve Alzheimer’s disease–like pathology and cognitive function through distinct mechanisms in a T2D–AD mouse model
A Young Sim, Da Hyun Choi, Jong Youl Kim, Eun Ran Kim, A-ra Goh, Yong-ho Lee, Jong Eun Lee
Biomedicine & Pharmacotherapy.2023; 168: 115755. CrossRef
Narrative review investigating the nephroprotective mechanisms of sodium glucose cotransporter type 2 inhibitors in diabetic and nondiabetic patients with chronic kidney disease
Emma S. Speedtsberg, Martin Tepel
Frontiers in Endocrinology.2023;[Epub] CrossRef
Management of CKD
Nimrit Goraya, Jennifer D. Moran
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Nonsteroidal mineralocorticoid receptor antagonism for cardiovascular and renal disorders − New perspectives for combination therapy
Peter Kolkhof, Amer Joseph, Ulrich Kintscher
Pharmacological Research.2021; 172: 105859. CrossRef
Sodium‐Glucose Cotransporter 2 Inhibitors, All‐Cause Mortality, and Cardiovascular Outcomes in Adults with Type 2 Diabetes: A Bayesian Meta‐Analysis and Meta‐Regression
Ayodele Odutayo, Bruno R. da Costa, Tiago V. Pereira, Vinay Garg, Samir Iskander, Fatimah Roble, Rahim Lalji, Cesar A. Hincapié, Aquila Akingbade, Myanca Rodrigues, Arnav Agarwal, Bishoy Lawendy, Pakeezah Saadat, Jacob A. Udell, Francesco Cosentino, Peter
Journal of the American Heart Association.2021;[Epub] CrossRef
Finerenone: A Potential Treatment for Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus
Luis D’Marco, María Jesús Puchades, Lorena Gandía, Claudia Forquet, Elena Giménez-Civera, Nayara Panizo, Javier Reque, Isabel Juan-García, Valmore Bermúdez, José Luis Gorriz
touchREVIEWS in Endocrinology.2021; 17(2): 84. CrossRef
Sodium-Glucose Cotransporter 2 Inhibitors Mechanisms of Action: A Review
Jorge I. Fonseca-Correa, Ricardo Correa-Rotter
Frontiers in Medicine.2021;[Epub] CrossRef

Original Articles

Clinical Study
Comparative Renal Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter 2 Inhibitors on Individual Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis: Jae Hyun Bae, Eun-Gee Park, Sunhee Kim, Sin Gon Kim, Seokyung Hahn, Nam Hoon Kim; Endocrinol Metab. 2021;36(2):388-400. Published online March 31, 2021; DOI: https://doi.org/10.3803/EnM.2020.912

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Background
To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with type 2 diabetes.
Methods
We searched electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) from inception to June 2019 to identity eligible randomized controlled trials of DPP-4 inhibitors or SGLT2 inhibitors that reported at least one kidney outcome in patients with type 2 diabetes. Outcomes of interest were microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage kidney disease (ESKD). We performed an arm-based network meta-analysis using Bayesian methods and calculated absolute risks and rank probabilities of each treatment for the outcomes.
Results
Seventeen studies with 87,263 patients were included. SGLT2 inhibitors significantly lowered the risks of individual kidney outcomes, including microalbuminuria (odds ratio [OR], 0.64; 95% credible interval [CrI], 0.41 to 0.93), macroalbuminuria (OR, 0.48; 95% CrI, 0.24 to 0.72), worsening nephropathy (OR, 0.65; 95% CrI, 0.44 to 0.91), and ESKD (OR, 0.65; 95% CrI, 0.46 to 0.98) as compared with placebo. However, DPP-4 inhibitors did not lower the risks. SGLT2 inhibitors were considerably associated with higher absolute risk reductions in all kidney outcomes than DPP-4 inhibitors, although the benefits were statistically insignificant. The rank probabilities showed that SGLT2 inhibitors were better treatments for lowering the risk of albuminuria and ESKD than placebo or DPP-4 inhibitors.
Conclusion
SGLT2 inhibitors were superior to DPP-4 inhibitors in reducing the risk of albuminuria and ESKD in patients with type 2 diabetes.

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Experimental and Clinical Endocrinology & Diabetes.2024;[Epub] CrossRef
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Clinical Study
Association of Vitamin D Deficiency with Diabetic Nephropathy: So-hyeon Hong, Young Bin Kim, Hoon Sung Choi, Tae-Dong Jeong, Jin Taek Kim, Yeon Ah Sung; Endocrinol Metab. 2021;36(1):106-113. Published online February 24, 2021; DOI: https://doi.org/10.3803/EnM.2020.826

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Background
Low 25-hydroxyvitamin D (25OHD) levels are associated with the incidence of type 2 diabetes mellitus (T2DM). However, the association between 25OHD and metabolic health status or diabetic complications is inconclusive. We evaluated this relationship between vitamin D status and metabolic parameters and complications of T2DM.
Methods
This study included 1,392 patients with T2DM who visited Eulji and Ewha Diabetes Center between January 2011 and August 2016. Anthropometric parameters and laboratory tests including glycated hemoglobin (HbA1c), lipid profile, liver and kidney function, and urinary albumin-to-creatinine ratio (UACR) were evaluated. Diabetic macro- and microvascular complications were determined through a medical record review. Serum 25OHD concentrations were measured by chemiluminescent immunoassay.
Results
The mean 25OHD level was 16.8±9.6 ng/mL. Vitamin D deficiency (<20 ng/mL) and severe deficiency (<10 ng/mL) were observed in 990 (71.1%) and 351 (25.2%) participants, respectively. 25OHD level was positively correlated with age and highdensity lipoprotein cholesterol (HDL-C) level and negatively correlated with HbA1c, triglyceride level, and UACR. HDL-C and UACR were significantly associated with 25OHD after adjusting for other variables. Vitamin D deficiency was independently related to nephropathy after adjusting for confounding variables.
Conclusion
Vitamin D deficiency was common among Korean T2DM patients; it was independently associated with microalbuminuria and HDL level, and positively related to diabetic nephropathy.

Citations

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Clinical Study
Short-Term Effects of Beraprost Sodium on the Markers for Cardiovascular Risk Prediction in Type 2 Diabetic Patients with Microalbuminuria: Yun Mi Choi, Hyuk-Sang Kwon, Kyung Mook Choi, Won-Young Lee, Eun-Gyoung Hong; Endocrinol Metab. 2019;34(4):398-405. Published online December 23, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.4.398

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Background

To evaluate the changes in cardiovascular risk markers including pulse wave velocity (PWV), microalbuminuria, inflammatory cytokines, and adhesion molecules after treatment with beraprost sodium (BPS) in patients with diabetic nephropathy.

Methods

This was a multicenter, prospective, randomized, double-blind, placebo-controlled trial. Type 2 diabetes mellitus patients with microalbuminuria were included. The primary endpoints were changes in microalbuminuria in spot urine and PWV after BPS or placebo (PCB) treatment for 24 weeks. The secondary endpoints were changes in clinical and metabolic parameters.

Results

A total of 52 patients completed the 24-week trial. Changes in PWV were not different significantly in the BPS and PCB groups (right, P=0.16; left, P=0.11). Changes in microalbuminuria were 14.2±157.0 and 34.5±146.6 (µg/mg Cr) in the BPS and PCB groups, respectively (P=0.63). Subgroup analysis in the high blood pressure (BP) group (baseline systolic BP >120 mm Hg and diastolic BP >80 mm Hg), showed that microalbuminuria decreased by −47.6 in the BPS group compared with an increase by 116.4 (µg/mg Cr) in the PCB group (P=0.04). Also, in the large waist circumference group (>95 cm), microalbuminuria decreased significantly in the BPS group (P=0.04).

Conclusion

Short-term treatment of BPS for patients with diabetic nephropathy did not show significant improvement in various cardiovascular risk factors. However, BPS significantly decreased microalbuminuria in study subjects with higher cardiovascular risk such as high BP or large waist circumference.

Citations

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Clinical efficacy of beraprost sodium in treating chronic kidney disease: A six-month prospective study
Chen Sun, Xin Wu, Xin Zhang, Shulin Li, Ruoyu Jia, Dong Sun
Heliyon.2024; 10(2): e24156. CrossRef
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Peng Yan, Ben Ke, Xiangdong Fang
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Dysregulated coagulation system links to inflammation in diabetic kidney disease
Mengyun Xiao, Donge Tang, Shaodong Luan, Bo Hu, Wenyu Gong, Wolfgang Pommer, Yong Dai, Lianghong Yin
Frontiers in Clinical Diabetes and Healthcare.2023;[Epub] CrossRef
The effects of beraprost sodium on renal function and cardiometabolic profile in patients with diabetes mellitus: a systematic review and meta-analysis of clinical trials
Peyman Nowrouzi-Sohrabi, Reza Tabrizi, Kamran Hessami, Mojtaba Shabani-Borujeni, Mahnaz Hosseini-Bensenjan, Shahla Rezaei, Mohammad Jalali, Pedram Keshavarz, Fariba Ahmadizar
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Diabetes
Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis: Jae Hyun Bae, Sunhee Kim, Eun-Gee Park, Sin Gon Kim, Seokyung Hahn, Nam Hoon Kim; Endocrinol Metab. 2019;34(1):80-92. Published online March 21, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.1.80

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Background

To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes.

Methods

MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify randomized controlled trials (RCTs) of DPP-4 inhibitors from inception to September 2017. We selected eligible RCTs comparing DPP-4 inhibitors with placebo or other antidiabetic agents and reporting at least one renal outcome. A meta-analysis was conducted to calculate standardized mean differences, weighted mean differences (WMDs), relative risks (RRs), and 95% confidence intervals (CIs) for each renal outcome.

Results

We included 23 RCTs with 19 publications involving 41,359 patients. Overall changes in urine albumin-to-creatinine ratio were comparable between DPP-4 inhibitors and controls (P=0.150). However, DPP-4 inhibitors were associated with significantly lower risk of incident microalbuminuria (RR, 0.89; 95% CI, 0.80 to 0.98; P=0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97; P=0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35; P<0.001) compared with controls. Although DPP-4 inhibitors were associated with small but significantly lower estimated glomerular filtration rate (WMD, −1.11 mL/min/1.73 m²; 95% CI, −1.78 to −0.44; P=0.001), there was no difference in the risk of end-stage renal disease between two groups (RR, 0.93; 95% CI, 0.76 to 1.14; P=0.475).

Conclusion

DPP-4 inhibitors had beneficial renal effects mainly by reducing the risk of development or progression of albuminuria compared with placebo or other antidiabetic agents.

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Review Article

Obesity and Metabolism
Current Challenges in Diabetic Nephropathy: Early Diagnosis and Ways to Improve Outcomes: Sang Soo Kim, Jong Ho Kim, In Joo Kim; Endocrinol Metab. 2016;31(2):245-253. Published online May 27, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.2.245

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Diabetes is often associated with chronic kidney disease (CKD) and is the primary cause of kidney failure in half of patients who receive dialysis therapy. Given the increasing prevalence of diabetes and its high morbidity and mortality, diabetic nephropathy is a serious drawback in individual patients and a tremendous socioeconomic burden on society. Despite growing concern for the management of diabetic nephropathy, the prevalence of CKD with diabetes is the same today as it was 20 years ago. The current strategy to manage diabetic nephropathy, including the control of hyperglycemia, dyslipidemia, and blood pressure and the wide-spread use of renin-angiotensin-aldosterone system inhibitors, is well established to be beneficial in the early stages of diabetic nephropathy. However, the effects are uncertain in patients with relatively progressed CKD. Therefore, early diagnosis or risk verification is extremely important in order to reduce the individual and socioeconomic burdens associated with diabetic nephropathy by providing appropriate management to prevent the development and progression of this condition. This review focuses on recent research and guidelines regarding risk assessment, advances in medical treatment, and challenges of and future treatments for diabetic nephropathy.

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