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Reducing Oxidative Stress and Inflammation by Pyruvate Dehydrogenase Kinase 4 Inhibition Is Important in Prevention of Renal Ischemia-Reperfusion Injury in Diabetic Mice
Ah Reum Khang, Dong Hun Kim, Min-Ji Kim, Chang Joo Oh, Jae-Han Jeon, Sung Hee Choi, In-Kyu Lee
Diabetes Metab J. 2024;48(3):405-417.   Published online February 1, 2024
DOI: https://doi.org/10.4093/dmj.2023.0196
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  • 238 Download
  • 2 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Reactive oxygen species (ROS) and inflammation are reported to have a fundamental role in the pathogenesis of ischemia-reperfusion (IR) injury, a leading cause of acute kidney injury. The present study investigated the role of pyruvate dehydrogenase kinase 4 (PDK4) in ROS production and inflammation following IR injury.
Methods
We used a streptozotocin-induced diabetic C57BL6/J mouse model, which was subjected to IR by clamping both renal pedicles. Cellular apoptosis and inflammatory markers were evaluated in NRK-52E cells and mouse primary tubular cells after hypoxia and reoxygenation using a hypoxia work station.
Results
Following IR injury in diabetic mice, the expression of PDK4, rather than the other PDK isoforms, was induced with a marked increase in pyruvate dehydrogenase E1α (PDHE1α) phosphorylation. This was accompanied by a pronounced ROS activation, as well as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and monocyte chemoattractant protein-1 (MCP-1) production. Notably, sodium dichloroacetate (DCA) attenuated renal IR injury-induced apoptosis which can be attributed to reducing PDK4 expression and PDHE1α phosphorylation levels. DCA or shPdk4 treatment reduced oxidative stress and decreased TNF-α, IL-6, IL-1β, and MCP-1 production after IR or hypoxia-reoxygenation injury.
Conclusion
PDK4 inhibition alleviated renal injury with decreased ROS production and inflammation, supporting a critical role for PDK4 in IR mediated damage. This result indicates another potential target for reno-protection during IR injury; accordingly, the role of PDK4 inhibition needs to be comprehensively elucidated in terms of mitochondrial function during renal IR injury.

Citations

Citations to this article as recorded by  
  • Exploring Renal Pyruvate Metabolism as a Therapeutic Avenue for Diabetic Kidney Injury
    Jaemin Lee
    Diabetes & Metabolism Journal.2024; 48(3): 385.     CrossRef
  • Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs
    Seahyoung Lee
    Antioxidants.2024; 13(6): 656.     CrossRef
Cardiovascular Risk/Epidemiology
Article image
The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients
Ah Reum Khang, Min Jin Lee, Dongwon Yi, Yang Ho Kang
Diabetes Metab J. 2023;47(3):415-425.   Published online March 6, 2023
DOI: https://doi.org/10.4093/dmj.2022.0177
  • 2,187 View
  • 121 Download
  • 2 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts.
Methods
We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine.
Results
A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9–1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9–1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9–1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9–1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD).
Conclusion
We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

Citations

Citations to this article as recorded by  
  • Intraindividual difference in estimated GFR by creatinine and cystatin C, cognitive trajectories and motoric cognitive risk syndrome
    Jinqi Wang, Yueruijing Liu, Rui Jin, Xiaoyu Zhao, Zhiyuan Wu, Ze Han, Zongkai Xu, Xiuhua Guo, Lixin Tao
    Nephrology Dialysis Transplantation.2024; 39(5): 860.     CrossRef
  • Research Progress of Creatinine, Cystatin C, and Their Ratio in Renal Diseases
    广智 杨
    Advances in Clinical Medicine.2024; 14(04): 976.     CrossRef
  • Muscle mass, creatinine, cystatin C and selective glomerular hypofiltration syndromes
    Linnea Malmgren, Anders Grubb
    Clinical Kidney Journal.2023; 16(8): 1206.     CrossRef
  • Investigating kidney function changes in young adults with COVID-19: Serum creatinine level, glomerular filtration rate, and biochemical profile analysis
    Nikita Matyushin, Dmitriy Ermakov, Inna Vasileva, Roza Vakolyuk, Anastasiya Spaska
    Electronic Journal of General Medicine.2023; 20(6): em547.     CrossRef
Metabolic Risk/Epidemiology
Synergistic Interaction between Hyperuricemia and Abdominal Obesity as a Risk Factor for Metabolic Syndrome Components in Korean Population
Min Jin Lee, Ah Reum Khang, Yang Ho Kang, Mi Sook Yun, Dongwon Yi
Diabetes Metab J. 2022;46(5):756-766.   Published online January 20, 2022
DOI: https://doi.org/10.4093/dmj.2021.0166
  • 5,451 View
  • 261 Download
  • 7 Web of Science
  • 8 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The present study investigated the role of synergistic interaction between hyperuricemia and abdominal obesity as a risk factor for the components of metabolic syndrome.
Methods
We performed a cross-sectional study using the data of 16,094 individuals from the seventh Korean National Health and Nutrition Examination Survey (2016 to 2018). The adjusted odds ratios of metabolic syndrome and its components were analyzed by multivariate logistic regression analysis. The presence of synergistic interaction between hyperuricemia and abdominal obesity was evaluated by calculating the additive scales—the relative excess risk due to interaction, attributable proportion due to interaction, and synergy index (SI).
Results
There was a synergistic interaction between hyperuricemia and abdominal obesity in hypertriglyceridemia (men: SI, 1.39; 95% confidence interval [CI], 1.01 to 1.98; women: SI, 1.61; 95% CI, 1.02 to 2.69), and low high-density lipoprotein cholesterol (HDL-C) (men: SI, 2.03; 95% CI, 1.41 to 2.91; women: SI, 1.70; 95% CI, 1.05 to 2.95). There was no significant synergistic interaction between hyperuricemia and abdominal obesity for the risk of high blood pressure (men: SI, 1.22; 95% CI, 0.85 to 1.77; women: SI, 1.53; 95% CI, 0.79 to 2.97), and hyperglycemia (men: SI, 1.03; 95% CI, 0.72 to 1.47; women: SI, 1.39; 95% CI, 0.75 to 2.57).
Conclusion
Hyperuricemia and abdominal obesity synergistically increased the risk of hypertriglyceridemia and low HDL-C in both sexes.

Citations

Citations to this article as recorded by  
  • Prevalence and factors associated with overweight, obesity and central obesity among adults in Shenmu City, Shaanxi Province, China
    Mingxia Liu, Chunjiao Jia, Yaoda Hu, Juan Liu, Lizhen Liu, Shengli Sun, Haiying Wang, Yonglin Liu
    Preventive Medicine Reports.2024; 40: 102673.     CrossRef
  • Synergistic interaction between hyperlipidemia and obesity as a risk factor for stress urinary incontinence in Americans
    Fangyi Zhu, Mao Chen, Ya Xiao, Xiaoyu Huang, Liying Chen, Li Hong
    Scientific Reports.2024;[Epub]     CrossRef
  • Uric Acid Inhibits Mice Pancreatic Steatosis via the Glycerophospholipid Pathway
    Yang Xiao, Lina Han, Han Wang, Helin Ke, Shaodan Xu, Zhibin Huang, Guorong Lyu, Shilin Li
    ACS Omega.2024; 9(20): 21829.     CrossRef
  • Association of resistome abundance with hyperuricaemia in elderly individuals: a metagenomics study
    Zhiyang Liu, Yingbo Shen, Yulin Fu, Da Sun, Liang Li, Ziquan Lv
    Frontiers in Microbiomes.2024;[Epub]     CrossRef
  • The role of cognitive function in the relationship between surrogate markers of visceral fat and depressive symptoms in general middle-aged and elderly population: A nationwide population-based study
    Na Zhang, Jianqian Chao, Xueyu Wu, Hongling Chen, Min Bao
    Journal of Affective Disorders.2023; 338: 581.     CrossRef
  • Biodegradation of Uric Acid by Bacillus paramycoides-YC02
    Xiaoyu Cao, Jingyuan Cai, Yu Zhang, Chao Liu, Meijie Song, Qianqian Xu, Yang Liu, Hai Yan
    Microorganisms.2023; 11(8): 1989.     CrossRef
  • A predictive model for hyperuricemia among type 2 diabetes mellitus patients in Urumqi, China
    Palizhati Abudureyimu, Yuesheng Pang, Lirun Huang, Qianqian Luo, Xiaozheng Zhang, Yifan Xu, Liang Jiang, Patamu Mohemaiti
    BMC Public Health.2023;[Epub]     CrossRef
  • Dietary Ferulic Acid Ameliorates Metabolism Syndrome-Associated Hyperuricemia in Rats via Regulating Uric Acid Synthesis, Glycolipid Metabolism, and Hepatic Injury
    Nanhai Zhang, Jingxuan Zhou, Lei Zhao, Ou Wang, Liebing Zhang, Feng Zhou
    Frontiers in Nutrition.2022;[Epub]     CrossRef
Letter
Letter: Clinical Characteristics of People with Newly Diagnosed Type 2 Diabetes between 2015 and 2016: Difference by Age and Body Mass Index (Diabetes Metab J 2018;42:137-46)
Ah Reum Khang
Diabetes Metab J. 2018;42(3):249-250.   Published online June 19, 2018
DOI: https://doi.org/10.4093/dmj.2018.0074
  • 3,222 View
  • 33 Download
  • 3 Web of Science
  • 3 Crossref
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Citations

Citations to this article as recorded by  
  • Trends of Diabetes and Prediabetes Prevalence among Korean Adolescents From 2007 to 2018
    Ji Hyun Kim, Jung Sub Lim
    Journal of Korean Medical Science.2021;[Epub]     CrossRef
  • Age-, sex- and ethnicity-related differences in body weight, blood pressure, HbA1c and lipid levels at the diagnosis of type 2 diabetes relative to people without diabetes
    Alison K. Wright, Paul Welsh, Jason M. R. Gill, Evangelos Kontopantelis, Richard Emsley, Iain Buchan, Darren M. Ashcroft, Martin K. Rutter, Naveed Sattar
    Diabetologia.2020; 63(8): 1542.     CrossRef
  • Remission of type 2 diabetes in a young, hypogonadal man under long-term testosterone therapy: A case report
    Mskhalaya George, Tishova Yulia, Alfaradzh Anas, Kalinchenko Svetlana
    Global Journal of Obesity, Diabetes and Metabolic Syndrome.2020; 7(2): 024.     CrossRef
Original Article
Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody
Yul Hwangbo, Jin Taek Kim, Eun Ky Kim, Ah Reum Khang, Tae Jung Oh, Hak Chul Jang, Kyong Soo Park, Seong Yeon Kim, Hong Kyu Lee, Young Min Cho
Diabetes Metab J. 2012;36(2):136-143.   Published online April 17, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.2.136
  • 4,860 View
  • 44 Download
  • 16 Crossref
AbstractAbstract PDFPubReader   
Background

Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes.

Methods

We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics.

Results

The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups.

Conclusion

The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Citations

Citations to this article as recorded by  
  • Utility of Fasting C-Peptide for the Diagnostic Differentiation of Patients with Type 1, Type 2 Diabetes, MODY, and LADA
    Ricardo Alemán-Contreras, Rita A. Gómez-Díaz, Maura E. Noyola-García, Rafael Mondragón-González, Niels Wacher, Aldo Ferreira-Hermosillo
    Life.2024; 14(5): 550.     CrossRef
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    Endocrine.2023; 82(1): 28.     CrossRef
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    BMJ Open Diabetes Research & Care.2022; 10(3): e002739.     CrossRef
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    BMC Endocrine Disorders.2022;[Epub]     CrossRef
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    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2021; Volume 14: 4223.     CrossRef
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