Diabetes & Metabolism Journal

Original Articles

Basic research
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; Received June 22, 2023 Accepted July 13, 2023 Published online February 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0196 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader 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.

Cardiovascular Risk/Epidemiology
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

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Background
The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFR_{cystatin C}/eGF_Rcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts.
Methods
We assessed whether the eGFR_{cystatin C}/eGFR_creatinine 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 eGFR_{cystatin C}/eGF_Rcreatinine 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 eGFR_{cystatin C}/eGFR_creatinine 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 eGFR_{cystatin C}/eGFR_creatinine ratio.

Citations

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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

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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

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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
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

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Citations

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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

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Abstract PDF PubReader

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

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The worldwide prevalence of latent autoimmune diabetes of adults among adult-onset diabetic individuals: a systematic review and meta-analysis
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Investigation of serum level relationship anti-glutamic acid decarboxylase antibody and inflammatory cytokines (IL1-β, IL-6) with vitamins D in type 2 diabetes
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Latent Autoimmune Diabetes in Adults (LADA) and its Metabolic Characteristics among Yemeni Type 2 Diabetes Mellitus Patients
Dhekra Al-Zubairi, Molham AL-Habori, Riyadh Saif-Ali
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Amelioration of Diabetes-induced Cognitive Deficits by GSK-3β Inhibition is Attributed to Modulation of Neurotransmitters and Neuroinflammation
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