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Original Articles
Complications
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Characterizing the Immune Cell Infiltration in Renal Interstitium and Therapeutic Targets of Drugs in Diabetic Nephropathy by Multiomics Study
Chongbin Liu, Zurong Zhang, Yiyun Xi, Ming Yang, Huafeng Liu, Lin Sun
Received January 6, 2025  Accepted September 20, 2025  Published online January 30, 2026  
DOI: https://doi.org/10.4093/dmj.2025.0016    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Immune cell infiltration in the renal interstitium contributes to the progression of diabetic nephropathy (DN), yet the precise mechanisms remain incompletely unclear.
Methods
Public multi-omics datasets were integrated for comprehensive bioinformatic analyses. Interactions between infiltrating immune cells and damaged tubular epithelial cells (TECs) were analyzed with the CellChat, and key regulators were identified by machine learning. DN was modeled in C57BL/6 mice by high-fat diet/streptozotocin. Human kidney 2 (HK-2) cells were exposed to high glucose plus palmitic acid (HGPA). Gene function was validated by Western blotting, real-time quantitative polymerase chain reaction, immunohistochemistry and surface plasmon resonance (SPR).
Results
Renal interstitium from DN patients displayed markedly increased infiltration of M1 macrophages, regulatory T-cells, natural killer cells and other immune subsets, all correlating with indices of renal injury. CellChat analysis indicated that damaged TECs communicated with infiltrating immune cells primarily through chemokine networks centered on C-X-C motif chemokine ligand (CXCL), C-X3-C motif chemokine ligand (CX3CL), and C-C motif chemokine ligand 2 (CCL2). Retinoic acid-induced 2 (RAI2) was upregulated in DN kidneys and showed significant associations with immune infiltration and renal injury via these chemokine pathways. Consistently, RAI2 expression was elevated in kidneys of DN mice and in HGPA-treated HK-2 cells. SPR demonstrated direct, high-affinity binding of resveratrol to human RAI2 protein. Knockdown of RAI2 or treatment with resveratrol attenuated HGPA-induced apoptosis and suppressed CCL2, CXCL, and CX3CL expression levels.
Conclusion
RAI2 is a pivotal mediator of tubule injury and immune cell infiltration in DN, and resveratrol via direct binding to RAI2 and suppressed its function.
Cardiovascular Risk/Epidemiology
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Association of Systolic and Diastolic Blood Pressure with the Risk of End-Stage Renal Disease in Older Type 2 Diabetes Mellitus Patients without Cardiovascular Disease: A Nationwide Population-Based Study
Sangmo Hong, Kyungdo Han, Kye-Yeung Park, Chang Beom Lee, Dong Sun Kim, Jung Hwan Park, Sung Hoon Yu
Diabetes Metab J. 2025;49(6):1308-1317.   Published online September 25, 2025
DOI: https://doi.org/10.4093/dmj.2023.0364
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
There is insufficient evidence to determine a precise blood pressure target in older adults with diabetes mellitus. In this study, we evaluated the potential relationship between blood pressure levels and end-stage renal disease (ESRD) in older type 2 diabetes mellitus (T2DM) patients without ESRD using a nationwide longitudinal population dataset.
Methods
We performed a retrospective, observational, cohort study including 267,156 older (≥65 years old) patients with T2DM and without ESRD from 2009 to 2018 based on the National Health Information Database. We divided the participants into eight groups based on their systolic blood pressure (SBP) and diastolic blood pressure (DBP). The primary outcome was ESRD. All outcomes were analyzed using Cox proportional hazards regression analysis while controlling for baseline covariates.
Results
During a median follow-up of 7.26 years, the incidence rate of ESRD was 2.03 per 1,000 person-years. In multivariable Cox proportional hazard modeling, the risk of the primary outcome was the lowest in groups with an SBP of 100–119 mm Hg and DBP of <80 mm Hg. In subgroup analysis according to the use of hypertension medication, there was a significant difference in DBP (P for interaction=0.026) but no difference in SBP (P for interaction=0.247). The risk of ESRD was the lowest in patients with an SBP of 110–129 mm Hg taking hypertension medication and the highest in the group with an SBP of ≥160 mm Hg.
Conclusion
Maintaining blood pressure at less than 120/80 mm Hg might prevent progression to ESRD in older T2DM patients without cardiovascular disease.

Citations

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  • Preventing End-Stage Kidney Disease in Older Adults with Type 2 Diabetes Mellitus: Optimal Blood Pressure Targets
    Jae-Seung Yun, Seung-Hyun Ko
    Diabetes & Metabolism Journal.2025; 49(6): 1198.     CrossRef
Basic and Translational Research
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PUM2 Lowers HDAC9 mRNA Stability to Improve Contrast-Induced Acute Kidney Injury through Attenuating Oxidative Stress and Promoting Autophagy
Wei Chen, Hengcheng Lu, Wenni Dai, Hao Li, Yinyin Chen, Guoyong Liu, Liyu He
Received July 18, 2024  Accepted May 21, 2025  Published online September 10, 2025  
DOI: https://doi.org/10.4093/dmj.2024.0396    [Epub ahead of print]
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Contrast-induced acute kidney injury (CIAKI) is the third cause of hospital-acquired acute kidney injury and diabetes mellitus (DM) was identified as a risk factor for CIAKI. However, the molecular mechanism underlying DM-CIAKI remains unclear, which needs further investigation.
Methods
DM-CIAKI models of mice and cells were established. The functions of kidneys were evaluated by detecting indicators and using hematoxylin and eosin staining. The abundance of genes and proteins was evaluated by real-time quantitative reverse transcription polymerase chain reaction, immunohistochemistry, immunofluorescence, and Western blot. Glutathione peroxidase, superoxide dismutase, and malondialdehyde were measured using commercial kits and reactive oxygen species was detected using dihydroethidium (DHE) probe and 2ʹ,7ʹ-dichloroflfluorescein diacetate (DCFH-DA) method. Apoptosis of tissues and cells was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Cell viability and proliferation were measured using Cell Counting Kit-8 and 5-ethynyl-2ʹ-deoxyuridine (EdU) assay. The interaction between pumilio RNA binding family member 2 (PUM2) and histone deacetylase 9 (HDAC9) was validated using RNA immunoprecipitation (RIP) and RNA pull-down.
Results
PUM2 expression was observably reduced in DM-CIAKI models while HDAC9 expression was notably boosted. Subsequently, PUM2 silencing resulted in aggravation of kidney injury in DM-CIAKI mice through enhancing oxidative stress and suppressing autophagy, while HDAC9 inhibitor or HDAC9 silencing achieved the opposite results. In terms of mechanism, PUM2 could suppress stability of HDAC9 mRNA to attenuate HDAC9 expression. Furthermore, HDAC9 overexpression abolished PUM2 overexpression-mediated oxidative stress inhibition and autophagy promotion in high glucose and contrast media treatments-induced human kidney-2 (HK-2) cells.
Conclusion
PUM2 overexpression suppressed oxidative stress and promoted autophagy to alleviate renal injury in DM-CIAKI through interacting with HDAC9 mRNA, which mediated degradation of HDAC9 mRNA and inhibition of HDAC9 expression.

Citations

Citations to this article as recorded by  
  • Purpurin Rescues Contrast-Induced Acute Rat Kidney Injury via Inducing Autophagy and Inhibiting Apoptosis
    Kangxu He, Xiaoying Sun, Xinhui Pan, Xiaoda Yang, Qi Wang, Kai Liao
    Pharmaceuticals.2026; 19(1): 116.     CrossRef
  • Rubia cordifolia L. Dichloromethane Extract Ameliorates Contrast-Induced Acute Kidney Injury by Activating Autophagy via the LC3B/p62 Axis
    Xiaoying Sun, Kangxu He, Guanzhong Chen, Xiaoda Yang, Xinhui Pan, Kai Liao
    Molecules.2026; 31(2): 316.     CrossRef
Complications
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Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study
Eun Roh, Ji Hye Heo, Han Na Jung, Kyung-Do Han, Jun Goo Kang, Seong Jin Lee, Sung-Hee Ihm
Diabetes Metab J. 2025;49(5):1106-1115.   Published online May 21, 2025
DOI: https://doi.org/10.4093/dmj.2024.0406
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Remnant cholesterol (remnant-C) has been linked to the risk of various vascular diseases, but the association between remnant-C and end-stage renal disease (ESRD) in patients with type 2 diabetes mellitus (T2DM) remains unclear.
Methods
Using a nationwide cohort, a total of 2,537,149 patients with T2DM without ESRD, who had participated in the national health screening in 2009, were enrolled and followed up until 2020. Low-density lipoprotein cholesterol (LDL-C) levels were assessed by the Martin-Hopkins method, and remnant-C was calculated as total cholesterol–LDL-C–high-density lipoprotein cholesterol.
Results
During a median follow-up period of 10.3 years, 26,246 patients with T2DM (1.03%) developed ESRD. Participants in the upper quartile of remnant-C had a higher risk of ESRD, with hazard ratios of 1.12 (95% confidence interval [CI], 1.08 to 1.17), 1.20 (95% CI, 1.15 to 1.24), and 1.33 (95% CI, 1.26 to 1.41) in the second, third, and fourth quartile, compared with the lowest quartile, in multivariable-adjusted analyses. The positive association between remnant-C and ESRD remained consistent, irrespective of age, sex, presence of pre-existing comorbidities, and use of anti-dyslipidemic medications. The increased risk of ESRD was more pronounced in high-risk subgroups, including those with hypertension, chronic kidney disease, obesity, and a longer duration of diabetes.
Conclusion
These findings suggest that remnant-C profiles in T2DM have a predictive role for future progression of ESRD, independent of traditional risk factors for renal dysfunction.

Citations

Citations to this article as recorded by  
  • Impact of Remnant Cholesterol on the Risk for End-Stage Renal Disease in Type 2 Diabetes Mellitus: A Nationwide Population-Based Cohort Study (Diabetes Metab J 2025;49:1106-15)
    Jun Hwa Hong
    Diabetes & Metabolism Journal.2026; 50(1): 190.     CrossRef
  • A Narrative Review of Remnant Cholesterol as an Independent Atherogenic Lipoprotein in Type 2 Diabetes: Pathophysiology and Clinical Implications
    Ramdhani Natsir, Eli Halimah, Ajeng Diantini, Jutti Levita
    Therapeutics and Clinical Risk Management.2026; Volume 22: 1.     CrossRef
Complications
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Risk of End-Stage Kidney Disease in Individuals with Diabetes Living Alone: A Large-Scale Population-Based Study
Kyunghun Sung, Jae-Seung Yun, Bongseong Kim, Hun-Sung Kim, Jae-Hyoung Cho, Yong-Moon Mark Park, Kyungdo Han, Seung-Hwan Lee
Diabetes Metab J. 2025;49(4):862-872.   Published online April 5, 2025
DOI: https://doi.org/10.4093/dmj.2024.0578
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Previous research has linked solitary living to various adverse health outcomes, but its association with diabetic complications among individuals with type 2 diabetes mellitus (T2DM) remains underexplored. We examined the risk of endstage kidney disease (ESKD) in individuals with diabetes living alone (IDLA).
Methods
This population-based cohort study used the National Health Information Database of Korea, which included 2,432,613 adults with T2DM. Household status was determined based on the number of registered family members. IDLA was defined as continuously living alone for 5 years or more. A multivariable Cox proportional hazards model was used to evaluate the association between living alone and the risk of developing ESKD.
Results
During a median follow-up of 6.0 years, 26,691 participants developed ESKD, with a higher incidence observed in the IDLA group than in the non-IDLA group. After adjusting for confounding variables, the hazard ratio for ESKD in the IDLA group was 1.10 (95% confidence interval, 1.06 to 1.14). The risk of ESKD was particularly elevated in younger individuals, those without underlying chronic kidney disease, with longer durations of living alone, and with low household income. Adherence to favorable lifestyle behaviors (no smoking, no alcohol consumption, and engaging in regular exercise) was associated with a significantly lower risk of ESKD, with a more pronounced effect in the IDLA group.
Conclusion
Living alone was associated with a higher risk of ESKD in individuals with T2DM. Tailored medical interventions and social support for IDLA are crucial for the prevention of diabetic complications.

Citations

Citations to this article as recorded by  
  • Elevated triglyceride‐glucose index is associated with increased risk of chronic kidney disease and end‐stage renal disease in type 1 diabetes: Nationwide cohort study
    Rosa Oh, Seohyun Kim, So Hyun Cho, Ji Yoon Kim, Myunghwa Jang, Sang Ho Park, You‐Bin Lee, Sang‐Man Jin, Kyu Yeon Hur, Gyuri Kim, Jae Hyeon Kim
    Diabetes, Obesity and Metabolism.2026;[Epub]     CrossRef
Complications
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Burden of End-Stage Kidney Disease by Type 2 Diabetes Mellitus Status in South Korea: A Nationwide Epidemiologic Study
Jwa-Kyung Kim, Han Na Jung, Bum Jun Kim, Boram Han, Ji Hye Huh, Eun Roh, Joo-Hee Kim, Kyung-Do Han, Jun Goo Kang
Diabetes Metab J. 2025;49(3):498-506.   Published online March 6, 2025
DOI: https://doi.org/10.4093/dmj.2024.0443
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  • 4 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background
Patients with diabetes are known to be at high risk for end-stage kidney disease (ESKD), but the accurate annual risk data for new-onset ESKD is still limited. In South Korea, the prevalence and incidence of ESKD are increasing more rapidly compared to the global average. This study aimed to determine the incidence rate (IR) of ESKD by diabetes status from 2012 to 2022.
Methods
Using data from the Korean National Health Insurance Service, we calculated the IR and hazard ratio (HR) for newonset ESKD in the general population. Individuals were categorized based on diabetes status into nondiabetes, impaired fasting glucose (IFG), diabetes duration <5 and ≥5 years.
Results
Among the participants, 67.6% were nondiabetic, 22.3% had IFG, and 10% had diabetes. In Korea, the IRs of ESKD were 139 per million population (pmp) for nondiabetes, 188 pmp for IFG, 632 pmp for diabetes <5 years, and 3,403 pmp for diabetes ≥5 years. An advanced estimated glomerular filtration rate (eGFR) category was the strongest risk factor for ESKD development. However, even in patients with normal renal function, those with long-standing diabetes had a 14-fold higher risk of ESKD compared to nondiabetic individuals. The risk of ESKD associated with diabetes increased exponentially with declining renal function. Notably, IFG showed an increasing tendency for ESKD in younger patients (<65 years) with early-stage chronic kidney disease (CKD; eGFR ≥60 mL/min/1.73 m²).
Conclusion
Longer diabetes duration amplifies ESKD risk, particularly as renal function declines. Even in patients with normal renal function, long-standing diabetes significantly increases ESKD risk, while IFG is associated with elevated risk only in younger individuals with early-stage CKD.

Citations

Citations to this article as recorded by  
  • Development and validation of a machine learning model to predict comorbid hypertension in patients with type 2 diabetes
    Hailu Yang, Changfeng Fan, Chunyan Liu
    Frontiers in Medicine.2026;[Epub]     CrossRef
Basic and Translational Research
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Revealing VCAN as a Potential Common Diagnostic Biomarker of Renal Tubules and Glomerulus in Diabetic Kidney Disease Based on Machine Learning, Single-Cell Transcriptome Analysis and Mendelian Randomization
Li Jiang, Jie Jian, Xulin Sai, Xiai Wu
Diabetes Metab J. 2025;49(3):407-420.   Published online January 24, 2025
DOI: https://doi.org/10.4093/dmj.2024.0233
  • 7,467 View
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Diabetic kidney disease (DKD) is recognized as a significant complication of diabetes mellitus and categorized into glomerular DKDs and tubular DKDs, each governed by distinct pathological mechanisms and biomarkers.
Methods
Through the identification of common features observed in glomerular and tubular lesions in DKD, numerous differentially expressed gene were identified by the machine learning, single-cell transcriptome and mendelian randomization.
Results
The diagnostic markers versican (VCAN) was identified, offering supplementary options for clinical diagnosis. VCAN significantly highly expressed in glomerular parietal epithelial cell and proximal convoluted tubular cell. It was mainly involved in the up-regulation of immune genes and infiltration of immune cells like mast cell. Mendelian randomization analysis confirmed that serum VCAN protein levels were a risky factor for DKD, while there was no reverse association. It exhibited the good diagnostic potential for estimated glomerular filtration rate and proteinuria in DKD.
Conclusion
VCAN showed the prospects into DKD pathology and clinical indicator.

Citations

Citations to this article as recorded by  
  • Transient versican expression is required for β1-integrin accumulation during podocyte layer morphogenesis in amphibian developing kidney
    Isabelle Buisson, Jean-François Riou, Muriel Umbhauer, Ronan Le Bouffant, Valérie Bello
    Cells & Development.2026; 185: 204062.     CrossRef
  • Multi-omics and machine learning identify FN1 and ALDH2 as diagnostic biomarkers and therapeutic targets in early and late diabetic kidney disease
    Jingwei Lin, Yingying Zheng, Diman Mai, Fuxiang Fang, Zhuokun Wei, Mengyu Liu, Trung Hieu Pham, Ming Li, Jiawen Zhao
    Renal Failure.2025;[Epub]     CrossRef
Pharmacotherapy
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Study Design and Protocol for a Randomized Controlled Trial of Enavogliflozin to Evaluate Cardiorenal Outcomes in Type 2 Diabetes (ENVELOP)
Nam Hoon Kim, Soo Lim, In-Kyung Jeong, Eun-Jung Rhee, Jun Sung Moon, Ohk-Hyun Ryu, Hyuk-Sang Kwon, Jong Chul Won, Sang Soo Kim, Sang Yong Kim, Bon Jeong Ku, Heung Yong Jin, Sin Gon Kim, Bong-Soo Cha, on Behalf of Investigators of ENVELOP Study
Diabetes Metab J. 2025;49(2):225-234.   Published online January 6, 2025
DOI: https://doi.org/10.4093/dmj.2024.0238
  • 7,414 View
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated.
Methods
This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243).
Conclusion
This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Citations

Citations to this article as recorded by  
  • Reverse translational approach to clarify the strong potency of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor
    Sun-Hwa Park, Hye-Young Ji, Ji-Soo Choi, Kyung Seok Oh, Jihoon Lee, Minyeong Pang, Im-Sook Song, Joon Seok Park
    The Journal of Pharmacology and Experimental Therapeutics.2025; 392(8): 103650.     CrossRef
Basic research
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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
  • 10,019 View
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  • 12 Web of Science
  • 13 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

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  • Advancements in early biomarkers of acute kidney injury: from traditional indicators to a paradigm shift in lactate metabolism
    Qian Wu, Xinyi Qiu, Hongyu Chen
    Annals of Medicine.2026;[Epub]     CrossRef
  • Targeting TFAM K76 acetylation attenuates mitochondrial dysfunction and kidney injury in diabetic kidney disease
    Tingting Fu, Shengnan Sun, Zhiye Wang, Fang Zhao, Junhui Zhen, Xingzhao Ji, Fuyuan Xue, Qian Mu, Ying Wang, Yi Liu, Qiang Wan
    Cardiovascular Diabetology.2026;[Epub]     CrossRef
  • Persistent subclinical renal injury in female rats following renal ischemia-reperfusion injury
    Desmond Moronge, Hannah Godley, Victor Ayulo, Elisabeth Mellott, Mona Elgazzaz, Gibson Cooper, Riyaz Mohamed, Safia Ogbi, Ellen Gillis, Jessica L. Faulkner, Jennifer C. Sullivan
    Clinical Science.2025; 139(04): 309.     CrossRef
  • Edaravone dexborneol exerts anti-epileptic effects on rodent temporal lobe epilepsy by promoting NMDAR deactivation and inhibiting oxidative stress
    Wanhua Qiu, Roumeng Chen, Lechen Pan, Yiqian Li, Yuchen Xu, Yuqian Li, Ang Guo, Wenting Huang, Tao Tan, Peijun Li, Chenglong Xie, Huiqin Xu, Li Lin, Xinshi Wang
    Phytomedicine.2025; 140: 156558.     CrossRef
  • Cardiac PDK4 promotes neutrophilic PFKL methylation and drives the innate immune response in diabetic myocardial infarction
    Song Yang, Longxin Yan, Lang Chen, Gaijuan Su, Long Yang, Lili Gong, Lihong Liu
    Pharmacological Research.2025; 215: 107731.     CrossRef
  • Targeting HDAC3 Suppresses Ferroptosis and Demyelination in White Matter Injury by Restoring PDK4‐Mediated Iron Homeostasis
    Ting Xu, Lisha Ye, Wenfeng Li, Fangming Liu, Tianjiao Wei, Wenhui Gu, Lihua Xu, Mingde Fang, Qianqian Luo, Chuanjie Wu, Guohua Wang
    CNS Neuroscience & Therapeutics.2025;[Epub]     CrossRef
  • Advances in the therapeutic applications of dichloroacetate as a metabolic regulator: A review
    Xiaohuan Wu, Min Shang, Meichuan Li, Yujuan Liu, Han Hu, Ping Zhang, Qiuyi He, Shide Lin
    Medicine.2025; 104(36): e44295.     CrossRef
  • Depression, anxiety, and stress impair sperm quality via dysregulation of the mitochondrial PDK–PDC axis
    Wang Wang, Wang Qikai, Wang Zilin, Shao Junyan, Jiang Xiaocui, Liu Qi, Chen Shuhui, Zhu Yangyang, Gao Mengjie, Chen Siyi, Cao Jigang, Xiao Min
    Reproductive Biology and Endocrinology.2025;[Epub]     CrossRef
  • Integrating Metabolomics LC-HRMS, and Network Pharmacology of Garcinia forbesii King Leaf Extract, Potential for Treatment of Renal Ischemic Reperfusion Injury
    Azma Rosida, Nia Kania, Mohammad Rudiansyah, Fujiati Fujiati, Oski Illiandri, Wivina R Devi
    Tropical Journal of Natural Product Research.2025;[Epub]     CrossRef
  • Identification and validation of mitochondrial-related genes in intestinal ischemia-reperfusion injury based on WGCNA and machine learning
    YiChen Hu, Jie Huang, XiaoLi Min, YuanPei Zhao, JiaHui Wang, HongYuan Liu, KaiWen Shi, WenLiang Li, WeiMing Li
    Frontiers in Molecular Biosciences.2025;[Epub]     CrossRef
  • 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
  • Sodium Phenylbutyrate Attenuates Cisplatin-Induced Acute Kidney Injury Through Inhibition of Pyruvate Dehydrogenase Kinase 4
    Chang Joo Oh, Wooyoung Choi, Ha Young Lee, In-Kyu Lee, Min-Ji Kim, Jae-Han Jeon
    Biomedicines.2024; 12(12): 2815.     CrossRef
Review
Others
Article image
Risk Prediction and Management of Chronic Kidney Disease in People Living with Type 2 Diabetes Mellitus
Ying-Guat Ooi, Tharsini Sarvanandan, Nicholas Ken Yoong Hee, Quan-Hziung Lim, Sharmila S. Paramasivam, Jeyakantha Ratnasingam, Shireene R. Vethakkan, Soo-Kun Lim, Lee-Ling Lim
Diabetes Metab J. 2024;48(2):196-207.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2023.0244
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
People with type 2 diabetes mellitus have increased risk of chronic kidney disease and atherosclerotic cardiovascular disease. Improved care delivery and implementation of guideline-directed medical therapy have contributed to the declining incidence of atherosclerotic cardiovascular disease in high-income countries. By contrast, the global incidence of chronic kidney disease and associated mortality is either plateaued or increased, leading to escalating direct and indirect medical costs. Given limited resources, better risk stratification approaches to identify people at risk of rapid progression to end-stage kidney disease can reduce therapeutic inertia, facilitate timely interventions and identify the need for early nephrologist referral. Among people with chronic kidney disease G3a and beyond, the kidney failure risk equations (KFRE) have been externally validated and outperformed other risk prediction models. The KFRE can also guide the timing of preparation for kidney replacement therapy with improved healthcare resources planning and may prevent multiple complications and premature mortality among people with chronic kidney disease with and without type 2 diabetes mellitus. The present review summarizes the evidence of KFRE to date and call for future research to validate and evaluate its impact on cardiovascular and mortality outcomes, as well as healthcare resource utilization in multiethnic populations and different healthcare settings.

Citations

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  • Integrated SERS-magnetic capture platform for multiplex detection of early tubular injury biomarkers in diabetic kidney disease progression
    Wendi Cao, Sirui Yang, Zhenhua Zhao, Xuelin Chen, Tenglong Liu, Xinran Yang, Leshan Cai, Xiaozhe Lin, Xia Zhou, Qiaoxin Zhang
    Sensors and Actuators Reports.2026; 11: 100412.     CrossRef
  • A Machine Learning-Based Prediction Model for Diabetic Kidney Disease in Korean Patients with Type 2 Diabetes Mellitus
    Kyung Ae Lee, Jong Seung Kim, Yu Ji Kim, In Sun Goak, Heung Yong Jin, Seungyong Park, Hyejin Kang, Tae Sun Park
    Journal of Clinical Medicine.2025; 14(6): 2065.     CrossRef
  • Chronic Kidney Disease in Diabetes: A Clinical Practice Guideline
    Sheldon W. Tobe, Harpreet S. Bajaj, Navdeep Tangri, Rahul Jain, Thuy Pham, Valerie Beaudin, Phil McFarlane
    Canadian Journal of Diabetes.2025; 49(2): 73.     CrossRef
  • Kidney failure risk equation (KFRE), A risk-based triage for nephrology referrals: A mixed-methods study at pre-implementation phase among healthcare providers
    Nur Raziana Rozi, Christine Shamala Selvaraj, Jia-Kai Tan, Zhan-Foong Lim, Noor Wahidah Nordin, Nuqman Hakimi Mazhar, Haris Hafizal, Hooi-Chin Beh, Quan-Hziung Lim, Ying-Guat Ooi, Adina Abdullah, Wan Ahmad Hafiz Wan Md Adnan, Pavai Sthaneswar, Soo-Kun Lim
    Primary Care Diabetes.2025; 19(6): 636.     CrossRef
  • Construction and validation of a clinical prediction model for diabetic ketoacidosis
    Chen Xu, Xingwen Jiang, Quanan He, Peng Xu
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Original Article
Drug/Regimen
Article image
Abrupt Decline in Estimated Glomerular Filtration Rate after Initiating Sodium-Glucose Cotransporter 2 Inhibitors Predicts Clinical Outcomes: A Systematic Review and Meta-Analysis
Min-Hsiang Chuang, Yu-Shuo Tang, Jui-Yi Chen, Heng-Chih Pan, Hung-Wei Liao, Wen-Kai Chu, Chung-Yi Cheng, Vin-Cent Wu, Michael Heung
Diabetes Metab J. 2024;48(2):242-252.   Published online January 26, 2024
DOI: https://doi.org/10.4093/dmj.2023.0201
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined.
Methods
We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis.
Results
We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group.
Conclusion
Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Citations

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Review
Complications
Article image
Dyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview
Sang Heon Suh, Soo Wan Kim
Diabetes Metab J. 2023;47(5):612-629.   Published online July 24, 2023
DOI: https://doi.org/10.4093/dmj.2023.0067
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AbstractAbstract PDFPubReader   ePub   
Dyslipidemia is a potentially modifiable cardiovascular risk factor. Whereas the recommendations for the treatment target of dyslipidemia in the general population are being more and more rigorous, the 2013 Kidney Disease: Improving Global Outcomes clinical practice guideline for lipid management in chronic kidney disease (CKD) presented a relatively conservative approach with respect to the indication of lipid lowering therapy and therapeutic monitoring among the patients with CKD. This may be largely attributed to the lack of high-quality evidence derived from CKD population, among whom the overall feature of dyslipidemia is considerably distinctive to that of general population. In this review article, we cover the characteristic features of dyslipidemia and impact of dyslipidemia on cardiovascular outcomes in patients with CKD. We also review the current evidence on lipid lowering therapy to modify the risk of cardiovascular events in this population. We finally discuss the association between dyslipidemia and CKD progression and the potential strategy to delay the progression of CKD in relation to lipid lowering therapy.

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Brief Reports
Complications
Article image
Trends in the Incidence, Prevalence, and Mortality of End-Stage Kidney Disease in South Korea
Min-Jeong Lee, Kyoung Hwa Ha, Dae Jung Kim, Inwhee Park
Diabetes Metab J. 2020;44(6):933-937.   Published online December 23, 2020
DOI: https://doi.org/10.4093/dmj.2020.0156
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Knowledge of the epidemiologic characteristics of end-stage kidney disease (ESKD) patients is essential. The trends in the prevalence, incidence, and mortality rates of ESKD were analyzed retrospectively using the Korean National Health Insurance ServiceNational Sample Cohort database between 2006 and 2015. From 2006 to 2015, the incidence of ESKD decreased from 28.6 to 24.0 per 100,000 people and showed a decreasing pattern with or without diabetes mellitus. However, the incidence of those aged ≥75 years increased, as did the mean age at the onset of ESKD. From 2007 to 2015, the prevalence of ESKD increased in all age groups, but particularly in those aged ≥75 years. The prevalence of ESKD differed by sex and diabetes mellitus status and this gap widened over time. Mortality rates in ESKD patients remained relatively constant throughout the study period. However, mortality rates in ESKD without diabetes decreased over the same period.

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Drug/Regimen
Evogliptin, a Dipeptidyl Peptidase-4 Inhibitor, Attenuates Renal Fibrosis Caused by Unilateral Ureteral Obstruction in Mice
Mi-Jin Kim, Na-young Kim, Yun-A Jung, Seunghyeong Lee, Gwon-Soo Jung, Jung-Guk Kim, In-Kyu Lee, Sungwoo Lee, Yeon-Kyung Choi, Keun-Gyu Park
Diabetes Metab J. 2020;44(1):186-192.   Published online October 31, 2019
DOI: https://doi.org/10.4093/dmj.2018.0271
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   

Renal fibrosis is considered to be the final common outcome of chronic kidney disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have demonstrated protective effects against diabetic kidney disease. However, the anti-fibrotic effect of evogliptin, a DPP-4 inhibitor, has not been studied. Here, we report the beneficial effects of evogliptin on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice. Evogliptin attenuated UUO-induced renal atrophy and tubulointerstitial fibrosis. Immunohistochemistry and Western blotting demonstrated that evogliptin treatment inhibits pro-fibrotic gene expressions and extracellular matrix production. In vitro findings showed that the beneficial effects of evogliptin on renal fibrosis are mediated by inhibition of the transforming growth factor-β/Smad3 signaling pathway. The present study demonstrates that evogliptin is protective against UUO-induced renal fibrosis, suggesting that its clinical applications could extend to the treatment of kidney disease of non-diabetic origin.

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Original Articles
Basic Research
Fibroblast Growth Factor 21 Attenuates Diabetes-Induced Renal Fibrosis by Negatively Regulating TGF-β-p53-Smad2/3-Mediated Epithelial-to-Mesenchymal Transition via Activation of AKT
Sundong Lin, Lechu Yu, Yongqing Ni, Lulu He, Xiaolu Weng, Xuemian Lu, Chi Zhang
Diabetes Metab J. 2020;44(1):158-172.   Published online October 28, 2019
DOI: https://doi.org/10.4093/dmj.2018.0235
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

Epithelial-to-mesenchymal transition (EMT) is required for renal fibrosis, which is a characteristic of diabetic nephropathy (DN). Our previous study demonstrated that fibroblast growth factor 21 (FGF21) prevented DN associated with the suppressing renal connective tissue growth factor expression, a key marker of renal fibrosis. Therefore, the effects of FGF21 on renal fibrosis in a DN mouse model and the underlying mechanisms were investigated in this study.

Methods

Type 1 diabetes mellitus was induced in C57BL/6J mice by intraperitoneal injections of multiple low doses of streptozotocin. Then, diabetic and non-diabetic mice were treated with or without FGF21 in the presence of pifithrin-α (p53 inhibitor) or 10-[4′-(N,N-Diethylamino)butyl]-2-chlorophenoxazine hydrochloride (10-DEBC) hydrochloride (Akt inhibitor) for 4 months.

Results

DN was diagnosed by renal dysfunction, hypertrophy, tubulointerstitial lesions, and glomerulosclerosis associated with severe fibrosis, all of which were prevented by FGF21. FGF21 also suppressed the diabetes-induced renal EMT in DN mice by negatively regulating transforming growth factor beta (TGF-β)-induced nuclear translocation of Smad2/3, which is required for the transcription of multiple fibrotic genes. The mechanistic studies showed that FGF21 attenuated nuclear translocation of Smad2/3 by inhibiting renal activity of its conjugated protein p53, which carries Smad2/3 into the nucleus. Moreover pifithrin-α inhibited the FGF21-induced preventive effects on the renal EMT and subsequent renal fibrosis in DN mice. In addition, 10-DEBC also blocked FGF21-induced inhibition of renal p53 activity by phosphorylation of mouse double minute-2 homolog (MDM2).

Conclusion

FGF21 prevents renal fibrosis via negative regulation of the TGF-β/Smad2/3-mediated EMT process by activation of the Akt/MDM2/p53 signaling pathway.

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Complications
Gemigliptin Attenuates Renal Fibrosis Through Down-Regulation of the NLRP3 Inflammasome
Jung Beom Seo, Yeon-Kyung Choi, Hye-In Woo, Yun-A Jung, Sungwoo Lee, Seunghyeong Lee, Mihyang Park, In-Kyu Lee, Gwon-Soo Jung, Keun-Gyu Park
Diabetes Metab J. 2019;43(6):830-839.   Published online March 5, 2019
DOI: https://doi.org/10.4093/dmj.2018.0181
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AbstractAbstract PDFPubReader   ePub   
Background

The hypoglycemic drugs dipeptidyl peptidase-4 (DPP-4) inhibitors have proven protective effects on diabetic kidney disease, including renal fibrosis. Although NOD-like receptor protein 3 (NLRP3) inflammasome activation is known to play an important role in the progression of renal fibrosis, the impact of DPP-4 inhibition on NLRP3-mediated inflammation while ameliorating renal fibrosis has not been fully elucidated. Here, we report that the renoprotective effect of gemigliptin is associated with a reduction in NLRP3-mediated inflammation in a murine model of renal fibrosis.

Methods

We examined the effects of gemigliptin on renal tubulointerstitial fibrosis induced in mice by unilateral ureteral obstruction (UUO). Using immunohistochemical and Western blot analysis, we quantitated components of the NLRP3 inflammasome in kidneys with and without gemigliptin treatment, and in vitro in human kidney tubular epithelial human renal proximal tubule cells (HK-2) cells, we further analyzed the effect of gemigliptin on transforming growth factor-β (TGF-β)-stimulated production of profibrotic proteins.

Results

Immunohistological examination revealed that gemigliptin ameliorated UUO-induced tubular atrophy and renal fibrosis. Gemigliptin-treated kidneys showed a reduction in levels of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin-1β, which had all been markedly increased by UUO. In line with the in vivo results, TGF-β markedly increased NLRP3 inflammasome markers, which were attenuated by gemigliptin treatment. Furthermore, gemigliptin treatment attenuated phosphorylated nuclear factor-κB levels, which had been increased in the UUO kidney as well as in TGF-β-treated cultured renal cells.

Conclusion

The present study shows that activation of the NLRP3 inflammasome contributes to UUO-induced renal fibrosis and the renoprotective effect of gemigliptin is associated with attenuation of NLRP3 inflammasome activation.

Citations

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Complication
Soluble Dipeptidyl Peptidase-4 Levels Are Associated with Decreased Renal Function in Patients with Type 2 Diabetes Mellitus
Eun-Hee Cho, Sang-Wook Kim
Diabetes Metab J. 2019;43(1):97-104.   Published online October 8, 2018
DOI: https://doi.org/10.4093/dmj.2018.0030
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AbstractAbstract PDFPubReader   ePub   
Background

Dipeptidyl peptidase-4 (DPP-4) is strongly expressed in the kidney, and soluble levels of this protein are used as a marker in various chronic inflammatory diseases, including diabetes, coronary artery disease, and cancer. This study examined the association between the serum soluble DPP-4 levels and renal function or cardiovascular risk in patients with type 2 diabetes mellitus.

Methods

In this retrospective analysis, soluble DPP-4 levels were measured in preserved sera from 140 patients with type 2 diabetes mellitus who had participated in our previous coronary artery calcium (CAC) score study.

Results

The mean±standard deviation soluble DPP-4 levels in our study sample were 645±152 ng/mL. Univariate analyses revealed significant correlations of soluble DPP-4 levels with the total cholesterol (r=0.214, P=0.019) and serum creatinine levels (r=−0.315, P<0.001) and the estimated glomerular filtration rate (eGFR; estimated using the modification of diet in renal disease equation) (r=0.303, P=0.001). The associations of soluble DPP-4 levels with serum creatinine and GFR remained significant after adjusting for age, body mass index, and duration of diabetes. However, no associations were observed between soluble DPP-4 levels and the body mass index, waist circumference, or CAC score.

Conclusion

These data suggest the potential use of serum soluble DPP-4 levels as a future biomarker of deteriorated renal function in patients with type 2 diabetes mellitus.

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Obesity and Metabolic Syndrome
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Sojib Bin Zaman, Naznin Hossain, Muntasirur Rahman
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DOI: https://doi.org/10.4093/dmj.2017.0052
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AbstractAbstract PDFPubReader   ePub   
Background

Chronic kidney disease (CKD) has emerged as a public health burden globally. Obesity and long-term hyperglycaemia can initiate the renal vascular complications in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the association of body mass index (BMI) with the CKD in patients with T2DM.

Methods

This study has used retrospective medical records, biochemical reports, and anthropometric measurements of 3,580 T2DM patients which were collected between January to December 2015 from a district hospital in Thailand. CKD was defined according to the measurement of estimated glomerular filtration rate (<60 mL/min/1.73 m2). Multiple logistic regression analysis was used to explore the association between BMI and CKD in patients with T2DM.

Results

The mean age of the participants was 60.86±9.67 years, 53.68% had poor glycaemic control, and 45.21% were overweight. About one-in-four (23.26%) T2DM patients had CKD. The mean BMI of non-CKD group was slightly higher (25.30 kg/m2 vs. 24.30 kg/m2) when compared with CKD patients. Multivariable analysis showed that older age, female sex, hypertension, and microalbuminuria were associated with the presence of CKD. No association was observed between CKD and poorly controlled glycosylated hemoglobin or hypercholesterolemia. Adjusted analysis further showed overweight and obesity were negatively associated with CKD (adjusted odds ratio [AOR], 0.73; 95% confidence interval [CI], 0.58 to 0.93) and (AOR, 0.53; 95% CI, 0.35 to 0.81), respectively.

Conclusion

The negative association of BMI with CKD could reflect the reverse causality. Lower BMI might not lead a diabetic patient to develop CKD, but there are possibilities that CKD leads the patient to experience reduced BMI.

Citations

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    Indian Journal of Nephrology.2024; 35: 670.     CrossRef
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Complications
Glycated Albumin Is a More Useful Glycation Index than HbA1c for Reflecting Renal Tubulopathy in Subjects with Early Diabetic Kidney Disease
Ji Hye Huh, Minyoung Lee, So Young Park, Jae Hyeon Kim, Byung-Wan Lee
Diabetes Metab J. 2018;42(3):215-223.   Published online May 2, 2018
DOI: https://doi.org/10.4093/dmj.2017.0091
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AbstractAbstract PDFPubReader   ePub   
Background

The aim of this study was to investigate which glycemic parameters better reflect urinary N-acetyl-β-D-glucosaminidase (uNAG) abnormality, a marker for renal tubulopathy, in subjects with type 2 diabetes mellitus (T2DM) subjects with normoalbuminuria and a normal estimated glomerular filtration rate (eGFR).

Methods

We classified 1,061 participants with T2DM into two groups according to uNAG level—normal vs. high (>5.8 U/g creatinine)—and measured their biochemical parameters.

Results

Subjects with high uNAG level had significantly higher levels of fasting and stimulated glucose, glycated albumin (GA), and glycosylated hemoglobin (HbA1c) and lower levels of homeostasis model assessment of β-cell compared with subjects with normal uNAG level. Multiple linear regression analyses showed that uNAG was significantly associated with GA (standardized β coefficient [β]=0.213, P=0.016), but not with HbA1c (β=−0.137, P=0.096) or stimulated glucose (β=0.095, P=0.140) after adjusting confounding factors. In receiver operating characteristic analysis, the value of the area under the curve (AUC) for renal tubular injury of GA was significantly higher (AUC=0.634; 95% confidence interval [CI], 0.646 to 0.899) than those for HbA1c (AUC=0.598; 95% CI, 0.553 to 0.640), stimulated glucose (AUC=0.594; 95% CI, 0.552 to 0.636), or fasting glucose (AUC=0.558; 95% CI, 0.515 to 0.600). The optimal GA cutoff point for renal tubular damage was 17.55% (sensitivity 59%, specificity 62%).

Conclusion

GA is a more useful glycation index than HbA1c for reflecting renal tubulopathy in subjects with T2DM with normoalbuminuria and normal eGFR.

Citations

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  • Diagnostic and therapeutic potential of PCSK9 in diabetic tubulopathy: Evidence from observational and experimental studies
    JingJing Quan, Si Li, Bin Yi, Zhijun Huang
    International Immunopharmacology.2026; 168: 115907.     CrossRef
  • Connecting glycation and lipotoxicity to mitochondrial dysfunction in diabetic kidney disease: A ‘tubulocentric’ perspective
    Mayura Apte, Girish Kumthekar, Rashmi Santosh Tupe
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  • Albumin does not induce IL-6 release and toll-like receptor activation in vitro: Role of endotoxin contamination and biochemical modifications
    Margret Paar, Vera H. Fengler, Martina Schweiger, Christine Rossmann, Christoph Nusshold, Martina Mairold, Doris Payerl, Gerhard Cvirn, Karl Oettl
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  • Glucagon-Like Peptide 1 Receptor Agonist Improves Renal Tubular Damage in Mice with Diabetic Kidney Disease
    Ran Li, Dunmin She, Zhengqin Ye, Ping Fang, Guannan Zong, Yong Zhao, Kerong Hu, Liya Zhang, Sha Lei, Keqin Zhang, Ying Xue
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 1331.     CrossRef
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    Guo-Yan Li, Hao-Yu Li, Qiang Li
    World Journal of Diabetes.2021; 12(2): 149.     CrossRef
  • Diabetic Kidney Disease, Cardiovascular Disease and Non-Alcoholic Fatty Liver Disease: A New Triumvirate?
    Carolina M. Perdomo, Nuria Garcia-Fernandez, Javier Escalada
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    Dongjun Dai, Yifei Mo, Jian Zhou
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Others
The Effect of Glycemic Status on Kidney Stone Disease in Patients with Prediabetes
Tzu-Hsien Lien, Jin-Shang Wu, Yi-Ching Yang, Zih-Jie Sun, Chih-Jen Chang
Diabetes Metab J. 2016;40(2):161-166.   Published online April 25, 2016
DOI: https://doi.org/10.4093/dmj.2016.40.2.161
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AbstractAbstract PDFPubReader   ePub   
Background

While the evidence supporting a positive association between diabetes mellitus and kidney stone disease (KSD) is solid, studies examining the association between impaired fasting glucose (IFG) and KSD show inconsistent results. Currently, there are no studies examining the relationship between impaired glucose tolerance (IGT) and KSD. The objective of this study is to investigate the effects of different glycemic statuses on KSD. The results may help to motivate patients with diabetes to conform to treatment regimens.

Methods

We conducted a cross sectional study of a population that underwent health check-ups between January 2000 and August 2009 at the Health Evaluation Center of National Cheng Kung University Hospital. A total of 14,186 subjects were enrolled. The following categories of glycemic status were used according to the criteria of the 2009 American Diabetes Association: normal glucose tolerance, isolated IGT, isolated IFG, combined IFG/IGT, and diabetes. The existence of KSD was evaluated using renal ultrasonography, and the presence of any hyperechoic structures causing acoustic shadowing was considered to be indicative of KSD.

Results

The prevalence of KSD was 7.4% (712/9,621), 9.3% (163/1,755), 10.8% (78/719), 12.0% (66/548), and 11.3% (174/1,543) in subjects with NGT, isolated IGT, isolated IFG, combined IFG/IGT, and diabetes, respectively. Isolated IFG, combined IFG/IGT, and diabetes were associated with KSD after adjusting for other clinical variables, but isolated IGT was not. Age (41 to 64 years vs. ≤40 years, ≥65 years vs. ≤40 years), male gender, hypertension, and hyperuricemia were also independently associated with KSD.

Conclusion

Isolated IFG, combined IFG/IGT, and diabetes, but not isolated IGT, were associated with a higher risk of KSD.

Citations

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    В. А. Слободянюк
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Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes
Qing-Lin Lou, Xiao-Jun Ouyang, Liu-Bao Gu, Yong-Zhen Mo, Ronald Ma, Jennifer Nan, Alice Kong, Wing-Yee So, Gary Ko, Juliana Chan, Chun-Chung Chow, Rong-Wen Bian
Diabetes Metab J. 2012;36(6):433-442.   Published online December 12, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.6.433
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AbstractAbstract PDFPubReader   ePub   
Background

To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009.

Methods

Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g.

Results

We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively.

Conclusion

In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes.

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Urinary Neutrophil Gelatinase-Associated Lipocalin Levels in Comparison with Glomerular Filtration Rate for Evaluation of Renal Function in Patients with Diabetic Chronic Kidney Disease
Kwang-Sook Woo, Jae-Lim Choi, Bo-Ram Kim, Ji-Eun Kim, Won-Suk An, Jin-Yeong Han
Diabetes Metab J. 2012;36(4):307-313.   Published online August 20, 2012
DOI: https://doi.org/10.4093/dmj.2012.36.4.307
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AbstractAbstract PDFPubReader   ePub   
Background

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker of acute kidney injury. There is a growing body of evidence suggesting that NGAL is also a marker of kidney disease and severity in chronic kidney disease (CKD). We studied the utility of urinary NGAL in more accurately predicting renal function in patients with diabetic CKD.

Methods

We studied possible relationships between urinary NGAL, estimated glomerular filtration rate (eGFR), and proteinuria in diabetic CKD patients and in healthy populations.

Results

Urinary NGAL levels were significantly higher in CKD patients than in healthy controls (96.0 [2.7 to 975.2] ng/mL vs. 18.8 [1.3 to 81.9] ng/mL, P=0.02), and the GFR was lower among CKD patients (49.3 [13.1 to 78.3] mL/min/1.73 m2 vs. 85.6 [72 to 106.7] mL/min/1.73 m2, P<0.0001). The urinary NGAL level showed a significant inverse correlation with GFR (r=-0.5634, P<0.0001). The correlation analyses between urinary protein level and urinary NGAL levels and GFR were as follows: urine protein and urinary NGAL (r=0.3009, P=0.0256), urine protein and GFR (r=-0.6245, P<0.0001), urine microalbumin and urinary NGAL (r=0.1794, P=0.2275), and urine microalbumin and GFR (r=-0.5190, P=0.0002).

Conclusion

From these results, we concluded that urinary NGAL is a reliable marker of renal function in diabetic CKD patients. However, urinary NGAL did not provide more accurate information regarding renal function than GFR.

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Review
Role of Peroxisome Proliferator-Activated Receptor α in Diabetic Nephropathy
Sungjin Chung, Cheol Whee Park
Diabetes Metab J. 2011;35(4):327-336.   Published online August 31, 2011
DOI: https://doi.org/10.4093/dmj.2011.35.4.327
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AbstractAbstract PDFPubReader   ePub   

With a developing worldwide epidemic of diabetes mellitus, the renal complications associated with diabetes have become a serious health concern. Primary therapy for treating diabetic nephropathy is a multifactorial process. Peroxisome proliferator-activated receptor alpha (PPARα) agonists have been used primarily in clinical practice for the treatment of dyslipidemia and insulin resistance. Given that PPARα expression and regulation of metabolic pathways are involved in oxidative stress, inflammation, blood pressure regulation, and the renin-angiotensin aldosterone system, PPARα likely influences the development and pathogenesis of diabetic nephropathy via indirect effects on glucose and lipid homeostasis and also by direct action on the kidneys. These findings suggest that PPARα may become an important therapeutic target for treating diabetic renal complications.

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Original Article
Differential Activation of the Renal Renin-Angiotensin System Components in Diabetic Rats.
Woon Jung Kim, Mi Young Lee, Tae Hyung Kim, Eun Kyoung Yang, Won Jung Lee
Korean Diabetes J. 1998;22(2):218-230.   Published online January 1, 2001
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  • 19 Download
AbstractAbstract PDF
BACKGROUND
The renin-angiotensin system(RAS) plays an important role in the physiologic regulation of the renal microcirculation and may contribute to the imbalance of resistances present at the preglomerular and postglomerular sites whirh are responsible for glomerular capillary hypertension, a major injurious factor in the diabetic kidney. Blockade of angiotensin(Ang II) with angiotensin converting enzyme(ACE) inhibitor or Ang II receptor antagonists reduces glomerular injury. However, the relationship between diabetes and the RAS is unclear. METHOD: To investigate changes of gene expression of the renal renin-angiotensin system in diabetic nephropathy, mRNA levels of the RAS components were determined with the methods of Northern blot and RT-PCR in streptozotocin-induced diabetic(STZ-D) rats. Sprague-Dawley rats(240~260 g) were made diabetic by double i.p. injections of 45 mg/kg STZ. Result: Plasma renin concentration increased significantly at the onset of diabetes, and then suppressed at 4 and 8 week sof diabetes. Changes in renal renin content and mRNA levels were in parallel with plasma renin concentration during 8 weeks of diabetes. Renal angiotensinogen mRNA levels of the STZ-D rats decreased initially and then returned to the baseline with the progression of diabetes. Gene expression of angiotensin II-AT1 receptor subtypes, AT1a and AT1b, was not significantly changed during 8 wk of diabetes. Plasma and renal ACE activity increased significantly at 4 and 8 wk of diabetes. CONCLUSION: Results of the present study show a marked decrease in renal renin mRNA levels and renin concentration, but significant increase in ACE activity in chronic diabetic rats. When considering renoprotective effect of ACE inhibitors and AT receptor antagonists, the present result may suggest an increased intrarenal generation of Ang II and its pathophysiologic role in diabetic nephropathy. However, further studies are required to clarify meanings of the differential activation of the renal renin-angiotensin system components in diabetic rats.
Diabetes Metab J : Diabetes & Metabolism Journal
© Korean Diabetes Association.
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