Diabetes & Metabolism Journal

Original Articles

Cardiovascular Risk/Epidemiology
Oxidized Lipoproteins as Independent Predictors of Major Adverse Cardiovascular Events in Type 2 Diabetes Mellitus with Coronary Heart Disease: A Multicenter Prospective Cohort Study: Jun-Xu Gu, Juan Huang, Ai-Min Zhang, Yue Yin, Zi-Wei Wang, Hui-Zhang Bao, Shan-Shan Li, Na Zhang, Li Qin, Zhi-Hong Yue, Kun Wang, Mei Jia, Chun-Yan Wang, Lin Pei, Ming Su; Received October 15, 2025 Accepted February 6, 2026 Published online May 12, 2026; DOI: https://doi.org/10.4093/dmj.2025.1029 [Epub ahead of print]

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Background
Oxidized lipoproteins contribute to atherosclerosis and metabolic dysfunction; however, their prognostic significance for major adverse cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM) and coexisting coronary heart disease (CHD) remains unclear.
Methods
This multicenter cohort included 3,733 patients with angiographically confirmed T2DM-CHD, followed for 5 years. Baseline circulating oxidized high-density lipoprotein cholesterol (ox-HDL-C), oxidized low-density lipoprotein cholesterol (ox- LDL-C), and oxidized lipoprotein(a) (ox-Lp(a)) were measured, and associations with coronary severity, β-cell function, and MACEs were analyzed using Cox regression, Kaplan-Meier, and restricted cubic spline models.
Results
Patients with MACEs had higher baseline ox-HDL-C, ox-LDL-C, and ox-Lp(a), correlating with greater coronary lesion burden and impaired β-cell function. Restricted cubic spline analyses revealed nonlinear, dose-dependent associations, with MACEs risk increasing above thresholds of 19.88 ng/mL (ox-HDL-C), 25.71 ng/mL (ox-LDL-C), and 19.96 μmol/L (ox-Lp(a)), with sexspecific differences observed. In Cox proportional hazards models, individuals in the highest quartile of oxidized lipoproteins had significantly elevated 5-year MACEs risk compared to those in the lowest quartile, and these associations remained robust after adjusting for confounders (ox-HDL-C: adjust hazard ratio [HR], 1.872; 95% confidence interval [CI], 1.408 to 2.489; P<0.001; ox- LDL-C: adjust HR, 2.239; 95% CI, 1.686 to 2.974; P<0.001; ox-Lp(a): adjust HR, 1.917; 95% CI, 1.442 to 2.549; P<0.001).
Conclusion
Oxidized lipoproteins are independent predictors of MACEs in patients with T2DM-CHD and reflect vascular and metabolic dysfunction. Incorporating oxidized lipoprotein profiling into clinical risk assessment may improve early identification of high-risk individuals and guide preventive strategies.

Citations

Citations to this article as recorded by

Global research trends and hotspots evolution in type 2 diabetes mellitus complicated with coronary heart disease: a bibliometric analysis from 2016 to 2026
Chunying He, Xiaohua Hu, Xiaolan Yin, Min Zhan, WeiYi Cao, Rui Li
Frontiers in Endocrinology.2026;[Epub] CrossRef
Reconceptualizing Dyslipidemia: Diversity of Lipid Imbalances and Their Clinical Implications; A Narrative Review
Ali Mansoursamaei, Amirhossein Yadegar, Fatemeh Mohammadi, Seyed Arsalan Seyedi, Soghra Rabizadeh, Sahar Karimpour Reyhan, Alireza Esteghamati, Manouchehr Nakhjavani
Health Science Reports.2026;[Epub] CrossRef

Basic Research
Extracellular Vimentin Alters Energy Metabolism And Induces Adipocyte Hypertrophy: Ji-Hae Park, Soyeon Kwon, Young Mi Park; Diabetes Metab J. 2024;48(2):215-230. Published online September 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0332

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Background
Previous studies have reported that oxidative stress contributes to obesity characterized by adipocyte hypertrophy. However, mechanism has not been studied extensively. In the current study, we evaluated role of extracellular vimentin secreted by oxidized low-density lipoprotein (oxLDL) in energy metabolism in adipocytes.
Methods
We treated 3T3-L1-derived adipocytes with oxLDL and measured vimentin which was secreted in the media. We evaluated changes in uptake of glucose and free fatty acid, expression of molecules functioning in energy metabolism, synthesis of adenosine triphosphate (ATP) and lactate, markers for endoplasmic reticulum (ER) stress and autophagy in adipocytes treated with recombinant vimentin.
Results
Adipocytes secreted vimentin in response to oxLDL. Microscopic evaluation revealed that vimentin treatment induced increase in adipocyte size and increase in sizes of intracellular lipid droplets with increased intracellular triglyceride. Adipocytes treated with vimentin showed increased uptake of glucose and free fatty acid with increased expression of plasma membrane glucose transporter type 1 (GLUT1), GLUT4, and CD36. Vimentin treatment increased transcription of GLUT1 and hypoxia-inducible factor 1α (Hif-1α) but decreased GLUT4 transcription. Adipose triglyceride lipase (ATGL), peroxisome proliferator-activated receptor γ (PPARγ), sterol regulatory element-binding protein 1 (SREBP1), diacylglycerol O-acyltransferase 1 (DGAT1) and 2 were decreased by vimentin treatment. Markers for ER stress were increased and autophagy was impaired in vimentin-treated adipocytes. No change was observed in synthesis of ATP and lactate in the adipocytes treated with vimentin.
Conclusion
We concluded that extracellular vimentin regulates expression of molecules in energy metabolism and promotes adipocyte hypertrophy. Our results show that vimentin functions in the interplay between oxidative stress and metabolism, suggesting a mechanism by which adipocyte hypertrophy is induced in oxidative stress.

Citations

Citations to this article as recorded by

Modulating Vimentin: A Systems-Level Therapeutic Strategy for Sepsis and Complex Diseases
Ruihuan Chen, Jianping Wu, Daniel Jafari, Annica K. B. Gad
Life.2026; 16(3): 457. CrossRef
Regulation of adipocyte metabolism: molecular mechanisms and pharmacological potential
Jianmei Yang, Jinsong Liu, Tingting Xu, Xiangbo Xie, Rui Fang, Lingyu Li, Chen Chen
Biochemical Pharmacology.2026; 253: 118337. CrossRef
The Mechanobiology of Adipocyte Hypertrophy: Cytoskeletal Remodelling as a Driver of Insulin Resistance in Obesity
Dhakshmi Sasankan, Renu Mohan
Cell Biochemistry and Function.2026;[Epub] CrossRef
Context-specific fatty acid uptake is a finely-tuned multi-level effort
Juan Wang, Huiling Guo, Lang-Fan Zheng, Peng Li, Tong-Jin Zhao
Trends in Endocrinology & Metabolism.2025; 36(6): 577. CrossRef
The unconventional role of vimentin intermediate filaments
Xinyi Huang, Shuangshuang Zhao, Yifan Xing, Xuedi Gao, Chenglin Miao, Yuhan Huang, Yaming Jiu
Current Opinion in Cell Biology.2025; 93: 102483. CrossRef
TRIM59 deficiency aggravates HFD-induced obesity in mice associated with increased adipose tissue inflammation, lipid accumulation, and apoptosis
Yinni Chen, Xiangnuo Han, Tongzhan Liu, Yuqi Ni, Xinxin Deng, Wenhan Wei, Meixiu Jiang
Cellular Signalling.2025; 134: 111954. CrossRef
Novel secreted regulators of glucose and lipid metabolism in the development of metabolic diseases
Lianna W. Wat, Katrin J. Svensson
Diabetologia.2024; 67(12): 2626. CrossRef
Mechanobiology in Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity
Emily L. Rudolph, LiKang Chin
Current Issues in Molecular Biology.2024; 46(7): 7134. CrossRef
The Functions of SARS-CoV-2 Receptors in Diabetes-Related Severe COVID-19
Adam Drzymała
International Journal of Molecular Sciences.2024; 25(17): 9635. CrossRef
The effect of radiofrequency treatment on insulin resistance in obese post-menopausal women: a randomized controlled trial
Shymaa Mohammed Abdo, Salwa M El-Badry, Wessam Ali Al-kholy, Dalia M Kamel, Hossam H Salem, Mona Ahmed Abdulmohsen
Physical Rehabilitation and Recreational Health Technologies.2024; 9(3): 161. CrossRef

Effect of Oxidized LDL on Neutrophil Adhesion and Transendothelial Migration.: Seok Man Son, In Ju Kim, Yong Ki Kim; Korean Diabetes J. 1999;23(1):12-24. Published online January 1, 2001

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Abstract PDF: BACKGROUND
It is well recognized that oxidized low density lipoproteins (ox-LDL) play a critical role in the pathogenesis of atherosclerosis. The activation of circulating leukocytes and their adhesion to the vascular endothelium in response to acute stimuli characterize the first step in initiation of an acute inflammatory response. Through the action of degranulation products, adherent leukocytes induce vascular hyperpermeability and contribute to vascular injury. So, we have investigated the neutrophil adhesion to vascular endothelium, a constant feature of early atherogenesis and transendothelial migration of neutrophil induced by ox-LDL. METHOD: In a series of experiments, human umbilical vascular endothelial cells (HUVECs) were incubated for 24 h after addition of native human LDL (100 ug/mL) and of ox-LDL (100 ug/mL) to the medium. The adherence of 51Cr-labeled neutrophils to endothelial monolayers was measured by neutrophil adhesion assay. For diapedesis experiments, HUVECs were grown to confluence on 8.0um pore cell culture inserts. 51Cr-labeled neutrophils were added to the apical surface of HUVEC monolayers and allowed to migrate into the lower chamber for 3 h under the same preparations of native and oxidized LDLs. Reaults: The secretion of IL-8 depended on the concentration of IL-1a and LPS used to stimulate endothelial monolayers in vitro. In addition, ox-LDL triggered secretion of IL-8 from cultured HUVECs compared to that of n-LDL (867.6 pg/mL vs. 273.1 pg/mL, p<0.01). Increased adherence of neutrophils to HUVECs vs observed with ox-LDL preparation compared to native LDL preparation (36.8+1.5% vs. 25.9+1.7%, p<0.05). Similarly, neutrophil migration across cultured endothelial monolayers was also significantly increased by ox-LDL (48.7+3.8% vs. 34.4+2.9%, p<0.05). CONCLUSION: These results show that ox-LD1. can induce increased neutrophil adhesion and migration through IL-8, a potent effector of neutophil functions, secreted by stimulated endothelial cells. So, we suggest that ox-LDL may affect many components of the atherogenic process, including the early step in the initiation of m acute inflammation of vascular endothelial cells.

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