Diabetes & Metabolism Journal

Reviews

Others
Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database: Kyung-Soo Kim, Bongseong Kim, Kyungdo Han; Diabetes Metab J. 2025;49(1):13-21. Published online January 1, 2025; DOI: https://doi.org/10.4093/dmj.2024.0780

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Abstract PDF Supplementary Material PubReader ePub: The Korean National Health Information Database (NHID), which contains nationwide real-world claims data including sociodemographic data, health care utilization data, health screening data, and healthcare provider information, is a powerful resource to test various hypotheses. It is also longitudinal in nature due to the recommended health checkup every 2 years and is appropriate for long-term follow-up study as well as evaluating the relationships between health outcomes and changes in parameters such as lifestyle factors, anthropometric measurements, and laboratory results. However, because these data are not collected for research purposes, precise operational definitions of diseases are required to facilitate big data analysis using the Korean NHID. In this review, we describe the characteristics of the Korean NHID, operational definitions of diseases used for research related to diabetes, and introduce representative research for diabetes-related diseases using the Korean NHID.

Lifestyle
Ultra-Processed Foods and the Impact on Cardiometabolic Health: The Role of Diet Quality: Xiaowen Wang, Qi Sun; Diabetes Metab J. 2024;48(6):1047-1055. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0659

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Abstract PDF PubReader ePub: The consumption of ultra-processed foods (UPFs) has surged globally, raising significant public health concerns due to their associations with a range of adverse health outcomes. This review aims to elucidate potential health impacts of UPF intake and underscore the importance of considering diet quality when interpreting study findings. UPF group, as classified by the Nova system based on the extent of industrial processing, contains numerous individual food items with a wide spectrum of nutrient profiles, as well as differential quality as reflected by their potential health effects. The quality of a given food may well misalign with the processing levels so that a UPF food can be nutritious and healthful whereas a non-UPF food can be of low quality and excess intake of which may lead to adverse health consequences. The current review argues that it is critical to focus on the nutritional content and quality of foods and their role within the overall dietary pattern rather than only the level of processing. Further research should dissect health effects of diet quality and food processing, investigate the health impacts of ingredients that render the UPF categorization, understand roles of metabolomics and the gut microbiome in mediating and modulating the health effects of food processing, and consider environmental sustainability in UPF studies. Emphasizing nutrient-dense healthful foods and dietary patterns shall remain the pivotal strategy for promoting overall health and preventing chronic diseases.

Complications
Rate-Dependent Depression of the Hoffmann Reflex: Practical Applications in Painful Diabetic Neuropathy: Lu Han, Nigel A. Calcutt, Xiajun Zhou; Diabetes Metab J. 2024;48(6):1029-1046. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0614

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Abstract PDF PubReader ePub: Measurement of the rate-dependent depression (RDD) of the Hoffmann (H) reflex, a technique developed over half a century ago, is founded on repeated stimulation of the H-reflex with tracking of sequentially evoked H-wave amplitudes in the resulting electromyogram. RDD offers insight into the integrity of spinal reflex pathways and spinal inhibitory regulation. Initially, RDD was predominantly utilized in the mechanistic exploration and evaluation of movement disorders characterized by spasticity symptoms, as may occur following spinal cord injury. However, there is increasing recognition that sensory input from the periphery is modified at the spinal level before ascending to the higher central nervous system and that some pain states can arise from, or be exaggerated by, disruption of spinal processing via a mechanism termed spinal disinhibition. This, along with the urgent clinical need to identify biological markers of pain generator and/or amplifier sites to facilitate targeted pain therapies, has prompted interest in RDD as a biomarker for the contribution of spinal disinhibition to neuropathic pain states. Current research in animals and humans with diabetes has revealed specific disorders of spinal GABAergic function associated with impaired RDD. Future investigations on RDD aim to further elucidate its underlying pathways and enhance its clinical applications.

Guideline/Fact Sheet
Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Review and Position Statement of the Fatty Liver Research Group of the Korean Diabetes Association: Jaehyun Bae, Eugene Han, Hye Won Lee, Cheol-Young Park, Choon Hee Chung, Dae Ho Lee, Eun-Hee Cho, Eun-Jung Rhee, Ji Hee Yu, Ji Hyun Park, Ji-Cheol Bae, Jung Hwan Park, Kyung Mook Choi, Kyung-Soo Kim, Mi Hae Seo, Minyoung Lee, Nan-Hee Kim, So Hun Kim, Won-Young Lee, Woo Je Lee, Yeon-Kyung Choi, Yong-ho Lee, You-Cheol Hwang, Young Sang Lyu, Byung-Wan Lee, Bong-Soo Cha, on Behalf of the Fatty Liver Research Group of the Korean Diabetes Association; Diabetes Metab J. 2024;48(6):1015-1028. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0541

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Abstract PDF PubReader ePub: Since the role of the liver in metabolic dysfunction, including type 2 diabetes mellitus, was demonstrated, studies on non-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD) have shown associations between fatty liver disease and other metabolic diseases. Unlike the exclusionary diagnostic criteria of NAFLD, MAFLD diagnosis is based on the presence of metabolic dysregulation in fatty liver disease. Renaming NAFLD as MAFLD also introduced simpler diagnostic criteria. In 2023, a new nomenclature, steatotic liver disease (SLD), was proposed. Similar to MAFLD, SLD diagnosis is based on the presence of hepatic steatosis with at least one cardiometabolic dysfunction. SLD is categorized into metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related/-associated liver disease, alcoholrelated liver disease, specific etiology SLD, and cryptogenic SLD. The term MASLD has been adopted by a number of leading national and international societies due to its concise diagnostic criteria, exclusion of other concomitant liver diseases, and lack of stigmatizing terms. This article reviews the diagnostic criteria, clinical relevance, and differences among NAFLD, MAFLD, and MASLD from a diabetologist’s perspective and provides a rationale for adopting SLD/MASLD in the Fatty Liver Research Group of the Korean Diabetes Association.

Basic Research
Systems Biology of Human Microbiome for the Prediction of Personal Glycaemic Response: Nikhil Kirtipal, Youngchang Seo, Jangwon Son, Sunjae Lee; Diabetes Metab J. 2024;48(5):821-836. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0382

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Abstract PDF PubReader ePub: The human gut microbiota is increasingly recognized as a pivotal factor in diabetes management, playing a significant role in the body’s response to treatment. However, it is important to understand that long-term usage of medicines like metformin and other diabetic treatments can result in problems, gastrointestinal discomfort, and dysbiosis of the gut flora. Advanced sequencing technologies have improved our understanding of the gut microbiome’s role in diabetes, uncovering complex interactions between microbial composition and metabolic health. We explore how the gut microbiota affects glucose metabolism and insulin sensitivity by examining a variety of -omics data, including genomics, transcriptomics, epigenomics, proteomics, metabolomics, and metagenomics. Machine learning algorithms and genome-scale modeling are now being applied to find microbiological biomarkers associated with diabetes risk, predicted disease progression, and guide customized therapy. This study holds promise for specialized diabetic therapy. Despite significant advances, some concerns remain unanswered, including understanding the complex relationship between diabetes etiology and gut microbiota, as well as developing user-friendly technological innovations. This mini-review explores the relationship between multiomics, precision medicine, and machine learning to improve our understanding of the gut microbiome’s function in diabetes. In the era of precision medicine, the ultimate goal is to improve patient outcomes through personalized treatments.

Drug/Regimen
Benefit and Safety of Sodium-Glucose Co-Transporter 2 Inhibitors in Older Patients with Type 2 Diabetes Mellitus: Ja Young Jeon, Dae Jung Kim; Diabetes Metab J. 2024;48(5):837-846. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0317

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People with type 2 diabetes mellitus (T2DM) are at higher risk of developing cardiovascular disease, heart failure, chronic kidney disease, and premature death than people without diabetes. Therefore, treatment of diabetes aims to reduce these complications. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown beneficial effects on cardiorenal and metabolic health beyond glucose control, making them a promising class of drugs for achieving the ultimate goals of diabetes treatment. However, despite their proven benefits, the use of SGLT2 inhibitors in eligible patients with T2DM remains suboptimal due to reports of adverse events. The use of SGLT2 inhibitors is particularly limited in older patients with T2DM because of the lack of treatment experience and insufficient long-term safety data. This article comprehensively reviews the risk-benefit profile of SGLT2 inhibitors in older patients with T2DM, drawing on data from prospective randomized controlled trials of cardiorenal outcomes, original studies, subgroup analyses across different age groups, and observational cohort studies.

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Trends in prescribing sodium‐glucose cotransporter 2 inhibitors for individuals with type 2 diabetes with and without cardiovascular‐renal disease in South Korea, 2015–2021
Kyoung Hwa Ha, Soyoung Shin, EunJi Na, Dae Jung Kim
Journal of Diabetes Investigation.2024;[Epub] CrossRef

Cardiovascular Risk/Epidemiology
Artificial Light at Night and Type 2 Diabetes Mellitus: Jong-Ha Baek, Yong Zhu, Chandra L. Jackson, Yong-Moon Mark Park; Diabetes Metab J. 2024;48(5):847-863. Published online September 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0237

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The widespread and pervasive use of artificial light at night (ALAN) in our modern 24-hour society has emerged as a substantial disruptor of natural circadian rhythms, potentially leading to a rise in unhealthy lifestyle-related behaviors (e.g., poor sleep; shift work). This phenomenon has been associated with an increased risk of type 2 diabetes mellitus (T2DM), which is a pressing global public health concern. However, to date, reviews summarizing associations between ALAN and T2DM have primarily focused on the limited characteristics of exposure (e.g., intensity) to ALAN. This literature review extends beyond prior reviews by consolidating recent studies from 2000 to 2024 regarding associations between both indoor and outdoor ALAN exposure and the incidence or prevalence of T2DM. We also described potential biological mechanisms through which ALAN modulates glucose metabolism. Furthermore, we outlined knowledge gaps and investigated how various ALAN characteristics beyond only light intensity (including light type, timing, duration, wavelength, and individual sensitivity) influence T2DM risk. Recognizing the detrimental impact of ALAN on sleep health and the behavioral correlates of physical activity and dietary patterns, we additionally summarized studies investigating the potential mediating role of each component in the relationship between ALAN and glucose metabolism. Lastly, we proposed implications of chronotherapies and chrononutrition for diabetes management in the context of ALAN exposure.

Citations

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Impact of bedroom light exposure on glucose metabolic markers and the role of circadian-dependent meal timing: A population-based cross-sectional study
Qi Li, Yu-xiang Xu, Xiu-zhen Lu, Yu-ting Shen, Yu-hui Wan, Pu-yu Su, Fang-biao Tao, Xin Chen, Ying Sun
Ecotoxicology and Environmental Safety.2025; 290: 117589. CrossRef
Circadian Deregulation: Back Facing the Sun Toward Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Development
Mariana Verdelho Machado
Nutrients.2024; 16(24): 4294. CrossRef

Others
T-Cell Senescence in Human Metabolic Diseases: Ha Thi Nga, Thi Linh Nguyen, Hyon-Seung Yi; Diabetes Metab J. 2024;48(5):864-881. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0140

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Immunosenescence denotes a state of dysregulated immune cell function characterized by a confluence of factors, including arrested cell cycle, telomere shortening, markers of cellular stress, mitochondrial dysfunction, loss of proteostasis, epigenetic reprogramming, and secretion of proinflammatory mediators. This state primarily manifests during the aging process but can also be induced in various pathological conditions, encompassing chronic viral infections, autoimmune diseases, and metabolic disorders. Age-associated immune system alterations extend to innate and adaptive immune cells, with T-cells exhibiting heightened susceptibility to immunosenescence. In particular, senescent T-cells have been identified in the context of metabolic disorders such as obesity, diabetes, and cardiovascular diseases. Recent investigations suggest a direct link between T-cell senescence, inflammation, and insulin resistance. The perturbation of biological homeostasis by senescent T-cells appears intricately linked to the initiation and progression of metabolic diseases, particularly through inflammation-mediated insulin resistance. Consequently, senescent T-cells are emerging as a noteworthy therapeutic target. This review aims to elucidate the intricate relationship between metabolic diseases and T-cell senescence, providing insights into the potential roles of senescent T-cells in the pathogenesis of metabolic disorders. Through a comprehensive examination of current research findings, this review seeks to contribute to a deeper understanding of the complex interplay between immunosenescence and metabolic health.

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The immune health assessment technique of the elderly population and its application and promotion in the prevention and treatment of common aged diseases
Qing Li, Ling-bing Meng
Journal of Aging and Rehabilitation.2024; 1(4): 93. CrossRef

Others
Holistic and Personalized Strategies for Managing in Elderly Type 2 Diabetes Patients: Jae-Seung Yun, Kyuho Kim, Yu-Bae Ahn, Kyungdo Han, Seung-Hyun Ko; Diabetes Metab J. 2024;48(4):531-545. Published online July 26, 2024; DOI: https://doi.org/10.4093/dmj.2024.0310

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Abstract PDF PubReader ePub: Due to increased life expectancy and lifestyle changes, the prevalence of diabetes among the elderly in Korea is continuously rising, as is the associated public health burden. Diabetes management in elderly patients is complicated by age-related physiological changes, sarcopenia characterized by loss of muscle mass and function, comorbidities, and varying levels of functional, cognitive, and mobility abilities that lead to frailty. Moreover, elderly patients with diabetes frequently face multiple chronic conditions that elevate their risk of cardiovascular diseases, cancer, and mortality; they are also prone to complications such as hyperglycemic hyperosmolar state, diabetic ketoacidosis, and severe hypoglycemia. This review examines the characteristics of and management approaches for diabetes in the elderly, and advocates for a comprehensive yet personalized strategy.

Others
Korean National Burden of Disease: The Importance of Diabetes Management: Chung-Nyun Kim, Yoon-Sun Jung, Young-Eun Kim, Minsu Ock, Seok-Jun Yoon; Diabetes Metab J. 2024;48(4):518-530. Published online July 26, 2024; DOI: https://doi.org/10.4093/dmj.2024.0087

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Abstract PDF PubReader ePub: Diagnosing the current health status and disease burden in a population is crucial for public health interventions. The ability to compare the burden of different diseases through a single measure, such as disability-adjusted life years has become feasible and continues to be produced and updated through the Global Burden of Diseases (GBD) study. However, the disease burden values of the GBD study do not accurately reflect the unique situation in a specific country with various circumstances. In response, the Korean National Burden of Disease (KNBD) study was conducted to estimate the disease burden in Koreans by considering Korea’s cultural context and utilizing the available data sources at the national level. Both studies identified non-communicable diseases, such as diabetes mellitus (DM), as the primary cause of disease burden among Koreans. However, the extent of public health interventions currently being conducted by the central and local governments does not align with the severity of the disease burden. This review suggests that despite the high burden of DM in South Korea, the current policies may not fully address its impact, underscoring the need for expanded chronic disease management programs and a shift towards prevention-focused healthcare paradigms.

Basic Research
Protein Arginine Methyltransferases: Emerging Targets in Cardiovascular and Metabolic Disease: Yan Zhang, Shibo Wei, Eun-Ju Jin, Yunju Jo, Chang-Myung Oh, Gyu-Un Bae, Jong-Sun Kang, Dongryeol Ryu; Diabetes Metab J. 2024;48(4):487-502. Published online July 24, 2024; DOI: https://doi.org/10.4093/dmj.2023.0362

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Abstract PDF PubReader ePub: Cardiovascular diseases (CVDs) and metabolic disorders stand as formidable challenges that significantly impact the clinical outcomes and living quality for afflicted individuals. An intricate comprehension of the underlying mechanisms is paramount for the development of efficacious therapeutic strategies. Protein arginine methyltransferases (PRMTs), a class of enzymes responsible for the precise regulation of protein methylation, have ascended to pivotal roles and emerged as crucial regulators within the intrinsic pathophysiology of these diseases. Herein, we review recent advancements in research elucidating on the multifaceted involvements of PRMTs in cardiovascular system and metabolic diseases, contributing significantly to deepen our understanding of the pathogenesis and progression of these maladies. In addition, this review provides a comprehensive analysis to unveil the distinctive roles of PRMTs across diverse cell types implicated in cardiovascular and metabolic disorders, which holds great potential to reveal novel therapeutic interventions targeting PRMTs, thus presenting promising perspectives to effectively address the substantial global burden imposed by CVDs and metabolic disorders.

Metabolic Risk/Epidemiology
Glucagon-Like Peptide-1: New Regulator in Lipid Metabolism: Tong Bu, Ziyan Sun, Yi Pan, Xia Deng, Guoyue Yuan; Diabetes Metab J. 2024;48(3):354-372. Published online April 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0277

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Glucagon-like peptide-1 (GLP-1) is a 30-amino acid peptide hormone that is mainly expressed in the intestine and hypothalamus. In recent years, basic and clinical studies have shown that GLP-1 is closely related to lipid metabolism, and it can participate in lipid metabolism by inhibiting fat synthesis, promoting fat differentiation, enhancing cholesterol metabolism, and promoting adipose browning. GLP-1 plays a key role in the occurrence and development of metabolic diseases such as obesity, nonalcoholic fatty liver disease, and atherosclerosis by regulating lipid metabolism. It is expected to become a new target for the treatment of metabolic disorders. The effects of GLP-1 and dual agonists on lipid metabolism also provide a more complete treatment plan for metabolic diseases. This article reviews the recent research progress of GLP-1 in lipid metabolism.

Citations

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Lipoprotein(a) in atherosclerotic cardiovascular disease, type 2 diabetes, and liver disease
Kathryn L. Williams, Maya Augustine, Eru Sujakhu, Justine Magadia, Lindsay Crawford, Aimee Knott, Skyler Hamilton, Uzoma Obiaka
Progress in Pediatric Cardiology.2025; 76: 101775. CrossRef
The protective effects of liraglutide in reducing lipid droplets accumulation and myocardial fibrosis in diabetic cardiomyopathy
Chien-Yin Kuo, Sing-Hua Tsou, Edy Kornelius, Kuei-Chuan Chan, Kai-Wei Chang, Jung-Chi Li, Chien-Ning Huang, Chih-Li Lin
Cellular and Molecular Life Sciences.2025;[Epub] CrossRef
An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance and long-term hypoglycemic and lipid metabolic benefits
Laxman Subedi, Arjun Dhwoj Bamjan, Susmita Phuyal, Jung-Hyun Shim, Seung-Sik Cho, Jong Bae Seo, Kwan-Young Chang, Youngro Byun, Seho Kweon, Jin Woo Park
Journal of Controlled Release.2025; 378: 637. CrossRef
Diabetes and Osteoarthritis: Exploring the Interactions and Therapeutic Implications of Insulin, Metformin, and GLP-1-Based Interventions
Iryna Halabitska, Liliia Babinets, Valentyn Oksenych, Oleksandr Kamyshnyi
Biomedicines.2024; 12(8): 1630. CrossRef
The Effect of Tirzepatide on Body Composition in People with Overweight and Obesity: A Systematic Review of Randomized, Controlled Studies
Vincenzo Rochira, Carla Greco, Stefano Boni, Francesco Costantino, Leonardo Dalla Valentina, Eleonora Zanni, Leila Itani, Marwan El Ghoch
Diseases.2024; 12(9): 204. CrossRef
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy
Zhikai Zheng, Yao Zong, Yiyang Ma, Yucheng Tian, Yidan Pang, Changqing Zhang, Junjie Gao
Signal Transduction and Targeted Therapy.2024;[Epub] CrossRef
Recent Advances and Therapeutic Benefits of Glucagon-Like Peptide-1 (GLP-1) Agonists in the Management of Type 2 Diabetes and Associated Metabolic Disorders
John O Olukorode, Dolapo A Orimoloye, Nwachukwu O Nwachukwu, Chidera N Onwuzo, Praise O Oloyede, Temiloluwa Fayemi, Oluwatobi S Odunaike, Petra S Ayobami-Ojo, Nwachi Divine, Demilade J Alo, Chukwurah U Alex
Cureus.2024;[Epub] CrossRef
Incretin hormones: Revolutionizing the treatment landscape for kidney and liver diseases in type 2 diabetes and obesity
Jae Hyun Bae, Young Min Cho
Journal of Diabetes Investigation.2024;[Epub] CrossRef
Interactions between glucagon like peptide 1 (GLP-1) and estrogens regulates lipid metabolism
Jorge F.A. Model, Rafaella S. Normann, Éverton L. Vogt, Maiza Von Dentz, Marjoriane de Amaral, Rui Xu, Tsvetan Bachvaroff, Poli Mara Spritzer, J. Sook Chung, Anapaula S. Vinagre
Biochemical Pharmacology.2024; 230: 116623. CrossRef
Changes in 24-Hour Urine Chemistry in Patients with Nephrolithiasis during Weight Loss with Glucagon-Like Peptide 1–Based Therapies
Karen Feghali, Xilong Li, Naim M. Maalouf
Kidney360.2024; 5(11): 1706. CrossRef
Liuweizhiji Gegen-Sangshen beverage protects against alcoholic liver disease in mice through the gut microbiota mediated SCFAs/GPR43/GLP-1 pathway
Mingyun Tang, Long Zhao, Fuchun Huang, Tiangang Wang, Xu Wu, Shanshan Chen, Juan Fu, Chaoli Jiang, Shulin Wei, Xuseng Zeng, Xiaoling Zhang, Xin Zhou, Mei Wei, Zhi Li, Guohui Xiao
Frontiers in Nutrition.2024;[Epub] CrossRef
Spotlight on the Mechanism of Action of Semaglutide
Ilias Papakonstantinou, Konstantinos Tsioufis, Vasiliki Katsi
Current Issues in Molecular Biology.2024; 46(12): 14514. CrossRef

Basic Research
Roles of Histone Deacetylase 4 in the Inflammatory and Metabolic Processes: Hyunju Kang, Young-Ki Park, Ji-Young Lee, Minkyung Bae; Diabetes Metab J. 2024;48(3):340-353. Published online March 22, 2024; DOI: https://doi.org/10.4093/dmj.2023.0174

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Histone deacetylase 4 (HDAC4), a class IIa HDAC, has gained attention as a potential therapeutic target in treating inflammatory and metabolic processes based on its essential role in various biological pathways by deacetylating non-histone proteins, including transcription factors. The activity of HDAC4 is regulated at the transcriptional, post-transcriptional, and post-translational levels. The functions of HDAC4 are tissue-dependent in response to endogenous and exogenous factors and their substrates. In particular, the association of HDAC4 with non-histone targets, including transcription factors, such as myocyte enhancer factor 2, hypoxia-inducible factor, signal transducer and activator of transcription 1, and forkhead box proteins, play a crucial role in regulating inflammatory and metabolic processes. This review summarizes the regulatory modes of HDAC4 activity and its functions in inflammation, insulin signaling and glucose metabolism, and cardiac muscle development.

Citations

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Butyrate Supplementation Improves Intestinal Health and Growth Performance in Livestock: A Review
Wenting Chen, Qingshan Ma, Yan Li, Lin Wei, Zhenwei Zhang, Adnan Khan, Muhammad Zahoor Khan, Changfa Wang
Biomolecules.2025; 15(1): 85. CrossRef

Metabolic Risk/Epidemiology
One-Carbon Metabolism Nutrients, Genetic Variation, and Diabetes Mellitus: Jie Zhu, Gunjana Saikia, Xiaotao Zhang, Xiaoxi Shen, Ka Kahe; Diabetes Metab J. 2024;48(2):170-183. Published online March 12, 2024; DOI: https://doi.org/10.4093/dmj.2023.0272

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Abstract PDF Supplementary Material PubReader ePub

Diabetes mellitus (DM) affects about 9.3% of the population globally. Hyperhomocysteinemia (HHcy) has been implicated in the pathogenesis of DM, owing to its promotion of oxidative stress, β-cell dysfunction, and insulin resistance. HHcy can result from low status of one-carbon metabolism (OCM) nutrients (e.g., folate, choline, betaine, vitamin B6, B12), which work together to degrade homocysteine by methylation. The etiology of HHcy may also involve genetic variation encoding key enzymes in OCM. This review aimed to provide an overview of the existing literature assessing the link between OCM nutrients status, related genetic factors, and incident DM. We also discussed possible mechanisms underlying the role of OCM in DM development and provided recommendations for future research and practice. Even though the available evidence remains inconsistent, some studies support the potential beneficial effects of intakes or blood levels of OCM nutrients on DM development. Moreover, certain variants in OCM-related genes may influence metabolic handling of methyl-donors and presumably incidental DM. Future studies are warranted to establish the causal inference between OCM and DM and examine the interaction of OCM nutrients and genetic factors with DM development, which will inform the personalized recommendations for OCM nutrients intakes on DM prevention.

Citations

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Vitamin B12 is correlated with insulin resistance and metabolism disorder markers in women with recurrent pregnancy loss
Xujing Deng, Dengke Qin, Qiuhong Ding, Liying Peng, Guohua Li, Shihua Bao
Journal of Gynecology Obstetrics and Human Reproduction.2025; 54(1): 102864. CrossRef
Association between chronic kidney disease and oxidative balance score: National Health and Nutrition Examination Survey (NHANES) 2005–2018
Cong Liu, Jiju Yang, Hongdian Li, Yuanyuan Deng, Pengfei He, Jiao Zhang, Mianzhi Zhang
Frontiers in Nutrition.2025;[Epub] CrossRef
Alterations in Choline Metabolism in Non-Obese Individuals with Insulin Resistance and Type 2 Diabetes Mellitus
Haya Al-Sulaiti, Najeha Anwardeen, Sara S. Bashraheel, Khaled Naja, Mohamed A. Elrayess
Metabolites.2024; 14(8): 457. CrossRef
Association between oxidative balance score and diabetic kidney disease, low estimated glomerular filtration rate and albuminuria in type 2 diabetes mellitus patients: a cross-sectional study
Cong Liu, Jiju Yang, Hongdian Li, Yuanyuan Deng, Pengfei He, Jiao Zhang, Mianzhi Zhang
Frontiers in Endocrinology.2024;[Epub] CrossRef
Choline Metabolites and 15-Year Risk of Incident Diabetes in a Prospective Cohort of Adults: Coronary Artery Risk Development in Young Adults (CARDIA) Study
Jessica K. Sprinkles, Anju Lulla, Autumn G. Hullings, Isis Trujillo-Gonzalez, Kevin C. Klatt, David R. Jacobs, Ravi V. Shah, Venkatesh L. Murthy, Annie Green Howard, Penny Gordon-Larsen, Katie A. Meyer
Diabetes Care.2024; 47(11): 1985. CrossRef
Hyperhomocysteinemia and Disease—Is 10 μmol/L a Suitable New Threshold Limit?
Giada Marroncini, Serena Martinelli, Sara Menchetti, Francesco Bombardiere, Francesco Saverio Martelli
International Journal of Molecular Sciences.2024; 25(22): 12295. CrossRef
The roles of the gut microbiota, metabolites, and epigenetics in the effects of maternal exercise on offspring metabolism
Jing Ren, Liyuan Zhou, Shunhua Li, Qian Zhang, Xinhua Xiao
American Journal of Physiology-Endocrinology and Metabolism.2024; 327(6): E760. CrossRef

Pathophysiology
Dysfunctional Mitochondria Clearance in Situ: Mitophagy in Obesity and Diabetes-Associated Cardiometabolic Diseases: Songling Tang, Di Hao, Wen Ma, Lian Liu, Jiuyu Gao, Peng Yao, Haifang Yu, Lu Gan, Yu Cao; Diabetes Metab J. 2024;48(4):503-517. Published online February 15, 2024; DOI: https://doi.org/10.4093/dmj.2023.0213

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Several mitochondrial dysfunctions in obesity and diabetes include impaired mitochondrial membrane potential, excessive mitochondrial reactive oxygen species generation, reduced mitochondrial DNA, increased mitochondrial Ca²⁺ flux, and mitochondrial dynamics disorders. Mitophagy, specialized autophagy, is responsible for clearing dysfunctional mitochondria in physiological and pathological conditions. As a paradox, inhibition and activation of mitophagy have been observed in obesity and diabetes-related heart disorders, with both exerting bidirectional effects. Suppressed mitophagy is beneficial to mitochondrial homeostasis, also known as benign mitophagy. On the contrary, in most cases, excessive mitophagy is harmful to dysfunctional mitochondria elimination and thus is defined as detrimental mitophagy. In obesity and diabetes, two classical pathways appear to regulate mitophagy, including PTEN-induced putative kinase 1 (PINK1)/Parkin-dependent mitophagy and receptors/adapters-dependent mitophagy. After the pharmacologic interventions of mitophagy, mitochondrial morphology and function have been restored, and cell viability has been further improved. Herein, we summarize the mitochondrial dysfunction and mitophagy alterations in obesity and diabetes, as well as the underlying upstream mechanisms, in order to provide novel therapeutic strategies for the obesity and diabetes-related heart disorders.

Citations

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Mitophagy in the Pathogenesis of Obesity-Associated Cardiovascular Diseases: New Mechanistic and Therapeutic Insights
Kexin Huang, Jun Ren
Trends in Medical Research.2024; 19(1): 112. CrossRef
A review: Polysaccharides targeting mitochondria to improve obesity
Yongchao Chen, Rong Gao, Jun Fang, Sujuan Ding
International Journal of Biological Macromolecules.2024; 277: 134448. CrossRef
Iron chelators as mitophagy agents: Potential and limitations
Tereza Brogyanyi, Zdeněk Kejík, Kateřina Veselá, Petr Dytrych, David Hoskovec, Michal Masařik, Petr Babula, Robert Kaplánek, Tomáš Přibyl, Jaroslav Zelenka, Tomáš Ruml, Martin Vokurka, Pavel Martásek, Milan Jakubek
Biomedicine & Pharmacotherapy.2024; 179: 117407. CrossRef
Influence of Mitochondrial NAD(P) + Transhydrogenase (NNT) on Hypothalamic Inflammation and Metabolic Dysfunction Induced by a High-Fat Diet in Mice
Giovanna Leite Santos, Ericka Francislaine Dias Costa, Ana Paula Dalla Costa, Ariane Maria Zanesco, Marcela Reymond Simoes, Fábio Rogério, Daniele Masselli Rodrigues Demolin, Claudia Daniele Carvalho Navarro, Lício Augusto Velloso, Annelise Francisco, Rog
Hormone and Metabolic Research.2024;[Epub] CrossRef

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