Diabetes & Metabolism Journal

Review

Basic and Translational Research
Extracellular Vesicle-Mediated Network in the Pathogenesis of Obesity, Diabetes, Steatotic Liver Disease, and Cardiovascular Disease: Joonyub Lee, Won Gun Choi, Marie Rhee, Seung-Hwan Lee; Diabetes Metab J. 2025;49(3):348-367. Published online May 1, 2025; DOI: https://doi.org/10.4093/dmj.2025.0184

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Abstract PDF: Extracellular vesicles (EVs) are lipid bilayer-enclosed particles carrying bioactive cargo, including nucleic acids, proteins, and lipids, facilitating intercellular and interorgan communication. In addition to traditional mediators such as hormones, metabolites, and cytokines, increasing evidence suggests that EVs are key modulators in various physiological and pathological processes, particularly influencing metabolic homeostasis and contributing to the progression of cardiometabolic diseases. This review provides an overview of the most recent insights into EV-mediated mechanisms involved in the pathogenesis of obesity, insulin resistance, diabetes mellitus, steatotic liver disease, atherosclerosis, and cardiovascular disease. EVs play a critical role in modulating insulin sensitivity, glucose homeostasis, systemic inflammation, and vascular health by transferring functional molecules to target cells. Understanding the EV-mediated network offers potential for identifying novel biomarkers and therapeutic targets, providing opportunities for EV-based interventions in cardiometabolic disease management. Although many challenges remain, this evolving field highlights the need for further research into EV biology and its translational applications in cardiovascular and metabolic health.

Original Articles

Complications
Does 10-Year Atherosclerotic Cardiovascular Disease Risk Predict Incident Diabetic Nephropathy and Retinopathy in Patients with Type 2 Diabetes Mellitus? Results from Two Prospective Cohort Studies in Southern China: Jiaheng Chen, Yu Ting Li, Zimin Niu, Zhanpeng He, Yao Jie Xie, Jose Hernandez, Wenyong Huang, Harry H.X. Wang, on Behalf of the Guangzhou Diabetic Eye Study Group; Diabetes Metab J. 2025;49(2):298-310. Published online February 4, 2025; DOI: https://doi.org/10.4093/dmj.2024.0239

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Background
Diabetic macrovascular and microvascular complications often coexist and may share similar risk factors and pathological pathways. We aimed to investigate whether 10-year atherosclerotic cardiovascular disease (ASCVD) risk, which is commonly assessed in diabetes management, can predict incident diabetic nephropathy (DN) and retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM).
Methods
This prospective cohort study enrolled 2,891 patients with clinically diagnosed T2DM who were free of ASCVD, nephropathy, or retinopathy at baseline in the Guangzhou (2017–2022) and Shaoguan (2019–2021) Diabetic Eye Study in southern China. The 10-year ASCVD risk was calculated by the Prediction for ASCVD Risk in China (China-PAR) equations. Multivariable- adjusted Cox proportional hazard models were developed to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). The area under the receiver operating characteristic curve (AUC) was used to evaluate predictive capability.
Results
During follow-up, a total of 171 cases of DN and 532 cases of DR were documented. Each 1% increment in 10-year ASCVD risk was associated with increased risk of DN (pooled HR, 1.122; 95% CI, 1.094 to 1.150) but not DR (pooled HR, 0.996; 95% CI, 0.979 to 1.013). The model demonstrated acceptable performance in predicting new-onset DN (pooled AUC, 0.670; 95% CI, 0.628 to 0.715). These results were consistent across cohorts and subgroups, with the association appearing to be more pronounced in women.
Conclusion
Ten-year ASCVD risk predicts incident DN but not DR in our study population with T2DM. Regular monitoring of ASCVD risk in routine diabetes practice may add to the ability to enhance population-based prevention for both macrovascular and microvascular diseases, particularly among women.

Citations

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Investigation of the Potential Association Between Atherosclerotic Cardiovascular Disease Risk Score and Diabetic Retinopathy in Patients with Type 2 Diabetes: A Cross-Sectional Study
Chrysa Agapitou, Theodoros N. Sergentanis, Effie G. Papageorgiou, Panagiotis Theodossiadis, Ignatios Ikonomidis, Vaia Lambadiari, Irini Chatziralli
Biomedicines.2025; 13(3): 633. CrossRef

Pharmacotherapy
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

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Abstract PDF Supplementary Material PubReader 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.

Cardiovascular Risk/Epidemiology
Cardiovascular Disease & Diabetes Statistics in Korea: Nationwide Data 2010 to 2019: Jin Hwa Kim, Junyeop Lee, Kyungdo Han, Jae-Taek Kim, Hyuk-Sang Kwon, on Behalf of the Diabetic Vascular Disease Research Group of the Korean Diabetes Association; Diabetes Metab J. 2024;48(6):1084-1092. Published online November 1, 2024; DOI: https://doi.org/10.4093/dmj.2024.0275

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Background
This study aimed to provide updated insights into the incidence and management of cardiovascular disease (CVD) in Korean adults with diabetes.
Methods
Using data from the Korean National Health Insurance Service and Korea National Health and Nutrition Examination Survey, we analyzed the representative national estimates of CVD in adults with diabetes.
Results
The age- and sex-standardized incidence rate of ischemic heart disease (IHD), ischemic stroke, and peripheral artery disease (PAD) decreased from 2010 to 2019 in individuals with type 2 diabetes mellitus (T2DM). However, an increase in the incidence of heart failure (HF) was observed during the same period. Only 4.96% of adults with diabetes and CVD achieved optimal control of all three risk factors (glycemic levels, blood pressure, and lipid control). Additionally, high-intensity statin treatment rates were 8.84% and 9.15% in individuals with IHD and ischemic stroke, respectively. Treatment with a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a glucagon-like peptide-1 receptor agonist (GLP-1RA) was relatively low in 2019, with only 11.87%, 7.10%, and 11.05% of individuals with IHD, ischemic stroke, and HF, respectively, receiving SGLT2i treatment. Furthermore, only 1.08%, 0.79%, and 1.06% of patients with IHD, ischemic stroke, and HF, respectively, were treated with GLP-1RA.
Conclusion
The incidence of most CVD (IHD, ischemic stroke, and PAD) decreased between 2010 and 2019, whereas the incidence of HF increased. The overall use of high-intensity statins, SGLT2i, and GLP-1RA remained low among individuals with T2DM and CVD.

Citations

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Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database
Kyung-Soo Kim, Bongseong Kim, Kyungdo Han
Diabetes & Metabolism Journal.2025; 49(1): 13. CrossRef

Review

Pathophysiology
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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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.

Citations

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Protein Arginine Methyltransferase 1: A Multi-Purpose Player in the Development of Cancer and Metabolic Disease
Daphne de Korte, Menno Hoekstra
Biomolecules.2025; 15(2): 185. CrossRef
Arginine Methylation by PRMT1 Affects ADAMTS13 Secretion and Enzymatic Activity
Szumam Liu, Min Ma, Jun Qu, Joshua Muia, Zhijian Wu, Quintijn Bonnez, Karen Vanhoorelbeke, Liang Zheng, Xinyang Zhao, X. Long Zheng
Arteriosclerosis, Thrombosis, and Vascular Biology.2025; 45(4): 506. CrossRef

Original Articles

Cardiovascular Risk/Epidemiology
Social Determinants of Health and Cardiovascular Risk among Adults with Diabetes: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study: Lisa Zhang, Evgeniya Reshetnyak, Joanna B. Ringel, Laura C. Pinheiro, April Carson, Doyle M. Cummings, Raegan W. Durant, Gargya Malla, Monika M. Safford; Diabetes Metab J. 2024;48(6):1073-1083. Published online July 22, 2024; DOI: https://doi.org/10.4093/dmj.2023.0380

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Abstract PDF Supplementary Material PubReader ePub: Background
Social determinants of health (SDOH) have been associated with diabetes risk; however, their association with cardiovascular disease (CVD) events in individuals with diabetes is poorly described. We hypothesized that a greater number of SDOH among individuals with diabetes would be associated with a higher risk of CVD events.
Methods
The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is a national, biracial cohort of 30,239 individuals ≥45 years old recruited in 2003–2007. We included 6,322 participants with diabetes at baseline, defined as healthcare professional diagnosis, diabetes medication use, or blood glucose values. Seven SDOH that were individually associated with CVD events were included (P<0.20). The outcome was CVD events, a composite of expert-adjudicated myocardial infarction, stroke, or cardiovascular death. We estimated Cox proportional hazard models to examine associations between number of SDOH (0, 1, 2, ≥3) and CVD events.
Results
In an age and sex adjusted model, the presence of multiple SDOH significantly increased the risk of any CVD event (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.26 to 1.74 for two SDOH; HR, 1.68; 95% CI, 1.43 to 1.96 for ≥3 SDOH). This finding was attenuated but remained statistically significant in a fully adjusted model (HR, 1.19; 95% CI, 1.01 to 1.40 for two SDOH; HR, 1.27; 95% CI, 1.07 to 1.50 for ≥3 SDOH).
Conclusion
Having multiple SDOH was independently associated with an increased risk of CVD events, a finding driven by cardiovascular death. Identifying individuals with diabetes who have multiple SDOH may be helpful for detecting those at higher risk of experiencing or dying from CVD events.

Metabolic Risk/Epidemiology
2023 Diabetic Kidney Disease Fact Sheet in Korea: Nam Hoon Kim, Mi-Hae Seo, Jin Hyung Jung, Kyung Do Han, Mi Kyung Kim, Nan Hee Kim, on Behalf of Diabetic Kidney Disease Research Group of the Korean Diabetes Association; Diabetes Metab J. 2024;48(3):463-472. Published online March 19, 2024; DOI: https://doi.org/10.4093/dmj.2023.0310

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Background
To investigate the prevalence, incidence, comorbidities, and management status of diabetic kidney disease (DKD) and diabetes-related end-stage kidney disease (ESKD) in South Korea.
Methods
We used the Korea National Health and Nutrition Examination Survey data (2019 to 2021, n=2,665) for the evaluation of prevalence, comorbidities, control rate of glycemia and comorbidities in DKD, and the Korean Health Insurance Service-customized database (2008 to 2019, n=3,950,857) for the evaluation of trends in the incidence and prevalence rate of diabetes-related ESKD, renin-angiotensin system (RAS) blockers and sodium glucose cotransporter 2 (SGLT2) inhibitors use for DKD, and the risk of atherosclerotic cardiovascular disease (ASCVD) and mortality according to DKD stages. DKD was defined as albuminuria or low estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² in patients with diabetes mellitus.
Results
The prevalence of DKD was 25.4% (albuminuria, 22.0%; low eGFR, 6.73%) in patients with diabetes mellitus aged ≥30 years. Patients with DKD had a higher rate of comorbidities, including hypertension, dyslipidemia, and central obesity; however, their control rates were lower than those without DKD. Prescription rate of SGLT2 inhibitors with reduced eGFR increased steadily, reaching 5.94% in 2019. Approximately 70% of DKD patients were treated with RAS blockers. The prevalence rate of diabetesrelated ESKD has been steadily increasing, with a higher rate in older adults. ASCVD and mortality were significantly associated with an in increase in DKD stage.
Conclusion
DKD is prevalent among Korean patients with diabetes and is an independent risk factor for cardiovascular morbidity and mortality, which requiring intensive management of diabetes and comorbidities. The prevalence of diabetes-related ESKD has been increasing, especially in the older adults, during past decade.

Citations

Citations to this article as recorded by

Glycemia Risk Index is Associated With Risk of Albuminuria Among Individuals With Type 1 Diabetes
Ji Yoon Kim, Jee Hee Yoo, Nam Hoon Kim, Jae Hyeon Kim
Journal of Diabetes Science and Technology.2025;[Epub] CrossRef
Big Data Research for Diabetes-Related Diseases Using the Korean National Health Information Database
Kyung-Soo Kim, Bongseong Kim, Kyungdo Han
Diabetes & Metabolism Journal.2025; 49(1): 13. CrossRef
Effect of Glomerular Hyperfiltration on Incident Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus
Seung Min Chung, Inha Jung, Da Young Lee, So Young Park, Ji Hee Yu, Jun Sung Moon, Ji A. Seo, Kyung-Do Han, Nan Hee Kim
Clinical Journal of the American Society of Nephrology.2025; 20(3): 410. CrossRef
Impact of Muscle Quality on Muscle Strength and Physical Performance Beyond Muscle Mass or Diabetes Status
Jung A Kim, Chol Shin, Inha Jung, So Young Park, Da Young Lee, Ji Hee Yu, Hyunjoo Cho, Seung Ku Lee, Kyoung Jin Kim, Eyun Song, Kyeong Jin Kim, Nam Hoon Kim, Hye Jin Yoo, Sin Gon Kim, Kyung Mook Choi, Nan Hee Kim, Ji A Seo
Journal of Cachexia, Sarcopenia and Muscle.2025;[Epub] 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
Optimal Management of Diabetic Kidney Disease
Jae-Han Jeon
The Journal of Korean Diabetes.2025; 26(1): 1. CrossRef
Association Between Healthy Dietary Patterns and Chronic Kidney Disease in Patients with Diabetes: Findings from Korean National Health and Nutrition Examination Survey 2019–2021
Minsang Kim, Jung Hun Koh, Jeong Min Cho, Semin Cho, Soojin Lee, Hyuk Huh, Seong Geun Kim, Sehyun Jung, Eunjeong Kang, Sehoon Park, Jin Hyuk Paek, Woo Yeong Park, Kyubok Jin, Seungyeup Han, Kwon Wook Joo, Kyungdo Han, Dong Ki Kim, Yaerim Kim
Nutrients.2025; 17(9): 1600. CrossRef
Endothelial NOX5 Obliterates the Reno-Protective Effect of Nox4 Deletion by Promoting Renal Fibrosis via Activation of EMT and ROS-Sensitive Pathways in Diabetes
Karin A. M. Jandeleit-Dahm, Haritha R. Kankanamalage, Aozhi Dai, Jaroslawna Meister, Sara Lopez-Trevino, Mark E. Cooper, Rhian M. Touyz, Christopher R. J. Kennedy, Jay C. Jha
Antioxidants.2024; 13(4): 396. CrossRef
Management Strategies for Potassium Levels During Non-steroidal Mineralocorticoid Receptor Antagonist Therapy: A Comprehensive Review
Hyung Eun Son
Electrolytes & Blood Pressure.2024; 22(2): 29. CrossRef
A New Era in Diabetic Kidney Disease Treatment: The Four Pillars and Strategies to Build Beyond
Sangyub Han, Sejoong Kim
Electrolytes & Blood Pressure.2024; 22(2): 21. CrossRef

Cardiovascular risk/Epidemiology
Risk of Cardiovascular Disease according to Baseline Low-Density Lipoprotein Cholesterol Level in Different Age Groups in Korean Diabetes Population: A Cohort Study: Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2024;48(2):265-278. Published online February 26, 2024; DOI: https://doi.org/10.4093/dmj.2022.0443

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Abstract PDF Supplementary Material PubReader ePub: Background
The association between low-density lipoprotein (LDL-C) levels and cardiovascular disease (CVD) risk in different age groups within the diabetes mellitus (DM) population remains unclear. The cohort study was conducted to investigate this relationship.
Methods
We assessed the 2009 to 2012 Korean National Health Screening and National Health Insurance Service records, with follow-up to the primary outcome (myocardial infarction [MI] or stroke) or December 2018. After excluding the participants with a history of MI or stroke, 2,227,394 participants with DM were included and categorized according to baseline LDL-C levels and age. Cox proportional hazards modeling was conducted. The CVD risk of age <40 years and LDL-C <70 mg/dL was set as the reference. In each age group, LDL-C <70 mg/dL was used as a reference for the subgroup analysis.
Results
The cut-off LDL-C value for increased MI risk in each age group varied (<40 years old, LDL-C ≥160 mg/dL: hazard ratios [HR], 2.03; 95% confidence interval [CI], 1.644 to 2.506) (40–49-year-old, LDL-C <115 mg/dL: HR, 1.245; 95% CI, 1.04 to 1.489) (50–59-year-old, LDL-C <115 mg/dL: HR, 1.21; 95% CI, 1.014 to 1.445) (60-69-year-old, LDL-C <145 mg/dL: HR, 1.229; 95% CI, 1.022 to 1.479) (≥70 years old group, LDL-C <100 mg/dL: HR, 1.238; 95% CI, 1.018 to 1.504). The cut-off LDL-C values for increased stroke risk varied in each age subgroup (<40 years old, LDL-C ≥160 mg/dL: HR, 1.395; 95% CI, 1.094 to 1.779) (40–49-year-old, LDL-C <145 mg/dL: HR, 1.13; 95% CI, 1.019 to 1.253) (50–59-year-old, LDL-C <160 mg/dL: HR, 1.079; 95% CI, 1.008 to 1.154) (60–69-year-old, LDL-C <130 mg/dL: HR, 1.07; 95% CI, 1.022 to 1.119) (≥70 years old, LDL-C <115 mg/dL: HR, 1.064; 95% CI, 1.019 to 1.112).
Conclusion
The effect of LDL-C on the risk of CVD differs depending on the age of the population with DM.

Drug/Regimen
Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: Double-Blind, Randomized, Placebo-Controlled Trial: Ji Hye Heo, Kyung Ah Han, Jun Hwa Hong, Hyun-Ae Seo, Eun-Gyoung Hong, Jae Myung Yu, Hye Seung Jung, Bong-Soo Cha; Diabetes Metab J. 2024;48(5):937-948. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0314

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Background
This study assessed the efficacy and safety of triple therapy with pioglitazone 15 mg add-on versus placebo in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and dapagliflozin.
Methods
In this multicenter, double-blind, randomized, phase 3 study, patients with T2DM with an inadequate response to treatment with metformin (≥1,000 mg/day) plus dapagliflozin (10 mg/day) were randomized to receive additional pioglitazone 15 mg/day (n=125) or placebo (n=125) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) levels from baseline to week 24 (ClinicalTrials.gov identifier: NCT05101135).
Results
At week 24, the adjusted mean change from baseline in HbA1c level compared with placebo was significantly greater with pioglitazone treatment (–0.47%; 95% confidence interval, –0.61 to –0.33; P<0.0001). A greater proportion of patients achieved HbA1c <7% or <6.5% at week 24 with pioglitazone compared to placebo as add-on to 10 mg dapagliflozin and metformin (56.8% vs. 28% for HbA1c <7%, and 23.2% vs. 9.6% for HbA1c <6.5%; P<0.0001 for all). The addition of pioglitazone also significantly improved triglyceride, highdensity lipoprotein cholesterol levels, and homeostatic model assessment of insulin resistance levels, while placebo did not. The incidence of treatment-emergent adverse events was similar between the groups, and the incidence of fluid retention-related side effects by pioglitazone was low (1.5%).
Conclusion
Triple therapy with the addition of 15 mg/day of pioglitazone to dapagliflozin plus metformin was well tolerated and produced significant improvements in HbA1c in patients with T2DM inadequately controlled with dapagliflozin plus metformin.

Citations

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Ideal Combination of Oral Hypoglycemic Agents for Patients with Type 2 Diabetes Mellitus
Hye Soon Kim
Diabetes & Metabolism Journal.2024; 48(5): 882. CrossRef

Metabolic Risk/Epidemiology
Harnessing Metabolic Indices as a Predictive Tool for Cardiovascular Disease in a Korean Population without Known Major Cardiovascular Event: Hyun-Jin Kim, Byung Sik Kim, Yonggu Lee, Sang Bong Ahn, Dong Wook Kim, Jeong-Hun Shin; Diabetes Metab J. 2024;48(3):449-462. Published online February 1, 2024; DOI: https://doi.org/10.4093/dmj.2023.0197

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Background
This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults.
Methods
The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period.
Results
A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619.
Conclusion
The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.

Citations

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Comparing non-alcoholic fatty liver disease indices in predicting the prevalence and incidence of metabolic syndrome in middle-aged adults
Byung Sik Kim, Hyun-Jin Kim, Seong Won Jeon, Kyung Hwan Kim, Dong Wook Kim, Jeong-Hun Shin
Heliyon.2025; 11(7): e43073. CrossRef
Association between mixed exposure to per- and polyfluoroalkyl substances and metabolic syndrome in Korean adults: Data from the Korean National environmental health survey cycle 4
Seung Min Chung, Kyun Hoo Kim, Jun Sung Moon, Kyu Chang Won
International Journal of Hygiene and Environmental Health.2024; 261: 114427. CrossRef
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Cardiovascular risk/Epidemiology
Real-World Treatment Patterns according to Clinical Practice Guidelines in Patients with Type 2 Diabetes Mellitus and Established Cardiovascular Disease in Korea: Multicenter, Retrospective, Observational Study: Ye Seul Yang, Nam Hoon Kim, Jong Ha Baek, Seung-Hyun Ko, Jang Won Son, Seung-Hwan Lee, Sang Youl Rhee, Soo-Kyung Kim, Tae Seo Sohn, Ji Eun Jun, In-Kyung Jeong, Chong Hwa Kim, Keeho Song, Eun-Jung Rhee, Junghyun Noh, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association; Diabetes Metab J. 2024;48(2):279-289. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0225

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Background
Recent diabetes management guidelines recommend that sodium-glucose cotransporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1RAs) with proven cardiovascular benefits should be prioritized for combination therapy in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD). This study was aimed at evaluating SGLT2i or GLP-1RA usage rates and various related factors in patients with T2DM and established CVD.
Methods
We enrolled adults with T2DM aged ≥30 years who were hospitalized due to established CVD from January 2019 to May 2020 at 13 secondary and tertiary hospitals in Korea in this retrospective observational study.
Results
Overall, 2,050 patients were eligible for analysis among 2,107 enrolled patients. The mean patient age, diabetes duration, and glycosylated hemoglobin level were 70.0 years, 12.0 years, and 7.5%, respectively. During the mean follow-up duration of 9.7 months, 25.7% of the patients were prescribed SGLT2is after CVD events. However, only 1.8% were prescribed GLP-1RAs. Compared with SGLT2i non-users, SGLT2i users were more frequently male and obese. Furthermore, they had a shorter diabetes duration but showed worse glycemic control and better renal function at the time of the event. GLP-1RA users had a longer duration of diabetes and worse glycemic control at the time of the event than GLP-1RA non-users.
Conclusion
The SGLT2i or GLP-1RA prescription rates were suboptimal in patients with T2DM and established CVD. Sex, body mass index, diabetes duration, glycemic control, and renal function were associated with the use of these agents.

Citations

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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.2025; 16(2): 215. CrossRef
Enhancing Patient Outcomes: Prioritizing SGLT2is and GLP-1RAs in Diabetes with CVD
Gwanpyo Koh
Diabetes & Metabolism Journal.2024; 48(2): 208. CrossRef
Cardiovascular Disease & Diabetes Statistics in Korea: Nationwide Data 2010 to 2019
Jin Hwa Kim, Junyeop Lee, Kyungdo Han, Jae-Taek Kim, Hyuk-Sang Kwon
Diabetes & Metabolism Journal.2024; 48(6): 1084. CrossRef

Drug Regimen
The Efficacy and Safety of Moderate-Intensity Rosuvastatin with Ezetimibe versus High-Intensity Rosuvastatin in High Atherosclerotic Cardiovascular Disease Risk Patients with Type 2 Diabetes Mellitus: A Randomized, Multicenter, Open, Parallel, Phase 4 Study: Jun Sung Moon, Il Rae Park, Sang Soo Kim, Hye Soon Kim, Nam Hoon Kim, Sin Gon Kim, Seung Hyun Ko, Ji Hyun Lee, Inkyu Lee, Bo Kyeong Lee, Kyu Chang Won; Diabetes Metab J. 2023;47(6):818-825. Published online November 24, 2023; DOI: https://doi.org/10.4093/dmj.2023.0171

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Background
To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM).
Methods
This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints.
Results
A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185).
Conclusion
In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

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Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes
Ji-Kui Wang, Di Zhang, Jin-Feng Wang, Wan-Lin Lu, Jing-Yuan Wang, Shi-Feng Liang, Ran Liu, Jing-Xin Jiang, Hong-Tao Li, Xuan Yang
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Cardiovascular Risk/Epidemiology
Glycemic Control and Adverse Clinical Outcomes in Patients with Chronic Kidney Disease and Type 2 Diabetes Mellitus: Results from KNOW-CKD: Ga Young Heo, Hee Byung Koh, Hyung Woo Kim, Jung Tak Park, Tae-Hyun Yoo, Shin-Wook Kang, Jayoun Kim, Soo Wan Kim, Yeong Hoon Kim, Su Ah Sung, Kook-Hwan Oh, Seung Hyeok Han; Diabetes Metab J. 2023;47(4):535-546. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0112

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Background
The optimal level of glycosylated hemoglobin (HbA1c) to prevent adverse clinical outcomes is unknown in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).
Methods
We analyzed 707 patients with CKD G1-G5 without kidney replacement therapy and T2DM from the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD), a nationwide prospective cohort study. The main predictor was time-varying HbA1c level at each visit. The primary outcome was a composite of development of major adverse cardiovascular events (MACEs) or all-cause mortality. Secondary outcomes included the individual endpoint of MACEs, all-cause mortality, and CKD progression. CKD progression was defined as a ≥50% decline in the estimated glomerular filtration rate from baseline or the onset of end-stage kidney disease.
Results
During a median follow-up of 4.8 years, the primary outcome occurred in 129 (18.2%) patients. In time-varying Cox model, the adjusted hazard ratios (aHRs) for the primary outcome were 1.59 (95% confidence interval [CI], 1.01 to 2.49) and 1.99 (95% CI, 1.24 to 3.19) for HbA1c levels of 7.0%–7.9% and ≥8.0%, respectively, compared with <7.0%. Additional analysis of baseline HbA1c levels yielded a similar graded association. In secondary outcome analyses, the aHRs for the corresponding HbA1c categories were 2.17 (95% CI, 1.20 to 3.95) and 2.26 (95% CI, 1.17 to 4.37) for MACE, and 1.36 (95% CI, 0.68 to 2.72) and 2.08 (95% CI, 1.06 to 4.05) for all-cause mortality. However, the risk of CKD progression did not differ between the three groups.
Conclusion
This study showed that higher HbA1c levels were associated with an increased risk of MACE and mortality in patients with CKD and T2DM.

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Review

Metabolic Risk/Epidemiology
Gestational Diabetes Mellitus and Its Implications across the Life Span: Brandy Wicklow, Ravi Retnakaran; Diabetes Metab J. 2023;47(3):333-344. Published online February 8, 2023; DOI: https://doi.org/10.4093/dmj.2022.0348

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Gestational diabetes mellitus (GDM) has historically been perceived as a medical complication of pregnancy that also serves as a harbinger of maternal risk of developing type 2 diabetes mellitus (T2DM) in the future. In recent decades, a growing body of evidence has detailed additional lifelong implications that extend beyond T2DM, including an elevated risk of ultimately developing cardiovascular disease. Furthermore, the risk factors that mediate this lifetime cardiovascular risk are evident not only after delivery but are present even before the pregnancy in which GDM is first diagnosed. The concept thus emerging from these data is that the diagnosis of GDM enables the identification of women who are already on an enhanced track of cardiometabolic risk that starts early in life. Studies of the offspring of pregnancies complicated by diabetes now suggest that the earliest underpinnings of this cardiometabolic risk profile may be determined in utero and may first manifest clinically in childhood. Accordingly, from this perspective, GDM is now seen as a chronic metabolic disorder that holds implications across the life span of both mother and child.

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Original Article

Cardiovascular Risk/Epidemiology
Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus: Min Kyong Moon, Junghyun Noh, Eun-Jung Rhee, Sang Hyun Park, Hyeon Chang Kim, Byung Jin Kim, Hae Jin Kim, Seonghoon Choi, Jin Oh Na, Young Youl Hyun, Bum Joon Kim, Kyung-Do Han, In-Kyung Jeong, on Behalf of the Committee of Practice Guideline of Korean Lipid and Atheroscelerosis; Diabetes Metab J. 2023;47(1):45-58. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2021.0344

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Background
There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data.
Methods
Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018.
Results
The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL.
Conclusion
For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

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Ji Yoon Kim, Nam Hoon Kim
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Lipid Management in Korean People With Type 2 Diabetes Mellitus: Korean Diabetes Association and Korean Society of Lipid and Atherosclerosis Consensus Statement
Ye Seul Yang, Hack-Lyoung Kim, Sang-Hyun Kim, Min Kyong Moon
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Ye Seul Yang
The Journal of Korean Diabetes.2023; 24(3): 135. CrossRef
2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association
Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Nan Hee Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, YoonJu Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang Youl Rhee, Hae J
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Journal of Korean Medical Science.2023;[Epub] CrossRef

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