Diabetes & Metabolism Journal

Original Articles

Guideline/Statement/Fact Sheet
Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society: Jong Han Choi, SuJin Song, Soo Kyoung Kim, Jae Won Cho, Jae Hyun Bae, Shinje Moon, Jeong Hyun Lim, YeonHee Lee, Ji-Yun Hwang, YoonJu Song, Sang Soo Kim; Diabetes Metab J. 2026;50(1):32-46. Published online January 1, 2026; DOI: https://doi.org/10.4093/dmj.2025.0848

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Background
Excess intake of added sugars contributes to obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease (CVD), and premature mortality. Sugar-sweetened beverages (SSBs), the main source of added sugars, are consistently linked to adverse outcomes. Artificially sweetened beverages (ASBs) have been suggested as short-term substitutes, but evidence regarding benefits and harms remains inconclusive, and guidance is lacking.
Methods
This consensus statement draws on a structured evidence review combining two approaches: an updated meta-analysis of randomized controlled trials (RCTs) assessing short- to intermediate-term effects of replacing SSBs with ASBs on weight and metabolic outcomes; and an umbrella review of systematic reviews of cohort studies evaluating long-term associations of SSBs and ASBs with major outcomes, including mortality, CVD, and T2DM.
Results
In 14 RCTs (3–76 weeks), replacing SSBs with ASBs produced modest reductions in body weight (–0.73 kg) and body fat (–0.72%), with inconsistent effects on glycemic and cardiometabolic markers. Evidence from 20 systematic reviews of cohorts (up to 34 years follow-up) showed that higher intake of both SSBs and ASBs was associated with increased risks of T2DM, CVD, and mortality, with relative risks for ASBs similar to those for SSBs.
Conclusion
ASBs may serve as a short-term substitution for individuals with high SSB intake, particularly those at elevated metabolic risk. However, regular or long-term use is not recommended due to uncertain safety and potential reinforcement of sweet preference. Public health strategies should emphasize reducing both SSBs and ASBs, prioritizing water and unsweetened beverages as the ultimate goal.

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Do Not Replace Your Sugar, Simply Eat Less!
Jeehyun Lee, Sunghwan Suh
Diabetes & Metabolism Journal.2026; 50(1): 30. CrossRef

Lifestyle and Behavioral Interventions
Association between the Life’s Essential 8 Health Behaviors Score and Mortality Risk in US Adults with Cardiovascular-Kidney-Metabolic Syndrome Stage 0–3: Junlin Zhang, Limei Yin, Yuping Liu, Xiang Xiao, Ping Shuai; Received April 26, 2025 Accepted June 16, 2025 Published online December 12, 2025; DOI: https://doi.org/10.4093/dmj.2025.0366 [Epub ahead of print]

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The American Heart Association’s novel cardiovascular-kidney-metabolic (CKM) syndrome framework underscores the interconnected pathophysiology of metabolic dysfunction, chronic kidney disease, and cardiovascular disease (CVD). While the Life’s Essential 8 (LE8) has demonstrated strong associations with CVD risk in general populations, its prognostic relevance remains unexplored in individuals stratified by CKM syndrome stages.
Methods
This study analyzed longitudinal data from the nationally representative National Health and Nutrition Examination Survey (2005–2018). The eight components of the LE8 metric—diet quality, physical activity, nicotine exposure, sleep health, body mass index, blood lipid profiles, glycemic status, and blood pressure—were systematically evaluated and scored on a 0–100 scale. A Cox proportional hazards regression model was implemented to assess associations between LE8 scores and all-cause mortality risk. Mortality outcomes were prospectively tracked through December 31, 2019, using linked mortality records from the National Center for Health Statistics.
Results
Among 9,152 participants (mean age 45.08±0.29 years; 48.24% male), baseline CKM staging distributed as follows: stage 0 (12.08%, n=916), stage 1 (25.76%, n=2,162), stage 2 (60.02%, n=5,721), and stage 3 (2.14%, n=353). Unexpectedly, during a median follow-up of 7.92 years, the total LE8 score was not related with all-cause mortality in individuals with CKM stage 2–3 (P>0.05). However, fully adjusted analyses revealed a 22% and 13% decreased all-cause mortality risk per 10-points LE8 health behaviors score increment in CKM 0-1 (hazard ratio [HR], 0.78; 95% confidence interval [CI], 0.68 to 0.88) and CKM 2-3 (HR, 0.87; 95% CI, 0.81 to 0.93), respectively. Restricted cubic spline models confirmed a negative linear dose-response relationship between health behaviors score and all-cause mortality across all CKM stages 0–3.
Conclusion
This national cohort study establishes LE8 health behaviors score as a robust, linearly associated predictor of all-cause mortality in CKM syndrome populations, independent of disease stage severity. These findings advocate for integrating LE8 health behaviors score into routine metabolic-cardiovascular risk stratification protocols, particularly for early intervention in CKM stage 0–3 individuals.

Cardiovascular Risk/Epidemiology
High Waist-to-Height Ratio Increases the Risk of Cardiovascular Outcomes in Adults with Type 1 Diabetes Mellitus: A Nationwide Cohort Study: Kyeong-Jin Kim, Seohyun Kim, Rosa Oh, So Hyun Cho, Myunghwa Jang, You-Bin Lee, Gyuri Kim, Sang-Man Jin, Kyu Yeon Hur, Ji Yoon Kim, Jae Hyeon Kim; Received March 4, 2025 Accepted June 21, 2025 Published online September 4, 2025; DOI: https://doi.org/10.4093/dmj.2025.0179 [Epub ahead of print]

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Central obesity contributes to an increased risk of cardiovascular disease (CVD) and mortality. The waist-to-height ratio (WHtR) is a practical marker of central obesity across sexes, ages, and ethnicities. However, its association with comprehensive cardiovascular (CV) outcomes in patients with type 1 diabetes mellitus (T1DM) remains unclear.
Methods
From a nationwide cohort database (2006–2020), 16,928 Korean adults with T1DM were included. Participants were categorized by their WHtR values using three criteria: a three-group classification (<0.5, 0.5 to <0.6, and ≥0.6) and two binary classifications (≥0.5 vs. <0.5; ≥0.6 vs. <0.6). The primary outcomes were composite CV events, including heart failure (HF), myocardial infarction (MI), ischemic stroke, and CVD-related deaths, with each component analyzed as a secondary outcome.
Results
During a median follow-up of 6.7 years (interquartile range, 5.2 to 8.8), 4,293 composite CV events occurred. Compared to the WHtR <0.5 group, the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the composite CV outcome were 1.14 (1.05 to 1.24) in the WHtR 0.5 to <0.6 group and 1.62 (1.38 to 1.90) in the WHtR ≥0.6 group (P for trend <0.001). Increasing trends in aHRs were noted with rising WHtR values for each component of the composite outcome. Compared to the WHtR <0.6 group, the aHRs for the WHtR ≥0.6 group were as follows: HF, 1.49 (95% CI, 1.28 to 1.73); MI, 1.31 (95% CI, 1.02 to 1.68); ischemic stroke, 1.24 (95% CI, 1.02 to 1.51); and CVD-related death, 2.09 (95% CI, 1.49 to 2.92).
Conclusion
High WHtR is associated with an increased risk of CV events in adults with T1DM.

Cardiovascular Risk/Epidemiology
Associations of Cardiocerebrovascular Risks and Exercise according to Menopausal Status in Women with Type 2 Diabetes Mellitus: A Nationwide Cohort Study: Ji-Hee Ko, Sun Joon Moon, Kyung-Do Han, Hye-Mi Kwon, Se-Eun Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2026;50(1):101-114. Published online August 13, 2025; DOI: https://doi.org/10.4093/dmj.2024.0487

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Menopausal status can increase the risk of cardiocerebrovascular diseases (CCVDs) in women with type 2 diabetes mellitus (T2DM). Regular exercise is well-known to reduce this risk. This study explored the impact of exercise on CCVD and mortality in women with T2DM according to their menopausal status.
Methods
A total of 32,477 premenopausal and 53,690 postmenopausal Korean women with T2DM aged 40 to 60 years from a national health examination cohort (2009 to 2018) were included. We evaluated risks for stroke, myocardial infarction (MI), and mortality based on exercise intensity. Cox proportional hazard regression analyses were performed to obtain the adjusted hazard ratio (aHR) and 95% confidence interval.
Results
Exercise reduced stroke, MI, and mortality risks in women with T2DM, regardless of menopausal status. The highest effects of aHR compared to the sedentary group were 0.68 for stroke, 0.66 for MI, and 0.81 for mortality. Postmenopausal women experienced significant MI risk reductions at most exercise intensities, with the greatest reduction in the ≥1,500 metabolic equivalent of task score group unlike premenopausal women. However, stroke and mortality risk reductions in postmenopausal women were less pronounced compared to premenopausal women.
Conclusion
Exercise reduces CCVD risk in women with T2DM across menopausal status. Postmenopausal women with T2DM had more benefits from exercise on MI but fewer benefits on stroke and mortality than premenopausal women. In premenopausal women with T2DM, exercise was not associated with a lower MI risk.

Cardiovascular Risk/Epidemiology
Comparative Efficacy of Initial Statin and Ezetimibe Combination versus Statin Monotherapy on Cardiovascular Outcomes in Diabetes Mellitus: A Nationwide Cohort Study: Minji Sohn, Young-Hwan Park, Soo Lim; Diabetes Metab J. 2025;49(6):1318-1330. Published online June 5, 2025; DOI: https://doi.org/10.4093/dmj.2024.0482

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Background
This study aimed to assess the efficacy of an initial combination therapy of statin and ezetimibe compared with statin monotherapy on major cardiovascular outcomes in individuals with diabetes.
Methods
In this population-based cohort study using National Health Insurance Service data (2010–2020), we included adults with diabetes who had not previously used any lipid-lowering medications. Those initiating statin monotherapy were matched 1:1 using propensity scores with patients starting combination therapy with a lower-potency statin and ezetimibe. This matching process resulted in 21,458 individuals in the primary prevention cohort and 10,094 in the secondary prevention cohort, respectively. The primary endpoint was a composite of myocardial infarction, stroke, and cardiovascular death. Hospitalizations for heart failure, angina, and all-cause mortality were analyzed. The impact of ezetimibe maintenance on the primary endpoint was analyzed, and other hospitalizations were categorized as adverse events.
Results
Compared with statin monotherapy, statin-ezetimibe combination significantly reduced the incidence of the primary endpoint (4.85 vs. 3.25 per 1,000 person-years: hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.56 to 0.81 in the primary cohort; and 19.5 vs. 15.7 per 1,000 person-years: HR, 0.80; 95% CI, 0.70 to 0.91 in the secondary cohort) and myocardial infarction (HR, 0.64; 95% CI, 0.46 to 0.82 in the primary cohort; and HR, 0.73; 95% CI, 0.60 to 0.89 in the secondary cohort). A longer maintenance period of ezetimibe was significantly related to better efficacy in the composite cardiovascular outcomes. High-intensity statin monotherapy was associated with an elevated risk of liver, muscle, and diabetes-related hospitalization in the primary prevention cohort.
Conclusion
Initial therapy with a statin-ezetimibe combination is associated with a reduced risk of cardiovascular events and fewer adverse events compared to statin monotherapy in individuals with diabetes, over a mean follow-up of 5.5 years (up to 9 years).

Citations

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Cardiovascular outcomes and adverse drug reactions associated with the use of ezetimibe in combination with a statin in diabetes mellitus patients with higher risk for myocardial infarction: a meta-analysis
Yan Zhou, Ji Jin
BMC Cardiovascular Disorders.2026;[Epub] CrossRef
Sirtuins and regulatory miRNAs as epigenetic determinants of empagliflozin-mediated recovery after acute myocardial infarction
Anna Nowak-Szwed, Ceren Eyileten, Zofia Wicik, Sara Ahmadova, Jeff Palatini, Jolanta Siller-Matula, Dirk von Lewinski, Harald Sourij, Marek Postula
Cardiovascular Diabetology.2025;[Epub] CrossRef

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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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.

Citations

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Postbiotics in Functional Foods: Microbial Derivatives Shaping Health, Immunity and Next‐Generation Nutrition
Alice Njolke Mafe, Javad Sharifi‐Rad, Daniela Calina, Ayobami Joshua Ogunyemi, Abiola O. Tubi
Food Frontiers.2026;[Epub] CrossRef
Decoding the Endocrine Code of Skeletal Muscle: Myokines, Exerkines, and Inter-Organ Crosstalk in Metabolic Health and Disease
Young-Sool Hah, Jeongyun Hwang, Seung-Jun Lee, Seung-Jin Kwag
Cells.2026; 15(4): 318. CrossRef
Extracellular Vesicles: Biology, Intercellular Communication and Therapeutic Potential in Diabetes
Swayam Prakash Srivastava, Lydia Herrmann, Eden Ozkan, Abhiram Kunamneni, Vinamra Swaroop, Geetika Nehra, Rohit Srivastava, Pratima Tripathi, Ken Inoki, Julie E. Goodwin
Advanced Therapeutics.2026;[Epub] CrossRef
Association between dyslipidemia and elevated liver enzymes: A cross-sectional study from the PERSIAN Guilan cohort study
Milad Shahdkar, Mahdi Orang Goorabzarmakhi, Mahdi Shafizadeh, Farahnaz Joukar, Saman Maroufizadeh, Niloofar Faraji, Tahereh Zeinali, Fariborz Mansour-Ghanaei
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Charalampos Voros, Georgios Papadimas, Despoina Mavrogianni, Aristotelis-Marios Koulakmanidis, Diamantis Athanasiou, Kyriakos Bananis, Antonia Athanasiou, Aikaterini Athanasiou, Ioannis Papapanagiotou, Dimitrios Vaitsis, Charalampos Tsimpoukelis, Maria An
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Molecular mechanisms linking adipose tissue-derived small extracellular vesicles/exosomes to the development or amelioration of obesity, insulin resistance, and diabetes-related complications
Linfeng Chen, Fatemeh Amraee, Sahar Sadegh-Nejadi, Mostafa Saberian, Seyed Arsalan Ghahari, Xiaolei Miao, Giuseppe Lisco, Reza Afrisham
European Journal of Medical Research.2025;[Epub] CrossRef
Mitochondria-Enriched Extracellular Vesicles (EVs) for Cardiac Bioenergetics Restoration: A Scoping Review of Preclinical Mechanisms and Source-Specific Strategies
Dhienda C. Shahannaz, Tadahisa Sugiura, Taizo Yoshida
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A Comprehensive Insight Into the Roles of Exosomal circRNAs in Metabolic Syndrome
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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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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

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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

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
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Andrea O. Y. Luk, Yingnan Fan, Baoqi Fan, Edith W. K. Chow, Tony C. K. O
Diabetologia.2025; 68(11): 2386. CrossRef
2024 Cardio-cerebrovascular disease fact sheet in Korea
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Comparison of ischemic cardiovascular events between dapagliflozin and empagliflozin in combination with metformin: A nationwide population-based cohort study
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BMJ Public Health.2025; 3(2): e002701. 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.

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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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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.

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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.

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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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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.

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Innovative Lipid-Lowering Strategies: RNA-Based, Small Molecule, and Protein-Based Therapies
Youngwoo Jang, Eun-Jung Rhee, Sung Hee Choi
Endocrinology and Metabolism.2025; 40(5): 668. CrossRef

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.

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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.

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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.

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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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Comparative outcomes of moderate-intensity statin with ezetimibe vs high-intensity statin therapy: A retrospective observational cohort study
Junpil Yun, Seokhun Yang, Doyeon Hwang, Jeehoon Kang, Han-Mo Yang, Kyung Woo Park, Hyun-Jae Kang, Bon-Kwon Koo, Jung-Kyu Han
Journal of Clinical Lipidology.2026; 20(1): 87. CrossRef
Cardiovascular outcomes and adverse drug reactions associated with the use of ezetimibe in combination with a statin in diabetes mellitus patients with higher risk for myocardial infarction: a meta-analysis
Yan Zhou, Ji Jin
BMC Cardiovascular Disorders.2026;[Epub] CrossRef
Lipid metabolism in homeostasis and disease
Zhenghao Li, Wende Deng, Lanxuan Yang, Changheng Tang, Jian-Min Yue, Olivia Monteiro, Daniel T. Baptista-Hon, Ting Li
Signal Transduction and Targeted Therapy.2026;[Epub] CrossRef
Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes
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World Journal of Diabetes.2025;[Epub] CrossRef
Overcoming β-Cell Dysfunction in Type 2 Diabetes Mellitus: CD36 Inhibition and Antioxidant System
Il Rae Park, Yong Geun Chung, Kyu Chang Won
Diabetes & Metabolism Journal.2025; 49(1): 1. CrossRef
Neuroprotective Effect of Rosuvastatin Calcium Combined with Hyperbaric Oxygen Mediated p38MAPK Pathway in Rats with Leukoaraiosis
Yafeng Shi, Gemin Zhu, Jun Yan, Linxin Zhang, Yongku Du, Zhuoqiong Bian, Jing Fan
Cell Biochemistry and Biophysics.2025; 83(3): 3205. CrossRef
Ezetimibe plus statin combination versus double-dose statin in patients with dyslipidemia and atherosclerotic cardiovascular disease risk: a comprehensive systematic review and meta-analysis of 47 randomized controlled trials
Abdelrahman Mahmoud, Hazem Mohamed Salamah, Hazem Rezq, Yazan Al-Mohtasib, Ali Ashraf Salah Ahmed, Mohamed R. Abdelraouf, Ahmed Mazen Amin, Ahmed A. Ibrahim, Yasmine Adel Mohammed, Omar Ahmed Abdelwahab, Majd M. AlBarakat, Salem Elshenawy, Husam Abu Suili
Baylor University Medical Center Proceedings.2025; 38(4): 474. CrossRef
Efficacy and safety of statins, ezetimibe, and fibrates monotherapy or combination therapy for hyperlipidemia: a systematic review and network meta-analysis
Shujie Zhang, Tingting Sun, Lina Song, Xiaodong Jin, Bo Li
European Journal of Medical Research.2025;[Epub] CrossRef
Effect of folic acid and vitamin B12 plus rosuvastatin in the treatment of coronary heart disease combined with hyperlipidemia
Hao Wang, Tiezheng Wang
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Management of dyslipidaemia in patients with comorbidities: facing the challenge: type 2 diabetes mellitus
Heinz Drexel, Andreas Festa, Thomas A Schmidt, Bianca Rocca, Dobromir Dobrev, Stefan Agewall, Juan Tamargo, Susanne Kaser
European Heart Journal - Cardiovascular Pharmacotherapy.2025; 11(8): 698. CrossRef
Pharmacokinetics of a single-pill combination of rosuvastatin and ezetimibe (2.5 mg/10 mg) in healthy Chinese subjects: an open-label, two-period, phase I study
Ying Wang, Jiaxiang Ding, Dongmei Cheng, Yuzhou Ding, Tonghao Zhang, Wang Hu, Xiaoni Wang, Xu Zhu, Yunqiu Xie, Huan Zhou
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Does Rosuvastatin/Ezetimibe Combination Therapy Offer Potential Benefits for Glucose Metabolism beyond Lipid-Lowering Efficacy in T2DM?
Il Rae Park, Jun Sung Moon
Diabetes & Metabolism Journal.2024; 48(3): 387. CrossRef
Efficacy and safety of double-dose statin monotherapy versus moderate-intensity statin combined with ezetimibe dual therapy in diabetic patients: a systematic review and meta-analysis of randomized controlled trials
Aman Goyal, Muhammad Daoud Tariq, Hritvik Jain, Abhigan Babu Shrestha, Laveeza Fatima, Romana Riyaz, Hritik Raj Yadav, Darsh Safi, Abdul Qahar K. Yasinzai, Rozi Khan, Amir Humza Sohail, Mohamed Daoud, Abu Baker Sheikh
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Efficacy and safety of moderate-intensity rosuvastatin plus ezetimibe versus high-intensity rosuvastatin monotherapy in the treatment of composite cardiovascular events with hypercholesterolemia: A meta-analysis
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PLOS ONE.2024; 19(11): e0310696. CrossRef

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 Articles

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.

Citations

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Clinical value of serum miR-214-3p expression in the diagnosis of type 2 diabetes mellitus and prediction of its chronic complications
Meng Ding, Siyu Yang, Junli Li, Lie Ma, Cunyou Xiong, Jie Zhang
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Cholesterol and Cardiovascular Risk in Type 2 Diabetes: The Role of Kidney Function
Ji-Hyun Kim, Seung-Hwan Lee, Kyu Na Lee, Kyungdo Han, Mee Kyoung Kim
Journal of Lipid and Atherosclerosis.2025; 14(2): 190. CrossRef
2025 Clinical Practice Guidelines for Diabetes Management in Korea: Recommendation of the Korean Diabetes Association
Shinae Kang, Seon Mee Kang, Jong Han Choi, Seung-Hyun Ko, Bo Kyung Koo, Hyuk-Sang Kwon, Mi Kyung Kim, Sang Yong Kim, Soo-Kyung Kim, Young-eun Kim, Eun Sook Kim, Jae Hyeon Kim, Chong Hwa Kim, Ji Min Kim, Hae Jin Kim, Min Kyong Moon, Sun Joon Moon, Jun Sung
Diabetes & Metabolism Journal.2025; 49(4): 582. CrossRef
Heterogeneity in the development of diabetes-related complications: narrative review of the roles of ancestry and geographical determinants
Andrea O. Y. Luk, Yingnan Fan, Baoqi Fan, Edith W. K. Chow, Tony C. K. O
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2023 Clinical Practice Guidelines for Diabetes Management in Korea: Full Version Recommendation of the Korean Diabetes Association
Jun Sung Moon, Shinae Kang, Jong Han Choi, Kyung Ae Lee, Joon Ho Moon, Suk Chon, Dae Jung Kim, Hyun Jin Kim, Ji A Seo, Mee Kyoung Kim, Jeong Hyun Lim, Yoon Ju Song, Ye Seul Yang, Jae Hyeon Kim, You-Bin Lee, Junghyun Noh, Kyu Yeon Hur, Jong Suk Park, Sang
Diabetes & Metabolism Journal.2024; 48(4): 546. CrossRef
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
Diabetes & Metabolism Journal.2023; 47(1): 1. CrossRef
Optimal Low-Density Lipoprotein Cholesterol Level for Primary Prevention in Koreans with Type 2 Diabetes Mellitus
Ji Yoon Kim, Nam Hoon Kim
Diabetes & Metabolism Journal.2023; 47(1): 42. CrossRef
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
Journal of Lipid and Atherosclerosis.2023; 12(1): 12. CrossRef
2023 Clinical Practice Guidelines for Diabetes: Management of Cardiovascular Risk Factors
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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Kyung Ae Lee
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Sang Yeub Lee, Kyung Hoon Cho, Jang Hoon Lee, Young Joon Hong, Jin yong Hwang, Myung Ho Jeong, Weon Kim
Journal of Korean Medical Science.2023;[Epub] CrossRef

Cardiovascular Risk/Epidemiology
Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study: Junghyun Noh, Min Kyong Moon, 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):59-71. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2021.0320

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Background
To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline.
Methods
We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018.
Results
The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70–99, 100–129, 130–159, 160–189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08–1.33), 1.27 (1.15–1.42), 1.39 (1.23–1.56), 1.69 (1.45–1.96), and 1.84 (1.49– 2.27) in very high-risk group, and 1.07 (1.02–1.13), 1.16 (1.10–1.21), 1.29 (1.22–1.36), 1.45 (1.36–1.55), and 1.73 (1.58–1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130–159, 160–189, and ≥190 mg/dL were 1.15 (1.11–1.20), 1.28 (1.22– 1.34), and 1.45 (1.36–1.54) in moderate-risk group and 1.07 (1.02–1.13), 1.20 (1.13–1.26), and 1.47 (1.37–1.57) in low-risk group.
Conclusion
We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

Citations

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Journal of Cardiovascular Pharmacology and Therapeutics.2023;[Epub] CrossRef

Reviews

Pathophysiology
Blood Pressure Target in Type 2 Diabetes Mellitus: Hyun-Jin Kim, Kwang-il Kim, on Behalf of the Policy Committee of Korean Society of Hypertension; Diabetes Metab J. 2022;46(5):667-674. Published online September 19, 2022; DOI: https://doi.org/10.4093/dmj.2022.0215

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The prevalence of diabetes mellitus continues to increase worldwide, and it is a well-established cardiovascular risk factor. Hypertension is also an important cardiovascular risk factor to be controlled and is common among patients with diabetes mellitus. Optimal blood pressure (BP) goals have been the subject of great debate in the management of hypertension among patients with diabetes mellitus. This review provides detailed results from randomized controlled trials and meta-analyses of clinical outcomes according to the target BP in patients with type 2 diabetes mellitus. In addition, the target BP in patients with diabetes mellitus recommended by different guidelines was summarized and presented. A target BP of <140/90 mm Hg is recommended for patients with hypertension and diabetes mellitus, and BP should be controlled to <130/80 mm Hg in patients with diabetes mellitus who have high-risk clinical features. We hope that this review will be helpful to clinicians and patients by promoting the understanding and appropriate application of BP control in the comprehensive management of patients with diabetes mellitus.

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New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins: Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi; Diabetes Metab J. 2022;46(4):517-532. Published online July 27, 2022; DOI: https://doi.org/10.4093/dmj.2022.0198; Correction in: Diabetes Metab J 2022;46(5):817

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Statins are the cornerstone of the prevention and treatment of atherosclerotic cardiovascular disease (ASCVD). However, even under optimal statin therapy, a significant residual ASCVD risk remains. Therefore, there has been an unmet clinical need for novel lipid-lowering agents that can target low-density lipoprotein cholesterol (LDL-C) and other atherogenic particles. During the past decade, several drugs have been developed for the treatment of dyslipidemia. Inclisiran, a small interfering RNA that targets proprotein convertase subtilisin/kexin type 9 (PCSK9), shows comparable effects to that of PCSK9 monoclonal antibodies. Bempedoic acid, an ATP citrate lyase inhibitor, is a valuable treatment option for the patients with statin intolerance. Pemafibrate, the first selective peroxisome proliferator-activated receptor alpha modulator, showed a favorable benefit-risk balance in phase 2 trial, but the large clinical phase 3 trial (PROMINENT) was recently stopped for futility based on a late interim analysis. High dose icosapent ethyl, a modified eicosapentaenoic acid preparation, shows cardiovascular benefits. Evinacumab, an angiopoietin-like 3 (ANGPTL3) monoclonal antibody, reduces plasma LDL-C levels in patients with refractory hypercholesterolemia. Novel antisense oligonucleotides targeting apolipoprotein C3 (apoC3), ANGPTL3, and lipoprotein(a) have significantly attenuated the levels of their target molecules with beneficial effects on associated dyslipidemias. Apolipoprotein A1 (apoA1) is considered as a potential treatment to exploit the athero-protective effects of high-density lipoprotein cholesterol (HDL-C), but solid clinical evidence is necessary. In this review, we discuss the mode of action and clinical outcomes of these novel lipid-lowering agents beyond statins.

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Original Articles

Drug/Regimen
Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease: Jong Ha Baek, Ye Seul Yang, Seung-Hyun Ko, Kyung Do Han, Jae Hyeon Kim, Min Kyong Moon, Jong Suk Park, Byung-Wan Lee, Tae Jung Oh, Suk Chon, Jong Han Choi, Kyu Yeon Hur, Committee of Clinical Practice Guidelines, Korean Diabetes Association; Diabetes Metab J. 2022;46(5):701-712. Published online June 3, 2022; DOI: https://doi.org/10.4093/dmj.2022.0002

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Background
To evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).
Methods
Prescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.
Results
Of all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.
Conclusion
The prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

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Endocrinology and Metabolism.2022; 37(5): 759. CrossRef

Cardiovascular Risk/Epidemiology
Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study: You-Bin Lee, Minji Koo, Eunjin Noh, Soon Young Hwang, Jung A Kim, Eun Roh, So-hyeon Hong, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo; Diabetes Metab J. 2022;46(5):722-732. Published online March 8, 2022; DOI: https://doi.org/10.4093/dmj.2021.0225

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Background
We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults.
Methods
The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616).
Results
During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up.
Conclusion
Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

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Endocrinology and Metabolism.2022; 37(5): 759. CrossRef

Review

Cardiovascular Risk/Epidemiology
Management of Cardiovascular Risk in Perimenopausal Women with Diabetes: Catherine Kim; Diabetes Metab J. 2021;45(4):492-501. Published online July 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0262

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Cardiovascular disease is the primary cause of mortality in women and men with diabetes. Due to age and worsening of risk factors over the menopausal transition, risk of coronary heart disease events increases in postmenopausal women with diabetes. Randomized studies have conflicted regarding the beneficial impact of estrogen therapy upon intermediate cardiovascular disease markers and events. Therefore, estrogen therapy is not currently recommended for indications other than symptom management. However, for women at low risk of adverse events, estrogen therapy can be used to minimize menopausal symptoms. The risk of adverse events can be estimated using risk engines for the calculation of cardiovascular risk and breast cancer risk in conjunction with screening tools such as mammography. Use of estrogen therapy, statins, and anti-platelet agents can be guided by such calculators particularly for younger women with diabetes. Risk management remains focused upon lifestyle behaviors and achieving optimal levels of cardiovascular risk factors, including lipids, glucose, and blood pressure. Use of pharmacologic therapies to address these risk factors, particularly specific hypoglycemic agents, may provide some additional benefit for risk prevention. The minimal benefit for women with limited life expectancy and risk of complications with intensive therapy should also be considered.

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Original Articles

Cardiovascular Risk/Epidemiology
Metabolic Syndrome Severity Score for Predicting Cardiovascular Events: A Nationwide Population-Based Study from Korea: Yo Nam Jang, Jun Hyeok Lee, Jin Sil Moon, Dae Ryong Kang, Seong Yong Park, Jerim Cho, Jang-Young Kim, Ji Hye Huh; Diabetes Metab J. 2021;45(4):569-577. Published online January 30, 2021; DOI: https://doi.org/10.4093/dmj.2020.0103

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Background
Recently, a metabolic syndrome severity score (MS score) using a dataset of the Korea National Health and Nutrition Examination Surveys has been developed. We aimed to determine whether the newly developed score is a significant predictor of cardiovascular (CV) events among the Korean population.
Methods
From the Korean National Health Insurance System, 2,541,364 (aged 40 to 59 years) subjects with no history of CV events (ischemic stroke or myocardial infarction [MI]), who underwent health examinations from 2009 to 2011 and were followed up until 2014 to 2017, were identified. Cox proportional hazard model was employed to investigate the association between MS score and CV events. Model performance of MS score for predicting CV events was compared to that of conventional metabolic syndrome diagnostic criteria (Adult Treatment Program III [ATP-III]) using the Akaike information criterion and the area under the receiver operating characteristic curve.
Results
Over a median follow-up of 6 years, 15,762 cases of CV events were reported. MS score at baseline showed a linear association with incident CV events. In the multivariable-adjusted model, the hazard ratios (95% confidence intervals) comparing the highest versus lowest quartiles of MS score were 1.48 (1.36 to 1.60) for MI and 1.89 (1.74 to 2.05) for stroke. Model fitness and performance of the MS score in predicting CV events were superior to those of ATP-III.
Conclusion
The newly developed age- and sex-specific continuous MS score for the Korean population is an independent predictor of ischemic stroke and MI in Korean middle-aged adults even after adjusting for confounding factors.

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Cardiovascular risk/Epidemiology
Increased Risk of Cardiovascular Disease and Mortality in Patients with Diabetes and Coexisting Depression: A Nationwide Population-Based Cohort Study: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2021;45(3):379-389. Published online December 11, 2020; DOI: https://doi.org/10.4093/dmj.2020.0008

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Background
Previous studies have suggested that depression in patients with diabetes is associated with worse health outcomes. The aim of this study was to evaluate the risk of cardiovascular disease (CVD) and mortality in patients with diabetes with comorbid depression.
Methods
We examined the general health check-up data and claim database of the Korean National Health Insurance Service (NHIS) of 2,668,615 participants with type 2 diabetes mellitus who had examinations between 2009 and 2012. As NHIS database has been established since 2002, those who had been diagnosed with depression or CVD since 2002 were excluded. The 2,228,443 participants were classified into three groups according to the claim history of depression; normal group (n=2,166,979), transient depression group (one episode of depression, n=42,124) and persistent depression group (at least two episodes of depression, n=19,340). The development of CVD and mortality were analyzed from 2009 to 2017.
Results
Those with depression showed a significantly increased risk for stroke (transient depression group: hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.15 to 1.26) (persistent depression group: HR, 1.54; 95% CI, 1.46 to 1.63). Those with depression had an increased risk for myocardial infarction (transient depression group: HR, 1.25; 95% CI, 1.18 to 1.31) (persistent depression group: HR, 1.38; 95% CI, 1.29 to 1.49). The persistent depression group had an increased risk for all-cause mortality (HR, 1.66; 95% CI, 1.60 to 1.72).
Conclusion
Coexisting depression in patients with diabetes has a deleterious effect on the development of CVD and mortality. We suggest that more attention should be given to patients with diabetes who present with depressive symptoms.

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Review

Drug/Regimen
Fibrates Revisited: Potential Role in Cardiovascular Risk Reduction: Nam Hoon Kim, Sin Gon Kim; Diabetes Metab J. 2020;44(2):213-221. Published online April 23, 2020; DOI: https://doi.org/10.4093/dmj.2020.0001

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Fibrates, peroxisome proliferator-activated receptor-α agonists, are potent lipid-modifying drugs. Their main effects are reduction of triglycerides and increase in high-density lipoprotein levels. Several randomized controlled trials have not demonstrated their benefits on cardiovascular risk reduction, especially as an “add on” to statin therapy. However, subsequent analyses by major clinical trials, meta-analyses, and real-world evidence have proposed their potential in specific patient populations with atherogenic dyslipidemia and metabolic syndrome. Here, we have reviewed and discussed the accumulated data on fibrates to understand their current status in cardiovascular risk management.

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Original Article

Metabolic Risk/Epidemiology
Sex-, Age-, and Metabolic Disorder-Dependent Distributions of Selected Inflammatory Biomarkers among Community-Dwelling Adults: So Mi Jemma Cho, Hokyou Lee, Jee-Seon Shim, Hyeon Chang Kim; Diabetes Metab J. 2020;44(5):711-725. Published online April 16, 2020; DOI: https://doi.org/10.4093/dmj.2019.0119

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Background

Inflammatory cytokines are increasingly utilized to detect high-risk individuals for cardiometabolic diseases. However, with large population and assay methodological heterogeneity, no clear reference currently exists.

Methods

Among participants of the Cardiovascular and Metabolic Diseases Etiology Research Center cohort, of community-dwelling adults aged 30 to 64 without overt cardiovascular diseases, we presented distributions of tumor necrosis factor (TNF)-α and -β, interleukin (IL)-1α, -1β, and 6, monocyte chemoattractant protein (MCP)-1 and -3 and high sensitivity C-reactive protein (hsCRP) with and without non-detectable (ND) measurements using multiplex enzyme-linked immunosorbent assay. Then, we compared each markers by sex, age, and prevalence of type 2 diabetes mellitus, hypertension, and dyslipidemia, using the Wilcoxon Rank-Sum Test.

Results

In general, there were inconsistencies in direction and magnitude of differences in distributions by sex, age, and prevalence of cardiometabolic disorders. Overall, the median and the 99th percentiles were higher in men than in women. Older participants had higher TNF-α, high sensitivity IL-6 (hsIL-6), MCP-1, hsCRP, TNF-β, and MCP-3 median, after excluding the NDs. Participants with type 2 diabetes mellitus had higher median for all assayed biomarkers, except for TNF-β, IL-1α, and MCP-3, in which the medians for both groups were 0.00 due to predominant NDs. Compared to normotensive group, participants with hypertension had higher TNF-α, hsIL-6, MCP-1, and hsCRP median. When stratifying by dyslipidemia prevalence, the comparison varied significantly depending on the treatment of NDs.

Conclusion

Our findings provide sex-, age-, and disease-specific reference values to improve risk prediction and diagnostic performance for inflammatory diseases in both population- and clinic-based settings.

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Thomas S. Buttle, Claire Y. Hummerstone, Thippeswamy Billahalli, Richard J. B. Ward, Korina E. Barnes, Natalie J. Marshall, Viktoria C. Spong, Graham H. Bothamley, Selvakumar Subbian
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Review

Basic Research
Histone Deacetylase 9: Its Role in the Pathogenesis of Diabetes and Other Chronic Diseases: Siqi Hu, Eun-Hee Cho, Ji-Young Lee; Diabetes Metab J. 2020;44(2):234-244. Published online March 24, 2020; DOI: https://doi.org/10.4093/dmj.2019.0243

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As a member of the class IIa histone deacetylases (HDACs), HDAC9 catalyzes the deacetylation of histones and transcription factors, commonly leading to the suppression of gene transcription. The activity of HDAC9 is regulated transcriptionally and post-translationally. HDAC9 is known to play an essential role in regulating myocyte and adipocyte differentiation and cardiac muscle development. Also, recent studies have suggested that HDAC9 is involved in the pathogenesis of chronic diseases, including cardiovascular diseases, osteoporosis, autoimmune disease, cancer, obesity, insulin resistance, and liver fibrosis. HDAC9 modulates the expression of genes related to the pathogenesis of chronic diseases by altering chromatin structure in their promotor region or reducing the transcriptional activity of their respective transcription factors. This review summarizes the current knowledge of the regulation of HDAC9 expression and activity. Also, the roles of HDAC9 in the pathogenesis of chronic diseases are discussed, along with potential underlying mechanisms.

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Original Articles

Cardiovascular Risk/Epidemiology
Validation of Risk Prediction Models for Atherosclerotic Cardiovascular Disease in a Prospective Korean Community-Based Cohort: Jae Hyun Bae, Min Kyong Moon, Sohee Oh, Bo Kyung Koo, Nam Han Cho, Moon-Kyu Lee; Diabetes Metab J. 2020;44(3):458-469. Published online January 13, 2020; DOI: https://doi.org/10.4093/dmj.2019.0061

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Background

To investigate the performance of the 2013 American College of Cardiology/American Heart Association Pooled Cohort Equations (PCE) in a large, prospective, community-based cohort in Korea and to compare it with that of the Framingham Global Cardiovascular Disease Risk Score (FRS-CVD) and the Korean Risk Prediction Model (KRPM).

Methods

In the Korean Genome and Epidemiology Study (KOGES)-Ansan and Ansung study, we evaluated calibration and discrimination of the PCE for non-Hispanic whites (PCE-WH) and for African Americans (PCE-AA) and compared their predictive abilities with the FRS-CVD and the KRPM.

Results

The present study included 7,932 individuals (3,778 men and 4,154 women). The PCE-WH and PCE-AA moderately overestimated the risk of atherosclerotic cardiovascular disease (ASCVD) for men (6% and 13%, respectively) but underestimated the risk for women (−49% and −25%, respectively). The FRS-CVD overestimated ASCVD risk for men (91%) but provided a good risk prediction for women (3%). The KRPM underestimated ASCVD risk for men (−31%) and women (−31%). All the risk prediction models showed good discrimination in both men (C-statistic 0.730 to 0.735) and women (C-statistic 0.726 to 0.732). Recalibration of the PCE using data from the KOGES-Ansan and Ansung study substantially improved the predictive accuracy in men.

Conclusion

In the KOGES-Ansan and Ansung study, the PCE overestimated ASCVD risk for men and underestimated the risk for women. The PCE-WH and the FRS-CVD provided an accurate prediction of ASCVD in men and women, respectively.

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Cardiovascular Risk/Epidemiology
Pre-existing Depression among Newly Diagnosed Dyslipidemia Patients and Cardiovascular Disease Risk: Jihoon Andrew Kim, Seulggie Choi, Daein Choi, Sang Min Park; Diabetes Metab J. 2020;44(2):307-315. Published online November 1, 2019; DOI: https://doi.org/10.4093/dmj.2019.0002

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Background

Whether depression before diagnosis of dyslipidemia is associated with higher cardiovascular disease (CVD) risk among newly diagnosed dyslipidemia patients is yet unclear.

Methods

The study population consisted of 72,235 newly diagnosed dyslipidemia patients during 2003 to 2012 from the National Health Insurance Service–Health Screening Cohort of South Korea. Newly diagnosed dyslipidemia patients were then detected for pre-existing depression within 3 years before dyslipidemia diagnosis. Starting from 2 years after the diagnosis date, patients were followed up for CVD until 2015. Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for CVD were calculated by Cox proportional hazards regression.

Results

Compared to dyslipidemia patients without depression, those with depression had higher risk for CVD (aHR, 1.24; 95% CI, 1.09 to 1.41). Similarly, pre-existing depression was associated with increased risk for stroke (aHR, 1.27; 95% CI, 1.06 to 1.53). The risk for CVD among depressed dyslipidemia patients for high (aHR, 1.42; 95% CI, 1.06 to 1.90), medium (aHR, 1.17; 95% CI, 0.91 to 1.52), and low (aHR, 1.25; 95% CI, 1.05 to 1.50) statin compliance patients tended to be increased compared to patients without pre-existing dyslipidemia. The risk-elevating effect of depression on CVD tended to be preserved regardless of subgroups of smoking, alcohol consumption, physical activity, and body mass index.

Conclusion

Dyslipidemia patients with pre-existing depression had increased risk for CVD. Future studies that determine CVD risk after management of depression among dyslipidemia patients are needed.

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Lifesytle
Changes in the Quality of Life in Patients with Type 2 Diabetes Mellitus According to Physician and Patient Behaviors: Young-Joo Kim, In-Kyung Jeong, Sin-Gon Kim, Dong Hyeok Cho, Chong-Hwa Kim, Chul-Sik Kim, Won-Young Lee, Kyu-Chang Won, Jin-Hye Cha, Juneyoung Lee, Doo-Man Kim; Diabetes Metab J. 2020;44(1):91-102. Published online October 23, 2019; DOI: https://doi.org/10.4093/dmj.2018.0251

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Background

Diabetes mellitus (DM) is the most common chronic metabolic disorder with an increasing prevalence worldwide. According to a previous study, physicians' treatment patterns or patients' behaviors change when they become aware of the risk for cardiovascular (CV) disease in patients with DM. However, there exist controversial reports from previous studies in the impact of physicians' behaviors on the patients' quality of life (QoL) improvements. So we investigate the changes in QoL according to physicians and patients' behavioral changes after the awareness of CV risks in patients with type 2 DM.

Methods

Data were obtained from a prospective, observational study where 799 patients aged ≥40 years with type 2 DM were recruited at 24 tertiary hospitals in Korea. Changes in physicians' behaviors were defined as changes in the dose/type of antihypertensive, lipid-lowering, and anti-platelet therapies within 6-month after the awareness of CV risks in patients. Changes in patients' behaviors were based on lifestyle modifications. Audit of Diabetes Dependent Quality of Life comprising 19-life-domains was used.

Results

The weighted impact score change for local or long-distance journey (P=0.0049), holidays (P=0.0364), and physical health (P=0.0451) domains significantly differed between the two groups; patients whose physician's behaviors changed showed greater improvement than those whose physician's behaviors did not change.

Conclusion

This study demonstrates that changes in physicians' behaviors, as a result of perceiving CV risks, improve QoL in some domains of life in DM patients. Physicians should recognize the importance of understanding CV risks and implement appropriate management.

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Yulan Li, Dan Chen, Chengmei Xu, Qingyujing Zhao, Yage Ma, Shenglan Zhao, Chaoyin Chen
Food & Function.2020; 11(6): 5538. CrossRef
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Obesity and Metabolic Syndrome
The Association between Z-Score of Log-Transformed A Body Shape Index and Cardiovascular Disease in Korea: Wankyo Chung, Jung Hwan Park, Hye Soo Chung, Jae Myung Yu, Shinje Moon, Dong Sun Kim; Diabetes Metab J. 2019;43(5):675-682. Published online April 26, 2019; DOI: https://doi.org/10.4093/dmj.2018.0169

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Background

In order to overcome the limitations of body mass index (BMI) and waist circumference (WC), the z-score of the log-transformed A Body Shape Index (LBSIZ) has recently been introduced. In this study, we analyzed the relationship between the LBSIZ and cardiovascular disease (CVD) in a Korean representative sample.

Methods

Data were collected from the Korea National Health and Nutrition Examination VI to V. The association between CVD and obesity indices was analyzed using a receiver operating characteristic curve. The cut-off value for the LBSIZ was estimated using the Youden index, and the odds ratio (OR) for CVD was determined via multivariate logistic regression analysis. ORs according to the LBSIZ value were analyzed using restricted cubic spline regression plots.

Results

A total of 31,227 Korean healthy adults were analyzed. Area under the curve (AUC) of LBSIZ against CVD was 0.686 (95% confidence interval [CI], 0.671 to 0.702), which was significantly higher than the AUC of BMI (0.583; 95% CI, 0.567 to 0.599) or WC (0.646; 95% CI, 0.631 to 0.661) (P<0.001). Similar results were observed for stroke and coronary artery diseases. The cut-off value for the LBSIZ was 0.35 (sensitivity, 64.5%; specificity, 64%; OR, 1.29, 95% CI, 1.12 to 1.49). Under restricted cubic spline regression, LBSIZ demonstrated that OR started to increase past the median value.

Conclusion

The findings of this study suggest that the LBSIZ might be more strongly associated with CVD risks compared to BMI or WC. These outcomes would be helpful for CVD risk assessment in clinical settings, especially the cut-off value of the LBSIZ suggested in this study.

Citations

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Associations of four obesity indices with diabetes mellitus in Korean middle-aged and older adults using the Korean Genome and Epidemiology Study (KoGES)
Yiseul Lee, Nam-Kyoo Lim, Hyun-Young Park
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Evaluating the potential of waist-to-BMI ratio, a body shape index, and other anthropometric parameters in predicting cardiovascular disease mortality: evidence from NHANES III
Thung-Lip Lee, Fang-Ju Lin, Chih-Fan Yeh, Yu-Chung Hsiao, Kai-Chien Yang, Chin-Feng Hsuan, Chau-Chung Wu
BMC Public Health.2025;[Epub] CrossRef
Associations of longitudinal trajectories of triglyceride-glucose index combined with classical and novel obesity indices and cardiovascular disease: evidence from a nationwide prospective cohort study in China
Chao Wang, Shiming He, Guobo Xie, Shuhua Zhang, Zhiyu Xiong, Hengcheng Lu, Qun Wang, Lin Xie, Wei Wang, Yang Zou, Xue Li
Cardiovascular Diabetology.2025;[Epub] CrossRef
Comparison of the TyG index, TyG-traditional obesity indices, and TyG-novel obesity indices: does increased complexity help in predicting cardiometabolic multimorbidity?
Fanzhi Zhang, Bin Zhang, Xinfang Huang, Zhenyu Wang, Juan Wang, Houhui Lan, Guobo Xie, Wei Wang, Yang Zou, Chao Wang
Lipids in Health and Disease.2025;[Epub] CrossRef
Body Shape Index and Cardiovascular Risk in Individuals With Obesity
Nazlı Hacıağaoğlu, Can Öner, Hüseyin Çetin, Engin Ersin Şimşek
Cureus.2022;[Epub] CrossRef
Association between body shape index and risk of mortality in the United States
Heysoo Lee, Hye Soo Chung, Yoon Jung Kim, Min Kyu Choi, Yong Kyun Roh, Wankyo Chung, Jae Myung Yu, Chang-Myung Oh, Shinje Moon
Scientific Reports.2022;[Epub] CrossRef
Utility of the Z-score of log-transformed A Body Shape Index (LBSIZ) in the assessment for sarcopenic obesity and cardiovascular disease risk in the United States
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Scientific Reports.2019;[Epub] CrossRef

Epidemiology
Association of Visit-to-Visit Variability of Blood Pressure with Cardiovascular Disease among Type 2 Diabetes Mellitus Patients: A Cohort Study: Zhe-Bin Yu, Die Li, Xue-Yu Chen, Pei-Wen Zheng, Hong-Bo Lin, Meng-Ling Tang, Ming-Juan Jin, Jian-Bing Wang, Kun Chen; Diabetes Metab J. 2019;43(3):350-367. Published online March 6, 2019; DOI: https://doi.org/10.4093/dmj.2018.0108

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Background

Increasing evidence has shown that visit-to-visit variability (VVV) of blood pressure (BP) is associated with an increased risk of cardiovascular disease (CVD). The objective of this study was to evaluate the impact of VVV of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on the risk of CVD among patients with type 2 diabetes mellitus (T2DM) in China.

Methods

We conducted a retrospective cohort study of 10,163 T2DM patients who were not previously diagnosed with CVD from January 2008 to December 2012 in Ningbo, China. The VVV of BP was calculated using five metrics, including standard deviation (SD), coefficient of variation (CV), variation independent of mean, average real variability, and successive variability (SV) of measurements, obtained over a 24-month measurement period. Hazard ratios and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression models for the associations of variability in BP with risk of CVD.

Results

A total of 894 CVD events were observed during a median follow-up of 49.5 months. The hazard ratio in the highest quintile of SD of SBP was 1.24 (95% CI, 1.01 to 1.52) compared with patients in the lowest quintile. The association between higher VVV of DBP and risk of CVD was not consistent across different metrics and sensitivity analyses.

Conclusion

Higher VVV of SBP was associated with an increased risk of CVD, irrespective of the mean SBP level. Future studies are needed to confirm these findings.

Citations

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Hypertension Research.2025; 48(5): 1702. CrossRef
Visit-to-visit blood pressure variability and cardiovascular outcomes: a systematic review and dose-response meta-analysis
Mifetika Lukitasari, Jitendra Jonnagaddala, Siaw-Teng Liaw, Bin Jalaludin
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Min Jeong Park, Kyung Mook Choi
Diabetes & Metabolism Journal.2022; 46(1): 49. CrossRef
Joint effect of blood pressure and glycemic variation on the risk of cardiovascular morbidity and mortality in persons with type 2 diabetes
Cheng-Chieh Lin, Chia-Ing Li, Ya-Ling Juan, Chiu-Shong Liu, Chih-Hsueh Lin, Shing-Yu Yang, Tsai-Chung Li
Metabolism.2022; 136: 155308. CrossRef
Visit‐to‐visit variability of blood pressure and risk of macrovascular and microvascular complications in patients with type 2 diabetes: A Chinese primary‐care cohort study
Ying Deng, Yin Liu, Shengchao Zhang, Hanbing Yu, Xiaozhou Zeng, Rongrong An, Zhenyuan Chen, Na Sun, Xiaoxv Yin, Yue Dong
Journal of Diabetes.2022; 14(11): 767. CrossRef
Visit‑to‑visit blood pressure variability is associated with arterial stiffness in Chinese adults: A prospective analysis
Yuwen Zhang, Lizhan Bie, Mian Li, Tiange Wang, Min Xu, Jieli Lu, Shuangyuan Wang, Jie Zhang, Yufang Bi, Weiqing Wang, Guang Ning, Yuhong Chen, Yu Xu
The Journal of Clinical Hypertension.2021; 23(4): 802. CrossRef
Variability of risk factors and diabetes complications
Antonio Ceriello, Francesco Prattichizzo
Cardiovascular Diabetology.2021;[Epub] CrossRef
Effectiveness of statin intensive therapy in type 2 diabetes mellitus with high visit-to-visit blood pressure variability
Shota Ikeda, Keisuke Shinohara, Nobuyuki Enzan, Shouji Matsushima, Takeshi Tohyama, Kouta Funakoshi, Junji Kishimoto, Hiroshi Itoh, Issei Komuro, Hiroyuki Tsutsui
Journal of Hypertension.2021; 39(7): 1435. CrossRef
Prognostic importance of visit-to-visit blood pressure variability for micro- and macrovascular outcomes in patients with type 2 diabetes: The Rio de Janeiro Type 2 Diabetes Cohort Study
Claudia R. L. Cardoso, Nathalie C. Leite, Gil F. Salles
Cardiovascular Diabetology.2020;[Epub] CrossRef
Impact of visit-to-visit variability in blood pressure on coronary plaque as assessed by integrated backscatter intravascular ultrasound
Yuta Kato, Atsushi Iwata, Makito Futami, Motoki Yamashita, Eiji Shigemoto, Takashi Kuwano, Makoto Sugihara, Shin-Ichiro Miura
Clinical and Experimental Hypertension.2020; 42(7): 608. CrossRef
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T.I. Nimtsovych, A.M. Kravchenko, O.Yu. Mishcheniuk, К.О. Mikhaliev, T.Ya. Chursina
Клінічна та профілактична медицина.2020; (2): 90. CrossRef
VISIT-TO-VISIT BLOOD PRESSURE VARIABILITY AND TARGET ORGAN DAMAGE IN RURAL DWELLERS WITH UNCOMPLICATED ARTERIAL HYPERTENSION
Tetiana I. Nimtsovych, Anatolii M. Kravchenko, Olha Yu. Mishcheniuk, Tamara Ya. Chursina, Кyrylo О. Mikhaliev, Viktor P. Polovyi
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Seung-Hwan Lee, Hun-Sung Kim, Yong-Moon Park, Hyuk-Sang Kwon, Kun-Ho Yoon, Kyungdo Han, Mee Kyoung Kim
The Journal of Clinical Endocrinology & Metabolism.2019; 104(11): 5633. CrossRef

Obesity and Metabolic Syndrome
The Risk of Myocardial Infarction and Ischemic Stroke According to Waist Circumference in 21,749,261 Korean Adults: A Nationwide Population-Based Study: Jung-Hwan Cho, Eun-Jung Rhee, Se-Eun Park, Hyemi Kwon, Jin-Hyung Jung, Kyung-Do Han, Yong-Gyu Park, Hye Soon Park, Yang-Hyun Kim, Soon-Jib Yoo, Won-Young Lee; Diabetes Metab J. 2019;43(2):206-221. Published online December 27, 2018; DOI: https://doi.org/10.4093/dmj.2018.0039

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Background

Waist circumference (WC) is a well-known obesity index that predicts cardiovascular disease (CVD). We studied the relationship between baseline WC and development of incident myocardial infarction (MI) and ischemic stroke (IS) using a nationwide population-based cohort, and evaluated if its predictability is better than body mass index (BMI).

Methods

Our study included 21,749,261 Koreans over 20 years of age who underwent the Korean National Health Screening between 2009 and 2012. The occurrence of MI or IS was investigated until the end of 2015 using National Health Insurance Service data.

Results

A total of 127,289 and 181,637 subjects were newly diagnosed with MI and IS. The incidence rate and hazard ratio of MI and IS increased linearly as the WC level increased, regardless of adjustment for BMI. When the analyses were performed according to 11 groups of WC, the lowest risk of MI was found in subjects with WC of 70 to 74.9 and 65 to 69.9 cm in male and female, and the lowest risk of IS in subjects with WC of 65 to 69.9 and 60 to 64.9 cm in male and female, respectively. WC showed a better ability to predict CVD than BMI with smaller Akaike information criterion. The optimal WC cutoffs were 84/78 cm for male/female for predicting MI, and 85/78 cm for male/female for predicting IS.

Conclusion

WC had a significant linear relationship with the risk of MI and IS and the risk began to increase from a WC that was lower than expected.

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Clinical Diabetes and Therapeutics
Cardio-Ankle Vascular Index as a Surrogate Marker of Early Atherosclerotic Cardiovascular Disease in Koreans with Type 2 Diabetes Mellitus: So Young Park, Sang Ook Chin, Sang Youl Rhee, Seungjoon Oh, Jeong-Taek Woo, Sung Woon Kim, Suk Chon; Diabetes Metab J. 2018;42(4):285-295. Published online July 27, 2018; DOI: https://doi.org/10.4093/dmj.2017.0080

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Background

Carotid artery intima medial thickness (IMT), brachial-ankle pulse wave velocity (baPWV), and ankle-brachial index (ABI) are commonly used surrogate markers of subclinical atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The cardio-ankle vascular index (CAVI) is a complement to the baPWV, which is affected by blood pressure. However, it is unclear which marker is the most sensitive predictor of atherosclerotic cardiovascular disease (ASCVD).

Methods

This was a retrospective non-interventional study that enrolled 219 patients with T2DM. The correlations among IMT, ABI, and CAVI as well as the relationship of these tests to the 10-year ASCVD risk were also analyzed.

Results

Among the 219 patients, 39 (17.8%) had ASCVD. In the non-ASCVD group, CAVI correlated significantly with IMT after adjusting for confounding variables, but ABI was not associated with CAVI or IMT. The analyses after dividing the non-ASCVD group into three subgroups according to the CAVI score (<8, ≥8 and <9, and ≥9) demonstrated the significant increase in the mean IMT, 10-year ASCVD risk and number of metabolic syndrome risk factors, and decrease in the mean ABI in the high-CAVI group. A high CAVI was an independent risk factor in the non-ASCVD group for both a high 10-year ASCVD risk (≥7.5%; odds ratio [OR], 2.42; P<0.001) and atherosclerosis (mean IMT ≥1 mm; OR, 1.53; P=0.007).

Conclusion

In Korean patients with T2DM without ASCVD, CAVI was the most sensitive of several surrogate markers for the detection of subclinical atherosclerosis.

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Complications
Serum Levels of PCSK9 Are Associated with Coronary Angiographic Severity in Patients with Acute Coronary Syndrome: Kwi-Hyun Bae, Sung Woo Kim, Yeon-Kyung Choi, Jung Beom Seo, Namkyun Kim, Chang-Yeon Kim, Won Kee Lee, Sungwoo Lee, Jung Guk Kim, In-Kyu Lee, Jang Hoon Lee, Keun-Gyu Park; Diabetes Metab J. 2018;42(3):207-214. Published online May 2, 2018; DOI: https://doi.org/10.4093/dmj.2017.0081

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Background

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that promotes degradation of the low density lipoprotein receptor. PCSK9 has emerged as a target for lipid-lowering therapy, but the predictive value of the serum level of PCSK9 for the severity of coronary disease is largely unknown.

Methods

From December 2009 to July 2012, 121 individuals who underwent coronary angiography (CAG) because of clinically suspected acute coronary syndrome were enrolled in this study. Serum levels of PCSK9 and metabolic parameters were measured. SYNTAX (SYNergy between percutaneous coronary intervention with [paclitaxel-eluting] TAXUS stent and cardiac surgery) and GRACE (Global Registry of Acute Coronary Events) scores were calculated.

Results

Individuals with CAG lesions (n=100) had significantly higher levels of PCSK9 than those without lesions (n=21). The study population was stratified into three groups according to serum levels of PCSK9. The odds radio for occurrence of one or more CAG lesions was significantly higher in the group with the highest level of PCSK9 (odds ratio, 7.468; P=0.011) than in the group with the lowest level of PCSK9. Serum PCSK9 was positively associated with the number of involved coronary arteries. Multivariable linear regression indicated that levels of PCSK9 were positively correlated with GRACE risk scores and SYNTAX scores.

Conclusion

Serum PCSK9 concentrations are higher in patients with coronary artery lesions, and are associated with SYNTAX and GRACE scores, suggesting that PCSK9 is a potential biomarker of the severity of coronary artery disease.

Citations

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Epidemiology
Ten-Year Mortality Trends for Adults with and without Diabetes Mellitus in South Korea, 2003 to 2013: Kyeong Jin Kim, Tae Yeon Kwon, Sungwook Yu, Ji A Seo, Nan Hee Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Sin Gon Kim, Yousung Park, Nam Hoon Kim; Diabetes Metab J. 2018;42(5):394-401. Published online April 26, 2018; DOI: https://doi.org/10.4093/dmj.2017.0088

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Background

To estimate and compare the trends of all-cause and cause-specific mortality rates for subjects with and without diabetes in South Korea, from 2003 to 2013.

Methods

Using a population-based cohort (2003 to 2013), we evaluated annual mortality rates in adults (≥30 years) with and without diabetes. The number of subjects in this analysis ranged from 585,795 in 2003 to 670,020 in 2013.

Results

Age- and sex-adjusted all-cause mortality rates decreased consistently in both groups from 2003 to 2013 (from 14.4 to 9.3/1,000 persons in subjects with diabetes and from 7.9 to 4.4/1,000 persons in those without diabetes). The difference in mortality rates between groups also decreased (6.61 per 1,000 persons in 2003 to 4.98 per 1,000 persons in 2013). The slope associated with the mortality rate exhibited a steeper decrease in subjects with diabetes than those without diabetes (regression coefficients of time: −0.50 and −0.33, respectively; P=0.004). In subjects with diabetes, the mortality rate from cardiovascular disease decreased by 53.5% (from 2.73 to 1.27 per 1,000 persons, P for trend <0.001). Notably, the decrease in mortality from ischemic stroke (79.2%, from 1.20 to 0.25 per 1,000 persowns) was more profound than that from ischemic heart disease (28.3%, from 0.60 to 0.43 per 1,000 persons).

Conclusion

All-cause and cardiovascular mortality rates decreased substantially from 2003 to 2013, and the decline in ischemic stroke mortality mainly contributed to the decreased cardiovascular mortality in Korean people with diabetes.

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Reviews

Clinical Diabetes & Therapeutics
Past and Current Status of Adult Type 2 Diabetes Mellitus Management in Korea: A National Health Insurance Service Database Analysis: Seung-Hyun Ko, Kyungdo Han, Yong-ho Lee, Junghyun Noh, Cheol-Young Park, Dae-Jung Kim, Chang Hee Jung, Ki-Up Lee, Kyung-Soo Ko; Diabetes Metab J. 2018;42(2):93-100. Published online April 19, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.2.93

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Korea's National Healthcare Program, the National Health Insurance Service (NHIS), a government-affiliated agency under the Korean Ministry of Health and Welfare, covers the entire Korean population. The NHIS supervises all medical services in Korea and establishes a systematic National Health Information database (DB). A health information DB system including all of the claims, medications, death information, and health check-ups, both in the general population and in patients with various diseases, is not common worldwide. On June 9, 2014, the NHIS signed a memorandum of understanding with the Korean Diabetes Association (KDA) to provide limited open access to its DB. By October 31, 2017, seven papers had been published through this collaborative research project. These studies were conducted to investigate the past and current status of type 2 diabetes mellitus and its complications and management in Korea. This review is a brief summary of the collaborative projects between the KDA and the NHIS over the last 3 years. According to the analysis, the national health check-up DB or claim DB were used, and the age category or study period were differentially applied.

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Obesity and Metabolic Syndrome
Being Metabolically Healthy, the Most Responsible Factor for Vascular Health: Eun-Jung Rhee; Diabetes Metab J. 2018;42(1):19-25. Published online January 26, 2018; DOI: https://doi.org/10.4093/dmj.2018.42.1.19

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The prevalence of obesity is rapidly increasing worldwide. One-thirds of world population is suffering from the deleterious effects of excessive fat and adipose tissue in their body. At the same time, the average life expectancy is becoming higher and higher every decade. Therefore, living healthy and longer is the dream for everyone. Simply being obese is not the primary cause for the consequence of obesity; rather, the depot where the fat is accumulated, is the primary key for the deleterious effects of obesity. Results from historical research suggest that visceral fat increases the risk for cardiovascular and metabolic diseases, such as diabetes, myocardial infarction and ischemic stroke, not subcutaneous fat. Therefore, body mass index (BMI), which reflects body weight relative to height might not reflect the appropriate size of metabolic burden of fat in our body. In contrast, waist circumference, which reflects abdominal obesity, would mirror the metabolic burden of fat better than BMI. Visceral fat is the marker of ectopic fat accumulation. In this review, I will introduce my researches mainly involved in uncovering the clues to the link between metabolic health and cardiovascular disease.

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Original Articles

Epidemiology
Dietary Sodium Intake in People with Diabetes in Korea: The Korean National Health and Nutrition Examination Survey for 2008 to 2010: Myung Shin Kang, Chong Hwa Kim, Su Jin Jeong, Tae Sun Park; Diabetes Metab J. 2016;40(4):290-296. Published online June 23, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.4.290

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Background

Diabetics are likely to receive advice from their physicians concerning lifestyle changes. To understand how much sodium is consumed by diabetics in Korea, we compared the average daily sodium intake between diabetics and non-diabetics after controlling for confounding factors.

Methods

We obtained the sodium intake data for 13,957 individuals who participated in the Korean National Health and Nutrition Examination Survey (KNHANES), 2008 to 2010, which consisted of a health interview and behavioral and nutritional surveys. The KNHANES uses a stratified, multistage, probability-sampling design, and weighting adjustments were conducted to represent the entire population.

Results

Our analysis revealed that, overall, diabetics tended to have lower sodium intake (4,910.2 mg) than healthy individuals (5,188.2 mg). However, both diabetic and healthy individuals reported higher sodium intake than is recommended by the World Health Organization (WHO). Stratified subgroup analyses revealed that the sodium intake (4,314.2 mg) among newly diagnosed diabetics was higher among women when compared to patients with known diabetes (3,812.5 mg, P=0.035). Female diabetics with cardiovascular disease had lower average sodium intake compared to those without cardiovascular disease after adjusting for sex, age, body mass index, and total energy intake (P=0.058). Sodium intake among male diabetics with hypercholesterolemia (P=0.011) and female diabetics with hypertriglyceridemia (P=0.067) tended to be higher than that among those who without dyslipidemia.

Conclusion

The average sodium intake of diabetics in Korea was higher than the WHO recommends. Sodium intake in newly diagnosed diabetics was significantly higher than that in non-diabetics and previously diagnosed diabetics among females. Prospective studies are needed to identify the exact sodium intake.

Citations

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Natália Gonçalves Ribeiro, Deborah F. Lelis, Rosane H. Griep, Sandhi M. Barreto, Maria del Carmen B Molina, Maria I. Schmidt, Bruce B. Duncan, Isabela Bensenor, Paulo A. Lotufo, José G. Mill, Marcelo Perim Baldo
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Complications
Severe Hypoglycemia and Cardiovascular or All-Cause Mortality in Patients with Type 2 Diabetes: Seon-Ah Cha, Jae-Seung Yun, Tae-Seok Lim, Seawon Hwang, Eun-Jung Yim, Ki-Ho Song, Ki-Dong Yoo, Yong-Moon Park, Yu-Bae Ahn, Seung-Hyun Ko; Diabetes Metab J. 2016;40(3):202-210. Published online April 5, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.3.202

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Background

We investigated the association between severe hypoglycemia (SH) and the risk of cardiovascular (CV) or all-cause mortality in patients with type 2 diabetes.

Methods

The study included 1,260 patients aged 25 to 75 years with type 2 diabetes from the Vincent Type 2 Diabetes Resgistry (VDR), who consecutively enrolled (n=1,260) from January 2000 to December 2010 and were followed up until May 2015 with a median follow-up time of 10.4 years. Primary outcomes were death from any cause or CV death. We investigated the association between the CV or all-cause mortality and various covariates using Cox proportional hazards regression analysis.

Results

Among the 906 participants (71.9%) who completed follow-up, 85 patients (9.4%) had at least one episode of SH, and 86 patients (9.5%) died (9.1 per 1,000 patient-years). Patients who had died were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline, as compared with surviving patients. The experience of SH was significantly associated with an increased risk of all-cause mortality (hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.39 to 5.02; P=0.003) and CV mortality (HR, 6.34; 95% CI, 2.02 to 19.87; P=0.002) after adjusting for sex, age, diabetic duration, hypertension, mean glycosylated hemoglobin levels, diabetic nephropathy, lipid profiles, and insulin use.

Conclusion

We found a strong association between SH and increased risk of all-cause and CV mortality in patients with type 2 diabetes.

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Review

Clinical Care/Education
Dipeptidyl Peptidase 4 Inhibitors and the Risk of Cardiovascular Disease in Patients with Type 2 Diabetes: A Tale of Three Studies: Jang Won Son, Sungrae Kim; Diabetes Metab J. 2015;39(5):373-383. Published online October 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.5.373

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Dipeptidyl peptidase 4 (DPP4) inhibitors have been touted as promising antihyperglycemic agents due to their beneficial effects on glycemia without inducing hypoglycemia or body weight gain and their good tolerability. Beyond their glucose-lowering effects, numerous clinical trials and experimental studies have suggested that DPP4 inhibitors may exert cardioprotective effects through their pleiotropic actions via glucagon-like peptide 1-dependent mechanisms or involving other substrates. Since 2008, regulatory agencies have required an assessment of cardiovascular disease (CVD) safety for the approval of all new anti-hyperglycemic agents, including incretin-based therapies. Three large prospective DPP4 inhibitor trials with cardiovascular (CV) outcomes have recently been published. According to the Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus (SAVOR-TIMI 53) and EXamination of cArdiovascular outcoMes with alogliptIN versus standard of carE in patients with type 2 diabetes mellitus and acute coronary syndrome (EXAMINE) trials, DPP4 inhibitors, including saxagliptin and alogliptin, did not appear to increase the risk of CV events in patients with type 2 diabetes and established CVD or high risk factors. Unexpectedly, saxagliptin significantly increased the risk of hospitalization for heart failure by 27%, a finding that has not been explained and that requires further exploration. More recently, the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) trial demonstrated the CV safety of sitagliptin, including assessments of the primary composite CV endpoint and hospitalization for heart failure in patients with type 2 diabetes and established CVD. The CV outcomes of an ongoing linagliptin trial are expected to provide new evidence about the CV effects of a DPP4-inhibitor in patients with type 2 diabetes.

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Original Articles

Complications
Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes: Jae-Seung Yun, Seung-Hyun Ko, Sun-Hye Ko, Ki-Ho Song, Ki-Dong Yoo, Kun-Ho Yoon, Yong-Moon Park, Yu-Bae Ahn; Diabetes Metab J. 2015;39(6):498-506. Published online July 8, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.6.498

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Background

To investigate whether a history of prior cardiovascular disease (CVD) is associated with severe hypoglycemia (SH) in patients with type 2 diabetes.

Methods

We conducted a prospective cohort study from January 2001 to December 2012 with a median follow-up time of 9.5 years (5,814 person-years). Patients aged 25 to 75 years with type 2 diabetes and without chronic kidney disease were enrolled (n=894), and 624 patients completed follow-up. SH was defined as hypoglycemic episodes requiring hospitalization or medical care in an emergency department. We used the Cox proportional hazards regression analysis to test associations between SH episodes and potential explanatory variables.

Results

Among the 624 participants who completed follow-up, 60 patients (9.6%) had previous CVD. Compared to patients without CVD, patients with previous CVD were older, had a longer duration of diabetes and hypertension, received more insulin, and had more diabetic microvascular complications at baseline. During follow-up, 62 patients (9.9%) experienced at least one SH episode (incidence of 1.33 per 100 patient-years). The development of SH was associated with a history of CVD (hazard ratio, 1.99; 95% confidence interval, 1.07 to 3.72; P=0.031) after adjusting for sex, age, diabetic duration, hypertension, hemoglobin A1c levels, diabetic complications, cardiovascular autonomic neuropathy, and insulin use.

Conclusion

A history of CVD was an independent risk factor for the development of SH in patients with type 2 diabetes mellitus. For patients with CVD, modulation of glycemic targets and diabetic education for the prevention of hypoglycemia should be implemented.

Citations

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Letter: Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes (Diabetes Metab J 2015;39:498-506)
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Response: Cardiovascular Disease Predicts Severe Hypoglycemia in Patients with Type 2 Diabetes (Diabetes Metab J 2015;39:498-506)
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Diabetes & Metabolism Journal.2016; 40(1): 85. CrossRef
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Severe Hypoglycemia and Cardiovascular Disease in Type 2 Diabetes
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Women Are Diagnosed with Type 2 Diabetes at Higher Body Mass Indices and Older Ages than Men: Korea National Health and Nutrition Examination Survey 2007-2010: Su Kyoung Kwon; Diabetes Metab J. 2014;38(1):74-80. Published online February 19, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.1.74

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Background

Many epidemiologic studies have shown that women with type 2 diabetes have an increased risk of developing cardiovascular disease compared with men with diabetes. The aim of this study is to elucidate whether disparities of adiposity, age and insulin resistance (IR) at the time of diabetes diagnosis exist between women and men in the adult Korean population.

Methods

Data from The Korea National Health and Nutrition Examination Survey, performed in Korea from 2007 to 2010, were used. In the survey, anthropometric data and blood samples were obtained during a fasting state. IR and β-cell function were calculated using the homeostasis model assessment (HOMA-IR and HOMA-β, respectvely).

Results

The mean age of diabetes diagnosis was 58.5 years in women and was 55.1 years in men (P=0.015). The mean body mass index (BMI) of newly diagnosed diabetes subjects was 26.1 kg/m² in women and 25.0 kg/m² in men (P=0.001). The BMI was inversely related to age in both genders, and the higher BMI in women than men was consistent throughout all age groups divided by decade. The HOMA-IR in women with diabetes is higher than in men with diabetes (7.25±0.77 vs. 5.20±0.32; P=0.012).

Conclusion

Korean adult women are diagnosed with type 2 diabetes at higher BMI and older age than men and are more insulin-resistant at the time of diabetes diagnosis. This may help explain why women with diabetes have an increased risk of developing cardiovascular disease after the diagnosis of diabetes, compared to men.

Citations

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Statin Discontinuation after Achieving a Target Low Density Lipoprotein Cholesterol Level in Type 2 Diabetic Patients without Cardiovascular Disease: A Randomized Controlled Study: Seung-Hwan Lee, Hyuk-Sang Kwon, Yong-Moon Park, Seung-Hyun Ko, Yoon-Hee Choi, Kun-Ho Yoon, Yu-Bae Ahn; Diabetes Metab J. 2014;38(1):64-73. Published online February 19, 2014; DOI: https://doi.org/10.4093/dmj.2014.38.1.64

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Background

This study investigated the rate of relapse of dyslipidemia and the factors which could predict relapse following a short-term statin discontinuation after achieving a target low density lipoprotein cholesterol (LDL-C) level in type 2 diabetic patients without cardiovascular disease (CVD).

Methods

Ninety-nine subjects on rosuvastatin treatment and whose LDL-C level was lower than 100 mg/dL were randomly assigned to discontinue or maintain statin treatment at a 2:1 ratio. The subjects were followed-up after 10 weeks. A relapse of dyslipidemia was defined as a reascent of LDL-C level to greater than 100 mg/dL.

Results

The statin discontinuation group had a significant rate of relapse compared to the maintenance group (79% vs. 3%, respectively). Pretreatment and baseline lipid levels, their ratios, and hemoglobin A1c level were significantly different between the relapse and nonrelapse groups. The pretreatment and baseline lipid profiles and their ratios were independently associated with relapse. The pretreatment LDL-C level was the most useful parameter for predicting a relapse, with a cutoff of 123 mg/dL. During the follow-up period, no CVD event was noted.

Conclusion

The relapse rate of dyslipidemia was high when statins were discontinued in type 2 diabetic patients without CVD. Statin discontinuation should be considered carefully based on the pretreatment lipid profiles of patients.

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Reviews

Diabetogenic Effect of Statins: A Double-Edged Sword?: Ji Sung Yoon, Hyoung Woo Lee; Diabetes Metab J. 2013;37(6):415-422. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.415

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Statins are widely prescribed cholesterol-lowering agents, which have been demonstrated to significantly reduce cardiovascular morbidity and mortality. However, recent trials have reported that statins cause worsening of hyperglycemia and increase the risk of new-onset diabetes. The association between the diabetogenic effect of statins with intensive dose and accompanying major risk factors for diabetes has been demonstrated. However, statins do not appear to have a class effect on insulin sensitivity in non-diabetic patients. Numerous mechanisms have been suggested to explain how statins cause β-cell insulin secretory dysfunction and peripheral insulin resistance leading to incident diabetes. According to findings from an aggregate of large clinical trials, the benefits of statin treatment appear to outweigh the risk of new-onset diabetes. Therefore, it would be inappropriate to discontinue the use of statins for prevention of cardiovascular events because of its potential risk for development of incident diabetes. This review addresses the currently available evidence related to statin use and new-onset diabetes from a clinical perspective.

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Resistin in Rodents and Humans: Hyeong Kyu Park, Rexford S. Ahima; Diabetes Metab J. 2013;37(6):404-414. Published online December 12, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.6.404

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Abstract PDF PubReader ePub

Obesity is characterized by excess accumulation of lipids in adipose tissue and other organs, and chronic inflammation associated with insulin resistance and an increased risk of type 2 diabetes. Obesity, type 2 diabetes, and cardiovascular diseases are major health concerns. Resistin was first discovered as an adipose-secreted hormone (adipokine) linked to obesity and insulin resistance in rodents. Adipocyte-derived resistin is increased in obese rodents and strongly related to insulin resistance. However, in contrast to rodents, resistin is expressed and secreted from macrophages in humans and is increased in inflammatory conditions. Some studies have also suggested an association between increased resistin levels and insulin resistance, diabetes and cardiovascular disease. Genetic studies have provided additional evidence for a role of resistin in insulin resistance and inflammation. Resistin appears to mediate the pathogenesis of atherosclerosis by promoting endothelial dysfunction, vascular smooth muscle cell proliferation, arterial inflammation, and formation of foam cells. Indeed, resistin is predictive of atherosclerosis and poor clinical outcomes in patients with coronary artery disease and ischemic stroke. There is also growing evidence that elevated resistin is associated with the development of heart failure. This review will focus on the biology of resistin in rodents and humans, and evidence linking resistin with type 2 diabetes, atherosclerosis, and cardiovascular disease.

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Resistin production does not affect outcomes in a mouse model of acute surgical sepsis
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Single-nucleotide polymorphisms as important risk factors of diabetes among Middle East population
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Hsin-Hua Chou, Lung-An Hsu, Jyh-Ming Jimmy Juang, Fu-Tien Chiang, Ming-Sheng Teng, Semon Wu, Yu-Lin Ko
International Journal of Molecular Sciences.2022; 23(8): 4292. CrossRef
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American Journal of Respiratory and Critical Care Medicine.2022; 205(8): 903. CrossRef
The Role of the Adipokine Resistin in the Pathogenesis and Progression of Epithelial Ovarian Cancer
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Biomedicines.2022; 10(4): 920. CrossRef
Resistin Modulates Low-Density Lipoprotein Cholesterol Uptake in Human Placental Explants via PCSK9
Sonia Nava-Salazar, Arturo Flores-Pliego, Giovanni Pérez-Martínez, Sandra Parra-Hernández, America Vanoye-Carlo, Francisco Ibarguengoitia-Ochoa, Otilia Perichart-Perera, Enrique Reyes-Muñoz, Juan Mario Solis-Paredes, Salvador Espino y Sosa, Guadalupe Estr
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Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study
Mohammad Muzaffar Mir, Rashid Mir, Mushabab Ayed Abdullah Alghamdi, Javed Iqbal Wani, Zia Ul Sabah, Mohammed Jeelani, Vijaya Marakala, Shahzada Khalid Sohail, Mohamed O’haj, Muffarah Hamid Alharthi, Mohannad Mohammad S. Alamri
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Immune system and sarcopenia: Presented relationship and future perspective
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Experimental Gerontology.2022; 164: 111823. CrossRef
Adipose Tissue Secretion Pattern Influences β-Cell Wellness in the Transition from Obesity to Type 2 Diabetes
Giuseppina Biondi, Nicola Marrano, Anna Borrelli, Martina Rella, Giuseppe Palma, Isabella Calderoni, Edoardo Siciliano, Pasquale Lops, Francesco Giorgino, Annalisa Natalicchio
International Journal of Molecular Sciences.2022; 23(10): 5522. CrossRef
Supplemental hydroxychloroquine therapy regulates adipokines in patients with systemic lupus erythematosus with stable disease
Risa Wakiya, Kiyo Ueeda, Hiromi Shimada, Shusaku Nakashima, Tomohiro Kameda, Nobuyuki Miyatake, Mikiya Kato, Taichi Miyagi, Koichi Sugihara, Mao Mizusaki, Rina Mino, Norimitsu Kadowaki, Hiroaki Dobashi
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Can soy isoflavones in combination with soy protein change serum concentration of adiponectin and resistin? A systematic review and meta‐analysis on randomized clinical trials
Mitra Hariri, Bahareh Amirkalali, Ensiyeh Mollanoroozy, Ali Gholami
Food Science & Nutrition.2022; 10(12): 4126. CrossRef
Adipokines: Deciphering the cardiovascular signature of adipose tissue
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Biochemical Pharmacology.2022; 206: 115324. CrossRef
Evaluation of the Anti-Obesity Effect of Zeaxanthin and Exercise in HFD-Induced Obese Rats
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Nutrients.2022; 14(23): 4944. CrossRef
Single High-Dose Vitamin D Supplementation as an Approach for Reducing Ultramarathon-Induced Inflammation: A Double-Blind Randomized Controlled Trial
Jan Mieszkowski, Andżelika Borkowska, Błażej Stankiewicz, Andrzej Kochanowicz, Bartłomiej Niespodziński, Marcin Surmiak, Tomasz Waldziński, Rafał Rola, Miroslav Petr, Jędrzej Antosiewicz
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Resistin mitigates stemness and metabolic profile of human adipose-derived mesenchymal stem cells via insulin resistance
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Cytokine.2021; 138: 155374. CrossRef
Resistin is co-secreted with adiponectin in white mouse adipocytes
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Biochemical and Biophysical Research Communications.2021; 534: 707. CrossRef
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The circulating levels of CTRP1 and CTRP5 are associated with obesity indices and carotid intima-media thickness (cIMT) value in patients with type 2 diabetes: a preliminary study
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Diabetology & Metabolic Syndrome.2021;[Epub] CrossRef
Corylin reduces obesity and insulin resistance and promotes adipose tissue browning through SIRT-1 and β3-AR activation
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Pharmacological Research.2021; 164: 105291. CrossRef
A Focused Review of the Metabolic Side-Effects of Clozapine
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Frontiers in Endocrinology.2021;[Epub] CrossRef
A Negative Energy Balance Is Associated with Metabolic Dysfunctions in the Hypothalamus of a Humanized Preclinical Model of Alzheimer’s Disease, the 5XFAD Mouse
Antonio J. López-Gambero, Cristina Rosell-Valle, Dina Medina-Vera, Juan Antonio Navarro, Antonio Vargas, Patricia Rivera, Carlos Sanjuan, Fernando Rodríguez de Fonseca, Juan Suárez
International Journal of Molecular Sciences.2021; 22(10): 5365. CrossRef
Resistin in pregnancy: Analysis of determinants in pairs of umbilical cord blood and maternal serum
Anne Floeck, Nina Ferrari, Christine Joisten, Maria T. Puth, Brigitte Strizek, Ramona Dolscheid-Pommerich, Ulrich Gembruch, Waltraut M. Merz
Cytokine: X.2021; 3(2): 100052. CrossRef
Is resistin the master link between inflammation and inflammation-related chronic diseases?
Mohammed Taouis, Yacir Benomar
Molecular and Cellular Endocrinology.2021; 533: 111341. CrossRef
The dynamics of human bone marrow adipose tissue in response to feeding and fasting
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Obesity is the basis of metabolic syndrome
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Human Milk Metabolic Hormones: Analytical Methods and Current Understanding
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Adipokines as Immune Cell Modulators in Multiple Sclerosis
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The Role of Adipokines in Cardiovascular Pathology
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Measurement of Plasma Resistin Concentrations in Horses with Metabolic and Inflammatory Disorders
Beatriz Fuentes-Romero, Alberto Muñoz-Prieto, José J. Cerón, María Martín-Cuervo, Manuel Iglesias-García, Escolástico Aguilera-Tejero, Elisa Díez-Castro
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EFFECT OF DIET AND EXERCISE-INDUCE WEIGHT LOSS ON LEVEL OF RESISTIN IN PATIENT WITH OBESITY
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Modern medical technology.2021; (4): 11. CrossRef
Alteration of gut microbiota affects expression of adiponectin and resistin through modifying DNA methylation in high-fat diet-induced obese mice
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Genes & Nutrition.2020;[Epub] CrossRef
Resistin hormone in diabetic kidney disease and its relation to iron status and hepcidin
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International Urology and Nephrology.2020; 52(4): 749. CrossRef
Proteoglycans in Obesity-Associated Metabolic Dysfunction and Meta-Inflammation
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Frontiers in Immunology.2020;[Epub] CrossRef
Resistin Is Increased in Periodontal Cells and Tissues: In Vitro and In Vivo Studies
Andressa V. B. Nogueira, Marjan Nokhbehsaim, Sema Tekin, Rafael S. de Molon, Luis C. Spolidorio, Svenja Memmert, Anna Damanaki, Andreas Jäger, Sigrun Eick, James Deschner, Joni A. Cirelli
Mediators of Inflammation.2020; 2020: 1. CrossRef
Adipose Tissue Distribution, Inflammation and Its Metabolic Consequences, Including Diabetes and Cardiovascular Disease
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Frontiers in Cardiovascular Medicine.2020;[Epub] CrossRef
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Minerva Endocrinologica.2020;[Epub] CrossRef
High Plasma Resistin Levels Portend the Insulin Resistance-Associated Susceptibility to Early Cognitive Decline in Patients with Type 2 Diabetes Mellitus
Chenchen Wang, Xi Huang, Sai Tian, Rong Huang, Dan Guo, Hongyan Lin, Jiaqi Wang, Shaohua Wang
Journal of Alzheimer’s Disease.2020; 75(3): 807. CrossRef
Resistin in metabolism, inflammation, and disease
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The FEBS Journal.2020; 287(15): 3141. CrossRef
Adipokines: New Potential Therapeutic Target for Obesity and Metabolic, Rheumatic, and Cardiovascular Diseases
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Frontiers in Physiology.2020;[Epub] CrossRef
Correlation of CCL18 with Levels of Adi-pokines in the Sera of Patients with Myocardial Infarction in a 6-Month Period: Case Series
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Iranian South Medical Journal.2020; 23(3): 222. CrossRef
Association of RETN − 420 C/G Genotypes with CRP, Brain Edema, GCS, and GOS Among Patients with Traumatic Cerebral Hemorrhagic Contusion
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Journal of Emergency Medicine, Trauma and Acute Care .2020;[Epub] CrossRef
The Mesentery, Systemic Inflammation, and Crohn’s Disease
Edgardo D Rivera, John Calvin Coffey, Dara Walsh, Eli D Ehrenpreis
Inflammatory Bowel Diseases.2019; 25(2): 226. CrossRef
Resistin and adenylyl cyclase-associated protein 1 (CAP1) regulate the expression of genes related to insulin resistance in BNL CL.2 mouse liver cells
Dimiter Avtanski, Karin Chen, Leonid Poretsky
Data in Brief.2019; 25: 104112. CrossRef
Proteomic profile of patients with atrial fibrillation undergoing cardiac surgery†
Ilias P Doulamis, George Samanidis, Aspasia Tzani, Asier Antoranz, Anastasios Gkogkos, Panagiotis Konstantopoulos, Vaia Pliaka, Angeliki Minia, Leonidas G Alexopoulos, Despina N Perrea, Konstantinos Perreas
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Angiotensin-(1-7), Adipokines and Inflammation
Deborah de Farias Lelis, Daniela Fernanda de Freitas, Amanda Souto Machado, Thaísa Soares Crespo, Sérgio Henrique Sousa Santos
Metabolism.2019; 95: 36. CrossRef
New Insights into Adipokines as Potential Biomarkers for Type-2 Diabetes Mellitus
Marta Olivera-Santa Catalina, Pedro C. Redondo, Maria P. Granados, Carlos Cantonero, Jose Sanchez-Collado, Letizia Albarran, Jose J. Lopez
Current Medicinal Chemistry.2019; 26(22): 4119. CrossRef
Myokine–adipokine cross-talk: potential mechanisms for the association between plasma irisin and adipokines and cardiometabolic risk factors in Mexican children with obesity and the metabolic syndrome
Adrian M. Gonzalez-Gil, Mariana Peschard-Franco, Elena C. Castillo, Gustavo Gutierrez-DelBosque, Victor Treviño, Christian Silva-Platas, Luisa Perez-Villarreal, Gerardo Garcia-Rivas, Leticia Elizondo-Montemayor
Diabetology & Metabolic Syndrome.2019;[Epub] CrossRef
Early Life Exposures to Perfluoroalkyl Substances in Relation to Adipokine Hormone Levels at Birth and During Childhood
Colleen Shelly, Philippe Grandjean, Youssef Oulhote, Peter Plomgaard, Ruth Frikke-Schmidt, Flemming Nielsen, Denis Zmirou-Navier, Pal Weihe, Damaskini Valvi
The Journal of Clinical Endocrinology & Metabolism.2019; 104(11): 5338. CrossRef
Overweight and obesity in childhood: Dietary, biochemical, inflammatory and lifestyle risk factors
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Obesity Medicine.2019; 15: 100112. CrossRef
Effects of major adipokines and the −420 C > G resistin gene polymorphism on the long-term outcome of patients with acute ischemic stroke
Stella Bouziana, Konstantinos Tziomalos, Antonis Goulas, Timoleon-Achilleas Vyzantiadis, Maria Papadopoulou, Athanasia Panderi, Apostolos Ι. Ηatzitolios
International Journal of Neuroscience.2019; 129(10): 978. CrossRef
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Frontiers in Neuroscience.2019;[Epub] CrossRef
Resistin: A reappraisal
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Mechanisms of Ageing and Development.2019; 178: 46. CrossRef
Implications of resistin in type 2 diabetes mellitus and coronary artery disease: Impairing insulin function and inducing pro‐inflammatory cytokines
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Journal of Cellular Physiology.2019; 234(12): 21758. CrossRef
Serum-based soluble markers differentiate psoriatic arthritis from osteoarthritis
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Annals of the Rheumatic Diseases.2019; 78(6): 796. CrossRef
Telmisartan prevents diet-induced obesity and preserves leptin transport across the blood-brain barrier in high-fat diet-fed mice
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Pflügers Archiv - European Journal of Physiology.2018; 470(11): 1673. CrossRef
Adipokines in human breast milk
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Best Practice & Research Clinical Endocrinology & Metabolism.2018; 32(1): 27. CrossRef
Addressing the Perfect Storm: Biomarkers in Obesity and Pathophysiology of Cardiometabolic Risk
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Clinical Chemistry.2018; 64(1): 142. CrossRef
Adipocytokine Involvement in Innate Immune Mechanisms
Paulina Żelechowska, Elżbieta Kozłowska, Joanna Pastwińska, Justyna Agier, Ewa Brzezińska-Błaszczyk
Journal of Interferon & Cytokine Research.2018; 38(12): 527. CrossRef
The effect of a garlic supplement on the pro-inflammatory adipocytokines, resistin and tumor necrosis factor-alpha, and on pain severity, in overweight or obese women with knee osteoarthritis
Sahar Dehghani, Elham Alipoor, Ahmad Salimzadeh, Mehdi Yaseri, Mostafa Hosseini, Christine Feinle-Bisset, Mohammad Javad Hosseinzadeh-Attar
Phytomedicine.2018; 48: 70. CrossRef
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Cardiovascular Diabetology.2018;[Epub] CrossRef
Usefulness of the Adipokines as Biomarkers of Ischemic Cardiac Dysfunction
Larisa-Diana Mocan Hognogi, Cerasela-Mihaela Goidescu, Anca-Daniela Farcaş
Disease Markers.2018; 2018: 1. CrossRef
Circulating fibroblast growth factor 21 in patients with liver cirrhosis
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Clinical and Experimental Medicine.2018; 18(1): 63. CrossRef
Association of Cord Blood Resistin with Neonatal Birth Weight and Gestational Age
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Journal of Comprehensive Pediatrics.2018;[Epub] CrossRef
Major Adipokines and the −420C>G Resistin Gene Polymorphism as Predictors of Acute Ischemic Stroke Severity and In-Hospital Outcome
Styliani D. Bouziana, Konstantinos Tziomalos, Antonios Goulas, Timoleon-Achilleas Vyzantiadis, Athanasia Panderi, Apostolos Ι. Ηatzitolios
Journal of Stroke and Cerebrovascular Diseases.2018; 27(4): 963. CrossRef
Resistin and NGAL are associated with inflammatory response, endothelial activation and clinical outcomes in sepsis
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Inflammation Research.2017; 66(7): 611. CrossRef
Reference values for fasting serum resistin in healthy children and adolescents
Ulrik Lausten-Thomsen, Michael Christiansen, Paula Louise Hedley, Tenna Ruest Haarmark Nielsen, Cilius Esmann Fonvig, Oluf Pedersen, Torben Hansen, Jens-Christian Holm
Clinica Chimica Acta.2017; 469: 161. CrossRef
Sarcopenic obesity or obese sarcopenia: A cross talk between age-associated adipose tissue and skeletal muscle inflammation as a main mechanism of the pathogenesis
Alexander Kalinkovich, Gregory Livshits
Ageing Research Reviews.2017; 35: 200. CrossRef
Is There Any Relationship between Plasma 25-Hydroxyvitamin D3, Adipokine Profiles and Excessive Body Weight in Type 2 Diabetic Patients?
Joanna Kocot, Piotr Dziemidok, Małgorzata Kiełczykowska, Jacek Kurzepa, Grzegorz Szcześniak, Irena Musik
International Journal of Environmental Research and Public Health.2017; 15(1): 19. CrossRef
Exogenous Adipokine Peptide Resistin Protects Against Focal Cerebral Ischemia/Reperfusion Injury in Mice
Jiangtao Zhu, Di Wu, Chenyu Zhao, Man Luo, Ronald C. Hamdy, Balvin H. L. Chua, Xingshun Xu, Zhigang Miao
Neurochemical Research.2017; 42(10): 2949. CrossRef
Adipokines in Liver Cirrhosis
Christa Buechler, Elisabeth Haberl, Lisa Rein-Fischboeck, Charalampos Aslanidis
International Journal of Molecular Sciences.2017; 18(7): 1392. CrossRef
The role of sex steroids in white adipose tissue adipocyte function
A E Newell-Fugate
Reproduction.2017; 153(4): R133. CrossRef
Odanacatib Inhibits Resistin-induced Cardiomyocyte Hypertrophy Through the Inactivation of ERK Signaling Pathway
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International Journal of Pharmacology.2017; 13(2): 212. CrossRef
Linking resistin, inflammation, and cardiometabolic diseases
Hyeong Kyu Park, Mi Kyung Kwak, Hye Jeong Kim, Rexford S. Ahima
The Korean Journal of Internal Medicine.2017; 32(2): 239. CrossRef
Translating the biology of adipokines in atherosclerosis and cardiovascular diseases: Gaps and open questions
M. Ruscica, A. Baragetti, A.L. Catapano, G.D. Norata
Nutrition, Metabolism and Cardiovascular Diseases.2017; 27(5): 379. CrossRef
Differences in Mean Levels of Maternal Resistin Serum between Early Onset Preeclampsia (EOPE) and Late Onset Preeclampsia (LOPE)
Yusrawati ., P. Alfajra, R. Machmud
Research Journal of Obstetrics and Gynecology.2016; 10(1): 1. CrossRef
Secret talk between adipose tissue and central nervous system via secreted factors—an emerging frontier in the neurodegenerative research
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The role of adipokines in ischemic stroke risk stratification
Styliani Bouziana, Konstantinos Tziomalos, Antonios Goulas, Apostolos Ι Ηatzitolios
International Journal of Stroke.2016; 11(4): 389. CrossRef
The endocrine function of human placenta: an overview
Mariana A. Costa
Reproductive BioMedicine Online.2016; 32(1): 14. CrossRef
Ursolic acid plays a protective role in obesity-induced cardiovascular diseases
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Canadian Journal of Physiology and Pharmacology.2016; 94(6): 627. CrossRef
Determinants of body weight regulation in humans
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Archives of Endocrinology and Metabolism.2016; 60(2): 152. CrossRef
Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats
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Bioscience Reports.2016;[Epub] CrossRef
Les adipokines : état des lieux et nouveautés
J.-P. Bastard, C. Bastard, S. Fellahi, C. Vatier, J. Capeau, B. Fève
Obésité.2016; 11(3): 181. CrossRef
Factors that promote macrophage homing to adipose tissue in metabolic syndrome
Ishwarlal Jialal, Beverley Adams-Huet, Sridevi Devaraj
Journal of Diabetes and its Complications.2016; 30(8): 1434. CrossRef
Uncovering Factors Related to Pancreatic Beta-Cell Function
Aoife M. Curran, Miriam F. Ryan, Elaine Drummond, Eileen R. Gibney, Michael J. Gibney, Helen M. Roche, Lorraine Brennan, Nigel Irwin
PLOS ONE.2016; 11(8): e0161350. CrossRef
Resistin’s, obesity and insulin resistance: the continuing disconnect between rodents and humans
X. Huang, Z. Yang
Journal of Endocrinological Investigation.2016; 39(6): 607. CrossRef
Adipocytokines in renal transplant recipients
Kristof Nagy, Shankar Prasad Nagaraju, Connie M. Rhee, Zoltan Mathe, Miklos Z. Molnar
Clinical Kidney Journal.2016; 9(3): 359. CrossRef
Endocrine alterations from concentric vs. eccentric muscle actions: A brief review
Robert R. Kraemer, V. Daniel Castracane
Metabolism.2015; 64(2): 190. CrossRef
Non-traditional cytokines: How catecholamines and adipokines influence macrophages in immunity, metabolism and the central nervous system
Mark A. Barnes, Monica J. Carson, Meera G. Nair
Cytokine.2015; 72(2): 210. CrossRef
Local and serum levels of adipokines in patients with obesity after periodontal therapy: one‐year follow‐up
Tiago Eduardo Dias Gonçalves, Glaucia Santos Zimmermann, Luciene Cristina Figueiredo, Monique de Carvalho Souza, Daniele Ferreira da Cruz, Marta Ferreira Bastos, Hélio Doyle Pereira da Silva, Poliana Mendes Duarte
Journal of Clinical Periodontology.2015; 42(5): 431. CrossRef
Newborn Adipokines and Birth Outcomes
Edwina H. Yeung, Alexander C. McLain, Nancy Anderson, David Lawrence, Nansi S. Boghossian, Charlotte Druschel, Erin Bell
Paediatric and Perinatal Epidemiology.2015; 29(4): 317. CrossRef
The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats
Márta Sárközy, Gergő Szűcs, Márton Pipicz, Ágnes Zvara, Katalin Éder, Veronika Fekete, Csilla Szűcs, Judit Bárkányi, Csaba Csonka, László G. Puskás, Csaba Kónya, Péter Ferdinandy, Tamás Csont
Cardiovascular Diabetology.2015;[Epub] CrossRef
Diet-induced variability of the resistin gene (Retn) transcript level and methylation profile in rats
Joanna Nowacka-Woszuk, Ewa Pruszynska-Oszmalek, Maciej Szydlowski, Slawomir Sadkowski, Izabela Szczerbal
BMC Genetics.2015;[Epub] CrossRef
INFLUENCE OF RESISTIN ON THE COURSE OF ISCHEMIC HEART DISEASE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS
A. T. Teplyakov, Sh. D. Akhmedov, T. Ye. Suslova, А. V. Andriyanova, A. V. Kuznetsova, N. V. Protopopova, V. V. Kalyuzhin, O. N. Nasanova
Bulletin of Siberian Medicine.2015; 14(5): 73. CrossRef
The Effects of a Single Developmentally Entrained Pulse of Testosterone in Female Neonatal Mice on Reproductive and Metabolic Functions in Adult Life
Hyeran Jang, Shalender Bhasin, Tyler Guarneri, Carlo Serra, Mary Schneider, Mi-Jeong Lee, Wen Guo, Susan K. Fried, Karol Pencina, Ravi Jasuja
Endocrinology.2015; 156(10): 3737. CrossRef
The Resin fromProtium heptaphyllumPrevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms
Karine Maria Martins Bezerra Carvalho, José Delano Barreto Marinho Filho, Tiago Sousa de Melo, Ana Jérsia Araújo, Josiane da Silva Quetz, Maria do Perpétuo Socorro Saldanha da Cunha, Karina Moura de Melo, Armenio Andre de Carvalho Almeida da Silva, Adrian
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Evolution of the Vertebrate Resistin Gene Family
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