Diabetes & Metabolism Journal

Original Articles

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.

Metabolic Risk/Epidemiology
Association of Remnant Cholesterol Inflammation Index with Cardiovascular Risks and All-Cause Mortality in Individuals with Diabetes or Prediabetes: Qi-Lin Ma, Lei-Lei Du, Jia Peng; Received April 8, 2025 Accepted June 27, 2025 Published online October 2, 2025; DOI: https://doi.org/10.4093/dmj.2025.0305 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Remnant cholesterol (RC) and low-grade inflammation are established contributors to cardiovascular disease (CVD) risks in diabetes. However, their combined prognostic impact remains unclear in dysglycemia. We evaluated the remnant cholesterol inflammation index (RCII), integrating RC and high-sensitivity C-reactive protein (hsCRP), for predicting mortality and CVD risks in diabetes/prediabetes.
Methods
This study included 2206 United States adults with diabetes/prediabetes from National Health and Nutrition Examination Survey 2015–2018. RCII was calculated as [RC (mg/dL)×hsCRP (mg/L)]/10. All-cause mortality was tracked via National Death Index until 2019; CVD risk was assessed cross-sectionally. Cox proportional hazard regression determined the hazard ratio (HR) and 95% confidence intervals (CIs) of RCII for all-cause mortality. Logistic regression models estimated the odds ratio (OR) and 95% CIs of RCII for CVD risks.
Results
For CVD risks, Q4 vs. Q1 demonstrated increased odds (OR, 2.32; 95% CI, 1.23 to 4.37), though per-standard deviation (SD) increments were non-significant (OR, 1.15; 95% CI, 0.98 to 1.35; P=0.083). During a median of 38 months follow-up, higher RCII quartiles showed graded associations with all-cause mortality (Q4 vs. Q1: HR, 2.45; 95% CI, 1.08 to 5.58; per 1-SD increase: HR, 1.21; 95% CI, 1.08 to 1.35). Restricted cubic splines confirmed dose-dependent relationships for CVD risks and all-cause mortality (all P=0.005 for overall). Subgroup analyses revealed consistent mortality associations but sex-specific CVD interactions (P=0.047 for interaction).
Conclusion
Our study found the RCII as a biomarker for predicting all-cause mortality and CVD risks in individuals with prediabetes or diabetes, highlighting the synergistic effects of RC and low-grade inflammation on adverse outcomes in this population and may facilitate early identification of individuals at heightened risk for CVD.

Cardiovascular Risk/Epidemiology
Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression: Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim; Diabetes Metab J. 2025;49(1):105-116. Published online August 28, 2024; DOI: https://doi.org/10.4093/dmj.2024.0066

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Background
The relationship between circulating lipid levels and the risk for heart failure (HF) is controversial. We aimed to examine this association, and whether it is modified by the duration of diabetes or treatment regimens in people with type 2 diabetes mellitus.
Methods
Individuals (n=2,439,978) who underwent health examinations in 2015 to 2016 were identified from the Korean National Health Information Database. Subjects were categorized according to the duration of diabetes (new-onset, <5, 5–10, or ≥10 years) and number of antidiabetic medications. Incident HF was defined according to the International Classification of Diseases, 10th Revision (ICD-10) code I50 as the primary diagnosis during hospitalization. The risk for HF was estimated using multivariate Cox proportional hazard analysis.
Results
During a median follow-up of 4.0 years, 151,624 cases of HF occurred. An inverse association between low-density lipoprotein cholesterol (LDL-C) levels and incident HF was observed in the new-onset diabetes group, with an approximately 25% lower risk in those with LDL-C levels of 100–129, 130–159, and ≥160 mg/dL, compared to those with levels <70 mg/dL. However, J-shaped associations were noted in the long-standing diabetes group, with a 16% higher risk in those with LDL-C level ≥160 mg/dL, compared to those with levels <70 mg/dL. Similar patterns were observed in the relationship between total cholesterol or non-high-density lipoprotein cholesterol and the risk for HF, and when subjects were grouped according to the number of antidiabetic medications instead of diabetes duration.
Conclusion
Different associations between lipid levels and the risk for HF were noted according to disease progression status among individuals with diabetes.

Citations

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J-shaped association between non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and heart failure: a cross-sectional study
Ping Lv, Chenze Zhao, Yu Shan
European Journal of Medical Research.2026;[Epub] CrossRef
Remnant cholesterol inflammatory index, calculated from residual cholesterol to C-reactive protein ratio, and stroke outcomes: a retrospective study using the National institutes of health stroke scale and modified Rankin scale
Yanmei Yu, Yiming Zhang, Chunyan Zhu, Tingting Duan, Zichen Rao
Lipids in Health and Disease.2025;[Epub] CrossRef
Association of outcome with non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio in hospitalized patients with congestive heart failure: a retrospective analysis
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Journal of Cardiothoracic Surgery.2025;[Epub] CrossRef

Review

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

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

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Original Article

Metabolic Risk/Epidemiology
Temporal Changes in Resting Heart Rate and Risk of Diabetes Mellitus: Mi Kyoung Son, Kyoungho Lee, Hyun-Young Park; Diabetes Metab J. 2024;48(4):752-762. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0305

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Background
To investigate the association between the time-varying resting heart rate (RHR) and change in RHR (∆RHR) over time and the risk of diabetes mellitus (DM) by sex.
Methods
We assessed 8,392 participants without DM or atrial fibrillation/flutter from the Korean Genome and Epidemiology Study, a community-based prospective cohort study that was initiated in 2001 to 2002. The participants were followed up until December 31, 2018. Updating RHR with biennial in-study re-examinations, the time-varying ∆RHR was calculated by assessing the ∆RHR at the next follow-up visit.
Results
Over a median follow-up of 12.3 years, 1,345 participants (16.2%) had DM. As compared with RHR of 60 to 69 bpm, for RHR of ≥80 bpm, the incidence of DM was significantly increased for both male and female. A drop of ≥5 bpm in ∆RHR when compared with the stable ∆RHR group (–5< ∆RHR <5 bpm) was associated significantly with lower risk of DM in both male and female. However, an increase of ≥5 bpm in ∆RHR was significantly associated with higher risk of DM only in female, not in male (hazard ratio for male, 1.057 [95% confidence interval, 0.869 to 1.285]; and for female, 1.218 [95% confidence interval, 1.008 to 1.471]).
Conclusion
In this community-based longitudinal cohort study, a reduction in ∆RHR was associated with a decreased risk of DM, while an increase in ∆RHR was associated with an increased risk of DM only in female.

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Unstable resting heart rate trajectory patterns are associated with an increase in incident risk of type 2 diabetes mellitus: the China-PAR project
Yuying Wu, Yang Zhao, Yanyan Zhang, Xueru Fu, Liuding Wen, Weifeng Huo, Jianxin Li, Xiangfeng Lu, Fulan Hu, Dongsheng Hu, Ming Zhang
Journal of Epidemiology and Community Health.2025; 79(10): 758. CrossRef

Reviews

Pathophysiology
Epicardial Adipose Tissue and Heart Failure, Friend or Foe?: Dong-Hyuk Cho, Seong-Mi Park; Diabetes Metab J. 2024;48(3):373-384. Published online February 2, 2024; DOI: https://doi.org/10.4093/dmj.2023.0190

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Heart failure (HF) management guidelines recommend individualized assessments based on HF phenotypes. Adiposity is a known risk factor for HF. Recently, there has been an increased interest in organ-specific adiposity, specifically the role of the epicardial adipose tissue (EAT), in HF risk. EAT is easily assessable through various imaging modalities and is anatomically and functionally connected to the myocardium. In pathological conditions, EAT secretes inflammatory cytokines, releases excessive fatty acids, and increases mechanical load on the myocardium, resulting in myocardial remodeling. EAT plays a pathophysiological role in characterizing both HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). In HFrEF, EAT volume is reduced, reflecting an impaired metabolic reservoir, whereas in HFpEF, the amount of EAT is associated with worse biomarker and hemodynamic profiles, indicating increased EAT activity. Studies have examined the possibility of therapeutically targeting EAT, and recent studies using sodium glucose cotransporter 2 inhibitors have shown potential in reducing EAT volume. However, further research is required to determine the clinical implications of reducing EAT activity in patients with HF.

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Pathophysiology
Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance: Yajie Fan, Zhipeng Yan, Tingting Li, Aolin Li, Xinbiao Fan, Zhongwen Qi, Junping Zhang; Diabetes Metab J. 2024;48(1):19-36. Published online January 3, 2024; DOI: https://doi.org/10.4093/dmj.2023.0110

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Insulin resistance has been regarded as a hallmark of diabetes heart disease (DHD). Numerous studies have shown that insulin resistance can affect blood circulation and myocardium, which indirectly cause cardiac hypertrophy and ventricular remodeling, participating in the pathogenesis of DHD. Meanwhile, hyperinsulinemia, hyperglycemia, and hyperlipidemia associated with insulin resistance can directly impair the metabolism and function of the heart. Targeting insulin resistance is a potential therapeutic strategy for the prevention of DHD. Currently, the role of insulin resistance in the pathogenic development of DHD is still under active research, as the pathological roles involved are complex and not yet fully understood, and the related therapeutic approaches are not well developed. In this review, we describe insulin resistance and add recent advances in the major pathological and physiological changes and underlying mechanisms by which insulin resistance leads to myocardial remodeling and dysfunction in the diabetic heart, including exosomal dysfunction, ferroptosis, and epigenetic factors. In addition, we discuss potential therapeutic approaches to improve insulin resistance and accelerate the development of cardiovascular protection drugs.

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Original Article

Cardiovascular Risk/Epidemiology
Comparison of on-Statin Lipid and Lipoprotein Levels for the Prediction of First Cardiovascular Event in Type 2 Diabetes Mellitus: Ji Yoon Kim, Jimi Choi, Sin Gon Kim, Nam Hoon Kim; Diabetes Metab J. 2023;47(6):837-845. Published online August 23, 2023; DOI: https://doi.org/10.4093/dmj.2022.0217

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Background
A substantial cardiovascular disease risk remains even after optimal statin therapy. Comparative predictiveness of major lipid and lipoprotein parameters for cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are treated with statins is not well documented.
Methods
From the Korean Nationwide Cohort, 11,900 patients with T2DM (≥40 years of age) without a history of cardiovascular disease and receiving moderate- or high-intensity statins were included. The primary outcome was the first occurrence of major adverse cardiovascular events (MACE) including ischemic heart disease, ischemic stroke, and cardiovascular death. The risk of MACE was estimated according to on-statin levels of low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), highdensity lipoprotein cholesterol (HDL-C), and non-HDL-C.
Results
MACE occurred in 712 patients during a median follow-up period of 37.9 months (interquartile range, 21.7 to 54.9). Among patients achieving LDL-C levels less than 100 mg/dL, the hazard ratios for MACE per 1-standard deviation change in ontreatment values were 1.25 (95% confidence interval [CI], 1.07 to 1.47) for LDL-C, 1.31 (95% CI, 1.09 to 1.57) for non-HDL-C, 1.05 (95% CI, 0.91 to 1.21) for TG, and 1.16 (95% CI, 0.98 to 1.37) for HDL-C, after adjusting for potential confounders and lipid parameters mutually. The predictive ability of on-statin LDL-C and non-HDL-C for MACE was prominent in patients at high cardiovascular risk or those with LDL-C ≥70 mg/dL.
Conclusion
On-statin LDL-C and non-HDL-C levels are better predictors of the first cardiovascular event than TG or HDL-C in patients with T2DM.

Citations

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Current Status of Continuous Glucose Monitoring Use in South Korean Type 1 Diabetes Mellitus Population–Pronounced Age-Related Disparities: Nationwide Cohort Study
Ji Yoon Kim, Seohyun Kim, Jae Hyeon Kim
Diabetes & Metabolism Journal.2025; 49(5): 1040. CrossRef
Managing dyslipidemia in chronic kidney disease: a comprehensive overview of evidence and recommendations
Ji Yoon Kim, Suk Min Chung, Nam Hoon Kim
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Review

Cardiovascular Risk/Epidemiology
The Role of Echocardiography in Evaluating Cardiovascular Diseases in Patients with Diabetes Mellitus: Sun Hwa Lee, Jae-Hyeong Park; Diabetes Metab J. 2023;47(4):470-483. Published online July 27, 2023; DOI: https://doi.org/10.4093/dmj.2023.0036

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Patients with diabetes mellitus are highly susceptible to cardiovascular complications, which are directly correlated with cardiovascular morbidity and mortality. In addition to coronary artery disease, there is growing awareness of the risk and prevalence of heart failure (HF) in patients with diabetes. Echocardiography is an essential diagnostic modality commonly performed in patients with symptoms suggestive of cardiovascular diseases (CVD), such as dyspnea or chest pain, to establish or rule out the cause of symptoms. Conventional echocardiographic parameters, such as left ventricular ejection fraction, are helpful not only for diagnosing CVD but also for determining severity, treatment strategy, prognosis, and response to treatment. Echocardiographic myocardial strain, a novel echocardiographic technique, enables the detection of early changes in ventricular dysfunction before HF symptoms develop. This article aims to review the role of echocardiography in evaluating CVD in patients with diabetes mellitus and how to use it in patients with suspected cardiac diseases.

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Chandu Siripuram, K. Balu Mahendran, Shreelaxmi V Hegde, Sanjana Murali Krishna, Shruti Suresh Suvarna, Ramesh Kandimalla
Cureus.2025;[Epub] CrossRef
Progression of cardiac dysfunction in patients with type 2 diabetes without overt cardiovascular disease: A three‐year follow‐up echocardiographic study (DIACAR)
Yara Antakly Hanon, Yoann Moeuf, Philippe Garçon, Aline Kalaydjian, Isabela Banu, Adela Voican, Olivier Dupuy, Romain Cador, Michel Komajda
Diabetes, Obesity and Metabolism.2025; 27(8): 4581. CrossRef
Artificial intelligence algorithm for predicting cardio-cerebrovascular risk in type 2 diabetes: concordance with clinical and instrumental assessments
Francesco Piarulli, Eugenio Ragazzi, Chiara Celeste Celsan, Annunziata Lapolla, Giovanni Sartore
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Early Detection of Diabetic Cardiomyopathy Using Speckle Tracking Echocardiography: A Systematic Review
Mohammad Burhanuddin, Zeeshan Ahmed, Ali Hamza, Muhammad Zeeshan, FNU Abdul Rehman , Syed Hassan M Gillani, Aiman Gul, Zara Rabbani, Osarenoma Mathilda Omonfuegbe, Syed Momin Ali
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Original Articles

Basic Research
Pharmacologic Activation of Angiotensin-Converting Enzyme II Alleviates Diabetic Cardiomyopathy in db/db Mice by Reducing Reactive Oxidative Stress: Donghyun Kim, Wooju Jeong, Yumin Kim, Jibeom Lee, Sung Woo Cho, Chang-Myung Oh, Raekil Park; Diabetes Metab J. 2023;47(4):487-499. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0125

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Background
Diabetes mellitus is one of the most common chronic diseases worldwide, and cardiovascular disease is the leading cause of morbidity and mortality in diabetic patients. Diabetic cardiomyopathy (DCM) is a phenomenon characterized by a deterioration in cardiac function and structure, independent of vascular complications. Among many possible causes, the renin-angiotensin-aldosterone system and angiotensin II have been proposed as major drivers of DCM development. In the current study, we aimed to investigate the effects of pharmacological activation of angiotensin-converting enzyme 2 (ACE2) on DCM.
Methods
The ACE2 activator diminazene aceturate (DIZE) was administered intraperitoneally to male db/db mice (8 weeks old) for 8 weeks. Transthoracic echocardiography was used to assess cardiac mass and function in mice. Cardiac structure and fibrotic changes were examined using histology and immunohistochemistry. Gene and protein expression levels were examined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. Additionally, RNA sequencing was performed to investigate the underlying mechanisms of the effects of DIZE and identify novel potential therapeutic targets for DCM.
Results
Echocardiography revealed that in DCM, the administration of DIZE significantly improved cardiac function as well as reduced cardiac hypertrophy and fibrosis. Transcriptome analysis revealed that DIZE treatment suppresses oxidative stress and several pathways related to cardiac hypertrophy.
Conclusion
DIZE prevented the diabetes mellitus-mediated structural and functional deterioration of mouse hearts. Our findings suggest that the pharmacological activation of ACE2 could be a novel treatment strategy for DCM.

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Empagliflozin in diabetic cardiomyopathy: elucidating mechanisms, therapeutic potentials, and future directions
Aiswarya Jaiswal, Poonam Yadav, Pushkar Singh Rawat, Maninder Kaur, Srivalliputturu Sarath Babu, Amit Khurana, Jasvinder Singh Bhatti, Umashanker Navik
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Integrative Analyses of Biomarkers and Pathways in Oxidative Stress‐Related Genes for Gestational Diabetes Mellitus
Yunyan Chen, Fuchu Qian, Yingying Chen
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Novel insights into the central protective role of ACE2 in diabetic cardiomyopathy: from underlying signaling pathways to therapeutic perspectives
Xinyi Li, Shunlin Qu
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Mechanisms of diabetic cardiomyopathy: Focus on inflammation
Myriam Bellemare, Liane Bourcier, Josep Iglesies‐Grau, Jacinthe Boulet, Eileen O'Meara, Nadia Bouabdallaoui
Diabetes, Obesity and Metabolism.2025; 27(5): 2326. CrossRef
Immune cell contribution to vascular complications in diabetes
Lingli Ma, Xuejiao Zhang, Zimeng Li, Qing Wang
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Peter Galis, Linda Bartosova, Veronika Farkasova, Monika Bartekova, Kristina Ferenczyova, Tomas Rajtik
Frontiers in Endocrinology.2024;[Epub] CrossRef
Vascular remodelling in cardiovascular diseases: hypertension, oxidation, and inflammation
Justyna Totoń-Żurańska, Tomasz P. Mikolajczyk, Blessy Saju, Tomasz J. Guzik
Clinical Science.2024; 138(13): 817. CrossRef

Cardiovascular Risk/Epidemiology
Two-Year Changes in Diabetic Kidney Disease Phenotype and the Risk of Heart Failure: A Nationwide Population-Based Study in Korea: Seung Eun Lee, Juhwan Yoo, Han Seok Choi, Kyungdo Han, Kyoung-Ah Kim; Diabetes Metab J. 2023;47(4):523-534. Published online April 25, 2023; DOI: https://doi.org/10.4093/dmj.2022.0096

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Background
Diabetic kidney disease (DKD) is a risk factor for hospitalization for heart failure (HHF). DKD could be classified into four phenotypes by estimated glomerular filtration rate (eGFR, normal vs. low) and proteinuria (PU, negative vs. positive). Also, the phenotype often changes dynamically. This study examined HHF risk according to the DKD phenotype changes across 2-year assessments.
Methods
The study included 1,343,116 patients with type 2 diabetes mellitus (T2DM) from the Korean National Health Insurance Service database after excluding a very high-risk phenotype (eGFR <30 mL/min/1.73 m2) at baseline, who underwent two cycles of medical checkups between 2009 and 2014. From the baseline and 2-year eGFR and PU results, participants were divided into 10 DKD phenotypic change categories.
Results
During an average of 6.5 years of follow-up, 7,874 subjects developed HHF. The cumulative incidence of HHF from index date was highest in the eGFR^lowPU– phenotype, followed by eGFR^norPU⁺ and eGFR^norPU^–. Changes in DKD phenotype differently affect HHF risk. When the persistent eGFR^norPU^– category was the reference, hazard ratios for HHF were 3.10 (95% confidence interval [CI], 2.73 to 3.52) in persistent eGFR^norPU⁺ and 1.86 (95% CI, 1.73 to 1.99) in persistent eGFR^lowPU^–. Among altered phenotypes, the category converted to eGFR^lowPU⁺ showed the highest risk. In the normal eGFR category at the second examination, those who converted from PU^– to PU⁺ showed a higher risk of HHF than those who converted from PU⁺ to PU^–.
Conclusion
Changes in DKD phenotype, particularly with the presence of PU, are more likely to reflect the risk of HHF, compared with DKD phenotype based on a single time point in patients with T2DM.

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Different Associations between Lipid Levels and Risk for Heart Failure according to Diabetes Progression
Seung-Hwan Lee, Kyu Na Lee, Jong-Chan Youn, Hun Sung Kim, Kyungdo Han, Mee Kyoung Kim
Diabetes & Metabolism Journal.2025; 49(1): 105. CrossRef
Persistent proteinuria is associated with the occurrence of cardiovascular disease: a nationwide population-based cohort study
Ho Geol Woo, Moo-Seok Park, Tae-Jin Song
Scientific Reports.2024;[Epub] CrossRef

Review

Guideline/Fact Sheet
Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement: Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon, The Committee of Clinical Practice Guidelines, Korean Diabetes Association and Committee of Clinical Practice Guidelines, Korean Society of Heart Failure; Diabetes Metab J. 2023;47(1):10-26. Published online January 26, 2023; DOI: https://doi.org/10.4093/dmj.2022.0420

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Diabetes mellitus is a major risk factor for the development of heart failure. Furthermore, the prognosis of heart failure is worse in patients with diabetes mellitus than in those without it. Therefore, early diagnosis and proper management of heart failure in patients with diabetes mellitus are important. This review discusses the current criteria for diagnosis and screening tools for heart failure and the currently recommended pharmacological therapies for heart failure. We also highlight the effects of anti-diabetic medications on heart failure.

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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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Drug/Regimen
Comparison of Serum Ketone Levels and Cardiometabolic Efficacy of Dapagliflozin versus Sitagliptin among Insulin-Treated Chinese Patients with Type 2 Diabetes Mellitus: Chi-Ho Lee, Mei-Zhen Wu, David Tak-Wai Lui, Darren Shing-Hei Chan, Carol Ho-Yi Fong, Sammy Wing-Ming Shiu, Ying Wong, Alan Chun-Hong Lee, Joanne King-Yan Lam, Yu-Cho Woo, Karen Siu-Ling Lam, Kelvin Kai-Hang Yiu, Kathryn Choon-Beng Tan; Diabetes Metab J. 2022;46(6):843-854. Published online April 28, 2022; DOI: https://doi.org/10.4093/dmj.2021.0319

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Background
Insulin-treated patients with long duration of type 2 diabetes mellitus (T2DM) are at increased risk of ketoacidosis related to sodium-glucose co-transporter 2 inhibitor (SGLT2i). The extent of circulating ketone elevation in these patients remains unknown. We conducted this study to compare the serum ketone response between dapagliflozin, an SGLT2i, and sitagliptin, a dipeptidyl peptidase-4 inhibitor, among insulin-treated T2DM patients.
Methods
This was a randomized, open-label, active comparator-controlled study involving 60 insulin-treated T2DM patients. Participants were randomized 1:1 for 24-week of dapagliflozin 10 mg daily or sitagliptin 100 mg daily. Serum β-hydroxybutyrate (BHB) levels were measured at baseline, 12 and 24 weeks after intervention. Comprehensive cardiometabolic assessments were performed with measurements of high-density lipoprotein cholesterol (HDL-C) cholesterol efflux capacity (CEC), vibration-controlled transient elastography and echocardiography.
Results
Among these 60 insulin-treated participants (mean age 58.8 years, diabetes duration 18.2 years, glycosylated hemoglobin 8.87%), as compared with sitagliptin, serum BHB levels increased significantly after 24 weeks of dapagliflozin (P=0.045), with a median of 27% increase from baseline. Change in serum BHB levels correlated significantly with change in free fatty acid levels. Despite similar glucose lowering, dapagliflozin led to significant improvements in body weight (P=0.006), waist circumference (P=0.028), HDL-C (P=0.041), CEC (P=0.045), controlled attenuation parameter (P=0.007), and liver stiffness (P=0.022). Average E/e’, an echocardiographic index of left ventricular diastolic dysfunction, was also significantly lower at 24 weeks in participants treated with dapagliflozin (P=0.037).
Conclusion
Among insulin-treated T2DM patients with long diabetes duration, compared to sitagliptin, dapagliflozin modestly increased ketone levels and was associated with cardiometabolic benefits.

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Ketosis and ketoacidosis in hospitalized patients receiving SGLT2 inhibitor therapy
Frank M. Gao, Kartik Kishore, Dinesh Pandey, Hossein Jahanabadi, Meg Stevens, Ashani Lecamwasam, Rinaldo Bellomo, Leonid Churilov, Elif I. Ekinci
Diabetes, Obesity and Metabolism.2025; 27(11): 6367. CrossRef
Monitoring Ketonemia in People with Diabetes: Preliminary Findings from Real-World Studies
Richard M. Bergenstal, Naunihal Virdi, Farhan Quadri, Shridhara Alva
Diabetes Technology & Therapeutics.2025; 27(S4): S25. CrossRef
Dipeptidyl Peptidase-4 Inhibitors Improved Lipid Levels in Patients With Type 2 Diabetes: A Meta-analysis of Randomized Clinical Trials
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Serum thrombospondin‐2 level changes with liver stiffness improvement in patients with type 2 diabetes
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Complications
Effect of the Glucagon-Like Peptide-1 Receptor Agonists on Autonomic Function in Subjects with Diabetes: A Systematic Review and Meta-Analysis: Carla Greco, Daniele Santi, Giulia Brigante, Chiara Pacchioni, Manuela Simoni; Diabetes Metab J. 2022;46(6):901-911. Published online April 12, 2022; DOI: https://doi.org/10.4093/dmj.2021.0314

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Background
In addition to the metabolic effects in diabetes, glucagon-like peptide 1 receptor (GLP-1R) agonists lead to a small but substantial increase in heart rate (HR). However, the GLP-1R actions on the autonomic nervous system (ANS) in diabetes remain debated. Therefore, this meta-analysis evaluates the effect of GLP-1R agonist on measures of ANS function in diabetes.
Methods
According to the Cochrane Collaboration and Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we conducted a meta-analysis considering clinical trials in which the autonomic function was evaluated in diabetic subjects chronically treated with GLP-1R agonists. The outcomes were the change of ANS function measured by heart rate variability (HRV) and cardiac autonomic reflex tests (CARTs).
Results
In the studies enrolled, HR significantly increased after treatment (P<0.001), whereas low frequency/high frequency ratio did not differ (P=0.410); no changes in other measures of HRV were detected. Considering CARTs, only the 30:15 value derived from lying-to-standing test was significantly lower after treatment (P=0.002), but only two studies reported this measurement. No differences in other CARTs outcome were observed.
Conclusion
The meta-analysis confirms the HR increase but seems to exclude an alteration of the sympatho-vagal balance due to chronic treatment with GLP-1R agonists in diabetes, considering the available measures of ANS function.

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Review

Cardiovascular Risk/Epidemiology
Association between Variability of Metabolic Risk Factors and Cardiometabolic Outcomes: Min Jeong Park, Kyung Mook Choi; Diabetes Metab J. 2022;46(1):49-62. Published online January 27, 2022; DOI: https://doi.org/10.4093/dmj.2021.0316

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Despite strenuous efforts to reduce cardiovascular disease (CVD) risk by improving cardiometabolic risk factors, such as glucose and cholesterol levels, and blood pressure, there is still residual risk even in patients reaching treatment targets. Recently, researchers have begun to focus on the variability of metabolic variables to remove residual risks. Several clinical trials and cohort studies have reported a relationship between the variability of metabolic parameters and CVDs. Herein, we review the literature regarding the effect of metabolic factor variability and CVD risk, and describe possible mechanisms and potential treatment perspectives for reducing cardiometabolic risk factor variability.

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Original Article

Lifestyle
Changes in Patterns of Physical Activity and Risk of Heart Failure in Newly Diagnosed Diabetes Mellitus Patients: Inha Jung, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Eun-Jung Rhee, Won-Young Lee; Diabetes Metab J. 2022;46(2):327-336. Published online November 24, 2021; DOI: https://doi.org/10.4093/dmj.2021.0046

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Background
Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients.
Methods
We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017.
Results
As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91).
Conclusion
Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

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Reviews

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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Cardiovascular Risk/Epidemiology
Diabetes Management in Patients with Heart Failure: Jia Shen, Barry H. Greenberg; Diabetes Metab J. 2021;45(2):158-172. Published online March 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0296

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Diabetes and heart failure (HF) are common diseases, each affecting large segments of the world population. Moreover, prevalence rates for both are expected to rise dramatically over coming decades. The high prevalence rates of both diseases and wellrecognized association of diabetes as a risk factor for HF make it inevitable that both diseases co-exist in a large number of patients, complicating their management and increasing the risk of a poor outcome. Management of diabetes has been shown to impact clinical events in patients with HF and there is emerging evidence that agents used to treat diabetes can reduce HF events, even in non-diabetic patients. In this review we summarize the clinical course and treatment of patients with type 2 diabetes mellitus (T2DM) and HF and review the efficacy and safety of pharmacological agents in patients with T2DM at risk for HF and those with established disease.

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Basic Research
Application of Animal Models in Diabetic Cardiomyopathy: Wang-Soo Lee, Jaetaek Kim; Diabetes Metab J. 2021;45(2):129-145. Published online March 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0285

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Diabetic heart disease is a growing and important public health risk. Apart from the risk of coronary artery disease or hypertension, diabetes mellitus (DM) is a well-known risk factor for heart failure in the form of diabetic cardiomyopathy (DiaCM). Currently, DiaCM is defined as myocardial dysfunction in patients with DM in the absence of coronary artery disease and hypertension. The underlying pathomechanism of DiaCM is partially understood, but accumulating evidence suggests that metabolic derangements, oxidative stress, increased myocardial fibrosis and hypertrophy, inflammation, enhanced apoptosis, impaired intracellular calcium handling, activation of the renin-angiotensin-aldosterone system, mitochondrial dysfunction, and dysregulation of microRNAs, among other factors, are involved. Numerous animal models have been used to investigate the pathomechanisms of DiaCM. Despite some limitations, animal models for DiaCM have greatly advanced our understanding of pathomechanisms and have helped in the development of successful disease management strategies. In this review, we summarize the current pathomechanisms of DiaCM and provide animal models for DiaCM according to its pathomechanisms, which may contribute to broadening our understanding of the underlying mechanisms and facilitating the identification of possible new therapeutic targets.

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Cardiovascular Risk/Epidemiology
Epidemiology, Pathophysiology, Diagnosis and Treatment of Heart Failure in Diabetes: Jin Joo Park; Diabetes Metab J. 2021;45(2):146-157. Published online March 25, 2021; DOI: https://doi.org/10.4093/dmj.2020.0282; Correction in: Diabetes Metab J 2021;45(5):796

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The cardiovascular disease continuum begins with risk factors such as diabetes mellitus (DM), progresses to vasculopathy and myocardial dysfunction, and finally ends with cardiovascular death. Diabetes is associated with a 2- to 4-fold increased risk for heart failure (HF). Moreover, HF patients with DM have a worse prognosis than those without DM. Diabetes can cause myocardial ischemia via micro- and macrovasculopathy and can directly exert deleterious effects on the myocardium. Hyperglycemia, hyperinsulinemia, and insulin resistance can cause alterations in vascular homeostasis. Then, reduced nitric oxide and increased reactive oxygen species levels favor inflammation leading to atherothrombotic progression and myocardial dysfunction. The classification, diagnosis, and treatment of HF for a patient with and without DM remain the same. Until now, drugs targeting neurohumoral and metabolic pathways improved mortality and morbidity in HF with reduced ejection fraction (HFrEF). Therefore, all HFrEF patients should receive guideline-directed medical therapy. By contrast, drugs modulating neurohumoral activity did not improve survival in HF with preserved ejection fraction (HFpEF) patients. Trials investigating whether sodium-glucose cotransporter-2 inhibitors are effective in HFpEF are on-going. This review will summarize the epidemiology, pathophysiology, and treatment of HF in diabetes.

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Original Articles

Drug/Regimen
Cardiovascular Safety of Sodium Glucose Cotransporter 2 Inhibitors as Add-on to Metformin Monotherapy in Patients with Type 2 Diabetes Mellitus: Ja Young Jeon, Kyoung Hwa Ha, Dae Jung Kim; Diabetes Metab J. 2021;45(4):505-514. Published online October 30, 2020; DOI: https://doi.org/10.4093/dmj.2020.0057

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Background
Using real-world data, cardiovascular safety was investigated in metformin users newly starting sodium glucose cotransporter 2 (SGLT2) inhibitors compared with other glucose-lowering drugs in Korea.
Methods
This was a retrospective observational study using the National Health Insurance Service claims database in Korea. The study period was from September 2014 to December 2016. The study included subjects who were newly prescribed SGLT2 inhibitors or other glucose-lowering drugs while on metformin monotherapy; cohort 1 was composed of new users of SGLT2 inhibitors versus dipeptidyl peptidase-4 (DPP-4) inhibitors and cohort 2 included new users of SGLT2 inhibitors versus sulfonylureas. To balance the patient characteristics, propensity score matching was performed at a 1:1 ratio. Cardiovascular outcomes included hospitalization for heart failure (HHF), all-cause mortality, HHF plus all-cause mortality, myocardial infarction (MI), stroke, and modified major adverse cardiovascular events (MACEs).
Results
After propensity score matching, each cohort group was well balanced at baseline (21,688 pairs in cohort 1 and 20,120 pairs in cohort 2). As the second-line treatment, use of SGLT2 inhibitors was associated with a lower risk of HHF and HHF plus all-cause mortality compared with DPP-4 inhibitors. In addition, use of SGLT2 inhibitors versus sulfonylurea as add-on therapy to metformin was associated with decreased risks of HHF, all-cause mortality, HHF plus all-cause mortality, MI, stroke, and modified MACEs.
Conclusion
SGLT2 inhibitors can be a good second-line drug to reduce the incidence of cardiovascular diseases compared with DPP-4 inhibitors or sulfonylureas in people with type 2 diabetes mellitus.

Citations

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Mayada Ahmed, Mohammed Altoyan, Raghad Hijazi, Joud AlJebreen, Mohammed H. Alshalan, Reema Aldhalaan, Lama Altarifi
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Effects of sodium-glucose cotransporter 2 inhibitors on cardiovascular and cerebrovascular diseases: a meta-analysis of controlled clinical trials
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Evaluation and Management of Patients With Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
Kyu-Sun Lee, Junghyun Noh, Seong-Mi Park, Kyung Mook Choi, Seok-Min Kang, Kyu-Chang Won, Hyun-Jai Cho, Min Kyong Moon
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Evaluation and Management of Patients with Diabetes and Heart Failure: A Korean Diabetes Association and Korean Society of Heart Failure Consensus Statement
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Effect of Sodium-Glucose Cotransporter Inhibitors on Major Adverse Cardiovascular Events and Hospitalization for Heart Failure in Patients With Type 2 Diabetes Mellitus and Atrial Fibrillation
Chang Hee Kwon, Ye-Jee Kim, Min-Ju Kim, Myung-Jin Cha, Min Soo Cho, Gi-Byoung Nam, Kee-Joon Choi, Jun Kim
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Cardiovascular Risk/Epidemiology
Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults: Eun-Jung Rhee, Hyemi Kwon, Se Eun Park, Kyung-Do Han, Yong-Gyu Park, Yang-Hyun Kim, Won-Young Lee; Diabetes Metab J. 2020;44(4):592-601. Published online April 20, 2020; DOI: https://doi.org/10.4093/dmj.2019.0104; Correction in: Diabetes Metab J 2020;44(5):783

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Background

Recent studies suggest an association between diabetes and increased risk of heart failure (HF). However, the associations among obesity status, glycemic status, and risk of HF are not known. In this study, we analyzed whether the risk of HF increases in participants according to baseline glycemic status and whether this increased risk is associated with obesity status.

Methods

We analyzed the risk of HF according to baseline glycemic status (normoglycemia, impaired fasting glucose [IFG], and diabetes) in 9,720,220 Koreans who underwent Korean National Health Screening in 2009 without HF at baseline with a median follow-up period of 6.3 years. The participants were divided into five and six groups according to baseline body mass index (BMI) and waist circumference, respectively.

Results

Participants with IFG and those with diabetes showed a 1.08- and 1.86-fold increased risk of HF, respectively, compared to normoglycemic participants. Compared to the normal weight group (BMI, 18.5 to 22.9 kg/m²), the underweight group (BMI <18.5 kg/m²) showed a 1.7-fold increased risk of HF, and those with BMI ≥30 kg/m² showed a 1.1-fold increased risk of HF, suggesting a J-shaped association with BMI. When similar analyses were performed for different glycemic statuses, the J-shaped association between BMI and HF risk was consistently observed in both groups with and without diabetes.

Conclusion

Participants with IFG and diabetes showed a significantly increased HF risk compared to normoglycemic participants. This increased risk of HF was mostly prominent in underweight and class II obese participants than in participants with normal weight.

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Letter: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601)
Darae Kim
Diabetes & Metabolism Journal.2020; 44(5): 777. CrossRef
Response: Associations among Obesity Degree, Glycemic Status, and Risk of Heart Failure in 9,720,220 Korean Adults (Diabetes Metab J 2020;44:592-601)
Eun-Jung Rhee, Won-Young Lee
Diabetes & Metabolism Journal.2020; 44(5): 781. CrossRef

Review

Basic Research
Mitochondrial Mechanisms in Diabetic Cardiomyopathy: Johannes Gollmer, Andreas Zirlik, Heiko Bugger; Diabetes Metab J. 2020;44(1):33-53. Published online February 21, 2020; DOI: https://doi.org/10.4093/dmj.2019.0185

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Mitochondrial medicine is increasingly discussed as a promising therapeutic approach, given that mitochondrial defects are thought to contribute to many prevalent diseases and their complications. In individuals with diabetes mellitus (DM), defects in mitochondrial structure and function occur in many organs throughout the body, contributing both to the pathogenesis of DM and complications of DM. Diabetic cardiomyopathy (DbCM) is increasingly recognized as an underlying cause of increased heart failure in DM, and several mitochondrial mechanisms have been proposed to contribute to the development of DbCM. Well established mechanisms include myocardial energy depletion due to impaired adenosine triphosphate (ATP) synthesis and mitochondrial uncoupling, and increased mitochondrial oxidative stress. A variety of upstream mechanisms of impaired ATP regeneration and increased mitochondrial reactive oxygen species have been proposed, and recent studies now also suggest alterations in mitochondrial dynamics and autophagy, impaired mitochondrial Ca²⁺ uptake, decreased cardiac adiponectin action, increased O-GlcNAcylation, and impaired activity of sirtuins to contribute to mitochondrial defects in DbCM, among others. In the current review, we present and discuss the evidence that underlies both established and recently proposed mechanisms that are thought to contribute to mitochondrial dysfunction in DbCM.

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Original Articles

Metabolic Risk/Epidemiology
Association between Non-Alcoholic Steatohepatitis and Left Ventricular Diastolic Dysfunction in Type 2 Diabetes Mellitus: Hokyou Lee, Gyuri Kim, Young Ju Choi, Byung Wook Huh, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Eun Jig Lee, Yong-ho Lee, Kap Bum Huh; Diabetes Metab J. 2020;44(2):267-276. Published online February 28, 2019; DOI: https://doi.org/10.4093/dmj.2019.0001

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Background

Impaired diastolic heart function has been observed in persons with non-alcoholic fatty liver disease (NAFLD) and/or with type 2 diabetes mellitus (T2DM). However, it is unclear whether NAFLD fibrotic progression, i.e., non-alcoholic steatohepatitis, poses an independent risk for diastolic dysfunction in T2DM. We investigated the association between liver fibrosis and left ventricular (LV) diastolic dysfunction in T2DM.

Methods

We analyzed 606 patients with T2DM, aged ≥50 years, who had undergone liver ultrasonography and pulsed-wave Doppler echocardiography. Insulin sensitivity was measured by short insulin tolerance test. Presence of NAFLD and/or advanced liver fibrosis was determined by abdominal ultrasonography and NAFLD fibrosis score (NFS). LV diastolic dysfunction was defined according to transmitral peak early to late ventricular filling (E/A) ratio and deceleration time, using echocardiography.

Results

LV diastolic dysfunction was significantly more prevalent in the NAFLD versus non-NAFLD group (59.7% vs. 49.0%, P=0.011). When NAFLD was stratified by NFS, subjects with advanced liver fibrosis exhibited a higher prevalence of diastolic dysfunction (49.0%, 50.7%, 61.8%; none, simple steatosis, advanced fibrosis, respectively; P for trend=0.003). In multivariable logistic regression, liver fibrosis was independently associated with diastolic dysfunction (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.07 to 2.34; P=0.022) after adjusting for insulin resistance and cardiometabolic risk factors. This association remained significant in patients without insulin resistance (OR, 4.32; 95% CI, 1.73 to 11.51; P=0.002).

Conclusions

Liver fibrosis was associated with LV diastolic dysfunction in patients with T2DM and may be an independent risk factor for diastolic dysfunction, especially in patients without systemic insulin resistance.

Citations

Citations to this article as recorded by

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Clinical Diabetes & Therapeutics
Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea: Sol Jae Lee, Su Jin Jeong, Yu Chang Lee, Yong Hoon Lee, Jung Eun Lee, Chong Hwa Kim, Kyung Wan Min, Bong Yun Cha; Diabetes Metab J. 2017;41(4):275-283. Published online July 6, 2017; DOI: https://doi.org/10.4093/dmj.2017.41.4.275

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Background

Diabetic cardiac autonomic neuropathy (CAN) is one of the important complications of diabetes. It is characterized by reduced heart rate variability (HRV).

Methods

In this randomized, double-blind, placebo-controlled, multicenter trial, 75 patients were randomly assigned to one of two groups. One group (n=41) received α-lipoic acid (ALA) at an oral dose of 600 mg/day for the first 12 weeks and then 1,200 mg/day for the next 12 weeks. The other group (n=34) received placebo treatment for 24 weeks. CAN was assessed by measuring HRVs in people with diabetes.

Results

Most of the baseline measures for HRVs were similar between the ALA and placebo groups. Although there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial, we found a positive tendency in some of the HRV parameters of the ALA group. The standard deviations of normal-to-normal RR intervals in the standing position increased by 1.87 ms in the ALA group but decreased by −3.97 ms in the placebo group (P=0.06). The power spectrum of the low frequency (LF) band in the standing position increased by 15.77 ms² in the ALA group, whereas it declined by −15.04 ms² in the placebo group (P=0.08). The high frequency/LF ratio in the upright position increased by 0.35 in the ALA group, whereas it declined by −0.42 in the placebo group (P=0.06). There were no differences between the two groups regarding rates of adverse events.

Conclusion

Although a slight improvement tendency was seen in HRV in the ALA group, there were no statistically significant HRV changes in the ALA group compared to the placebo group after 24 weeks of trial. However, the high oral dose of ALA was well-tolerated.

Citations

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Effects of alpha-lipoic acid supplementation on cardiometabolic risk factors: A systematic review and dose-response meta-analysis
Shooka Mohammadi, Damoon Ashtary-Larky, Navid Alaghemand, Ilnaz Alavi, Mahsa Erfanian-Salim, Pouyan Sanjari Pirayvatlou, Yeganeh Ettehad, Aida Borzabadi, Milad Mehrbod, Omid Asbaghi
Nutrition, Metabolism and Cardiovascular Diseases.2026; 36(2): 104370. CrossRef
Effectiveness of Alpha Lipoic Acid in Type 2 Diabetes Mellitus patients with Cardiac Autonomic Neuropathy
Geetha. P, Bharathi. D, Deepa. N, Gopi. G, Shamshath Begum, Devi. T
Research Journal of Science and Technology.2025; : 286. CrossRef
Protocol for the FibroCAN study: a randomised controlled trial of finerenone treatment for early-stage cardiovascular autonomic neuropathy in type 2 diabetes
Maria Bitsch Poulsen, Tina Okdahl, Jens Hove Buciek, Asbjørn Mohr Drewes, Pall Karlsson, Tarunveer Singh Ahluwalia, Birgitte Brock, Christina Brock, Peter Rossing, Christian Stevns Hansen
BMJ Open.2025; 15(10): e101074. CrossRef
Cardiovascular autonomic neuropathy in diabetes: an update with a focus on management
Aikaterini Eleftheriadou, Vincenza Spallone, Abd A. Tahrani, Uazman Alam
Diabetologia.2024; 67(12): 2611. CrossRef
Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics
Anthony J. Evans, Yu-Long Li
International Journal of Molecular Sciences.2024; 25(22): 12464. CrossRef
Effect of Ramipril on Cardiac Autonomic Neuropathy in Patients With Type II Diabetes Mellitus
Chaitali A Chindhalore, Ganesh N Dakhale, Prathamesh H Kamble, Bharatsing D Rathod, Sunita Kumbhalkar, Mrunal S Phatak
Cureus.2023;[Epub] CrossRef
Evaluating treatment options for cardiovascular autonomic neuropathy in patients with diabetes mellitus: a systematic review
Jasmine KaiLi Goh, Leroy Koh
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The effects of alpha lipoic acid (ALA) supplementation on blood pressure in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials
Mahdi Vajdi, Nooshin Noshadi, Shirin Hassanizadeh, Atefeh Bonyadian, Hooria Seyedhosseini-Ghaheh, Gholamreza Askari
Frontiers in Cardiovascular Medicine.2023;[Epub] CrossRef
Combination Therapy of Alpha-Lipoic Acid, Gliclazide and Ramipril Protects Against Development of Diabetic Cardiomyopathy via Inhibition of TGF-β/Smad Pathway
George J. Dugbartey, Quinsker L. Wonje, Karl K. Alornyo, Louis Robertson, Ismaila Adams, Vincent Boima, Samuel D. Mensah
Frontiers in Pharmacology.2022;[Epub] CrossRef
Diabetic Gastroenteropathy: Soothe the Symptoms or Unravel a Cure?
Sondre Meling, Davide Bertoli, Dag A. Sangnes, Christina Brock, Asbjørn Drewes, Niels Ejskjaer, Georg Dimcevski, Eirik Søfteland
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Efficacy and safety of oral alpha-lipoic acid supplementation for type 2 diabetes management: a systematic review and dose–response meta-analysis of randomized trials
Aliyu Tijani Jibril, Ahmad Jayedi, Sakineh Shab-Bidar
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Cardiac Autonomic Neuropathy in Type 1 and 2 Diabetes: Epidemiology, Pathophysiology, and Management
Scott Williams, Siddig Abdel Raheim, Muhammad Ilyas Khan, Umme Rubab, Prathap Kanagala, Sizheng Steven Zhao, Anne Marshall, Emily Brown, Uazman Alam
Clinical Therapeutics.2022; 44(10): 1394. CrossRef
An updated systematic review and dose-response meta-analysis of the effects of α-lipoic acid supplementation on glycemic markers in adults
Mahsa Mahmoudi-Nezhad, Mahdi Vajdi, Mahdieh Abbasalizad Farhangi
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Management of diabetic neuropathy
Simona Cernea, Itamar Raz
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Effect of alpha-lipoic acid on arterial stiffness parameters in type 2 diabetes mellitus patients with cardiac autonomic neuropathy
Victoria A. Serhiyenko, Ludmila M. Serhiyenko, Volodymyr B. Sehin, Alexandr A. Serhiyenko
Endocrine Regulations.2021; 55(4): 224. CrossRef
The Role of Alpha-lipoic Acid Supplementation in the Prevention of Diabetes Complications: A Comprehensive Review of Clinical Trials
Sarah Jeffrey, Punitha Isaac Samraj, Behin Sundara Raj
Current Diabetes Reviews.2021;[Epub] CrossRef
Safety Evaluation of α-Lipoic Acid Supplementation: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Clinical Studies
Federica Fogacci, Manfredi Rizzo, Christoffer Krogager, Cormac Kennedy, Coralie M.G. Georges, Tamara Knežević, Evangelos Liberopoulos, Alexandre Vallée, Pablo Pérez-Martínez, Eliane F.E. Wenstedt, Agnė Šatrauskienė, Michal Vrablík, Arrigo F.G. Cicero
Antioxidants.2020; 9(10): 1011. CrossRef
Update on the Impact, Diagnosis and Management of Cardiovascular Autonomic Neuropathy in Diabetes: What Is Defined, What Is New, and What Is Unmet
Vincenza Spallone
Diabetes & Metabolism Journal.2019; 43(1): 3. CrossRef
Alpha-lipoic acid (ALA) supplementation effect on glycemic and inflammatory biomarkers: A Systematic Review and meta- analysis
Mehran Rahimlou, Maryam Asadi, Nasrin Banaei Jahromi, Anahita Mansoori
Clinical Nutrition ESPEN.2019; 32: 16. CrossRef
Alpha-lipoic acid and diabetic cardiac autonomic neuropathy
Victoria Serhiyenko, Ludmila Serhiyenko, Alexandr Serhiyenko
MOJ Public Health.2019; 8(1): 8. CrossRef
Response: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J 2017;41:275-83)
Chong Hwa Kim, Sol Jae Lee, Bong Yun Cha
Diabetes & Metabolism Journal.2017; 41(5): 420. CrossRef
Letter: Effects of High-Dose α-Lipoic Acid on Heart Rate Variability of Type 2 Diabetes Mellitus Patients with Cardiac Autonomic Neuropathy in Korea (Diabetes Metab J2017;41:275-83)
Jeongmin Lee, Jae Hyoung Cho
Diabetes & Metabolism Journal.2017; 41(5): 417. CrossRef

Epidemiology
Application of the 2013 American College of Cardiology/American Heart Association Cholesterol Guideline to the Korean National Health and Nutrition Examination Surveys from 1998 to 2012: Young Shin Song, Tae Jung Oh, Kyoung Min Kim, Jae Hoon Moon, Sung Hee Choi, Hak Chul Jang, Kyong Soo Park, Soo Lim; Diabetes Metab J. 2017;41(1):38-50. Published online December 16, 2016; DOI: https://doi.org/10.4093/dmj.2017.41.1.38

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Background

The 2013 American College of Cardiology/American Heart Association (ACC/AHA) guideline for the treatment of blood cholesterol recommends statin therapy for individuals at high risk of atherosclerotic cardiovascular disease (ASCVD). The aim of this study was to investigate serial trends in the percentages of Korean adults considered eligible for statin therapy according to the new ACC/AHA cholesterol guideline.

Methods

Data from the Korean National Health and Nutrition Examination Survey (KNHANES) I (1998, n=7,698), II (2001, n=5,654), III (2005, n=5,269), IV (2007 to 2009, n=15,727), and V (2010 to 2012, n=16,304), which used a stratified, multistage, probability sampling design, were used as representative of the entire Korean population.

Results

The percentage of adults eligible for statin therapy according to the ACC/AHA cholesterol guideline increased with time: 17.0%, 19.0%, 20.8%, 20.2%, and 22.0% in KNHANES I, II, III, IV, and V, respectively (P=0.022). The prevalence of ASCVD was 1.4% in KNHANES I and increased to 3.3% in KNHANES V. The percentage of diabetic patients aged 40 to 75 years with a low density lipoprotein cholesterol levels of 70 to 189 mg/dL increased from 4.8% in KNHANES I to 6.1% in KNHANES V. People with an estimated 10-year ASCVD risk ≥7.5% and aged 40 to 75 years accounted for the largest percentage among the four statin benefit groups: 9.1% in KNHANES I and 11.0% in KNHANES V.

Conclusion

Application of the 2013 ACC/AHA guideline has found that the percentage of Korean adults in the statin benefit groups has increased over the past 15 years.

Citations

Citations to this article as recorded by

Sex differences in risk factors for subclinical hypothyroidism
Jeonghoon Ha, Jeongmin Lee, Kwanhoon Jo, Dong-Jun Lim, Moo Il Kang, Bong Yun Cha, Min-Hee Kim
Endocrine Connections.2018; 7(4): 511. CrossRef

Pathophysiology
Protective Effects of Ginger (Zingiber officinale) Extract against Diabetes-Induced Heart Abnormality in Rats: Behrouz Ilkhanizadeh, Alireza Shirpoor, Mohamad hasan Khadem Ansari, Samira Nemati, Yusef Rasmi; Diabetes Metab J. 2016;40(1):46-53. Published online February 19, 2016; DOI: https://doi.org/10.4093/dmj.2016.40.1.46

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Background

Diabetic cardiomyopathy is an important causal factor in morbidity and mortality among diabetic patients, and currently, no effective means are available to reverse its pathological progress. The purpose of the present study was to investigate the effect of ginger extract on apolipoproteins (apo) A and B, hyperhomocysteinemia, cathepsin G and leptin changes, as well as cardiac fibrosis and heart muscle cell proliferation under hyperglycemic conditions in vivo.

Methods

Twenty-four male Wistar rats were divided into three groups, namely: control, non-treated diabetic, and ginger extract-treated diabetic groups. The ginger extract-treated diabetic group received a 50 mg daily dose of ginger extract intragastrically for 6 weeks.

Results

The results revealed concurrent significant increases in plasma C-reactive protein (CRP), homocysteine (Hcy), cathepsin G and apoB levels and decreases in apoA and leptin levels in the non-treated diabetic group compared to the control group. Moreover, heart structural changes, including fibrosis and heart muscle cell proliferation, were observed in non-treated diabetic rats compared to the control rats. Significant amelioration of changes in the heart structure together with restoration of the elevated levels of Hcy and CRP, leptin, cathepsin G, and apoA and B were found in the ginger extract-treated diabetic group compared to the non-treated diabetic group.

Conclusion

The findings indicated that ginger extract significantly reduces heart structural abnormalities in diabetic rats and that these effects might be associated with improvements in serum apo, leptin, cathepsin G, and Hcy levels and with the antioxidant properties of ginger extract.

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Agreement between Framingham Risk Score and United Kingdom Prospective Diabetes Study Risk Engine in Identifying High Coronary Heart Disease Risk in North Indian Population: Dipika Bansal, Ramya S. R. Nayakallu, Kapil Gudala, Rajavikram Vyamasuni, Anil Bhansali; Diabetes Metab J. 2015;39(4):321-327. Published online July 8, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.4.321

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Background

The aim of the study is to evaluate the concurrence between Framingham Risk score (FRS) and United Kingdom Prospective Diabetes Study (UKPDS) risk engine in identifying coronary heart disease (CHD) risk in newly detected diabetes mellitus patients and to explore the characteristics associated with the discrepancy between them.

Methods

A cross-sectional study involving 489 subjects newly diagnosed with type 2 diabetes mellitus was conducted. Agreement between FRS and UKPDS in classifying patients as high risk was calculated using kappa statistic. Subjects with discrepant scores between two algorithms were identified and associated variables were determined.

Results

The FRS identified 20.9% subjects (range, 17.5 to 24.7) as high-risk while UKPDS identified 21.75% (range, 18.3 to 25.5) as high-risk. Discrepancy was observed in 17.9% (range, 14.7 to 21.7) subjects. About 9.4% had high risk by UKPDS but not FRS, and 8.6% had high risk by FRS but not UKPDS. The best agreement was observed at high-risk threshold of 20% for both (κ=0.463). Analysis showed that subjects having high risk on FRS but not UKPDS were elderly females having raised systolic and diastolic blood pressure. Patients with high risk on UKPDS but not FRS were males and have high glycosylated hemoglobin.

Conclusion

The FRS and UKPDS (threshold 20%) identified different populations as being at high risk, though the agreement between them was fairly good. The concurrence of a number of factors (e.g., male sex, low high density lipoprotein cholesterol, and smoking) in both algorithms should be regarded as increasing the CHD risk. However, longitudinal follow-up is required to form firm conclusions.

Citations

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Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database: Sunghwan Suh, Gi Hyeon Seo, Chang Hee Jung, Mee-Kyoung Kim, Sang-Man Jin, You-Cheol Hwang, Byung-Wan Lee, Jae Hyeon Kim; Diabetes Metab J. 2015;39(3):247-252. Published online April 22, 2015; DOI: https://doi.org/10.4093/dmj.2015.39.3.247

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Background

We assessed the association of dipeptidyl peptidase 4 inhibitors (DPP4i) with hospitalization for heart failure (HF) using the Korean Health Insurance claims database.

Methods

We collected data on newly prescribed sitagliptin, vildagliptin, and pioglitazone between January 1, 2009 and December 31, 2012 (mean follow-up of 336.8 days) to 935,519 patients with diabetes (518,614 males and 416,905 females) aged 40 to 79 years (mean age of 59.4 years).

Results

During the study, 998 patients were hospitalized for primary HF (115.7 per 100,000 patient-years). The incidence rate of hospitalization for HF was 117.7 per 100,000 per patient-years among patients on pioglitazone, 105.7 for sitagliptin, and 135.8 for vildagliptin. The hospitalization rate for HF was greatest in the first 30 days after starting the medication, which corresponded to a significantly higher incidence at days 0 to 30 compared with days 31 to 360 for all three drugs. The hazard ratios were 1.85 (pioglitazone), 2.00 (sitagliptin), and 1.79 (vildagliptin). The incidence of hospitalization for HF did not differ between the drugs for any time period.

Conclusion

This study showed an increase in hospitalization for HF in the initial 30 days of the DPP4i and pioglitazone compared with the subsequent follow-up period. However, the differences between the drugs were not significant.

Citations

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Letter: Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database (Diabetes Metab J2015;39:247-52)
Dae Ho Lee
Diabetes & Metabolism Journal.2015; 39(4): 348. CrossRef
Response: Increased Risk of Hospitalization for Heart Failure with Newly Prescribed Dipeptidyl Peptidase-4 Inhibitors and Pioglitazone Using the Korean Health Insurance Claims Database (Diabetes Metab J2015;39:247-52)
Sunghwan Suh, Gi Hyeon Seo, Chang Hee Jung, Mee-Kyoung Kim, Sang-Man Jin, You-Cheol Hwang, Byung-Wan Lee, Jae Hyeon Kim
Diabetes & Metabolism Journal.2015; 39(4): 350. CrossRef
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Dipeptidyl Peptidase-4 Inhibitor Alarms: Is Heart Failure Caused by a Class Effect?
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Review

Nutritional Status and Cardiac Autophagy: Jihyun Ahn, Jaetaek Kim; Diabetes Metab J. 2013;37(1):30-35. Published online February 15, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.1.30

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Autophagy is necessary for the degradation of long-lasting proteins and nonfunctional organelles, and is activated to promote cellular survival. However, overactivation of autophagy may deplete essential molecules and organelles responsible for cellular survival. Lifelong calorie restriction by 40% has been shown to increase the cardiac expression of autophagic markers, which suggests that it may have a cardioprotective effect by decreasing oxidative damage brought on by aging and cardiovascular diseases. Although cardiac autophagy is critical to regulating protein quality and maintaining cellular function and survival, increased or excessive autophagy may have deleterious effects on the heart under some circumstances, including pressure overload-induced heart failure. The importance of autophagy has been shown in nutrient supply and preservation of energy in times of limitation, such as ischemia. Some studies have suggested that a transition from obesity to metabolic syndrome may involve progressive changes in myocardial inflammation, mitochondrial dysfunction, fibrosis, apoptosis, and myocardial autophagy.

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Original Articles

Smaller Mean LDL Particle Size and Higher Proportion of Small Dense LDL in Korean Type 2 Diabetic Patients: Sunghwan Suh, Hyung-Doo Park, Se Won Kim, Ji Cheol Bae, Alice Hyun-Kyung Tan, Hye Soo Chung, Kyu Yeon Hur, Jae Hyeon Kim, Kwang-Won Kim, Moon-Kyu Lee; Diabetes Metab J. 2011;35(5):536-542. Published online October 31, 2011; DOI: https://doi.org/10.4093/dmj.2011.35.5.536

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Background

Small dense low density lipoprotein (sdLDL) has recently emerged as an important risk factor of coronary heart disease.

Methods

The mean LDL particle size was measured in 203 patients with type 2 diabetes mellitus (T2DM) and 212 matched subjects without diabetes using polyacrylamide tube gel electrophoresis. Major vascular complications were defined as stroke, angiographically-documented coronary artery disease or a myocardial infarction. Peripheral vascular stenosis, carotid artery stenosis (≥50% in diameter) or carotid artery plaque were considered minor vascular complications. Overall vascular complications included both major and minor vascular complications.

Results

Diabetic patients had significantly smaller mean-LDL particle size (26.32 nm vs. 26.49 nm) and a higher percentage of sdLDL to total LDL compared to those of subjects without diabetes (21.39% vs. 6.34%). The independent predictors of sdLDL in this study were serum triglyceride level and body mass index (odds ratio [OR], 1.020 with P<0.001 and OR 1.152 with P<0.027, respectively). However, no significant correlations were found between sdLDL and major vascular complications (P=0.342), minor vascular complications (P=0.573) or overall vascular complications (P=0.262) in diabetic subjects.

Conclusion

Diabetic patients had a smaller mean-LDL particle size and higher proportion of sdLDL compared to those of subjects without diabetes. Obese diabetic patients with hypertriglyceridemia have an increased risk for atherogenic small dense LDL. However, we could not verify an association between LDL particle size and vascular complications in this study.

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The Status of Diabetes Mellitus and Effects of Related Factors on Heart Rate Variability in a Community.: Kyeong Soon Chang, Kwan Lee, Hyun Sul Lim; Korean Diabetes J. 2009;33(6):537-546. Published online December 1, 2009; DOI: https://doi.org/10.4093/kdj.2009.33.6.537

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Abstract PDF

BACKGROUND
This study was performed to examine the status of diabetes mellitus (DM) in the community and effects of related factors on heart rate variability (HRV). METHODS: The author conducted HRV testing, a questionnaire survey, and blood chemistry analysis for fasting blood sugar (FBS) and HbA1c levels in 855 patients in a community over a period of 10 days, from August 14 to 25, 2006. The subjects were divided into a DM group and normal group by our study criteria. RESULTS: The proportion of DM was 12.6% and increased with old age. The mean measures of HRV (SDNN, Tp, Vlf, Lf, Hf, Lf/Hf) in the DM group were 22.7 (1.6) msec, 364.9 (2.7) msec2, 174.1 (3.0) msec2, 88.1 (3.2) msec2, 55.3 (3.2) msec2, and 1.6 (2.6), respectively, while those in the normal group were 32.2 (1.6) msec, 676.6 (2.8) msec2, 295.7 (3.1) msec2, 169.2 (3.4) msec2, 117.2 (3.2) msec2, and 1.4 (2.6), respectively. All parameters except for Lf/Hf were significantly lower in the DM group than in the normal group (P < 0.01). The Spearman's correlation coefficients between HRV and FBS or HbA1c were SDNN -0.222/-0.244 (P < 0.01), Tp -0.211/-0.212 (P < 0.01), Vlf -0.149/-0.132 (P < 0.01), Lf -0.188/-0.235 (P < 0.01), Hf -0.207/-0.204 (P < 0.01), and Lf/Hf (P > 0.05), respectively. CONCLUSION: This study shows that the DM group had a reduced HRV and increased pulse rate in comparison with the normal group. According to our results, the HRV test may be used accessorily for the early detection of cardiovascular autonomic neuropathy (CAN) and its related factors, as well as to prevent CAN.

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Abstract PDF

BACKGROUND
We compared the prevalences of two criteria of metabolic syndrome, that is, American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and International Diabetes Federation (IDF), in Korean male adults and compared the predictability of insulin resistance and future cardiovascular diseases using Framingham Risk Score. METHODS: In total 23,467 male adults (mean age 43.3 years) who participated in medical check-up in 2005, the prevalences of metabolic syndrome according to AHA/NHLBI and IDF criteria and the presence of insulin resistance, defined by the highest quartile of Homeostasis Model Assessment of insulin resistance index (HOMA-IR), were compared. The relative risk (calculated risk/average risk) for 10-year risk for coronary artery disease (CHD) assessed by Framingham Risk Score were compared. RESULTS: 5.8% of the subjects had diabetes mellitus. 20.7% and 13.2%of the subjects had metabolic syndrome defined by AHA/NHLBI and IDF criteria, and the two criteria showed high agreement with kappa value of 0.737 (P < 0.01). More subjects in IDF-defined group had insulin resistance compared with AHA/NHLBI definition (59.8 vs. 54%, P < 0.01). The odds ratio for increased relative risk (> 1.0) for 10-year CHD were higher in AHA/NHLBI-defined subjects compared with IDF-defined subject (3.295 vs. 3.082). The Kappa values for the analysis of agreement between each criteria and prediction of insulin resistance or cardiovascular disease risk, were too low for comparison. CONCLUSION: In Korean males, the prevalence for metabolic syndrome defined by AHA/NHLBI criteria was higher than those defined by IDF criteria. IDF criteria detected more subjects with insulin resistance, but didn't have better predictability for CHD compared with AHA/NHLBI criteria.

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Value of Coronary Calcium Score in Type 2 Diabetics.: Ji Eun Lee, Mi Jung Eun, Kyung Ah Chun, Jae Hong Kim, Ji Sung Yoon, Ihn Ho Cho, Kyu Chang Won, Hyoung Woo Lee; Korean Diabetes J. 2006;30(4):303-311. Published online July 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.4.303

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Abstract PDF: BACKGROUND
Cardiovascular disease including coronary heart disease (CHD) is the most common cause of morbidity and mortality in patients with diabetes. But traditional risk factor assessment is limited to predict CHD in asymptomatic high-risk individuals. In this study, relationship between coronary calcium score (CCS) and CHD was evaluated to determine value of coronary artery calcification detected by multi-slice spiral computed tomography to predict CHD in high risk asymptomatic patients with type 2 diabetes. METHODS: 127 patients were enrolled who admitted in Yeungnam University Hospital between December 2004 and May 2005. Standard cardiovascular risk factors and the CCS measured by multi-slice spiral computed tomography were assessed. RESULTS: Enrolled subjects were consisted of 56 subjects with diabetes and 71 subjects without diabetes. The mean CCS was significantly greater in patients with diabetes than without diabetics (P < 0.01). In both groups, patients with higher CCS had higher prevalence of CHD (P < 0.05). In all subjects, LDL cholesterol levels and CCS were significantly associated in multi-variate analysis (P < 0.05). In patients without diabetes, age was only associated with presence of CHD (P < 0.05). CCS was only associated with CHD in patients with diabetes, even after adjusting for the effects of age, LDL cholesterol and CRP (P < 0.05). CONCLUSION: Therefore, multi-slice spiral computed tomography can non-invasively and accurately detect coronary calcification. By detection of coronary artery calcification, it may be possible to predict coronary heart disease early in high-risk asymptomatic patients with type 2 diabetes.

The Association of Pro12Ala Polymorphism in PPAR-gamma Gene with Coronary Artery Disease in Korean Subjects.: Chang Hee Kwon, Eun Jung Rhee, Se Yeon Kim, Eun Ran Kim, Chang Uk Chon, Chan Hee Jung, Ji Ho Yun, Byung Jin Kim, Ki Chul Sung, Bum Su Kim, Won Young Lee, Ki Won Oh, Jin Ho Kang, Sun Woo Kim, Man Ho Lee, Jung Roe Park; Korean Diabetes J. 2006;30(2):122-129. Published online March 1, 2006; DOI: https://doi.org/10.4093/jkda.2006.30.2.122

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Abstract PDF: BACKGROUND
PPAR-gamma, a member of nuclear family, which is involved in the differentiation of adipose tissue, is reported to be associated in the pathogenesis of type 2 diabetes mellitus, insulin resistance and atherosclerosis. We conducted a research to see whether the prevalence of coronary artery disease is associated with Pro12Ala polymorphism in exon B of PPAR-gamma in Korean adults. METHODS: The study was conducted in 161 subjects (97 males, 64 females, mean age 57 year old) who underwent coronary angiogram due to chest pain. We assessed cardiovascular risk factors in all subjects, such as blood pressure, body mass index (BMI), fasting blood sugar and serum lipid profiles. Subjects were divided into four groups as normal, 1-vessel, 2-vessel and 3-vessel disease according to the number of stenosed coronary arteries. Genotypings of Pro12Ala polymorphism were done with Real-time polymerase chain reaction. RESULTS: Allelic frequency for proline was 0.957 and 0.043 for alanine, and they were in compliance with Hardy-Weinberg equilibrium (P = 0.85). 79 subjects (43.5%) had normal coronary artery, 52 subjects (31%), 1-vessel disease, 24 subjects (14.9%), 2-vessel disease and 15 subjects (9.3%), 3-vessel disease. When the cardiovascular risk factors were compared among these four groups, there were no meaningful differences except the age and high-density lipoprotein cholesterol levels, which were lost after adjustment for age and BMI. There were no significant differences in the prevalence or severity of coronary artery diseases according to the different genotypes of Pro12Ala polymorphism. CONCLUSIONS: There was no significantassociation between Pro12Ala polymorphism in exon B of PPAR-gamma and prevalence or severity of coronary artery disease in Korean adults. It is considered that further studies on the correlation between Pro12Ala polymorphism and coronary artery disease should be carried out in larger Korean population in the future

Detection of Diabetic Autonomic Neuropathy by 24-Hour Heart Rate Variability Analysis in Type 2 Diabetes Mellitus Patients.: Young Hee Rho, Nan Hee Kim, Dong Lim Kim, Dong Hyun Shin, Sin Gon Kim, Kyung Mook Choi, Woo Hyuk Song, Sei Hyun Baik, Woo Keun Seo, Min Kyu Park, Dong Seop Choi; Korean Diabetes J. 2002;26(3):208-219. Published online June 1, 2002

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Abstract PDF: BACKGROUND
Diabetic autonomic neuropathy is a relatively common diabetic complication, associated with high long-term mortality. Ewing's test is known as the 'gold standard' for evaluating and diagnosing this disease, yet is not widely used due to the inconvenient procedures of the test. 24-hour Holter EKG monitoring, and the analytical product, heart rate variability, is being introduced as a relatively simple and reliable procedure for the evaluation of diabetic autonomic neuropathy. We explored whether such heart rate variability products derived from Holter monitoring, correlated with the presence, absence, or severity of diabetes mellitus, and whether it correlated well with conventional autonomic tests. METHODS: We compared 59 type 2 diabetic patients with 71 normal subjects. All underwent 24-hr Holter EKG monitoring and basic autonomic evaluations, such as the head-up tilting, hand grip, and deep breathing-heart rate variability tests. Those who had diabetes also underwent evaluation for basic blood chemistry, and complication studies, for things such as: 24-hour urine albumin excretion, fundoscopy and nerve conduction. RESULTS: Variables for heart rate variability were expressed as SDDN, rMSSD, LF, HF, and LF/HF, where SDDN is the Standard Deviation of all RR intervals, rMSSD the square root of the mean of the sum of the squares of differences between adjacent RR intervals, LF the power in the Low Frequency range and HF the power in the High Frequency range, with LF/HF being the ratio between LF and HF. Heart rate variability was significantly lower in terms of rMSSD, LF, HF, but not in terms of the LF/HF ratio, for the diabetic patients compared to the normal subjects. These three variables also correlated with the conventional autonomic tests of systolic blood pressure changes during standing up (negatively), and heart rate variability during deep breathing (positively). SDDN, rMSSD, LF, and HF also correlated negatively with the duration of diabetes. SDDN, LF and HF were significantly lower among patients who had complications such as: retinopathy, nephropathy or peripheral neuropathy, than in those who did not. CONCLUSION: Heart rate variability was lower in type 2 diabetic patients than the control subjects, which correlated well with the duration of diabetes mellitus, diabetic chronic complications and the conventional autonomic nervous function tests, so could be an useful adjunct or even a replacement, for conventional autonomic nervous system testing procedures. More research is needed in this field.

Relationship between Angiotensin I Converting Enzyme Gene Polymorphism and Vascular complications in Non-Insulin Dependent Diabetic Patients.: Byoung Gue Na, Tae Geun Oh, Sang Moo Jung, Sang Woo Oh, Jae Hong Choi, Ji Hyun Lee, Seong Su Koong, Seung Taik Kim; Korean Diabetes J. 1997;21(2):138-146. Published online January 1, 2001

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