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Original Articles
Lipid Variability Induces Endothelial Dysfunction by Increasing Inflammation and Oxidative Stress
Marie Rhee, Joonyub Lee, Eun Young Lee, Kun-Ho Yoon, Seung-Hwan Lee
Received December 22, 2023  Accepted March 14, 2024  Published online May 16, 2024  
DOI: https://doi.org/10.3803/EnM.2023.1915    [Epub ahead of print]
  • 467 View
  • 13 Download
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study investigates the impact of fluctuating lipid levels on endothelial dysfunction.
Methods
Human aortic and umbilical vein endothelial cells were cultured under varying palmitic acid (PA) concentrations: 0, 50, and 100 μM, and in a variability group alternating between 0 and 100 μM PA every 8 hours for 48 hours. In the lipid variability group, cells were exposed to 100 μM PA during the final 8 hours before analysis. We assessed inflammation using real-time polymerase chain reaction, Western blot, and cytokine enzyme-linked immunosorbent assay (ELISA); reactive oxygen species (ROS) levels with dichlorofluorescin diacetate assay; mitochondrial function through oxygen consumption rates via XF24 flux analyzer; and endothelial cell functionality via wound healing and cell adhesion assays. Cell viability was evaluated using the MTT assay.
Results
Variable PA levels significantly upregulated inflammatory genes and adhesion molecules (Il6, Mcp1, Icam, Vcam, E-selectin, iNos) at both transcriptomic and protein levels in human endothelial cells. Oscillating lipid levels reduced basal respiration, adenosine triphosphate synthesis, and maximal respiration, indicating mitochondrial dysfunction. This lipid variability also elevated ROS levels, contributing to a chronic inflammatory state. Functionally, these changes impaired cell migration and increased monocyte adhesion, and induced endothelial apoptosis, evidenced by reduced cell viability, increased BAX, and decreased BCL2 expression.
Conclusion
Lipid variability induce endothelial dysfunction by elevating inflammation and oxidative stress, providing mechanistic insights into how lipid variability increases cardiovascular risk.

Citations

Citations to this article as recorded by  
  • Can Daily Dietary Choices Have a Cardioprotective Effect? Food Compounds in the Prevention and Treatment of Cardiometabolic Diseases
    Elżbieta Szczepańska, Barbara Janota, Marika Wlazło, Magdalena Gacal
    Metabolites.2024; 14(6): 296.     CrossRef
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Miscellaneous
Prediction of Cardiovascular Complication in Patients with Newly Diagnosed Type 2 Diabetes Using an XGBoost/GRU-ODE-Bayes-Based Machine-Learning Algorithm
Joonyub Lee, Yera Choi, Taehoon Ko, Kanghyuck Lee, Juyoung Shin, Hun-Sung Kim
Endocrinol Metab. 2024;39(1):176-185.   Published online November 21, 2023
DOI: https://doi.org/10.3803/EnM.2023.1739
  • 1,393 View
  • 71 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Cardiovascular disease is life-threatening yet preventable for patients with type 2 diabetes mellitus (T2DM). Because each patient with T2DM has a different risk of developing cardiovascular complications, the accurate stratification of cardiovascular risk is critical. In this study, we proposed cardiovascular risk engines based on machine-learning algorithms for newly diagnosed T2DM patients in Korea.
Methods
To develop the machine-learning-based cardiovascular disease engines, we retrospectively analyzed 26,166 newly diagnosed T2DM patients who visited Seoul St. Mary’s Hospital between July 2009 and April 2019. To accurately measure diabetes-related cardiovascular events, we designed a buffer (1 year), an observation (1 year), and an outcome period (5 years). The entire dataset was split into training and testing sets in an 8:2 ratio, and this procedure was repeated 100 times. The area under the receiver operating characteristic curve (AUROC) was calculated by 10-fold cross-validation on the training dataset.
Results
The machine-learning-based risk engines (AUROC XGBoost=0.781±0.014 and AUROC gated recurrent unit [GRU]-ordinary differential equation [ODE]-Bayes=0.812±0.016) outperformed the conventional regression-based model (AUROC=0.723± 0.036).
Conclusion
GRU-ODE-Bayes-based cardiovascular risk engine is highly accurate, easily applicable, and can provide valuable information for the individualized treatment of Korean patients with newly diagnosed T2DM.
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Diabetes, obesity and metabolism
Big Data Articles (National Health Insurance Service Database)
Long-Term Cumulative Exposure to High γ-Glutamyl Transferase Levels and the Risk of Cardiovascular Disease: A Nationwide Population-Based Cohort Study
Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
Endocrinol Metab. 2023;38(6):770-781.   Published online November 6, 2023
DOI: https://doi.org/10.3803/EnM.2023.1726
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  • 51 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population.
Methods
Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model.
Results
During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death.
Conclusion
Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Citations

Citations to this article as recorded by  
  • Interplay of serum biomarkers bilirubin and γ-glutamyltranspeptidase in predicting cardiovascular complications in type-2 diabetes mellitus
    Ebtesam Abdullah Al-Suhaimi, Abdullah Ahmed Al-Rubaish
    World Journal of Diabetes.2024; 15(6): 1074.     CrossRef
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Diabetes, obesity and metabolism
Coronary Artery Calcium Score as a Sensitive Indicator of Cardiovascular Disease in Patients with Type 2 Diabetes Mellitus: A Long-Term Cohort Study
Dae-Jeong Koo, Mi Yeon Lee, Sun Joon Moon, Hyemi Kwon, Sang Min Lee, Se Eun Park, Cheol-Young Park, Won-Young Lee, Ki Won Oh, Sung Rae Cho, Young-Hoon Jeong, Eun-Jung Rhee
Endocrinol Metab. 2023;38(5):568-577.   Published online October 10, 2023
DOI: https://doi.org/10.3803/EnM.2023.1770
  • 2,062 View
  • 121 Download
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Coronary artery calcium score (CACS) has become an important tool for evaluating cardiovascular disease (CVD). This study evaluated the significance of CACS for future CVD through more than 10 years of follow-up in asymptomatic Korean populations with type 2 diabetes mellitus (T2DM) known to have a relatively low CACS burden.
Methods
We enrolled 981 asymptomatic T2DM patients without CVD at baseline who underwent CACS evaluation using multidetector computed tomography between January 2008 and December 2014. They were grouped into five predefined CACS categories based on Agatston scores and followed up by August 2020. The primary endpoint was incident CVD events, including coronary, cerebrovascular, and peripheral arterial disease.
Results
The relative risk of CVD was significantly higher in patients with CACS ≥10, and the significance persisted after adjustment for known confounders. A higher CACS category indicated a higher incidence of future CVD: hazard ratio (95% confidence interval) 4.09 (1.79 to 9.36), 12.00 (5.61 to 25.69), and 38.79 (16.43 to 91.59) for 10≤ CACS <100, 100≤ CACS <400, and CACS ≥400, respectively. During the 12-year follow-up period, the difference in event-free survival more than doubled as the category increased. Patients with CACS below 10 had very low CVD incidence throughout the follow-up. The receiver operating characteristic analysis showed better area under curve when the CACS cutoff was 10 than 100.
Conclusion
CACS can be a sensitive marker of CVD risk. Specifically, CACS above 10 is an indicator of CVD high-risk requiring more intensive medical treatment in Koreans with T2DM.
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Diabetes, obesity and metabolism
Triglyceride-Glucose Index Predicts Future Atherosclerotic Cardiovascular Diseases: A 16-Year Follow-up in a Prospective, Community-Dwelling Cohort Study
Joon Ho Moon, Yongkang Kim, Tae Jung Oh, Jae Hoon Moon, Soo Heon Kwak, Kyong Soo Park, Hak Chul Jang, Sung Hee Choi, Nam H. Cho
Endocrinol Metab. 2023;38(4):406-417.   Published online August 3, 2023
DOI: https://doi.org/10.3803/EnM.2023.1703
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  • 188 Download
  • 7 Web of Science
  • 7 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
While the triglyceride-glucose (TyG) index is a measure of insulin resistance, its association with cardiovascular disease (CVD) has not been well elucidated. We evaluated the TyG index for prediction of CVDs in a prospective large communitybased cohort.
Methods
Individuals 40 to 70 years old were prospectively followed for a median 15.6 years. The TyG index was calculated as the Ln [fasting triglycerides (mg/dL)×fasting glucose (mg/dL)/2]. CVDs included any acute myocardial infarction, coronary artery disease or cerebrovascular disease. We used a Cox proportional hazards model to estimate CVD risks according to quartiles of the TyG index and plotted the receiver operating characteristics curve for the incident CVD.
Results
Among 8,511 subjects (age 51.9±8.8 years; 47.5% males), 931 (10.9%) had incident CVDs during the follow-up. After adjustment for age, sex, body mass index, diabetes mellitus, hypertension, total cholesterol, smoking, alcohol, exercise, and C-reactive protein, subjects in the highest TyG quartile had 36% increased risk of incident CVD compared with the lowest TyG quartile (hazard ratio, 1.36; 95% confidence interval, 1.10 to 1.68). Carotid plaque, assessed by ultrasonography was more frequent in subjects in the higher quartile of TyG index (P for trend=0.049 in men and P for trend <0.001 in women). The TyG index had a higher predictive power for CVDs than the homeostasis model assessment of insulin resistance (HOMA-IR) (area under the curve, 0.578 for TyG and 0.543 for HOMA-IR). Adding TyG index on diabetes or hypertension alone gave sounder predictability for CVDs.
Conclusion
The TyG index is independently associated with future CVDs in 16 years of follow-up in large, prospective Korean cohort.

Citations

Citations to this article as recorded by  
  • Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus
    Kaisheng Yuan, Bing Wu, Ruiqi Zeng, Fuqing Zhou, Ruixiang Hu, Cunchuan Wang
    Diabetes, Obesity and Metabolism.2024; 26(1): 169.     CrossRef
  • Association between the triglyceride glucose index and chronic total coronary occlusion: A cross-sectional study from southwest China
    Kaiyong Xiao, Huili Cao, Bin Yang, Zhe Xv, Lian Xiao, Jianping Wang, Shuiqing Ni, Hui Feng, Zhongwei He, Lei Xv, Juan Li, Dongmei Xv
    Nutrition, Metabolism and Cardiovascular Diseases.2024; 34(4): 850.     CrossRef
  • The association between TyG and all-cause/non-cardiovascular mortality in general patients with type 2 diabetes mellitus is modified by age: results from the cohort study of NHANES 1999–2018
    Younan Yao, Bo Wang, Tian Geng, Jiyan Chen, Wan Chen, Liwen Li
    Cardiovascular Diabetology.2024;[Epub]     CrossRef
  • Comparison of triglyceride glucose index and modified triglyceride glucose indices in prediction of cardiovascular diseases in middle aged and older Chinese adults
    Cancan Cui, Yitian Qi, Jiayin Song, Xinyun Shang, Tianjiao Han, Ning Han, Siqi Yue, Yining Zha, Zhonghang Xu, Jiannan Li, Lin Liu
    Cardiovascular Diabetology.2024;[Epub]     CrossRef
  • Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers
    Min Jin Lee, Ji Hyun Bae, Ah Reum Khang, Dongwon Yi, Mi Sook Yun, Yang Ho Kang
    Diabetes Research and Clinical Practice.2024; 210: 111640.     CrossRef
  • Prognostic value of triglyceride-glucose index for left ventricular remodeling in nondiabetic ST-elevation myocardial infarction patients
    Tolga Han Efe, Engin Algül
    Biomarkers in Medicine.2024; : 1.     CrossRef
  • Evaluation of the novel three lipid indices for predicting five- and ten-year incidence of cardiovascular disease: findings from Kerman coronary artery disease risk factors study (KERCADRS)
    Alireza Jafari, Hamid Najafipour, Mitra Shadkam, Sina Aminizadeh
    Lipids in Health and Disease.2023;[Epub]     CrossRef
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Diabetes, Obesity and Metabolism
Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients
Ja Young Jeon, Shin Han-Bit, Bum Hee Park, Nami Lee, Hae Jin Kim, Dae Jung Kim, Kwan-Woo Lee, Seung Jin Han
Endocrinol Metab. 2023;38(1):139-145.   Published online February 6, 2023
DOI: https://doi.org/10.3803/EnM.2022.1594
  • 1,863 View
  • 128 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients.
Methods
We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model.
Results
Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE.
Conclusion
Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

Citations

Citations to this article as recorded by  
  • Effect of post-transplant diabetes mellitus on cardiovascular events and mortality: a single‐center retrospective cohort study
    Uğur Ünlütürk, Tolga Yıldırım, Merve Savaş, Seda Hanife Oğuz, Büşra Fırlatan, Deniz Yüce, Nesrin Damla Karakaplan, Cemile Selimova, Rahmi Yılmaz, Yunus Erdem, Miyase Bayraktar
    Endocrine.2024;[Epub]     CrossRef
  • Prevalence of new-onset diabetes mellitus after kidney transplantation: a systematic review and meta-analysis
    Qiufeng Du, Tao Li, Xiaodong Yi, Shuang Song, Jing Kang, Yunlan Jiang
    Acta Diabetologica.2024;[Epub]     CrossRef
  • Safety and efficacy of semaglutide in post kidney transplant patients with type 2 diabetes or Post-Transplant diabetes
    Moeber Mohammed Mahzari, Omar Buraykan Alluhayyan, Mahdi Hamad Almutairi, Mohammed Abdullah Bayounis, Yazeed Hasan Alrayani, Amir A. Omair, Awad Saad Alshahrani
    Journal of Clinical & Translational Endocrinology.2024; 36: 100343.     CrossRef
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Diabetes, Obesity and Metabolism
Big Data Articles (National Health Insurance Service Database)
Association between the Diabetes Drug Cost and Cardiovascular Events and Death in Korea: A National Health Insurance Service Database Analysis
Seung Min Chung, Ji-In Lee, Eugene Han, Hyun-Ae Seo, Eonju Jeon, Hye Soon Kim, Ji Sung Yoon
Endocrinol Metab. 2022;37(5):759-769.   Published online October 5, 2022
DOI: https://doi.org/10.3803/EnM.2022.1515
  • 3,534 View
  • 199 Download
  • 1 Web of Science
  • 1 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
This study aimed to investigate the long-term effects of diabetes drug costs on cardiovascular (CV) events and death.
Methods
This retrospective observational study used data from 2009 to 2018 from the National Health Insurance in Korea. Among the patients with type 2 diabetes, those taking antidiabetic drugs and who did not have CV events until 2009 were included. Patients were divided into quartiles (Q1 [lowest]–4 [highest]) according to the 2009 diabetes drug cost. In addition, the 10-year incidences of CV events (non-fatal myocardial infarction, stroke, hospitalization for heart failure, and coronary revascularization) and CV death (death due to CV events) were analyzed.
Results
A total of 441,914 participants were enrolled (median age, 60 years; men, 57%). CV events and death occurred in 28.1% and 8.36% of the patients, respectively. The 10-year incidences of CV events and deaths increased from Q1 to 4. After adjusting for sex, age, income, type of diabetes drugs, comorbidities, and smoking and drinking status, the risk of CV events significantly increased according to the sequential order of the cost quartiles. In contrast, the risk of CV death showed a U-shaped pattern, which was the lowest in Q3 (hazard ratio [HR], 0.953; 95% confidence interval [CI], 0.913 to 0.995) and the highest in Q4 (HR, 1.266; 95% CI, 1.213 to 1.321).
Conclusion
Diabetes drug expenditure affects 10-year CV events and mortality. Therefore, affording an appropriate diabetes drug cost at a similar risk of CV is an independent protective factor against CV death.

Citations

Citations to this article as recorded by  
  • Impact of mental disorders on the risk of heart failure among Korean patients with diabetes: a cohort study
    Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
    Cardiovascular Diabetology.2023;[Epub]     CrossRef
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Review Article
Diabetes, Obesity and Metabolism
Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia
Joon Ho Moon, Kyuho Kim, Sung Hee Choi
Endocrinol Metab. 2022;37(4):575-586.   Published online August 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.402
  • 9,173 View
  • 467 Download
  • 14 Web of Science
  • 17 Crossref
AbstractAbstract PDFPubReader   ePub   
High levels of triglycerides (TG) and triglyceride-rich lipoproteins (TGRLs) confer a residual risk of cardiovascular disease after optimal low-density lipoprotein cholesterol (LDL-C)–lowering therapy. Consensus has been made that LDL-C is a non-arguable primary target for lipid lowering treatment, but the optimization of TGRL for reducing the remnant risk of cardiovascular diseases is urged. Omega-3 fatty acids and fibrates are used to reduce TG levels, but many patients still have high TG and TGRL levels combined with low high-density lipoprotein concentration that need to be ideally treated. Lipoprotein lipase (LPL) is a key regulator for TGs that hydrolyzes TGs to glycerol and free fatty acids in lipoprotein particles for lipid storage and consumption in peripheral organs. A deeper understanding of human genetics has enabled the identification of proteins regulating the LPL activity, which include the apolipoproteins and angiopoietin-like families. Novel therapeutic approach such as antisense oligonucleotides and monoclonal antibodies that regulate TGs have been developed in recent decades. In this article, we focus on the biology of LPL and its modulators and review recent clinical application, including genetic studies and clinical trials of novel therapeutics. Optimization of LPL activity to lower TG levels could eventually reduce incident atherosclerotic cardiovascular disease in conjunction with successful LDL-C reduction.

Citations

Citations to this article as recorded by  
  • The chylomicron saga: time to focus on postprandial metabolism
    Alejandro Gugliucci
    Frontiers in Endocrinology.2024;[Epub]     CrossRef
  • Sanghuangporus vaninii extract ameliorates hyperlipidemia in rats by mechanisms identified with transcriptome analysis
    Ning Gao, Yuanzhen Liu, Guangjie Liu, Bo Liu, Yupeng Cheng
    Food Science & Nutrition.2024; 12(5): 3360.     CrossRef
  • Targeting host-specific metabolic pathways—opportunities and challenges for anti-infective therapy
    Monika I. Konaklieva, Balbina J. Plotkin
    Frontiers in Molecular Biosciences.2024;[Epub]     CrossRef
  • Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024
    Harold Edward Bays, Carol Kirkpatrick, Kevin C. Maki, Peter P. Toth, Ryan T. Morgan, Justin Tondt, Sandra Michelle Christensen, Dave Dixon, Terry A. Jacobson
    Obesity Pillars.2024; 10: 100108.     CrossRef
  • Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review
    Chaicharn Deerochanawong, Sin Gon Kim, Yu-Cheng Chang
    Diabetes & Metabolism Journal.2024; 48(2): 184.     CrossRef
  • Xanthohumol, a prenylated chalcone, regulates lipid metabolism by modulating the LXRα/RXR-ANGPTL3-LPL axis in hepatic cell lines and high-fat diet-fed zebrafish models
    Wan-Yun Gao, Pei-Yi Chen, Hao-Jen Hsu, Je-Wen Liou, Chia-Ling Wu, Ming-Jiuan Wu, Jui-Hung Yen
    Biomedicine & Pharmacotherapy.2024; 174: 116598.     CrossRef
  • Obesity, dyslipidemia, and cardiovascular disease: A joint expert review from the Obesity Medicine Association and the National Lipid Association 2024
    Harold Edward Bays, Carol Kirkpatrick, Kevin C. Maki, Peter P. Toth, Ryan T. Morgan, Justin Tondt, Sandra Michelle Christensen, Dave Dixon, Terry A. Jacobson
    Journal of Clinical Lipidology.2024;[Epub]     CrossRef
  • Factors associated with treatment responses to pioglitazone in patients with steatotic liver disease: A 3‐year prospective cohort study
    Ming‐Ling Chang, Jennifer Tai, Jur‐Shan Cheng, Wei‐Ting Chen, Sien‐Sing Yang, Cheng‐Hsun Chiu, Rong‐Nan Chien
    Diabetes, Obesity and Metabolism.2024; 26(7): 2969.     CrossRef
  • Efficacy and safety of omega‐3‐acid ethyl acetate 90 capsules in severe hypertriglyceridemia: A randomized, controlled, multicenter study
    Wang Zhao, Yangang Wang, Jin Li, Tao Chen, Delu Yin, Hailong Dai, Zhuhua Yao, Shuiping Zhao
    Lipids.2024;[Epub]     CrossRef
  • High producer variant of lipoprotein lipase may protect from hepatocellular carcinoma in alcohol-associated cirrhosis
    Franziska Schmalz, Janett Fischer, Hamish Innes, Stephan Buch, Christine Möller, Madlen Matz-Soja, Witigo von Schönfels, Benjamin Krämer, Bettina Langhans, Alexandra Klüners, Michael Soyka, Felix Stickel, Jacob Nattermann, Christian P. Strassburg, Thomas
    JHEP Reports.2023; 5(4): 100684.     CrossRef
  • Measurement of Serum Low Density Lipoprotein Cholesterol and Triglyceride-Rich Remnant Cholesterol as Independent Predictors of Atherosclerotic Cardiovascular Disease: Possibilities and Limitations
    Dieter Lütjohann, Hans-Ulrich Klör, Frans Stellaard
    Nutrients.2023; 15(9): 2202.     CrossRef
  • Influence of antipsychotic medications on hyperlipidemia risk in patients with schizophrenia: evidence from a population-based cohort study and in vitro hepatic lipid homeostasis gene expression
    Tien-Yuan Wu, Ni Tien, Cheng-Li Lin, Yu-Cun Cheah, Chung Y. Hsu, Fuu-Jen Tsai, Yi-Jen Fang, Yun-Ping Lim
    Frontiers in Medicine.2023;[Epub]     CrossRef
  • Triglyceride-Rich Lipoprotein Metabolism: Key Regulators of Their Flux
    Alejandro Gugliucci
    Journal of Clinical Medicine.2023; 12(13): 4399.     CrossRef
  • Sugar and Dyslipidemia: A Double-Hit, Perfect Storm
    Alejandro Gugliucci
    Journal of Clinical Medicine.2023; 12(17): 5660.     CrossRef
  • Dyslipidemia in Patients with Chronic Kidney Disease: An Updated Overview
    Sang Heon Suh, Soo Wan Kim
    Diabetes & Metabolism Journal.2023; 47(5): 612.     CrossRef
  • Peroxisome Proliferator-Activated Receptor α in Lipoprotein Metabolism and Atherosclerotic Cardiovascular Disease
    Elena Valeria Fuior, Evangelia Zvintzou, Theodosios Filippatos, Katerina Giannatou, Victoria Mparnia, Maya Simionescu, Anca Violeta Gafencu, Kyriakos E. Kypreos
    Biomedicines.2023; 11(10): 2696.     CrossRef
  • Developing a model to predict the early risk of hypertriglyceridemia based on inhibiting lipoprotein lipase (LPL): a translational study
    Julia Hernandez-Baixauli, Gertruda Chomiciute, Juan María Alcaide-Hidalgo, Anna Crescenti, Laura Baselga-Escudero, Hector Palacios-Jordan, Elisabet Foguet-Romero, Anna Pedret, Rosa M. Valls, Rosa Solà, Miquel Mulero, Josep M. Del Bas
    Scientific Reports.2023;[Epub]     CrossRef
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Original Article
Diabetes, Obesity and Metabolism
High Cardiorespiratory Fitness Protects against Molecular Impairments of Metabolism, Heart, and Brain with Higher Efficacy in Obesity-Induced Premature Aging
Patcharapong Pantiya, Chanisa Thonusin, Natticha Sumneang, Benjamin Ongnok, Titikorn Chunchai, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Busarin Arunsak, Natthaphat Siri-Angkul, Sirawit Sriwichaiin, Nipon Chattipakorn, Siriporn C. Chattipakorn
Endocrinol Metab. 2022;37(4):630-640.   Published online August 5, 2022
DOI: https://doi.org/10.3803/EnM.2022.1430
  • 4,428 View
  • 125 Download
  • 3 Web of Science
  • 3 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
High cardiorespiratory fitness (CRF) protects against age-related diseases. However, the mechanisms mediating the protective effect of high intrinsic CRF against metabolic, cardiac, and brain impairments in non-obese versus obese conditions remain incompletely understood. We aimed to identify the mechanisms through which high intrinsic CRF protects against metabolic, cardiac, and brain impairments in non-obese versus obese untrained rats.
Methods
Seven-week-old male Wistar rats were divided into two groups (n=8 per group) to receive either a normal diet or a highfat diet (HFD). At weeks 12 and 28, CRF, carbohydrate and fatty acid oxidation, cardiac function, and metabolic parameters were evaluated. At week 28, behavior tests were performed. At the end of week 28, rats were euthanized to collect heart and brain samples for molecular studies.
Results
The obese rats exhibited higher values for aging-related parameters than the non-obese rats, indicating that they experienced obesity-induced premature aging. High baseline CRF levels were positively correlated with several favorable metabolic, cardiac, and brain parameters at follow-up. Specifically, the protective effects of high CRF against metabolic, cardiac, and brain impairments were mediated by the modulation of body weight and composition, the lipid profile, substrate oxidation, mitochondrial function, insulin signaling, autophagy, apoptosis, inflammation, oxidative stress, cardiac function, neurogenesis, blood-brain barrier, synaptic function, accumulation of Alzheimer’s disease-related proteins, and cognition. Interestingly, this effect was more obvious in HFD-fed rats.
Conclusion
The protective effect of high CRF is mediated by the modulation of several mechanisms. These effects exhibit greater efficacy under conditions of obesity-induced premature aging.

Citations

Citations to this article as recorded by  
  • Associations that Cardiorespiratory Fitness and Body Mass Index Loss Have with Deficit Accumulation Frailty
    KAYLONI OLSON, DENISE K. HOUSTON, JOHNATHAN ROSS, RENA R. WING, FELICIA R. SIMPSON, AMBARISH PANDEY, MICHAEL P. WALKUP, MIA YANG, MARK A. ESPELAND
    Medicine & Science in Sports & Exercise.2024; 56(4): 717.     CrossRef
  • Interplay between obesity and aging on myocardial geometry and function: Role of leptin-STAT3-stress signaling
    Wei Jin, Fei Tu, Feng Dong, Qinqin Deng, Miyesaier Abudureyimu, Wei Yu, Guo-jun Cai, Jian-ming Pei, Zhaohui Pei, Jun Ren
    Biochimica et Biophysica Acta (BBA) - General Subjects.2023; 1867(2): 130281.     CrossRef
  • Epidemiological, mechanistic, and practical bases for assessment of cardiorespiratory fitness and muscle status in adults in healthcare settings
    Jaime A. Gallo-Villegas, Juan C. Calderón
    European Journal of Applied Physiology.2023; 123(5): 945.     CrossRef
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Review Articles
Adrenal Gland
Long-Term Outcomes of Congenital Adrenal Hyperplasia
Anna Nordenström, Svetlana Lajic, Henrik Falhammar
Endocrinol Metab. 2022;37(4):587-598.   Published online July 8, 2022
DOI: https://doi.org/10.3803/EnM.2022.1528
  • 30,985 View
  • 296 Download
  • 13 Web of Science
  • 15 Crossref
AbstractAbstract PDFPubReader   ePub   
A plethora of negative long-term outcomes have been associated with congenital adrenal hyperplasia (CAH). The causes are multiple and involve supra-physiological gluco- and mineralocorticoid replacement, excess adrenal androgens both intrauterine and postnatal, elevated steroid precursor and adrenocorticotropic hormone levels, living with a congenital condition as well as the proximity of the cytochrome P450 family 21 subfamily A member 2 (CYP21A2) gene to other genes. This review aims to discuss the different long-term outcomes of CAH.

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  • Increased Prevalence of Accidents and Injuries in Congenital Adrenal Hyperplasia: A Population-based Cohort Study
    Henrik Falhammar, Angelica Lindén Hirschberg, Agneta Nordenskjöld, Henrik Larsson, Anna Nordenström
    The Journal of Clinical Endocrinology & Metabolism.2024; 109(3): e1175.     CrossRef
  • International Newborn Screening Practices for the Early Detection of Congenital Adrenal Hyperplasia
    Tracey A. Conlon, Colin P. Hawkes, Jennifer J. Brady, J. Gerard Loeber, Nuala Murphy
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    Ugochi Chinenye Okorafor, Uchechi Chioma Okorafor
    Journal of Clinical Medicine of Kazakhstan.2024; 21(1): 14.     CrossRef
  • Increased risk of nephrolithiasis: an emerging issue in children with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
    Mariangela Chiarito, Crescenza Lattanzio, Vito D’Ascanio, Donatella Capalbo, Paolo Cavarzere, Anna Grandone, Francesca Aiello, Giorgia Pepe, Malgorzata Wasniewska, Thomas Zoller, Mariacarolina Salerno, Maria Felicia Faienza
    Endocrine.2024; 84(2): 727.     CrossRef
  • Memory in female adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency
    Tania M. Espinosa Reyes, Dainy Cordero Martín, Miguel Ángel Álvarez, Henrik Falhammar
    Endocrine.2024;[Epub]     CrossRef
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    Bleuenn Dreves, Yves Reznik, Antoine Tabarin
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  • Interpretation of Steroid Biomarkers in 21-Hydroxylase Deficiency and Their Use in Disease Management
    Kyriakie Sarafoglou, Deborah P Merke, Nicole Reisch, Hedi Claahsen-van der Grinten, Henrik Falhammar, Richard J Auchus
    The Journal of Clinical Endocrinology & Metabolism.2023; 108(9): 2154.     CrossRef
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    Heike Hoyer-Kuhn, Alexander J Eckert, Gerhard Binder, Walter Bonfig, Angelika Dübbers, Stefan Riedl, Joachim Woelfle, Helmuth G Dörr, Reinhard W Holl
    The Journal of Clinical Endocrinology & Metabolism.2023; 108(11): e1199.     CrossRef
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    Henrik Falhammar
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    Tania M. Espinosa Reyes, Alba Katherine Pesántez Velepucha, Julio Oscar Cabrera Rego, Wendy Valdés Gómez, Emma Domínguez Alonso, Henrik Falhammar
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    Mara Carsote, Ana-Maria Gheorghe, Claudiu Nistor, Alexandra-Ioana Trandafir, Oana-Claudia Sima, Anca-Pati Cucu, Adrian Ciuche, Eugenia Petrova, Adina Ghemigian
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    Semra Çaglar Çetinkaya
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    Andreea Gabriela Nicola, Mara Carsote, Ana-Maria Gheorghe, Eugenia Petrova, Alexandru Dan Popescu, Adela Nicoleta Staicu, Mihaela Jana Țuculină, Cristian Petcu, Ionela Teodora Dascălu, Tiberiu Tircă
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Diabetes, Obesity and Metabolism
Extra-Glycemic Effects of Anti-Diabetic Medications: Two Birds with One Stone?
Eun-Jung Rhee
Endocrinol Metab. 2022;37(3):415-429.   Published online June 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.304
  • 4,871 View
  • 274 Download
  • 3 Web of Science
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AbstractAbstract PDFPubReader   ePub   
The world is suffering from a rapid increase in the number of people with diabetes due to the increased prevalence of obesity and lengthened life span. Since the development of insulin thanks to the efforts of Prof. Banting and Dr. Best in 1922, for which they won the Nobel Prize, remarkable developments in anti-diabetic medications have dramatically lengthened the lifespan of patients with diabetes. However, the control rate of hyperglycemia in patients with diabetes remains unsatisfactory, since glycemic control requires both medication and lifestyle modifications to slow the deterioration of pancreatic beta-cell function and prevent diabetic complications. From the initial “triumvirate” to the “ominous octet,” and now the “egregious eleven,” the number of organs recognized as being involved in hyperglycemia and diabetes has increased with the development of anti-diabetic medications. Recent unexpected results from outcome trials of anti-diabetic medications have enabled anti-diabetic medications to be indicated for the prevention of chronic kidney disease and heart failure, even in patients without diabetes. In this review, I would like to summarize the extra-glycemic effects of anti-diabetic medications.

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  • Glucagon-Like Peptide Receptor Agonist Inhibits Angiotensin II-Induced Proliferation and Migration in Vascular Smooth Muscle Cells and Ameliorates Phosphate-Induced Vascular Smooth Muscle Cells Calcification
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    Diabetes & Metabolism Journal.2024; 48(1): 83.     CrossRef
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    Wen-Ling Lee, Peng-Hui Wang, Szu-Ting Yang, Chia-Hao Liu, Wen-Hsun Chang, Fa-Kung Lee
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Original Articles
Diabetes, Obesity and Metabolism
Big Data Articles (National Health Insurance Service Database)
Improvement in Age at Mortality and Changes in Causes of Death in the Population with Diabetes: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
Eugene Han, Sun Ok Song, Hye Soon Kim, Kang Ju Son, Sun Ha Jee, Bong-Soo Cha, Byung-Wan Lee
Endocrinol Metab. 2022;37(3):466-474.   Published online June 29, 2022
DOI: https://doi.org/10.3803/EnM.2022.1440
  • 4,151 View
  • 141 Download
  • 4 Web of Science
  • 4 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Diabetes is a leading cause of death that is responsible for 1.6 million annual deaths worldwide. However, the life expectancy and age at death of people with diabetes have been a matter of debate.
Methods
The National Health Insurance Service claims database, merged with death records from the National Statistical Information Service in Korea from 2006 to 2018, was analyzed.
Results
In total, 1,432,567 deaths were collected. The overall age at death increased by 0.44 and 0.26 year/year in the diabetes and control populations, respectively. The disparity in the mean age at death between the diabetes and control populations narrowed from 5.2 years in 2006 to 3.0 years in 2018 (p<0.001). In a subgroup analysis according to the presence of comorbid diseases, the number and proportion of deaths remained steady in the group with diabetes only, but steadily increased in the groups with diabetes combined with dyslipidemia and/or hypertension. Compared to the control population, the increase in the mean death age was higher in the population with diabetes. This trend was more prominent in the groups with dyslipidemia and/or hypertension than in the diabetes only group. Deaths from vascular disease and diabetes decreased, whereas deaths from cancer and pneumonia increased. The decline in the proportion of deaths from vascular disease was greater in the diabetes groups with hypertension and/or dyslipidemia than in the control population.
Conclusion
The age at death in the population with diabetes increased more steeply and reached a comparable level to those without diabetes.

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  • Analysis of Cause-of-Death Mortality in Children and Young Adults with Diabetes: A Nationwide 10-Year Follow-Up Cohort Study
    Iee-Ho Choi, Sang-Woo Yeom, Sun-Young Kim, Jihye You, Jong-Seung Kim, Minsun Kim
    Children.2023; 10(2): 358.     CrossRef
  • Age at Mortality in Patients with Type 2 Diabetes Who Underwent Kidney Transplantation: An Analysis of Data from the Korean National Health Insurance and Statistical Information Service, 2006 to 2018
    Sun Ok Song, Eugene Han, Kang Ju Son, Bong-Soo Cha, Byung-Wan Lee
    Journal of Clinical Medicine.2023; 12(9): 3160.     CrossRef
  • Risk of Cause-Specific Mortality across Glucose Spectrum in Elderly People: A Nationwide Population-Based Cohort Study
    Joonyub Lee, Hun-Sung Kim, Kee-Ho Song, Soon Jib Yoo, Kyungdo Han, Seung-Hwan Lee
    Endocrinology and Metabolism.2023; 38(5): 525.     CrossRef
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    Han-Sang Baek, Bongseong Kim, Seung-Hwan Lee, Dong-Jun Lim, Hyuk-Sang Kwon, Sang-Ah Chang, Kyungdo Han, Jae-Seung Yun
    Endocrinology and Metabolism.2023; 38(6): 770.     CrossRef
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Diabetes, Obesity and Metabolism
Comparative Study of Ex Vivo Antiplatelet Activity of Aspirin and Cilostazol in Patients with Diabetes and High Risk of Cardiovascular Disease
Sangmo Hong, Woo Je Lee, Cheol-Young Park
Endocrinol Metab. 2022;37(2):233-242.   Published online April 6, 2022
DOI: https://doi.org/10.3803/EnM.2021.1353
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The role of aspirin in primary cardiovascular disease prevention in patients with diabetes remains controversial. However, some studies have suggested beneficial effects of cilostazol on cardiovascular disease in patients with diabetes. We prospectively investigated the antiplatelet effects of cilostazol compared with aspirin in patients with diabetes and cardiovascular risk factors.
Methods
We randomly assigned 116 patients with type 2 diabetes and cardiovascular risk factors but no evident cardiovascular disease to receive aspirin at a dose of 100 mg or cilostazol at a dose of 200 mg daily for 14 days. The primary efficacy outcome was antiplatelet effects of aspirin and cilostazol assessed with the VerifyNow system (aspirin response units [ARU]) and PFA-100 (closure time [CT]). Secondary outcomes were changes of clinical laboratory data (ClinicalTrials.gov Identifier: NCT02933788).
Results
After 14 days, there was greater decrease in ARU in aspirin (–28.9%±9.9%) compared cilostazol (–0.4%±7.1%, P<0.001) and was greater increase in CT in aspirin (99.6%±63.5%) compared cilostazol (25.7%±54.1%, P<0.001). The prevalence of aspirin resistance was 7.5% according to VerifyNow (defined by ARU ≥550) and 18.9% according to PFA-100 (CT <192 seconds). Compared with aspirin, cilostazol treatment was associated with increased high density lipoprotein cholesterol (7.1%±12.7% vs. 4.2%±18.0%, P=0.006) and decreased triglycerides (–9.4%±33.7% vs. 4.4%±17.57%, P=0.016). However, there were no significant changes in total and low density lipoprotein cholesterol, C-reactive protein level, and cluster of differentiation 40 ligand between cilostazol and aspirin groups.
Conclusion
Aspirin showed better antiplatelet effects assessed with VerifyNow and PFA-100 compared with cilostazol. However, there were favorable changes in atherogenic dyslipidemia only in the cilostazol.
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Namgok Lecture 2021
Diabetes, Obesity and Metabolism
The Influence of Obesity and Metabolic Health on Vascular Health
Eun-Jung Rhee
Endocrinol Metab. 2022;37(1):1-8.   Published online February 28, 2022
DOI: https://doi.org/10.3803/EnM.2022.101
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  • 312 Download
  • 16 Web of Science
  • 21 Crossref
AbstractAbstract PDFPubReader   ePub   
The prevalence of obesity is rapidly increasing worldwide. Obesity should not be understood only as the accumulation of fat in the body, but instead as a phenomenon that exerts different effects on our health according to the place of fat deposition and its stability. Obesity is the starting point of most metabolic diseases, such as diabetes, hypertension, metabolic syndrome, sleep apnea, and eventually cardiovascular disease. There are different kinds of obesity, ranging from simple obesity to sarcopenic obesity. The main purpose of intervening to address obesity is to decrease the ultimate consequence of obesity—namely, cardiovascular disease. The main mechanism through which obesity, especially abdominal obesity, increases cardiovascular risk is the obesity-induced derangement of metabolic health, leading to the development of metabolic diseases such as diabetes, non-alcoholic fatty liver disease, and metabolic syndrome, which are the main initiators of vascular damage. In this review, I discuss the influence of various types of obesity on the risk of metabolic diseases, and how these diseases increase cardiovascular disease risk.

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Original Article
Diabetes, Obesity and Metabolism
Big Data Articles (National Health Insurance Service Database)
Frequency of Exposure to Impaired Fasting Glucose and Risk of Mortality and Cardiovascular Outcomes
Seung-Hwan Lee, Kyungdo Han, Hyuk-Sang Kwon, Mee Kyoung Kim
Endocrinol Metab. 2021;36(5):1007-1015.   Published online October 21, 2021
DOI: https://doi.org/10.3803/EnM.2021.1218
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  • 128 Download
  • 12 Web of Science
  • 13 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Metabolic abnormalities, such as impaired fasting glucose (IFG), are dynamic phenomena; however, it is unclear whether the timing of IFG exposure and cumulative exposure to IFG are related to cardiovascular disease (CVD) and mortality risk.
Methods
Data were extracted from a nationwide population-based cohort in South Korea for adults (n=2,206,679) who were free of diabetes and had 4 years of consecutive health examination data. Fasting blood glucose levels of 100 to 125 mg/dL were defined as IFG, and the number of IFG diagnoses for each adult in the 4-year period was tabulated as the IFG exposure score (range, 0 to 4). Adults with persistent IFG for the 4-year period received a score of 4.
Results
The median follow-up was 8.2 years. There were 24,820 deaths, 13,502 cases of stroke, and 13,057 cases of myocardial infarction (MI). IFG exposure scores of 1, 2, 3, and 4 were associated with all-cause mortality (multivariable-adjusted hazard ratio [aHR], 1.11; 95% confidence interval [CI], 1.08 to 1.15; aHR, 1.16; 95% CI, 1.12 to 1.20; aHR, 1.20; 95% CI, 1.15 to 1.25; aHR, 1.18; 95% CI, 1.11 to 1.25, respectively) compared with an IFG exposure score of 0. Adjusting for hypertension and dyslipidemia attenuated the slightly increased risk of MI or stroke associated with high IFG exposure scores, but significant associations for allcause mortality remained.
Conclusion
The intensity of IFG exposure was associated with an elevated risk of all-cause mortality, independent of cardiovascular risk factors. The association between IFG exposure and CVD risk was largely mediated by the coexistence of dyslipidemia and hypertension.

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    Kyungdo Han, Mee Kyoung Kim
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    Heekyoung Jeong, Kyungdo Han, Soon Jib Yoo, Mee Kyoung Kim
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Endocrinol Metab : Endocrinology and Metabolism