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Original Articles
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
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  • 100 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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  • 158 Download
  • 2 Web of Science
  • 4 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
  • 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
  • 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
  • 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.2023;[Epub]     CrossRef
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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
  • 6,060 View
  • 291 Download
  • 13 Web of Science
  • 17 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.

Citations

Citations to this article as recorded by  
  • Associations of omega-3 fatty acids vs. fenofibrate with adverse cardiovascular outcomes in people with metabolic syndrome: propensity matched cohort study
    Nam Hoon Kim, Ji Yoon Kim, Jimi Choi, Sin Gon Kim
    European Heart Journal - Cardiovascular Pharmacotherapy.2024; 10(2): 118.     CrossRef
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  • Anti-obesity effects of fucoidan from Sargassum thunbergii in adipocytes and high fat diet induced obese mice through inhibiting adipogenic specific transcription factor
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    Food Science and Human Wellness.2024; 13(3): 1608.     CrossRef
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    Sunmin Park
    Nutrients.2024; 16(4): 534.     CrossRef
  • Ancistrocladus tectorius Extract Inhibits Obesity by Promoting Thermogenesis and Mitochondrial Dynamics in High-Fat Diet-Fed Mice
    Minju Kim, Jin Hyub Paik, Hwa Lee, Min Ji Kim, Sang Mi Eum, Soo Yong Kim, Sangho Choi, Ho-Yong Park, Hye Gwang Jeong, Tae-Sook Jeong
    International Journal of Molecular Sciences.2024; 25(7): 3743.     CrossRef
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    Dragan Milenkovic, Tatjana Ruskovska
    Molecular Aspects of Medicine.2023; 89: 101101.     CrossRef
  • Pharmacological Support for the Treatment of Obesity—Present and Future
    Marcin Kosmalski, Kacper Deska, Bartłomiej Bąk, Monika Różycka-Kosmalska, Tadeusz Pietras
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    Donna H. Ryan, John E. Deanfield, Stephan Jacob
    Cardiovascular Endocrinology & Metabolism.2023; 12(1): e0279.     CrossRef
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    Seunghyun Lee, Kyoungmyoung Ko, Sungjae Shin, Hye Sun Park, Namki Hong, Yumie Rhee
    Archives of Osteoporosis.2023;[Epub]     CrossRef
  • Design, synthesis and evaluation of 2-pyrimidinylindole derivatives as anti-obesity agents by regulating lipid metabolism
    Shi-Yao Guo, Li-Yuan Wei, Bing-Bing Song, Yu-Tao Hu, Zhi Jiang, Dan-Dan Zhao, Yao-Hao Xu, Yu-Wei Lin, Shu-Min Xu, Shuo-Bin Chen, Zhi-Shu Huang
    European Journal of Medicinal Chemistry.2023; 260: 115729.     CrossRef
  • Short-Term L-Citrulline Supplementation Does Not Affect Blood Pressure, Pulse Wave Reflection, or Arterial Stiffness at Rest and during Isometric Exercise in Older Males
    Andrea Tryfonos, Filippos Christodoulou, George M. Pamboris, Stephanos Christodoulides, Anastasios A. Theodorou
    Sports.2023; 11(9): 177.     CrossRef
  • Skinfold Thickness as a Cardiometabolic Risk Predictor in Sedentary and Active Adult Populations
    Sughey González-Torres, Luis Miguel Anaya-Esparza, Gabriel Fermín Trigueros del Valle, Edgar Alfonso Rivera-León, Zuamí Villagrán, Sergio Sánchez-Enríquez
    Journal of Personalized Medicine.2023; 13(9): 1326.     CrossRef
  • Impact of COVID-19 Lockdown on Non-Alcoholic Fatty Liver Disease and Insulin Resistance in Adults: A before and after Pandemic Lockdown Longitudinal Study
    Ángel Arturo López-González, Bárbara Altisench Jané, Luis Masmiquel Comas, Sebastiana Arroyo Bote, Hilda María González San Miguel, José Ignacio Ramírez Manent
    Nutrients.2022; 14(14): 2795.     CrossRef
  • Fenofibrate enhances lipid deposition via modulating PPARγ, SREBP-1c, and gut microbiota in ob/ob mice fed a high-fat diet
    Ying Zhang, Xiu-Bin Jia, Yun-Chao Liu, Wen-Qian Yu, Yan-Hong Si, Shou-Dong Guo
    Frontiers in Nutrition.2022;[Epub]     CrossRef
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    Lizheng Guan, Tiantian Li, Xuan Wang, Kang Yu, Rong Xiao, Yuandi Xi
    Nutrients.2022; 14(19): 3911.     CrossRef
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    Profilakticheskaya meditsina.2022; 25(9): 39.     CrossRef
  • Assessment of Vitamin D Levels in Relation to Statin Therapy in Elderly Hypertensive Patients with Comorbidities
    Kinga-Ilona Nyulas, Zsuzsánna Simon-Szabó, Zoltán Preg, Sándor Pál, Arundhati Sharma, Tünde Pál, Márta Germán-Salló, Enikő Nemes-Nagy
    Journal of Interdisciplinary Medicine.2022; 7(4): 88.     CrossRef
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Original Articles
Diabetes, Obesity and Metabolism
The Effects of PPAR Agonists on Atherosclerosis and Nonalcoholic Fatty Liver Disease in ApoE−/−FXR−/− Mice
Yenna Lee, Bo-Rahm Kim, Geun-Hyung Kang, Gwan Jae Lee, Young Joo Park, Haeryoung Kim, Hak Chul Jang, Sung Hee Choi
Endocrinol Metab. 2021;36(6):1243-1253.   Published online December 28, 2021
DOI: https://doi.org/10.3803/EnM.2021.1100
  • 5,454 View
  • 155 Download
  • 11 Web of Science
  • 11 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Farnesoid X receptor (FXR), a bile acid–activated nuclear receptor, is a potent regulator of glucose and lipid metabolism as well as of bile acid metabolism. Previous studies have demonstrated that FXR deficiency is associated with metabolic derangements, including atherosclerosis and nonalcoholic fatty liver disease (NAFLD), but its mechanism remains unclear. In this study, we investigated the role of FXR in atherosclerosis and NAFLD and the effect of peroxisome proliferator-activated receptor (PPAR) agonists in mouse models with FXR deficiency.
Methods
En face lipid accumulation analysis, liver histology, serum levels of glucose and lipids, and mRNA expression of genes related to lipid metabolism were compared between apolipoprotein E (ApoE)−/− and ApoE−/−FXR−/− mice. The effects of PPARα and PPARγ agonists were also compared in both groups of mice.
Results
Compared with ApoE−/− mice, ApoE−/−FXR−/− mice showed more severe atherosclerosis, hepatic steatosis, and higher levels of serum cholesterol, low-density lipoprotein cholesterol, and triglycerides, accompanied by increased mRNA expression of FAS, ApoC2, TNFα, IL-6 (liver), ATGL, TGH, HSL, and MGL (adipocytes), and decreased mRNA expressions of CPT2 (liver) and Tfam (skeletal muscle). Treatment with a PPARα agonist, but not with a PPARγ agonist, partly reversed atherosclerosis and hepatic steatosis, and decreased plasma triglyceride levels in the ApoE−/−FXR−/− mice, in association with increased mRNA expression of CD36 and FATP and decreased expression of ApoC2 and ApoC3 (liver).
Conclusion
Loss of FXR is associated with aggravation of atherosclerosis and hepatic steatosis in ApoE-deficient mice, which could be reversed by a PPARα agonist through induction of fatty acid uptake, β-oxidation, and triglyceride hydrolysis.

Citations

Citations to this article as recorded by  
  • Evaluation of the hepatotoxicity of Psoralea corylifolia L. based on a zebrafish model
    Shu-Yan Gao, Jing-Cheng Zhao, Qing Xia, Chen Sun, Maimaiti Aili, Ainiwaer Talifu, Shi-Xia Huo, Yun Zhang, Zhi-Jian Li
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
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    Min Yao, Ping Zhou, Yan-Yan Qin, Li Wang, Deng-Fu Yao
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Close layer
Endocrine Research
Effects of Glucagon-Like Peptide-1 Analogue and Fibroblast Growth Factor 21 Combination on the Atherosclerosis-Related Process in a Type 2 Diabetes Mouse Model
Jin Hee Kim, Gha Young Lee, Hyo Jin Maeng, Hoyoun Kim, Jae Hyun Bae, Kyoung Min Kim, Soo Lim
Endocrinol Metab. 2021;36(1):157-170.   Published online February 24, 2021
DOI: https://doi.org/10.3803/EnM.2020.781
  • 6,675 View
  • 173 Download
  • 10 Web of Science
  • 10 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Glucagon-like peptide-1 (GLP-1) analogues regulate glucose homeostasis and have anti-inflammatory properties, but cause gastrointestinal side effects. The fibroblast growth factor 21 (FGF21) is a hormonal regulator of lipid and glucose metabolism that has poor pharmacokinetic properties, including a short half-life. To overcome these limitations, we investigated the effect of a low-dose combination of a GLP-1 analogue and FGF21 on atherosclerosis-related molecular pathways.
Methods
C57BL/6J mice were fed a high-fat diet for 30 weeks followed by an atherogenic diet for 10 weeks and were divided into four groups: control (saline), liraglutide (0.3 mg/kg/day), FGF21 (5 mg/kg/day), and low-dose combination treatment with liraglutide (0.1 mg/kg/day) and FGF21 (2.5 mg/kg/day) (n=6/group) for 6 weeks. The effects of each treatment on various atherogenesisrelated pathways were assessed.
Results
Liraglutide, FGF21, and their low-dose combination significantly reduced atheromatous plaque in aorta, decreased weight, glucose, and leptin levels, and increased adiponectin levels. The combination treatment upregulated the hepatic uncoupling protein-1 (UCP1) and Akt1 mRNAs compared with controls. Matric mentalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were downregulated and phosphorylated Akt (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) were upregulated in liver of the liraglutide-alone and combination-treatment groups. The combination therapy also significantly decreased the proliferation of vascular smooth muscle cells. Caspase-3 was increased, whereas MMP-9, ICAM-1, p-Akt, and p-ERK1/2 were downregulated in the liraglutide-alone and combination-treatment groups.
Conclusion
Administration of a low-dose GLP-1 analogue and FGF21 combination exerts beneficial effects on critical pathways related to atherosclerosis, suggesting the synergism of the two compounds.

Citations

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    Maria Paula Carbonetti, Fernanda Almeida-Oliveira, David Majerowicz
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    Jang Won Son
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Close layer
Review Article
Diabetes
Recent Updates on Vascular Complications in Patients with Type 2 Diabetes Mellitus
Chan-Hee Jung, Ji-Oh Mok
Endocrinol Metab. 2020;35(2):260-271.   Published online June 24, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.2.260
  • 7,346 View
  • 281 Download
  • 13 Web of Science
  • 11 Crossref
AbstractAbstract PDFPubReader   ePub   
It is well known that patients with type 2 diabetes mellitus (T2DM) are at an increased risk of morbidity and mortality from atherosclerotic cardiovascular (CV) complications. Previously, the concept that diabetes mellitus (DM) is a “coronary artery disease (CAD) risk equivalent” was widely accepted, implying that all DM patients should receive intensive management. However, considerable evidence exist for wide heterogeneity in the risk of CV events among T2DM patients and the concept of a “CAD risk equivalent” has changed. Recent guidelines recommend further CV risk stratification in T2DM patients, with treatment tailored to the risk level. Although imaging modalities for atherosclerotic cardiovascular disease (ASCVD) have been used to improve risk prediction, there is currently no evidence that imaging-oriented therapy improves clinical outcomes. Therefore, controversy remains whether we should screen for CVD in asymptomatic T2DM. The coexistence of T2DM and heart failure (HF) is common. Based on recent CV outcome trials, sodium glucose cotransporter-2 inhibitors and glucagon like peptide-1 receptor agonists are recommended who have established ASCVD, indicators of high risk, or HF because of their demonstrated benefits for CVD. These circumstances have led to an increasing emphasis on ASCVD and HF in T2DM patients. In this review, we examine the literature published within the last 5 years on the risk assessment of CVD in asymptomatic T2DM patients. In particular, we review recent guidelines regarding screening for CVD and research focusing on the role of coronary artery calcium, coronary computed tomography angiography, and carotid intima-media thickness in asymptomatic T2DM patients.

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  • 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
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Original Article
Clinical Study
Associations of Perirenal Fat Thickness with Renal and Systemic Calcified Atherosclerosis
Bo Kyung Koo, Julie O. Denenberg, C. Michael Wright, Michael H. Criqui, Matthew A. Allison
Endocrinol Metab. 2020;35(1):122-131.   Published online March 19, 2020
DOI: https://doi.org/10.3803/EnM.2020.35.1.122
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background

We investigated associations between perirenal fat thickness and atherosclerotic calcification in six different vascular beds.

Methods

Using a community-based cohort (n=3,919), perirenal fat thickness was estimated from computed tomography scans. It was classified as Q1 (the lowest quartile) to Q4 (the highest quartile) in each sex. Calcification in the carotid arteries, coronary arteries, thoracic aorta, abdominal aorta, iliac arteries, and renal arteries was evaluated.

Results

Perirenal fat thickness was associated with older age (P<0.01) and a higher prevalence of obesity, hypertension, and dyslipidemia (P<0.01 for all). Perirenal fat thickness was independently associated with renal arterial calcification even after adjustment for age, sex, body mass index, hypertension, dyslipidemia, smoking history, and family history of heart diseases in first-degree relatives (odds ratio [OR] per quartile of perirenal fat thickness, 1.25; 95% confidence interval [CI], 1.09 to 1.44). Compared to Q1, the odds of renal arterial calcification in Q4 was about two times higher (OR, 2.05; 95% CI, 1.29 to 3.25). After adjustment for renal arterial calcification and atherosclerotic risk factors, the only other vascular bed where perirenal fat thickness showed a significant association with calcification was the abdominal aorta (OR, 1.11; 95% CI, 1.00 to 1.23; P=0.045).

Conclusion

Perirenal fat thickness was independently associated with vascular calcification in the renal artery and abdominal aorta.

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Review Articles
Fibroblast Growth Factor 21 Mimetics for Treating Atherosclerosis
Kelvin H. M. Kwok, Karen S. L. Lam
Endocrinol Metab. 2017;32(2):145-151.   Published online May 19, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.2.145
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AbstractAbstract PDFPubReader   ePub   

Fibroblast growth factor 21 (FGF21) is an atypical member of the FGF family. Acting in an endocrine fashion, it increases glucose uptake, modulates lipid metabolism, and sensitizes insulin response in metabolically active organs, including the liver and adipose tissue. Emerging evidence shows a strong correlation between circulating FGF21 levels and the incidence and severity of atherosclerosis. Animal studies have demonstrated a beneficial role of FGF21 in protecting against aberrant lipid profile, while recent development in FGF21 mimetics has provided further insight into the lipid-lowering effects of FGF21 signaling. The present review summarizes the physiological roles of FGF21, and discusses major breakthroughs and limitations of FGF21 mimetic-based therapeutic strategies for treating atherosclerosis.

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The Implication of Coronary Artery Calcium Testing for Cardiovascular Disease Prevention and Diabetes
Ron Blankstein, Ankur Gupta, Jamal S. Rana, Khurram Nasir
Endocrinol Metab. 2017;32(1):47-57.   Published online March 20, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.47
  • 4,721 View
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AbstractAbstract PDFPubReader   

Over the last two decades coronary artery calcium (CAC) scanning has emerged as a quick, safe, and inexpensive method to detect the presence of coronary atherosclerosis. Data from multiple studies has shown that compared to individuals who do not have any coronary calcifications, those with severe calcifications (i.e., CAC score >300) have a 10-fold increase in their risk of coronary heart disease events and cardiovascular disease. Conversely, those that have a CAC of 0 have a very low event rate (~0.1%/year), with data that now extends to 15 years in some studies. Thus, the most notable implication of identifying CAC in individuals who do not have known cardiovascular disease is that it allows targeting of more aggressive therapies to those who have the highest risk of having future events. Such identification of risk is especially important for individuals who are not on any therapies for coronary heart disease, or when intensification of treatment is being considered but has an uncertain role. This review will highlight some of the recent data on CAC testing, while focusing on the implications of those findings on patient management. The evolving role of CAC in patients with diabetes will also be highlighted.

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The Role of Macrophage Lipophagy in Reverse Cholesterol Transport
Se-Jin Jeong, Mi-Ni Lee, Goo Taeg Oh
Endocrinol Metab. 2017;32(1):41-46.   Published online March 20, 2017
DOI: https://doi.org/10.3803/EnM.2017.32.1.41
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  • 72 Download
  • 31 Web of Science
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AbstractAbstract PDFPubReader   

Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

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Obesity and Metabolism
High-Density Lipoprotein, Lecithin: Cholesterol Acyltransferase, and Atherosclerosis
Alice Ossoli, Chiara Pavanello, Laura Calabresi
Endocrinol Metab. 2016;31(2):223-229.   Published online June 10, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.2.223
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AbstractAbstract PDFPubReader   

Epidemiological data clearly show the existence of a strong inverse correlation between plasma high-density lipoprotein cholesterol (HDL-C) concentrations and the incidence of coronary heart disease. This relation is explained by a number of atheroprotective properties of HDL, first of all the ability to promote macrophage cholesterol transport. HDL are highly heterogeneous and are continuously remodeled in plasma thanks to the action of a number of proteins and enzymes. Among them, lecithin:cholesterol acyltransferase (LCAT) plays a crucial role, being the only enzyme able to esterify cholesterol within lipoproteins. LCAT is synthetized by the liver and it has been thought to play a major role in reverse cholesterol transport and in atheroprotection. However, data from animal studies, as well as human studies, have shown contradictory results. Increased LCAT concentrations are associated with increased HDL-C levels but not necessarily with atheroprotection. On the other side, decreased LCAT concentration and activity are associated with decreased HDL-C levels but not with increased atherosclerosis. These contradictory results confirm that HDL-C levels per se do not represent the functionality of the HDL system.

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Namgok Lecture 2015
Obesity and Metabolism
The Impact of Organokines on Insulin Resistance, Inflammation, and Atherosclerosis
Kyung Mook Choi
Endocrinol Metab. 2016;31(1):1-6.   Published online March 16, 2016
DOI: https://doi.org/10.3803/EnM.2016.31.1.1
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AbstractAbstract PDFPubReader   

Immoderate energy intake, a sedentary lifestyle, and aging have contributed to the increased prevalence of obesity, sarcopenia, metabolic syndrome, type 2 diabetes, and cardiovascular disease. There is an urgent need for the development of novel pharmacological interventions that can target excessive fat accumulation and decreased muscle mass and/or strength. Adipokines, bioactive molecules derived from adipose tissue, are involved in the regulation of appetite and satiety, inflammation, energy expenditure, insulin resistance and secretion, glucose and lipid metabolism, and atherosclerosis. Recently, there is emerging evidence that skeletal muscle and the liver also function as endocrine organs that secrete myokines and hepatokines, respectively. Novel discoveries and research into these organokines (adipokines, myokines, and hepatokines) may lead to the development of promising biomarkers and therapeutics for cardiometabolic disease. In this review, I summarize recent data on these organokines and focus on the role of adipokines, myokines, and hepatokines in the regulation of insulin resistance, inflammation, and atherosclerosis.

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Original Article
Clinical Study
Subclinical Atherosclerosis in Patients with Cushing Syndrome: Evaluation with Carotid Intima-Media Thickness and Ankle-Brachial Index
Luigi Petramala, D'Elia Lorenzo, Gino Iannucci, Antonio Concistré, Laura Zinnamosca, Cristiano Marinelli, Giuseppe De Vincentis, Antonio Ciardi, Giorgio De Toma, Claudio Letizia
Endocrinol Metab. 2015;30(4):488-493.   Published online December 31, 2015
DOI: https://doi.org/10.3803/EnM.2015.30.4.488
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AbstractAbstract PDFPubReader   
Background

Cushing syndrome (CS) has been described as a killing disease due its cardiovascular complications. In fact, chronic cortisol excess leads to a constellation of complications, including hypertension, hyperglycemia, adiposity, and thromboembolism. The main vascular alteration associated with CS is atherosclerosis.

Methods

Aim of this study was to analyze carotid intima-media thickness (cIMT) and ankle-brachial index (ABI), two surrogate markers of subclinical atherosclerosis in a consecutive series of CS patients, compared to patients with essential hypertension (EH) and health subjects (HS).

Results

Patients with CS showed a significant increase (P<0.05) of cIMT (0.89±0.17 mm) compared to EH (0.81±0.16 mm) and HS (0.75±0.4 mm), with a high prevalence of plaque (23%; P<0.03). Moreover, CS patients showed a mean ABI values (1.07±0.02) significantly lower respect to HS (1.12±0.11; P<0.05), and a higher percentage (20%) of pathological values of ABI (≤0.9; P<0.03).

Conclusion

In conclusion, we confirmed and extended the data of cIMT in CS, and showed that the ABI represent another surrogate marker of subclinical atherosclerosis in this disease.

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Review Article
Obesity and Metabolism
High Density Lipoprotein: A Therapeutic Target in Type 2 Diabetes
Philip J. Barter
Endocrinol Metab. 2013;28(3):169-177.   Published online September 13, 2013
DOI: https://doi.org/10.3803/EnM.2013.28.3.169
  • 3,638 View
  • 32 Download
  • 25 Crossref
AbstractAbstract PDFPubReader   

High density lipoproteins (HDLs) have a number of properties that have the potential to inhibit the development of atherosclerosis and thus reduce the risk of having a cardiovascular event. These protective effects of HDLs may be reduced in patients with type 2 diabetes, a condition in which the concentration of HDL cholesterol is frequently low. In addition to their potential cardioprotective properties, HDLs also increase the uptake of glucose by skeletal muscle and stimulate the synthesis and secretion of insulin from pancreatic β cells and may thus have a beneficial effect on glycemic control. This raises the possibility that a low HDL concentration in type 2 diabetes may contribute to a worsening of diabetic control. Thus, there is a double case for targeting HDLs in patients with type 2 diabetes: to reduce cardiovascular risk and also to improve glycemic control. Approaches to raising HDL levels include lifestyle factors such as weight reduction, increased physical activity and stopping smoking. There is an ongoing search for HDL-raising drugs as agents to use in patients with type 2 diabetes in whom the HDL level remains low despite lifestyle interventions.

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Original Article
The Association between Low Serum Bilirubin and Carotid Atherosclerosis in Subjects with Type 2 Diabetes.
Byoung Hyun Park, Hye Jung Nho, Chung Gu Cho
Endocrinol Metab. 2012;27(2):126-131.   Published online June 20, 2012
DOI: https://doi.org/10.3803/EnM.2012.27.2.126
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  • 22 Download
  • 3 Crossref
AbstractAbstract PDF
BACKGROUND
Bilirubin prevents oxidative modification of low density lipoprotein, and may protect vessels from atherosclerosis. Several studies showed an inverse relationship between serum bilirubin and coronary artery disease. However, there are some needs to clarify the relationship between serum bilirubin and carotid atherosclerosis in type 2 diabetes, especially. METHODS: A total of 346 type 2 diabetic patients, between 35 and 95 years of age (146 men and 200 women), were studied. Subjects with normal serum total bilirubin were divided into two groups, according to their serum total bilirubin levels (group I, total bilirubin > or = 1.0 mg/dL [n = 59]; group II, total bilirubin < or = 0.5 mg/dL [n = 76]). Carotid intima-media thickness (IMT) and plaque scores were measured by ultrasonography. Carotid atherosclerosis was defined by the presence of plaque or more than 1 mm of common carotid IMT. RESULTS: Carotid IMT was positively correlated with age, duration of diabetes and hypertension, high sensitive C-reactive protein (hs-CRP) and fibrinogen, but, it was negatively correlated with bilirubin, gamma glutaryltransferase, albumin, hemoglobin, cystatin C and estimated-glomerular filtration rate (GFR) in all subjects. After controlling for sex, age and levels of hemoglobin, direct bilirubin only was negatively correlated with carotid IMT (r = -0.151, P = 0.034). Low serum total bilirubin group had a lot of female, long duration of diabetes and hypertension, higher hs-CRP, platelet counts, serum creatinine, HbA1c and homeostasis model assessment-insulin resistance, lower albumin, hemoglobin, estimated-GFR and quantitative insulin sensitivity check index. Carotid IMT and plaque scores were significantly greater in low serum bilirubin group (0.785 +/- 0.210 mm vs. 0.678 +/- 0.146 mm, P < 0.01; 1.95 +/- 2.56 vs. 1.03 +/- 1.40, P < 0.05, respectively) than in the high serum bilirubin group. Multivariate logistic regression analysis showed that age, serum albumin and total bilirubin were independent associated factors for carotid atherosclerosis in type 2 diabetic women. CONCLUSION: Total bilirubin is inversely correlated with carotid atherosclerosis in type 2 diabetic patients, and it is an independent associated factor for carotid atherosclerosis in women.

Citations

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    Ai-Ching Boon, Andrew C. Bulmer, Jeff S. Coombes, Robert G. Fassett
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Endocrinol Metab : Endocrinology and Metabolism