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Original Article
Cardiovascular risk/Epidemiology
Risk of Cardiovascular Disease according to Baseline Low-Density Lipoprotein Cholesterol Level in Different Age Groups in Korean Diabetes Population: A Cohort Study
Tae Kyung Yoo, Kyung-Do Han, Eun-Jung Rhee, Won-Young Lee
Diabetes Metab J. 2024;48(2):265-278.   Published online February 26, 2024
DOI: https://doi.org/10.4093/dmj.2022.0443
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
The association between low-density lipoprotein (LDL-C) levels and cardiovascular disease (CVD) risk in different age groups within the diabetes mellitus (DM) population remains unclear. The cohort study was conducted to investigate this relationship.
Methods
We assessed the 2009 to 2012 Korean National Health Screening and National Health Insurance Service records, with follow-up to the primary outcome (myocardial infarction [MI] or stroke) or December 2018. After excluding the participants with a history of MI or stroke, 2,227,394 participants with DM were included and categorized according to baseline LDL-C levels and age. Cox proportional hazards modeling was conducted. The CVD risk of age <40 years and LDL-C <70 mg/dL was set as the reference. In each age group, LDL-C <70 mg/dL was used as a reference for the subgroup analysis.
Results
The cut-off LDL-C value for increased MI risk in each age group varied (<40 years old, LDL-C ≥160 mg/dL: hazard ratios [HR], 2.03; 95% confidence interval [CI], 1.644 to 2.506) (40–49-year-old, LDL-C <115 mg/dL: HR, 1.245; 95% CI, 1.04 to 1.489) (50–59-year-old, LDL-C <115 mg/dL: HR, 1.21; 95% CI, 1.014 to 1.445) (60-69-year-old, LDL-C <145 mg/dL: HR, 1.229; 95% CI, 1.022 to 1.479) (≥70 years old group, LDL-C <100 mg/dL: HR, 1.238; 95% CI, 1.018 to 1.504). The cut-off LDL-C values for increased stroke risk varied in each age subgroup (<40 years old, LDL-C ≥160 mg/dL: HR, 1.395; 95% CI, 1.094 to 1.779) (40–49-year-old, LDL-C <145 mg/dL: HR, 1.13; 95% CI, 1.019 to 1.253) (50–59-year-old, LDL-C <160 mg/dL: HR, 1.079; 95% CI, 1.008 to 1.154) (60–69-year-old, LDL-C <130 mg/dL: HR, 1.07; 95% CI, 1.022 to 1.119) (≥70 years old, LDL-C <115 mg/dL: HR, 1.064; 95% CI, 1.019 to 1.112).
Conclusion
The effect of LDL-C on the risk of CVD differs depending on the age of the population with DM.
Review
Basic Research
Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
Byung Soo Kong, Changhan Lee, Young Min Cho
Diabetes Metab J. 2023;47(3):315-324.   Published online February 24, 2023
DOI: https://doi.org/10.4093/dmj.2022.0333
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  • 3 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Mitochondria are complex metabolic organelles with manifold pathophysiological implications in diabetes. Currently published mitochondrial-encoded peptides, which are expressed from the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c), 16S rRNA (humanin and short humanin like peptide 1-6 [SHLP1-6]), or small human mitochondrial open reading frame over serine tRNA (SHMOOSE) are associated with regulation of cellular metabolism and insulin action in age-related diseases, such as type 2 diabetes mellitus. This review focuses mainly on recent advances in MOTS-c research with regards to diabetes, including both type 1 and type 2. The emerging understanding of MOTS-c in diabetes may provide insight into the development of new therapies for diabetes and other age or senescence-related diseases.

Citations

Citations to this article as recorded by  
  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Mitochondrial Stress and Mitokines: Therapeutic Perspectives for the Treatment of Metabolic Diseases
    Benyuan Zhang, Joon Young Chang, Min Hee Lee, Sang-Hyeon Ju, Hyon-Seung Yi, Minho Shong
    Diabetes & Metabolism Journal.2024; 48(1): 1.     CrossRef
  • Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes
    Alejandra María Rivera Nieves, Brian Michael Wauford, Accalia Fu
    Frontiers in Molecular Biosciences.2024;[Epub]     CrossRef
Sulwon Lecture 2021
Basic Research
Exercise, Mitohormesis, and Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c)
Tae Kwan Yoon, Chan Hee Lee, Obin Kwon, Min-Seon Kim
Diabetes Metab J. 2022;46(3):402-413.   Published online May 25, 2022
DOI: https://doi.org/10.4093/dmj.2022.0092
  • 5,267 View
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  • 8 Web of Science
  • 9 Crossref
AbstractAbstract PDFPubReader   ePub   
Low levels of mitochondrial stress are beneficial for organismal health and survival through a process known as mitohormesis. Mitohormetic responses occur during or after exercise and may mediate some salutary effects of exercise on metabolism. Exercise-related mitohormesis involves reactive oxygen species production, mitochondrial unfolded protein response (UPRmt), and release of mitochondria-derived peptides (MDPs). MDPs are a group of small peptides encoded by mitochondrial DNA with beneficial metabolic effects. Among MDPs, mitochondrial ORF of the 12S rRNA type-c (MOTS-c) is the most associated with exercise. MOTS-c expression levels increase in skeletal muscles, systemic circulation, and the hypothalamus upon exercise. Systemic MOTS-c administration increases exercise performance by boosting skeletal muscle stress responses and by enhancing metabolic adaptation to exercise. Exogenous MOTS-c also stimulates thermogenesis in subcutaneous white adipose tissues, thereby enhancing energy expenditure and contributing to the anti-obesity effects of exercise training. This review briefly summarizes the mitohormetic mechanisms of exercise with an emphasis on MOTS-c.

Citations

Citations to this article as recorded by  
  • Mitochondrial-derived peptides: Antidiabetic functions and evolutionary perspectives
    Satadeepa Kal, Sumana Mahata, Suborno Jati, Sushil K. Mahata
    Peptides.2024; 172: 171147.     CrossRef
  • Beneficial Effects of Low-Grade Mitochondrial Stress on Metabolic Diseases and Aging
    Se Hee Min, Gil Myoung Kang, Jae Woo Park, Min-Seon Kim
    Yonsei Medical Journal.2024; 65(2): 55.     CrossRef
  • Roles of Myokines and Muscle-Derived Extracellular Vesicles in Musculoskeletal Deterioration under Disuse Conditions
    Jie Zhang, Yunfang Gao, Jiangwei Yan
    Metabolites.2024; 14(2): 88.     CrossRef
  • Antifragility and antiinflammaging: Can they play a role for a healthy longevity?
    Fabiola Olivieri, Francesco Prattichizzo, Fabrizia Lattanzio, Anna Rita Bonfigli, Liana Spazzafumo
    Ageing Research Reviews.2023; 84: 101836.     CrossRef
  • MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation
    Yuejun Zheng, Zilin Wei, Tianhui Wang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • MOTS-c: A potential anti-pulmonary fibrosis factor derived by mitochondria
    Zewei Zhang, Dongmei Chen, Kaili Du, Yaping Huang, Xingzhe Li, Quwen Li, Xiaoting Lv
    Mitochondrion.2023; 71: 76.     CrossRef
  • Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases
    Byung Soo Kong, Changhan Lee, Young Min Cho
    Diabetes & Metabolism Journal.2023; 47(3): 315.     CrossRef
  • MOTS-c Serum Concentration Positively Correlates with Lower-Body Muscle Strength and Is Not Related to Maximal Oxygen Uptake—A Preliminary Study
    Remigiusz Domin, Michał Pytka, Mikołaj Żołyński, Jan Niziński, Marcin Rucinski, Przemysław Guzik, Jacek Zieliński, Marek Ruchała
    International Journal of Molecular Sciences.2023; 24(19): 14951.     CrossRef
  • Unique Properties of Apicomplexan Mitochondria
    Ian M. Lamb, Ijeoma C. Okoye, Michael W. Mather, Akhil B. Vaidya
    Annual Review of Microbiology.2023; 77(1): 541.     CrossRef
Original Articles
Complications
Fatty Acid-Binding Protein 4 in Patients with and without Diabetic Retinopathy
Ping Huang, Xiaoqin Zhao, Yi Sun, Xinlei Wang, Rong Ouyang, Yanqiu Jiang, Xiaoquan Zhang, Renyue Hu, Zhuqi Tang, Yunjuan Gu
Diabetes Metab J. 2022;46(4):640-649.   Published online April 28, 2022
DOI: https://doi.org/10.4093/dmj.2021.0195
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  • 2 Web of Science
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AbstractAbstract PDFPubReader   ePub   
Background
Fatty acid-binding protein 4 (FABP4) has been demonstrated to be a predictor of early diabetic nephropathy. However, little is known about the relationship between FABP4 and diabetic retinopathy (DR). This study explored the value of FABP4 as a biomarker of DR in patients with type 2 diabetes mellitus (T2DM).
Methods
A total of 238 subjects were enrolled, including 20 healthy controls and 218 T2DM patients. Serum FABP4 levels were measured using a sandwich enzyme-linked immunosorbent assay. The grade of DR was determined using fundus fluorescence angiography. Based on the international classification of DR, all T2DM patients were classified into the following three subgroups: non-DR group, non-proliferative diabetic retinopathy (NPDR) group, and proliferative diabetic retinopathy (PDR) group. Multivariate logistic regression analyses were employed to assess the correlation between FABP4 levels and DR severity.
Results
FABP4 correlated positively with DR severity (r=0.225, P=0.001). Receiver operating characteristic curve analysis was used to assess the diagnostic potential of FABP4 in identifying DR, with an area under the curve of 0.624 (37% sensitivity, 83.6% specificity) and an optimum cut-off value of 76.4 μg/L. Multivariate logistic regression model including FABP4 as a categorized binary variable using the cut-off value of 76.4 μg/L showed that the concentration of FABP4 above the cut-off value increased the risk of NPDR (odds ratio [OR], 3.231; 95% confidence interval [CI], 1.574 to 6.632; P=0.001) and PDR (OR, 3.689; 95% CI, 1.306 to 10.424; P=0.014).
Conclusion
FABP4 may be used as a serum biomarker for the diagnosis of DR.

Citations

Citations to this article as recorded by  
  • Circulating AFABP, FGF21, and PEDF Levels as Prognostic Biomarkers of Sight-threatening Diabetic Retinopathy
    Chi-Ho Lee, David Tak-Wai Lui, Chloe Yu-Yan Cheung, Carol Ho-Yi Fong, Michele Mae-Ann Yuen, Yu-Cho Woo, Wing-Sun Chow, Ian Yat-Hin Wong, Aimin Xu, Karen Siu-Ling Lam
    The Journal of Clinical Endocrinology & Metabolism.2023; 108(9): e799.     CrossRef
  • A Prediction Model for Sight-Threatening Diabetic Retinopathy Based on Plasma Adipokines among Patients with Mild Diabetic Retinopathy
    Yaxin An, Bin Cao, Kun Li, Yongsong Xu, Wenying Zhao, Dong Zhao, Jing Ke, Takayuki Masaki
    Journal of Diabetes Research.2023; 2023: 1.     CrossRef
Cardiovascular Risk/Epidemiology
Myocardial Infarction, Stroke, and All-Cause Mortality according to Low-Density Lipoprotein Cholesterol Level in the Elderly, a Nationwide Study
You-Bin Lee, Minji Koo, Eunjin Noh, Soon Young Hwang, Jung A Kim, Eun Roh, So-hyeon Hong, Kyung Mook Choi, Sei Hyun Baik, Geum Joon Cho, Hye Jin Yoo
Diabetes Metab J. 2022;46(5):722-732.   Published online March 8, 2022
DOI: https://doi.org/10.4093/dmj.2021.0225
  • 6,873 View
  • 329 Download
  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
We assessed the myocardial infarction (MI), stroke, and all-cause death risks during follow-up according to the low-density lipoprotein cholesterol (LDL-C) levels among older adults.
Methods
The Korean National Health Insurance Service datasets (2002 to 2020) were used for this population-based cohort study. The hazards of MI, stroke, and all-cause mortality during follow-up were analyzed according to LDL-C level in individuals aged ≥65 years without baseline cardiovascular diseases (n=1,391,616).
Results
During a mean 7.55 years, 52,753 MIs developed; 84,224 strokes occurred over a mean 7.47 years. After a mean 8.50 years, 233,963 died. A decrease in LDL-C was associated with lower hazards of MI and stroke. The decreased hazard of stroke in lower LDL-C was more pronounced in statin users, and individuals with diabetes or obesity. The hazard of all-cause death during follow-up showed an inverted J-shaped pattern according to the LDL-C levels. However, the paradoxically increased hazard of mortality during follow-up in lower LDL-C was attenuated in statin users and individuals with diabetes, hypertension, or obesity. In statin users, lower LDL-C was associated with a decreased hazard of mortality during follow-up.
Conclusion
Among the elderly, lower LDL-C was associated with decreased risks of MI and stroke. Lower LDL-C achieved by statins in the elderly was associated with a decreased risk of all-cause death during follow-up, suggesting that LDL-C paradox for the premature death risk in the elderly should not be applied to statin users. Intensive statin therapy should not be hesitated for older adults with cardiovascular risk factors including diabetes.

Citations

Citations to this article as recorded by  
  • Combination of low- or moderate-intensity statin and ezetimibe vs. high-intensity statin monotherapy on primary prevention of cardiovascular disease and all-cause death: a propensity-matched nationwide cohort study
    Ji Eun Jun, In-Kyung Jeong, Kyu Jeong Ahn, Ho Yeon Chung, You-Cheol Hwang
    European Journal of Preventive Cardiology.2024;[Epub]     CrossRef
  • Associations of Low-density Lipoprotein Cholesterol With All-cause and Cause-specific Mortality in Older Adults in China
    Wenqing Ni, Yuebin Lv, Xueli Yuan, Yan Zhang, Hongmin Zhang, Yijing Zheng, Xiaoming Shi, Jian Xu
    The Journal of Clinical Endocrinology & Metabolism.2024;[Epub]     CrossRef
  • The relationship of low-density lipoprotein cholesterol and all-cause or cardiovascular mortality in patients with type 2 diabetes: a retrospective study
    Chin-Huan Chang, Shu-Tin Yeh, Seng-Wei Ooi, Chung-Yi Li, Hua-Fen Chen
    PeerJ.2023; 11: e14609.     CrossRef
  • ERCC1 polymorphism and its expression associated with ischemic stroke in Chinese population
    Xiao-Dong Deng, Jian-Lin Ke, Tai-Yu Chen, Qin Gao, Zhuo-Lin Zhao, Wei Zhang, Huan Liu, Ming-Liang Xiang, Li-Zhen Wang, Ying Ma, Yun Liu
    Frontiers in Neurology.2023;[Epub]     CrossRef
  • New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins
    Kyuho Kim, Henry N. Ginsberg, Sung Hee Choi
    Diabetes & Metabolism Journal.2022; 46(4): 517.     CrossRef
  • 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
    Endocrinology and Metabolism.2022; 37(5): 759.     CrossRef
Cardiovascular Risk/Epidemiology
Mean and Variability of Lipid Measurements and Risk for Development of Subclinical Left Ventricular Diastolic Dysfunction
Jiyun Park, Mira Kang, Jiyeon Ahn, Min Young Kim, Min Sun Choi, You-Bin Lee, Gyuri Kim, Kyu Yeon Hur, Jae Hyeon Kim, Jeong Hoon Yang, Sang-Man Jin
Diabetes Metab J. 2022;46(2):286-296.   Published online November 22, 2021
DOI: https://doi.org/10.4093/dmj.2021.0080
  • 5,587 View
  • 196 Download
  • 1 Web of Science
  • 2 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population.
Methods
This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram.
Results
Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents.
Conclusion
The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

Citations

Citations to this article as recorded by  
  • Separate and Joint Associations of Remnant Cholesterol Accumulation and Variability With Carotid Atherosclerosis: A Prospective Cohort Study
    Jinqi Wang, Rui Jin, Xiaohan Jin, Zhiyuan Wu, Haiping Zhang, Ze Han, Zongkai Xu, Yueruijing Liu, Xiaoyu Zhao, Xiuhua Guo, Lixin Tao
    Journal of the American Heart Association.2023;[Epub]     CrossRef
  • Variability of Metabolic Risk Factors: Causative Factor or Epiphenomenon?
    Hye Jin Yoo
    Diabetes & Metabolism Journal.2022; 46(2): 257.     CrossRef
Obesity and Metabolic Syndrome
Premeal Consumption of a Protein-Enriched, Dietary Fiber-Fortified Bar Decreases Total Energy Intake in Healthy Individuals
Chang Ho Ahn, Jae Hyun Bae, Young Min Cho
Diabetes Metab J. 2019;43(6):879-892.   Published online June 25, 2019
DOI: https://doi.org/10.4093/dmj.2018.0202
  • 4,880 View
  • 84 Download
  • 3 Web of Science
  • 6 Crossref
AbstractAbstract PDFSupplementary MaterialPubReader   
Background

A premeal load of protein can increase satiety and reduce energy intake. Dietary fiber also conveys metabolic benefits by modulating energy intake. We made a protein-enriched, dietary fiber-fortified bar (PFB) and aimed to investigate its effects on food intake and gut hormone secretion in healthy individuals.

Methods

Twenty subjects with normal glucose tolerance were enrolled. On three separate visits, the subjects received, in a randomized order, one of the following: a PFB containing 73 kcal with 10.7 g of protein and 12.7 g of dietary fiber; a usual bar (UB) containing the same calories as the PFB but only 0.9 g of protein and no dietary fiber; or water (control). After 15 minutes, the subjects had ad libitum intake of a test meal. Food consumption, appetite, and plasma gut hormone levels were measured.

Results

Total energy intake, including the bar and the test meal, was significantly reduced with the PFB preload compared to the water (904.4±534.9 kcal vs. 1,075.0±508.0 kcal, P=0.016). With the UB preload, only the intake of the test meal was reduced (P=0.044) but not the total energy intake (P=0.471) than the water. Fullness was also significantly increased after the PFB. In addition, postprandial glucose levels decreased and glucagon-like peptide-1 levels increased with the PFB compared with both the UB and water.

Conclusion

In healthy individuals, a premeal supplementation of PFB reduced total energy intake and decreased postprandial glucose excursion. This finding necessitates long-term studies regarding clinical use in obesity.

Citations

Citations to this article as recorded by  
  • Citrus pectin protects mice from burn injury by modulating intestinal microbiota, GLP-1 secretion and immune response
    Ji-Wei Hao, Hong-Sheng Liu, Ling-Ying Liu, Qing-Hong Zhang
    International Immunopharmacology.2024; 131: 111912.     CrossRef
  • Effect of Two Different Meal Compositions on 1-hour Plasma Ghrelin Levels in Young Men
    Brinnell Annette Caszo, Sangeetha Shyam, Purushotham Krishnappa, Justin Vijay Gnanou
    Malaysian Journal of Medicine and Health Sciences.2023; 19(5): 185.     CrossRef
  • Intake of Fibre-Associated Foods and Texture Preferences in Relation to Weight Status Among 9–12 Years Old Children in 6 European Countries
    Marlies Hörmann-Wallner, Raphaela Krause, Begoña Alfaro, Hannah Jilani, Monica Laureati, Valérie L. Almli, Mari Sandell, Pernilla Sandvik, Gertrude G. Zeinstra, Lisa Methven
    Frontiers in Nutrition.2021;[Epub]     CrossRef
  • Response: Premeal Consumption of a Protein-Enriched, Dietary Fiber-Fortified Bar Decreases Total Energy Intake in Healthy Individuals (Diabetes Metab J 2019;43:879–92)
    Chang Ho Ahn, Jae Hyun Bae, Young Min Cho
    Diabetes & Metabolism Journal.2020; 44(1): 207.     CrossRef
  • Letter: Premeal Consumption of a Protein-Enriched, Dietary Fiber-Fortified Bar Decreases Total Energy Intake in Healthy Individuals (Diabetes Metab J 2019;43:879–92)
    Mi-kyung Kim
    Diabetes & Metabolism Journal.2020; 44(1): 203.     CrossRef
  • Spent coffee (Coffea arabicaL.) grounds promote satiety and attenuate energy intake: A pilot study
    Rocio Campos‐Vega, Andrea Arreguín‐Campos, Miguel A. Cruz‐Medrano, María Dolores Castillo Bilbao
    Journal of Food Biochemistry.2020;[Epub]     CrossRef
Clinical Diabetes & Therapeutics
Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus
You-Cheol Hwang, Ji Eun Jun, In-Kyung Jeong, Kyu Jeung Ahn, Ho Yeon Chung
Diabetes Metab J. 2019;43(5):582-589.   Published online January 16, 2019
DOI: https://doi.org/10.4093/dmj.2018.0124
  • 6,447 View
  • 183 Download
  • 14 Web of Science
  • 12 Crossref
AbstractAbstract PDFPubReader   
Background

The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy.

Methods

This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks.

Results

After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation.

Conclusion

A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Citations

Citations to this article as recorded by  
  • Moderate-Intensity Rosuvastatin/Ezetimibe Combination versus Quadruple-Dose Rosuvastatin Monotherapy: A Meta-Analysis and Systemic Review
    Yura Kang, Jung Mi Park, Sang-Hak Lee
    Yonsei Medical Journal.2024; 65(1): 19.     CrossRef
  • Combination Therapy of Ezetimibe and Rosuvastatin for Dyslipidemia: Current Insights
    Maya R Chilbert, Dylan VanDuyn, Sara Salah, Collin M Clark, Qing Ma
    Drug Design, Development and Therapy.2022; Volume 16: 2177.     CrossRef
  • Ezetimibe and diabetes mellitus:a new strategy for lowering cholesterol
    V.A. Serhiyenko, A.A. Serhiyenko
    INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine).2022; 18(5): 302.     CrossRef
  • The Effect of Rosuvastatin on Plasma/Serum Levels of High-Sensitivity C-Reactive Protein, Interleukin-6, and D-Dimer in People Living with Human Immunodeficiency Virus: A Systematic Review and Meta-Analysis
    Akililu Alemu Ashuro, Yin-Guang Fan, Yuan-Sheng Fu, Dong-Sheng Di, Napoleon Bellua Sam, Hai-Feng Pan, Dong-Qing Ye
    AIDS Research and Human Retroviruses.2021; 37(11): 821.     CrossRef
  • Comparison of the Efficacy and Safety of Rosuvastatin/Ezetimibe Combination Therapy and Rosuvastatin Monotherapy on Lipoprotein in Patients With Type 2 Diabetes: Multicenter Randomized Controlled Study
    Jiwoo Lee, You-Cheol Hwang, Woo Je Lee, Jong Chul Won, Kee-Ho Song, Cheol-Young Park, Kyu Jeung Ahn, Joong-Yeol Park
    Diabetes Therapy.2020; 11(4): 859.     CrossRef
  • Comparison of Renal Effects of Ezetimibe–Statin Combination versus Statin Monotherapy: A Propensity-Score-Matched Analysis
    Jaehyun Bae, Namki Hong, Byung-Wan Lee, Eun Seok Kang, Bong-Soo Cha, Yong-ho Lee
    Journal of Clinical Medicine.2020; 9(3): 798.     CrossRef
  • Combined use of rosuvastatin and ezetimibe improves hepatic steatosis in patients with dyslipidemia
    Won Dong Lee, Beom Kyung Kim, Jun Yong Park, Do Young Kim, Sang Hoon Ahn, Kwang-Hyub Han, Seung Up Kim
    European Journal of Gastroenterology & Hepatology.2020; 32(12): 1538.     CrossRef
  • Influence of rosuvastatin dose on total fatty acids and free fatty acids in plasma
    Cristian I. Ciucanu, Sonia Olariu, Daliborca C. Vlad, Victor Dumitraşcu
    Medicine.2020; 99(48): e23356.     CrossRef
  • The effect of switching from statin-monotherapy to statin/ezetimibe combination therapy on lipid profiles in patients with type 2 diabetes and dyslipidemia: a multicenter open-label study (EUCLID)
    Mitsuhide Takeshita, Atsushi Tanaka, Atsushi Kawaguchi, Keiko Sato, Shigeru Toyoda, Teruo Inoue, Koichi Node
    Vascular Failure.2020; 4(1): 22.     CrossRef
  • Response: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J 2019;43:582–9)
    You-Cheol Hwang
    Diabetes & Metabolism Journal.2019; 43(6): 915.     CrossRef
  • Letter: Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus (Diabetes Metab J2019;43:582–9)
    Tae Seo Sohn
    Diabetes & Metabolism Journal.2019; 43(6): 909.     CrossRef
  • Changes in Plasma Free Fatty Acids Associated with Type-2 Diabetes
    Amélie I. S. Sobczak, Claudia A. Blindauer, Alan J. Stewart
    Nutrients.2019; 11(9): 2022.     CrossRef
Obesity and Metabolic Syndrome
Higher High Density Lipoprotein 2 (HDL2) to Total HDL Cholesterol Ratio Is Associated with a Lower Risk for Incident Hypertension
You-Cheol Hwang, Wilfred Y. Fujimoto, Steven E. Kahn, Donna L. Leonetti, Edward J. Boyko
Diabetes Metab J. 2019;43(1):114-122.   Published online September 28, 2018
DOI: https://doi.org/10.4093/dmj.2018.0053
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Background

Recent studies have suggested that high density lipoprotein (HDL) cholesterol is inversely associated with the development of hypertension. We aimed to determine the association between different HDL cholesterol subclasses and risk of future hypertension.

Methods

A total of 270 Japanese Americans (130 men, 140 women) without hypertension between the ages of 34 to 75 years were enrolled. Blood pressure was measured with a mercury sphygmomanometer, and average blood pressure was calculated. Incident hypertension was determined 5 to 6 and 10 to 11 years after enrollment. HDL2, HDL3, and total HDL cholesterol were measured at baseline.

Results

During 10 years of follow-up, the cumulative incidence of hypertension was 28.1% (76/270). In univariate analysis, age, diabetes, waist circumference, systolic and diastolic blood pressure, fasting glucose, insulin resistance index, total and low density lipoprotein cholesterol, and visceral adipose tissue were significant predictors for incident hypertension. Among the HDL cholesterol subclass, HDL2 cholesterol was inversely associated with hypertension incidence, but both total and HDL3 cholesterol were not. In addition, HDL2/HDL cholesterol was inversely associated with future hypertension risk. In multivariate analysis, age (odds ratio [OR], 1.71; 95% confidence interval [CI], 1.26 to 2.31; P=0.001), systolic blood pressure (OR, 1.83; 95% CI, 1.31 to 2.56; P<0.001), and HDL2/HDL cholesterol (OR, 0.71; 95% CI, 0.52 to 0.98; P=0.035), were associated with future development of hypertension.

Conclusion

A higher proportion of HDL2 cholesterol among total HDL cholesterol predicted a lower risk for incident hypertension. However, concentrations of total HDL, HDL2, and HDL3 cholesterol were not independent predictors of incident hypertension.

Citations

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    Diabetes, Metabolic Syndrome and Obesity.2024; Volume 17: 363.     CrossRef
  • Long-term PM1 exposure and hypertension hospitalization: A causal inference study on a large community-based cohort in South China
    Yuqin Zhang, Shirui Chen, Jing Wei, Jie Jiang, Xiao Lin, Ying Wang, Chun Hao, Wenjing Wu, Zhupei Yuan, Jie Sun, Han Wang, Zhicheng Du, Wangjian Zhang, Yuantao Hao
    Science Bulletin.2024;[Epub]     CrossRef
  • High-Density Lipoprotein Signaling via Sphingosine-1-Phosphate Receptors Safeguards Spontaneously Hypertensive Rats against Myocardial Ischemia/Reperfusion Injury
    Aishah Al-Jarallah, Fawzi A. Babiker
    Pharmaceutics.2024; 16(4): 497.     CrossRef
  • Effects of cardiometabolic risk factors on blood pressure in outpatients at Sominé DOLO hospital, Mopti, Mali
    Modibo Coulibaly, Adama Kondé, Djibril Traoré, Ousmane Bah, Valentin Sagara, Bakary Maiga
    International Journal of Clinical Biochemistry and Research.2023; 10(1): 87.     CrossRef
  • The association of lipid metabolism with bone metabolism and the role of human traits: a Mendelian randomization study
    Jian Kang, Shuangli Zhao, Xize Wu, Can Wang, Zongkun Jiang, Shixuan Wang
    Frontiers in Endocrinology.2023;[Epub]     CrossRef
  • The role of different lipid measures for incident hypertension during more than 12-year follow-up: Tehran Lipid and Glucose Study
    Amirreza Hadaegh, Samaneh Akbarpour, Maryam Tohidi, Niloofar Barzegar, Somayeh Hosseinpour-Niazi, Fereidoun Azizi, Farzad Hadaegh
    British Journal of Nutrition.2022; 128(9): 1700.     CrossRef
  • High Density Lipoprotein Reduces Blood Pressure and Protects Spontaneously Hypertensive Rats Against Myocardial Ischemia-Reperfusion Injury in an SR-BI Dependent Manner
    Aishah Al-Jarallah, Fawzi Babiker
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Association between the Uric Acid to High Density Lipoprotein Cholesterol Ratio and Systolic Pressure in Chinese Short Stature Children and Adolescents
    广欣 李
    Advances in Clinical Medicine.2022; 12(09): 8266.     CrossRef
  • Associations Between Peripheral Blood Microbiome and the Risk of Hypertension
    Yang Jing, Hui Zhou, Honghong Lu, Xiaofang Chen, Liangyue Zhou, Jingqi Zhang, Jing Wu, Chen Dong
    American Journal of Hypertension.2021; 34(10): 1064.     CrossRef
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The Relationship Between Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes.
Hyun Ae Seo, Yeon Kyung Choi, Jae Han Jeon, Jung Eun Lee, Ji Yun Jeong, Seong Su Moon, In Kyu Lee, Bo Wan Kim, Jung Guk Kim
Korean Diabetes J. 2009;33(6):485-493.   Published online December 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.6.485
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AbstractAbstract PDF
BACKGROUND
The incidence of type 2 diabetes mellitus is increasing annually and patient mortality is high. Coronary artery calcification is a predictor of coronary artery disease. Cardiovascular events, which are the main cause of death in type 2 diabetes patients, may be preventable by addressing risk factors associated with coronary artery calcification. We examined the relationships between coronary artery calcification, lipid profiles, and apolipoprotein levels. METHODS: We calculated the coronary calcium scores (CCS) of 254 subjects with type 2 diabetes (113 males, 141 females) via multi-detector row computed tomography (MDCT). Height, body weight, blood pressure, HbA1c, c-peptide, lipid profile and apolipoprotein were assessed concurrently. RESULTS: In patients with type 2 diabetes, Agatston score and apolipoprotein A-1 were significantly negatively correlated in both males and females (males P = 0.015, females P = 0.021). The negative correlation between Agatston score and apolipoprotein A-1 was retained for the entire patient sample after adjustments for age and sex (P = 0.022). Stepwise multiple regression anaylses with the Agatston score as the dependent variable indicate that apolipoprotein A-1 is a independent predictor (beta coefficient = -0.047, 95%CI = -0.072 ~ -0.021, P < 0.001) of coronary artery calcification. CONCLUSION: The results of our study suggest that apolipoprotein A-1 is a useful independent indicator of coronary artery calcification.

Citations

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  • The Risk of Coronary Artery Calcification according to Different Lipid Parameters and Average Lipid Parameters
    Tae Kyung Yoo, Mi Yeon Lee, Ki-Chul Sung
    Journal of Atherosclerosis and Thrombosis.2024;[Epub]     CrossRef
  • Coronary Artery Calcification and Serum Apolipoprotein A-1 in Patients with Type 2 Diabetes
    Ki Won Oh
    Korean Diabetes Journal.2009; 33(6): 464.     CrossRef
The long-term effect of ramipril on Gialpha2-protein and Protein Tyrosine Phosphatase 1B in an animal model of type 2 diabetes(OLETF rat).
Jung Min Lee, Ok Ki Hong, Hyuk Sang Kwon, Sung Dae Moon, Sang Ah Chang, Hyun Shik Son, Kun Ho Yoon, Bong Yun Cha, Sung Koo Kang
Korean Diabetes J. 2006;30(1):25-38.   Published online January 1, 2006
DOI: https://doi.org/10.4093/jkda.2006.30.1.25
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BACKGROUND
The regulation of tyrosine phosphorylation/dephosphorylation is an important mechanism in various intracellular metabolism. Also impaired insulin signal transduction is important in pathogenesis of type 2 diabetes. It has been reported that PTP1B is a negative regulator of insulin action, and Gialpha2-protein is related to the regulation of PTP1B. Herein we investigated the long-term effects of ramipril on PTP1B/insulin signal protein interaction and the relation between Gialpha2 and PTP1B in animal model of type 2 diabetes (OLETF rat). METHODS: OLETF rats and age-matched LETO rats were divided into two groups. One group of rats received ramipril (10 mg/kg body weight) for 12 weeks, and another group did not. Finally, each group was divided into 2 subgroups, with or without insulin injection intravenously, before sacrifice. After sacrifice, tissues extracts of liver, hind limb muscle, and epididymal fat were obtained for quantification of PTP1B, Gialpha2, and several insulin signal proteins by western blotting. RESULTS: In liver and muscle, the levels of basal PTP1B and activated PTP1B of OLETF rats treated with ramipril and insulin were significantly decreased. The levels of Gialpha2, activated IRS-2, and activated p-85alpha were significantly increased in OLETF rats treated with ramipril and insulin. In adipose tissue, the levels of Gialpha2 and activated p-85alpha of OLETF rats treated with ramipril and insulin were slightly increased as in liver and muscle. But, the levels of basal PTP1B and activated PTP1B were significantly increased. And, the levels of activated IRS-1 and activated IRS-2 were decreased. CONCLUSION: These results suggest that the improvement of insulin sensitivity by treatment with ramipril was related to the decreased level of activated PTP1B. Also, we could suggest that the changes of activated PTP1B level was related with the changes of Gialpha2-protein. However, the results of adipose tissue were different from those of liver and muscle. So it seemed likely that there would be various major modulators for regulation of insulin signal pathway according to tissue.
Effect of Gi-proteins on Insulin Binding, Internalization and Recycling of Insulin Receptor in Bovine Aorta Endothelial Cell.
Hyuk Ho Kwon, Hyun Shik Son, Jung Min Lee, Seung Hyun Ko, Ok Ki Hong, Sung Dae Moon, Sang Ah Chang, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2003;27(1):26-38.   Published online February 1, 2003
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BACKGROUND
Guanine nucleotide binding proteins (G-proteins) play important roles in the hormonal actions of many signal transduction systems. Possible roles for the Gi-protein in insulin action have been suggested. It is reported that Gi-protein is associated with insulin actions to a greater extent than Gs-protein. There are at least three different subtypes of Gi-proteins (Gi(alpha1), Gi(alpha2), and Gi(alpha3)), however, it is not certain which subtypes are associated with insulin receptors and their action. METHODS: To investigate the effects of Gi-proteins on insulin action, the Gi-proteins were overexpressed in cultured bovine aortic endothelial cells (BAEC), using the DNA-polylysine-adenovirus complex transfection method. After incubating for 24 hours, the BAEC were treated with 200 ng/mL insulin to evaluate the insulin binding, receptor internalization and recycling. RESULTS: The following results were found : 1) The binding of specific insulin bindings to the insulin receptors of endothelial cells were time-dependent, reaching their maximal levels in all cells after 30 minutes. The maximal specific bindings of the control, Gi(alpha1), Gi(alpha2), and Gi(alpha3) were 0.58+/-0.1, 0.54+/-0.08, 0.54+/-0.1, 0.53+/-0.09%, respectively. 2) The internalization of 125I-insulin, into endothelial cells, was assessed by the acid washing dissociation method, and occurred rapidly. There was a significant difference in the internalized radioactivity of the 125I-insulin in the overexpressed Gi(alpha2) protein group compared to the two groups. 3) The recycling of the insulin receptors in the three types of Gi-protein showed no significant difference between the three group. CONCLUSION: In conclusion, the Gi(alpha2) protein may be associated with internalization of the insulin-insulin receptor complex, and appears to be important in both the action of insulin and the intracellular processing of insulin receptors.
Effect of Oxidized LDL on the Amount of Insulin Receptor and Gi-proteins in the Caveolae of Bovine Aortic Endothelial Cells (BAEC).
Sung Yoon Jeon, Hyun Shik Son, Jung Min Lee, Sung Dae Moon, Kun Ho Yoon, Bong Yun Cha, Kwang Woo Lee, Ho Young Son, Sung Koo Kang
Korean Diabetes J. 2001;25(1):71-82.   Published online February 1, 2001
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BACKGROUND
AND AIMS: Oxidized LDL (ox-LDL) may induce endothelial cell dysfunction and suggested to have an association with atherosclerosis or insulin resistance. Several studies have shown that ox-LDL inhibits signaling pathways mediated by inhibitory GTP-binding proteins (Gi-proteins). G-protein coupled receptors (GPCRs) can be internalized via caveolae. Caveolae are small flask-shaped invaginations of the plasma membrane, characterized by high levels of cholesterol and glycosphingolipids and also by the presence of caveolin, a 20-24 kDa integral membrane protein. G-proteins are enriched within caveolae membranes, where caveolin-1 directly interacts with the -subunits of G-proteins. It is reported that functional changes of G-proteins such as mutational or pharmacological activation of G-proteins affect direct interaction between G-proteins and caveolin-1. Thus, we investigated the effect of ox-LDL on the change of the amount of insulin receptor and Gi proteins in the caveolae. MATERIALS AND METHODS: ox-LDL was prepared by exposing samples of native LDL (n-LDL) to CuSO4 for 24 hours. Caveolae were extracted after treating BAECs at several concentrations of ox-LDL (10, 50, 100 g/mL) for various durations (0-48 hr), and we investigated the changes of the amount of caveolin-1, Gi -proteins and insulin receptor using immunoblot. RESULTS: While the amount of caveolin-1 was decreased, the amount of insulin receptor, Gi 2 and Gi 3 proteins in caveolae were also decreased after treatment of ox-LDL on the BAECs (insulin receptor: 66%; Gi 2 protein: 33%; Gi 3 protein: 66%, p<0.05). The amount of caveolin-1 was increased for the first 6 hours and then decreased, however, the amount of Gi -proteins and insulin receptor were vice versa during 48 hours incubation. CONCLUSION: These results indicate that ox-LDL can affect the change of the amount of insulin receptor and Gi-proteins in caveolae and it may induce endothelial cell dysfunction.

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