- Diabetes, obesity and metabolism
- Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate-Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE)
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Nam Hoon Kim, Juneyoung Lee, Suk Chon, Jae Myung Yu, In-Kyung Jeong, Soo Lim, Won Jun Kim, Keeho Song, Ho Chan Cho, Hea Min Yu, Kyoung-Ah Kim, Sang Soo Kim, Soon Hee Lee, Chong Hwa Kim, Soo Heon Kwak, Yong‐ho Lee, Choon Hee Chung, Sihoon Lee, Heung Yong Jin, Jae Hyuk Lee, Gwanpyo Koh, Sang-Yong Kim, Jaetaek Kim, Ju Hee Lee, Tae Nyun Kim, Hyun Jeong Jeon, Ji Hyun Lee, Jae-Han Jeon, Hye Jin Yoo, Hee Kyung Kim, Hyeong-Kyu Park, Il Seong Nam-Goong, Seongbin Hong, Chul Woo Ahn, Ji Hee Yu, Jong Heon Park, Keun-Gyu Park, Chan Ho Park, Kyong Hye Joung, Ohk-Hyun Ryu, Keun Yong Park, Eun-Gyoung Hong, Bong-Soo Cha, Kyu Chang Won, Yoon-Sok Chung, Sin Gon Kim
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Endocrinol Metab. 2024;39(5):722-731. Published online August 22, 2024
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DOI: https://doi.org/10.3803/EnM.2024.1995
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Abstract
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- Background
Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined.
Methods This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months.
Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.
- Adrenal Gland
- Metabolic Subtyping of Adrenal Tumors: Prospective Multi-Center Cohort Study in Korea
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Eu Jeong Ku, Chaelin Lee, Jaeyoon Shim, Sihoon Lee, Kyoung-Ah Kim, Sang Wan Kim, Yumie Rhee, Hyo-Jeong Kim, Jung Soo Lim, Choon Hee Chung, Sung Wan Chun, Soon-Jib Yoo, Ohk-Hyun Ryu, Ho Chan Cho, A Ram Hong, Chang Ho Ahn, Jung Hee Kim, Man Ho Choi
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Endocrinol Metab. 2021;36(5):1131-1141. Published online October 21, 2021
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DOI: https://doi.org/10.3803/EnM.2021.1149
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6,577
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Conventional diagnostic approaches for adrenal tumors require multi-step processes, including imaging studies and dynamic hormone tests. Therefore, this study aimed to discriminate adrenal tumors from a single blood sample based on the combination of liquid chromatography-mass spectrometry (LC-MS) and machine learning algorithms in serum profiling of adrenal steroids.
Methods The LC-MS-based steroid profiling was applied to serum samples obtained from patients with nonfunctioning adenoma (NFA, n=73), Cushing’s syndrome (CS, n=30), and primary aldosteronism (PA, n=40) in a prospective multicenter study of adrenal disease. The decision tree (DT), random forest (RF), and extreme gradient boost (XGBoost) were performed to categorize the subtypes of adrenal tumors.
Results The CS group showed higher serum levels of 11-deoxycortisol than the NFA group, and increased levels of tetrahydrocortisone (THE), 20α-dihydrocortisol, and 6β-hydroxycortisol were found in the PA group. However, the CS group showed lower levels of dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEA-S) than both the NFA and PA groups. Patients with PA expressed higher serum 18-hydroxycortisol and DHEA but lower THE than NFA patients. The balanced accuracies of DT, RF, and XGBoost for classifying each type were 78%, 96%, and 97%, respectively. In receiver operating characteristics (ROC) analysis for CS, XGBoost, and RF showed a significantly greater diagnostic power than the DT. However, in ROC analysis for PA, only RF exhibited better diagnostic performance than DT.
Conclusion The combination of LC-MS-based steroid profiling with machine learning algorithms could be a promising one-step diagnostic approach for the classification of adrenal tumor subtypes.
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Citations
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- Treating Primary Aldosteronism-Induced Hypertension: Novel Approaches and Future Outlooks
Nathan Mullen, James Curneen, Padraig T Donlon, Punit Prakash, Irina Bancos, Mark Gurnell, Michael C Dennedy Endocrine Reviews.2024; 45(1): 125. CrossRef - Steroid profiling in adrenal disease
Danni Mu, Dandan Sun, Xia Qian, Xiaoli Ma, Ling Qiu, Xinqi Cheng, Songlin Yu Clinica Chimica Acta.2024; 553: 117749. CrossRef - Plasma Steroid Profiling Combined With Machine Learning for the Differential Diagnosis in Mild Autonomous Cortisol Secretion From Nonfunctioning Adenoma in Patients With Adrenal Incidentalomas
Danni Mu, Xia Qian, Yichen Ma, Xi Wang, Yumeng Gao, Xiaoli Ma, Shaowei Xie, Lian Hou, Qi Zhang, Fang Zhao, Liangyu Xia, Liling Lin, Ling Qiu, Jie Wu, Songlin Yu, Xinqi Cheng Endocrine Practice.2024; 30(7): 647. CrossRef - Mild autonomous cortisol secretion: pathophysiology, comorbidities and management approaches
Alessandro Prete, Irina Bancos Nature Reviews Endocrinology.2024; 20(8): 460. CrossRef - Plasma Steroid Profiling Between Patients With and Without Diabetes Mellitus in Nonfunctioning Adrenal Incidentalomas
Yui Nakano, Maki Yokomoto-Umakoshi, Kohta Nakatani, Hironobu Umakoshi, Hiroshi Nakao, Masamichi Fujita, Hiroki Kaneko, Norifusa Iwahashi, Tatsuki Ogasawara, Tazuru Fukumoto, Yayoi Matsuda, Ryuichi Sakamoto, Yoshihiro Izumi, Takeshi Bamba, Yoshihiro Ogawa Journal of the Endocrine Society.2024;[Epub] CrossRef - Peak-Based Machine Learning for Plastic Type Classification in Time-of-Flight Secondary Ion Mass Spectrometry
Jin Gyeong Son, Hyun Kyong Shon, Ji-Eun Kim, In−Ho Lee, Tae Geol Lee Journal of the American Society for Mass Spectrometry.2024; 35(12): 3107. CrossRef - Serum and hair steroid profiles in patients with nonfunctioning pituitary adenoma undergoing surgery: A prospective observational study
Seung Shin Park, Yong Hwy Kim, Ho Kang, Chang Ho Ahn, Dong Jun Byun, Man Ho Choi, Jung Hee Kim The Journal of Steroid Biochemistry and Molecular Biology.2023; 230: 106276. CrossRef - Recent Updates on the Management of Adrenal Incidentalomas
Seung Shin Park, Jung Hee Kim Endocrinology and Metabolism.2023; 38(4): 373. CrossRef - LC-MS based simultaneous profiling of adrenal hormones of steroids, catecholamines, and metanephrines
Jongsung Noh, Chaelin Lee, Jung Hee Kim, Seung Woon Myung, Man Ho Choi Journal of Lipid Research.2023; 64(11): 100453. CrossRef - 2023 Korean Endocrine Society Consensus Guidelines for the Diagnosis and Management of Primary Aldosteronism
Jeonghoon Ha, Jung Hwan Park, Kyoung Jin Kim, Jung Hee Kim, Kyong Yeun Jung, Jeongmin Lee, Jong Han Choi, Seung Hun Lee, Namki Hong, Jung Soo Lim, Byung Kwan Park, Jung-Han Kim, Kyeong Cheon Jung, Jooyoung Cho, Mi-kyung Kim, Choon Hee Chung Endocrinology and Metabolism.2023; 38(6): 597. CrossRef - Toward Systems-Level Metabolic Analysis in Endocrine Disorders and Cancer
Aliya Lakhani, Da Hyun Kang, Yea Eun Kang, Junyoung O. Park Endocrinology and Metabolism.2023; 38(6): 619. CrossRef - Prevalence and Characteristics of Adrenal Tumors in an Unselected Screening Population
Ying Jing, Jinbo Hu, Rong Luo, Yun Mao, Zhixiao Luo, Mingjun Zhang, Jun Yang, Ying Song, Zhengping Feng, Zhihong Wang, Qingfeng Cheng, Linqiang Ma, Yi Yang, Li Zhong, Zhipeng Du, Yue Wang, Ting Luo, Wenwen He, Yue Sun, Fajin Lv, Qifu Li, Shumin Yang Annals of Internal Medicine.2022; 175(10): 1383. CrossRef
- Diabetes, Obesity and Metabolism
- Association of Protein Z with Prediabetes and Type 2 Diabetes
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Yun-Ui Bae, Ji Hong You, Nan Hee Cho, Leah Eunjung Kim, Hye Min Shim, Jae-Hyung Park, Ho Chan Cho
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Endocrinol Metab. 2021;36(3):637-646. Published online June 2, 2021
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DOI: https://doi.org/10.3803/EnM.2021.962
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Abstract
PDFSupplementary MaterialPubReader ePub
- Background
Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease. Early detection of prediabetes is important to reduce the risk of T2DM. Some cytokines are known to be associated with T2DM. Therefore, we aimed to identify cytokines as novel biomarkers of glucose dysmetabolism.
Methods The first stage of the study included 43 subjects (13 subjects with newly diagnosed T2DM, 13 with prediabetes, and 16 with normoglycemia) for cytokine microarray analysis. Blood samples of the subjects were assessed for 310 cytokines to identify potential indicators of prediabetes. The second stage included 142 subjects (36 subjects with T2DM, 35 with prediabetes, and 71 with normoglycemia) to validate the potential cytokines associated with prediabetes.
Results We identified 41 cytokines that differed by 1.5-fold or more in at least one out of the three comparisons (normoglycemia vs. prediabetes, normoglycemia vs. T2DM, and prediabetes vs. T2DM) among 310 cytokines. Finally, we selected protein Z (PROZ) and validated this finding to determine its association with prediabetes. Plasma PROZ levels were found to be decreased in patients with prediabetes (1,490.32±367.19 pg/mL) and T2DM (1,583.34±465.43 pg/mL) compared to those in subjects with normoglycemia (1,864.07±450.83 pg/mL) (P<0.001). There were significantly negative correlations between PROZ and fasting plasma glucose (P=0.001) and hemoglobin A1c (P=0.010).
Conclusion PROZ levels were associated with prediabetes and T2DM. We suggest that PROZ may be a promising biomarker for the early detection of prediabetes. Further large-scale studies are needed to evaluate the relationship and mechanism between PROZ and prediabetes and T2DM.
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Citations
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- On the human health benefits of microalgal phytohormones: An explorative in silico analysis
Angelo Del Mondo, Annamaria Vinaccia, Luigi Pistelli, Christophe Brunet, Clementina Sansone Computational and Structural Biotechnology Journal.2023; 21: 1092. CrossRef - Role of F-box WD Repeat Domain Containing 7 in Type 1 Diabetes
Sarah W. Mohammed, Zainab M. Qassam, Ekhlass M. Taha, Nameer M. Salih Ibn AL-Haitham Journal For Pure and Applied Sciences.2023; 36(3): 167. CrossRef - Identification of Protein Z as a Potential Novel Biomarker for the Diagnosis of Prediabetes
Seung-Hoi Koo Endocrinology and Metabolism.2021; 36(3): 572. CrossRef - Association of Protein Z with Prediabetes and Type 2 Diabetes (Endocrinol Metab 2021;36:637-46, Yun-Ui Bae et al.)
Ji Hong You, Yun-Ui Bae, Ho Chan Cho Endocrinology and Metabolism.2021; 36(5): 1149. CrossRef - Association of Protein Z with Prediabetes and Type 2 Diabetes (Endocrinol Metab 2021;36:637-46, Yun-Ui Bae et al.)
Tiffany Pascreau, Maia Tchikviladze, Emilie Jolly, Sara Zia-Chahabi, Bertrand Lapergue, Marc Vasse Endocrinology and Metabolism.2021; 36(5): 1147. CrossRef
- Effects of Alpha-lipoic Acid on SREBP-1c Expression in HepG2 Cells.
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Tae Sung Yun, Ae Kyung Min, Nam Kyung Kim, Mi Kyung Kim, Ho Chan Cho, Hye Soon Kim, Jae Seok Hwang, Seong Yeol Ryu, Keun Gyu Park, In Kyu Lee
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J Korean Endocr Soc. 2008;23(1):27-34. Published online February 1, 2008
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DOI: https://doi.org/10.3803/jkes.2008.23.1.27
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- BACKGROUND
Non-alcoholic fatty liver disease is common in patients with insulin resistance. Sterol regulatory element binding protein-1c (SREBP-1c) is a member of a family of transcription factors that have been recognized as key regulators for lipid accumulation in the liver that activate enzymes involved in the fatty acid biosynthetic pathway. This study was designed to evaluate whether alpha-lipoic acid (ALA) inhibits insulin-stimulated SREBP-1c expression. METHODS: We investigated the effects of ALA on insulin-stimulated SREBP-1c expression in a human hepatoma cell line (HepG2 cells) using Northern and Western blot analysis. We also examined the effect of ALA on the promoter activity of the SREBP-1c gene to examine whether ALA can affect SREBP-1c expression at the transcriptional level. To discern the mechanism by which ALA inhibits SREBP-1c expression, we examined the role of AMP-activated protein kinase (AMPK). RESULTS: Insulin increased the expression of SREBP-1c mRNA and protein in HepG2 cells in a dose depended manner. Co-treatment with ALA inhibited the insulin increased SREBP-1c expression in a dose-dependent manner. ALA also inhibited insulin-stimulated activation of the SREBP-1c promoter activity, indicating that ALA inhibited SREBP-1c expression at the transcriptional level. ALA increased phosphorylation of AMPK in HepG2 cells. Inhibition of the AMPK activity by compound C markedly reversed the inhibitory effects of ALA for insulin-stimulated SREBP-1c expression. These results suggest that ALA-induced suppression of SREBP-1c expression is at least in part mediated via AMPK activation. CONCLUSION: The present study suggests that ALA has an inhibitory effect on insulin-stimulated SREBP-1c expression. Therefore, further studies on the effects of ALA on hepatic steatosis in an animal model need to be performed.
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- Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon Journal of Nutrition and Health.2015; 48(1): 1. CrossRef - Effects of an aqueous extract of purple sweet potato on nonalcoholic fatty liver in high fat/cholesterol-fed mice
You Jin Lee, Yoon Kyoung Yang, You Jin Kim, Oran Kwon Journal of Nutrition and Health.2015; 48(1): 1. CrossRef
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