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Serag H, Wakeel LE, William V, Abdelsalam M, Abdelsalam A, Sayed R. Effect of trimetazidine on left ventricular functions and cardiac biomarkers in diabetic patients with left ventricular diastolic dysfunction: a randomized controlled trial. Sci Rep 2025; 15:2115. [PMID: 39814796 PMCID: PMC11736023 DOI: 10.1038/s41598-024-83213-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2024] [Accepted: 12/12/2024] [Indexed: 01/18/2025] Open
Abstract
We investigated the impact of trimetazidine treatment on left ventricular (LV) functions and cardiac biomarkers in diabetic patients with diastolic dysfunction as an early stage of diabetic cardiomyopathy. Sixty-three patients were randomly assigned to receive either trimetazidine or a placebo for 3 months. At baseline and after 3-months of treatment, measurements of serum levels of glycemic control parameters, lipid profile, tumor necrosis factor alpha, transforming growth factor beta 1, n-terminal pro brain natriuretic peptide and assessment of modified Medical Research Council (mMRC) dyspnea score, echocardiographic indices of LV functions and LV global longitudinal strain (GLS) were performed. After 3-months, trimetazidine group exhibited a significant reduction in left atrial volume index by 6.99% versus an increase by 0.66% in placebo group, p = 0.034. Moreover, average e' increased by a significantly higher percentage in trimetazidine versus placebo group (8.46 ± 18.64 vs. -2.49 ± 14.52, respectively. p = 0.015). Trimetazidine treatment resulted in a significant increase in LVGLS by 6.66% versus LVGLS reduction by 2.79% in placebo group (p = 0.004). Trimetazidine group had a significantly lower median mMRC dyspnea score compared to placebo (0 vs. 1, respectively, p = 0.015) and a significantly lower low-density lipoprotein (LDL-C) (103.43 ± 28.31 vs. 125.34 ± 45.27, respectively, p = 0.032). There was no significant difference between both groups in levels of other biomarkers. Three-months treatment with trimetazidine improved diastolic function parameters, LVGLS, dyspnea severity and LDL-C levels in diabetic patients with diastolic dysfunction.
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Affiliation(s)
- Heba Serag
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
| | - Lamia El Wakeel
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Viola William
- Department of Cardiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Mona Abdelsalam
- Department of Internal medicine, Endocrinology and Metabolism, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Ahmed Abdelsalam
- Department of Cardiology, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Rana Sayed
- Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
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Ianoș RD, Cozma A, Lucaciu RL, Hangan AC, Negrean V, Mercea DC, Ciulei G, Pop C, Procopciuc LM. Role of Circulating Biomarkers in Diabetic Cardiomyopathy. Biomedicines 2024; 12:2153. [PMID: 39335666 PMCID: PMC11428922 DOI: 10.3390/biomedicines12092153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2024] [Revised: 09/18/2024] [Accepted: 09/21/2024] [Indexed: 09/30/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a metabolic disorder that has alarmingly increased in incidence in recent decades. One of the most serious complications of T2DM is diabetic cardiomyopathy (DCM), an often underrecognized yet severe condition that is a leading cause of mortality among diabetic patients. In the early stages of DCM, patients typically show no symptoms and maintain normal systolic and diastolic left ventricle function, making early detection challenging. Currently available clinical markers are often not specific enough to detect the early stage of DCM. Conventional biomarkers of cardiac mechanical stress and injury, such as natriuretic peptides (NPs) and cardiac troponin I (cTnI), have shown limited predictive value for patients with T2DM. NPs have proven efficacy in detecting diastolic dysfunction in diabetic patients when used alongside 2D echocardiography, but their utility as biomarkers is limited to symptomatic individuals. While cTnI is a reliable indicator of general cardiac damage, it is not specific to cardiac injury caused by high glucose levels or T2DM. This underscores the need for research into biomarkers that can enable early diagnosis and management of DCM to reduce mortality rates. Promising novel biomarkers that showed good performance in detecting diastolic dysfunction or heart failure in diabetic patients include galectin-3, ST2, FGF-21, IGFBP-7, GDF-15, and TGF-β. This review summarizes the current understanding of DCM biomarkers, aiming to generate new ideas for the early recognition and treatment of DCM by exploring related pathophysiological mechanisms.
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Affiliation(s)
- Raluca Diana Ianoș
- Department of Cardiology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400001 Cluj-Napoca, Romania;
| | - Angela Cozma
- 4th Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (V.N.); (G.C.)
| | - Roxana Liana Lucaciu
- Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, “Iuliu-Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Adriana Corina Hangan
- Department of Inorganic Chemistry, Faculty of Pharmacy, “Iuliu-Hațieganu” University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania;
| | - Vasile Negrean
- 4th Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (V.N.); (G.C.)
| | - Delia Corina Mercea
- Department of Cardiology, Emergency County Hospital, 430031 Baia Mare, Romania; (D.C.M.); (C.P.)
| | - George Ciulei
- 4th Department of Internal Medicine, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400015 Cluj-Napoca, Romania; (V.N.); (G.C.)
| | - Călin Pop
- Department of Cardiology, Emergency County Hospital, 430031 Baia Mare, Romania; (D.C.M.); (C.P.)
- Faculty of Medicine Arad, “Vasile Goldis” Western University, 310045 Arad, Romania
| | - Lucia Maria Procopciuc
- Department of Medical Biochemistry, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400349 Cluj-Napoca, Romania;
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Galis P, Bartosova L, Farkasova V, Bartekova M, Ferenczyova K, Rajtik T. Update on clinical and experimental management of diabetic cardiomyopathy: addressing current and future therapy. Front Endocrinol (Lausanne) 2024; 15:1451100. [PMID: 39140033 PMCID: PMC11319149 DOI: 10.3389/fendo.2024.1451100] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Accepted: 07/12/2024] [Indexed: 08/15/2024] Open
Abstract
Diabetic cardiomyopathy (DCM) is a severe secondary complication of type 2 diabetes mellitus (T2DM) that is diagnosed as a heart disease occurring in the absence of any previous cardiovascular pathology in diabetic patients. Although it is still lacking an exact definition as it combines aspects of both pathologies - T2DM and heart failure, more evidence comes forward that declares DCM as one complex disease that should be treated separately. It is the ambiguous pathological phenotype, symptoms or biomarkers that makes DCM hard to diagnose and screen for its early onset. This re-view provides an updated look on the novel advances in DCM diagnosis and treatment in the experimental and clinical settings. Management of patients with DCM proposes a challenge by itself and we aim to help navigate and advice clinicians with early screening and pharmacotherapy of DCM.
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Affiliation(s)
- Peter Galis
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
| | - Linda Bartosova
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
| | - Veronika Farkasova
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Monika Bartekova
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
- Institute of Physiology, Faculty of Medicine, Comenius University Bratislava, Bratislava, Slovakia
| | - Kristina Ferenczyova
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
| | - Tomas Rajtik
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University Bratislava, Bratislava, Slovakia
- Institute for Heart Research, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovakia
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Khan AR, Alnoud MAH, Ali H, Ali I, Ahmad S, Ul Hassan SS, Shaikh AL, Hussain T, Khan MU, Khan SU, Khan MS, Khan SU. Beyond the beat: A pioneering investigation into exercise modalities for alleviating diabetic cardiomyopathy and enhancing cardiac health. Curr Probl Cardiol 2024; 49:102222. [PMID: 38000567 DOI: 10.1016/j.cpcardiol.2023.102222] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2023] [Accepted: 11/18/2023] [Indexed: 11/26/2023]
Abstract
Patients with preexisting cardiovascular disease or those at high risk for developing the condition are often offered exercise as a form of therapy. Patients with cancer who are at an increased risk for cardiovascular issues are increasingly encouraged to participate in exercise-based, interdisciplinary programs due to the positive correlation between these interventions and clinical outcomes following myocardial infarction. Diabetic cardiomyopathy (DC) is a cardiac disorder that arises due to disruptions in the homeostasis of individuals with diabetes. One of the primary reasons for mortality in individuals with diabetes is the presence of cardiac structural damage and functional abnormalities, which are the primary pathological features of DC. The aetiology of dilated cardiomyopathy is multifaceted and encompasses a range of processes, including metabolic abnormalities, impaired mitochondrial function, dysregulation of calcium ion homeostasis, excessive cardiomyocyte death, and fibrosis. In recent years, many empirical investigations have demonstrated that exercise training substantially impacts the prevention and management of diabetes. Exercise has been found to positively impact the recovery of diabetes and improve several metabolic problem characteristics associated with DC. One potential benefit of exercise is its ability to increase systolic activity, which can enhance cardiometabolic and facilitate the repair of structural damage to the heart caused by DC, leading to a direct improvement in cardiac health. In contrast, exercise has the potential to indirectly mitigate the pathological progression of DC through its ability to decrease circulating levels of sugar and fat while concurrently enhancing insulin sensitivity. A more comprehensive understanding of the molecular mechanism via exercise facilitates the restoration of DC disease must be understood. Our goal in this review was to provide helpful information and clues for developing new therapeutic techniques for motion alleviation DC by examining the molecular mechanisms involved.
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Affiliation(s)
- Ahsan Riaz Khan
- Department of Interventional and Vascular Surgery, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China
| | - Mohammed A H Alnoud
- Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
| | - Hamid Ali
- Department of Biosciences, COMSATS University Islamabad, Park Road Tarlai Kalan, Islamabad 44000, Pakistan
| | - Ijaz Ali
- Centre for Applied Mathematics and Bioinformatics, Gulf University for Science and Technology, Hawally 32093, Kuwait
| | - Saleem Ahmad
- Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans 70112 LA, USA
| | - Syed Shams Ul Hassan
- Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310002, China
| | | | - Talib Hussain
- Women Dental College Abbottabad, KPK, 22020, Pakistan
| | - Munir Ullah Khan
- MOE Key Laboratory of Macromolecular Synthesis and Functionalization, International Research Center for X Polymers, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
| | - Safir Ullah Khan
- Hefei National Laboratory for Physical Sciences at the Microscale, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
| | - Muhammad Shehzad Khan
- Hong Kong Centre for Cerebro-Cardiovascular Health Engineering (COCHE), Shatin city, (HKSAR), Hong Kong
| | - Shahid Ullah Khan
- Integrative Science Center of Germplasm Creation in Western China (CHONGQING) Science City and Southwest University, College of Agronomy and Biotechnology, Southwest University, Chongqing 400715, China; Department of Biochemistry, Women Medical and Dental College, Khyber Medical University, Abbottabad, 22080, Khyber Pakhtunkhwa, Pakistan.
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Miyakuni S, Maeda D, Matsue Y, Yoshioka K, Dotare T, Sunayama T, Nabeta T, Naruse Y, Kitai T, Taniguchi T, Tanaka H, Okumura T, Baba Y, Matsumura A, Minamino T. The Prognostic Value of B-Type Natriuretic Peptide in Patients With Cardiac Sarcoidosis Without Heart Failure: Insights From ILLUMINATE-CS. J Am Heart Assoc 2022; 11:e025803. [PMID: 36515231 PMCID: PMC9798822 DOI: 10.1161/jaha.122.025803] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Background The prognostic role of BNP (B-type natriuretic peptide) in patients with cardiac sarcoidosis without evident heart failure is unknown. Methods and Results This is a post hoc analysis of ILLUMINATE-CS (Illustration of the Management and Prognosis of Japanese Patients With Cardiac Sarcoidosis), a multicenter, retrospective, and observational study that evaluated the clinical characteristics and prognosis of cardiac sarcoidosis. We analyzed patients with cardiac sarcoidosis without evident heart failure at the time of diagnosis. The association between baseline BNP levels and prognosis was investigated. The primary end point was the combined end point of all-cause death, heart failure hospitalization, and fatal ventricular arrhythmia. In total, 238 patients (61.0±11.1 years, 37% men) were analyzed, and 61 primary end points were observed during a median follow-up period of 3.0 (interquartile range, 1.7-5.8) years. Patients with high BNP (BNP above the median value of BNP) were older and had a lower renal function and left ventricular ejection fraction than those with low BNP values. Kaplan-Meier curve analysis indicated that high BNP levels were significantly associated with a high incidence of primary end points (log-rank P=0.004), and this association was retained even in multivariable Cox regression (hazard ratio, 2.06 [95% CI, 1.19-3.55]; P=0.010). Log-transformed BNP as a continuous variable was associated with the primary end point (hazard ratio, 2.12 [95% CI, 1.31-3.43]; P=0.002). Conclusions High baseline BNP level was an independent predictor of future adverse events in patients with cardiac sarcoidosis without heart failure at the time of diagnosis. Registration URL: https://www.umin.ac.jp/english/; Unique Identifier: UMIN-CTR: UMIN000034974.
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Affiliation(s)
- Shota Miyakuni
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan,Department of CardiologyKameda Medical CenterChibaJapan
| | - Daichi Maeda
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Yuya Matsue
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | | | - Taishi Dotare
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Tsutomu Sunayama
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan
| | - Takeru Nabeta
- Department of Cardiovascular MedicineKitasato University School of MedicineSagamiharaJapan
| | - Yoshihisa Naruse
- Division of Cardiology, Internal Medicine IIIHamamatsu University School of MedicineHamamatsuJapan
| | - Takeshi Kitai
- Department of Cardiovascular MedicineNational Cerebral and Cardiovascular CenterOsakaJapan
| | - Tatsunori Taniguchi
- Department of Cardiovascular MedicineOsaka University Graduate School of MedicineOsakaJapan
| | - Hidekazu Tanaka
- Division of Cardiovascular Medicine, Department of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Takahiro Okumura
- Department of CardiologyNagoya University Graduate School of MedicineNagoyaJapan
| | - Yuichi Baba
- Department of Cardiology and Geriatrics, Kochi Medical SchoolKochi UniversityNankokuJapan
| | | | - Tohru Minamino
- Department of Cardiovascular Biology and MedicineJuntendo University Graduate School of MedicineTokyoJapan,Japan Agency for Medical Research and Development‐Core Research for Evolutionary Medical Science and Technology (AMED‐CREST)Japan Agency for Medical Research and DevelopmentTokyoJapan
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Hao M, Deng J, Huang X, Li H, Ou H, Cai X, She J, Liu X, Chen L, Chen S, Liu W, Yan D. Metabonomic Characteristics of Myocardial Diastolic Dysfunction in Type 2 Diabetic Cardiomyopathy Patients. Front Physiol 2022; 13:863347. [PMID: 35651872 PMCID: PMC9150260 DOI: 10.3389/fphys.2022.863347] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Accepted: 03/28/2022] [Indexed: 12/26/2022] Open
Abstract
Diabetic cardiomyopathy (DCM) is one of the most essential cardiovascular complications in diabetic patients associated with glucose and lipid metabolism disorder, fibrosis, oxidative stress, and inflammation in cardiomyocytes. Despite increasing research on the molecular pathogenesis of DCM, it is still unclear whether metabolic pathways and alterations are probably involved in the development of DCM. This study aims to characterize the metabolites of DCM and to identify the relationship between metabolites and their biological processes or biological states through untargeted metabolic profiling. UPLC-MS/MS was applied to profile plasma metabolites from 78 patients with diabetes (39 diabetes with DCM and 39 diabetes without DCM as controls). A total of 2,806 biochemical were detected. Compared to those of DM patients, 78 differential metabolites in the positive-ion mode were identified in DCM patients, including 33 up-regulated and 45 down-regulated metabolites; however, there were only six differential metabolites identified in the negative mode including four up-regulated and two down-regulated metabolites. Alterations of several serum metabolites, including lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the development of DCM. KEGG enrichment analysis showed that there were three signaling pathways (metabolic pathways, porphyrin, chlorophyll metabolism, and lysine degradation) that were changed in both negative- and positive-ion modes. Our results demonstrated that differential metabolites and lipids have specific effects on DCM. These results expanded our understanding of the metabolic characteristics of DCM and may provide a clue in the future investigation of reducing the incidence of DCM. Furthermore, the metabolites identified here may provide clues for clinical management and the development of effective drugs.
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Affiliation(s)
- Mingyu Hao
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
| | - Jianxin Deng
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Xiaohong Huang
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Haiyan Li
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Huiting Ou
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Xiangsheng Cai
- Institute of Translational Medicine, University of Chinese Academy of Science-Shenzhen Hospital, Shenzhen, China
| | - Jiajie She
- Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China
- The First Affiliated Hospital of Shenzhen University, Reproductive Medicine Centre, Shenzhen Second People’s Hospital, Shenzhen, China
| | - Xueting Liu
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Ling Chen
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Shujuan Chen
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
| | - Wenlan Liu
- Department of Neurosurgery, Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People’s Hospital, Shenzhen University First Affiliated Hospital, Shenzhen, China
| | - Dewen Yan
- Department of Endocrinology, Shenzhen Clinical Research Center for Metabolic Diseases, Shenzhen Second People’s Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center of Shenzhen University, Shenzhen, China
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Zhao X, Liu S, Wang X, Chen Y, Pang P, Yang Q, Lin J, Deng S, Wu S, Fan G, Wang B. Diabetic cardiomyopathy: Clinical phenotype and practice. Front Endocrinol (Lausanne) 2022; 13:1032268. [PMID: 36568097 PMCID: PMC9767955 DOI: 10.3389/fendo.2022.1032268] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 11/22/2022] [Indexed: 12/12/2022] Open
Abstract
Diabetic cardiomyopathy (DCM) is a pathophysiological condition of cardiac structure and function changes in diabetic patients without coronary artery disease, hypertension, and other types of heart diseases. DCM is not uncommon in people with diabetes, which increases the risk of heart failure. However, the treatment is scarce, and the prognosis is poor. Since 1972, one clinical study after another on DCM has been conducted. However, the complex phenotype of DCM still has not been fully revealed. This dilemma hinders the pace of understanding the essence of DCM and makes it difficult to carry out penetrating clinical or basic research. This review summarizes the literature on DCM over the last 40 years and discusses the overall perspective of DCM, phase of progression, potential clinical indicators, diagnostic and screening criteria, and related randomized controlled trials to understand DCM better.
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Affiliation(s)
- Xudong Zhao
- Department of Endocrine and Metabolic Diseases, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Shengwang Liu
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Xiao Wang
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Yibing Chen
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Pai Pang
- Department of Endocrine and Metabolic Diseases, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Qianjing Yang
- Department of Endocrine and Metabolic Diseases, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Jingyi Lin
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Shuaishuai Deng
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Shentao Wu
- Department of Endocrine and Metabolic Diseases, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Guanwei Fan
- Tianjin Key Laboratory of Translational Research of TCM Prescription and Syndrome, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
| | - Bin Wang
- Department of Endocrine and Metabolic Diseases, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Xiqing, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Xiqing, Tianjin, China
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8
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Kumric M, Ticinovic Kurir T, Borovac JA, Bozic J. Role of novel biomarkers in diabetic cardiomyopathy. World J Diabetes 2021; 12:685-705. [PMID: 34168722 PMCID: PMC8192249 DOI: 10.4239/wjd.v12.i6.685] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Revised: 01/22/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023] Open
Abstract
Diabetic cardiomyopathy (DCM) is commonly defined as cardiomyopathy in patients with diabetes mellitus in the absence of coronary artery disease and hypertension. As DCM is now recognized as a cause of substantial morbidity and mortality among patients with diabetes mellitus and clinical diagnosis is still inappropriate, various expert groups struggled to identify a suitable biomarker that will help in the recognition and management of DCM, with little success so far. Hence, we thought it important to address the role of biomarkers that have shown potential in either human or animal studies and which could eventually result in mitigating the poor outcomes of DCM. Among the array of biomarkers we thoroughly analyzed, long noncoding ribonucleic acids, soluble form of suppression of tumorigenicity 2 and galectin-3 seem to be most beneficial for DCM detection, as their plasma/serum levels accurately correlate with the early stages of DCM. The combination of relatively inexpensive and accurate speckle tracking echocardiography with some of the highlighted biomarkers may be a promising screening method for newly diagnosed diabetes mellitus type 2 patients. The purpose of the screening test would be to direct affected patients to more specific confirmation tests. This perspective is in concordance with current guidelines that accentuate the importance of an interdisciplinary team-based approach.
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Affiliation(s)
- Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Tina Ticinovic Kurir
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Department of Endocrinology, University Hospital of Split, Split 21000, Croatia
| | - Josip A Borovac
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
- Emergency Medicine, Institute of Emergency Medicine of Split-Dalmatia County, Split 21000, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
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9
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Echocardiography, an Indispensable Tool for the Management of Diabetics, with or without Coronary Artery Disease, in Clinical Practice. ACTA ACUST UNITED AC 2020; 56:medicina56120709. [PMID: 33352952 PMCID: PMC7767240 DOI: 10.3390/medicina56120709] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/16/2020] [Accepted: 12/16/2020] [Indexed: 12/28/2022]
Abstract
Diabetes mellitus is a major factor contributing to the development of cardiovascular disease. As morbidity and mortality rates rise dramatically, when target organ damage develops pre-symptomatic assessment is critical for the management of diabetic patients. Echocardiography is a noninvasive and reproducible method that may aid in risk stratification and in evaluation of treatment effects. The aim of this review is to analyze the echocardiographic techniques which can detect early alteration in cardiac function in patients with diabetes.
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Hamza M, Fatima M, Masood M, Masood HU, Tasleem G, Ahmed H, Nadir M, Satti Z. Relationship of left ventricular and atrial dimensions with moderate to severe left ventricular diastolic dysfunction (grade II and above). Afr Health Sci 2020; 20:1749-1753. [PMID: 34394235 PMCID: PMC8351830 DOI: 10.4314/ahs.v20i4.27] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Introduction Left ventricular diastolic dysfunction (DD) is an entity in which the ventricle fails to fill up properly due to impaired ventricular relaxation and/or decreased compliance. The diagnosis of diastolic dysfunction is based on a variety of parameters in doppler echocardiograpy. However, some parameters like interventricular septal thickness in diastole (IVSd), posterior wall thickness in diastole (PWd), left ventricular internal end diastolic and systolic diameters (LVIDD and LVISD) along with left atrial diameters (LAD) have yet to be evaluated for the diagnostic workup of DD. Methods A case control study was done in the cardiology department from patient records from 2016 to 2018. Patients were diagnosed as diastolic dysfunction grade II and above by doppler echocardiography. IVSd, PWd, LVIDD, LAD, LVISD were obtained through 2-D echocardiography. Results Patients with DD had greater LAD, IVSd and PWd and decreased LVIDD and LVISD as compared to control group. Overall, IVSD was the most significant predictor (OR 1.52 95%CI 1.35–1.71) of DD followed by PWd and LAD. Similarly, LAD, IVSd and PWd had higher sensitivity and specificity than LVIDD and LVIDS. Conclusion IVSd, LAD and PWd showed significant performance in the diagnosis of diastolic dysfunction and hence can be used as a screening and diagnostic tool in diastolic dysfunction of grade ll and above.
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Abstract
The presence of comorbidities significantly influences long-term morbidity and mortality of symptomatic and asymptomatic heart failure (HF) patients. Metabolic syndrome and diabetic cardiomyopathy are two clinical conditions that share multiple pathophysiological mechanisms and that might be both responsible for cardiac dysfunction. However, it is argued whether metabolic syndrome (MS) independently increases HF risk or the association between MS and HF merely reflects the impact of individual risk factors included in its definition on HF development. Similarly, in the context of diabetic cardiomyopathy, many aspects are still challenging starting from the definition up to the therapeutic management. In this clinical review, we focused the attention on molecular pathways, myocyte alterations, and specific patterns of metabolic syndrome and diabetic cardiomyopathy in order to better define the potential diagnostic and therapeutic approaches of these two pathological conditions.
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Han BG, Lee JY, Kim MR, Shin H, Kim JS, Yang JW, Kim JY. Fluid overload is a determinant for cardiac structural and functional impairments in type 2 diabetes mellitus and chronic kidney disease stage 5 not undergoing dialysis. PLoS One 2020; 15:e0235640. [PMID: 32730268 PMCID: PMC7392282 DOI: 10.1371/journal.pone.0235640] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2020] [Accepted: 06/19/2020] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease. METHODS Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy. RESULTS Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors. CONCLUSIONS Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.
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Affiliation(s)
- Byoung-Geun Han
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
| | - Jun Young Lee
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
| | - Mi Ryung Kim
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
| | - Hanwul Shin
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
| | - Jae-Seok Kim
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
| | - Jae-Won Yang
- Department of Nephrology, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
| | - Jong Yeon Kim
- Department of Neurosurgery, Yonsei University Wonju College of Medicine, Wonju, Kang-won, Korea
- * E-mail:
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Johnson R, Nxele X, Cour M, Sangweni N, Jooste T, Hadebe N, Samodien E, Benjeddou M, Mazino M, Louw J, Lecour S. Identification of potential biomarkers for predicting the early onset of diabetic cardiomyopathy in a mouse model. Sci Rep 2020; 10:12352. [PMID: 32703998 PMCID: PMC7378836 DOI: 10.1038/s41598-020-69254-x] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 06/23/2020] [Indexed: 01/10/2023] Open
Abstract
Type 2 diabetes (T2D) is characterized by metabolic derangements that cause a shift in substrate preference, inducing cardiac interstitial fibrosis. Interstitial fibrosis plays a key role in aggravating left ventricular diastolic dysfunction (LVDD), which has previously been associated with the asymptomatic onset of heart failure. The latter is responsible for 80% of deaths among diabetic patients and has been termed diabetic cardiomyopathy (DCM). Through in silico prediction and subsequent detection in a leptin receptor-deficient db/db mice model (db/db), we confirmed the presence of previously identified potential biomarkers to detect the early onset of DCM. Differential expression of Lysyl Oxidase Like 2 (LOXL2) and Electron Transfer Flavoprotein Beta Subunit (ETFβ), in both serum and heart tissue of 6–16-week-old db/db mice, correlated with a reduced left-ventricular diastolic dysfunction as assessed by high-resolution Doppler echocardiography. Principal component analysis of the combined biomarkers, LOXL2 and ETFβ, further displayed a significant difference between wild type and db/db mice from as early as 9 weeks of age. Knockdown in H9c2 cells, utilising siRNA of either LOXL2 or ETFβ, revealed a decrease in the expression of Collagen Type I Alpha1 (COL1A1), a marker known to contribute to enhanced myocardial fibrosis. Additionally, receiver-operating curve (ROC) analysis of the proposed diagnostic profile showed that the combination of LOXL2 and ETFβ resulted in an area under the curve (AUC) of 0.813, with a cut-off point of 0.824, thus suggesting the favorable positive predictive power of the model and further supporting the use of LOXL2 and ETFβ as possible early predictive DCM biomarkers.
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Affiliation(s)
- Rabia Johnson
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa. .,Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa.
| | - Xolisa Nxele
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa.,Department of Biotechnology, University of Western Cape, Cape Town, South Africa
| | - Martin Cour
- Hospices Civils de Lyon, Hôpital Edouard Herriot, Service de Médecine Intensive-Réanimation, Lyon Cedex 03, France.,Hatter Institute for Cardiovascular Research in Africa (HICRA), Faculty of Health Sciences, University of Cape Town, Observatory, South Africa
| | - Nonhlakanipho Sangweni
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa.,Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
| | - Tracey Jooste
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa.,Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg, South Africa
| | - Nkanyiso Hadebe
- Hatter Institute for Cardiovascular Research in Africa (HICRA), Faculty of Health Sciences, University of Cape Town, Observatory, South Africa.,Department of Anaesthesia, Faculty of Health Sciences, University of Cape Town, Observatory, South Africa
| | - Ebrahim Samodien
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa
| | - Mongi Benjeddou
- Department of Biotechnology, University of Western Cape, Cape Town, South Africa
| | - Mikateko Mazino
- Biostatistics Research Unit, South African Medical Research Council (SAMRC), Cape Town, South Africa
| | - Johan Louw
- Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council (SAMRC), Tygerberg, 7505, South Africa.,Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, Richards Bay, South Africa
| | - Sandrine Lecour
- Hatter Institute for Cardiovascular Research in Africa (HICRA), Faculty of Health Sciences, University of Cape Town, Observatory, South Africa
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Bobenko A, Duvinage A, Mende M, Holzendorf V, Nolte K, Herrmann-Lingen C, Binder L, Düngen HD, Hasenfuss G, Pieske B, Wachter R, Edelmann F. Outcome assessment using estimation of left ventricular filling pressure in asymptomatic patients at risk for heart failure with preserved ejection fraction. IJC HEART & VASCULATURE 2020; 28:100525. [PMID: 32420447 PMCID: PMC7218096 DOI: 10.1016/j.ijcha.2020.100525] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2019] [Revised: 04/21/2020] [Accepted: 04/22/2020] [Indexed: 01/09/2023]
Abstract
AIMS High prevalence and lack of pharmacological treatment are making heart failure with preserved ejection fraction (HFpEF) a growing public health problem. No algorithm for the screening of asymptomatic patients with risk for HFpEF exists to date. We assessed whether HFA/ESC 2007 diagnostic criteria for HFpEF are helpful to investigate the cardiovascular outcome in asymptomatic patients. METHODS AND RESULTS We performed an analysis of the Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure (DIAST-CHF) that recruited patients with cardiovascular risk factors. All patients underwent a comprehensive diagnostic workup at baseline. Asymptomatic patients with preserved LVEF (>50%) were selected and classified according to HFA/ESC surrogate criteria for left ventricular elevated filling pressure (mean E/e' >15 or E/e' >8 and presence of either NT-proBNP > 220 ng/l, BNP > 200 ng/l or atrial fibrillation) into elevated filling pressure (FPe) or controls. Cardiovascular hospitalizations and all-cause death were assessed for both groups over a 10-year-follow-up.851 asymptomatic patients (age 65.5 ± 7.6 years, 44% female) were included in the analysis. FPe-patients were significantly older (p < 0.001), more often female (p = 0.003) and more often had a history of coronary artery disease, atrial fibrillation and renal dysfunction (p < 0.001, respectively) compared to controls. Incidence of death was significantly higher in the FPe group after a 10-year follow-up (p < 0.001), whereas cardiovascular hospitalization did not differ between groups. CONCLUSION Asymptomatic patients that fulfill HFA/ESC diagnostic criteria for HFpEF are at higher risk of symptomatic HFpEF and have a worse 10-year-outcome than those who do not fulfill criteria.
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Affiliation(s)
- Anna Bobenko
- Charité Universitätsmedizin Berlin, Department of Cardiology Internal Medicine and Cardiology, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
| | - André Duvinage
- Technische Universität München, Department of Prevention, Rehabilitation and Sports Medicine, Munich, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
| | - Meinhard Mende
- University of Leipzig, Clinical Trial Centre (KKS), Leipzig, Germany
| | - Volker Holzendorf
- University of Leipzig, Clinical Trial Centre (KKS), Leipzig, Germany
| | - Kathleen Nolte
- University of Göttingen Medical Centre, Clinic for Cardiology and Pneumology, Göttingen, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
| | - Christoph Herrmann-Lingen
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
- University of Göttingen Medical Centre, Department of Psychosomatic Medicine and Psychotherapy, Göttingen, Germany
| | - Lutz Binder
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
- University of Göttingen Medical Centre, Department of Clinical Chemistry, Göttingen, Germany
| | - Hans-Dirk Düngen
- Charité Universitätsmedizin Berlin, Department of Cardiology Internal Medicine and Cardiology, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Gerd Hasenfuss
- University of Göttingen Medical Centre, Clinic for Cardiology and Pneumology, Göttingen, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
| | - Burkert Pieske
- Charité Universitätsmedizin Berlin, Department of Cardiology Internal Medicine and Cardiology, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
- Deutsches Herzzentrum Berlin (DHZB), Department of Cardiology, Berlin, Germany
| | - Rolf Wachter
- University of Göttingen Medical Centre, Clinic for Cardiology and Pneumology, Göttingen, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
- Clinic and Policlinic for Cardiology, University Hospital Leipzig, Germany
| | - Frank Edelmann
- Charité Universitätsmedizin Berlin, Department of Cardiology Internal Medicine and Cardiology, Berlin, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
- Berlin Institute of Health (BIH), Berlin, Germany
- University of Göttingen Medical Centre, Clinic for Cardiology and Pneumology, Göttingen, Germany
- DZHK (German Centre for Cardiovascular Research), Partner Site Göttingen, Göttingen, Germany
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Zakria E, Elsayed NM, Ghanem NS, Youssif E, Kalaf MM, ElGabarty S. Assessment of left ventricular functions in patients with type 2 diabetes mellitus using tissue Doppler imaging and its correlation with a novel cardiac biomarker. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2017. [DOI: 10.4103/ejim.ejim_48_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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16
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Novo G, Cadeddu C, Sucato V, Pagliaro P, Romano S, Tocchetti CG, Zito C, Longobardo L, Nodari S, Penco M. Role of biomarkers in monitoring antiblastic cardiotoxicity. J Cardiovasc Med (Hagerstown) 2016; 17 Suppl 1:e27-e34. [PMID: 27183522 DOI: 10.2459/jcm.0000000000000379] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their sensitivity, specificity, and accuracy are not yet available, and many challenges, such as the optimal time of assessing, optimal schedule for evaluation, optimal cut-off point for positivity with the highest level of specificity, and optimal comparability of different assays for the measurements, remain unresolved. Given the importance of having a reliable and accurate tool for monitoring anticancer drug-induced CTX, this review will focus on the available data on the most effective and widely used biomarkers and the studies that are currently underway that aim to identify the effectiveness of new approaches in this therapeutic setting.
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Affiliation(s)
- Giuseppina Novo
- aDepartment of Internal Medicine and Specialties (DIBIMIS), Chair of Cardiology, University of Palermo, Palermo Italy bDepartment of Medical Sciences 'Mario Aresu', University of Cagliari, Cagliari Italy cDepartment of Clinical and Biological Sciences, University of Turin, Orbassano Italy dDepartment of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy eDepartment of Translational Medical Sciences, University of Napoli Federico II, Naples Italy fDepartment of Clinical and Experimental Medicine. Section of Cardiology, University of Messina, Messina Italy gDepartment of Clinical and Surgical Specialities, Radiological Sciences and Public Health University of Brescia, Brescia, Italy
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León LE, Rani S, Fernandez M, Larico M, Calligaris SD. Subclinical Detection of Diabetic Cardiomyopathy with MicroRNAs: Challenges and Perspectives. J Diabetes Res 2016; 2016:6143129. [PMID: 26770988 PMCID: PMC4684873 DOI: 10.1155/2016/6143129] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Revised: 07/17/2015] [Accepted: 07/26/2015] [Indexed: 02/08/2023] Open
Abstract
The prevalence of cardiac diabetic diseases has been increased around the world, being the most common cause of death and disability among diabetic patients. In particular, diabetic cardiomyopathy is characterized with a diastolic dysfunction and cardiac remodelling without signs of hypertension and coronary artery diseases. In an early stage, it is an asymptomatic disease; however, clinical studies demonstrate that diabetic myocardia are more vulnerable to injury derived by acute myocardial infarct and are the worst prognosis for rehabilitation. Currently, biochemical and imaging diagnostic methods are unable to detect subclinical manifestation of the disease (prior to diastolic dysfunction). In this review, we elaborately discuss the current scientific evidences to propose circulating microRNAs as promising biomarkers for early detection of diabetic cardiomyopathy and, then, to identify patients at high risk of diabetic cardiomyopathy development. Moreover, here we summarise the research strategies to identify miRNAs as potential biomarkers, present limitations, challenges, and future perspectives.
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Affiliation(s)
- Luis E. León
- Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, 7710162 Santiago, Chile
| | - Sweta Rani
- Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland
| | | | | | - Sebastián D. Calligaris
- Centro de Medicina Regenerativa, Facultad de Medicina, Clínica Alemana-Universidad del Desarrollo, 7710162 Santiago, Chile
- *Sebastián D. Calligaris:
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18
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Aloud BM, Raj P, O'Hara K, Shao Z, Yu L, Anderson HD, Netticadan T. Conjugated linoleic acid prevents high glucose-induced hypertrophy and contractile dysfunction in adult rat cardiomyocytes. Nutr Res 2015; 36:134-42. [PMID: 26826429 DOI: 10.1016/j.nutres.2015.11.012] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Revised: 11/13/2015] [Accepted: 11/18/2015] [Indexed: 01/22/2023]
Abstract
Diabetes mellitus is associated with increased risk and incidence of cardiovascular morbidity and mortality, independently of other risk factors typically associated with diabetes such as coronary artery disease and hypertension. This promotes the development of a distinct condition of the heart muscle known as diabetic cardiomyopathy. We have previously shown that conjugated linoleic acid (CLA) prevents endothelin-1-induced cardiomyocyte hypertrophy. However, the effects of CLA in preventing alterations in cardiomyocyte structure and function due to high glucose are unknown. We therefore hypothesized that CLA will have protective effects in an in vitro model of diabetic cardiomyopathy using adult rat cardiomyocytes exposed to high glucose. Our results demonstrate that subjecting adult rat cardiomyocytes to high glucose (25 mmol/L) for 24 hours significantly impaired the contractile function as evidenced by decreases in maximal velocity of shortening, peak shortening, and maximal velocity of relengthening. High glucose-induced contractile dysfunction was inhibited by pretreatment with CLA (30 μmol/L; 1 hour). In addition to contractile aberrations, exposing adult rat cardiomyocytes to high glucose for 48 hours induced cardiomyocyte hypertrophy. High glucose-induced cardiomyocyte hypertrophy was likewise prevented by CLA. The antihypertrophic effects of CLA were abolished when cardiomyocytes were pretreated with the pharmacologic inhibitor of peroxisome proliferator-activated receptor γ, GW9662 (1 μmol/L). In conclusion, our findings show that exposing cardiomyocytes to high glucose results in cardiomyocyte functional and structural abnormalities, and these abnormalities are prevented by pretreatment with CLA and mediated, in part, by peroxisome proliferator-activated receptor γ activation.
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Affiliation(s)
- Basma Milad Aloud
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6
| | - Pema Raj
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6
| | - Kimberley O'Hara
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6
| | - Zongjun Shao
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6
| | - Liping Yu
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6
| | - Hope D Anderson
- Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6; College of Pharmacy, University of Manitoba, Winnipeg, MB, Canada R3E 0T5.
| | - Thomas Netticadan
- Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, MB, Canada R3E 0J9; Canadian Centre for Agri-Food Research in Health and Medicine, Winnipeg, MB, Canada R2H 2A6.
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Ward ML, Crossman DJ. Mechanisms underlying the impaired contractility of diabetic cardiomyopathy. World J Cardiol 2014; 6:577-584. [PMID: 25068018 PMCID: PMC4110606 DOI: 10.4330/wjc.v6.i7.577] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2014] [Revised: 03/25/2014] [Accepted: 04/29/2014] [Indexed: 02/06/2023] Open
Abstract
Cardiac dysfunction is a well-known consequence of diabetes, with sustained hyperglycaemia leading to the development of a cardiomyopathy that is independent of cardiovascular disease or hypertension. Animal models of diabetes are commonly used to study the pathophysiology of diabetic cardiomyopathy, with the hope that increased knowledge will lead ultimately to better therapeutic strategies being developed. At physiological temperature, left ventricular trabeculae isolated from the streptozotocin rat model of type 1 diabetes showed decreased stress and prolonged relaxation, but with no evidence that decreased contractility was a result of altered myocardial Ca2+ handling. Although sarcoplasmic reticulum (SR) Ca2+ reuptake appeared slower in diabetic trabeculae, it was offset by an increase in action-potential duration, thereby maintaining SR Ca2+ content and favouring increased contraction force. Frequency analysis of t-tubule distribution by confocal imaging of ventricular tissue labeled with wheat germ agglutinin or ryanodine receptor antibodies showed a reduced T-power for diabetic tissue, but the differences were minor in comparison to other models of heart failure. The contractile dysfunction appeared to be the result of disrupted F-actin in conjunction with the increased type I collagen, with decreased myofilament Ca2+ sensitivity contributing to the slowed relaxation.
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Dominguez-Rodriguez A, Abreu-Gonzalez P, Avanzas P. Usefulness of growth differentiation factor-15 levels to predict diabetic cardiomyopathy in asymptomatic patients with type 2 diabetes mellitus. Am J Cardiol 2014; 114:890-4. [PMID: 25073564 DOI: 10.1016/j.amjcard.2014.06.020] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2014] [Revised: 06/12/2014] [Accepted: 06/12/2014] [Indexed: 12/15/2022]
Abstract
Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that increased in patients with established type 2 diabetes mellitus (DM). Diabetic cardiomyopathy (DC), defined as left ventricular diastolic dysfunction (LVDD) in patients with type 2 DM in the absence of arterial hypertension, heart disease, or other heart disease, was assessed by GDF-15 levels in type 2 DM patients with and without DC. A total of 213 DM outpatients had blood samples drawn and on the same day (basal) underwent echocardiography and treadmill exercise testing. Plasma GDF-15 concentrations were measured by an enzyme-linked immunosorbent assay (ELISA) at baseline. DC was diagnosed in the presence of LVDD, defined when early mitral valve flow velocity (E) and early diastolic lengthening velocity (E') ratio was E/E' ≥ 15. The prevalence of DC was 21.13%. GDF-15 levels were higher in patients with DC compared with those without DC (5,273 [8,708.4] vs 2,812.66 [7,662.1] pg/ml, respectively, p <0.001). We assessed predictors of DC using multivariate regression analysis. GDF-15 (odds ratio 9.9; 95% confidence interval [3.9 to 24.5], p <0.001) was the unique independent predictor of DC. The results of receiver operating characteristic curve show that the cut-off point of 3,812 pg/ml of GDF-15 was indicative for DC (AUC = 0.83, sensitivity = 82.2% and specificity = 70.2%, p <0.0001). In conclusion, GDF-15 represents a useful and novel tool to screen DC in patients with type 2 DM.
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Affiliation(s)
- Alberto Dominguez-Rodriguez
- Department of Cardiology, Hospital Universitario de Canarias, Tenerife, Spain; Instituto Universitario de Tecnología Biomédicas, Tenerife, Spain.
| | - Pedro Abreu-Gonzalez
- Instituto Universitario de Tecnología Biomédicas, Tenerife, Spain; Department of Physiology, University of La Laguna, Tenerife, Spain
| | - Pablo Avanzas
- Department of Cardiology, Hospital Universitario Central de Asturias, Oviedo, Spain
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Derosa G, Maffioli P. Assessment and management of left ventricular hypertrophy in Type 2 diabetes patients with high blood pressure. Expert Rev Cardiovasc Ther 2014; 11:719-28. [PMID: 23750681 DOI: 10.1586/erc.13.36] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Diabetes is associated with left ventricular hypertrophy (LVH). This article reviews the assessment and management of LVH in Type 2 diabetic patients and the available evidence on blood-pressure management in these patients in order to reduce LVH. The best treatment of LVH starts with early identification and rapid implementation of adequate treatment, especially in populations at higher risk. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors should be the first-line therapy, because they are proven to be the most effective in reducing LVH in Type 2 diabetic patients. In patients where angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors are contraindicated or not tolerated, calcium-channel blockers should be the second option.
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Affiliation(s)
- Giuseppe Derosa
- Department of Internal Medicine and Therapeutics, University of Pavia, Fondazione IRCCS Policlinico S. Matteo, P.le Golgi, 2-27100, Pavia, Italy.
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Pappachan JM, Varughese GI, Sriraman R, Arunagirinathan G. Diabetic cardiomyopathy: Pathophysiology, diagnostic evaluation and management. World J Diabetes 2013; 4:177-189. [PMID: 24147202 PMCID: PMC3797883 DOI: 10.4239/wjd.v4.i5.177] [Citation(s) in RCA: 124] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2013] [Revised: 07/02/2013] [Accepted: 08/17/2013] [Indexed: 02/05/2023] Open
Abstract
Diabetes affects every organ in the body and cardiovascular disease accounts for two-thirds of the mortality in the diabetic population. Diabetes-related heart disease occurs in the form of coronary artery disease (CAD), cardiac autonomic neuropathy or diabetic cardiomyopathy (DbCM). The prevalence of cardiac failure is high in the diabetic population and DbCM is a common but underestimated cause of heart failure in diabetes. The pathogenesis of diabetic cardiomyopathy is yet to be clearly defined. Hyperglycemia, dyslipidemia and inflammation are thought to play key roles in the generation of reactive oxygen or nitrogen species which are in turn implicated. The myocardial interstitium undergoes alterations resulting in abnormal contractile function noted in DbCM. In the early stages of the disease diastolic dysfunction is the only abnormality, but systolic dysfunction supervenes in the later stages with impaired left ventricular ejection fraction. Transmitral Doppler echocardiography is usually used to assess diastolic dysfunction, but tissue Doppler Imaging and Cardiac Magnetic Resonance Imaging are being increasingly used recently for early detection of DbCM. The management of DbCM involves improvement in lifestyle, control of glucose and lipid abnormalities, and treatment of hypertension and CAD, if present. The role of vasoactive drugs and antioxidants is being explored. This review discusses the pathophysiology, diagnostic evaluation and management options of DbCM.
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Vigili de Kreutzenberg S, Avogaro A. The limited clinical value of a specific diabetic cardiomyopathy. Nutr Metab Cardiovasc Dis 2013; 23:599-605. [PMID: 23725770 DOI: 10.1016/j.numecd.2013.03.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2012] [Revised: 01/29/2013] [Accepted: 03/30/2013] [Indexed: 02/07/2023]
Abstract
AIMS Diabetic patients show a higher likelihood of developing heart failure (HF), independently of the atherosclerotic process, than their nondiabetic counterparts. This suggests the presence of an intrinsic vulnerability of the heart in patients with diabetes mellitus. DATA SYNTHESIS A cardiomyopathy specific to the diabetic patient was first hypothesized by Rubler and co-workers, in 1972 and recognized as a nosologic entity by the World Health Organization (WHO) in 1995. All patients falling under Rubler's definition had ascertained diabetic glomerusclerosis, but were unaffected by major coronary artery disease (CAD). Notably, the mean plasma glucose in those patients was 417 ± 209 mg/dl. Since then, several studies conducted in both animals and in humans have focused on pathogenetic mechanisms, clinical manifestations, diagnostic as well as therapeutic approaches utilized for the treatment of diabetic cardiomyopathy (DCM). Despite the large body of literature available, the clinical entity and significance of this diabetic complication continue to be elusive. CONCLUSIONS In the present report, recent pathophysiological findings and diagnostic strategies to treat DCM are reviewed. Particular attention is dedicated to the clinical manifestation of DCM, that is to heart failure (HF), and to the implications of co-morbidities and metabolic control on its evolution.
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Nunes S, Soares E, Fernandes J, Viana S, Carvalho E, Pereira FC, Reis F. Early cardiac changes in a rat model of prediabetes: brain natriuretic peptide overexpression seems to be the best marker. Cardiovasc Diabetol 2013; 12:44. [PMID: 23497124 PMCID: PMC3599663 DOI: 10.1186/1475-2840-12-44] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Accepted: 03/04/2013] [Indexed: 12/15/2022] Open
Abstract
Background Diabetic cardiomyopathy (DCM) is defined as structural and functional changes in the myocardium due to metabolic and cellular abnormalities induced by diabetes mellitus (DM). The impact of prediabetic conditions on the cardiac tissue remains to be elucidated. The goal of this study was to elucidate whether cardiac dysfunction is already present in a state of prediabetes, in the presence of insulin resistance, and to unravel the underlying mechanisms, in a rat model without obesity and hypertension as confounding factors. Methods Two groups of 16-week-old Wistar rats were tested during a 9 week protocol: high sucrose (HSu) diet group (n = 7) – rats receiving 35% of sucrose in drinking water vs the vehicle control group (n = 7). The animal model was characterized in terms of body weight (BW) and the glycemic, insulinemic and lipidic profiles. The following parameters were assessed to evaluate possible early cardiac alterations and underlying mechanisms: blood pressure, heart rate, heart and left ventricle (LV) trophism indexes, as well as the serum and tissue protein and/or the mRNA expression of markers for fibrosis, hypertrophy, proliferation, apoptosis, angiogenesis, endothelial function, inflammation and oxidative stress. Results The HSu-treated rats presented normal fasting plasma glucose (FPG) but impaired glucose tolerance (IGT), accompanied by hyperinsulinemia and insulin resistance (P < 0.01), confirming this rat model as prediabetic. Furthermore, although hypertriglyceridemia (P < 0.05) was observed, obesity and hypertension were absent. Regarding the impact of the HSu diet on the cardiac tissue, our results indicated that 9 weeks of treatment might be associated with initial cardiac changes, as suggested by the increased LV weight/BW ratio (P < 0.01) and a remarkable brain natriuretic peptide (BNP) mRNA overexpression (P < 0.01), together with a marked trend for an upregulation of other important mediators of fibrosis, hypertrophy, angiogenesis and endothelial lesions, as well as oxidative stress. The inflammatory and apoptotic markers measured were unchanged. Conclusions This animal model of prediabetes/insulin resistance could be an important tool to evaluate the early cardiac impact of dysmetabolism (hyperinsulinemia and impaired glucose tolerance with fasting normoglycemia), without confounding factors such as obesity and hypertension. Left ventricle hypertrophy is already present and brain natriuretic peptide seems to be the best early marker for this condition.
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Affiliation(s)
- Sara Nunes
- Laboratory of Pharmacology and Experimental Therapeutics, IBILI, Faculty of Medicine, University of Coimbra, Coimbra, Portugal
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Abstract
Diabetes causes cardiomyopathy, both directly and by potentiating the effect of its common comorbidities, coronary artery disease and hypertension, on its development. With the common and growing prevalence of diabetes worldwide, diabetic cardiomyopathy is a significant public health problem. Recent research identifies both mitochondrial dysfunction and epigenetic effects as newly recognized factors in the complex pathogenesis of diabetic cardiomyopathy. Diagnostically, specialized echocardiography techniques, cardiac magnetic resonance imaging, and serologic biomarkers all appear to have promise in detecting the early stages of diabetic cardiomyopathy. Research into treatments includes both traditional diabetes and heart failure therapies, but also explores the potential of newer metabolic and anti-inflammatory agents. These recent insights provide important additions to our knowledge about diabetic cardiomyopathy, but much remains unknown.
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Çiftel S, Içağasıoğlu S, Yıldız G, Tekin G, Aydin H. Association of left ventricular diastolic dysfunction with elevated NT-proBNP in type 2 diabetes mellitus patients with preserved ejection fraction: the supplemantary role of tissue doppler imaging parameters and NT-proBNP levels. Diabetes Res Clin Pract 2012; 96:179-86. [PMID: 22240157 DOI: 10.1016/j.diabres.2011.12.021] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/07/2011] [Revised: 12/11/2011] [Accepted: 12/13/2011] [Indexed: 01/07/2023]
Abstract
BACKGROUND Early diagnosis of cardiovascular disease in diabetic patients may be important to introduce treatment early. Echocardiography is a method used to show the ventricular functions. A ventricular hormone, BNP is used to identify the changes in the ventricular function in early period. NT-proBNP which is a more stable compound with a longer half-life is used in measurement of BNP. METHODS Left ventricular diastolic dysfunction (LVDD) was detected and NT-proBNP levels were measured in forty-four asymptomatic patients with ages of 30-70 and type 2 DM and control group consisted of 40 healthy individuals from the same age group. RESULTS NT-proBNP levels were found as 566.7 ± 738.5 pg/ml in the diabetics with LVDD detected, 166.3 ± 137.1 pg/ml in the diabetics without LVDD and 134.5 ± 77.2 pg/ml in the control group. Levels of NT-proBNP were significantly higher in the group with left ventricular diastolic dysfunction (p<0.05). However, when the levels of NT-proBNP in the diabetic patients without LVDD were compared with the controls, the difference was not significant (p>0.05). NT-proBNP levels were found significantly higher in LVDD group compared to the controls without a difference between the ejection fractions (p<0.05). CONCLUSION High levels of NT-proBNP was correlated tissue Doppler echocardiography findings in type 2 DM patients with preserved ejection fraction.
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Affiliation(s)
- Sedat Çiftel
- Department of Internal Medicine, Cumhuriyet University Faculty of Medicine, 58140 Sivas, Turkey
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Reinhard H, Hansen PR, Wiinberg N, Kjær A, Petersen CL, Winther K, Parving HH, Rossing P, Jacobsen PK. NT-proBNP, echocardiographic abnormalities and subclinical coronary artery disease in high risk type 2 diabetic patients. Cardiovasc Diabetol 2012; 11:19. [PMID: 22390472 PMCID: PMC3310741 DOI: 10.1186/1475-2840-11-19] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Accepted: 03/05/2012] [Indexed: 01/20/2023] Open
Abstract
Background Intensive multifactorial treatment aimed at prevention of cardiovascular (CV) disease may reduce left ventricular (LV) echocardiographic abnormalities in diabetic subjects. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the association between P-NT-proBNP and the putative residual abnormalities in such patients are not well described. This study examined echocardiographic measurements of LV hypertrophy, atrial dilatation and LV dysfunction and their relation to P-NT-proBNP levels or subclinical coronary artery disease (CAD) in type 2 diabetic patients with microalbuminuria receiving intensive multifactorial treatment. Methods Echocardiography including tissue Doppler imaging and P-NT-proBNP measurements were performed in 200 patients without prior CAD. Patients with P-NT-proBNP > 45.2 ng/L and/or coronary calcium score ≥ 400 were stratified as high risk patients for CAD(n = 133) and examined for significant CAD by myocardial perfusion imaging and/or CT-angiography and/or coronary angiography. Results LV mass index was 41.2 ± 10.9 g/m2.7 and 48 (24%) patients had LV hypertrophy. LA and RA dilatation were found in 54(27%) and 45(23%) patients, respectively, and LV diastolic dysfunction was found in 109(55%) patients. Patients with increased P-NT-proBNP levels did not have more major echocardiographic abnormalities. In 70(53%) of 133 high risk patients significant CAD was demonstrated and patients with LV hypertrophy had increased risk of significant CAD(adjusted odd ratio[CI] was 4.53[1.14-18.06]). Conclusion Among asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment, P-NT-proBNP levels is not associated with echocardiographic abnormalities. LV diastolic dysfunction was frequently observed, whereas LV hypertrophy was less frequent but associated with significant CAD.
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Affiliation(s)
- Henrik Reinhard
- Steno Diabetes Center, Niels Steensenvej 1, DK-2820 Gentofte, Denmark.
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Reinhard H, Wiinberg N, Hansen PR, Kjær A, Petersen CL, Winther K, Parving HH, Rossing P, Jacobsen PK. NT-proBNP levels, atherosclerosis and vascular function in asymptomatic type 2 diabetic patients with microalbuminuria: peripheral reactive hyperaemia index but not NT-proBNP is an independent predictor of coronary atherosclerosis. Cardiovasc Diabetol 2011; 10:71. [PMID: 21812947 PMCID: PMC3164620 DOI: 10.1186/1475-2840-10-71] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2011] [Accepted: 08/03/2011] [Indexed: 12/13/2022] Open
Abstract
UNLABELLED Intensive multifactorial treatment aimed at cardiovascular (CV) risk factor reduction in type 2 diabetic patients with microalbuminuria can diminish fatal and non-fatal CV. Plasma N-terminal (NT)-proBNP predicts CV mortality in diabetic patients but the utility of P-NT-proBNP in screening for atherosclerosis is unclear. We examined the interrelationship between P-NT-proBNP, presence of atherosclerosis and/or vascular dysfunction in the coronary, carotid and peripheral arteries in asymptomatic type 2 diabetic patients with microalbuminuria that received intensive multifactorial treatment. METHODS AND RESULTS P-NT-proBNP was measured in 200 asymptomatic type 2 patients without known cardiac disease that received intensive multifactorial treatment for CV risk reduction. Patients were examined for coronary, carotid and peripheral atherosclerosis, as defined by coronary calcium score≥400, carotid intima-media thickness (CIMT)>0.90 mm, ankle-brachial index<0.90, and/or toe-brachial index<0.64, respectively. Carotid artery compliance was also determined and the reactive hyperaemia index (RHI) measured by peripheral artery tonometry was used as a surrogate for endothelial function.P-NT-proBNP was associated with atherosclerosis in the unadjusted analysis, but not after adjustment for conventional risk factors. P-NT-proBNP was not associated with vascular dysfunction. The prevalence of atherosclerosis in the coronary, carotid and peripheral arteries was 35%, 10% and 21% of all patients, respectively. In total 49% had atherosclerosis in one territory and 15.6% and 1.0% in two and three territories. Low RHI was an independent predictor of coronary atherosclerosis (odds ratio [CI], 2.60 [1.15-5.88] and systolic blood pressure was the only independent determinant of CIMT (0.02 mm increase in CIMT per 10 mmHg increase in systolic blood pressure [p=0.003]). CONCLUSIONS Half of asymptomatic patients with type 2 diabetes mellitus and microalbuminuria had significant atherosclerosis in at least one vascular territory despite receiving intensive multifactorial treatment for CV risk reduction. Coronary atherosclerosis was most prevalent, whereas carotid disease was more rarely observed. RHI but not plasma NT-proBNP was predictive of coronary atherosclerosis.
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Somaratne JB, Whalley GA, Poppe KK, ter Bals MM, Wadams G, Pearl A, Bagg W, Doughty RN. Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community. Cardiovasc Diabetol 2011; 10:29. [PMID: 21492425 PMCID: PMC3094210 DOI: 10.1186/1475-2840-10-29] [Citation(s) in RCA: 50] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2010] [Accepted: 04/14/2011] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Left ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes. METHODS Prospective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated. RESULTS 294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA 1c 7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68. CONCLUSIONS LVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.
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Affiliation(s)
- Jithendra B Somaratne
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Gillian A Whalley
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Katrina K Poppe
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Mariska M ter Bals
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Gina Wadams
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Ann Pearl
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Warwick Bagg
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
| | - Rob N Doughty
- Cardiovascular Research Group, Department of Medicine, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland 1142, New Zealand
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Edelmann F, Wachter R, Düngen HD, Störk S, Richter A, Stahrenberg R, Neumann T, Lüers C, Angermann CE, Mehrhof F, Gelbrich G, Pieske B. Heart failure therapy in diabetic patients-comparison with the recent ESC/EASD guideline. Cardiovasc Diabetol 2011; 10:15. [PMID: 21303531 PMCID: PMC3045292 DOI: 10.1186/1475-2840-10-15] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2010] [Accepted: 02/08/2011] [Indexed: 01/20/2023] Open
Abstract
Background To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function. Methods 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes. Results The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function. Conclusions Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.
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Affiliation(s)
- Frank Edelmann
- Department of Cardiology and Pneumology, University of Göttingen, Göttingen, Germany.
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