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      Diabetic Cardiomyopathy and Ischemic Heart Disease: Prevention and Therapy by Exercise and Conditioning

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          Abstract

          Metabolic syndrome, diabetes, and ischemic heart disease are among the leading causes of death and disability in Western countries. Diabetic cardiomyopathy is responsible for the most severe signs and symptoms. An important strategy for reducing the incidence of cardiovascular disease is regular exercise. Remote ischemic conditioning has some similarity with exercise and can be induced by short periods of ischemia and reperfusion of a limb, and it can be performed in people who cannot exercise. There is abundant evidence that exercise is beneficial in diabetes and ischemic heart disease, but there is a need to elucidate the specific cardiovascular effects of emerging and unconventional forms of exercise in people with diabetes. In addition, remote ischemic conditioning may be considered among the options to induce beneficial effects in these patients. The characteristics and interactions of diabetes and ischemic heart disease, and the known effects of exercise and remote ischemic conditioning in the presence of metabolic syndrome and diabetes, are analyzed in this brief review.

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          Most cited references159

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          The metabolic syndrome—a new worldwide definition

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            Physical Activity/Exercise and Diabetes: A Position Statement of the American Diabetes Association.

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              Diabetic Cardiomyopathy

              Heart failure and related morbidity and mortality are increasing at an alarming rate, in large part, because of increases in aging, obesity, and diabetes mellitus. The clinical outcomes associated with heart failure are considerably worse for patients with diabetes mellitus than for those without diabetes mellitus. In people with diabetes mellitus, the presence of myocardial dysfunction in the absence of overt clinical coronary artery disease, valvular disease, and other conventional cardiovascular risk factors, such as hypertension and dyslipidemia, has led to the descriptive terminology, diabetic cardiomyopathy. The prevalence of diabetic cardiomyopathy is increasing in parallel with the increase in diabetes mellitus. Diabetic cardiomyopathy is initially characterized by myocardial fibrosis, dysfunctional remodeling, and associated diastolic dysfunction, later by systolic dysfunction, and eventually by clinical heart failure. Impaired cardiac insulin metabolic signaling, mitochondrial dysfunction, increases in oxidative stress, reduced nitric oxide bioavailability, elevations in advanced glycation end products and collagen-based cardiomyocyte and extracellular matrix stiffness, impaired mitochondrial and cardiomyocyte calcium handling, inflammation, renin-angiotensin-aldosterone system activation, cardiac autonomic neuropathy, endoplasmic reticulum stress, microvascular dysfunction, and a myriad of cardiac metabolic abnormalities have all been implicated in the development and progression of diabetic cardiomyopathy. Molecular mechanisms linked to the underlying pathophysiological changes include abnormalities in AMP-activated protein kinase, peroxisome proliferator-activated receptors, O-linked N-acetylglucosamine, protein kinase C, microRNA, and exosome pathways. The aim of this review is to provide a contemporary view of these instigators of diabetic cardiomyopathy, as well as mechanistically based strategies for the prevention and treatment of diabetic cardiomyopathy.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                21 April 2020
                April 2020
                : 21
                : 8
                : 2896
                Affiliations
                [1 ]Department of Medical Sciences and Public Health, University of Cagliari, 09124 Cagliari, Italy; crisafulli@ 123456tiscali.it (A.C.); silvy_rob@ 123456yahoo.it (S.R.); giuseppemercuro@ 123456gmail.com (G.M.)
                [2 ]Department of Clinical and Biological Science, University of Torino, 10043 Obassano (TO), Italy; manuela.aragno@ 123456unito.it (M.A.); claudia.penna@ 123456unito.it (C.P.)
                [3 ]Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy; lucia.cugusi@ 123456uniss.it
                [4 ]School of Biology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece; lazou@ 123456bio.auth.gr
                [5 ]Pole of Cardiovascular Research, IREC Institute, UCLouvain, 1200 Brussels, Belgium; christophe.beauloye@ 123456uclouvain.be (C.B.); luc.bertrand@ 123456uclouvain.be (L.B.)
                [6 ]Division of Cardiology, Cliniques Universitaires Saint-Luc, 1200 Brussels, Belgium
                [7 ]Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore, Singapore 169857, Singapore; d.hausenloy@ 123456ucl.ac.uk
                [8 ]National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore 169609, Singapore
                [9 ]Yong Loo Lin School of Medicine, National University Singapore, Singapore 119228, Singapore
                [10 ]The Hatter Cardiovascular Institute, University College London, London WC1E 6HX, UK
                [11 ]Cardiovascular Research Center, College of Medical and Health Sciences, Asia University, Taichung 41354, Taiwan
                Author notes
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-4386-1383
                https://orcid.org/0000-0001-7650-0640
                https://orcid.org/0000-0002-7889-9648
                https://orcid.org/0000-0003-0655-7099
                https://orcid.org/0000-0003-0729-4956
                https://orcid.org/0000-0002-0453-5235
                Article
                ijms-21-02896
                10.3390/ijms21082896
                7215312
                32326182
                4b8eebd2-c577-43cf-936e-837cbbfcb4e9
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 16 March 2020
                : 18 April 2020
                Categories
                Review

                Molecular biology
                diabetic cardiomyopathy,hyperglycemia,ischemia/reperfusion injury,metabolism,mitochondria,remote conditioning,exercise

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