![]() Therefore, the cardiovascular (CV) implications and the effects of antidiabetic therapy on CV risk factors have been a key aspect for clinicians in the last decades, with the primary aim to prevent death and morbidity due to CV and microvascular diseases. Rather than an adverse effect of hyperglycemia on the heart, this relationship seems to be attributable more to hyperinsulinemia ( 2– 4). ![]() Also, HF is highly prevalent in patients with diabetes (25% in chronic HF and up to 40% in acute HF), who are at a higher risk (up to 2-fold in men and 5-fold in women) of developing HF than patients without diabetes. According to epidemiologic analyses, patients with HF have an increased risk of developing T2DM compared to the general population. The pathophysiologic aspects of both pathologies are closely related to the underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations ( 1). Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, insulin resistance, dyslipidemia, inflammation, and thrombophilia. At The Bedside Heart Failure and Diabetes: Pathophysiology and Epidemiology In this review, we summarize clinical trials, studies on human cells, and animal models, that provide a vast array of data in support of repurposing this class of antidiabetic drugs. The restoration of cardiac Na + levels with consequent positive effects on Ca 2+ handling can directly translate into improved contractility and relaxation of cardiomyocytes and have antiarrhythmic effects. At the moment, intracellular sodium level reduction is the most explored mechanism of direct cardiac effects of SGLT2 inhibitors that mediate the benefits in heart failure in addition to glucose excretion and diuresis. Moreover, the research focus was widened toward cellular targets other than cardiomyocytes. In search of the possible underlying mechanisms, a research campaign has been launched proposing varied mechanisms of action that include intracellular ion homeostasis, autophagy, cell death, and inflammatory processes. Cardiovascular benefits of sodium-glucose cotransporter 2 (SGLT2) inhibitors observed in diabetic and non-diabetic patients are also related to their cardiac-specific, SGLT-independent mechanisms, in addition to the metabolic and hemodynamic effects. ![]() Type 2 diabetes mellitus (T2DM) and heart failure (HF) are multifactorial diseases sharing common risk factors, such as obesity, hyperinsulinemia, and inflammation, with underlying mechanisms including endothelial dysfunction, inflammation, oxidative stress, and metabolic alterations. 3Department of Experimental and Clinical Medicine, University “Magna Graecia” of Catanzaro, Catanzaro, Italy.2Department of Medical and Surgical Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, Italy.1Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Naples, Italy.Donato Cappetta 1 †, Antonella De Angelis 1 †, Gabriella Bellocchio 1, Marialucia Telesca 1, Eleonora Cianflone 2, Daniele Torella 3, Francesco Rossi 1, Konrad Urbanek 3 ‡ and Liberato Berrino 1 * ‡
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