Amy S Shah1, Sakthivel Sadayappan2, Elaine M Urbina3. 1. Department of Pediatrics, Division of Endocrinology, Cincinnati Children's Hospital Medical Center and The University of Cincinnati, 3333 Burnet Ave., Cincinnati, OH, 45229, USA. amy.shah@cchmc.org. 2. Division of Cardiovascular Health and Disease, Department of Internal Medicine, Heart, Lung and Vascular Institute, University of Cincinnati, Cincinnati, OH, USA. 3. Department of Pediatrics, The Heart Institute, Cincinnati Children's Hospital Medical Center and The University of Cincinnati, 3333 Burnet Ave., Cincinnati, OH, 45229, USA.
Abstract
PURPOSE OF THE REVIEW: Obesity and type 2 diabetes (T2D) with onset in youth are emerging public health concerns. Youth with obesity and T2D are at risk for the development of heart failure with preserved ejection fraction (HFpEF) due to diabetes-related cardiomyopathy with evidence of precursor stages, namely diastolic dysfunction, present in youth. We review the literature regarding diastolic dysfunction in youth with obesity and T2D; discuss the potential mechanisms including the role of lipids, contractile proteins and their post-translational modifications, and conclude with studies to guide future treatments. RECENT FINDINGS: The diabetes milieu namely hyperglycemia, hyperinsulinemia, and lipotoxicity favor development of diastolic dysfunction and HFpEF. Recent studies show HFpEF is associated with slow left ventricular relaxation and sarcomere stiffness induced by reduced calcium (Ca2+) and β-adrenergic responses. There are currently no effective therapies available for treating HFpEF. Targeting the sarcomere is an area of ongoing research.
PURPOSE OF THE REVIEW: Obesity and type 2 diabetes (T2D) with onset in youth are emerging public health concerns. Youth with obesity and T2D are at risk for the development of heart failure with preserved ejection fraction (HFpEF) due to diabetes-related cardiomyopathy with evidence of precursor stages, namely diastolic dysfunction, present in youth. We review the literature regarding diastolic dysfunction in youth with obesity and T2D; discuss the potential mechanisms including the role of lipids, contractile proteins and their post-translational modifications, and conclude with studies to guide future treatments. RECENT FINDINGS: The diabetes milieu namely hyperglycemia, hyperinsulinemia, and lipotoxicity favor development of diastolic dysfunction and HFpEF. Recent studies show HFpEF is associated with slow left ventricular relaxation and sarcomere stiffness induced by reduced calcium (Ca2+) and β-adrenergic responses. There are currently no effective therapies available for treating HFpEF. Targeting the sarcomere is an area of ongoing research.
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