Key result
Type-2 diabetes induces LAA structural remodeling independent of AF, driven by myocardial glycogen accumulation.
Why the study?
Remodeling of the left atrial appendage in diabetic patients has been described with atrial fibrillation, but whether it occurs independently of atrial fibrillation is unknown.
Does diabetes induce remodeling of the left atrial appendage independently of atrial fibrillation in a rodent model?
Does diabetes induce remodeling of the left atrial appendage independently of atrial fibrillation in a rodent model?
Diabetes induces structural and functional remodeling of the left atrial appendage and left atrium independently of atrial fibrillation in a rodent model, which is associated with myocardial accumulation of glycogen granules.
Hypothesis-generating for diabetes-related atrial remodeling; leaves open translation to human LAA changes independent of AF.
BACKGROUND: Diabetic patients have an increased predisposition to thromboembolic events, in most cases originating from thrombi in the left atrial appendage (LAA). Remodeling of the LAA, which predisposes to thrombi formation, has been previously described in diabetic patients with atrial fibrillation, but whether remodeling of the LAA occurs in diabetics also in the absence of atrial fibrillation is unknown. To investigate the contribution of diabetes, as opposed to atrial fibrillation, to remodeling of the LAA, we went from humans to the animal model. METHODS: We studied by echocardiography the structure and function of the heart over multiple time points during the evolution of diabetes in the Cohen diabetic sensitive rat (CDs/y) provided diabetogenic diet over a period of 4 months; CDs/y provided regular diet and the Cohen diabetic resistant (CDr/y), which do not develop diabetes, served as controls. All animals were in sinus rhythm throughout the study period. RESULTS: Compared to controls, CDs/y developed during the evolution of diabetes a greater heart mass, larger left atrial diameter, wider LAA orifice, increased LAA depth, greater end-diastolic and end-systolic diameter, and lower E/A ratio-all indicative of remodeling of the LAA and left atrium (LA), as well as the development of left ventricular diastolic dysfunction. To investigate the pathophysiology involved, we studied the histology of the hearts at the end of the study. We found in diabetic CDs/y, but not in any of the other groups, abundance of glycogen granules in the atrial appendages , atria and ventricles, which may be of significance as glycogen granules have previously been associated with cell and organ dysfunction in the diabetic heart. CONCLUSIONS: We conclude that our rodent model of diabetes, which was in sinus rhythm, reproduced structural and functional alterations previously observed in hearts of human diabetics with atrial fibrillation. Remodeling of the LAA and of the LA in our model was unrelated to atrial fibrillation and associated with accumulation of glycogen granules. We suggest that myocardial accumulation of glycogen granules is related to the development of diabetes and may play a pathophysiological role in remodeling of the LAA and LA, which predisposes to atrial fibrillation, thromboembolic events and left ventricular diastolic dysfunction in the diabetic heart.
No takes yet. Share an insight, caveat, or question.
Yosefy et al. (2021) studied Type-2 diabetes (n=42). Diabetogenic diet (Type-2 diabetes induction) vs. Regular diet and diabetes-resistant strain was evaluated on Left atrial appendage (LAA) remodeling (orifice diameter and depth). In a rodent model of type-2 diabetes in normal sinus rhythm, diabetes induced significant structural remodeling of the left atrial appendage independently of atrial fibrillation, associated with myocardial glycogen accumulation.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: