The current state of preclinical modeling of human diabetic cardiomyopathy using rodents

The prevalence of diabetic cardiomyopathy (DCM), a specific cardiovascular complication of diabetes mellitus, has recently increased. Its pathogenesis is not fully understood, and no consensus regarding therapeutic options has been reached. Experimental studies on rodents are expected to yield further data at the preclinical stage. The present paper describes and quantitatively compares the experimental protocols intended to mimic human DCM. Experimental articles (conducted between 1990 and 2022) were identified from online electronic databases according to the PRISMA Protocol. The Cochrane Q-test was used to estimate study heterogeneity; the quality of each individual study was assessed using SYRCLE's risk of bias tool for animal studies. Sensitivity analysis was performed according to the leave-one-out method. Publication bias across studies was assessed using Egger's weighted regression and Duval and Tweedie 'trim and fill' method. A wide spectrum of protocols - from 651 papers, was examined (type 1 or 2 diabetes mellitus, as well as obesity models). They were found to vary in their presentation of DCM according to a variety of hemodynamic, echocardiographic, histopathologic and metabolic parameters. Particular attention was paid to comorbid conditions, and cardiac performance featured as systolic, diastolic dysfunction, or refractory heart failure. The majority of models displayed diastolic dysfunction, as well as myocardial fibrosis and left ventricle hypertrophy, which mimics early stage DCM. Unlike in humans, animal DCM rarely progressed to the symptomatic heart failure with reduced ejection fraction (HFrEF). The ability of individual procedures to reflect refractory heart failure or biventricular dysfunction - in the end-stage DCM has remained unclear.