Value of circulating miRNA-21 in the diagnosis of subclinical diabetic cardiomyopathy

Diabetic cardiomyopathy (DCM) is a type of cardiac dysfunction that affects approximately 12% of diabetic patients, ultimately leading to heart failure or even death. However, there is currently no efficient or specific biomarker for DCM diagnosis. A total of 266 subjects with type II diabetes (T2DM) were enrolled in this study and were divided into the T2DM with cardiac dysfunction (DCM) group and T2DM without cardiac dysfunction (non-DCM) group. The diagnostic efficacy of miR-21 was determined and compared with that of serum hemoglobin A1c% (HbA1c%). Db/db mice and H9c2 cells stimulated with high glucose (HG)/high fatty acid (PA) were used as in vivo and in vitro models of DCM, respectively. Through echocardiography and gated-myocardial perfusion imaging (gated-MPI), 49 patients were selected to be enrolled in the DCM group, with 49 matched controls in the non-DCM group. The circulating miR-21 levels were significantly decreased in the DCM group compared to the non-DCM group (P < 0.001). The diagnostic efficiency of miR-21 (area under the curve AUC = 0.899) was higher than that of other parameters, including HbA1c%. Moreover, when miR-21 was combined with the duration of diabetes, HbA1c%, and lipid profiles, the AUC was the highest (AUC = 0.939) and had the highest diagnostic efficiency. Furthermore, overexpression of miR-21 improved the impaired mitochondrial biogenesis and decreased the cardiomyocyte apoptosis induced by HG/PA, while inhibition of miR-21 exerted the opposite effects. Our findings identify circulating miR-21 as a novel biomarker in the diagnosis of DCM and provide an underlying mechanism for miRNA-based therapy for the treatment of DCM. The study was approved by the Ethics Committee of the Third Affiliated Hospital of Soochow University and has been registered in the Chinese Clinical Trial Registry (ChiCTR1900027080).