Serum Annexin A2 concentrations are increased in patients with diabetic cardiomyopathy and are linked to cardiac dysfunctions

Abstract

Background: Diabetic cardiomyopathy (DbCM) is defined as the existence of abnormal myocardial structure and functions in the absence of other cardiac diseases, such as coronary artery disease, hypertension, and significant valvular disease, in individuals with diabetes. Although abundant epidemic evidence demonstrates that diabetes is independently associated with the risk of developing heart failure, DbCM is not normally diagnosed in clinical practices due to its exclusive diagnosis, and no diagnostic biomarker was applied in a clinical test.

Methods: To detect the concentrations of serum Annexin A2 in non-diabetic subjects, type 2 diabetic (T2DM) patients with or without DbCM, and analyzed its relationship to parameters of cardiac functions, glucose, lipid metabolism, and renal functions. 266 eligible participants were included and were divided into 3 groups including non-diabetic subjects (NGR), T2DM patients without DbCM (T2DM group), and the DbCM group. Echocardiography, coronary computed tomography angiography, electrocardiogram, blood pressure, thyroid function, and clinical and other biochemical parameters were measured in all participants.

Results: Serum Annexin A2 concentrations were higher in DbCM (P < 0.05) and T2DM (P < 0.05) groups compared with the NGR group, especially in DbCM patients. Correlation analysis showed that serum Annexin A2 levels were negatively associated with left ventricular (LV) ejection fraction (EF), LV fractional shortening (FS), the ratio of early (E-wave) and late (A-wave) LV diastolic filling velocities (E/A ratio), and estimated glomerular filtration rate (eGFR), and were positively correlated with age, blood urea nitrogen (BUN) and creatinine (Cr) (all P < 0.05). Multiple logistical regression analyses revealed that serum in both the second and the third tertiles of Annexin A2 concentration were significantly associated with DbCM. E/A ratio is the independent factor for Annexin A2 concentration when adjusted for LV FS%, BUN, and Cr.

Conclusions: Circulating Annexin A2 concentrations might be induced in DbCM patients and were negatively associated with cardiac systolic and diastolic functions, which suggested it might be a predictor of early diagnosis in DbCM and might be a potential therapeutic target for DbCM.

Keywords: Annexin A2; Cardiac function; Diabetes; Diabetic cardiomyopathy.