Usefulness of Growth Differentiation Factor-15 Levels to Predict Diabetic Cardiomyopathy in Asymptomatic Patients With Type 2 Diabetes Mellitus

Abstract

Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine that increased in patients with established type 2 diabetes mellitus (DM). Diabetic cardiomyopathy (DC), defined as left ventricular diastolic dysfunction (LVDD) in patients with type 2 DM in the absence of arterial hypertension, heart disease, or other heart disease, was assessed by GDF-15 levels in type 2 DM patients with and without DC. A total of 213 DM outpatients had blood samples drawn and on the same day (basal) underwent echocardiography and treadmill exercise testing. Plasma GDF-15 concentrations were measured by an enzyme-linked immunosorbent assay (ELISA) at baseline. DC was diagnosed in the presence of LVDD, defined when early mitral valve flow velocity (E) and early diastolic lengthening velocity (E') ratio was E/E' ≥ 15. The prevalence of DC was 21.13%. GDF-15 levels were higher in patients with DC compared with those without DC (5,273 [8,708.4] vs 2,812.66 [7,662.1] pg/ml, respectively, p <0.001). We assessed predictors of DC using multivariate regression analysis. GDF-15 (odds ratio 9.9; 95% confidence interval [3.9 to 24.5], p <0.001) was the unique independent predictor of DC. The results of receiver operating characteristic curve show that the cut-off point of 3,812 pg/ml of GDF-15 was indicative for DC (AUC = 0.83, sensitivity = 82.2% and specificity = 70.2%, p <0.0001). In conclusion, GDF-15 represents a useful and novel tool to screen DC in patients with type 2 DM.