Sex-related differences of diabetic cardiomyopathy

Aims: It is well known that patients with type 2 diabetes (T2D) have an increased risk of both ischemic and non-ischemic heart disease. We studied sex differences in the microvascular function and myocardial extracellular fibrosis that underlie cardiac dysfunction. Methods: In a cross-sectional echocardiography and cardiovascular magnetic resonance imaging study, myocardial extracellular volume fraction (ECV), myocardial blood flow at rest (MBF_rest) and during adenosine-induced stress (MBF_stress), and the myocardial perfusion reserve (MPR) were determined in 221 patients with T2D without ischemic heart disease and 25 age-matched controls. We investigated sex-related differences in MBF, MPR, ECV, and diastolic and systolic function. Results: Both in unadjusted analyses and after multiple linear regression analyses adjusted for known confounders, women with T2D had higher MBF_rest, MBF_stress, and ECV than men. The differences in microvascular function resulted in T2D men and women both having lower MPR compared to healthy controls, but the underlying causes differed. Female sex associated with lower lateral e’ and higher E/e’ independently of MBF_stress and ECV. Conclusions: These findings highlight distinct sex-specific mechanisms of microvascular dysfunction and myocardial remodeling in T2D. Recognizing these differences may be critical for improving risk stratification and guiding targeted preventive strategies in diabetic cardiomyopathy.