Male sex adversely affects the phenotypic expression of diabetic heart disease

Objectives: We aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with type 2 diabetes (T2D). Background: T2D is associated with an increased risk of heart failure (HF) and cardiovascular mortality. A large-scale meta-analysis on HF found that diabetes was more frequent in women than men, and diabetes appeared to have attenuated the otherwise protective effect of female sex on progression of cardiomyopathy. The exact underlying mechanisms for this remain unclear. Methods:Sixty-two male (mean age 44±8years, BMI 33±5kg/m2, mean HBA1c of 7.8±1.8%), sixty-seven female (44±10years, BMI 35±6kg/m2, HBA1c 7.6±1.2%) T2D patients on oral glucose lowering treatment; sixteen male (48±17years, BMI 25±3kg/m2) and fourteen female (50±10years, BMI 25±4kg/m2) controls were recruited. Left ventricular (LV) volumes, mass, function, and deformation, and left atrial (LA) volumes and function were assessed using CMR imaging. Results:Participants in all groups were of similar age; and there were no significant differences in BP, diabetes duration, or metabolic profile between the two diabetes groups. Concentric remodeling was present in both sexes (P<0.0001), with greater degree of concentric hypertrophy in males (12%, P=0.0015). Biplane LA ejection fraction (LAEF) (P=0.038), peak systolic circumferential strain (P<0.0001) and diastolic strain rates (P=0.001) were significantly reduced in men compared to women with T2D. There were no significant differences in biplane LAEF, peak systolic circumferential strain and diastolic strain rates in women with T2D compared to female controls. While in women with T2D glycaemic control was linked to LV contractile function, there was no such relationship in men with T2D.Conclusions:Male sex adversely affects the phenotypic expression of diabetic heart disease. The striking differences in the cardiac phenotype between male and female patients with T2D promote awareness of gender-specific risk factors in search of treatment and prevention of diabetes-associated heart failure.