Male sex adversely affects the phenotypic expression of diabetic heart disease
Authors: Athithan Lavanya , Chowdhary Amrit , Swarbrick Daniel , Gulsin Gaurav S. , Singh Anvesha , Jex Nicholas , Jain Manali , Khan Jamal N. , Graham-Brown Matthew P. M. , Wormleighton Joanne V. , Parke Kelly S. , Davies Melanie J. , Karamitsos Theodoros , Clarke Kieran , Neubauer Stefan , Levelt Eylem , McCann Gerry P. 
Published: May 2020

Background: Type 2 diabetes (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. Here, we aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. Methods: A total of 62 male [mean age 44 ± 8 years, body mass index (BMI) 33 ± 5 kg/m2, mean HBA1c of 7.8 ± 1.8%] and 67 female (44 ± 10 years, BMI 35 ± 6 kg/m2, HBA1c 7.6 ± 1.2%) T2D patients on oral glucose-lowering treatment, and 16 male (48 ± 17 years, BMI 25 ± 3 kg/m2) and 14 female (50 ± 10 years, BMI 25 ± 4 kg/m2) controls were recruited. Left ventricular (LV) volumes, mass, function and deformation, and left atrial (LA) volumes and function were assessed using cardiac magnetic resonance imaging (CMR). Results: Participants in all groups were of similar age, and there were no significant differences in blood pressure (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 with women with T2D. There were no significant differences in biplane LAEF, peak systolic circumferential strain and diastolic strain rates in women with T2D compared with female controls. Whereas in women with T2D, glycaemic control was linked to LV contractile function, there was no such relationship in men with T2D. Conclusion: 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 HF. Condensed Abstract: We aimed to determine the effect of sex on the phenotypic expression of diabetic heart disease in patients with T2D. While our findings support the notion that in T2D, male sex adversely affects the phenotypic expression of diabetic heart disease, this is in apparent conflict with the previous large-scale study showing diabetes attenuates the otherwise protective effect of female sex on progression of cardiomyopathy. Further longitudinal studies looking at gender differences in clinical outcomes in T2D patients are needed. These sex-related differences promote awareness of sex-specific risk factors in search of treatment and prevention of diabetes-associated HF.