Abstract
Type 2 diabetes is a chronic disease associated with micro- and macro-vascular complications, including myocardial ischemia, and also with a specific and intrinsic cardiac dysfunction called diabetic cardiomyopathy (DCM). Both clinical and animal studies demonstrate significant sex differences in prevalence, pathophysiology, and outcomes of cardiovascular diseases (CVDs), including those associated with diabetes. The increased risk of CVDs with diabetes is higher in women compared to men with 50% higher risk of coronary artery diseases and increased mortality when exposed to acute myocardial infarction. Clinical studies also reveal a sexual dimorphism in the incidence and outcomes of DCM. Based on these clinical findings, growing experimental research was initiated to understand the impact of sex on CVDs associated with diabetes and to identify the molecular mechanisms involved. Endothelial dysfunction, atherosclerosis, coagulation, and fibrosis are mechanisms found to be sex-differentially modulated in the diabetic cardiovascular system. Recently, impairment of energy metabolism also emerged as a determinant of multiple CVDs associated with diabetes. Therefore, future studies should thoroughly analyze the sex-specific metabolic determinants to propose new therapeutic targets. With current medicine tending toward more personalized care of patients, we finally propose to discuss the importance of sex as determinant in the treatment of diabetes-associated cardiac diseases to promote a more systemic inclusion of both males and females in clinical and preclinical studies.
Highlights
An alarming report from the International Federation of Diabetes recently highlighted that prevalence of diabetes keeps increasing worldwide, affecting 463 million people in 2019 (International Diabetes Federation, 2019)
In humans suffering from aortic stenosis, Kararigas et al (2014) reveal that cardiac hypertrophy is related to increased activation of profibrotic and inflammatory markers in men compared with women
When considering coronary artery diseases (CADs), women have a 50% higher risk than men, presenting increased mortality when exposed to acute myocardial infarction (MI) (Kannel, 1987; Toedebusch et al, 2018) with a strong impact of long-standing diabetes in women (Natarajan et al, 2005)
Summary
Natacha Fourny1*, Christophe Beauloye, Monique Bernard, Sandrine Horman, Martine Desrois and Luc Bertrand. Type 2 diabetes is a chronic disease associated with micro- and macro-vascular complications, including myocardial ischemia, and with a specific and intrinsic cardiac dysfunction called diabetic cardiomyopathy (DCM). Both clinical and animal studies demonstrate significant sex differences in prevalence, pathophysiology, and outcomes of cardiovascular diseases (CVDs), including those associated with diabetes. With current medicine tending toward more personalized care of patients, we propose to discuss the importance of sex as determinant in the treatment of diabetes-associated cardiac diseases to promote a more systemic inclusion of both males and females in clinical and preclinical studies
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