Sex Differences of the Diabetic Heart

The effects of empagliflozin, an inhibitor of sodium-glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known.

Based on 20 years of surveillance of the Framingham cohort relating subsequent cardiovascular events to prior evidence of diabetes, a twofold to threefold increased risk of clinical atherosclerotic disease was reported. The relative impact was greatest for intermittent claudication (IC) and congestive heart failure (CHF) and least for coronary heart disease (CHD), which was, nevertheless, on an absolute scale the chief sequela. The relative impact was substantially greater for women than for men. For each of the cardiovascular diseases (CVD), morbidity and mortality were higher for diabetic women than for nondiabetic men. After adjustment for other associated risk factors, the relative impact of diabetes on CHD, IC, or stroke incidence was the same for women as for men; for CVD death and CHF, it was greater for women. Cardiovascular mortality was actually about as great for diabetic women as for diabetic men.

The steep rise of type 2 diabetes mellitus (T2DM) and associated complications go along with mounting evidence of clinically important sex and gender differences. T2DM is more frequently diagnosed at lower age and body mass index in men; however, the most prominent risk factor, which is obesity, is more common in women. Generally, large sex-ratio differences across countries are observed. Diversities in biology, culture, lifestyle, environment, and socioeconomic status impact differences between males and females in predisposition, development, and clinical presentation. Genetic effects and epigenetic mechanisms, nutritional factors and sedentary lifestyle affect risk and complications differently in both sexes. Furthermore, sex hormones have a great impact on energy metabolism, body composition, vascular function, and inflammatory responses. Thus, endocrine imbalances relate to unfavorable cardiometabolic traits, observable in women with androgen excess or men with hypogonadism. Both biological and psychosocial factors are responsible for sex and gender differences in diabetes risk and outcome. Overall, psychosocial stress appears to have greater impact on women rather than on men. In addition, women have greater increases of cardiovascular risk, myocardial infarction, and stroke mortality than men, compared with nondiabetic subjects. However, when dialysis therapy is initiated, mortality is comparable in both males and females. Diabetes appears to attenuate the protective effect of the female sex in the development of cardiac diseases and nephropathy. Endocrine and behavioral factors are involved in gender inequalities and affect the outcome. More research regarding sex-dimorphic pathophysiological mechanisms of T2DM and its complications could contribute to more personalized diabetes care in the future and would thus promote more awareness in terms of sex- and gender-specific risk factors.