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.

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Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus.

Sex and gender: modifiers of health, disease, and medicine.

Cardiovascular disease (CVD) is the leading cause of death in women, who have a notable increase in the risk for this disease after menopause and typically develop coronary heart disease several years later than men. This observation led to the hypothesis that the menopause transition (MT) contributes to the increase in coronary heart disease risk. Over the past 20 years, longitudinal studies of women traversing menopause have contributed significantly to our understanding of the relationship between the MT and CVD risk. By following women over this period, researchers have been able to disentangle chronological and ovarian aging with respect to CVD risk. These studies have documented distinct patterns of sex hormone changes, as well as adverse alterations in body composition, lipids and lipoproteins, and measures of vascular health over the MT, which can increase a woman's risk of developing CVD postmenopausally. The reported findings underline the significance of the MT as a time of accelerating CVD risk, thereby emphasizing the importance of monitoring women's health during midlife, a critical window for implementing early intervention strategies to reduce CVD risk. Notably, the 2011 American Heart Association guidelines for CVD prevention in women (the latest sex-specific guidelines to date) did not include information now available about the contribution of the MT to increased CVD in women. Therefore, there is a crucial need to discuss the contemporary literature on menopause and CVD risk with the intent of increasing awareness of the significant adverse cardiometabolic health-related changes accompanying midlife and the MT. This scientific statement provides an up-to-date synthesis of the existing data on the MT and how it relates to CVD.

Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention: A Scientific Statement From the American Heart Association

By 2017 estimates, diabetes mellitus affects 425 million people globally; approximately 90–95% of these have type 2 diabetes. This narrative review highlights two domains of sex differences related to the burden of type 2 diabetes across the life span: sex differences in the prevalence and incidence of type 2 diabetes, and sex differences in the cardiovascular burden conferred by type 2 diabetes. In the presence of type 2 diabetes, the difference in the absolute rates of cardiovascular disease (CVD) between men and women lessens, albeit remaining higher in men. Large-scale observational studies suggest that type 2 diabetes confers 25–50% greater excess risk of incident CVD in women compared with men. Physiological and behavioural mechanisms that may underpin both the observed sex differences in the prevalence of type 2 diabetes and the associated cardiovascular burden are discussed in this review. Gender differences in social behavioural norms and disparities in provider-level treatment patterns are also highlighted, but not described in detail. We conclude by discussing research gaps in this area that are worthy of further investigation.

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Sex differences in the burden of type 2 diabetes and cardiovascular risk across the life course

Park characteristics, use, and physical activity: A review of studies using SOPARC (System for Observing Play and Recreation in Communities).

Strong evidence suggests that type 2 diabetes confers a stronger excess risk of cardiovascular diseases in women than in men; with women having a 27 % higher relative risk of stroke and a 44 % higher relative risk of coronary heart disease compared with men. The mechanisms that underpin these sex differences in the associations between diabetes and cardiovascular disease risk are not fully understood. Some of the excess risk may be the result of a sex disparity in the management and treatment of diabetes, to the detriment of women. However, accruing evidence suggests that real biological differences between men and women underpin the excess risk of diabetes-related cardiovascular risk in women such that there is a greater decline in risk factor status in women than in men in the transition from normoglycemia to overt diabetes. This greater risk factor decline appears to be associated with women having to put on more weight than men, and thus attain a higher body mass index, to develop diabetes. Further studies addressing the mechanisms responsible for sex differences in the excess risk of cardiovascular diseases associated with diabetes are needed to improve the prevention and management of diabetes in clinical practise.

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Sattar A. E. Peters

Papers

Sex Differences in the Excess Risk of Cardiovascular Diseases Associated with Type 2 Diabetes: Potential Explanations and Clinical Implications.