Sex differences in the risk of vascular disease associated with diabetes

Abstract

Diabetes is a strong risk factor for vascular disease. There is compelling evidence that the relative risk of vascular disease associated with diabetes is substantially higher in women than men. The mechanisms that explain the sex difference have not been identified. However, this excess risk could be due to certain underlying biological differences between women and men. In addition to other cardiometabolic pathways, sex differences in body anthropometry and patterns of storage of adipose tissue may be of particular importance in explaining the sex differences in the relative risk of diabetes-associated vascular diseases. Besides biological factors, differences in the uptake and provision of health care could also play a role in women's greater excess risk of diabetic vascular complications. In this review, we will discuss the current knowledge regarding sex differences in both biological factors, with a specific focus on sex differences adipose tissue, and in health care provided for the prevention, management, and treatment of diabetes and its vascular complications. While progress has been made towards understanding the underlying mechanisms of women's higher relative risk of diabetic vascular complications, many uncertainties remain. Future research to understanding these mechanisms could contribute to more awareness of the sex-specific risk factors and could eventually lead to more personalized diabetes care. This will ensure that women are not affected by diabetes to a greater extent and will help to diminish the burden in both women and men.

Fig. 1

Results from prior meta-analyses of sex differences in the effects of diabetes on vascular outcomes and cancer expressed as the women-to-men ratio of relative risks (RRR) and the additional risks [7, 8, 10, 11, 13]. RRR, relative risk ratio; RR, relative risk; NR, not reported

Fig. 2

Sex differences in visceral and subcutaneous fat and their association with the time of diagnosis of diabetes

Fig. 3

Sex differences in adiposity in association with diabetes and cardiovascular disease. The figure illustrates the associations between adiposity, insulin resistance, type 2 diabetes, and cardiovascular disease in women compared with men. BMI, body mass index; IR, insulin resistance; CVD, cardiovascular disease

Fig. 4

Disparities in the uptake and provision of healthcare may in part explain the excess risk of vascular disease in women with diabetes compared to their male counterparts. Potential differences in the uptake and provision of healthcare between the sexes may occur throughout the pathway—starting with healthy men and women being exposed to certain risk factors, at some point being diagnosed with diabetes and eventually developing cardiovascular complications—and may include, i.e., diagnostic delay, inadequate risk factor screening, disparities in adequate interventions, and non-adherence as shown by the arrows. The green-colored box displays normal glucose tolerance, and the red-colored boxes display negative events (i.e., type 2 diabetes, cardiovascular complications) irrespective of the sexes