Sex, Gender, and the Diabetes Penalty: Cardiovascular Risk, Outcomes, and Therapy in Diabetes and Metabolic Syndrome

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, yet its burden is not shared equally across sexes and genders. A well-established body of evidence has long suggested that premenopausal women enjoy a degree of cardioprotection relative to age-matched men — a biological advantage rooted in the interplay of sex hormones, metabolic regulation, and vascular physiology. However, this protection is paradoxically and disproportionately eroded in women with diabetes or metabolic syndrome, resulting in excess cardiovascular risk and worse outcomes compared to their male counterparts. This reversal — the so-called “diabetes penalty” — represents one of the most clinically significant yet mechanistically underexplored phenomena in cardiovascular medicine.Beyond biology, gender-linked determinants — including differences in health-seeking behaviour, access to care, psychosocial burden, and adherence to therapy — compound these disparities across the full spectrum of CVD. Hormonal transitions, particularly menopause and pregnancy-related metabolic disturbances, represent critical inflection points that amplify cardiovascular risk in women with pre-existing metabolic dysfunction. Meanwhile, gender-diverse individuals and elderly populations with diabetes remain profoundly under-represented in both clinical trials and mechanistic research.The emergence of transformative cardiometabolic therapies — GLP-1 receptor agonists, SGLT2 inhibitors, and novel hormonal interventions — has opened a new chapter in CVD management, yet sex- and gender-disaggregated evidence from diabetic and metabolic syndrome cohorts remains sparse.This RT will focus on:-The mechanistic basis of the diabetes-mediated reversal of female cardioprotection-The impact of hormonal life-course transitions (menopause, gestational diabetes, PCOS, reproductive history) on CV risk in metabolic cohorts-Sex- and gender-stratified outcomes with GLP-1 RAs, SGLT2 inhibitors, and hormone therapy — including real-world data and sex-disaggregated trial reanalyses-Gender-specific barriers to CVD care in diabetic and metabolic syndrome populations-Cardiovascular outcomes in postmenopausal women, gender-diverse individuals, and elderly patients with diabetes Topic editors: Yifan Chen, Zeye Liu, Evelyne Yehudit Bischof Source: https://www.frontiersin.org/research-topics/81372/sex-gender-and-the-diabetes-penalty-cardiovascular-risk-outcomes-and-therapy-in-diabetes-and-metabolic-syndrome