Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews

Background: Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed. Methods and results: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males. Conclusions: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.