Sex differences in the association between myocardial function and prognosis in type 1 diabetes without known heart disease: the Thousand & 1 Study

Aims: In type 1 diabetes mellitus (T1DM), recent findings suggest that women have a greater excess risk of cardiovascular diseases (CVDs) compared to men. Impaired diastolic function is a common feature in T1DM. We investigated the association between myocardial function by echocardiography and outcomes in T1DM males and females without known heart disease.

Methods and results: A prospective cohort of individuals with T1DM without known heart disease from the outpatient clinic of Steno Diabetes Center Copenhagen. Follow-up was performed through Danish national registers. Outcomes, major adverse cardiovascular events (MACE) and all-cause mortality, were investigated. A total of 1079 participants (mean age: 49.6 ± 14.5 years, 52.6% male, mean duration of diabetes 25.8 ± 14.6 years) were included in the study. During follow-up (median 6.3 years, interquartile range 5.7-6.9), 142 (13.2%) experienced MACE and 63 (5.8%) died. Gender modified the relationship between E/e' and both MACE and all-cause mortality (P = 0.016 and 0.007, respectively). In females, after multivariable adjustment, both E/e' and global longitudinal strain (GLS) were significantly associated with MACE [E/e': hazard ratio (HR) 1.15 confidence interval (CI) 95%: 1.07-1.24, per 1unit increase; and GLS: HR 1.19 CI 95%: 1.04-1.35, per 1% decrease] and with all-cause mortality (E/e': HR 1.26 CI 95%: 1.11-1.44; and GLS: HR 1.27 CI 95%: 1.03-1.56). In males, the association between E/e' and GLS and outcomes did not reach statistical significance.

Conclusion: In female individuals with T1DM both E/e' and GLS provided independent prognostic information, whereas the associations were not significant in males. These results suggest that T1DM affects myocardial function differently in males and females, which may be related to the observed sex difference in CVD risk in T1DM.