Gender Differences in the Risk of Adverse Outcomes After Incident Diabetic Foot Hospitalization: A Population Cohort Study

Background: Diabetic Foot Disease (DFD) is more prevalent among males and is associated with an excess risk of cardiovascular events or mortality. Aims: This study aimed at exploring the risk of cardiovascular events, renal failure, and all-cause mortality after incident DFD hospitalizations, separately in males and females, to detect any gender difference in a cohort of 322,140 people with diabetes retrospectively followed up through administrative data sources in Tuscany, Italy, over the years 2011-2018. Methods: The Hazard Ratio (HR) for incident adverse outcomes after first hospitalizations for DFD, categorized as major/minor amputations (No.=449;3.89%), lower limbs’ revascularizations (LLR: No.=2854;24.75%), and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to the risk of patients having a background of DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). Results: DFD incidence rate was higher among males compared to females (1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD, the overall risk of coronary artery disease was significantly associated with the male gender and of stroke with the female gender. LEAD-no proc and LLR were associated with the risk of stroke only in females, whereas they were found to be associated with the risk of coronary artery disease among females to a significantly greater extent compared to males. The incident of renal failure was not associated with any DFD category. Amputations and LEAD-no proc significantly predicted high mortality risk only in females, while LLR showed reduced risk in both genders. Moreover, females had a greater risk of composite outcomes (death or cardiovascular events). Compared to the background of DFD, the risk was found to be 34% higher after amputations (HR: 1.34(1.04-1.72)) and 10% higher after LEAD-no proc (HR:1.10(1.03-1.18)), confirming that after incident DFD associated with vascular pathogenesis, females are at an increased risk of adverse events. Conclusion: After incident DFD hospitalizations, females with DFD associated with amputations or arterial disease are at a greater risk of subsequent adverse cardiovascular events than those with a DFD background.