Sex differences in diabetic foot ulcer severity and outcome in Belgium

Abstract

Background: Sex differences are increasingly recognized to play an important role in the epidemiology, treatment and outcomes of many diseases. This study aims to describe differences between sexes in patient characteristics, ulcer severity and outcome after 6 months in individuals with a diabetic foot ulcer (DFU).

Methods: A total of 1,771 patients with moderate to severe DFU participated in a national prospective, multicenter cohort study. Data were collected on demographics, medical history, current DFU and outcome. For data analysis, a Generalized Estimating Equation model and an adjusted Cox proportional hazards regression were used.

Results: The vast majority of patients included were male (72%). Ulcers in men were deeper, more frequently displaying probe to bone, and more frequently deeply infected. Twice as many men presented with systemic infection as women. Men demonstrated a higher prevalence of previous lower limb revascularization, while women presented more frequently with renal insufficiency. Smoking was more common in men than in women. No differences in presentation delay were observed. In the Cox regression analysis, women had a 26% higher chance of healing without major amputation as a first event (hazard ratio 1.258 (95% confidence interval 1.048-1.509)).

Conclusions: Men presented with more severe DFU than women, although no increase in presentation delay was observed. Moreover, female sex was significantly associated with a higher probability of ulcer healing as a first event. Among many possible contributing factors, a worse vascular state associated with a higher rate of (previous) smoking in men stands out.

Fig 1. Location of the index DFU.

A color-coded diagram was used by the DFC to indicate the location of the index DFU: Plantar forefoot (orange), plantar midfoot (yellow), heel (green), malleolus (purple), dorsum (blue) and toes (red). The number and proportion (%) of men and women with a DFU at a known location is indicated next to the respective color. The sum of percentages can exceed 100%, as a DFU can span multiple locations. The proportions of both groups were compared using generalized estimating equations.

Fig 2. Outcome of the index DFU after 6 months for patients not lost to follow-up.

A-E. Proportion of all patients (green, n = 1,707), male patients (blue, n = 1,238) or female patients (red, n = 469) who achieved the specified outcome during the follow-up period of maximum 6 months, being A. Healing without any amputation; B. Healing with minor amputation; C. Resolved by major amputation; D. Death or E. Chronic ulcer. Deaths were recorded throughout the follow-up period, bringing the total sum of the percentages above 100%, as some patients deceased after healing or major amputation. F-I. Boxplots showing the spread of the time (in days) to an event, being F. Healing without any amputation; G. Healing with minor amputation; H. Major amputation or I. Death. The median time-to-event is indicated by the horizontal line, the mean time-to-event by the circle.