Our study in patients with DFUs is the first to report the negative impact of frailty (as evaluated using the FI) on poor DFUs outcomes and rehospitilizations. We show that frailty is very common in this relatively young cohort (median age 65) of patients with a prevalence of 71%. This prevalence is significantly higher than what is reported in the literature, even in much older non-diabetic populations (6, 15). These results confirm that frailty is not exclusively a condition of old age, but can exist among young individuals exposed to specific conditions accelerating the aging process. DFUs and their associated complications (e.g., amputations) can indeed be seen as major contributors to the fragilization of the individual, leading to disabling conditions and adverse outcomes by feeding the vicious cycle of frailty. Interestingly, previous studies have found that frailty is associated with poorer outcomes also at a young age (16).
We also report here that frailty predicts non-healing of DFUs. Sarcopenia, neuropathy, and inflammatory mechanisms may represent some of the underlying shared mechanisms. There is established evidence that chronic conditions, such as heart failure, renal impairment, and depression, interfere with the healing of DFUs (17–19). The cumulative effect of multiple pathologies (potentially accounting for frailty) on DFUs has not been evaluated. The high prevalence of frailty may explain why some DFUs still fail to improve despite removing barriers to healing (e.g., infection, edema, reduced blood supply). Polypharmacy, another critical issue in frail individuals, might also have a direct effect on tissue repair. In fact, drugs like steroids, nicorandil, diuretics, antihypertensive agents, and immunosuppressants are known to slow down wound healing (20). It is also possible that the exhausted homeostatic reserves characterizing the frail individual may play a role in the non-healing of the DFUs.
Our findings on the increased risk of rehospitalisation in patients with DFUs and frailty are consistent with the literature from other studies in older non-diabetic cohorts (7, 21, 22).
We also observed a higher prevalence of frailty in men than women, which is opposite to what is generally reported in the literature (23, 24). A possible explanation may be that DFUs are more common in men (who are also at higher risk of amputations) than women.
We did not observe in multivariable analyses a significant independent association between frailty and mortality in our cohort. This finding contrasts with recent studies of hospitalized older patients, where the FI significantly correlated with the risk of in-hospital death and 1-year mortality (25). The relatively younger age of our cohort as well as the limited sample size may explain why we did not observe a similar increased risk of mortality.
The FI provides an accurate clinical instrument to identify frail patients, and potentially an opportunity to person-tailor post-discharge interventions. The FI is easy to administer at the bedside, does not require any special equipment, and is predictive of adverse clinical outcomes. Importantly, its quantitative and not qualitative nature makes it easily applicable and adaptable to routine clinical practice.
The early identification of patients at risk of adverse events and assessing the severity of frailty have important clinical implications. Several studies have demonstrated that targeted post-discharge care planning using the FI can improve the patient’s outcomes (26–29).
We acknowledge several limitations of our study. First, the number of patients recruited was relatively small, and the DFUs size was not directly measured. We cannot exclude that the size of the lesion may have impacted on our findings. However, as the DFU might be considered a health deficit per se, it is likely that the FI is highly correlated with the size and severity of the lesion. Second, we did not evaluate the frailty status at discharge. Numerous studies have shown that hospital admission per se plays a role in subsequent functional deterioration. Finally, we included patients admitted to a tertiary hospital, a regional centre for DFUs treatment. Thus, the results may not be generalizable.
Despite these limitations, our data highlight the impact of frailty on patients with DFUs. The strengths of our study are the robust evaluation of frailty by using a validated model, the standardized clinical care process, the optimal DFUs evaluation and treatments that patients received, and the long duration of follow-up to assess the relevant outcomes (for both the patient and the healthcare system).
Our findings should foster research into the possible extension of the multidimensional approach to young people with diabetes and DFUs. Indeed, the distinction according to chronological age in these frail patients might be arguable (and even lead to ageistic approaches). In this context, the FI might allow more sound clinical decisions relying on a surrogate of biological age. A better understanding of frailty will enable to improve the individualization of care planning for patients with DFUs.