Assessment of Non Vascular Risk Factors for Severity of Diabetic Foot Ulcers (DFUs)

Diabetes mellitus is a chronic disease that arises either from insufficient insulin production by the pancreas or from the body's inability to use insulin effectively. It encompasses a wide spectrum of subtypes, including type 1 diabetes (absolute insulin deficiency), type 2 diabetes (insulin resistance), gestational diabetes, maturity-onset diabetes of the young (MODY), neonatal diabetes, Wolfram syndrome, latent autoimmune diabetes in adults (LADA), type 3C diabetes, steroid-induced diabetes, cystic fibrosis-related diabetes, and malnutrition-related diabetes, which affects approximately 20-25 million people primarily in Asia and Africa . According to the World Health Organization (WHO), the global number of people living with diabetes increased dramatically from 200 million in 1990 to 830 million in 2022 . The latest International Diabetes Federation (IDF) Atlas (2025) reports that 11.1% of adults aged 20-79 years-equivalent to one in nine-are living with diabetes, with nearly 40% of them unaware of their condition .

One of the most serious and costly complications of diabetes is the diabetic foot ulcer (DFU). Globally, the prevalence of DFUs is estimated at around 6.3%, with an annual incidence ranging from 9.1 to 26.1 million cases . This implies that roughly one in sixteen people with diabetes will experience a foot ulcer during their lifetime. DFUs are defined as wounds or ulcerations on the feet of individuals with diabetes, typically resulting from a combination of neuropathy, peripheral artery disease, trauma, and increased plantar pressure . These ulcers may progress to severe complications, including deep infection, osteomyelitis, and lower-limb amputation, leading not only to pain, disability, and psychological distress, but also to increased mortality . Beyond their devastating impact on patients and their families, DFUs pose a significant economic burden on healthcare systems due to high treatment costs and loss of productivity .

To reduce this burden, a clear understanding of the underlying risk factors is critical-not only to treat but also to prevent DFUs. In addition to vascular impairment, non-vascular risk factors have been shown to play a central role in ulcer development, severity, and healing. These include peripheral neuropathy, poor glycemic control, obesity, malnutrition, smoking, repetitive stress and pressure, inadequate foot care, infections such as onychomycosis or tinea pedis, high body mass index, and systemic conditions such as iron-deficiency anemia . Recent studies further emphasized the role of hematologic and nutritional abnormalities (e.g., anemia, hypoalbuminemia , elevated inflammatory markers) as independent predictors of ulcer severity . A systematic assessment of these non-vascular contributors enables clinicians to identify patients at higher risk, tailor treatment strategies, and implement preventive measures at earlier stages. When combined with vascular evaluation, this approach provides a comprehensive risk profile, improves clinical outcomes, reduces the need for amputation. and ultimately enhances quality of life for individuals with diabetes .