The scale of the problem documented in the study is striking. Among the 462 participants, 28.9 percent exhibited established factors associated with increased odds of ulceration, such as peripheral neuropathy, impaired arterial supply, or structural foot deformity. A further 16.6 percent presented with active diabetic foot ulcers, meaning open lesions that had already breached the skin. Taken together, 32.5 percent of the cohort demonstrated either risk factors or existing ulceration. For clinicians, these numbers translate into a continuous stream of patients whose feet are one unnoticed injury away from infection, gangrene, and amputation. For public health planners, they signal that foot pathology in Pakistani diabetes clinics is not an occasional crisis but a routine, systemic feature of the disease landscape.

Diabetic foot ulceration is widely regarded as one of the most feared consequences of type 2 diabetes because it sits at the intersection of two parallel degenerative processes. Chronic hyperglycemia damages the long nerves of the lower limbs, producing peripheral neuropathy in which patients progressively lose protective sensation. A person with neuropathic feet may step on a sharp object, develop a blister from ill-fitting shoes, or sustain a minor burn without feeling any pain, and the wound therefore goes untreated until it becomes deeply infected. Simultaneously, elevated glucose accelerates atherosclerosis of the small and medium arteries of the leg, a condition known as peripheral arterial disease or angiopathy, which starves the tissues of the oxygen needed for healing. When numbness and poor blood supply coexist, even a trivial lesion can progress to a limb-threatening ulcer within days.

The Karachi study was designed to quantify exactly how these processes manifest in a real clinical population and to identify which factors independently predict who ends up in the danger zone. Following written informed consent, the researchers documented each participant’s demographic characteristics, diabetes history, and anthropometric measurements, and then performed standardized clinical foot examinations. Neuropathy was assessed using 10-g monofilament testing, a technique in which a nylon filament is pressed against specific points on the sole until it bows; a patient who cannot feel the filament at a tested site is classified as having lost protective sensation. Peripheral arterial disease was evaluated through the ankle-brachial index, a noninvasive measurement that compares blood pressure at the ankle with blood pressure in the arm, with low values indicating compromised arterial flow to the feet. Fasting blood samples were also obtained to calculate HOMA-IR, the homeostatic model assessment of insulin resistance, which estimates how strongly the body’s tissues resist the glucose-lowering action of insulin.

Participants were then sorted into three clinically meaningful categories: those with no detectable foot risk, those classified as at-risk because of neuropathy, angiopathy, or foot deformity, and those with an active ulcer. Binary logistic regression, a statistical technique that estimates the odds of an outcome as a function of multiple explanatory variables, was used to identify which factors were independently associated with risk or ulceration, with statistical significance set at a p-value below 0.05. This two-stage analytical approach matters because many variables that appear related to foot complications in simple comparisons are actually proxies for one another; multivariable modeling strips away those overlaps and isolates the factors that carry independent predictive weight.

The univariate analysis, which examined each factor in isolation, revealed significant positive associations between risk or ulcer status and a broad range of characteristics: advancing age, elevated body mass index, raised diastolic blood pressure, smoking, a prior history of ulceration or amputation, insulin resistance as measured by HOMA-IR, dry skin, hyperkeratotic lesions, fissures, and nail deformities. Each of these associations tells a mechanistic story. Smoking worsens arterial disease and impairs tissue oxygenation. Elevated BMI and blood pressure track with metabolic syndrome and its vascular consequences. Dry skin, calluses, corns, and fissures represent the mechanical and dermatological consequences of neuropathy, because denervated skin loses its normal sweating and its ability to distribute pressure evenly, causing thickened, cracked patches that readily break down into ulcers.

When the researchers moved to multivariable analysis, a tighter set of independent predictors emerged. HOMA-IR, indicating insulin resistance, remained significantly associated with foot risk or ulceration, as did the presence of calluses, corns, or fissures, nail deformity, onychomycosis, a history of previous amputation, and daily foot inspection behavior. The inclusion of onychomycosis, a fungal infection of the toenails, is particularly noteworthy because thickened, dystrophic nails can create pressure points, harbor pathogens, and serve as entry sites for bacteria, yet fungal nail disease is often dismissed as a cosmetic nuisance rather than a genuine limb-threat marker. The appearance of previous amputation as an independent predictor underscores a sobering clinical reality: patients who have already lost part of a foot remain at high risk of losing more, because the biomechanics of the remaining foot are altered and pressure distribution becomes even more hazardous.

One of the most provocative findings concerns foot inspection behavior, which appeared as an independent factor in the multivariable model. Daily self-examination of the feet is the cornerstone of diabetic foot prevention, recommended by every major clinical guideline precisely because it allows patients to catch blisters, cuts, and color changes before they escalate. Its emergence in the analysis highlights a double-edged reality: patients who inspect their feet daily are often those who have already been educated about their risk or who have experienced a complication, while those who do not inspect may be accumulating silent damage. The authors emphasize that this pattern points toward systematic patient education as a low-cost, high-yield intervention, particularly in settings where specialist podiatry services are scarce and where a single clinic visit may be the only structured foot assessment a patient ever receives.

The study’s implications extend well beyond Karachi. Pakistan carries one of the world’s heaviest diabetes burdens, and diabetic foot complications contribute substantially to morbidity, lower-extremity amputation, and healthcare expenditure, with costs that cascade through families and already strained health systems. The authors argue that the substantial burden of risk factors and active ulceration observed in their cohort underscores the imperative for systematic foot surveillance, patient education, and early intervention strategies targeting modifiable metabolic and dermatological precursors. In practical terms, that means integrating monofilament testing and ankle-brachial index measurement into routine diabetes visits, treating calluses and fungal nail infections before they ulcerate, aggressively managing insulin resistance and vascular risk factors, and teaching every patient to look at their feet every day. The study, approved by the institutional review boards of the University of Karachi, the Aga Khan Health Service Centre, and the Tabba Heart Institute, and conducted in accordance with the Declaration of Helsinki, received no external funding. Its message is ultimately an optimistic one: the factors that most strongly predict limb loss in this population are visible, measurable, and modifiable, which means that with systematic screening and education, a large share of these amputations and ulcers could be prevented before they ever begin.

Subject of Research: Prevalence and risk factors for diabetic foot complications among type 2 diabetes patients in Pakistan

Article Title: Prevalence and factors associated with diabetic foot complications among type 2 diabetes patients in Pakistan: a cross-sectional analysis of clinical risk factors and preventive opportunities

Article References: Riaz, N., Yasmeen, G., & Khan, M. A. (2026). Prevalence and factors associated with diabetic foot complications among type 2 diabetes patients in Pakistan: a cross-sectional analysis of clinical risk factors and preventive opportunities. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02531-4

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02531-4

Keywords: diabetic foot ulcer, type 2 diabetes, peripheral neuropathy, insulin resistance, HOMA-IR, foot care behavior, onychomycosis, peripheral arterial disease, amputation risk, Pakistan, cross-sectional study, preventive care