The study, led by Fatimah Z. Alenazi of Qassim University together with colleagues in Saudi Arabia, Lebanon, South Africa, and Portugal, set out to answer a deceptively simple question: which factors independently predict whether a patient’s feet fall into the danger zone, and whether they have already developed an active ulcer? The team focused on three candidate variables with strong clinical plausibility: glycated hemoglobin (HbA1c), the standard laboratory marker of average blood sugar over the preceding two to three months; age; and sex. Using a census sampling approach, they extracted every eligible record with a confirmed diabetes diagnosis and a documented foot assessment between January 2022 and December 2024, excluding only nine records with missing or non-numeric HbA1c values.

The technical backbone of the analysis was a pair of multivariable binary logistic regression models, one for each outcome. The primary outcome was at-risk diabetic foot status, defined as an IWGDF risk category of 1 or higher under the 2019 stratification system, which grades patients from category 0 (no loss of protective sensation or arterial disease) up to category 3 (previous ulceration or amputation). The secondary outcome was active foot ulceration, defined as a full-thickness wound distal to the ankle identified by the treating clinician during the same visit. Age and HbA1c were entered as continuous variables, with the HbA1c estimate expressed per 1% increase, and the models were assessed for calibration using the Hosmer–Lemeshow test and for explanatory power using the Nagelkerke R-squared statistic.

The results delivered a clear verdict on two of the three variables. Older age emerged as the strongest predictor of at-risk foot status, with each additional year of life raising the odds by 2.8% (odds ratio 1.028; 95% confidence interval 1.016–1.039; P < 0.001). The descriptive data traced the same gradient: at-risk status affected 39.6% of patients under 50, 55.3% of those aged 50 to 65, and 62.1% of those over 65. Male sex carried an independent 40% increase in the odds of at-risk status (OR 1.403; 95% CI 1.036–1.901; P = 0.029), with 58.3% of men classified as at risk compared with 48.4% of women. Both findings align with established biology: aging brings cumulative microvascular and macrovascular damage, progressive peripheral neuropathy, worsening peripheral arterial disease, thinner skin, slower tissue repair, and a heavier comorbidity burden, while men in many cohorts show higher rates of arterial disease and less favorable cardiovascular risk profiles.

The surprise came from HbA1c. Despite its reputation as the master metric of diabetes control, the glycemic marker showed no independent association with at-risk foot status (OR 1.037; P = 0.422) and fell short of statistical significance for active ulceration (OR 1.224; P = 0.077). Yet the raw descriptive numbers told a more suggestive story. Foot ulcer prevalence climbed steadily across HbA1c categories, from 1.9% among patients with HbA1c below 7.0% to 2.6% in the 7.0–9.0% band and 6.3% among those exceeding 9.0%. The authors argue that this gradient is biologically plausible and consistent with the known pathophysiology of wound breakdown, which involves chronic inflammation, immune dysfunction, endothelial impairment, and delayed repair, all of which are sensitive to current metabolic state.

Why might a single HbA1c reading fail to predict foot risk while still tracking ulceration descriptively? The researchers offer a mechanistic explanation rooted in the different time scales of the two outcomes. The IWGDF classification is built on structural, cumulative risk factors, including peripheral neuropathy, peripheral arterial disease, foot deformity, previous ulceration, and amputation, which develop over years or decades of glycemic exposure and vascular injury. A single recent HbA1c measurement captures only a snapshot of that long arc. Active ulceration, by contrast, represents acute tissue breakdown and impaired healing, processes that may respond more directly to current metabolic control. In other words, the foot risk category reflects the accumulated damage of the past, while the open wound may reflect the metabolic environment of the present.

The authors are careful, however, not to overstate what their data can support. The dataset lacked a long list of variables that any foot specialist would consider essential: diabetes duration, severity of neuropathy and peripheral arterial disease, renal function and chronic kidney disease, diabetic retinopathy, body mass index, smoking status, medication use, nationality, and socioeconomic status. Because these potential confounders could not be adjusted for, residual confounding cannot be excluded, and the independent role of HbA1c in diabetic foot risk cannot be confirmed or ruled out on the basis of this study alone. The team also notes that the most recent HbA1c value may not correspond in time to the foot assessment, introducing possible exposure misclassification, and that a single measurement may poorly represent long-term glycemic variability.

Several other quirks in the data deserve cautious reading. Active ulceration was recorded in only 21 patients, or 3.0% of the cohort, and its distribution across subgroups was uneven in ways that resist simple interpretation. Ulcer prevalence peaked in the 50-to-65 age group at 4.4% rather than among the over-65s at 2.6%, a pattern the authors attribute plausibly to survivor bias, more intensive surveillance of older patients, and reduced mobility in the oldest group, which may limit the repetitive mechanical trauma that drives skin breakdown even as structural risk rises. Similarly, although men carried higher at-risk status, active ulcers were actually more frequent in women, 3.7% versus 2.0%, a discrepancy that could reflect differences in healthcare utilization, footwear, mobility, or wound healing rather than biology. With so few ulcer events, the statistical models had limited precision, and the authors emphasize that their age–sex–HbA1c models were never intended as comprehensive risk-prediction tools.

The study’s strengths lie in its design discipline. The census approach avoided discretionary subsampling, the standardized IWGDF framework allowed comparison with international benchmarks, and reporting followed the STROBE guidelines for observational research. Its limitations are equally clear: the single tertiary center limits generalizability to primary care and community settings, the cross-sectional design forbids any causal inference, and the absence of the total number of diabetic patients seen at the center means the completeness of screening coverage could not be determined. A history of lower-extremity amputation was documented in only four patients and was deliberately excluded from the models, partly because amputation history is itself a defining criterion of IWGDF category 3, which would make its inclusion circular.

The practical message for clinicians and health systems is nonetheless concrete. With more than half of specialist-attending patients already in an at-risk category, the authors argue that foot screening and preventive care should be tailored to demographic profiles, with intensified surveillance for older patients and men, and delivered through multidisciplinary teams spanning podiatry, vascular assessment, endocrinology, and patient education. Glycemic optimization remains a cornerstone of diabetic foot prevention, but the study suggests that blood sugar control alone cannot identify who is in danger. What is needed next, the researchers conclude, are prospective, multicenter, longitudinal studies that capture the full spectrum of clinical, laboratory, and behavioral variables, so that risk-prediction models can be built and validated for Saudi Arabia and the wider Middle East and North Africa region, where the diabetes epidemic is still gathering force.

Subject of Research: Associations of glycemic control, age, and sex with diabetic foot risk and active foot ulceration in patients with diabetes in Saudi Arabia

Article Title: Associations of Glycemic Control, Age, and Sex with Diabetic Foot Risk and Active Foot Ulceration among Patients with Diabetes in Saudi Arabia: A Cross-Sectional Study

Article References: Alenazi, F. Z., Alslamah, T., Alharbi, B., Alotaibi, W. I., Fawaz, M., Algeffari, M., Alsalamah, Y. S., & Raposo, A. (2026). Associations of Glycemic Control, Age, and Sex with Diabetic Foot Risk and Active Foot Ulceration among Patients with Diabetes in Saudi Arabia: A Cross-Sectional Study. Diabetes Therapy. https://doi.org/10.1007/s13300-026-01923-y

Image Credits: AI Generated

DOI: 10.1007/s13300-026-01923-y

Keywords: diabetic foot, foot ulceration, HbA1c, glycemic control, IWGDF risk stratification, type 2 diabetes, peripheral neuropathy, peripheral arterial disease, Saudi Arabia, cross-sectional study, logistic regression, diabetes complications

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

The study drew on claims data from AOK – Die Gesundheitskasse, one of Germany’s largest statutory health insurers, allowing the investigators to identify 99,415 patients hospitalized for peripheral arterial disease between January 1, 2019 and December 31, 2020. This scale matters. Most previous studies of mental health in vascular disease have been small, single-center efforts that often conflated depression, anxiety, and cognitive impairment into a single category of psychological comorbidity. By contrast, the German dataset offered the statistical power to compare these disorders head to head, using multivariable-adjusted analyses and Cox regression models to account for age, sex, disease severity, and other cardiovascular risk factors.

The headline finding is striking in its simplicity: 47 percent of patients hospitalized for peripheral arterial disease had at least one of the three mental disorders. That figure alone should reshape how vascular teams think about their patient population. Patients with these conditions were more frequently female, presented with more advanced stages of arterial disease, and carried a heavier overall cardiovascular risk profile. In other words, the sickest patients with the most compromised circulation were also the ones most likely to be living with a mental health diagnosis, a convergence that sets the stage for the treatment disparities the study went on to document.

When the researchers disaggregated the three conditions, the picture became far more nuanced than the conventional wisdom suggests. Dementia stood out as the condition associated with the most pronounced disparities in care. Patients with dementia underwent revascularization, the procedures that restore blood flow to blocked leg arteries, at substantially lower rates than their peers. They also received statin therapy, the cornerstone guideline-recommended cholesterol-lowering treatment for atherosclerotic disease, far less often, despite presenting with more advanced disease at the time of hospitalization. This pattern of undertreatment in the face of greater need represents what the authors describe as an important and underrecognized gap in vascular care.

The prognostic consequences of dementia were equally dramatic. In the Cox regression models, dementia emerged as a strong independent predictor of all-cause mortality, with hazard ratios ranging from 1.57 to 1.62, meaning that patients with dementia faced a roughly 60 percent higher risk of death during follow-up compared with otherwise similar patients. Dementia also predicted the composite outcome of amputation and/or death, with hazard ratios between 1.49 and 1.56, and both associations were highly statistically significant. For a condition that is often treated as a background characteristic rather than a clinical variable, these numbers place dementia firmly in the category of major prognostic factors in peripheral arterial disease.

Depression, by contrast, told a quieter story. Although depression was the most prevalent of the three conditions and has been the focus of most prior research linking mental health to vascular outcomes, its association with adverse outcomes in this cohort was only modest after full statistical adjustment. Anxiety disorders fared even worse as prognostic markers, showing no consistent association with increased risk once the models accounted for other clinical variables. The authors conclude that mental disorders in peripheral arterial disease are not prognostically homogeneous, a phrase that carries real weight for trial designers, guideline writers, and clinicians who have traditionally bundled these conditions together under a single comorbidity flag.

Why might dementia exert such a disproportionate influence? The study itself points toward a combination of biological and systems-level mechanisms. On the biological side, dementia and peripheral arterial disease share deep vascular roots: atherosclerosis, endothelial dysfunction, and chronic inflammation injure both the brain and the limbs, and prior nationwide studies have shown that the risk of dementia differs across cardiovascular diseases and dementia subtypes. On the systems side, cognitive impairment complicates every step of vascular care. Patients with dementia may report claudication symptoms late or not at all, may struggle to adhere to complex medication regimens including statins and antiplatelet agents, and may be deemed poor candidates for revascularization by clinicians weighing procedural risk against limited expected benefit. Previous work in vascular surgery populations has documented that cognitive impairment is common and frequently undiagnosed in older patients undergoing vascular procedures, and that patients with dementia undergoing major limb amputation have particularly poor outcomes.

The treatment disparities documented in the study echo a pattern seen in other cardiovascular fields. Research on stroke care has shown that dementia is associated with poorer quality of care and worse outcomes after stroke, and the new findings suggest that a similar dynamic operates in the peripheral circulation. Whether the lower rates of revascularization and statin therapy in patients with dementia reflect explicit clinical judgment, implicit bias, communication barriers, or patient and family preferences cannot be determined from claims data alone. But the result is a vulnerable population that receives less of the therapy that guidelines recommend for everyone with atherosclerotic disease, while simultaneously bearing the highest risk of dying or losing a limb.

The study’s methodology deserves attention as well. Claims data offer unmatched scale and the ability to capture real-world treatment patterns across an entire country, but they also carry limitations inherent to administrative records. Diagnoses depend on coding practices, the severity of dementia and depression cannot be graded, and over-the-counter medications and care delivered outside the hospital may escape detection. The authors also note that the data are held by the Wissenschaftliches Institut der AOK in Berlin and are not publicly available, with access governed by contractual and data protection regulations. The work was funded as part of the LINCARE project by the Innovation Fund of the Federal Joint Committee, the German body that steers innovation in statutory health care.

For clinicians, the practical message is that screening for cognitive impairment should become as routine in vascular clinics as measuring the ankle-brachial index. For researchers, the findings argue for disaggregating mental health comorbidities in future trials and registries rather than collapsing them into a single variable. And for health systems, the study highlights a population in which coordinated care, involving vascular specialists, geriatricians, psychiatrists, and primary care physicians working together, could plausibly change outcomes that are currently among the worst in cardiovascular medicine. As the authors put it, dementia identifies a particularly vulnerable and undertreated peripheral arterial disease population, and recognizing that distinction is the first step toward closing a gap in care that has remained invisible for far too long.

Subject of Research: The differential impact of depression, anxiety, and dementia on prognosis and treatment patterns in patients hospitalized for peripheral arterial disease

Article Title: Not all mental disorders matter equally in peripheral arterial disease: Dementia drives prognosis and care disparities

Article References: Not all mental disorders matter equally in peripheral arterial disease: Dementia drives prognosis and care disparities. (n.d.). https://doi.org/10.1007/s00392-026-03027-w

Image Credits: AI Generated

DOI: 10.1007/s00392-026-03027-w

Keywords: peripheral arterial disease, dementia, depression, anxiety disorders, revascularization, statin therapy, amputation, mortality, claims data, health care disparities, cardiovascular risk, vascular care