Keywords
diabetic foot ulcers, Type 2 Diabetes Mellitus, Thi Qar, Iraq, local studies, characteristics,
This study aimed to evaluate the characteristics of diabetic foot ulcers in individuals with type 2 diabetes mellitus (T2DM) in Iraq.
The study included 881 participants with T2DM and different types of foot ulcers, who attended a specialized diabetes center. Data on demographics, clinical characteristics, biochemical investigations, comorbidities, and treatment regimens were collected and analyzed.
The majority of the cases (96.8%) were due to T2DM, with an average age of 58 years and a mean BMI of 30 kg/m2. Participants had elevated serum creatinine, blood urea, and glucose levels, with uncontrolled HbA1c levels. Comorbidities included hypertension, ischemic heart disease, diabetic neuropathy, and retinopathy. Most participants were on insulin and statins. Diabetic foot ulcers were mainly on the right foot (48%) and classified as Grade 2 in Wagner’s system. Some participants had Charcot deformity or stages of amputation.
Random plasma glucose levels and diabetic retinopathy were significantly associated with the classification of foot ulcers. Further research is needed to explore additional variables related to T2DM and foot ulcers, emphasizing the importance of glucose control and retinopathy in ulcer classification.
diabetic foot ulcers, Type 2 Diabetes Mellitus, Thi Qar, Iraq, local studies, characteristics,
This revised Version 3 addresses the reservations raised by Reviewer Haeril Amir and introduces the following key amendments relative to Version 2:
1. Expanded Methods — Participants subsection: Explicit inclusion criteria (adult T2DM patients ≥18 years with active DFU attending TDEMC, January 2021–June 2022), exclusion criteria (T1DM, incomplete records, declined consent), and sampling method (consecutive sampling) have been added to improve methodological transparency and allow assessment of representativeness.
2. Expanded Methods — Data Collection subsection: Operational definitions have been added for five key clinical variables previously mentioned without specification: diabetic retinopathy (ophthalmologic examination/fundoscopy per the International Clinical Diabetic Retinopathy Severity Scale), diabetic neuropathy (10-g monofilament, vibration, and ankle reflex examination per ADA criteria), ischaemic heart disease (documented cardiologist diagnosis), hypertension (documented diagnosis or antihypertensive use), and smoking status (patient self-report; current/ex-smoker/never-smoker).
3. New Statistical Analysis — Multivariate Regression (Tables 4A and 4B): The statistical analysis has been substantially expanded beyond descriptive statistics and chi-square tests. An ordinal logistic regression model (Wagner grade 1–5 as ordinal outcome) and a binary logistic regression model (severe DFU: Wagner ≥3 versus non-severe: Wagner <3) were performed on the T2DM cohort (n=853). These analyses identified diabetic retinopathy (OR=0.58, 95% CI 0.41–0.81, p=0.002), diabetic neuropathy (OR=0.65, 95% CI 0.48–0.88, p=0.006), and eGFR (OR=0.86, 95% CI 0.74–0.99, p=0.040) as independent significant predictors of higher Wagner grade after adjustment for all confounders.
4. Expanded Discussion: Three new paragraphs provide pathophysiological interpretations of the key associations, including the shared microvascular mechanisms linking retinopathy and neuropathy to DFU severity, the attenuation of random plasma glucose in the multivariate model, and the role of renal function in DFU progression.
5. Updated Abstract and Conclusion: Both sections have been revised to incorporate the multivariate regression findings.
See the authors' detailed response to the review by Haeril Amir
See the authors' detailed response to the review by Nassar Alibrahim
Diabetes mellitus (DM) represents a significant global health issue, anticipated to affect 700 million people by 2045.1 Diabetic foot ulcers carry a heavy burden both in economic terms and human suffering. Despite advancements in treatment and increased awareness, DFUs remain a prevalent issue among those with diabetes, especially T2DM. One of the severe consequences of DM is the formation of diabetic foot ulcers (DFUs), which can drastically diminish the quality of life for patients, lead to costly economic outcomes, and, at worst, necessitate the amputation of affected limbs.2 Diabetic foot encompasses a range of foot-related health issues, from infections and ulcerations to deep tissue damage arising from the complications of diabetes itself.3 An estimated 80% of non-traumatic amputations are attributed to DFUs, underscoring their severe impact.4
The typical etiology of DFUs involves a combination of neuropathic, traumatic, ischemic, and infectious factors.5 Globally, the prevalence of diabetic foot stands at approximately 6.3%, with a higher incidence among males, those with type 2 diabetes (T2DM), elderly individuals, patients with a lower body mass index (BMI), smokers, and those with a longer duration of disease. Patients with retinopathy, hypertension, or previous history of DFUs are at increased risk.6 Further studies suggest that up to 15% of patients with diabetes will eventually develop a DFU, and 7-20% of these cases may result in an amputation, amounting to an amputation resulting from diabetic causes every 30 seconds.7 Given that 85% of amputation cases could have been prevented with earlier detection and proper treatment of DFUs,8 annual comprehensive foot examinations are recommended to identify potential problems at an early stage.9 Effective prevention of DFUs can be achieved through systematic screening and management of risk factors.10
The absence of localized studies prompted the current research, intended to appraise the characteristics and prevailing conditions of DFUs to enhance both prevention and treatment strategies for this significant health concern. The research was conducted at the Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) and focused on evaluating the specificities of DFUs in patients with T2DM in the southern region of Iraq.
This cross-sectional observational study, approved by the ethical committee of TDEMC (approval number IQ.TDEMC.REG.125/35), adhered to the Helsinki declaration and involved informed consent from all participants. The study encompassed 881 individuals with DFUs of various etiologies who presented at TDEMC between January 2021 and June 2022. According to the requirements of the EQUATOR (Enhancing the QUAlity and Transparency Of health Research) protocol guidelines, a cross-sectional study follow the STROBE (STrengthening the Reporting of OBservational studies in Epidemiology) guidelines.
This was a cross-sectional observational study conducted at a specialized diabetes center in Iraq.
Inclusion criteria: adult patients (≥18 years) with confirmed type 2 diabetes mellitus presenting with an active diabetic foot ulcer at Thi-Qar Specialized Diabetes Endocrine and Metabolism Center (TDEMC) between January 2021 and June 2022. Exclusion criteria: patients with type 1 diabetes mellitus, those with incomplete medical records, and individuals who declined to provide written informed consent. Participants were recruited consecutively as they attended the outpatient clinic.
Data on demographics (age, gender), clinical characteristics (BMI, blood pressure), biochemical investigations (serum creatinine, blood urea, estimated glomerular filtration rate [eGFR], fasting blood glucose [FBS], random blood sugar [RBS], HbA1c, lipid profile), and comorbidities were collected from medical records and participant interviews. Clinical variables were defined as follows: diabetic retinopathy was diagnosed by fundoscopic examination using the International Clinical Diabetic Retinopathy Severity Scale; diabetic peripheral neuropathy was assessed using the 10-g monofilament test, vibration perception, and ankle reflex testing per American Diabetes Association (ADA) guidelines; ischaemic heart disease (IHD) was defined as a documented physician diagnosis or prior cardiac investigation; hypertension was defined as a documented diagnosis or current use of antihypertensive medication; and smoking status was classified by self-report as non-smoker, current smoker, or ex-smoker. Wagner’s grading system was used to classify DFU severity (grades 1–5).
Descriptive statistics were used to summarize characteristics, including frequencies, means, and standard deviations. Associations between clinical and biochemical variables and Wagner grade classification were analyzed using chi-square tests. To identify independent predictors of DFU severity, two multivariate regression models were constructed on the T2DM cohort (n=853): (1) Ordinal logistic regression with Wagner grade (1–5) as the ordinal outcome variable, adjusting simultaneously for age, sex, BMI, diabetes duration, RBS, FBS, HbA1c, total cholesterol, triglycerides, eGFR, hypertension, IHD, smoking, diabetic retinopathy, and diabetic neuropathy; (2) Binary logistic regression comparing severe DFU (Wagner grade ≥3, n=172, 20.2%) versus non-severe DFU (Wagner grade <3, n=681, 79.8%) using the same covariates. Statistical significance was defined as p < 0.05. All analyses were performed using SPSS version 26.
The study was conducted in accordance with ethical guidelines and obtained approval from the institutional review board. Informed consent was obtained from all participants before data collection.
The study was limited by its cross-sectional design, which precluded the establishment of causal relationships. Additionally, the study was conducted at a single center, which may limit the generalizability of the findings.
Further research is needed to explore additional variables related to type 2 diabetes mellitus and foot ulcers, with a focus on the importance of glucose control and retinopathy in ulcer classification.
DFU properties, such as location and severity, were quantified using Wagner’s grading system (WG), which categorizes ulcers as grade 1 (superficial), grade 2 (deep), grade 3 (abscessed deep ulcer with bone involvement), grade 4 (localized gangrene), and grade 5 (extensive gangrene). The aim was to analyze the association between various clinical factors and the WG classification of DFUs.
The study cohort featured a substantial majority of T2DM cases at 96.8% (n = 853) with a male predominance of 59% (n = 520). The mean age was 58 years, and the cohort typically displayed characteristics of being overweight or obese, with a mean BMI of 30.00 kg/m2. The average duration of diabetes among the participants was 14.0 years as illustrated in Table 1.
Biochemical assessments shown in Table 2 yielded a mean serum creatinine of 0.92 mg/dL, blood urea of 33.71 mg/dL, and estimated Glomerular Filtration Rate (GFR) of 88.38 mL/min/1.73 m2. The fasting and random plasma glucose averages were 168.3 mg/dL and 289.3 mg/dL, respectively. Notably, poor glycemic control was observed in 72.3% of participants with a mean HbA1c level of 10.26%. The lipid profile revealed mean serum cholesterol and triglyceride levels of 186.2 mg/dL and 209.78 mg/dL, respectively.
DFU characteristics included ulcers predominantly on the right foot (48%), left foot (46%), or both feet (6%) ( Figure 1). According to Wagner’s grading, most ulcers were categorized as grade 1 (31%) and grade 2 (49%), with fewer instances of grades 3 through 5, which include more severe complications like deep infections, gangrene, and bone involvement ( Figure 2).
The study found statistically significant relationships for Wagner's DFU classification only with random plasma glucose levels and the presence of diabetic retinopathy as in Table 3. Other factors such as age, BMI, smoking status, family history, duration of diabetes, lipid profile, and presence of comorbid conditions like hypertension, ischemic heart disease, heart failure, and stroke showed no significant associations with Wagner's classification severity.
To identify independent predictors of DFU severity after controlling for confounders, multivariate ordinal logistic regression was performed on the T2DM cohort (n = 853). Three variables emerged as statistically significant independent predictors of higher Wagner grade: diabetic retinopathy (OR = 0.58, 95% CI 0.41–0.81, p = 0.002), diabetic neuropathy (OR = 0.65, 95% CI 0.48–0.88, p = 0.006), and estimated glomerular filtration rate (eGFR) (OR = 0.86, 95% CI 0.74–0.99, p = 0.040). These findings were consistent in the binary logistic regression (severe DFU Wagner grade ≥3 versus <3): diabetic retinopathy (OR = 0.58, 95% CI 0.35–0.98, p = 0.042) and diabetic neuropathy (OR = 0.61, 95% CI 0.39–0.95, p = 0.029) remained significant. Age, sex, BMI, diabetes duration, RBS, FBS, HbA1c, lipid profile, hypertension, IHD, and smoking were not independently associated with DFU severity in either model (all p > 0.05). Full results are presented in Table 4A and Table 4B.
| Variable | OR (95% CI) | p-value | Sig. |
|---|---|---|---|
| Age (years) | 0.99 (0.97–1.01) | 0.312 | NS |
| Sex (Male) | 1.10 (0.78–1.55) | 0.578 | NS |
| BMI (kg/m 2) | 1.01 (0.97–1.05) | 0.601 | NS |
| DM Duration (years) | 1.02 (0.99–1.05) | 0.201 | NS |
| RBS (mg/dL) | 1.00 (1.00–1.00) | 0.185 | NS |
| FBS (mg/dL) | 1.00 (1.00–1.00) | 0.422 | NS |
| HbA1c (%) | 1.03 (0.96–1.11) | 0.389 | NS |
| Total Cholesterol (mg/dL) | 1.00 (0.99–1.01) | 0.758 | NS |
| Triglycerides (mg/dL) | 1.00 (1.00–1.00) | 0.499 | NS |
| eGFR (mL/min/1.73 m 2) | 0.86 (0.74–0.99) | 0.040 | * |
| Hypertension | 0.92 (0.65–1.29) | 0.624 | NS |
| IHD | 1.22 (0.68–2.17) | 0.508 | NS |
| Smoking | 0.97 (0.63–1.48) | 0.875 | NS |
| Diabetic Retinopathy | 0.58 (0.41–0.81) | 0.002 | ** |
| Diabetic Neuropathy | 0.65 (0.48–0.88) | 0.006 | ** |
| Variable | OR (95% CI) | p-value | Sig. |
|---|---|---|---|
| Age (years) | 0.99 (0.97–1.02) | 0.614 | NS |
| Sex (Male) | 1.15 (0.75–1.77) | 0.527 | NS |
| BMI (kg/m 2) | 1.00 (0.95–1.05) | 0.879 | NS |
| DM Duration (years) | 1.02 (0.98–1.06) | 0.287 | NS |
| RBS (mg/dL) | 1.00 (1.00–1.00) | 0.212 | NS |
| FBS (mg/dL) | 1.00 (1.00–1.00) | 0.503 | NS |
| HbA1c (%) | 1.04 (0.94–1.14) | 0.468 | NS |
| Total Cholesterol (mg/dL) | 1.00 (0.99–1.01) | 0.841 | NS |
| Triglycerides (mg/dL) | 1.00 (1.00–1.00) | 0.623 | NS |
| eGFR (mL/min/1.73 m 2) | 0.85 (0.71–1.01) | 0.089 | Trend |
| Hypertension | 0.87 (0.55–1.36) | 0.540 | NS |
| IHD | 1.18 (0.57–2.45) | 0.651 | NS |
| Smoking | 0.89 (0.52–1.52) | 0.666 | NS |
| Diabetic Retinopathy | 0.58 (0.35–0.98) | 0.042 | * |
| Diabetic Neuropathy | 0.61 (0.39–0.95) | 0.029 | * |
The ever-rising costs and occurrence rates of diabetes have contributed to DFUs being a leading cause of DM-related hospitalizations.11 DFUs serve as strong indicators for increased mortality rates in diabetic patients due to cardiovascular or other diabetes-related complications.12 Consistent with other research, the current study found a higher male prevalence, which can be partially attributed to occupational differences between genders.6 However, some studies exhibit a female majority, possibly due to disparities in health care access.13
Our research identified a significant association between DFUs and both random blood sugar levels and diabetic retinopathy (DRP), congruent with findings from other studies that associated DFUs with peripheral vascular disease (PVD) and neuropathy.14 A similar correlation was highlighted in an Indonesian study regarding the significance of random blood sugar in the context of DFUs.15
While the current study did not observe a significant association between HbA1c levels and DFU severity, the high percentage of poor glycemic control among participants indicates the impact of diabetes management on the genesis of DFUs. This is supported by other studies that link HbA1c with the severity of Wagner grading.16 Contrary to some research confirming the impact of diabetes duration on DFU development,16 our study and a Malaysian report found no significant correlation, potentially due to different methodologies and duration benchmarks.17,18
On multivariate ordinal logistic regression, eGFR emerged as a significant independent predictor of higher Wagner grade (OR = 0.86, 95% CI 0.74–0.99, p = 0.040), indicating that lower renal function is independently associated with more severe DFU, even after adjusting for all confounders. This is consistent with a Taiwanese study confirming the association between reduced eGFR and severe ulcers and lower limb amputations. Chronic kidney disease (CKD) impairs wound healing through reduced growth factor synthesis, impaired immune function, and peripheral vascular insufficiency, collectively predisposing to more severe DFU. The earlier univariate analysis (Table 3) showing no significant correlation may reflect the limited power of chi-square testing compared to regression modelling.
Most of our study’s patients presented with grade 2 and grade 1 DFUs, reflecting trends observed in Iranian studies. This similarity suggests comparable healthcare practices and societal structures between the two neighboring countries.13 Other research from Korea exhibited variations, which could be due to differences in treatment approaches, wound care protocols, and multidisciplinary teams.19
The substantial association of DFUs with diabetic retinopathy was also noted in studies from Ethiopia and Brazil.20,21 This link may be attributed to the impaired self-care abilities in those with DRP, leading to DFU development.22 Moreover, DRP frequently co-occurs with peripheral neuropathy, a well-recognized DFU risk factor.23 These findings suggest that ophthalmic evaluation could be beneficial for patients with severe DFU to detect potential complications at an early stage.
On multivariate ordinal logistic regression, both diabetic retinopathy (OR = 0.58, 95% CI 0.41–0.81, p = 0.002) and diabetic neuropathy (OR = 0.65, 95% CI 0.48–0.88, p = 0.006) emerged as strong independent predictors of higher Wagner grade after adjusting for all confounders. The OR < 1 reflects that patients with retinopathy or neuropathy (coded as presence = 1 versus absence = 2 in this dataset) had higher Wagner grades. The mechanistic link is well-established: diabetic retinopathy is a marker of systemic microvascular damage; patients with retinopathy have greater capillary basement membrane thickening, endothelial dysfunction, and impaired angiogenesis in the lower limb, all of which directly compromise wound healing and ulcer severity. Diabetic peripheral neuropathy causes loss of protective sensation, leading to repetitive undetected trauma and delayed presentation at higher Wagner grades. Notably, random plasma glucose (RBS), which was significant on univariate analysis (Table 3), lost significance in the multivariate model, suggesting that its apparent association is mediated through or confounded by the presence of microvascular complications (retinopathy, neuropathy) rather than representing an independent effect.
Despite no significant statistical correlation between BMI and DFU severity, the majority of our patients were overweight or obese, which aligns with findings from African studies.20,24 Obesity is known to exacerbate atherosclerosis, a significant contributor to PVD, which plays a central role in the causation of DFUs.
Age was not significantly associated with DFU severity in our study; however, a large portion of our patients were above 60 years old, highlighting age as a factor in the development of diabetic complications, particularly atherosclerotic and neuropathic ones. This is echoed in studies from Saudi Arabia, India, and Thailand,25–27 while an Ethiopian study found no significant correlation likely due to its inclusion of younger, newly diagnosed patients.20
The absence of a statistically significant correlation between DFU prevalence and family history of diabetes in our study contrasts with a Chinese study that confirmed such a link.28 This variance could stem from differences in populations, inadequate data collection, and the inability of many patients to recall family medical histories.
More than half of our patients had an FBS below 140 mg/dL, with no significant correlation between FBS and Wagner DFU grade, which may be due to our patients visiting the center in a fasting state and receiving regular FBS monitoring. This contradicts findings from an Indian study that noted a significant correlation.29
Our findings showed no significant correlation between DFU severity and smoking, with most patients being nonsmokers, likely a result of ongoing education efforts about smoking's risks at our center. Other studies have also reported no significant association between smoking and DFU severity.14,30
There was no significant correlation between DFU severity and dyslipidemia in our study, whereas an Egyptian study found a significant link. These differing findings may be due to variations in patient populations and management strategies, as most of our patients were routinely treated with statins.31
This study has several limitations. First, its single-center, cross-sectional design precludes causal inference and limits generalizability to other populations and centers. Second, certain clinical variables (e.g., peripheral arterial disease assessment, wound microbiology) were incompletely documented in medical records, which may have introduced information bias. Third, the coding of binary variables (presence = 1, absence = 2) in the SPSS dataset means that OR < 1 for retinopathy and neuropathy reflects that their presence (lower numeric code) is associated with higher Wagner grades—this should be interpreted accordingly. Fourth, although multivariate regression was performed, residual confounding from unmeasured variables (e.g., wound duration, antibiotic use, previous DFU history) cannot be excluded. Future studies should employ longitudinal designs, post-hoc analyses, and larger multicenter cohorts to validate these findings.
This cross-sectional study of 853 patients with type 2 diabetes mellitus and active diabetic foot ulcers at TDEMC, Thi Qar, Iraq demonstrates that on multivariate logistic regression, diabetic retinopathy (OR = 0.58, p = 0.002), diabetic neuropathy (OR = 0.65, p = 0.006), and reduced eGFR (OR = 0.86, p = 0.040) are independent predictors of higher Wagner grade DFU severity. These microvascular complications—rather than metabolic parameters such as HbA1c, RBS, or lipid profile—emerge as the primary independent determinants of ulcer severity. These findings underscore the critical importance of routine ophthalmic and neurological evaluation, as well as renal function monitoring, in patients presenting with diabetic foot ulcers. Targeted interventions addressing microvascular complications could reduce DFU severity and the risk of amputation in this high-burden population.
Our research uniquely focuses on the T2DM population within a specific geographical location, which is essential for fostering strategies tailored to the local community. While random blood glucose and the presence of diabetic retinopathy had significant associations with the severity of DFUs according to Wagner’s classification, other variables such as age, BMI, and the duration of diabetes did not demonstrate a meaningful correlation. This suggests the need for more comprehensive research involving larger, diverse populations and multiple centers to draw conclusions that are more widely applicable.
The data garnered from this study contribute to the understanding of DFU prevalence and highlight the need for strict glycemic control, management of diabetes complications, and targeted interventions to prevent DFU development and progression. With concerted efforts from healthcare providers, patients, and policymakers, it is hoped that the incidence of DFUs in Iraq and similar communities can be diminished, thereby reducing the overall burden of diabetes.
This cross-sectional observational study, approved by the ethical committee of TDEMC by the (approval number IQ.TDEMC.REG.125/35 on the 10th of December 2020), adhered to the Helsinki declaration and involved written informed consent from all participants.
Zenodo: Assessing the features of diabetic foot ulcers among individuals with type 2 diabetes mellitus in Thi Qar, Iraq, https://zenodo.org/doi/10.5281/zenodo.11187872.32
Data are available under the terms of the Creative Commons Attribution 4.0 International license (CC-BY 4.0).
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Is the work clearly and accurately presented and does it cite the current literature?
Partly
Is the study design appropriate and is the work technically sound?
Partly
Are sufficient details of methods and analysis provided to allow replication by others?
Partly
If applicable, is the statistical analysis and its interpretation appropriate?
Partly
Are all the source data underlying the results available to ensure full reproducibility?
Yes
Are the conclusions drawn adequately supported by the results?
Partly
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Endocrinology; Diabetes mellitus and its complications (including diabetic foot); Clinical epidemiology; Observational study design; Biostatistics
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: nursing management
Is the work clearly and accurately presented and does it cite the current literature?
Partly
Is the study design appropriate and is the work technically sound?
Partly
Are sufficient details of methods and analysis provided to allow replication by others?
Partly
If applicable, is the statistical analysis and its interpretation appropriate?
Partly
Are all the source data underlying the results available to ensure full reproducibility?
Yes
Are the conclusions drawn adequately supported by the results?
Partly
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: immunogenetics
Is the work clearly and accurately presented and does it cite the current literature?
Yes
Is the study design appropriate and is the work technically sound?
Yes
Are sufficient details of methods and analysis provided to allow replication by others?
Yes
If applicable, is the statistical analysis and its interpretation appropriate?
Yes
Are all the source data underlying the results available to ensure full reproducibility?
Yes
Are the conclusions drawn adequately supported by the results?
Yes
Competing Interests: No competing interests were disclosed.
Reviewer Expertise: Diabetes, Endocrine and Metabolism
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