Diabetic foot disease is an important and disabling complication of diabetes mellitus, causing significant morbidity and increased risk for lower-limb amputation. The global burden of diabetes is rising. There are predicted to be 463 million adults aged 20-79 with diabetes in 2019, which is expected to rise substantially over the next few decades. Foot disease is regarded as one of the most serious complications of diabetes. It affects about 15-25% of diabetic patients at some stage in their life. The pathophysiology of diabetic foot disease is complex, multifactorial, and includes neuropathy, peripheral arterial disease, and infection-all of them exacerbated by chronic hyperglycemia and associated metabolic disturbances.

It clinically forms an extensive spectrum of conditions ranging from superficial skin ulcers to deep infections, gangrene, etc. Neuropathy affects the limbs by depriving them of sensation, hence unnoticed injuries may occur. On the other hand, PAD reduces blood supply and impairs healing, thereby making the affected limb predisposed to infection. Chronic hyperglycemia complicates the situation by impairing the immune function and encouraging microbial activities. Early recognition of these clinical manifestations is essential for effective treatment and prevention of progression into more advanced stages.

Glycemic control is a critical component of the treatment of diabetic foot disease. Several retrospective studies have associated poor glycemic control with the development of foot ulcers and delayed healing. Chronic hyperglycemia impairs vascular endothelial function through various mechanisms, including advanced glycosylation end-product formation, which decreases nitric oxide bioavailability and creates arterial stiffness, impairing limb vascularity. Such retrospective data analyses suggest that the longer patients live with hyperglycemia, the more devastating limb complications they are likely to experience and therefore highlight the urgent need for early glycemic control. Doppler ultrasound, CT angiography, and MRI are important diagnostic imaging techniques in assessing limb perfusion in diabetic foot disease and in evaluating the extent of involvement. This not only helps in diagnosing but also assists in guiding the therapeutic approach and helps clinicians decide on revascularization strategies along with other further interventions.

The treatment for diabetic foot disease is multi-disciplinary, by combining medical management with surgical debridement and revascularization procedures along with antimicrobial therapy. The objectives are maximum smoothing of glycemic control, restoration of sufficient limb perfusion and eradication of infection. Retrospective effectiveness analysis of treatment on patients and outcomes has, over recent periods, shown that novel treatments incorporated into practice include negative pressure wound therapy, hyperbaric oxygen therapy and the application of biologics, such as growth factors and stem cell therapies to improve diabetic foot ulcer healing rates.

This review shall cover the clinical presentation of diabetic foot disease, how glycemic status influences disease progression, assessment of limb vasculature through advanced imaging techniques, and treatment options available. That will hugely help improve the outcomes for diabetic foot disease patients across the globe.

Study Design and Setting: A Retrospective Observational Study conducted in the Department of General Surgery at Bangalore Medical College and Research Institute Between June 2022 and June 2023 Among Diabetic Patients Coming into the Tertiary Care Institution with Foot Complications Retrospective assessment of clinical presentations, glycemic status, limb vascularity, and corresponding treatment modalities using the patient record for the purpose of the study.

Study Population: In this study, patients were recruited who were aged 18 years or older, diagnosed with either type 1 or type 2 diabetes mellitus, and were presenting with foot ulcers, infections, gangrene, or other diabetic foot complications. Participants were excluded if their foot ulcers or infections were identified to be due to non-diabetic causes such as certain vascular occlusive diseases unrelated to diabetes. Prevalence studies and statistical power calculations regarding significant associations between glycemic control, vascularity, and clinical outcomes estimate the sample size at 200 patients.

Inclusion and Exclusion criteria: All diabetic patients aged ≥18 years with a registered diagnosis of diabetes mellitus along with diabetic foot disease in clinical history. Also included were those with complete records of glycemic control, imaging studies, and the course of treatment.

Participants with non-diabetic foot disease, end-stage renal disease and the need for dialysis and patients whose medical records were incomplete, were excluded from the study.

Data Source: The data collection was done retrospectively by reviewing the participant's medical records. This entailed clinical examination records, laboratory tests, and imaging studies. Data recording also included the clinical characteristics of diabetic foot disease, like the size, depth, and infection status of the existing lesions. The glycemic control of the patients was evaluated through the levels of FPG, PPBG, and HbA1c. For the purpose of the study, the two categories of the patients have been divided with respect to their glycemic control: the well-controlled diabetes patients having an HbA1c level less than 7% and the poorly controlled diabetes patients having an HbA1c level of 7% or more. Radiological imaging with Doppler ultrasound was scrutinized in relation to the assessment of arterial flow and for the determination of the ankle-brachial index of peripheral arterial disease. If there had been a history of suspicion of critical limb ischemia, computed tomographic angiography and magnetic resonance angiography had to determine the degree of occlusion and status of limb perfusion.

Treatment Modalities: The treatment modalities include medical, surgical as well as adjunctive therapies. Medical treatment has constituents of glycemic control, which entails the use of insulin or oral hypoglycemic agents, along with antibiotic therapy for infected ulcers. Surgical interventions included debridement, minor amputations, and major amputations in serious cases. Limb revascularization procedures like angioplasty or bypass surgery were documented based on the vascular imaging studies. In certain cases, adjunctive therapies including the use of negative pressure wound therapy and NPWT were also noted as various measures to aid the process of wound healing.

Follow-up: The patient outcomes were estimated based on the follow-up records of 6 months. Among all the primary endpoints taken into consideration, wound healing, limb salvage with no requirement for amputation, and mortality were important. Secondary endpoints included improvements in glycemic control and limb vascularity after the treatment.

Statistical Analysis: Data were analyzed by using SPSS version 26.0. Continuous variables like the levels of glycemia, size of ulcers were summarized as mean ± SD and assessed by t-test or ANOVA, when appropriate. Categorical variables such as the status of wound infection and amputation rates were evaluated using chi-square tests or Fisher's exact test. The effect of glycemic control and vascularity in explaining clinical outcomes was studied using logistic regression. P value < 0.05 was considered to be significant.

Two hundred patients with diabetic foot disease were enrolled, with a mean age of 56.4 ± 10.2 years; 65% were males and 35% females. The duration of diabetes ranged from 5-20 years, with a mean of 12.3 ± 4.8 years. Results are provided in three broad categories, namely clinical presentations, glycemic status, limb vascularity, and treatment modalities used.

Clinical Presentations

Most of the patients presented with foot ulceration, 78%, infections including cellulitis and osteomyelitis seen in 52%, while gangrene was present in 15% of the cohort. The ulcers were categorized using the Wagner grading system: [Table 1]

Table 1: Distribution of Patients According to Wagner Grading of Diabetic Foot Ulcers.

Most ulcers, 40% of them, were classified as Grade 2, while severe ones with gangrene accounted for 10%: Grade 4 and 5 of the study population.

Glycemic Status

The patients were then stratified as well-controlled, represented by an HbA1c of less than 7%, and poorly controlled, represented by HbA1c of 7% or above. Overall, a poorly controlled glycemic status included 60% of the entire cohort, represented by an average HbA1c of 8.5 ± 1.4%. There was a statistically significant association between poor glycemic control and severity of foot disease, represented by the fact that patients in a poor controlled status are more likely to be presented with higher Wagner grades, represented by a p-value of 0.01. [Table 2]

Table 2: Distribution of Patients According to Glycemic Control and Mean HbA1c Levels

Limb Vascularity

Doppler ultrasound showed impaired arterial flow of the lower limbs in 45% and critical limb ischemia, with an ankle-brachial index (ABI) of less than 0.5, in 25%. Further imaging with CTA or MRA was available in 40 patients where clinically suspected. Of these, significant occlusions were revealed in 30 patients, 75% of whom required vascular interventions. [Table 3]

Table 3: Distribution of Patients Based on Limb Vascularity

Treatment Modalities

Treatment modalities depended on the clinical severity and vascular status and ranged from medical, surgical, and adjunctive therapy. Antibiotic therapy was needed for 65% of cases, while 40% underwent surgical debridement. Percentages for minor and major amputation were 18% and 12%, respectively. Revascularization was possible in 28 patients either by angioplasty or bypass; significant improvement in limb perfusion was achieved.[Table 4]

Table 4: Treatment Modalities Administered to Patients with Diabetic Foot Disease

Outcomes

Whereas at 6-month follow-up, complete wound healing was seen in 60%, partial healing was observed in 25%. Limb salvage rate in this series was 88%. Overall mortality rate was 5%. Poor glycemic control HbA1c ≥ 7%, and critical limb ischemia were associated with poor outcomes-higher amputation and mortality rates p < 0.05. [Table 5]

Table 5: Outcomes at 6-Month Follow-Up

Graph 1: Distribution of Diabetic Foot Disease by Wagner Grade

Graph 2: Relationship Between Glycemic Control (HbA1c Levels) and Wagner Grades

Graph 3: Distribution of Patients According to Limb Vascularity

Graph 4: Comparison of Treatment Modalities and Outcomes.

The aim of the present study was to retrospectively investigate the clinical presentations, the glycemic status and limb vascularity, and various treatment modalities of patients diagnosed with DFD. These findings presented in this report further elaborate the complex, multifactorial pathophysiology of DFD but at the same time indicate the paramount role of glycemic control and vascular status for the clinical outcome.

The vast majority of patients had active diabetic foot ulcers, at 78%, while a considerable number also presented with infection, 52%, and gangrene, 15%. This agrees with previous literature indicating that foot ulcers are a common complication of diabetes due to peripheral neuropathy and PAD.  The Wagner classification of distribution of ulcers indicated that the majority of ulcers fell into Grade 2, which is regarded as moderately severe, while more severe presentations of Grades 4 and 5 accounted for 10% of cases. These results are consistent with other studies reporting similar trends in diabetic foot ulcer severity in hospitalized patients .

Thus, glycemic control is the major determinant in the development and outcomes of diabetic foot disease. Further, this study demonstrated that 60% of patients had poor glycemic control, HbA1c ≥ 7%, which was directly related to a higher Wagner grade with worse outcomes, including an increased risk of infection, amputation, and mortality. These findings indeed confirm the important role of hyperglycemia in enhancing endothelial dysfunction, impaired wound healing, and increased risk of infection, identified from studies such as that by Amin and Nawito (2012). Moreover, hyperglycemia fosters the development of advanced glycation end-products, which enhance vascular and neural damage, contributing to the risk of severe foot complications .

In these patients, the limb vascular assessment, as aided by Doppler ultrasound and other sophisticated imaging studies, was compromised in 45%, while critical limb ischemia, as depicted by ABI < 0.5, was realized in 25% of the patients. These findings are essentially in agreement with the results of previous series that emphasize the role of atherosclerotic PAD in diabetic foot disease, typified by decreased flow resulting in ischemia and impeded wound healing.  Advanced imaging using CTA and MRA showed the real situation of occlusion and aided in the planning of revascularization methods. The same guidelines of the European intermittent claudication have again emphasized the role of revascularization measures in critical limb ischemia, which tallies with the findings in this study .

This paper adopted a multidisciplinary approach in the management of diabetic foot disease: medical management involving glycemic control and antibiotics, surgical debridement, limb revascularization, and adjunctive therapies like NPWT. Medical management alone was done in as many as 65% of patients, while surgical debridement and amputations were carried out on more severe cases. The limb salvage rate in this series stands at 88%, while the overall mortality rate was 5%.

These results indicate the effectiveness of a multidisciplinary approach to therapy that emphasizes the importance of timely surgical input along with state-of-the-art wound care practices. The results are in accordance with other studies where timely revascularization, along with proper wound care treatment, has been associated with improved outcomes in patients with diabetic foot disease regarding limb salvage and overall survival rates.

It was specifically mentioned that NPWT, as adjuvant treatments, have presented better results in wound healing and selected limb salvage. More so, NPWT has been said to improve tissue oxygenation, which improves the course of wound healing in ischemic-infected foot ulcers. This thus agrees with the work of Balestra et al. (2023), who have pointed out the therapeutic benefit of hyperbaric oxygen for chronic diabetic wounds.

The findings of the current study bear significant importance regarding early diagnosis and intervention in patients with diabetic foot disease. Poor glycemic control and critical limb ischemia portended a worse clinical outcome, with higher amputation and mortality rates. Therefore, strict control of glycemia and regular follow-up of vascular status by Doppler and advanced imaging will improve the overall clinical outcome.

This would require a multidisciplinary approach to optimize the management of such patients, involving vascular surgeons, diabetologists, and wound care specialists. Results support international guidelines recommendations on the need for revascularization of patients with critical ischemia to improve the outcomes in limb salvage, as Mazzone et al. (2013) stated.

Although the case series has provided a valuable insight into the clinical, radiological, and therapeutic features of DFD, several limitations exist: the single-center study may limit the generalization to findings in populations with different demographics and access to health care. Furthermore, extended follow-up longer than six months could provide further information about the durability of wound healing and limb salvage.

These findings from the present study suggest a mutually interrelated scenario of glycemic control, vascular status, and treatment modalities that dictates the outcome of diabetic foot disease management. Poor glycemic control and impaired vascularity emerged as independent predictors of poor clinical outcome in the form of higher amputation and mortality rates. Comprehensive multidisciplinary management, including glycemic optimization, wound care, and revascularization, holds the key for improving patient outcomes. Long-term outcomes from future research may reflect advantages of novel therapies, such as adjunctive wound-healing techniques.

The study has accentuated the role of glycemic control and vascular status on the clinical outcome in diabetic foot disease. Those with poor glycemic control and impaired vascularity had a higher complication rate, including severe ulceration, infection, and loss of the limb. It also stressed that the limb salvage and mortality improved in a multidisciplinary approach using optimization of glycemia, radiological assessment of vascularity, timely revascularization, and advanced techniques of wound care. These findings again point towards the demand for early intervention and comprehensive management, besides continued research into novel therapeutic approaches, all put together to optimize the outcome in patients with diabetic foot disease.

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