Expression of antimicrobial peptides in diabetic foot ulcer

Background

Foot ulcers are one of the main diabetes complications due to its high frequency and difficulty of complete healing. There are several factors that participate in diabetic ulcers development and limited information exists about the role of antimicrobial peptides (AMP) in its pathogenesis.

Objective

The aim of this study was to analyze the expression pattern of the main AMPs: Human Neutrophil Peptide (HNP)-1, Human β-defensin (HBD)-1, HBD-2, HBD-3, HBD-4 and cathelicidin LL-37 in biopsies from diabetic foot ulcers (DFU).

Methods

20 biopsies from DFU grade 3 according to Wagner's classification and 20 biopsies from healthy donors were obtained. Real time PCR, immunohistochemistry and primary cell cultures were performed.

Results

β-Defensins were overexpressed in DFU, whereas LL-37 has low or none expression in comparison with healthy skin. When primary cell culture from these biopsies were performed and infected with Staphylococcus aureus, epidermal cell from diabetic ulcers showed lower LL-37 expression compared with cell cultures from healthy donors skin.

Conclusion

These results suggest that though most AMPs are expressed in DFU, this production is not appropriate to promote wound healing and contain secondary infections.     

Specialty specific quality measures needed to improve outcomes in wound care

Despite the health care community's best efforts, 20% of diabetic patients who develop a diabetic foot ulcer will require some form of amputation. Those undergoing a major lower extremity amputation risk an increase in their five-year mortality rate to 56.6%, which is comparable to or higher than many forms of cancer. Given this perspective, quality measures need to be considered at each patient inflection point to drive increased compliance with best practices in order to redirect patients whose therapies fail. Medicare limited datasets (October 2015 through October 2019) retrospectively analyzed patients with diabetes receiving care for chronic lower extremity diabetic ulcers (LEDUs). The analysis demonstrated that only 21% of Medicare patients with hard-to-heal LEDUs received sharp debridement at intervals of every 7 days and less, while only 40% received sharp debridement at intervals of every 8 to 14 days. This is despite landmark prospective randomized controlled trials showing the benefits of frequent sharp debridement to patients with LEDUs. According to the Medicare data, when patients received debridement at intervals of 7 days or less with concurrently applied skin substitutes, observed amputation rates dropped by 65% to the lowest levels identified among Medicare LEDU episodes (2.1%). Optimal use of debridement and adjunctive use of skin substitutes significantly improves outcomes and lowers the use of healthcare resources. Another unexpected finding highlighted in the Medicare data analysis was that wound care providers have not been applying skin substitutes early enough. Clinical guidelines related to LEDUs have long relied on the seminal Sheehan marker study, which identified that diabetic ulcers that have not progressed to at least 53% healing after four weeks of conservative care have only a 9% chance of proceeding to closure by 12 weeks. It is therefore vital that patients move to advanced therapies within 30 to 45 days after initiation of failed conservative care; however, the Medicare claims data shows this is not happening regularly enough (average time to first skin substitute application >69 days) to benefit both the patient and the healthcare system. There is a demonstrable need for quality measures that encourage (1) frequent and adequate debridement throughout wound treatment, (2) earlier adoption of advanced treatments, such as skin substitutes, for LEDUs to align with clinical guidelines, (3) the application of skin substitutes to better align with medical evidence, which is associated with improved patient outcomes, as well as (4) expansion of best practices across all demographic and socioeconomic populations.     

Comparison of vitamin D levels in diabetes mellitus patients with and without diabetic foot ulcers: An analytical observational study in Jakarta,Indonesia

Diabetic foot ulcer (DFU) is a form of chronic wound which becomes a serious complication in diabetes mellitus (DM). Recently, the role of vitamin D on T cell-mediated immunity, pancreatic insulin secretion, and its mechanism on cell growth and healing processes have been reported. This study aims to compare the vitamin D level of DM patients with DFU and without DFU to assess the duration and severity of DFU and its correlation with vitamin D levels. The sociodemographic characteristics and DFU duration were documented. The severity was examined in accordance with PEDIS classification. 25-hydroxyvitamin D (25[OH]D) was analysed using in-vitro chemiluminescent immunoassay (CLIA). Statistical analysis was performed and the P-value <.05 was considered as statistically significant. The vitamin D levels in DM patients with and without DFU were 8.90 ng/mL (6.52–10.90) and 16.25 ng/mL (13–19.59), respectively, with P < .001. There was no correlation between the duration of DFU and DFU severity by PEDIS score with vitamin D levels. Vitamin D levels in DM patients with DFU are lower than those in patients without DFU. However, there was insufficient evidence to conclude that there is no correlation between the DFU duration and DFU severity by PEDIS score with vitamin D levels.