Research progress and application prospect of adipose-derived stem cell secretome in diabetes foot ulcers healing.

Diabetic foot ulcers (DFUs) are chronic wounds and one of the most common complications of diabetes, imposing significant physical and mental burdens on patients due to their poor prognosis and treatment efficacy. Adipose-derived stem cells (ADSCs) have been proven to promote wound healing, with studies increasingly attributing these beneficial effects to their paracrine actions. Consequently, research on ADSC secretome as a novel and promising alternative for DFU treatment has been extensively conducted. This article provides a comprehensive review of the mechanisms underlying refractory DFU wounds, the secretome of ADSCs, and its role in promoting wound healing in diabetes foot ulcers. And the review aims to provide reliable evidence for the clinical application of ADSC secretome in the treatment of refractory DFU wounds.

[Free vastus lateralis flap combined with skin grafting for repairing small- and medium-sized lacunar defects in non-weight-bearing area of diabetic foot].

Objective: To explore the feasibility and effectiveness of free vastus lateralis flap combined with skin grafting for repairing small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot. Methods: Between January 2022 and October 2023, 8 patients (8 feet) with small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot were admitted. There were 6 males and 2 females, with an average age of 64.3 years (range, 58-76 years). The duration of the diabetic foot ulcer ranged from 2 to 7 weeks (mean, 4.3 weeks). The wound was located between the metatarsal bones in 4 cases, on the medial side of the foot in 2 cases, on the lateral side of the foot in 1 case, and on the dorsal and lateral sides of the foot in 1 case. The length of wound was 4.0-12.0 cm, the width was 3.0-5.0 cm, and the depth was 1.2-2.0 cm. The free vastus lateralis flaps were designed to repair the wounds, and skin grafting covered the vastus lateralis flaps. The length of the vastus lateralis flap was 5.0-14.0 cm, the width was 3.5-6.0 cm, and the thickness was 1.0-1.5 cm. The donor sites of the muscle flaps were directly sutured. Results: The time for vastus lateralis flaps harvested ranged from 30 to 80 minutes (mean, 55.0 minutes), and the total operation time ranged from 125 to 170 minutes (mean, 147.5 minutes). All muscle flaps and skin grafts survived successfully, and the wounds and the incisions at the donor sites healed by first intention. All patients were followed up 6-24 months, with an average of 12.8 months. The appearances of 3 patients who did not follow the doctor's instructions for pressure treatment of the muscle flaps were a little bloated, and the rest had a good appearance. The texture of the muscle flaps was soft. There were linear scars at the donor sites. There was no recurrence of ulcers during follow-up. All patients could walk independently without limitation of daily activities at last follow-up. Conclusion: The application of free vastus lateralis flap combined with skin grafting to repair small- and medium-sized lacunar defects in the non-weight-bearing area of diabetic foot has the advantages of simple operation and time-saving as well as small damage to the donor site, with good repair effect, especially for the elderly patients who are not suitable for prolonged anesthesia.

[Etiopathogenetic features of bone metabolism in patients with diabetes mellitus and Charcot foot].

Diabetic neuropathy is one of the most common diabetes mellitus complications associated with mediocalcinosis of the lower extremities, a significant decrease in feet bone mineral density, and a high incidence of cardiovascular disease. In most cases, calcium-phosphorus metabolism changes occur in patients with diabetic neuroarthropathy, or Charcot foot, when we can observe feet local osteoporosis, which in 90% of cases associated with a vessel's calcification of the lower extremities in the majority of diabetes population. A large number of studies presented literature have demonstrated that patients with Charcot foot can have accelerated bone metabolism and increased bone resorption. Patients with Charcot foot often have crucial abnormalities in the calcium-phosphorus parameters, bone metabolism, and levels of vitamin D and its metabolites. In addition, the duration of diabetes mellitus, the degree of its compensation widely affects the development of its micro- and macrovascular complications, which could also accelerate the development of mineral and bone disorders in these types of patients. Multifactorial pathogenesis of these disorders complicates the management of patients with a long and complicated course of diabetes mellitus. This review discusses the peculiarities of vitamin D metabolism, the importance of timely diagnosis in phosphorus-calcium disorders, and the specifics of therapy in these patients. Special attention is paid to the timely diagnosis of the Charcot's foots acute stage based on the bone marrow edema by MRI evaluation and the possibility of reducing the immobilization period.

Healthcare workers' perspectives on diabetic foot complications among type 2 diabetes mellitus patients in Fiji.

INTRODUCTION: Diabetic Foot Complications (DFCs) are a growing cause of morbidity and mortality with less than one third of physicians able to discern the signs of diabetes related peripheral neuropathy. DFCs and resultant amputations account for a considerable proportion of surgeries in Fiji, with very limited literature available to verify the factors that influence these alarming figures. This study aimed to explore Health Care Workers' (HCWs) perspectives on diabetic foot complications and challenges of foot care management in Fiji. METHOD: An exploratory descriptive qualitative design was used among HCWs at the Sigatoka Sub Divisional Hospital (SDH), Fiji in 2021. HCWs at the SDH were required to have a minimum work experience of at least six months in public health. All participants who met the inclusion criteria were selected through purposive sampling. Data was collected using a focus group discussion guide composed of semi-structured open-ended questions to guide the Focus Group Discussions (FGDs). Focus discussions were audio recorded and transcribed with thematic analysis applied to derive the themes and sub-themes outlined in the study. RESULTS: Twenty HCWs participated in four FGDs with four major themes identified. The first theme was HCWs' perceptions and practice of foot care which revealed that all participants had adequate diabetic foot care knowledge. The second theme was factors affecting foot care which was mainly focused on identified barriers such as inadequate patient foot care knowledge, the lack of resources such as manpower, and health system challenges like the COVID-19 pandemic. The third theme is creating awareness among patients and HCWs to improve foot care practices. The fourth theme is strengthening foot care practices at the different levels of health care that is aimed at optimizing diabetic foot outcomes. CONCLUSION: Various foot care barriers namely patient factors and the lack of resources is a concern depicted in this study. There is a need to address health system barriers and enforce diabetic foot education, screening and care for patients and the community.

Enhancing diabetic foot ulcer healing: Impact of the regulation of the FUS and ILF2 RNA­binding proteins through negative pressure wound therapy.

Diabetic foot ulcer (DFU) is a destructive complication of diabetes. Negative pressure wound therapy (NPWT) promotes DFU wound healing through an undetermined mechanism. In the present study, RNA sequencing was performed on wound granulation tissue from 3 patients with DFU before and after 1 week of NPWT. The fused in sarcoma (FUS) and interleukin enhancer binding factor 2 (ILF2) encoding RNA­binding proteins (RBPs) were screened from the sequencing data, and wound tissue samples from 24 patients with DFU were validated and analyzed before and after receiving NPWT by reverse transcription­quantitative PCR, western blotting and immunohistochemistry. In addition, in vitro and in vivo experiments were conducted to determine the effect of the expression of FUS and ILF2 on the function of human epidermal keratinocyte cells (HaCaT cells) and the healing of diabetic skin wounds. The results indicated that NPWT induced the upregulation of 101 genes and the downregulation of 98 genes in DFU wound granulation tissue. After NPWT, the expression of FUS and ILF2 was significantly upregulated (P<0.05). Pearson's correlation coefficient showed that the changes in FUS and ILF2 before and after NPWT were negatively correlated with changes in white blood cells, the neutrophil percentage, C­reactive protein, tumor necrosis factor­α, reactive oxygen species, lipid peroxides, matrix metalloproteinase (MMP) 2 and MMP9 (P<0.05), but positively correlated with the anti­inflammatory factor, IL­4 (P<0.01). There was also a positive correlation (P<0.05) with the 4­week ulcer healing rate. Additionally, the knockdown of FUS and ILF2 expression inhibited the proliferation and migration of HaCaT cells, while increasing cell apoptosis. In vivo, the knockdown of FUS and ILF2 significantly reduced the rate of skin wound healing in diabetic mice. The results of the present study therefore provide new insights into the mechanism by which NPWT promotes DFU wound healing. In conclusion, the RBPs, FUS and ILF2, promoted DFU wound healing by regulating the function of keratinocytes and reducing the inflammatory response and oxidative stress.

The correlation between serum vitamin D status and the occurrence of diabetic foot ulcers: a comprehensive systematic review and meta-analysis.

The association between vitamin D concentrations and the occurrence of diabetic foot ulcers (DFUs) remains a topic of ongoing debate. In order to provide a comprehensive and updated review, we conducted this meta-analysis to further investigate the relationship between vitamin D concentrations and DFUs occurrence. The following databases, including Cochrane Library, EMBASE, Web of Science, PubMed, CBM, CNKI, WANFANG DATA and VIP Database, were systematically searched for studies published up to Dec. 20th, 2023. The combined estimation was calculated using both fixed-effects and random-effects models. The overall effect size was reported as a weighted mean difference (WMD) with a corresponding 95% confidence interval (95%CI). Data analysis was performed utilizing Review Manager 5.4 and Stata 14. The Protocol has been registered in PROSPERO CRD42024503468. This updated meta-analysis, incorporating thirty-six studies encompassing 11,298 individuals with or without DFUs, demonstrated a significant association between vitamin D deficiency/insufficiency and an elevated risk of DFUs occurrence (< 25 nmol/L, OR 3.28, P < 0.00001; < 50 nmol/L, OR 2.25, P < 0.00001; < 75 nmol/L, OR 1.67, P = 0.0003). Vitamin D concentrations were significantly lower in individuals with DFUs compared to those without DFUs (P < 0.00001). Subgroup analyses consistently demonstrated this trend among the older population (> 50 years, P < 0.00001), individuals with long duration of diabetes (> 10 years, P < 0.00001), and those with poor glycemic control (mean HbA1c 8%-9% and > 9%, P < 0.00001).

Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice.

Background: Diabetic foot ulcers (DFUs) pose a substantial healthcare challenge due to their high rates of morbidity, recurrence, disability, and mortality. Current DFU therapeutics continue to grapple with multiple limitations. Senescent cells (SnCs) have been found to have a beneficial effect on acute wound healing, however, their roles in chronic wounds, such as DFU, remain unclear. Methods and results: We collected skin, fat, and muscle samples from clinical patients with DFU and lower limb fractures. RNA-sequencing combined with qPCR analyses on these samples demonstrate a significant accumulation of SnCs at DFU, as indicated by higher senescence markers (e.g., p16 and p21) and a senescence-associated secretory phenotype (SASP). We constructed a type 2 diabetic model of db/db mice, fed with a high-fat diet (Db-HFD), which were wounded using a 6 mm punch to the dorsal skin. HFD slightly affected wound healing in wild-type (WT) mice, but high glucose significantly delayed wound healing in the Db-HFD mice. We injected the mice with a previously developed fluorescent probe (XZ1208), which allows the detection of SnCs in vivo, and observed a strong senescence signal at the wound site of the Db-HFD mice. Contrary to the beneficial effects of SnCs in acute wound healing, our results demonstrated that clearance of SnCs using the senolytic compound ABT263 significantly accelerated wound healing in Db-HFD mice. Conclusion: Collectively, these findings suggest that SnCs critically accumulate at wound sites, delaying the healing process in DFUs. Thus, targeting SnCs with senolytic therapy represents a promising approach for DFU treatment, potentially improving the quality of life for patients with DFUs.

Accelerating diabetic wound healing with Ramulus Mori (Sangzhi) alkaloids via NRF2/HO-1/eNOS pathway.

Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus. Ramulus Mori (Sangzhi) alkaloids (SZ-A), an approved oral medication for type 2 diabetes, have not been explored for their potential to enhance the processes involved in diabetic wound healing. This study aims to investigate SZ-A's role in diabetic wound healing mechanisms. The in vivo experimentation involves dividing the subjects into NC and SZ-A groups, with SZ-A dosed at 200 and 400 mg/kg, to assess the therapeutic efficacy of SZ-A. The results of the animal studies show that SZ-A intervention accelerates the processes of diabetic angiogenesis and wound healing in a manner dependent on its concentration. Additionally, a pathological model using advanced glycation end products (AGEs) in HUVECs demonstrates SZ-A's cytoprotective effect. In vitro, SZ-A intervention significantly increases cell proliferation, migration and tube formation, protecting HUVECs from oxidative stress injury induced by AGEs. Mechanistically, SZ-A exerts a protective effect on HUVECs from oxidative stress damage through the activation of the NRF2/HO-1/eNOS signaling pathway. The findings suggest that SZ-A exhibits considerable potential as a promising candidate for treating DFUs, which will aid in more effectively integrating plant-based therapies into clinical settings.

Effectiveness of negative pressure wound therapy in treating diabetic foot ulcers: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Diabetic foot ulcers (DFUs) present devastating complications. Management of these wounds includes applying a vacuum device composed of a fenestrated tube embedded in a foam dressing and connected to a vacuum pump to collect the fluid in a vessel. OBJECTIVE: To review the effectiveness of negative pressure wound therapy (NPWT) in treating DFUs and evaluate the clinical outcomes of full and partial wound healing. METHODS: A systematic review and meta-analysis of randomized controlled trials was conducted after searching the PubMed, Web of Science, and Cochrane Library databases. Studies that described the use of NPWT in the management of DFUs were included and compared with different interventions for the proposed outcomes. RESULTS: A total of 14 studies were included, 1 of which was later excluded during internal validation. Wound healing outcomes were analyzed in 2 studies, showing the superiority of total wound healing in the NPWT group. Ten studies compared the effect of different interventions on wound area reduction and 8 of these results were best with NPWT. Three studies showed clinical and statistical homogeneity (I² = 100%), making it possible to conduct a meta-analysis. CONCLUSION: Although the articles included in this systematic review have limitations regarding methodological quality and clinical heterogeneity, the results showed the potential benefit of NPWT in healing and wound area reduction. These outcomes are essential in the prevention of amputation in patients with DFU.

Methicillin-resistant Staphylococcus aureus in diabetic and non-diabetic foot infections.

To identify the incidence of methicillin-resistant Staphylococcus aureus (MRSA) infection, reinfection and clinical outcomes. Four hundred forty-six patients that were admitted to the hospital with moderate or severe foot infections were retrospectively reviewed. Tissue and bone cultures were obtained from the index hospital admission. Conversion was defined as methicillin susceptible Staphylococcus aureus in the first culture and subsequently MRSA when there was a reinfection. The incidence of MRSA was 7.8% (n = 35), with no significant difference between soft tissue infections (7.7%) and osteomyelitis (8.0%). MRSA incidence was 9.4 times higher in non-diabetics (23.8% vs. 3.2%, p = <0.01). The incidence of reinfection was 40.8% (n = 182). Conversion to MRSA was seen in 2.2% (n = 4) total, occurring in 5.4%. Non-diabetics were 20.1 times more likely to have MRSA reinfection than people with diabetes (28.6% vs. 1.9%, p < 0.001). MRSA patients had a higher proportion of healed wounds (82.4% vs. 69.3%, p = 0.02). There were no differences in other clinical outcomes in MRSA vs. other infections in reinfection (28.6% vs. 24.3%, p = 0.11), amputation (48.6% vs. 52.0%, p = 0.69) or hospitalization (28.6% vs. 42.6, p = 0.11). The incidence of MRSA for the first infection (7.8%), reinfection (6.0%) and conversion to MRSA (2.2%) was low. MRSA was 9.4 times more common in people without diabetes.

[Acupuncture artery technique at Zusanli (ST 36) for Wagner grade 0 diabetic foot].

OBJECTIVE: To observe the clinical efficacy of acupuncture artery technique at Zusanli (ST 36) for Wagner grade 0 diabetic foot. METHODS: Sixty patients with Wagner grade 0 diabetic foot were randomly divided into an observation group and a control group, with 30 patients in each group. Both groups selected bilateral Zusanli (ST 36). In the control group, the needle was inserted about 10 mm under ultrasound guidance to avoid blood vessels in the Zusanli (ST 36) area, with needle retention for 5 min without manipulation. In the observation group, the needle was inserted about 25 mm under ultrasound guidance to the anterior tibial artery branch below Zusanli (ST 36), followed by lifting and thrusting manipulation for 5 min before withdrawing the needle. Both groups were treated twice a week for 4 weeks. The traditional Chinese Medicine (TCM) syndrome scores were observed; infrared thermography was used to measure the temperature difference between the left and right sides in four areas, i.e. the medial malleolus, lateral malleolus, and upper and lower parts of the sole of the foots; Doppler ultrasound was used to measure the logarithm of the peak systolic velocity (ln PS) and the logarithm of the time average maximum velocity (ln TAMAX) of the anterior tibial artery below the right Zusanli (ST 36); the ankle-brachial index (ABI) was measured using Doppler blood flow detector and blood pressure monitor before treatment, after the first treatment, and at the end of treatment. Clinical efficacy was compared between the two groups. RESULTS: Compared before treatment, the TCM syndrome scores in both groups were reduced after the first treatment and at the end of treatment (P<0.01, P<0.05), and the scores in the observation group were lower than those in the control group (P<0.01). In the observation group, compared before treatment, the maximum, minimum, and average temperature differences between the left and right sides of the upper and lower parts of the sole of the foots, medial malleolus, and lateral malleolus were reduced after the first treatment and at the end of treatment (P<0.05, P<0.01). After the first treatment, the maximum temperature difference between the left and right sides of the upper part of the sole of the foots and the medial malleolus in the observation group was lower than that in the control group (P<0.05). At the end of treatment, except for the average temperature difference of the medial malleolus, the maximum, minimum, and average temperature differences between the left and right sides of the upper and lower parts of the sole of the foots, medial malleolus, and lateral malleolus in the observation group were lower than those in the control group (P<0.01, P<0.05). After the first treatment and at the end of treatment, the ln PS, ln TAMAX, and ABI of the anterior tibial artery below the right Zusanli (ST 36) in the observation group were higher than those before treatment (P<0.01) and higher than those in the control group (P<0.01). The total effective rate in the observation group was 96.7% (29/30), higher than 3.3% (1/30) in the control group (P<0.05). CONCLUSION: Acupuncture artery technique at Zusanli (ST 36) could effectively improve the clinical symptoms of patients with Wagner grade 0 diabetic foot, increase blood flow velocity in the lower limb vessels, and reduce the temperature difference between the left and right lower limbs.

A multicentre clinical trial evaluating the outcomes of two application regimens of a unique keratin-based graft in the treatment of Wagner grade one non-healing diabetic foot ulcers.

Diabetic foot complications that lead to lower extremity amputations pose a significant challenge to the entire global health system. In this multicentre clinical trial, 26 patients with chronic Wagner one diabetic foot ulcers (DFUs) were treated with a unique human keratin matrix graft applied either weekly or bi-weekly, in addition to standard of care. The hypothesis was that bi-weekly application would be similar to weekly application. The primary endpoint was complete wound closure by 12 weeks, and secondary endpoints included healing time, percent area reduction and weekly changes in peripheral neuropathy, pain and quality of life. In the intent-to-treat population, 77% (10/13) of DFUs treated with bi-weekly application healed compared with 69% (9/13) treated with weekly application. The mean time to heal within 12 weeks in the bi-weekly group was 61 days and in the weekly group was 54 days. The mean percent area reduction at 12 weeks was 94.7% in the bi-weekly group compared with 84.8% in the weekly group. The number of grafts used in the bi-weekly group was 3.9 compared with 6.2 in the weekly group. The results of this trial confirm our hypothesis that whether bi-weekly or weekly application of the unique keratin matrix graft is used to treat nonhealing indolent DFUs, there is a high rate of complete healing. Based on these results, future studies should be conducted that further investigate the use of this novel human keratin matrix graft for the treatment of chronic DFUs.

Biomarkers of local inflammation at the skin's surface may predict both pressure and diabetic foot ulcers.

This commentary considers the similarities which exist between pressure ulcers (PUs) and diabetic foot ulcers (DFUs). It aims to describe what is known to be shared-both in theory and practice-by these wound types. It goes on to detail the literature surrounding the role of inflammation in both wound types. PUs occur following prolonged exposure to pressure or pressure in conjunction with shear, either due to impaired mobility or medical devices. As a result, inflammation occurs, causing cell damage. While DFUs are not associated with immobility, they are associated with altered mobility occurring as a result of complications of diabetes. The incidence and prevalence of both types of lesions are increased in the presence of multimorbidity. The prediction of either type of ulceration is challenging. Current risk assessment practices are reported to be ineffective at predicting when ulceration will occur. While systemic inflammation is easily measured, the presence of local or subclinical inflammation is harder to discern. In patients at risk of either DFUs or PUs, clinical signs and symptoms of inflammation may be masked, and systemic biomarkers of inflammation may not be elevated sufficiently to predict imminent damage until ulceration appears. The current literature suggests that the use of local biomarkers of inflammation at the skin's surface, namely oedema and temperature, may identify early tissue damage.

Efficacy and safety of autologous whole blood clot in diabetic foot ulcers: a randomised controlled trial.

OBJECTIVE: Diabetic foot ulcers (DFUs) present a significant global health challenge, resulting in high morbidity and economic costs. Current available treatments often fail to achieve satisfactory healing rates, highlighting the need for novel therapies. This study evaluated the safety and efficacy of a novel autologous whole blood clot (AWBC)-a blood-based, biodegradable provisional matrix-in conjunction with standard of care (SoC) when compared to SoC alone in the treatment of hard-to-heal DFUs. METHOD: A multicentre, prospective, blinded assessor, randomised controlled trial was conducted at 16 sites across the US, South Africa and Turkey. A cohort of patients with hard-to-heal DFUs was enrolled and randomised to either the AWBC group or the control group. The primary endpoint was complete wound closure at 12 weeks, while secondary endpoints included time to heal and percentage area reduction (PAR) at four and eight weeks. Data were analysed using both intention-to-treat (ITT) and per-protocol (PP) populations. RESULTS: The cohort included 119 patients. AWBC treatment resulted in a significantly higher healing rate compared to the control in both ITT (41% versus 15%, respectively; p=0.002) and PP populations (51% versus 18%, respectively; p=0.0075). AWBC treatment also resulted in a shorter mean time to heal and higher durability of wound closure. Safety analysis showed a similar incidence of adverse events (AEs) between groups, with no device-related AEs. CONCLUSION: The AWBC system, by modulating the wound microenvironment and providing a functional extracellular matrix, offered a promising new approach to treating hard-to-heal DFUs, demonstrating superior healing outcomes compared to SoC alone in this study.

Tibial transverse transport promotes wound healing in diabetic foot ulcers by stimulating endothelial progenitor cell mobilization and homing mediated neovascularization.

BACKGROUND: Diabetic foot ulcers (DFUs) are a common and serious complication of diabetes, often leading to amputation and decreased quality of life. Current treatment methods have limited success rates, highlighting the need for new approaches. This study investigates the potential of tibial transverse transport (TTT) to promote wound healing in DFUs. METHODS: To test this hypothesis, the study used New Zealand White rabbits to establish a diabetic model and simulate foot ulcers, followed by the treatment of unilateral TTT or bilateral TTT. The study employed histological analysis, flow cytometry, ELISA, and qPCR to assess the impact of TTT on tissue repair and endothelial progenitor cell (EPC) mobilization and homing, aiming to understand the underlying biological processes in wound healing. RESULTS: TTT significantly enhanced wound healing in diabetic rabbit foot ulcers. Specifically, bilateral TTT led to complete wound healing by day 19, faster than the unilateral TTT group, which healed by day 26, and the sham operation group, which nearly healed by day 37. Histological analysis showed improved tissue architecture, collagen deposition, and neovascularization in TTT-treated groups. Furthermore, TTT treatment resulted in a significant increase in VEGFR2 expression and VEGFR2/Tie-2 positive cells, particularly in the bilateral group. These findings were corroborated by qPCR results, which showed increased expression of VEGFA and CXCL12 by TTT. Conclusions: TTT may be a promising treatment for DFUs, significantly enhancing wound healing by stimulating EPC mobilization and homing mediated angiogenesis. This novel approach could substantially improve treatment outcomes for diabetic patients with chronic foot ulcers.

TTT accelerates wound healing in diabetic rabbit instep ulcers, with both unilateral and bilateral surgeries effective, and bilateral TTT showing enhanced efficacy.TTT boosts angiogenesis and collagen fiber formation, leading to increased granulation tissue and re-epithelialization of wounds.TTT induces the mobilization and homing of endothelial progenitor cells to promote angiogenesis and wound healing.

Exploring potential risk factors for lower limb amputation in people with diabetes-A national observational cohort study in Sweden.

AIMS: Risk factors for lower limb amputation (LLA) in individuals with diabetes have been under-studied. We examined how 1/demographic and socioeconomic, 2/medical, and 3/lifestyle risk factors may be associated with LLA in people with newly diagnosed diabetes. METHODS: Using the Swedish national diabetes register from 2007 to 2016, we identified all individuals ≥18 years with an incident diabetes diagnosis and no previous amputation. These individuals were followed from the date of diabetes diagnosis to amputation, emigration, death, or the end of the study in 2017 using data from the In-Patient Register and the Total Population Register. The cohort consisted of 66,569 individuals. Information about demographic, socioeconomic, medical, and lifestyle risk factors was ascertained around the time of the first recorded diabetes diagnosis, derived from the above-mentioned registers. Cox proportional hazard models were used to obtain hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: During the median follow-up time of 4 years, there were 133 individuals with LLA. The model adjusting for all variables showed a higher risk for LLA with higher age, HR 1.08 (95% CI 1.05-1.10), male sex, HR 1.57 (1.06-2.34), being divorced, HR 1.67 (1.07-2.60), smokers HR 1.99 (1.28-3.09), insulin treated persons HR 2.03 (1.10-3.74), people with low physical activity (PA) HR 2.05 (1.10-3.74), and people with an increased foot risk at baseline HR > 4.12. People with obesity had lower risk, HR 0.46 (0.29-0.75). CONCLUSIONS: This study found a higher risk for LLA among people with higher age, male sex, who were divorced, had a higher foot risk group, were on insulin treatment, had lower PA levels, and were smokers. No significant association was found between risk for LLA and education level, country of origin, type of diabetes, blood glucose level, hypertension, hyperlipidemia, creatinine level, or glomerular filtration rate. Obesity was associated with lower risk for LLA. Identified variables may have important roles in LLA risk among people with diabetes.

Pressure-Relieving Effect of Different Insole Top Covers in People with Diabetes at High Risk of Foot Ulceration.

Pressure-relieving footwear helps prevent foot ulcers in people with diabetes. The footwear design contributes to this effect and includes the insole top cover. We aimed to assess the offloading effect of materials commonly used as insole top cover. We measured 20 participants with diabetes and peripheral neuropathy for in-shoe peak pressures while walking in their prescribed footwear with the insole covered with eight different materials, tested in randomized order. Top covers were a 3 mm or 6 mm thick open or closed-cell foam or a 6 mm thick combination of open- and closed-cell foams. We re-assessed pressures after one month of using the top cover. Peak pressures were assessed per anatomical foot region and a region of interest (i.e., previous ulceration or high barefoot pressure). Walking comfort was assessed using a 10-point Likert scale. Mean peak pressure at the region of interest varied between 167 (SD:56) and 186 (SD:65) kPa across top covers (p < 0.001) and was significantly higher for the 3 mm thick PPT than for four of the seven 6 mm thick top covers. Across 6 mm thick top covers, only two showed a significant peak pressure difference between them. Over time, peak pressures changed non-significantly from -2.7 to +47.8 kPa across top cover conditions. Comfort ratings were 8.0 to 8.4 across top covers (p = 0.863). The 6 mm thick foams provided more pressure relief than the 3 mm thick foam during walking in high-risk people with diabetes. Between the 6 mm thick foams and over time, only small differences exist. The choice of which 6 mm thick insole top cover to use may be determined more by availability, durability, ease of use, costs, or hygienic properties than by superiority in pressure-relief capacity.

The Effect of Dimple Insole Design on the Plantar Temperature and Pressure in People with Diabetes and in Healthy Individuals.

An increase in plantar pressure and skin temperature is commonly associated with an increased risk of diabetic foot ulcers. However, the effect of insoles in reducing plantar temperature has not been commonly studied. The aim was to assess the effect of walking in insoles with different features on plantar temperature. Twenty-six (F/M:18/8) participants-13 with diabetes and 13 healthy, aged 55.67 ± 9.58 years-participated in this study. Skin temperature at seven plantar regions was measured using a thermal camera and reported as the difference between the temperature after walking with an insole for 20 m versus the baseline temperature. The mixed analyses of variance indicated substantial main effects for the Insole Condition, for both the right [Wilks' Lambda = 0.790, F(14, 492) = 4.393, p < 0.01, partial eta squared = 0.111] and left feet [Wilks' Lambda = 0.890, F(14, 492) = 2.103, p < 0.011, partial eta squared = 0.056]. The 2.5 mm-tall dimple insole was shown to be significantly more effective at reducing the temperature in the hallux and third met head regions compared to the 4 mm-tall dimple insole. The insoles showed to be significantly more effective in the diabetes group versus the healthy group, with large effect size for the right [Wilks' Lambda = 0.662, F(14, 492) = 8.037, p < 0.000, Partial eta-squared = 0.186] and left feet [Wilks' Lambda = 0.739, F(14, 492) = 5.727, p < 0.000, Partial eta-squared = 0.140]. This can have important practical implications for designing insoles with a view to decrease foot complications in people with diabetes.

Incidence and risk factors for amputation in Chinese patients with diabetic foot ulcers: a systematic review and meta-analysis.

Objective: This study aimed to comprehensively analyze the incidence of amputation in Chinese patients with diabetic foot ulcers (DFUs). Methods: The Preferred Reporting Items for a Systematic Review and Meta-analysis (PRISMA) guidelines were used. The CNKI, Wanfang Data, VIP, PubMed, Web of Science, and Embase databases were searched to collect relevant literature on the incidence of amputation in Chinese patients with DFUs. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias. The data were systematically analyzed using Stata 17.0 software to determine the incidence of amputation in this patient population. Results: A total of 25 papers were included in the study, revealing an incidence of amputation in Chinese patients with DFUs of 22.4% (95% confidence interval: 18.3-26.5%). The subgroup analysis revealed that a history of ulcers, Wagner grade >3, and diabetic peripheral vascular disease were the primary risk factors associated with a higher incidence of amputation in Chinese patients with DFUs (P<0.05). Among Chinese patients with DFUs, the amputation group and the non-amputation group showed significant differences in body mass index, duration of DFUs, total cholesterol, triglyceride, fasting blood glucose, white blood cell count, hemoglobin A1c, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein, and uric acid (P<0.05). Conclusion: The high incidence of amputation among Chinese patients with DFUs indicates that interventions should be implemented to prevent or minimize amputations. Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42023463976.