Complications related to diabetic foot ulcers (DFU) due to diabetes are increasing. One of the factors influencing the management and treatment of complications related to DFU is the vitamin D serum levels of patients. Therefore, we sought to comprehensively review meta-analyses from randomized controlled trials and observational studies examining the link between serum vitamin D levels and DFU outcomes in diabetic patients.

We searched PubMed, Scopus, and ISI Web of Science until September 2024 and extracted the required data from related articles according to Inclusion criteria. The certainty of the evidence and the quality of conduct of the published meta-analyses were rated using the ASMTAR 2 tools, respectively.

A total of 8 meta-analyses studies that met inclusion criteria were included. Based on the obtained results, it has been noted that individuals with DFU exhibit serum vitamin D levels significantly lower, ranging from -7.14 (5.44, 8.83) to -0.93 (95% CI: 0.17, 1.68) ng/ml, compared to those with diabetes but without DFU. Furthermore, individuals exhibiting severe vitamin D deficiency are found to be at least 1.82 times more susceptible to developing DFU. Conversely, administering varying doses of vitamin D supplementation has been shown to positively affect the size and number of ulcers in DFU patients.

This study suggests a potential link between lower levels of vitamin D in the blood and the risk of DFU, hinting at the benefits of vitamin D supplementation in improving outcomes associated with DFU. However, caution is warranted due to the potential bias present in the included studies.

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).

Both diabetes and peripheral arterial disease (PAD) have complex interactions with COVID-19. PAD is one of the most important underlying factors in the development of diabetic foot. The COVID-19 pandemic has also caused an increase in cardiovascular complications in those with chronic diseases, including diabetics, due to both the thrombophilic course of the viral disease and the lockdown measures applied for prevention. Since both COVID-19 and diabetes mellitus predispose to thrombosis, PAD is likely to have a more severe course in diabetic patients with COVID-19. The aim of our study is to discuss the complications, prophylaxis, and treatment of PAD, which is a serious complication of diabetes, during the pandemic period.

To determine the correlation between initial serum 25-hydroxyvitamin D (25(OH)D) levels with granulation growth in diabetic foot ulcers (DFUs) after 21 days of treatment.

This cohort study involved patients with type 2 diabetes who had a DFU treated at hospital. Blood samples were taken from patients on admission. The chemiluminescent immunoassay technique was used to measure 25(OH)D levels. Granulation tissue growth was analysed by comparing the photographs from the initial treatment to day 21 of treatment.

The median value of 25(OH)D levels at initial treatment was 8 ng/ml. The result showed no correlation between 25(OH)D levels and the granulation growth in DFUs (p=0.86).

The initial serum 25(OH)D level was not correlated with the growth of granulation tissue in DFUs.

Vitamin D was found to regulate inflammatory response and angiogenesis, which were often impaired in diabetic wound healing. This study aimed to investigate the effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on diabetic wound healing both in vivo and in vitro. Diabetes was induced by high-fat diet combined with streptozotocin. After four weeks of establishing diabetic mouse model, full-thickness excisional wounds were created on their dorsal skin. Then 1,25(OH)2D3 was administered via intraperitoneal injection for 14 consecutive days. Human umbilical vein endothelial cells (HUVECs) were cultured with normal glucose, high glucose, high glucose plus 1,25(OH)2D3. Cell proliferation, migration, tube formation, and expression levels of relevant pathway components were measured. Intervention with 1,25(OH)2D3 significantly increased wound closure rates of diabetic mice. During the inflammatory phase, 1,25(OH)2D3 alleviated excessive inflammation and promoted the transition of macrophages from M1 to M2 phenotype. Regarding vascular endothelial function, 1,25(OH)2D3 significantly up-regulated eNOS protein expression and inhibited Vcam-1 mRNA expression in diabetic mice (P < 0.05). As for angiogenesis, 1,25(OH)2D3 markedly increased CD31-positive area, the protein and mRNA expression of VEGF, VEGFR2, PDGF, and PDGFRβ, as well as the mRNA expression of Bfgf and Egfr (P < 0.05). In vitro, 1,25(OH)2D3 restored impaired cell proliferation, migration, and tube formation induced by high-glucose, and up-regulated expression of angiogenesis-related factors. These protective effects might be mediated through PI3K/AKT/HIF-1α pathway. These findings suggested that 1,25(OH)2D3 accelerated diabetic wound healing by modulating inflammation, restoring vascular endothelial dysfunction, and promoting angiogenesis.

Diabetes mellitus leading to foot ulcer is a serious complication, and it is considered a global epidemic. Neuropathyand high blood glucose levels are the primary causes of foot ulcers. Fifteen percent of people with diabetes develop foot ulcers, and these foot disorders are the main cause of lower extremity amputation among such patients.

Complications of diabetic foot, affecting the lower extremities are common and quite complex and life-threatening. This review focuses on the life-threatening factors associated with diabetic foot ulcers and also the diagnosing and preventive measures. Neuropathy assessment and the range of foot ulcers were accurately examined.

Novel therapies focusing on the vascularity of the lower limbs, infection control, and ischemic control are being developed to mainly treat nonhealing ulcers.

Vitamin D deficiency (VDD) has been implicated in knee osteoarthritis (KOA) development and progression. Prevalence of hypovitaminosis D and osteoporosis in KOA is widely reported in Indian population. However, there is no attempt to critically evaluate the outcome of these studies. We aimed a systematic review of these studies.

Pubmed, Google Scholar and Web of Science last updated March 2023, were searched. We reviewed eligible studies on the association between KOA and vitamin D levels in Indian and Asian population for comparison. The mean difference (MD) of vitamin D levels and odds ratio (OR) of vitamin D status were calculated. Data were interpreted by RevMan 5.4 software. The risk of bias was assessed using the Cochrane Risk of Bias tool.

A total of 15 studies that involved 1503 KOA cases and 1609 controls were included. There was significantly reduced level of vitamin D in KOA (MD -8.68 ng/mL, 95%CI -12.21 to -5.15; P = <0.00001, I2 = 82 %) in Indian population. Similarly, in other Asian population significantly reduced vitamin D levels in KOA (MD 18.36 ng/mL, 95%CI -34.72 to -2.00; P = <0.00001, I2 = 100 %) was observed in KOA. VDD was found to be positively correlated with an increased risk of KOA.

Early diagnosis and management of VDD may provide the opportunity to delay the ongoing degenerative process of KOA and this study indicates the importance of screening VDD even in sunlight rich regions.

A meta-analysis investigation to measure the influence of the usage of postoperative antibiotic prophylaxis (POP) compared with non-usage for stented distal hypospadias repair (SDHR). A comprehensive literature inspection till February 2023 was applied and 1067 interrelated investigations were reviewed. The 10 chosen investigations enclosed 1398 individuals with SDHR in the chosen investigations starting point, 812 of them were using POP, and 586 were not using POP. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the effect of the usage of POP compared with non-usage for SDHR by the dichotomous and continuous approaches and a fixed or random model. No significant difference was found between individuals using POP and not using POP in posthypospadias repair problem (PRP) (OR, 0.99; 95% CI, 0.42-2.34, P = .97) with moderate heterogeneity (I2  = 69%), posthypospadias repair infection problem (PRIP) (OR, 0.56; 95% CI, 0.30-1.06, P = .08) with no heterogeneity (I2  = 15%), and overall composite posthypospadias repair wound healing associated problem (OCPRWHAP) (OR, 1.27; 95% CI, 0.61-2.63, P = .53) with moderate heterogeneity (I2  = 59%) for SDHR. No significant difference was found between individuals using POP and not using POP in PRP, PRIP, and OCPRWHAP for SDHR. However, cautilised of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values, for example, the low P-value of the PRIP.

A meta-analysis investigation was performed to measure the influence of cortical bone trajectory screw fixation (CBTSF) and traditional pedicle screw fixation (TPSF) on surgical site wound infection (SSWI) in posterior lumbar fusion (PLF). A comprehensive literature inspection till February 2023 was applied and 1657 interrelated investigations were reviewed. The 13 chosen investigations enclosed 1195 individuals with PLF in the chosen investigations' starting point, 578 of them were using CBTSF, and 617 were using TPSF. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilised to compute the value of the effect of the CBTSF and TPSF on SSWI in PLF by the dichotomous approaches and a fixed or random model. No significant difference was found between individuals using CBTSF and TPSF in SSWI (OR, 0.68; 95% CI, 0.35-1.33, P = .26), superficial SSWI (OR, 0.62; 95% CI, 0.22-1.79, P = .38), and deep SSWI (OR, 0.30; 95% CI, 0.06-1.50, P = .14) in PLF. No significant difference was found between individuals using CBTSF and TPSF in SSWI, superficial SSWI, and deep SSWI in PLF. However, care must be exercised when dealing with its values because of the small sample sizes of several chosen investigations for this meta-analysis and the low number of selected investigations for a certain type of SSWI.

A meta-analysis was conducted to measure hepatic and pancreatic tumour resection (HPTR) risk factors (RFs) for surgical site wound infections (SSWIs). A comprehensive literature inspection was conducted until February 2023, and 2349 interrelated investigations were reviewed. The nine chosen investigations included 22 774 individuals who were in the chosen investigations' starting point, 20 831 of them were with pancreatic tumours (PTs), and 1934 with hepatic tumours (HTs). Odds ratio (OR) and 95% confidence intervals (CIs) were used to compute the value of the HPTR RFs for SSWIs using dichotomous and continuous approaches, and a fixed or random model. HT patients with biliary reconstruction had significantly higher SSWI (OR, 5.81; 95% CI, 3.42-9.88, P < .001) than those without biliary reconstruction. Nevertheless, there was no significant difference between individuals with PT who underwent pancreaticoduodenectomy and those who underwent distal pancreatectomy in SSWI (OR, 1.63; 95% CI, 0.95-2.77, P = .07). HT individuals with biliary reconstruction had significantly higher SSWI compared with those without biliary reconstruction. Nevertheless, there was no significant difference between PT individuals who underwent pancreaticoduodenectomy and those who underwent distal pancreatectomy in SSWI. However, owing to the small number of selected investigations for this meta-analysis, care must be exercised when dealing with its values.

A meta-analysis investigation to measure the relationship between vitamin D deficiency (VDD) and diabetic foot ulcer (DFU). A comprehensive literature inspection till February 2023 was applied and 1765 interrelated investigations were reviewed. The 15 chosen investigations enclosed 2648 individuals with diabetes mellitus in the chosen investigations' starting point, 1413 of them were with DFUs, and 1235 were without DFUs. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the relationship between VDD and DFU by the dichotomous and continuous approaches and a fixed or random model. Individuals with DFUs had significantly lower vitamin D levels (VDL) (MD, -7.14; 95% CI, -8.83 to -5.44, P < 0.001) compared to those without DFU individuals. Individuals with DFUs had a significantly higher number of VDD individuals (OR, 2.27; 95% CI, 1.63-3.16, P < 0.001) compared to those without DFU individuals. Individuals with DFU had significantly lower VDL and a significantly higher number of VDD individuals compared to those without DFU individuals. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Background. Chronic foot ulcers are a major cause of morbidity in people with diabetes with a lifetime risk of 25%. Treatment is challenging and the recurrence rates of foot ulcers are >50% after 3 years. Vitamin D deficiency is more common in people with diabetes with chronic foot ulcers, compared to both people without diabetes as well as people with diabetes but without foot ulcers. Purpose/aim of study. To assess the efficacy of high-dose compared to low-dose Cholecalciferol vitamin D3 on healing of chronic diabetic foot ulcers. Materials and methods. We included people with diabetes with one or more foot ulcers lasting for more than 6 weeks. Patients were randomly allocated to either a daily oral intake of high-dose (170 μg) or low-dose (20 μg) vitamin D3 (Cholecalciferol). We saw patients in the outpatient clinic after 4, 12, 24, 36, and 48 weeks. At each visit, we measured the ulcer with a specialized camera, and associated software and the area (cm2) was calculated. Patients and assessors were blinded to treatment allocation. We followed all patients for 48 weeks or until wound healing or surgical treatment. Findings/results. We included 48 patients in the analysis (24 in each group), with a total of 64 ulcers. Among them 41 ulcers were followed until healing or 48-week follow-up and 20 ulcers were surgically treated during the study period. Three patients were lost for follow-up. The intention-to-treat analysis showed a significantly higher rate of ulcer healing in the high-dose group with 21 of 30 (70%) healed ulcers compared to 12 of 34 (35%) in the low-dose group (P = .012). Median ulcer reduction at final follow-up was 100% (interquartile range [IQR]: 72-100) in the high-dose group and 57% (IQR: -28 to 100) in the low-dose group. Furthermore, we found a significant effect of high-dose vitamin D on ulcer reduction in the repeated measures analysis of variance. Conclusions. We found high-dose vitamin D3 to be efficient, compared to low-dose vitamin D3, in promoting healing in chronic diabetic foot ulcers.

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.

Vitamin D insufficiency or deficiency (VDD) is a very prevalent condition in the general population. Vitamin D is necessary for optimal bone mineralization, but apart from the bone effects, preclinical and observational studies have suggested that vitamin D may have pleiotropic actions, whereas VDD has been linked to several diseases and higher all-cause mortality. Thus, supplementing vitamin D has been considered a safe and inexpensive approach to generate better health outcomes-and especially so in frail populations. Whereas it is generally accepted that prescribing of vitamin D in VDD subjects has demonstrable health benefits, most randomized clinical trials, although with design constraints, assessing the effects of vitamin D supplementation on a variety of diseases have failed to demonstrate any positive effects of vitamin D supplementation. In this narrative review, we first describe mechanisms through which vitamin D may exert an important role in the pathophysiology of the discussed disorder, and then provide studies that have addressed the impact of VDD and of vitamin D supplementation on each disorder, focusing especially on randomized clinical trials and meta-analyses. Despite there already being vast literature on the pleiotropic actions of vitamin D, future research approaches that consider and circumvent the inherent difficulties in studying the effects of vitamin D supplementation on health outcomes are needed to assess the potential beneficial effects of vitamin D. The evaluation of the whole vitamin D endocrine system, rather than only of 25-hydroxyvitamin D levels before and after treatment, use of adequate and physiologic vitamin D dosing, grouping based on the achieved vitamin D levels rather than the amount of vitamin D supplementation subjects may receive, and sufficiently long follow-up are some of the aspects that need to be carefully considered in future studies.

Diabetic Foot Ulcer (DFU) is a combination of neuropathy and ischaemia on diabetic patient's lower limbs. It has a high burden of limb amputation rate, mortality rate, disability, economic burden, and lower quality of life on diabetic patients. It took mostly 3-6 months and up to 1 year for DFU to heal. DFU patients also have an increased risk of vitamin D deficiency. Meanwhile vitamin D has effects on immune response, insulin secretion, and sensitivity. The long duration of DFU healing is a problem for the patient's health, job, income, quality of life, economy and healthcare. Therefore, we aim to conduct a meta-analysis to assess reliability of vitamin D supplementation on diabetic foot ulcer clinical outcome.

We conducted systematic literature search according to PRISMA guideline on Cochrane Library, PubMed, Google Scholar, ProQuest, EBSCO and ScienceDirect from 16 until 24 June 2022. Effect of vitamin D supplementation on diabetic foot ulcer patients was analyzed with a comprehensive meta-analysis tool. Pooled ulcer area, total cholesterol, triglyceride, C-reactive protein, HbA1c, and fasting plasma glucose assessed with 95% confidence intervals were estimated using fixed-effects or random-effects models.

We included 4 papers with 197 people as sample reporting vitamin D capability as treatment for DFU patients. The pooled analysis showed significant differences in ulcer area, serum Vitamin D, Total Cholesterol, Fasting Plasma Glucose, Triglyceride, C-Reactive Protein, and HbA1c. Insignificant results on Erythrocyte Sedimentation Rate and High Density Lipoprotein levels.

Vitamin D supplementation is beneficial to be given as adjuvant treatment for diabetic foot ulcer. It may fasten the wound healing and decrease the burden caused by diabetic foot ulcers.

Low vitamin D levels have been associated with several diseases as its receptors are expressed in almost all tissues of the human body. Literature data have shown delayed diabetic foot ulcer (DFU) healing in patients with low vitamin D; however, data on the association between vitamin D levels and DFU in Mediterranean countries are scarce. In this cross-sectional study we examined for differences in serum vitamin D levels between patients with DFU, people with diabetes mellitus (DM) without DFU and healthy individuals in a Southern European country. A total of 96 subjects (33 patients with DFU, 35 patients without DFU and 28 healthy controls) were recruited. Medical and dietary history was obtained and total serum 25-hydroxyvitamin D [25(OH)D] levels were determined. Serum vitamin D levels differed significantly among the three groups of participants; sub-analysis showed that healthy individuals had higher vitamin D levels when compared with patients with and without DFU, while vitamin D levels did not differ between patients with and without DFU (17.9 ± 6.7 vs. 19.8 ± 8.7 ng/mL, P = 0.329, respectively). More than half of patients with DM with or without DFU had vitamin D levels <20 ng/ml. A positive correlation was found between vitamin D and sun exposure duration in participants without DFU. In conclusion, although serum vitamin D levels did not differ between people with and without DFU, the prevalence of deficiency and insufficiency was high in both groups in a Mediterranean country. This finding highlights the need for screening and supplementation with vitamin D in individuals with DM.

At present, there is no clinical study to elucidate the correlation between vitamin D deficiency and the incidence of diabetic foot osteomyelitis (DFO).This study aims to clarify levels of 25-hydroxyvitamin D [25(OH)VD] in peripheral blood and vitamin D receptor (VDR) expression in wound margin tissues (T-VDR) of patients with type 2 diabetes mellitus (T2DM) with diabetic foot ulcer (DFU) and DFO, and to determine its correlation with treatment outcomes of DFU and DFO, and and its value as a potential biomarker for the diagnosis of DFU and DFO.

156 T2DM patients with DFU (DFU group), 100 T2DM patients without DFU (T2DM group), and 100 healthy controls (NC group). The DFU group patients were subdivided into DFO (n = 80) and NDFO groups (n = 76). The level of serum 25(OH)VD was measured via chemiluminescence immunoassay, and T-VDR expression level was determined by quantitative real-time PCR.

The levels of serum 25(OH)VD in the DFU group were significantly lower than the T2DM group [(10.3 (5.8, 18.7) vs 15.7 (8.6, 24.6) ng/mL, P = 0.002)]. Similarly, the levels of serum 25(OH)VD and T-VDR expression in the DFO group were statistically lower than the NDFO group [9.2 (5.2, 20.5) vs 12.8 (6.9, 22.1) ng/mL, P = 0.006)], [1.96 (0.61, 3.97) vs 3.11 (1.36, 5.11), P = 0.004)], respectively. Furthermore, the levels of serum 25(OH)VD and T-VDR expression in DFU patients were positively correlated with the ulcer healing rate of foot ulcer after 8 weeks of treatment ( P = 0.031, P = 0.016, respectively). Multivariate logistic regression analysis showed that low level of serum 25(OH)VD was an independent risk factor for DFU and DFO (OR_DFU = 2.42, OR_DFO = 3.05, P = 0.008, 0.001, respectively), and decreased T-VDR expression level was an independent risk factor for DFO (OR = 2.83, P = 0.004). Meanwhile, the ROC curve analysis indicated that the AUC of serum 25(OH)VD level for the diagnosis of DFU and DFO was 0.821 (95% CI, 0.754-0.886, P < 0.001) and 0.786 (95%CI, 0.643-0.867, P < 0.001), respectively. When establishing a diagnosis of DFO, the AUC of T-VDR expression level was 0.703 (95%CI: 0.618-0.853, P < 0.001).

The levels of serum 25(OH)VD and T-VDR expression in DFU and DFO decreased. Serum 25(OH)VD and T-VDR are potentially valuable biomarkers for diagnosis and prognosis of DFU and DFO. .

Diabetic foot ulcers (DFUs) are common complications of diabetes mellitus that affect patients' quality of life and pose a burden on the healthcare system. Although malnutrition and specific nutritional deficiencies can seriously impact wound healing in patients with chronic nonhealing wounds, the role of nutrition in the prevention and management of DFUs is still not clear. This review discusses the significance of frequent diet assessment and nutritional education of patients with DFUs with individualized correction of deficiencies and emphasis on adequate protein intake along with correction of vitamins D, C, E, and selenium status. Future research should clarify the impact of nutritional interventions, potentially involving the use of probiotics, zinc, and omega-3 fatty acids, and successfully translating the findings into practical guidelines for use in everyday clinical practice.

Infections are becoming more difficult to treat, at least partly on account of microbes that produce biofilms. Reports suggest that decreased levels of antimicrobial peptides like cathelicidin, elevated levels of inflammatory cytokines, and biofilm formation are all associated with vitamin D deficiency, making vitamin D - deficient individuals more susceptible to infection. Infections attributable to biofilm-producing microbes can be managed by adjuvant therapy with vitamin D because of its immunomodulatory role, particularly because of the ability of vitamin D-pathway to induce the antimicrobial peptides like cathelicidin and decrease proinflammatory cytokines.

This narrative review covers biofilm formation, infections associated with biofilm due to vitamin D deficiency, putative role of vitamin D in host protection and the effect of vitamin D supplementation in biofilm-associated infections. A comprehensive literature search in PubMed and Google Scholar utilizing suitable keywords at multiple time points extracted relevant articles.

Although vitamin D deficiency has been associated with infections by biofilm producing microbes, comprehensive clinical trials in various ethnicities are required to understand the likely relationships between vitamin D receptor gene expression, cathelicidin levels, and infection outcome. Current evidence hypothesizes that maintaining normal vitamin D level can help prevent and treat these infections.

Diabetic foot ulcers (DFU) are a major complication of diabetes mellitus (DM). Nutrient deficiencies are among the major risk factors in DFU development and healing. In this context, we aimed to investigate the possible association between micronutrient status and risk of DFU.

A systematic review (Prospero registration: CRD42021259817) of articles, published in PubMed, Web of Science, Scopus, CINAHL Complete, and Embase, that measured the status of micronutrients in DFU patients was performed.

Thirty-seven studies were considered, of which thirty were included for meta-analysis. These studies reported levels of 11 micronutrients: vitamins B9, B12, C, D, E, calcium, magnesium, iron, selenium, copper, and zinc. DFU, compared to healthy controls (HC) had significantly lower vitamin D (MD: -10.82 14 ng/ml, 95% CI: -20.47, -1.16), magnesium (MD: -0.45 mg/dL, 95% CI: -0.78, -0.12) and selenium (MD: -0.33 µmol/L, 95% CI: -0.34, -0.32) levels. DFU, compared to DM patients without DFU, had significantly lower vitamin D (MD: -5.41 ng/ml, 95% CI: -8.06, -2.76), and magnesium (MD: -0.20 mg/dL, 95% CI: -0.25, -0.15) levels. The overall analysis showed lower levels of vitamin D [15.55ng/ml (95% CI:13.44, 17.65)], vitamin C [4.99µmol/L (95% CI:3.16, 6.83)], magnesium [1.53mg/dL (95% CI:1.28, 1.78)] and selenium [0.54µmol/L (95% CI:0.45, 0.64)].

This review provides evidence that micronutrient levels significantly differ in DFU patients, suggesting an association between micronutrient status and risk of DFU. Therefore, routine monitoring and supplementations are warranted in DFU patients. We suggest that personalized nutrition therapy may be considered in the DFU management guidelines.

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259817, identifier CRD42021259817.

Observational studies, randomized controlled trials (RCTs), and Mendelian randomization (MR) studies have yielded inconsistent results on the associations of vitamin D concentrations with multiple health outcomes. In the present umbrella review we aimed to evaluate the effects of low vitamin D concentrations and vitamin D supplementation on multiple health outcomes. We summarized current evidence obtained from meta-analyses of observational studies that examined associations between vitamin D concentrations and multiple health outcomes, meta-analyses of RCTs that investigated the effect of vitamin D supplementation on multiple health outcomes, and MR studies that explored the causal associations of vitamin D concentrations with various diseases (international prospective register of systematic reviews PROSPERO registration number CRD42018091434). A total of 296 meta-analyses of observational studies comprising 111 unique outcomes, 139 meta-analyses of RCTs comprising 46 unique outcomes, and 73 MR studies comprising 43 unique outcomes were included in the present umbrella review. Twenty-eight disease outcomes were identified by both meta-analyses of observational studies and MR studies. Seventeen of these reported disease outcomes had consistent results, demonstrating that lower concentrations of vitamin D were associated with a higher risk for all-cause mortality, Alzheimer's disease, hypertension, schizophrenia, and type 2 diabetes. The combinations of consistent evidence obtained by meta-analyses of observational studies and MR studies together with meta-analyses of RCTs showed that vitamin D supplementation was associated with a decreased risk for all-cause mortality but not associated with the risk for Alzheimer's disease, hypertension, schizophrenia, or type 2 diabetes. The results indicated that vitamin D supplementation is a promising strategy with long-term preventive effects on multiple chronic diseases and thus has the potential to decrease all-cause mortality. However, the current vitamin D supplementation strategy might not be an efficient intervention approach for these diseases, suggesting that new strategies are highly needed to improve the intervention outcomes.

To assess the association between vitamin D and diabetic foot (DF) in patients with type 2 diabetes mellitus (T2DM), in order to summarize clinical evidence in the prevention and treatment of DF.

Between January 2012 and December 2019, a total of 1,721 hospitalized patients with type 2 diabetes mellitus were continuously enrolled in West China Hospital, Sichuan University, and divided into DF and non-DF groups according to whether they had DF, and divided into four subgroups according to the admission season. The 25-OH-vitamin D levels were compared between groups and subgroups, and independent risk factors discussed for the occurrence of DF.

The vitamin D insufficiency and deficiency rate were higher in the DF group (77.51%) than in the non-DF group (59.2%). The 25-OH-vitamin D levels were lower in the DF group (35.80 nmol/L) than in the non-DF group (45.48 nmol/L) (P < 0.001). Patients with poor glycemic control had lower 25-OH-vitamin D levels (P = 0.01). The levels of 25-OH-vitamin D were lower in winter and spring. In the same season, the levels of 25-OH-vitamin D in patients with DF were still lower (P < 0.001). The 25-OH-vitamin D levels of patients with Wagner grades 0 to 5 showed a downward trend (P = 0.114). The 25-OH-vitamin D level was independently associated with diabetic foot (P < 0.001, OR = 0.986).

The low serum vitamin D level was significantly associated with a higher prevalence of DF among Chinese patients with type 2 diabetes mellitus. Although vitamin D levels vary seasonally, patients with DF were always at higher risk of having vitamin D insufficiency and deficiency.

A 64-year-old White woman was admitted to the hospital with complaint of progressive right hip ulceration at the wound site following a total right hip arthroplasty. Initial history and physical examination gave a leading differential diagnosis of pyoderma gangrenosum. Until recently, the exclusion of infection for pyoderma gangrenosum has been largely clinical and supported by cultures/biopsies demonstrating the absence of infection. The MolecuLight i:X (MolecuLight, Toronto, Ontario, Canada) is a novel bedside fluorescent imaging device capable of determining the bacterial burden within a wound in real time. Fluorescent imaging excluded infection at the initial visit, and debridement was avoided. Subsequently, pathergy was avoided as well. The patient was started on topical clobetasol with hypochlorous acid-soaked dressings. She also received 80 mg daily of prednisone and high-dose vitamin D3 (10,000 IU). Recovery was complicated by a deep tunnel along the incisional line at 3 months postdiagnosis, which required slowing of the prednisone taper and the addition of colchicine. Repeat cultures grew Parvimonas, Pseudomonas, and Streptococcus species. Appropriate antibiotics were given. The patient was transitioned from prednisone to adalimumab and started on negative-pressure wound therapy. Negative-pressure wound therapy was discontinued at 5 months, and the wound resolved at 6 months.

The fat-soluble molecule vitamin D has attracted much attention since its pleiotropism was discovered. Its effectiveness can be attributed to the presence of vitamin D receptors in most of the body's tissues. Based on the classical role of vitamin D in regulating calcium and phosphorus metabolism and maintaining bone health, the role of vitamin D in immunity, type 2 diabetes mellitus (T2DM), tumor and cardiovascular diseases has been further discovered. Some experiments have shown that vitamin D can restore the production of antimicrobial peptides (AMP) in primary diabetic foot ulcer (DFU) cells, which can improve in vitro wound healing, indicating its potential therapeutic use in DFU therapy. In addition, vitamin D can also inhibit the secretion of T-helper type 1 (Th1) cytokines IFN-Y and IL-2 while stimulating the production of Th2 cytokines, thereby promoting wound healing.

To investigate the relationship between 25-OH-vitamin D level and DFU in diabetes mellitus (DM) patients, and to provide a theoretical basis for the early prevention and treatment of DFU.

The clinical data of 429 hospitalized patients with DM were retrospectively analyzed in this case-control study. The patients were divided into the DFU group (n = 242) and non-DFU group (n = 187). Fasting venous blood was drawn from all subjects to detect serum 25-OH-vitamin D levels and blood biochemical parameters, the difference of parameters between DFU group and non-DFU group were analyzed, and the risk factors of DFU were analyzed by logistic regression.

The difference between the two groups in age, DM duration, gender, diastolic blood pressure, serum creatinine, total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, albumin, white blood cell count, hemoglobin, hematocrit, 25-OH-vitamin D was statistically significant (p < 0.05). Multivariate logistic regression analysis showed that 25-OH-vitamin D is an independent protective factor for DFU [OR 95%, CI 0.984 (0.969, 0.998), p < 0.05]. 25-OH-vitamin D nutrition status distribution was different between non-DFU group and DFU group (P < 0.05). Vitamin D deficiency (< 50 nmol/L) accounted for 86.78% of all DFU patients, which was only 74.33% in non-DFU patients. The 25-OH-vitamin D levels of DFU patients from Wagner Grades 1 to 5 showed a downward trend (p < 0.01).

In conclusion, our study confirms that 25-OH-vitamin D is closely correlated with DFU and that 25-OH-vitamin D is an independent protective factor for DFU. Therefore, vitamin D screening or supplementation might be beneficial to prevent DFU and improve the prognosis of DM patients.

We reviewed the literature to evaluate potential associations between vitamins, nutrients, nutritional status or nutritional interventions and presence or healing of foot ulceration in diabetes. Embase, Medline, PubMed, and the Cochrane Library were searched for studies published prior to September 2020. We assessed eligible studies for the association between nutritional status or interventions and foot ulcers. Fifteen studies met the inclusion criteria and were included in this review. Overall, there is a correlation between poor nutritional status and the presence of foot ulceration or a delay in healing. However, there is not enough data to reach conclusions about whether the relationships are causal or only association. Further research is required to test whether any forms of nutritional supplementation improve foot ulcer healing.

Diabetic Foot Ulcer (DFU) is one of the common and serious complications in patients with Diabetes Mellitus (DM) worldwide. Given the considerable tendency of patients suffering from DFU to use the complementary therapies, the objectives of this study were to: (i) summarize the effects of dietary and herbal supplements on DFU characteristics and metabolic parameters in both animal models and clinical trials, and (ii) evaluate any links between the serum levels of micronutrients and DFU in observational studies.

A systematic search in five electronic databases including PubMed/Medline, Scopus, Web of Science, Embase, and Cochrane Library was conducted to find relevant English language published from 1990 until 31 December 2018.

Of a total of 8603 studies, 30 eligible papers including animal studies (n = 15), clinical trials (n = 7), and observational works (n = 8) were included in the systematic review. We found that some dietary/herbal supplements and micronutrients had positive effects on the wound healing. However, limited evidence is existed. Also, lower serum levels of vitamin D, C, vitamin E, and selenium in patients with DFU were likely to increase the risk of DFU, leading to impaired wound healing.

Findings suggested that some dietary and herbal supplements such as Vitamin D, Magnesium, Vitamin E, Probiotic, Zinc, and Pycnogenol would be effective on wound healing of DFUs. However, further high-quality randomized controlled clinical trials and prospective cohort studies are needed to clarify the roles of micronutrients and other dietary and herbal supplements on the progress and treatment of DFU.

Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, as it can physically and emotionally impact the person. Its management can be challenging and expensive, depending on the severity of the wound and the presence of infection.

The fat-soluble molecule, vitamin D, has gained great importance ever since its pleiotropism has been recognized. Its efficacy could be attributed to the presence of vitamin D receptors in most of the body tissues. Vitamin D plays a significant role in cell proliferation, differentiation, and immune modulation. It modulates the T and B cells resulting in the suppression of the immunoglobulins, autoimmunity, and inflammation.

We performed a literature search with the objective to highlight the role of vitamin D in peripheral vascular disease and peripheral neuropathy, which are the major risk factors for DFU, as well as evidences of its role in wound healing and management of DFU.

Preclinical and clinical studies have shown that vitamin D influences multiple phases of wound healing and thereby accelerates the process. It modulates various cells involved in proliferation and remodelling phases. Vitamin D also enhances the expression of antimicrobial peptides that help to eliminate the microbes, as well as suppress the proinflammatory responses while enhancing the anti-inflammatory responses.

This review concludes vitamin D to have a protective role in the immune and vascular system, improve glycaemic outcomes, and wound healing. Therefore, vitamin D could be a preferred adjuvant in the management of DFU.

The aim of this study was to assess vitamin D status in patients with type 2 diabetes and diabetic foot ulcers (DFU). A total of 242 participants with type 2 diabetes, mean age 59.1 ± 10 years, mean body mass index 31.4 ± 6.3 kg/m², and estimated glomerular filtration rate ≥45 mL/min/1.73m², were divided into 2 groups: 73 with DFU (35 with and 38 without active infection) and 169 without DFU (106 with diabetic peripheral neuropathy, 63 without complications). Neuropathy was assessed by 10 g monofilament, Rydel-Seiffer 128 Hz tuning fork, and temperature discrimination. Serum 25(OH)D (25-hydroxy vitamin D) was assessed by ECLIA (electro-chemiluminescence immunoassay) method. Median 25(OH)D level was 12.6 ng/mL (IQR [interquartile range] 9.3-17.6 ng/mL) in the studied cohort. The DFU group presented with lower 25(OH)D level as compared with diabetic patients without foot ulcers (non-DFU group): 11.6 ng/mL (IQR 8.5-15.8 ng/mL) versus 13.5 ng/mL (IQR 9.6-18.6 ng/mL), P = .001; the diabetic peripheral neuropathy subgroup demonstrated lower 25(OH)D level in comparison with participants without complications: 12.5 ng/mL (IQR 9-17.2 ng/mL) versus 15.9 ng/mL (IQR 10.4-20.8 ng/mL), P = .031. This remained significantly different even after correction for age and duration of diabetes. There was no difference in 25(OH)D level between the subgroups according to the presence of active infection. In conclusion, vitamin D deficiency may play a role in the development of diabetes complications.

Background: Vitamin D deficiency has been associated with an increased risk in several diabetic complications. We aimed to evaluate the association between vitamin D and diabetic foot ulcer (DFU) in patients with type 2 diabetes. Methods: Fifty one patients were included in the study and divided into two groups for study of vitamin D, cholesterol, and triglycerides in blood serum on DFU. The association between vitamin D and DFU was measured by binary logistic regression analysis. The cut point of vitamin D for DFU was assessed by the receiver operating characteristic curve. Results: Levels of 25-OH-vitamin D were lower in patients with DFU than in DM group (P < 0.0001). The AUC of 25-OH-vitamin D was 0.8254 and had an optimal cut point value (13.68 ng/ml) for the identification of DFU, with a sensitivity of 90% and a specificity of 66.67% in all patients. Multivariate logistic regression analysis indicated that the significant risk factors included 25-OH-vitamin D level (P = 0.001, OR = 0.618) and HDL-C level (P = 0.038, OR = 0.012). Conclusion: Low serum 25-OH-vitamin D level was associated with DFU. This indication was more specific than cholesterol and triglycerides levels.

Objective The goal of this study was to evaluate foot-care practices by physicians throughout India who had participated in the Diabetic Foot Education Program (DFEP). Methods A structured questionnaire was administered to physicians throughout India, and their responses were analyzed descriptively. Results A total of 377 doctors responded to the DFEP opinion survey, including 261 doctors who belonged to independent diabetic foot clinics. Of these doctors, 44.4% reported managing fewer than five diabetic foot patients per week and 42.8% reported managing 5-10 patients per week. Most of these patients had non-ischemic foot, followed by those with ischemic and Charcot foot. About 58% of these physicians reported performing comprehensive clinical examinations and providing optimal preventive and therapeutic care in the treatment of diabetic foot, whereas only 25.7% reported performing only callus removal and changing dressings. Basic instruments to manage diabetic foot included the monofilament, tuning fork, biothesiometer, handheld Doppler, and pedometer, which were used by 76%, 75.5%, 59.5%, 27.7%, and 12.8% of doctors, respectively. The most common comorbidities were neuropathy, reported by 333 doctors, followed by peripheral vascular disease, reported by 297 doctors. Tools for diabetic foot education included posters in the clinic, used by 75% of doctors; pamphlets, used by 56.2%; videos, used by 45.2%; and diabetic foot applications, used by 36.7% of doctors. Conclusions There is a need to promote diabetic foot awareness and implement foot-care strategies to prevent diabetic foot and effectively manage this condition. Diabetic foot education programs will encourage clinicians to effectively use diagnostic tools for assessment and management of diabetic foot and to establish independent diabetic foot clinics.

Vitamin D is very important for children's health. Previous studies have shown that vitamin D deficiency leads to a series of diseases in adults. However, pediatricians are mostly aware of rickets caused by vitamin D deficiency in children and poorly aware of other symptoms. This study aimed to retrospectively analyze the different clinical features of vitamin D deficiency to enhance identification by pediatricians, thus minimizing misdiagnosis. In this study, we retrospectively analyzed the clinical features of vitamin D deficiency in 268 children aged 0-14 years from June 2016 to May 2018 in the Third Affiliated Hospital of Zhengzhou University. Serum 25-hydroxy vitamin D [25(OH)D] levels were determined using the chemiluminescence method. Of the 268 cases, 101 cases showed movement disorder (37.7%) and 167 nervous system abnormalities (62.3%). Among all cases, 6 were misdiagnosed as febrile seizures (2.23%), 5 as epilepsy (1.86%), 2 as Tourette syndrome (0.74%), and 2 as developmental retardation (0.74%). There were significant differences in patients with clinical characteristics of movement disorder and nervous system abnormalities partly between Pre-and post-vitamin D treatment. This analysis revealed that vitamin D deficiency occurs not only in children but also in adolescents, with diverse clinical features. Therefore, pediatricians should pay more attention to clinical different signs and symptoms, and future studies should be conducted to confirm the mechanisms of these processes.

Background: Vitamin D status has been linked to diabetes-related complications due to multiple extraskeletal effects. We aimed to investigate the association between vitamin D deficiency (VDD) and diabetic vascular complications, including diabetic retinopathy (DR), diabetic kidney disease (DKD), and diabetic foot ulcers (DFU). Methods: A total of 4,284 Chinese patients with type 2 diabetic mellitus (T2DM) were enrolled into the cross-sectional study. VDD was defined as serum 25-hydroxyvitamin D <50 nmol/L. Demographic data, physical measurements, laboratory measurements, comorbidities, and related medications were collected and analyzed by VDD status. Poisson regression with robust variance estimation and binary logistic regression were performed to explore the relationship between VDD and diabetic complications. Results: The prevalence of VDD, DR, DKD, DFU accounted to 71.7% (95% confidence intervals [CI]: 70.3-73.0%), 28.5% (95% CI: 27.2-29.9%), 28.2% (95% CI: 26.8-29.5%), and 5.7% (95% CI: 5.1-6.5%), respectively. The prevalence ratios (95% CI) for DR and DKD by VDD status, adjusted for demographics, physical measurements, laboratory measurements, related complications, and comorbidities, and medications, were 1.093 (0.983-1.215) and 1.041 (0.937-1.156), respectively. The odds ratio (95% CI) for DFU by VDD status was 1.656 (1.159-2.367) in the final adjusted model. Meanwhile, the prevalence of VDD was significantly higher in patients with DFU compared with patients without DFU. Conclusions: The present study firstly indicated that VDD was significantly associated with a higher prevalence of DFU among Chinese T2DM patients. The association between VDD status and DR or DKD was not significant when adjusting for all potential covariates. Vitamin D screening or supplementation may be beneficial to prevent DFU and improve the prognosis of T2DM patients.