The study aimed to determine the association of vitamin D3 status with biochemical, clinical, and quality of life (QoL) in diabetic foot infection (DFI) patients.

A longitudinal study was conducted in a tertiary care hospital. Baseline biochemical (glycemic, renal, plasma vitamin D3), clinical, and QoL data of the DFI patients were collected. Patients were followed up with over the telephone for four months to assess clinical outcomes (healed/not healed). A subgroup analysis was performed to investigate the effect of vitamin D3 supplementation.

Eighty-nine DFI patients were enrolled, with a median age of 55 years and a male predominance (89.9%). A significant association between vitamin D3 levels and clinical outcome was not observed (p = 0.66). A moderate correlation was observed with the neutrophil-lymphocyte ratio (r = 0.24, p = 0.02). Regarding QoL, emotions (domain) were significantly associated with vitamin D3 levels (p < 0.01). The subgroup analysis showed that vitamin D3 supplements did not affect the clinical outcome.

The plasma vitamin D3 levels and vitamin D3 supplements do not significantly affect the biochemical, clinical, and humanistic outcomes, indicating vitamin D3 did not have a positive effect on DFI patients.

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).

Diabetic foot ulcers (DFUs) pose significant clinical challenges, representing severe complications in diabetes mellitus patients and contributing to non-traumatic amputations. Identifying reliable biomarkers can optimize early diagnosis and improve therapeutic outcomes. This study focused on evaluating the association between serum levels of 25-hydroxyvitamin D [25-(OH)D], Serum Retinol Binding Protein (RBP), and Cyclooxygenase-2 (COX-2) in elderly DFU patients. A retrospective study involving 240 participants, from March 2020 to March 2023. The participants were segmented into three cohorts: 80 with DFUs, 80 diabetic patients without DFUs, and 80 healthy controls. Serum concentrations of the three biomarkers were assayed using methods like enzyme-linked immunosorbent assay (ELISA), chemiluminescence immunoassay, and an automated biochemistry analyser. Comparisons were made both between groups and within the DFU group based on disease severity. Statistical analysis revealed significant differences in biomarker levels across the groups (p < 0.05). COX-2 and RBP concentrations were highest in the DFU group, followed by the non-DFU diabetic group, and lowest in the control group. Conversely, 25(OH)D levels were highest in the control group, followed by the non-DFU diabetic group, and lowest in the DFU group. Within the DFU group, RBP and COX-2 levels increased with disease severity, while 25(OH)D levels decreased. These variations were especially pronounced in patients with the most severe Wagner grading. A significant positive correlation was observed between disease severity and levels of RBP (r = 0.651, p < 0.05) and COX-2 (r = 0.356, p < 0.05). Conversely, a significant negative correlation was identified between disease severity and 25(OH)D levels (r = -0.658, p < 0.05). Assessing 25(OH)D, RBP, and COX-2 serum levels offers a promising tool for evaluating the severity and progression of DFUs. Monitoring these biomarkers can enrich our understanding of the metabolic and inflammatory pathways of the disease and potentially refine therapeutic strategies.

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.

A meta-analysis investigation to measure the usefulness of platelet-rich plasma (PRP) to manage skin wounds (SWs). A comprehensive literature inspection till February 2023 was applied and 1349 interrelated investigations were reviewed. The 22 chosen investigations enclosed animals' SWs were in the chosen investigations' starting point, 3348 of them were treated with PRP, and 2259 were control. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were used to compute the value of the usefulness of PRP to manage SWs by the dichotomous and continuous approaches and a fixed or random model. PRP significantly higher percent of decreases in open wound area (OWA) (MD, 10.07; 95% CI, 6.55-13.59, P < 0.001), and lower healing time (HT) (MD, -6.31; 95% CI, -10.69 to -1.93, P = 0.005) compared to control in animals' SWs. PRP had a significantly higher percent of decreases in OWA and lower HT compared to control in animals' SWs. However, caused of the small sample sizes of several chosen investigations for this meta-analysis, care must be exercised when dealing with its values.

Both 25-autoimmunity and(25(OH)D: calcifediol) and its active form, 1,25-dihydroxyvitamin D (1,25(OH)2D: calcitriol), play critical roles in protecting humans from invasive pathogens, reducing risks of autoimmunity, and maintaining health. Conversely, low 25(OH)D status increases susceptibility to infections and developing autoimmunity. This systematic review examines vitamin D's mechanisms and effects on enhancing innate and acquired immunity against microbes and preventing autoimmunity. The study evaluated the quality of evidence regarding biology, physiology, and aspects of human health on vitamin D related to infections and autoimmunity in peer-reviewed journal articles published in English. The search and analyses followed PRISMA guidelines. Data strongly suggested that maintaining serum 25(OH)D concentrations of more than 50 ng/mL is associated with significant risk reduction from viral and bacterial infections, sepsis, and autoimmunity. Most adequately powered, well-designed, randomized controlled trials with sufficient duration supported substantial benefits of vitamin D. Virtually all studies that failed to conclude benefits or were ambiguous had major study design errors. Treatment of vitamin D deficiency costs less than 0.01% of the cost of investigation of worsening comorbidities associated with hypovitaminosis D. Despite cost-benefits, the prevalence of vitamin D deficiency remains high worldwide. This was clear among those who died from COVID-19 in 2020/21-most had severe vitamin D deficiency. Yet, the lack of direction from health agencies and insurance companies on using vitamin D as an adjunct therapy is astonishing. Data confirmed that keeping an individual's serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) (and above 40 ng/mL in the population) reduces risks from community outbreaks, sepsis, and autoimmune disorders. Maintaining such concentrations in 97.5% of people is achievable through daily safe sun exposure (except in countries far from the equator during winter) or taking between 5000 and 8000 IU vitamin D supplements daily (average dose, for non-obese adults, ~70 to 90 IU/kg body weight). Those with gastrointestinal malabsorption, obesity, or on medications that increase the catabolism of vitamin D and a few other specific disorders require much higher intake. This systematic review evaluates non-classical actions of vitamin D, with particular emphasis on infection and autoimmunity related to the immune system.

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.

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. .

Vitamin D has been linked to diabetic neuropathy (DN) in previous epidemiological observational studies, however, their findings are inconsistent. The causal relationship between vitamin D and DN remains unknown. In this study we aim to investigate the causal association of serum 25-hydroxyvitamin D (25OHD) and DN.

Based on summary statistics from publicly available genome-wide association studies (GWAS) database, we detected the genetic correlation between serum 25OHD levels and DN by a two-sample Mendelian randomization (MR) analysis. The inverse-variance weighted (IVW) method was used as the primary analysis, weighted median and MR-Egger were applied as complementary methods for MR estimates. In addition, we took sensitivity analyses including Cochran's Q test, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO) and leave-one-out analysis to ensure that we obtained stable and reliable results.

Our MR study showed no significant genetic association between serum 25OHD levels and DN (OR = 1.13, 95% CI = 0.81-1.57, P = 0.46). Furthermore, in the reverse direction analysis, we did not find a significant causal effect of DN and serum 25OHD levels (OR = 0.99, 95% CI = 0.98-1.00, P = 0.09). Results of MR-Egger, Weighted Median were consistent with those of the IVW method. The sensitivity analysis suggesting that no significant heterogeneity and genetic pleiotropy was observed.

Our results provided no evidence to support the causal association of serum 25OHD levels with DN.

A meta-analysis was performed to evaluate the association between vitamin D deficiency and diabetic foot ulcer wounds in diabetic subjects. A systematic literature search up to March 2022 incorporated 7586 subjects with diabetes mellitus at the beginning of the study; 1565 were using diabetic subjects with foot ulcer wounds, and 6021 were non-ulcerated diabetic subjects. Statistical tools like the dichotomous and contentious method were used within a random or fixed-influence model to establish the odds ratio (OR) and mean difference (MD) with 95% confidence intervals (CIs) to evaluate the influence of vitamin D deficiency in managing diabetic foot ulcer wound. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels (MD, -6.48; 95% CI, -10.84 to -2.11, P < .004), higher prevalence of vitamin D deficiency (<50 nmoL/L) (OR, 1.82; 95% CI, 1.32-2.52, P < .001), and higher prevalence of severe vitamin D deficiency (OR, 2.53; 95% CI, 1.65-3.89, P < .001) compared with non-ulcerated diabetic subjects. Diabetic subjects with foot ulcer wounds had significantly lower vitamin D levels, higher prevalence of vitamin D deficiency, and higher prevalence of severe vitamin D deficiency compared with non-ulcerated diabetic subjects. Further studies are required to validate these findings.

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.

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.

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.

Hard-to-heal wounds are a major biological, psychological, social and financial burden on both individual patients and the broader health system. They are associated with a variety of comorbidities and have a complex aetiology, but are typically associated with nutritional deficiencies, such as low vitamin D levels. This systematic literature review evaluates the current research regarding the connection between inadequate vitamin D status and wound healing.

PubMed and EBSCO databases were searched following PRISMA guidelines for primary research studies relating to pressure ulcers, diabetic ulcers or venous ulcers and vitamin D status.

A total of 10 studies, involving 2359 participants, met the inclusion criteria. There was a strong correlation between low levels of 25-hydroxyvitamin D and the presence of all three types of hard-to-heal wounds.

Research suggests a correlation between low vitamin D levels and hard-to-heal wounds. However, it is not clear if the relationship is causal or only correlational. There is also emerging evidence on the use of vitamin D supplementation for the treatment of hard-to-heal wounds. More research is needed to understand the correlation between vitamin D and hard-to-heal wounds.

Hard-to-heal wounds are a major biological, psychological, social and financial burden on both individual patients and the broader health system. They are associated with a variety of comorbidities and have a complex aetiology, but are typically associated with nutritional deficiencies, such as low vitamin D levels. This systematic literature review evaluates the current research regarding the connection between inadequate vitamin D status and wound healing.

PubMed and EBSCO databases were searched following PRISMA guidelines for primary research studies relating to pressure ulcers, diabetic ulcers or venous ulcers and vitamin D status.

A total of 10 studies, involving 2359 participants, met the inclusion criteria. There was a strong correlation between low levels of 25-hydroxyvitamin D and the presence of all three types of hard-to-heal wounds.

Research suggests a correlation between low vitamin D levels and hard-to-heal wounds. However, it is not clear if the relationship is causal or only correlational. There is also emerging evidence on the use of vitamin D supplementation for the treatment of hard-to-heal wounds. More research is needed to understand the correlation between vitamin D and hard-to-heal wounds.

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.

Some reports indicated that Vitamin D may improve glycaemia indices in diabetic patients. The aim of this systematic and meta-analysis was to evaluate effects of Vitamin D fortification on indices of glycemic control. Six databases (PubMed/Medline, ISI Web of Knowledge, Cochrane Library, Science Direct, Scopus, and Google Scholar) were searched, for randomized controlled trials that were published up to September 2018 and that compared the effect of Vitamin D-fortified food versus regular diet in relation to glycemic control. Of the 4,379 studies originally found, 11 articles remained to be assessed for meta-analysis. Vitamin D fortification was associated with a significant improvement in fasting serum glucose (mean difference [MD]: -2.772; 95% confidence interval [CI]: -5.435 to -0.109) and fasting serum insulin (MD: -2.937; 95% CI: -4.695 to -1.178) in patients with Type 2 diabetes mellitus. A diet with food enriched with Vitamin D was associated with a significant improvement in homeostatic model assessment of insulin resistance (MD: -1.608; 95% CI: -3.138 to -0.079) but was not associated with a significant reduction in hemoglobin A1C (MD: 0.034; 95% CI: -0.655 to 0.069). This meta-analysis indicates that Vitamin D fortification improves indices of glycemic control. Hence, food fortified with Vitamin D may be of potential therapeutic value in diabetic patients, as an adjuvant therapy.

Vitamin D is an essential vitamin that targets several tissues and organs and plays an important role in calcium homeostasis. Vitamin D deficiency is common, particularly at higher latitudes, where there is reduced exposure to ultraviolet B radiation. We reviewed the role of vitamin D and its deficiency in foot and ankle pathology.

The effects of vitamin D deficiency have been extensively studied, but only a small portion of the literature has focused on the foot and ankle. Most evidence regarding the foot and ankle consists of retrospective studies, which cannot determine whether vitamin D deficiency is, in fact, the cause of the pathologies being investigated.

The available evidence suggests that insufficient vitamin D levels may result in an increased incidence of foot and ankle fractures. The effects of vitamin D deficiency on fracture healing, bone marrow edema syndrome, osteochondral lesions of the talus, strength around the foot and ankle, tendon disorders, elective foot and ankle surgery, and other foot and ankle conditions are less clear.

Based on the available evidence, we cannot recommend routine testing or supplementation of vitamin D in patients with foot and ankle pathology. However, supplementation is cheap, safe, and may be of benefit in patients at high risk for deficiency. When vitamin D is supplemented, the evidence suggests that calcium should be co-supplemented. Further high-quality research is needed into the effect of vitamin D in the foot and ankle. Cost-benefit analyses of routine testing and supplementation of vitamin D for foot and ankle pathology are also required.

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.

It has been demonstrated that Vitamin D (25(OH)D) deficiency is associated with diabetes and with diabetic neuropathy. Some reports stated that vitamin D deficiency is also associated with diabetic foot ulcer and/or infection. Knowing the beneficial effect of vitamin D on wound healing, a quantitative evidence synthesis is needed to look for such association. Medline, Embase, Scopus, CINAHL, Cochrane Library, and Google Scholar were searched for from inception. The outcomes were set to be either the serum 25(OH)D level or the prevalence of patients with 25(OH)D with severe deficiency. Ten studies met the inclusion criteria with 1,644 patients; 817 diabetic patients with foot ulcers and 827 patients having diabetes without foot complications. The weighted mean differences was -0.93 (95% CI = -1.684 to -0.174, I² = 97.8%, p = 0.01). The odds ratio of having severe vitamin D deficiency was 3.6 (95% CI = 2.940 to 4.415, I² = 40.9%, p < 0.0001), in favor of the foot group. The quality of the included studies was found to be good to excellent. Diabetic foot complications are associated with significantly lower levels of vitamin D. Patients with diabetic ulcers or diabetic infection are at higher risk of bearing severe vitamin D deficiency. Knowing the beneficial effect of vitamin D on wound healing, it is likely that recognizing and supplementing with vitamin D could prevent or improve the outcomes of diabetic foot complications.

There is growing evidence that suggests the association of vitamin D status with the development and progression of heart failure (HF). The objective of the present study is to assess the impact of concentration of serum 25-hydroxyvitamin D (25(OH)D) on cardiac prognosis in patients with HF. Between 1 January 2015 and 31 December 2016, we consecutively recruited patients with HF. Patients were followed prospectively for a median duration of 1 year. Serum concentration of 25(OH)D was measured with competitive chemiluminescent immunoassay. The endpoints were cardiac events, including CVD death and rehospitalisation for worsening HF. Univariate and multivariable adjustments were performed with Cox proportional-hazard regression analyses. The 25(OH)D concentration was obtained in 343 patients with a median value of 17·4 (interquartile range 12·6-23·4) ng/ml. There were 102 cardiac events, including forty-three deaths and fifty-nine rehospitalisations. Multivariate Cox hazard analysis found that the serum concentration 25(OH)D was independently associated with cardiac events (hazard ratio 0·93, 95 % CI 0·88, 0·97) and CVD mortality (hazard ratio 0·83; 95 % CI 0·77, 0·89) after adjustment for confounding factors. We divided the HF patients into four groups according to the 25(OH)D quartiles. Kaplan-Meier analysis found that the patients with lower serum 25(OH)D concentration had a higher risk of cardiac events or CVD mortality than those with high serum 25(OH)D concentration (log-rank test P < 0·001 and P = 0·032). Decreased serum concentrations of 25(OH)D were associated with cardiac prognosis and CVD mortality in a Chinese population with HF independent of other baseline HF markers.

Approximately 15% of patients with diabetes mellitus (DM) are prone to developing diabetic foot ulcers (DFU) in their lifetime. The term vitamin D status or 25-hydroxyvitamin D (25(OH)D) levels is used interchangeably to represent the status of vitamin D in individuals throughout this article. Evidence suggests a relationship between 25(OH)D levels and DFU. However, very minimal data are available on the association between DFU and vitamin D deficiency. After a careful review of the literature, it was inferred that vitamin D could be associated with DFU and diabetic foot infections. Available evidence on vitamin D and DFU suggests a negative correlation between 25(OH)D levels and the presence of DFU. Evidence also supports a negative relationship between 25(OH)D levels and diabetic foot infections. Further large-scale randomized controlled studies need to be done to confirm the relationship between 25(OH)D levels and DFU including the use of vitamin D in the management of DFU and diabetic foot infections.

Monocyte chemotactant protein-1 (MCP-1), a pro-inflammatory cytokine, plays an important role in inflammatory process. In present study, we evaluated the association of MCP-1 gene rs1024611 polymorphism with risk and clinical characteristics of diabetic foot ulcers (DFUs).This study recruited 116 patients with DFUs, 135 patients with diabetes mellitus (DM) without complications (non-DFU), and 149 healthy controls (HCs). MCP-1 gene rs1024611 polymorphism was genotyped by direct sequencing. The expression of MCP-1 was analyzed using quantitative real-time polymerase chain reaction. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assume the association strength.Individuals with rs1024611 AG and GG genotypes exhibited significantly higher susceptibility to DFUs, in the comparison with HCs (AG vs AA, OR = 2.364, 95% CI = 1.021-5.470; GG vs AA, OR = 2.686, 95% CI = 1.154-6.255). Meanwhile, G allele was associated with increased DFUs susceptibility (OR = 1.457, 95% CI = 1.014-2.093). Besides, rs1024611 SNP was slightly correlated with increased DFUs susceptibility in patients with DM. GG genotype of rs1024611 was significantly correlated with higher epidermal thickness and lower dermis thickness in patients with DFUs (P < .01). Patients with DFU exhibited upregulation of MCP-1 mRNA, and GG genotype was correlated with enhanced MCP-1 expression in DFU and non-DFU groups.Rs1024611 polymorphism was significantly associated with MCP-1 expression and individual susceptibility to DFUs.

We estimated proportions of different types of diabetes, comorbidities, treatment (the use of oral glucose-lowering agents and insulin), control (hyperglycemia, dyslipidemia and hypertension) and chronic microvascular and macrovascular complications among people with diabetes presenting to the tertiary-care academic diabetes outpatient clinics in Iran. This study is the prospective analysis of data (n = 30,202) from the registry of university-affiliated adult outpatient diabetes clinics in the country during 2015-2016. The proportions of type 1 diabetes, types 2 diabetes, and other types of diabetes were 11.4%, 85.5%, and 1.3%, respectively. The frequencies of drug-naivety, use of oral agents, insulin monotherapy and insulin combination therapy were 2.9%, 60.5%, 11.5%, and 25.1%, respectively. Around 13.2%, 11.9% and 43.3% of patients with diabetes had controlled hyperglycemia, hyperlipidemia and hypertension, respectively. The proportions of retinopathy, nephropathy, peripheral neuropathy, diabetic foot, and ischemic heart disease were 21.9%, 17.6%, 28.0%, 6.2%, and 23.9%, respectively. Despite the wide availability of medications and insulin coverage in Iran, the estimated national control of hyperglycemia, hyperlipidemia and hypertension (especially for young men and old women) remains subpar. The present study further suggests that the frequencies of chronic vascular complications among patients with diabetes are relatively high in Iran.

Diabetic foot ulceration (DFU) represents a common vascular complication of diabetes mellitus (DM) with high morbidity and disability resulting from amputation. Netrin-1 level was decreased in type 2 DM patients and has been identified as a protective regulator against diabetes-triggered myocardial infarction and nephropathy. Unfortunately, its role and molecular mechanism in DFU remain poorly elucidated. Here, netrin-1 levels were reduced in DM and DFU patients relative to healthy controls, with netrin-1 levels being the lowest in DFU patients. Moreover, exposure to high glucose (HG) also suppressed netrin-1 expression in human umbilical vein endothelial cells (HUVECs). Elevated netrin-1 expression by infection with Ad-netrin-1 adenovirus vector protected against HUVEC injury in response to HG by ameliorating the inhibitory effects on cell viability, lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, cell apoptotic rate and caspase-3 activity. Importantly, HG-impaired angiogenesis was improved after netrin-1 overexpression by elevating cell migration, capillary-like tube formation and VEGF production. Mechanism assay substantiated that netrin-1 elevation increased the phosphorylation levels of AKT and eNOS, and NO production, which was notably suppressed by HG, indicating that netrin-1 overexpression restored HG-triggered impairment of the PI3K/AKT-eNOS pathway. More intriguingly, preconditioning with LY294002 (PI3K/AKT antagonist) or N^G-monomethyl-l-arginine (eNOS inhibitor) antagonized netrin-1-induced activation of the PI3K/AKT-eNOS pathway. Concomitantly, treatment with these antagonists also attenuated the protective role of netrin-1 in endothelial dysfunction upon HG stimulation. These results suggest that elevation of netrin-1 may restore HG-triggered impairment of HUVEC and angiogenesis by activating the PI3K/AKT-eNOS pathway, indicating a potential agent for wound healing in DFU patients.