Previous studies have shown that vitamin D deficiency was associated with both cardiac autonomic dysfunction and the development of diabetic foot (DF). However, the impact of vitamin D levels on heart rate variability (HRV) in individuals with DF, a high-risk group, remains unclear. We explored the association between vitamin D status and HRV in individuals with DF.

A total of 458 individuals with DF were assessed for vitamin D levels by 25-hydroxyvitamin D (25(OH)D) and evaluated for cardiovascular autonomic function using both time and frequency domains of the HRV measures. Multivariate regression analysis and restricted cubic spline regression were employed to examine the associations.

Vitamin D levels were positively associated with HRV indices in people with DF, including standard deviation of the normal sinus interval (SDNN), standard deviation of the 5-min average RR intervals (SDANN), low-frequency power (LF), high-frequency power (HF), and the LF/HF ratio (all p < 0.05). The associations between serum 25(OH)D and cardiac autonomic dysfunction were nonlinear. When 25(OH)D levels were < 50 nmol/L, the odds ratio (OR) for predicted cardiac autonomic dysfunction per SD increase in 25(OH)D was 0.56 (95% CI, 0.44-0.72). However, no significant effect was observed when 25(OH)D levels exceeded 50 nmol/L.

This study demonstrates that lower 25(OH)D levels are associated with reduced HRV in individuals with DF. Specifically, when 25(OH)D levels fall below 50 nmol/L, the risk of cardiac autonomic dysfunction in people with DF significantly increases.

Type 2 diabetes mellitus (T2DM) is a growing global health concern. The pathogenesis of T2DM is multifactorial and intricate, involving a complex interplay of genetic predisposition, environmental factors, and molecular interactions. Vitamin D (circulating 25-hydroxyvitamin D concentration) regulates factors crucial for T2DM, including insulin secretion, sensitivity, and inflammation. Thus, vitamin D deficiency has been linked to poor health outcomes in T2DM patients. The cholesterol-synthesizing enzyme 7-dehydrocholesterol reductase (DHCR7) represents a critical regulatory switch between cholesterol and vitamin D3 synthesis. Recent findings suggest that the enzyme DHCR7 may indicate T2DM glycolipid metabolic disorder and is associated with deficient circulating vitamin D (circulating 25-hydroxyvitamin D concentration) status. In this PRISMA-guided systematic review, articles were sourced from two databases, namely, PubMed and Cochrane Library, to evaluate the impact of vitamin D deficiency in patients with T2DM and to explore the emerging role of DHCR7 in T2DM pathogenesis. Our findings strongly indicate a positive correlation between deficient vitamin D status and poor health outcomes in T2DM patients. Finally, this systematic review presents a novel perspective on T2DM development, focusing on the interplay between T2DM-associated hyperglycemia, expression of DHCR7, and abrogation of vitamin D synthesis.

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).

In the last few decades, vitamin D has undeniably been one of the most studied nutrients. Despite our ability to produce vitamin D through sunlight exposure, its presence in several natural food sources and fortified foods, and its widespread availability as a dietary supplement, vitamin D deficiency is a serious public health problem, affecting nearly 50% of the global population. Low serum levels of vitamin D are being associated with increased susceptibility to numerous health conditions, including respiratory infections, mental health, autoimmune diseases, and different cancer types. Although the association between vitamin D status and health is well-established, the exact beneficial effects of vitamin D are still inconclusive and indefinite, especially when considering the prevention and treatment of different health conditions and the determination of an appropriate dosage to exert those beneficial effects in various population groups. Therefore, further research is needed. With constant improvements in our understanding of individual variations in vitamin D metabolism and requirements, in the future, precision nutrition and personalized supplementation plans could prove beneficial.

The protein tyrosine phosphatase 1B (PTP1B) plays a crucial role in the development of insulin resistance. Aerobic training (AT) and vitamin D (Vit D) supplementation have been shown to individually improve glucose tolerance and diabetes-related factors. However, the impact of their combined effect on PTP1B gene expression and serum irisin in the visceral adipose tissue remains unknown. This study aims to investigate whether 8 weeks of combined AT with Vit D supplementation can improve the expression of PTP1B in adipose tissue and serum irisin in obese rats with type 2 diabetes (T2D).

Fifty male Wistar rats were divided into two groups: diabetic (n = 40) and non-diabetic (ND; n = 10). The diabetic rats were further divided into four groups: aerobic training with vitamin D supplementation (D + AT + Vit D; n = 10), aerobic training only (D + AT; n = 10), vitamin D supplementation only (D + Vit D; n = 10), and control (D + C; n = 10). The D + Vit D and D + AT + Vit D groups received 5000 IU of vitamin D via injection once a week, while the D + AT and D + C groups received sesame oil. Diabetes was induced in all groups except the nondiabetic group by intraperitoneal (IP) injection of streptozotocin. At the end of the intervention, blood and adipose tissue samples were collected, and RNA was extracted from adipose tissue for real-time PCR analysis of PPTP1B gene expression.

There was an increase in serum Vit D and irisin levels and a decrease in HOMA-IR and PTP1B gene expression in the diabetic rat model treated with D + AT and injected with 50,000 IU/kg/week of Vit D. Comparatively, when treated with D + AT + Vit D, the downregulation of PTP1B was significantly higher (p = 0.049; p = 0.004), and there was a significant increase in irisin (p = 0.010; p = 0.001).

The present study shows that the combined AT and Vit D supplementation positively impacts the expression of PTP1B in adipose tissue and serum irisin in rats with T2D. These findings suggest that combining AT with Vit D supplementation can provide a new and effective strategy to improve glucose tolerance and diabetes-related factors in individuals with T2D by regulating the expression of PTP1B in adipose tissue and promoting the synthesis of beneficial irisin protein.

This retrospective cross-sectional study aimed to evaluate the predictive value of SII (Systemic Immune Inflammation Index) and PNI (Prognostic Nutritional Index) with blood ratios on mortality in diabetic foot patients who underwent below-knee amputation. A total of 231 living (n = 71; 30.7%) and exitus (n = 160; 69.3%) patients were evaluated. The mortality group was divided into 3 groups: 30-day mortality (n = 62; 38.8%), 1-year mortality (n = 62; 38.8%), and over-1-year mortality (n = 36; 22.5%). The hemogram, SII, and PNI parameters of the patients were evaluated. Age, some blood count parameters and SII were significantly higher in the exitus group (P < .05). The lymphocyte, monocyte, eosinophil, albumin, and PNI levels were significantly higher in the living group (P < .05). Mortality was significantly predicted by age (B [regression coefficient] = 0.026, P < .05), NLR (neutrophil lymphocyte ratio) (B = -0.065, P < .05), PNI (B = -0.100, P < .01), and SII (B = 0.00000024, P < .01). The predictive values of CAR (C reactive protein albumin ratio), PNI, and SII were 77.3%, 77.0%, and 76.1%, respectively. For CAR of 30.88 cutoff value, the sensitivity and specificity were 79.4% and 64.8%, respectively. For the PNI 22.0143 cutoff value, the sensitivity and specificity were 66.9% and 5.6%, respectively. For the SII 732249.2481 cutoff value, the sensitivity and specificity were 91.9% and 31.0%, respectively. The predictive value of the PNI was significant for mortality time (B = 0.058; P < .01). The predictive value of PNI for 30-day mortality was significant (AUC (area under curve):0.632; P < .01), whereas its predictive value for 1-year mortality and over-1-year mortality after below-knee amputation was statistically insignificant (P > .05). Both the SII and PNI may be evaluated and used to predict mortality after below-knee amputation. The SII had a significant predictive value for 30-day mortality after below-knee amputation.

Background and aims: Diabetic foot is one of the most severe complications in patients with diabetes mellitus and has been linked to 25-OH-vitamin D status. This study aims to determine the prevalence of 25-OH-vitamin D deficiency and its association with diabetic foot. Methods: Patients with type 2 diabetes mellitus were enrolled in this study. The patients were divided into the diabetic foot group (n = 95) and the non-diabetic foot group (n = 388). Weight, height, and waist circumference were measured. The 25-OH-vitamin D and the other biochemical tests were extracted from the electronic medical records. The difference in clinical parameters between the diabetic foot group and the non-diabetic foot group was analyzed, and the risk factors of the diabetic foot group were analyzed using logistic regression. Results: The prevalence of 25-OH-vitamin D deficiency was 44.6%, accounting for 57.9% of all the diabetic foot group patients and only 41.0% of the non-diabetic foot group patients. The mean serum 25-OH-vitamin D level was significantly different between the diabetic foot group and the non-diabetic foot group (19.8 ± 9.5 vs 24.1 ± 11.8; P = .011). Serum 25-OH-vitamin D and B12 were found to have a significant positive correlation (r = 0.410, P = <.01). The 25-OH-vitamin D level and body mass index were independently associated with diabetic foot (P = .043, OR = 1.21; P = .009, OR =  1.47), respectively. Conclusions: The 25-OH-vitamin D deficiency was higher in the diabetic foot group. More research is needed to understand the role of 25-OH-vitamin D in the development of diabetic foot.

Vitamin D deficiency and insufficiency are public health concerns that have contributed to multiple negative health outcomes. Recent studies have revealed that vitamin D deficiency and insufficiency influence glycaemic control and the development of diabetes complications. The goal of this systematic review is to summarise the latest evidence on the impact of vitamin D deficiency and insufficiency on the outcome of Type 2 Diabetes Mellitus (T2DM) patients. In this PRISMA-guided systematic review, articles were sourced from three databases, namely, PubMed, Scopus, and Web of Science. The review only included literature published from 2012 until 2022, and 33 eligible studies met the inclusion criteria for this review. The included articles were critically appraised using the Mixed Method Appraisal Tool (MMAT). According to our findings, vitamin D deficiency or insufficiency is associated with mental health status, macrovascular and microvascular complications of T2DM, metabolic syndrome, increased risk of obesity, increased blood pressure, dyslipidaemia, glycaemic control, nerve-related disease, musculoskeletal-related complications, and reduced quality of life. Due to the diverse implications of vitamin D deficiency and insufficiency, screening for vitamin D levels in T2DM patients may be beneficial.

The aims of this study were to evaluate parathormone (PTH) levels in people with diabetic foot ulcers (DFU) and investigate the relationship between PTH levels and osteomyelitis (OM) in this population.

Eighty-eight patients were admitted for DFU in a tertiary-care centre from October 2021 to May 2022. OM was diagnosed by clinical, laboratory, and radiological evaluations. Laboratory measurements and clinical parameters were collected from medical records. Participants in the study were divided into two groups according to the diagnosis of OM (patients with OM, group 1 [n = 54] and patients without OM, group 2 [n = 34]).

Compared with group 2, patients in group 1 were younger and had a longer duration of diabetes. Erythrocyte sedimentation rate and fibrinogen were significantly higher in group 1 compared with group 2. PTH levels were significantly lower (group 1 vs. group 2, median [interquartile range] 16.2 (11.6, 31.0) vs. 23.7 (17.0, 38.1), p = 0.008) and alkaline phosphatase was significantly higher (97.0 (79.0, 112.0) vs. 88.0 (63.0, 107.0), p = 0.031) in group 1. In multiple linear regression analysis, the only independent predictors of PTH concentrations were alkaline phosphatase levels (β-coefficient 0.441, p < 0.001) and the presence of OM (β-coefficient -0.290, p = 0.038).

In a population of patients with diabetes and OM admitted to a tertiary university centre, PTH levels were lower as compared with diabetic individuals without OM. The OM and alkaline phosphatase levels were independent predictors of PTH levels in this selected population.

The relationship between atherogenic index of plasma (AIP) values and 25-hydroxyvitamin D (25[OH] D) was examined in type 2 diabetes mellitus (T2DM).

Six hundred and ninety-eight T2DM patients were included. Patients were allocated to two groups, namely, the vitamin D-deficient and non-deficient groups (threshold of 20 ng/mL). The AIP was determined as log (TG [mmol/L] / HDL-C [mmol/L]). The patients were then allocated to two further groups according to the median AIP value.

AIP level in the vitamin D-deficient group was significantly higher than that in non-deficient group (P<0.05). Patients with high AIP values had markedly reduced levels of vitamin D levels compared with those in the low-AIP group [15.89 (11.97, 20.29) VS 18.22 (13.89, 23.08), P<0.001]. Patients in the high AIP group had a higher rate of vitamin D deficiency (73.3% VS 60.6%). It was found that AIP values were adversely and independently correlated with vitamin D levels. The AIP value was shown to independently predict vitamin D deficiency risk in T2DM patients.

Patients with T2DM were shown to have an increased risk of vitamin D insufficiency when their AIP levels were low. This suggests that AIP is associated with vitamin D insufficiency in Chinese patients with type 2 diabetes.

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.

The aim of this study was to examine the correlation between serum vitamin D concentrations and prognosis among Chinese individuals with diabetic foot ulcers (DFUs).

We retrospectively recruited 488 adults with DFUs in West China Hospital from 1 January 2012 to 31 December 2019. After telephone follow up, 275 patients were finally included. We compared serum vitamin D concentrations among DFUs patients with different prognostic status, and examined the association of vitamin D status with prognostic variables by Kaplan-Meier analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals for all-cause mortality.

The median concentration of serum vitamin D of patients with DFUs was 37.78 nmol/L (interquartile range 27.91-50.66 nmol/L), with 31.6% having vitamin D deficiency (<30 nmol/L) and 42.2% having insufficient vitamin D (<50 nmol/L). During a median follow-up period of 52 months, 65 patients died, with an all-cause mortality of 23.64%. Vitamin D deficiency was independently linked to increased all-cause mortality after multivariable adjustments (hazard ratio 0.565, 95% confidence interval 0.338-0.946, P = 0.030). There were no significant differences between vitamin D concentrations and other outcomes of DFUs. Patients who suffered amputations had a tendency of lower vitamin D concentrations (34.00 [interquartile range 26.90-41.81] vs 40.21 [interquartile range 29.60-53.96] nmol/L, P = 0.053).

Vitamin D deficiency was significantly associated with increased all-cause mortality in Chinese individuals with DFUs. Vitamin D supplementation might be a potential therapy for DFUs to prevent premature death and improve outcomes.

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.