Diabetic Foot Ulcer 1.4 to 3.6 X more likely if low vitamin D – several meta-analyses

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Diabetic foot ulcers 3.3X more likely if less than 10 ng of vitamin D – meta-analysis Sept 2024

The correlation between serum vitamin D status and the occurrence of diabetic foot ulcers: a comprehensive systematic review and meta-analysis
Sci Rep. 2024 Sep 20;14(1):21932. doi: 10.1038/s41598-024-73133-0
Weiwei Tang # 1, Dawei Chen # 1, Lihong Chen 1, Guanjian Liu 2, Shiyi Sun 1, Chun Wang 1, Yun Gao 1, Xingwu Ran 3

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).
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Association between vitamin D deficiency and diabetic foot ulcer wound in diabetic subjects: A meta-analysis - May 2022

Int Wound J . 2022 May 14. doi: 10.1111/iwj.13836
Juan Lin 1, Xinxin Mo 1, Yejun Yang 2, Chao Tang 1, Jia Chen 3

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.
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Vitamin D and diabetic foot ulcer: a systematic review and meta-analysis - March 2019

3.2X March 2019
Nutrition & Diabetes volume 9, Article number: 8 (2019)
Jiezhi Dai, Chaoyin Jiang, Hua Chen & Yimin Chai
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We aimed to evaluate the association between vitamin D deficiency and diabetic foot ulcer (DFU) in patients with diabetes. Pubmed, EMBASE, BIOSIS, the Cochrane Library, and Web of Knowledge, last updated in July 2018, were searched. We assessed eligible studies for the association between vitamin D deficiency and DFU in diabetic patients. The mean difference (MD) or the odds ratio (OR) was calculated for continuous or dichotomous data respectively. Data were analyzed by using the Cochrane Collaboration’s RevMan 5.0 software. Seven studies that involved 1115 patients were included in this study. There were significantly reduced vitamin D levels in DFU (MD −13.47 nmol/L, 95%CI −16.84 to −10.10; P  =  0.34, I2 = 12%).
Severe vitamin D deficiency was significantly associated with an increased risk of DFU (OR 3.22, 95%CI 2.42−4.28; P  = 0.64, I2 = 0%). This is the first meta-analysis demonstrating the association between serum vitamin D levels and DFU. Severe vitamin D deficiency is significantly associated with an increased risk of DFU.

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Is there an association between vitamin D and diabetic foot disease? A meta-analysis - Oct 2019

3.6X Oct 2019
Wound Repair Regen. 2019 Oct 21. doi: 10.1111/wrr.12762.
Yammine K1,2,3, Hayek F4, Assi C1,3.
1 Dept of Orthopedic Surgery, Lebanese American University Medical Center-Rizk Hospital, Lebanese American University, School of Medicine, Beirut, Lebanon.
2 Diabetic Foot Clinic, Lebanese American University Medical Center-Rizk Hospital, Beirut, Lebanon.
3 Center for Evidence-Based Anatomy, Sport & Orthopedics Research, Beirut, Lebanon.
4 Division of Vascular Surgery, Lebanese American University Medical Center-Rizk Hospital, Lebanese American University, School of Medicine, Beirut, Lebanon.

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.

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Diabetic foot ulcers healed 1.4 X better with vitamin D (7 studies) – meta-analysis Aug 2024

Effects of vitamin D supplementation on diabetic foot ulcer healing: a meta-analysis
Postgrad Med J 2024 Aug 31:qgae107. doi: 10.1093/postmj/qgae107 PDF behind $42 paywall
Xiaokun Wu 1, Jinchan Zeng 2, Xuemei Ye 3, Mengmiao Peng 3, Yutao Lan 4, Shuyao Zhang 5, Haiyan Li 6

Purpose: To systematically review the effect of vitamin D supplementation on diabetic foot ulcer (DFU) healing.

Methods: The PubMed, Web of Science, Science direct, Ebsco host, CNKI, WanFang, VIP, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) on the impact of vitamin D supplementation on DFUs from inception to 19 November 2022. Two researchers independently screened the literature, extracted the data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using RevMan 5.3 software.

Results: A total of seven studies involving 580 patients were included. The results of meta-analysis showed that compared with control group, the wound healing efficiency rate (RR = 1.42, 95%CI 1.03 to 1.95, P = 0.03) and wound reduction rate (MD = 13.11, 95%CI 4.65 to 21.56, P < 0.01) of the experimental group were higher; the change values of the wound area (MD = -3.29, 95%CI -4.89 to 1.70, P < 0.01) and 25 (OH) D (MD = 9.63, 95%CI 6.96 to 12.31, P < 0.01) were larger. Supplementation of vitamin D on DFU patients can improve glucose metabolism and insulin indexes: hemoglobin A1c (MD = -0.44, 95%CI -0.62 to -0.26, P < 0.01), fasting insulin (MD = -3.75, 95%CI -5.83 to -1.67, P < 0.01), HOMA - β (MD = -5.14, 95%CI -8.74 to -1.54, P < 0.01), and quantitative insulin sensitivity check index (MD = 0.02, 95%CI 0.01 to 0.02, P < 0.01). It can also improve inflammation and oxidative stress markers: high sensitivity C-reactive protein (MD = -0.83, 95%CI -1.06 to -0.59, P < 0.01), erythrocyte sedimentation rate (MD = -15.74, 95%CI -21.78 to -9.71, P<0.01), nitric oxide (MD = 1.81, 95%CI 0.07 to 3.55, P = 0.04), and malondialdehyde (MD = -0.43, 95%CI -0.61 to -0.24, P<0.01). There was no statistically significant difference in changes of fasting plasma glucose, homeostasis model of assessment-insulin resistance, total antioxidant capacity, glutathione, very low density lipoprotein cholesterol, low density lipoprotein cholesterol, and high density lipoprotein cholesterol (P>0.05).

Conclusion: The current evidence suggests that vitamin D supplementation can significantly promote DFU healing by lowering blood sugar and alleviating inflammation and oxidative stress. Key messages What is already known on this topic Diabetic foot ulcer (DFU) is a major complication of diabetes mellitus, with high morbidity, mortality and resource utilization. Vitamin D has the effect of lowering blood sugar, improving insulin sensitivity, and increasing anti-inflammatory response. Clinical research on vitamin D supplementation for the treatment of DFU is increasing, but due to the lack of combing and integration, the actual efficacy of vitamin D in patients is unclear. What this study adds This meta-analysis has shown that vitamin D supplementation can significantly promote DFU healing by lowering blood glucose and alleviating inflammation and oxidative stress. How this study might affect research, practice or policy This study preliminarily found the effectiveness of vitamin D supplementation on the healing of DFU, which can provide a reference for the treatment of DFU by medical staff.

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VitaminDWiki Diabetes pages with FOOT in the title (5 as of May 2022)

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A diabetic foot severity grade from the web

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