The effects of vitamin D supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: A randomized, double-blind, placebo-controlled trial
Introduction
The diabetic foot ulcer (DFU) is a common complication of diabetes mellitus affecting 10%–25% of people with diabetes (Armstrong et al., 2014). The annual incidence of ulceration and amputation among patients with DFU is as high as 2.5%–10.7% and 0.25%–1.8%, respectively (Tiaka, Papanas, Manolakis, & Maltezos, 2011). Patients with diabetic foot ulcer have a higher mortality compared with patients with diabetes who have not developed food ulcer. DFU is a major cause of morbidity in diabetic patients, and the mortality rate is about twice that of diabetic patients without foot ulcer (Daousi et al., 2004). Diabetic neuropathy and peripheral vascular disease are the main etiological factors in DFU (Sinwar, 2015). Furthermore, insulin resistance, dyslipidemia, inflammation and oxidative stress play a significant role in the pathogenesis of DFU (Karadurmus et al., 2010, Sytze Van Dam et al., 2013).
In recent years, there has been an effort to understand possible roles of vitamin D inadequacy including its role in pancreatic insulin secretion and insulin action, the immune system particularly on T cell medicated immunity and decreased inflammation and oxidative stress (Asemi et al., 2013, Zubair et al., 2013). Circulating levels of 25(OH)D were low in patients with DFU (Asemi et al., 2013, Tiwari et al., 2013) and the beneficial effects of vitamin D supplementation on markers of insulin resistance, biomarkers of inflammation and oxidative among patients without DFU were reported. We have previously indicated that supplementation with 50,000 IU vitamin D/week among patients with major depressive disorder for 8 weeks had the beneficial effects on parameters of glucose homeostasis, and oxidative stress, but did not affect lipid profiles (Sepehrmanesh et al., 2016). However, improvement in vitamin D status following administration with 280 μg/day for 2 weeks and 140 μg/day for 10 weeks did not improve insulin resistance among patients with diabetes (Kampmann et al., 2014).
The favorable effects of vitamin D supplementations on wound healing, insulin resistance, biomarkers of inflammation and oxidative stress may be mediated by its impact on stimulating the phagocytosis and killing the bacteria by macrophages (van Etten, Decallonne, Bouillon, & Mathieu, 2004), suppressing interferon-g-mediated macrophage activation (Helming et al., 2005), activating insulin receptor expression, and the downregulation of cytokine generation (Pittas, Lau, Hu, & Dawson-Hughes, 2007). As there is evidence that vitamin D intake may accelerate wound healing and has anti-inflammatory and antioxidant effects, we hypothesized that vitamin D supplementation might help patients with DFU to heal their wound faster, and have better metabolic profiles, and biomarkers of inflammation and oxidative stress. The objective of this study was to evaluate the effects of vitamin D supplementation on wound healing and metabolic status in patients with DFU.
Section snippets
Trial design
The current study was a prospective randomized double-blind placebo-controlled clinical trial.
Participants
In the current study, 60 patients with grade 3 DFU aged 40–85 years who referred to the Shahid Beheshti Clinic in Kashan, Iran, between November 2015 and January 2016 were recruited. The Wagner–Meggitt’s original system has six grades of lesions. This system assesses ulcer depth and the presence of osteomyelitis or gangrene by using the following grades: grade 0 (pre-or postulcerative lesion), grade 1
Results
Among participants in the placebo group, 2 patients [withdrawn for personal reasons (n = 2)] were excluded (Fig. 1). At the end, 58 patients with DUF [vitamin D (n = 30) and placebo (n = 28)] completed the trial. However, as the analysis was based on the ITT principle, all 60 patients (30 in each group) were included in the final analyses.
Gender distribution, mean age, weight and BMI at the baseline and end-of-trial, METs at the baseline and end-of-trial, and insulin and metformin therapy were not
Discussion
In this trial, which to the best of our knowledge is the first of its kind, we evaluated effects of vitamin D supplementation on wound healing, glycemia status, lipid concentrations, and biomarkers of inflammation and oxidative stress among patients with DFU. We demonstrated that vitamin D supplementation for 12 weeks among patients with DFU had beneficial effects on glucose homeostasis, total-, LDL-, total-/HDL-cholesterol, ESR, hs-CRP and MDA levels, but it did not had any effect on FPG, other
Acknowledgments
The current study was funded by a grant from the Vice-chancellor for Research, KUMS, and Iran. The authors would like to thank the staff of Shahid Beheshti Clinic (Kashan, Iran) for their assistance on this project. The authors gratefully acknowledge Dr. Fariba Kolahdooz, who reviewed the manuscript and offered critical comments.
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Clinical trial registration number: http://www.irct.ir: IRCT201510315623N54.
Conflicts of interest: None declared.