To study the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism

To Critically Assess the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism.This is a single-Centre prospective randomized, control-controlled study was conducted in Department of Surgery Datta Meghe Medical College, Hingna, Nagpur, in collaboration with Datta Meghe Institute of Medical Sciences (DMIMS) Deemed to be University from June 2019 TO March 2020. Total 60 patients were included in this study randomized grouping were done, group A vitamin d supplements and group B as control group.In group A vitamin D levels were signi(cid:977)icantly increased after 12 weeks of intervention as compared to baseline while in group B no change was seen after intervention. After 12 week of intervention, comparison of group A vs. group B, we found that Vitamin D HbA1c, TC, HDL and Wound surface area, signi(cid:977)icantly improved while there was no change seen in triglycerides levels in both the group.After intervention with vitamin D supplements for 12 weeks among patients with diabetic foot ulcer had good result and bene(cid:977)icial effect on glucose metabolism, vitamin D levels, lipid pro(cid:977)ile and wound healing.

Vit D, TCH, TG, HDL and diabetic foot ulcer ABSTRACT To Critically Assess the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism.This is a single-Centre prospective randomized, control-controlled study was conducted in Department of Surgery Datta Meghe Medical College, Hingna, Nagpur, in collaboration with Datta Meghe Institute of Medical Sciences (DMIMS) Deemed to be University from June 2019 TO March 2020. Total 60 patients were included in this study randomized grouping were done, group A vitamin d supplements and group B as control group.In group A vitamin D levels were signi icantly increased after 12 weeks of intervention as compared to baseline while in group B no change was seen after intervention. After 12 week of intervention, comparison of group A vs. group B, we found that Vitamin D HbA1c, TC, HDL and Wound surface area, signi icantly improved while there was no change seen in triglycerides levels in both the group.After intervention with vitamin D supplements for 12 weeks among patients with diabetic foot ulcer had good result and bene icial effect on glucose metabolism, vitamin D levels, lipid pro ile and wound healing.

INTRODUCTION
Diabetes mellitus is major problem in worldwide in year 2015, 415 million population were known to have diabetes mellitus. There is increase in diabetic population around 642 million approximately by year 2040. (International Diabetes Federation, 2015) 69.2 million Population are affected in India, according to recent estimate. (International Diabetes Federation, 2015) Complication of diabetes mellitus leading to 5 million deaths globally in 2015. (WHO, 2017) As complication of diabetes mellitus leads to increase morbidity, mortality and health expenditure (Alexiadou and Doupis, 2012).
Diabetic foot is one of the most signi icant and devastating complications of diabetes and is characterized as a group of syndromes with neuropathy, ischemia and infection leading to tissue breakdown and eventual amputation. (Forlee, 2010) Diabetic patients are at greater risk of developing Dia-betic foot infection and ulcer formation and leading to non-traumatic amputation of foot. It is estimated that approximately 45,000 lower limbs are amputated every year in India and the vast majority of these are probably preventable. (Jain and Viswanath, 2015) Vitamin D has immunomodulatory role with homeostasis of calcium and bone metabolism. (Baeke et al., 2007;Cantorna et al., 2004) Vitamin D has direct effect on the function of the pancreatic cells and treatment with vitamin D supplements wound improve in glucose induce insulin secretion. (Lee et al., 1994) Foot infection accounts for 20 % of hospitalisation of diabetic patients annually (Lavin and Neal, 1988). Immunological defects in addition to neuropathy and vascular abnormality are the prime contributors in the pathogenesis of diabetic foot and subsequent infections. (Geerlings, 1999) Different studies have shown that de iciency of vitamin D leads to immune cell dysfunction, b cell damage and impaired insulin production. In addition to hyperglycaemia, vitamin D de iciency could also be linked to an altered immune system of patients with diabetes, rendering them susceptible to foot infection and unfavourable prognosis (Hayes et al., 2003;Mattila et al., 2007;Holick et al., 2011).
So we design this study to evaluate the effect of vitamin D supplements for 12 week in diabetic foot ulcer patient with grade II and grade III wagner diabetic foot ulcer classi ication comparing with control group.

Aim
To Critically Assess the effect of oral vitamin D supplements on wound healing in patient with diabetic foot ulcer and its effect on lipid metabolism.

Objective
This study is conducted to evaluate the effect of oral vitamin D supplements on wound healing inpatient with diabetic foot ulcer.
To study the effect of oral vitamin D supplements on lipid pro ile.

Study Setting
This is a single-Centre prospective randomized, control-controlled study was conducted in Department of Surgery Datta Meghe Medical College Hingna, Nagpur in collaboration with Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences, Sawangi, Wardha, Maharashtra, come under Datta Meghe Institute of Medical Sciences (DMIMS) Deemed to be University.

Duration of study
June 2019 TO March 2020.

Sample size
Total 60 patients were included in this study.

Group A-vitamin D supplements
Group B-control group

Nondiabetic ulcer
Patients with chronic kidney disease (CKD) Taking immunosuppressant, Calcium supplements and drugs that interfere with vitamin D metabolism.

Liver diseases.
Wagner's grade I, IV and V ulcer.
Lost to follow up.

Trial design
The current study was a prospective randomized controlled clinical trail Participants 60 patients with grade II/III patients, between 2019 to 2020.

Study design
All participants were strati ied for gender, type and duration of DM. Participants were randomly divided into two groups group A received vitamin D supplements every weekly for 12 weeks. Participants were followed-up at every weekly for 12 weeks for assessment of wound healing and vitamin D supplements. Group B were monitored every weekly and no medication were given that wound interfere in vitamin D metabolism.

Intervention
Patient received supplements every weekly for 12 weeks. Group A received cholecalciferol 60000 IU sachet and no medication were given to control group that wound interfere the vitamin D metabolism.
The data was collected from 60 patients with diabetic ulcers satisfying all the inclusion criteria mentioned above. Selection of patients was done from

Sample collection
Blood samples with and without anti-coagulant was collected for estimating glycosylated HbA1c and serum 25-hydroxyvitamin D (25(OH) D), Lipid Proile, respectively.

Adequacy of vitamin D
Different cut-offs of vitamin D level for de iciency is chosen, i.e., ≤25 (severe), ≤50(moderate) and ≤75(mild) nmol/l for evaluating the most appropriate risk factor in patients with diabetic foot infection. The three cut-offs of vitamin D de iciency chosen are in accordance with the recommendation of Endocrine Society practice guidelines (Holick et al., 2011) and Institute of Medicine de initions ( Institute Of Medicine, 2011).

The Wagner Diabetic Foot Ulcer Grade Classi ication System
The Wagner diabetic foot ulcer classi ication system assesses ulcer depth and the presence of osteomyelitis or gangrene by using the following grades: 1. Grade 0 -intact Skin 2. Grade 1 -super icial ulcer of skin or subcutaneous tissue 3. Grade 2 -ulcers extend into tendon, bone, or capsule 4. Grade 3 -deep ulcer with osteomyelitis, or abscess 5. Grade 4 -partial foot gangrene 6. Grade 5 -whole foot gangrene

Statistical Analysis
Data collected was entered into Microsoft Excel Worksheet and statistically analysed by using SPSS (Statistical Package for Social Sciences) version 20. For quantitative data mean, standard mean, standard deviation, t-test and Karl Pearson's Coef icient of Correlation were calculated. P value < 0.05 (0.01) will be considered as statically signi icant (highly signi icant) at 95% con idence interval.

Ethical Consideration
Informed and written consent (Marathi and English) was taken from each subject before collecting data and blood sample. Only those individuals, who volunteer to participate in the study, was included and the data was kept con idential. The study was not imposing any burden on the subjects and the Institute; therefore, the study is ethically justi ied. The proposed study was undertaken subject to approval by Institutional Ethical Committee. Table 1 shows the demographic characteristic of two groups. In vitamin D group males were 25 and females were 5 out of 25 while in control group males were 23 and females were 7 respectively. Mean age was 60.2±9.3 in group A and 59.7±8.4 in group B, height was 172.7±14.7 in group A and 169.4±12.5 in group B respectively. In group A mean weight of patient at baseline was 78.6±12.9 and at the end of trial was 78.5±12.8, while in group B baseline was74.2±15.5 and at the end of trial was 74.1±15.6. Weight change was 0.01±0.6 and 0.01±1.1 in group A and B respectively. In group A, BMI at baseline and end of trial was 26.4±4.2 and 26.4±4.1, while change was 0.001±0.04. In group B, BMI at baseline and end of trial was 25.9±3.8 and 25.9±3.9, while change was 0.001±0.04 respectively. Table 2shows in group A vitamin D levels were signi icantly increased after 12 weeks of intervention as compared to baseline (18.5±11.6 vs. 31±9.8, p=0.0001). There was signi icant change in HbA1c level after intervention in group A (9.1±2.1 vs. 7.9±2.7, p=0.008). Similar results were seen in total cholesterol levels after intervention in group A (180.8±30.3 vs. 165.5±30.7, p=0.05). Wound surface area was (29.83±15.02 vs. 21.76±11.30, p=0.02) in group A. The level of high-density lipoprotein in group A (34.8±3.8 vs. 36.1±2.4, p=0.118) after 12 weeks of intervention. High density lipoprotein in group A was 34.8±3.8 in baseline and at the end of trial was 36.1±2.4 and change was -1.3±1.2 and no signi icant change was observed p value is 0.118. Table 3 shows in group B no change was seen after intervention (20.5±9.3 vs. 20.1±8.5, p=0.86). HbA1c level after intervention in was group B (9.8±3.5 vs. 9.9±4.8, p=0.92). Total cholesterol levels after intervention in group B (172.4±38.2 vs. 179.2±40.6, p=0.5). Wound surface area was in group B (25.06±14.02 vs. 21.3±13.19, p=0.28). The level of high-density lipoprotein in group B (37.6±4.6 vs. 32.6±5.1, p=0.002) was signi icantly lower level after 12 weeks of intervention. No signif-  In our study, we study the effect of vitamin D supplements in diabetic foot ulcer patients. We supplemented patients with oral cholecalciferol sachet (60,000-IU) every weekly for 12 week and patients were followed up every weekly for supplements and for examination. Control groups were not given any medication which will interfere with vitamin D metabolism. After 12 weeks of intervention, we evaluated wound surface area, lipid concentration (total cholesterol, triglyceride and high-density lipoprotein) and glycoslated hemoglobin.  (Razzaghi et al., 2017).

RESULTS AND DISCUSSION
In our study we found that there was increase in vitamin D levels and decrease in glycosylated hemoglobin and decrease wound surface area after 12 week intervention, Hu, Zhiwei MM et al suggested that Vitamin D supplementation in diabetic mellitus patients can improve HbA1c, insulin resistance, and insulin in short-term intervention, suggesting that vitamin D can be considered as a therapeutic agent along with the other treatments for T2D. Studies have shown that vitamin D de iciency is associated with the development of T2D, T2D nephropathy, T2D microvascular or macrovascular disease, diabetic retinopathy, and diabetic peripheral neuropathy (Mozaffari-Khosravi et al., 2016;Hu et al., 2019).

CONCLUSIONS
Present study supports that vitamin D de iciency is more prominent in diabetic foot patients and impaired wound healing and glucose metabolism. After intervention with vitamin D supplements for 12 weeks among patients with diabetic foot ulcer had good result and bene icial effect on glucose metabolism, vitamin D levels, lipid pro ile and wound healing. The only limitation was that, this study had small sample size and diabetic subjects with diabetic foot ulcer.

Con lict of Interest
Nil.

Source of Funding
Nil.