The Correlation between Serum 25 (OH) D3 Levels and Diabetic Foot Wound Healing: a Nested Case-control Study

Abstract

Background Diabetic foot (DF) is one of the most serious chronic complications in patients with diabetes. There is an incidence of DF of 15% in China, with a poor prognosis, an amputation rate of 22%, and a mortality rate of 11%, which greatly reduces the quality of life and life expectancy of patients with DF. DF wound healing may benefit from vitamin D, however, sufficient clinical studies are lacking to confirm this claim. Objective To explore the correlation between serum 25 (OH) D3 and DF wound healing. Methods A nested case-control study method was used to select DF patients with Wagner grading 2-4 who were hospitalized in the Affiliated Hospital of Zunyi Medical University from 2020 to 2021. The patients were discharged from the hospital and followed up for 3 months, and 55 patients whose DF wounds still had not healed were selected as the case group. As the control group, 110 patients whose DF wounds healed within 3 months of discharge were matched 1∶2 according to their age, gender, and Wagner grade with the patients in the case group. In the early stages of treatment, 2 mL of venous blood was obtained and serum 25 (OH) D3 levels were determined before vitamin D supplementation. Detailed basic data, biochemical and imaging indices of the patients were collected, including general demographics (age, gender, place of residence, education), BMI, diabetes duration and family history, hospitalization duration, lifestyle habits (alcohol consumption, smoking status), history of hypertension and Wagner classification. The biochemical parameters included 25 (OH) D3, glycosylated hemoglobin (HbA1c), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). An MRI was performed to determine if the patient had osteomyelitis. Logistic regression was used to analyze the relationship between different 25 (OH) D3 levels and DF wound healing. Results The duration of diabetes in the case group was longer than that in the control group (P<0.001), the proportion of patients with a family history of diabetes was less than that in the control group (P=0.046), and the serum 25 (OH) D3 levels was lower than that in the control group (P<0.001) ; There was a statistically significant difference in the comparison of smoking status between the patients in the case group and the control group (P<0.001). Comparison of age, gender, residence, BMI, length of hospital stay, education level, alcohol consumption, proportion of patients with a history of hypertension, Wagner grade, incidence of osteomyelitis, HbA1c, ESR, and CRP between the two groups showed no statistically significant difference (P>0.05). Once age, gender, place of residence, education, BMI, alcohol consumption, smoking, history of hypertension, family history of diabetes mellitus, diabetes duration, length of hospitalization, Wagner grade, osteomyelitis, HbA1c, ESR, and CRP have corrected for, patients with serum 25 (OH) D3 levels of 20 to <30 ng/mL, 10 to <20 ng/mL, and <10 ng/ mL, the risk of diabetic foot wound non-healing was 1.30 times (95%CI=1.12 to 1.63), 2.01 times (95%CI=1.55 to 2.80) and 2.29 times (95%CI=1.66 to 3.92) higher than that of patients with serum 25 (OH) D3 levels≥30 ng/mL, respectively. Conclusion Serum 25 (OH) D3 levels <30 ng/mL is an independent risk factor for DF wound nonhealing.

Keywords

• 25-dihydroxyvitamin d3|diabetic foot|wound healing|paired case-control study