Vitamin D supplementation for improvement of chronic low-grade inflammation in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

Background: Vitamin D has been proposed to have anti-inflammatory properties; however, the effect of vitamin D supplementation on inflammation in type 2 diabetes has not been established. Objective: The aim of this systematic review and meta-analysis was to examine the effect of vitamin D supplementation on inflammatory markers in patients with type 2 diabetes and to identify relevant gaps in knowledge. Data sources: MEDLINE, CINAHL, Embase, and EBM Reviews were searched systematically from inception to January 25, 2017. Study selection: Randomized controlled trials (RCTs) investigating the effects of vitamin D supplementation (any form, route, and duration, and with any cosupplementation) compared with placebo or usual care on inflammatorymarkers in patients with type 2 diabetes were selected. Data extraction: Study and sample characteristics and aggregate outcome data were extracted, risk of bias was determined, and quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results: Twenty-eight RCTs were included, 20 of which had data available for pooling. In meta-analyses of 20 RCTs (n=1270 participants), vitamin D-supplemented groups had lower levels of C-reactive protein (standardized mean difference [SMD] -0.23; 95%CI, -0.37 to -0.09; P=0.002) and tumor necrosis factor a (SMD -0.49; 95%CI, -0.84 to -0.15; P=0.005), a lower erythrocyte sedimentation rate (SMD -0.47; 95%CI, -0.89 to -0.05; P=0.03), and higher levels of leptin (SMD 0.42; 95%CI, 0.04-0.81; P=0.03) compared with control groups. No differences were observed for adiponectin, interleukin 6, or E-selectin (all P > 0.05). In meta-regression and subgroup analyses, age, sex, body mass index, duration of diabetes, baseline vitamin D status, and dose and duration of supplementation did not alter the results. Conclusions: This meta-analysis provides level 1 evidence that vitamin D supplementation may reduce chronic low-grade inflammation in patients with type 2 diabetes.