A novel mechanism of vitamin D anti-inflammatory/antioxidative potential in type 2 diabetic patients on metformin therapy
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Primary Health Care Center, University of Montenegro, Faculty of Medicine, Podgorica, Montenegro
Clinic for Endocrinology, Faculty of Medicine, University of Nis, Nis, Serbia
Institute of Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia
Submission date: 2019-10-02
Final revision date: 2019-11-03
Acceptance date: 2020-01-09
Online publication date: 2020-02-04
Publication date: 2020-08-06
Arch Med Sci 2020;16(5):1004–1012
The performed study focused on determining the effect of vitamin D supplementation on enzymes involved in both inflammation and reactive oxygen species (ROS) production and ROS degradation in patients with type 2 diabetes mellitus (T2DM).

Material and methods:
The 6-month follow-up, randomized, controlled study included 140 patients with T2DM, ≥ 30 years old, with good metabolic control, treated with metformin and lifestyle advice only. All patients were randomly assigned to two groups (70 each). Patients from the first group (Intervention group) were assigned to receive vitamin D3 50 000 IU or 14 000 IU regarding their vitamin D baseline levels. Patients from the second (Metformin) group continued to receive only metformin during the 6-month study period.

After 6 months, the myeloperoxidase activity was significantly lower and gradually decreased in the Intervention group by about 40%, compared to the baseline measurement (p = 0.015) and compared to the Metformin group (p = 0.001). After 6 months, the xanthine oxidase (XO) activity decreased significantly in the Intervention group compared to the baseline and 3rd month levels (p < 0.001). In the Metformin group there was also a significant decrease in XO after 6 months compared to baseline (p < 0.001) and the 3rd month (p = 0.003). The catalase activity significantly increased within the Intervention group only when comparing the 3rd and 6th month (p = 0.027).

Our study showed that vitamin D may improve endothelial dysfunction in patients with T2DM on metformin therapy by influencing two important factors implicated in the pathogenesis of diabetic complications – ROS production and inflammation, which can additionally contribute to a stable metabolic control during metformin therapy.