Interaction of Vitamin D Status and VDR-FokI Polymorphism on Oxidative Stress in Type 2 Diabetes Subjects: Randomized Controlled Trial

The interaction of environmental factors and genetic determines the development of type 2 diabetes (T2D). The objectives were to evaluate the effects of improvement of vitamin D status on the biomarkers of oxidative stress (OS) in T2D subjects and whether vitamin D receptor (VDR)-FokI polymorphism could modulate the response to vitamin D3 intake. Subjects with T2D were allocated to one of the two groups to receive either plain doogh (PD n1= 50) or vitamin D3-fortified doogh (FD, containing 500 IU/250 ml, n= 50) twice a day for 12 weeks. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH)D), superoxide dismutase, glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA). VDR genotypes in 140 T2D subjects in FD were determined by FokI restriction enzyme. After 12 weeks, serum 25(OH)D increased significantly in FD (from 38.5 ± 202.2 to 72.0 ± 23.5, P=0.001) as compared with PD (from 38.8 ± 22.8 to 33.4 ± 22.8, P = 0.28). Comparisons between FD and PD revealed significant differences in changes of serum MDA (-0.54 ± 0.82 µmol/l vs +0.17 ± 1 µmol/l, P=0.001), GSH (+8.4 ± 40.1 ng/l vs - 13.1 ± 29.4 ng/l, P = 0.002) and TAC (+0.14 ± 0.43 mmol/l vs +0.02 ± 0.45 mmol/l bovine serum albumin equivalent, P = 0.03). Although there was no significant association between FokI genotypes and OS biomarkers, ff variant subgroup showed the weakest response to vitamin D. Improvement of vitamin D status via daily intake of FD ameliorates OS biomarkers in T2D subjects, and the interactive effect of FokI genotypes cannot be ruled out.