Abstract
Objective To investigate the effect of single nucleotide polymorphisms (SNPs) of the key genes in vitamin D metabolic pathway on the serum 25(OH)D level after long-term vitamin D3 supplementation and provide a theoretical basis for rational vitamin D3 supplementation in diabetic patients with different genetic backgrounds. Methods Patients with type 2 diabetes (T2DM) who met the inclusive criteria were given 800 IU of vitamin D3 daily for 30 consecutive months. Serum 25(OH)D levels was measured at enrollment and every 6 months after enrollment. The average value of four-time measurements represented individual serum 25(OH)D level during vitamin D3 supplementation. Multiplex TaqMan genotyping was used to determine the distribution of eight candidate SNPs in genes of DHCR7, CYP2R1, CYP27B1, CYP24A1, and VDR, which are key genes in the vitamin D metabolic pathway, in diabetic patients. Results At baseline, the average serum 25(OH)D level was 22.71 ± 6.87 ng/mL, and 17.9% of patients had a ≥30 ng/mL level. During supplementation, the level of 25(OH)D increased significantly at each time point, and the average 25(OH)D level increased to 30.61 ± 5.04 ng/mL; however, there were 44.6% of patients whose serum 25(OH)D levels were still below 30 ng/mL. In the patients with CYP27B1 (rs10877012) G/T genotype, 71.79% achieved sufficient level of 25(OH)D, which was significantly higher than the other two genotypes (P < 0.05). Compared with those with T/T genotype, the RR of the patients with rs10877012 for <30 ng/mL level was 0.544 (95% CI: 0.291-0.917), and the RR after adjusting age and outdoor activity was 0.560 (95% CI: 0.292-0.970). Conclusion The serum 25(OH)D level in patients with diabetes mellitus after long-term vitamin D3 supplementation is associated with CYP27B1 polymorphism. Patients with rs10877012 G/T allele have a better response to vitamin D3 supplementation. Trial Registration This trial is registered with ChiCTR-IPC-17012657.
Highlights
Vitamin D has been found to be involved in a variety of public health-significant diseases including bone diseases [1], diabetes [2], cardiovascular diseases [3], cancer [4], and metabolic syndrome [4]
A total of 112 patients with diabetes were included in the SNPs analysis, Table 1: Basic characteristics of diabetic patients
We found that the SNPs of vitamin D metabolism-related genes rs10877012 and rs4646536 were correlated with serum 25(OH)D concentration after long-term adequate supplementation of 800 IU/day vitamin D3 per day for 30 months in diabetic patients
Summary
Vitamin D has been found to be involved in a variety of public health-significant diseases including bone diseases [1], diabetes [2], cardiovascular diseases [3], cancer [4], and metabolic syndrome [4]. Due to its various extraosseous effects and the association between its deficiency and insulin resistance along with diabetes initiation, the serum vitamin D levels gain an extensive attention in the field of endocrinology [5]. 25(OH)D which could predict the risk of type 2 diabetes, vitamin D supplementation reduced the incidence of diabetes [7, 10]. Consistent with this, there was evidence to show that vitamin D deficiency is significantly higher in diabetic patients than in normal population in China [11]. Recent studies find that vitamin D3 supplementation improved insulin secretion in diabetic patients [12] and show beneficial effects in diabetic patients with poor glycemic control [13]. Maintaining adequate vitamin D level in the population will be an important strategy to reduce the incidence of diabetes. Before that, there is still an important question, in view of the potential hazard of excessive vitamin D3 supplementation, what the level of vitamin D is sufficient for diabetic patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
