Effects of vitamin D supplementation on advanced glycation end products signaling pathway in T2DM patients: a randomized, placebo-controlled, double blind clinical trial

Mahsa Omidian, Mahmoud Djalali, Mohammad Hassan Javanbakht, Mohammad Reza Eshraghian, Maryam Abshirini, Parisa Omidian, Ehsan Alvandi, Maryam Mahmoudi, Mahsa Omidian, Mahmoud Djalali, Mohammad Hassan Javanbakht, Mohammad Reza Eshraghian, Maryam Abshirini, Parisa Omidian, Ehsan Alvandi, Maryam Mahmoudi

Abstract

Background: Several researches have recommended vitamin D possible health benefits on diabetic complications development, but a few number of studies have been accomplished on the molecular and cellular mechanisms. Certain cellular pathways modification and also some transcription factors activation may protect cells from hyperglycemia condition induced damages. This study purpose was to determine the vitamin D supplementation effect on some key factors [advanced glycation end products (AGEs) signaling pathway] that were involved in the diabetic complications occurrence and progression for type-2 diabetes participants.

Methodology: 48 type-2 diabetic patients (T2DM) randomly divided into two groups (n = 24 per group), receiving: 100-µg vitamin D or placebo for 3 months. At this study beginning and the end, the receptor expression for advanced glycation end products (RAGE) and glyoxalase I (GLO1) enzyme from peripheral blood mononuclear cells (PBMCs) and AGEs and tumor necrosis factor-α (TNF-α) serum levels were measured by the use of real-time PCR and ELISA methods, respectively.

Results: This study results demonstrated that vitamin D supplementation could down-regulate RAGE mRNA [fold change = 0.72 in vitamin D vs. 0.95 in placebo) P = 0.001)]. In addition, no significant changes were observed for GLO1 enzyme expression (P = 0.06). This study results also indicated that vitamin D serum level significantly increased in vitamin D group (P < 0.001). Moreover, AGES and TNF-α serum levels significantly reduced in vitamin D group, but they were remained unchanged in the placebo group.

Conclusion: In conclusion, vascular complications are more frequent in diabetic patients, and vitamin D treatment may prevent or delay the complications onset in these patients by AGEs serum level and RAGE gene expression reducing.Trial registration NCT03008057. Registered December 2016.

Keywords: AGEs; Diabetic complications; GLO1; RAGE; TNF-α; Vitamin D.

Conflict of interest statement

Competing interestsThe authors declare that they have no competing interests.

© The Author(s) 2019.

Figures

Fig. 1
Fig. 1
Trial profile
Fig. 2
Fig. 2
Effect of 12-week supplementation with vitamin D or placebo on expression ratio of the receptor for advanced glycation end products (RAGE) gene in PBMCs of T2DM patients. Error bars indicate standard error of the mean. Independent t-test was used (P-value = 0.001, * 

Fig. 3

Effect of 12-week supplementation with…

Fig. 3

Effect of 12-week supplementation with vitamin D or placebo on expression ratio of…

Fig. 3
Effect of 12-week supplementation with vitamin D or placebo on expression ratio of glyoxalase I (GLO 1) gene in PBMCs of T2DM patients. Error bars indicate standard error of the mean. Independent t-test was used (P-value = 0.06)
Fig. 3
Fig. 3
Effect of 12-week supplementation with vitamin D or placebo on expression ratio of glyoxalase I (GLO 1) gene in PBMCs of T2DM patients. Error bars indicate standard error of the mean. Independent t-test was used (P-value = 0.06)

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