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

Abstract

BackgroundSeveral 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.Methodology48 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.ResultsThis 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.ConclusionIn 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

Fibrosis in Chronic Kidney Disease: Pathogenesis and Consequences

“…The VDRAs beneficial effects have been also described in the diabetic nephropathy due to the links between VDRAs and the glucose metabolism through the upregulation of the glucose transporter 4 (GLUT4) [ 175 ] and insulin secretion [ 176 ]. Moreover, a recent meta-analysis of randomized controlled trials found that supplementation with VDRAs to type-2 diabetic patients may reduce inflammation [ 177 ], down-regulating RAGE gene expression in peripheral blood mononuclear cells and decreasing serum AGES and TNF-α levels [ 178 ]. In addition to the protective anti-inflammatory effect of VDRAs on the diabetic nephropathy, several clinical and experimental studies have attributed to the VDRAs a role in the control of the progression of diabetic nephropathy, mainly through their combined effects on the RAS, inflammation, and suppression of the renal tubular EMT.…”

Effect of vitamin D supplementation versus placebo on essential hypertension in patients with vitamin D deficiency: a double‐blind randomized clinical trial

“…Third, vitamin D deficiency leads to vascular endothelial dysfunction. Studies have shown that 1,25 dihydroxy vitamin D [1,25(OH)2 D] reduces the deleterious effects of advanced glycation end product on the endothelium 34,35 . Furthermore, vitamin D improves the activity of the nitric acid system and reduces inflammatory and atherosclerotic factors, and its deficiency is a risk factor for hypertension 36 .…”

The Glyoxalase System in Age-Related Diseases: Nutritional Intervention as Anti-Ageing Strategy

“…Vitamin D was also reported to exert a protective role against glycative stress [210,211]. Vitamin D supplementation in type-2 diabetes participants showed a trend in increasing GLO1 expression, a transcriptional downregulation of RAGE receptor and decreased in AGE serum in a double-blind randomized placebo-controlled [211]. Nevertheless, the action of vitamins remains controversial because vitamin-treatment had no significant impact in other studies.…”