Vitamin D deficiency could increase risk of diabetes related coronary heart disease

Camille Bienvenu
Tue, 05 Jul 2016
Vitamin D deficiency could increase risk of diabetes related coronary heart disease
Researchers from Creighton University School of Medicine have linked vitamin D deficiency with the development and progression of coronary artery disease (CAD), a common serious diabetes complication.

The study, conducted in collaboration with the American Heart Association and published in the Arteriosclerosis, Thrombosis and Vascular Biology journal, looked at the role of vitamin D in CAD through markers of chronic inflammation in epicardial adipose tissue (EAT).

A previous study already found that the inflammatory effects of vitamin D deficiency is associated with an increased prevalence of diabetic retinopathy in young people with type 1 diabetes.

Here, research scientists at the Department of Clinical and Translational Science identified that an elevation in the levels of a nuclear protein could be a possible mechanistic link behind vitamin D deficiency-enhanced inflammation in EAT.

The research team noticed that - the biologically active form of vitamin D - 1.25-dihydroxyvitamin D dictates NF-kB expression in the EAT of diseased coronary arteries.

NF-kB is a nuclear factor whose target genes include two extremely pro-inflammatory cytokines called tumour necrosis factor (TNF-alpha) and Interleukin-6 (IL6).

The researchers discovered that vitamin D deficiency also promoted the overexpression of karyopherin alpha4 (KPNA4), a shuttling protein involved in the nuclear translocation of the cytokines molecules mentioned previously.

The hypothesis tested by researchers is that vitamin D deficiency negatively up-regulate nuclear factor kB levels and KPNA4, which in turn drives up inflammation and accelerates the progression of cardiovascular disease.

Preliminary animal findings corroborated their theory by showing that administration of exogenous 1.25-dihydroxyvitamin D in swine inhibited NF-kB activation and reduced KPNA4 levels.

Inversely, vitamin-D deficient animals presented both increased levels of KPN4 and nuclear NF-kB, as well as chronic inflammation-induced advanced atherosclerotic plaques in their arteries, which can rapidly lead to coronary artery disease.

This suggests that vitamin D supplementation may have an important anti-inflammatory signalling role in EAT. Another study on inflammation-mediated vascular disease has demonstrated that pretreatment with 1.25-dihydroxyvitamin D3 resulted in a 60 to 65 per cent reduction in the activation of TNF-alpha-mediated inflammation.
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