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Does Vitamin D Deficiency Promote Insulin Resistance?

Last updated March 24, 2015

Approved by: Maulik P. Purohit MD MPH

It is generally understood that people suffering from diabetes carry an increased risk of cardiovascular disease. Diabetes also accelerates the thickening of blood vessels, a condition known as atherosclerosis.


According to a report released by the American Diabetes Association in June 2014, diabetes was the 7th leading cause of death in the United States in 2010.  It is generally understood that people suffering from diabetes carry an increased risk of cardiovascular disease. Diabetes also accelerates the thickening of blood vessels, a condition known as atherosclerosis. As a result, heart attacks and strokes are the most common causes of death in diabetic patients. The most prevalent type of diabetes is Type-2, which is characterized by insulin resistance. Insulin resistance occurs when the body does not respond to insulin properly, resulting in elevated blood glucose levels.

Inflammation is a key factor that links insulin resistance, cardiovascular disease, and atherosclerosis. Monocytes and macrophages are central to the inflammatory response in the human body. Monocytes are a type of white blood cells that exist in all tissues and become mobilized in response to a tissue or organ that is injured or infected. Once at the affected site, monocytes differentiate into macrophages. Macrophages are versatile molecules that aid the immune system by clearing pathogens. 

The process of macrophage differentiation is regulated by Endoplasmic Reticulum (ER) stress caused by excess lipids in obesity, atherosclerosis, inflammatory signals, etc. Vitamin D is considered a natural macrophage ER stress reliever in inflammation and the Vitamin D receptor, or VDR, is ubiquitous in immune cells.

In the study being reported, scientists compromised the VDR of monocytes and, therefore, macrophages in mice. These VDR compromised mice, which could not process Vitamin D, were found to show insulin resistance and atherosclerosis. In the absence of Vitamin D, the monocytes were saturated with fat, which was then transported and deposited in blood vessel walls. This triggered a secretion of factors associated with inflammation and diseases like diabetes and atherosclerosis.

When bone marrow from mice expressing VDR in their cells was transplanted to mice with VDR compromised cells, increased insulin sensitivity was observed. Additionally, symptoms of atherosclerosis were also suppressed. This implies that deficiency of Vitamin D, at least in mice, is reversible.

Vitamin D deficiency is thought to be a risk factor in inflammation and for developing Type-2 diabetes. The reversal observed in symptoms of insulin resistance and atherosclerosis in mice in the study reported here upon supplementing Vitamin D by intact VDR gives new hope to patients with type-2 diabetes. The link established between inflammation, diabetes, atherosclerosis, and Vitamin D could be an effective tool in designing new therapeutic targets for Type-2 diabetes and associated disorders.

Written by Mangala Sarkar Ph.D.

Primary Reference:

Oh J., Riek A.E. et al(2015). Deletion of Macrophage Vitamin D Receptor Promotes Insulin Resistance and Monocyte Cholesterol Transport to Accelerate Atherosclerosis in Mice. Cell Reports,10, pp. 1-15. Retrieved fromhttp://www.cell.com/cell-reports/fulltext/S2211-1247(15)00201-6

Additional References:

(2015, Feb 19). Statistics About Diabetes. Retrieved from http://www.diabetes.org/diabetes-basics/statistics/

Simon, H. (2013 Jun 25). Type 2 Diabetes. Retrieved from http://www.nytimes.com/health/guides/disease/type-2-diabetes/complications.html

Monocytes and Macrophages.Retrieved from http://www.nature.com/nri/focus/macrophages/index.html

Oh, J. et al. (2012). Endoplasmic Reticulum Stress Controls M2 Macrophage Differentiation and Foam Cell Formation. J Biol Chem, 287(15), pp.11629-11641. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320912/

Ziegler, D. (2005). Curr Mol Med, 5(3), pp. 309-22.

Dalgard, C., Petersen, M.S., Weihe, P., Grandjean, P. (2011). Vitamin D Status in Relation to Glucose Metabolism and Type 2 Diabetes in Septuagenarians. Diabetes Care, 34(6), pp. 1284-1288. Retrieved from http://care.diabetesjournals.org/content/34/6/1284.full

Reviewed and Approved by a member of the DoveMed Editorial Board
First uploaded: March 24, 2015
Last updated: March 24, 2015