How Vitamin D May Affect Heart Disease, Diabetes

Vitamin D deficiency has been linked to heart disease and type 2 diabetes. Chronic inflammation plays a role in both of these diseases, and most immune cells have receptors for vitamin D. Binding of vitamin D to its receptor regulates many key processes inside cells. However, the mechanisms connecting activation of the immune system with these diseases aren't well understood.

Heart disease stems from atherosclerosis, which occurs when a substance called plaque builds up inside blood vessels. Plaque consists of fat, cholesterol, calcium, and other materials found in the blood. Over time, the buildup can cause hardening and narrowing of arteries and can lead to coronary heart disease, heart attack, and stroke.

Type 2 diabetes usually begins with insulin resistance, a condition in which the body produces insulin but isn't able to use it effectively. As a result, glucose builds up in blood and may ultimately damage nerves, blood vessels, and other body parts.

A team of researchers led by Dr. Carlos Bernal-Mizrachi at Washington University School of Medicine set out to examine the connections among vitamin D, immune function, atherosclerosis, and insulin resistance. They genetically altered mice to lack vitamin D receptors in 2 types of inflammation-related immune cells: monocytes and macrophages. Without these receptors, the cells couldn't respond to vitamin D. The study was supported in part by NIH's National Heart, Lung, and Blood Institute (NHLBI). Results appeared on March 24, 2015, in Cell Reports.

Both types of mice developed insulin resistance. Macrophages accumulated in the liver, which made excess glucose. The engineered mice also developed atherosclerosis that was spurred by monocytes lacking vitamin D receptors. The monocytes became filled with cholesterol and carried the cholesterol to plaques. This process of atherosclerosis is different from that involving LDL cholesterol.

When the researchers added normal immune cells back into the engineered mice, their insulin sensitivity improved and atherosclerosis declined. This finding showed that vitamin D pathways in immune cells play a key role in chronic inflammation that, in turn, affects development of insulin resistance and atherosclerosis.

"Inactivation of the vitamin D receptor induced diabetes and atherosclerosis, so normalizing vitamin D levels may have the opposite effect," Bernal-Mizrachi says. "The identification of monocyte cholesterol transport as a mechanism for atherosclerosis in our animal model opens up a new area of research that could identify novel therapies for heart disease."

The group is now conducting clinical trials in people with type 2 diabetes to see whether vitamin D treatment can prevent some of the complications of diabetes and inflammation.

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SOURCE: NIH, March 30, 2015

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