Arsenic and Diabetes Link: Study

New research demonstrates how chronic arsenic exposure disrupts the body’s natural antioxidant defenses, which may contribute to the development of diseases such as Type 2 diabetes.

Backstory

“One of the main risk factors is environmental toxicant exposure, particularly chronic exposure to arsenic, which has been shown to affect insulin production and sensitivity, blood sugar levels, and lipid profiles, all common features of diabetes onset and progression.”

Because arsenic is a natural metalloid found in soil, it can be one of the most significant contaminants in drinking water globally, especially when ingested at unsafe levels. Arsenic is present throughout the U.S. and can be in high concentrations (>10 μg/L) in southwestern states such as in pocketed areas in Oregon, Nevada and California and it is in almost all groundwater sources in Arizona, particularly in rural areas.  The USGS estimates approximately 2.1 million Americans with private wells have arsenic above acceptable levels in their water.

Study overview

New scientific research has uncovered a biological mechanism by which chronic arsenic exposure led to insulin resistance and glucose intolerance, two key features of diabetes progression.  “The study examined the effect of arsenic exposure on nuclear factor-erythroid 2 related factor 2 (NRF2)* activation. NRF2 is a protein that plays an important role in maintaining cellular homeostatis, especially during times of oxidative stress when there is an imbalance of free oxygen radicals and antioxidants in the body…

Results overview

“The research team found that arsenic exposure results in the prolonged and uncontrolled activation of NRF2, which previously was determined to be a driver of cancer progression and resistance to anti-cancer therapy. In this study, they found that arsenic exposure resulted in glucose intolerance and decreased insulin sensitivity. In particular, prolonged NRF2 activation by chronic arsenic exposure caused shifts in pathways that control amino acid, fatty acid, carbohydrate, lipid and drug metabolism.

The findings demonstrated that prolonged NRF2 activation in response to arsenic increased glucose production in the liver and the release of that glucose to the bloodstream, which could represent a key driver of changes in systemic blood glucose.”

*NRF2 is the body’s governing regulator against oxidative stress. When the body enters an oxidative stress state, NRF2 is activated and the process of cellular protection begins. When cellular homeostatis is restored, NRF2 levels return to normal.


Journal reference: Liu, P., et al.  Non-canonical NRF2 activation promotes a pro-diabetic shift in hepatic glucose metabolism, Molecular Metabolism Journal,  Volume 51, September 2021. 

https://doi.org/10.1016/j.molmet.2021.101243.  overview / study PDF