An unusual form of diabetes may be caused by drinking arsenic-contaminated water

Like a careless criminal, even small amounts of toxic arsenic leave telltale fingerprints on victims’ bodies—although these fingerprints are different if the victim as Type 2 Diabetes, scientists report. And arsenic has many potential victims: more than 200 million people worldwide drink freshwater naturally contaminated with small amounts of arsenic. But for the first time, scientists have captured arsenic’s molecular fingerprint in the body fluids of people with and without diabetes from arsenic-contaminated Chihuahua, Mexico. By capturing these molecular fingerprints, the scientists have taken the first step towards reconstructing how arsenic may cause a little-understood form of Type 2 Diabetes.

While arsenic has many potential victims, Type 2 Diabetes has many confirmed ones. Roughly one out of fifteen adults—approximately 256 million people worldwide—has Type 2 Diabetes, and the excess glucose in their blood can damage their heart, kidneys, and nerves over time. But while people who drink arsenic-contaminated water are more likely to develop Type 2 Diabetes, scientists have observed that these arsenic-linked diabetics are different from most diabetics. Unlike most diabetics, their cells react normally to insulin, a hormone released by the pancreas that tells the cells to gobble up glucose from the blood. The problem—at least, the problem in arsenic-drinking lab rats which develop rat diabetes—is that the pancreas’s insulin-making cells seem to be poisoned by arsenic.

To figure out if this is true in humans, the scientists studied 176 people in Chihuaha, where the municipal water is contaminated with more than twice the WHO’s safety limit for arsenic. For each person with Type 2 Diabetes, the scientists matched them to another person the same gender, age, body-mass index, and the amount of arsenic in their tap water at home. The people with and without diabetes then donated their urine and blood plasma—body fluids which contain hundreds of known metabolites, the chemical residues of metabolism.

By examining the pattern of these metabolites, the scientists reconstructed how arsenic had changed people’s metabolism. When they looked at the metabolites unique to people who drank arsenic-contaminated water, they found that the people with diabetes had very different types of metabolites than people without diabetes. The diabetics’ different metabolites suggested that arsenic had changed how their bodies metabolize vitamins and amino acids, as well as how they get energy from food. Surprisingly, the metabolite pattern of the arsenic-linked diabetics was also very different from the metabolite patterns of most diabetics—providing the scientists with “a metabolic fingerprint” that hinted at molecular differences between these forms of diabetes.

 

Reference:
Martin, E., Gonzalez-Horta, C., Rager, J., Bailey, K., Sanchez-Ramirez, B., Ballinas-Casarrubias, L., Ishida, M., Gutierrez-Torres, D., Hernandez Ceron, R., Viniegra Morales, D., Baeza Terrazas, F., Jesse Saunders, R., Drobna, Z., Mendez, M., Buse, J., Loomis, D., Jia, W., Garcia-Vargas, G., Del Razo, L., Styblo, M., & Fry, R. (2015). Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico Toxicological Sciences, 144 (2), 338-346 DOI: 10.1093/toxsci/kfu318

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Arsenic, cadmium, and lead: A toxic trinity of risk factors for Alzheimer’s disease?

ResearchBlogging.orgA modern cause of Alzheimer’s disease may lie in the ancient poisons of arsenic, lead, and cadmium. Indian researchers recently reported that young rats exposed to water contaminated with these toxic metals developed symptoms of Alzheimer’s disease, a form of dementia affecting more than 25 million people worldwide. Disturbingly, rats which drank water contaminated with all three metals–water similar to that drank by many Indian people–developed much worse symptoms than rats which drank water with fewer metals. The researchers cautioned that people who drink contaminated water during childhood may develop symptoms of Alzheimer’s disease decades earlier than normal.

How do three ancient poisons work together to create such a potent brew? To tease out the answer, the researchers examined the toxic effects of each metal alone, and the effects of different combinations. Compared to arsenic and cadmium, lead provoked the rats’ brains to make more amyloid-beta–the sticky protein which congeals into plaques in the brains of Alzheimer’s patients. Rats which consumed lead with arsenic had even more amyloid-beta. But when rats consumed lead with arsenic and cadmium, the three metals acted synergistically–the toxic equivalent of shouting into a bullhorn hooked up to an amplifier. The metals amplified each other’s damage to the rats’ brains, and even caused the brains to become inflamed.

With their damaged brains, the rats were worse at figuring out a maze. They were losing their ability to learn and remember–just like humans with Alzheimer’s disease.

Citation:
Ashok A, Rai NK, Tripathi S, & Bandyopadhyay S (2014). Exposure to As-, Cd-, and Pb-Mixture Induces Aβ, Amyloidogenic APP Processing and Cognitive Impairments via Oxidative Stress-Dependent Neuroinflammation in Young Rats. Toxicological sciences : an official journal of the Society of Toxicology PMID: 25288670

Unintended consequences: Arsenic, iron, and your gut bacteria

Francesco_I_de_Medici

Francesco de Medici, a possible victim of arsenic poisoning, may have something in common with the human gut microbiome.  Image via Wikipedia.

Arsenic—the infamous “king of poisons” used by the murderous Borgias—can poison humans and bacteria alike.  But it doesn’t just poison bad bacteria–arsenic hurts the helpful bacteria that make up our gut microbiome, which protects us from E. coli and helps digest our food.  Even worse, the microbiome may be harmed by a common method of mixing iron into water to remove the arsenic.  Chinese researchers reported recently that mice which consumed arsenic-contaminated water with iron had healthier intestines than mice which drank only the water without iron.  However, the healthier mice still had unhealthy microbiomes.  Their gut bacteria had evolved methods for protecting themselves against the toxic metals—methods, unfortunately, which also protected them against antibiotics.  The researchers cautioned that people drinking iron-treated water to avoid arsenic poisoning may develop antibiotic-resistant bacteria, making them vulnerable to dangerous infections.