Arsenic Exposure, Arsenic Metabolism, and Incident Diabetes in the Strong Heart Study

Chronic exposure to arsenic has been associated with the development of diabetes mellitus (DM), a disease characterized by hyperglycemia resulting from dysregulation of glucose homeostasis. This review summarizes four major mechanisms by which arsenic induces diabetes, namely inhibition of insulin-dependent glucose uptake, pancreatic β-cell damage, pancreatic β-cell dysfunction and stimulation of liver gluconeogenesis that are supported by both in vivo and in vitro studies. Additionally, the role of polymorphic variants associated with arsenic toxicity and disease susceptibility, as well as epigenetic modifications associated with arsenic exposure, are considered in the context of arsenic-associated DM. Taken together, in vitro, in vivo and human genetic/ epigenetic studies support that arsenic has the potential to induce DM phenotypes and impair key pathways involved in the regulation of glucose homeostasis.

Chronic arsenic exposure leads to systemic illness involving multiple organ systems, and has been associated with the development of diabetes mellitus (DM). While the majority of the literature surrounding arsenic-induced DM is from areas where the arsenic content of drinking water is high, population-based studies in North America have shown a similar association. Here, we present a case of newly-diagnosed DM thought to be secondary to chronic arsenic exposure. The patient was a previously healthy 54-year-old female who presented with progressive fatigue, weight loss and anorexia, and eventually developed colitis, cachexia, skin eruptions, and alopecia. She was also diagnosed with DM, and treatment was complicated by episodes of severe hyper-and hypoglycemia. She was evaluated for autoimmune, rheumatologic, oncologic, and infectious etiologies of her symptoms, all of which were negative. Also negative was an extensive workup for secondary causes of DM. During her final hospitalization, she underwent a workup for heavy metal toxicity, which revealed elevated serum (11 mcg/L, reference range < 5 mcg/L) and urine (233.5 mcg/gram creatinine, reference range < 50 mcg/gram creatinine) arsenic levels. A diagnosis of arsenic toxicity was made, and the patient underwent chelation therapy with British anti-Lewisite (BAL). This is an interesting case of DM that was thought to be secondary to chronic arsenic exposure. While BAL was effective at lowering arsenic levels, we were unable to observe clinical improvement due to the patient's death shortly after completion of therapy. In cases where other secondary causes of DM are ruled out, it may be prudent to evaluate for heavy metal toxicity to allow for early diagnosis and initiation of treatment. Further studies are needed to determine the efficacy of different treatment strategies for arsenic-induced DM, and whether resolution of arsenic toxicity will reverse the diabetogenic effects.

In this recent era, occupational and accidental spills have been dramatically increased since last few decades due to globalization throughout the world. Concurrently, the concerns on health issues are being a burning question to the all corporate as well as health care professional personnel. Currently, arsenic and arsenic related problems have drawn a great attention as this compound acts not only as slow poison but also works as beneficial molecule in the treatment of some diseases. Laboratory animals showed several dysfunctions including keratinocytes dysfunctions, loss of hair and most importantly inflammation. Arsenic-mediated cell stress/oxidative stress also plays a major role in the development of multiple pathways like JNK, AP-1, PKC and caspase which further either lead to apoptosis or cancer. Countries like Bangladesh, India, Mexico, Chile and China are in great risk and the human from these areas are losing their lives due to chronic arsenic exposures. Therefore, this study will try to explain the proposed molecular mechanisms of arsenic-induced skin diseases, hair fall and inflammation. Finally, a possible treatment approach would be disclosed against arsenic-mediated disorders.