Biochemical investigation of association of arsenic exposure with risk factors of diabetes mellitus in Pakistani population and its validation in animal model.

Arsenic is one of the naturally occurring heavy metal that has been reported to cause damaging effects on different body organs. This study was aimed to determine the arsenic level in different water sources and investigate the effect of arsenic exposure on risk factors of diabetes mellitus (DM) in human participants and experimental animals. We recruited 150 participants to investigate the arsenic exposure in their urine and from drinking water. We found that males contained significantly higher (P < 0.001) concentrations of urinary arsenic as compared with that of their female counterparts. Similarly, urinary arsenic concentration was high and showed significant association in the age of ≥ 60 years (P < 0.05), illiterate (P < 0.001), smokers (P < 0.0001), and diabetic (P < 0.0001) participants. Moreover, urinary arsenic exposure was also associated with higher levels of fasting (P < 0.001) and random blood glucose (P < 0.001), HbA1c (P < 0.001), AST, ALT, MDA, IL-6, CRP, blood urea nitrogen, and creatinine in arsenic-exposed diabetics as compared with that of unexposed diabetics. Further, we also exposed the white albino rats with arsenic in drinking water for 30 days and their blood glucose was measured at 15th and 30th days of treatment that was significantly higher (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. Similarly, arsenic-exposed animals failed to tolerate exogenously administered glucose (P < 0.001) as compared with that of unexposed animals. Likewise, insulin and glutathione concentrations were also significantly decreased (P < 0.001) in arsenic-exposed animals as compared with that of unexposed animals. The alterations in normal values of glucose, insulin, and glutathione exhibited the damaging effects of arsenic exposure in experimental rats. This study showed that arsenic exposed to human beings and animals through drinking water resulted in the disruption of pancreatic β-cell functioning that provoked the risk factor for development of DM. This study also suggested that long-term arsenic exposure induces hyperglycemia, inflammation, and oxidative stress that may lead to the onset of development of DM.