Biochemical investigation of association of arsenic exposure with risk factors of diabetes mellitus in Pakistani population and its validation in animal model Kanwal Rehman & Fiza Fatima & Muhammad Sajid Hamid Akash Received: 8 April 2019 /Accepted: 18 July 2019 # Springer Nature Switzerland AG 2019 Abstract 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 uri- nary 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 creat- inine 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 glu- cose (P < 0.001) as compared with that of unexposed animals. Likewise, insulin and glutathione concentra- tions were also significantly decreased (P < 0.001) in arsenic-exposed animals as compared with that of un- exposed 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 disrup- tion of pancreatic β-cell functioning that provoked the risk factor for development of DM. This study also suggested that long-term arsenic exposure induces hy- perglycemia, inflammation, and oxidative stress that may lead to the onset of development of DM. Keywords Arsenic exposure . Diabetes mellitus . Arsenic in drinking water . Urinary arsenic Introduction Arsenic is one of the toxic heavy metals that occurs naturally and its toxicity is a matter of global concern. Arsenic is found in the environment in organic and inorganic forms. Inorganic forms are more toxic than that of the organic forms of arsenic (Jomova et al. 2011; Orloff et al. 2009). Similarly, there are numerous Environ Monit Assess (2019) 191:511 https://doi.org/10.1007/s10661-019-7670-2 K. Rehman : F. Fatima Institute of Pharmacy, Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan M. S. H. Akash (*) Department of Pharmaceutical Chemistry, Government College University, Faisalabad, Pakistan e-mail: sajidakash@gcuf.edu.pk e-mail: sajidakash@gmail.com