Differences in Urinary Arsenic Metabolites between Diabetic and Non-Diabetic Subjects in Bangladesh

Abstract

Ingestion of inorganic arsenic (iAs) is considered to be related to the development of diabetes mellitus. In order to clarify the possible differences in the metabolism in diabetics, we measured urinary iAs metabolites in diabetic cases and non-diabetic control subjects in Faridpur, an arsenic-contaminated area in Bangladesh. Physician-diagnosed type 2 diabetic cases (140 persons) and non-diabetic controls (180 persons) were recruited. Drinking water and spot urine samples were collected. Mean concentrations of total arsenic in drinking water did not differ between cases (85.1 μg/L) and controls (85.8 μg/L). The percentage of urinary iAs (iAs%) was significantly lower in cases (8.6%) than in controls (10.4%), while that of dimethylarsinic acid (DMA%) was higher in cases (82.6%) than in controls (79.9%). This may have been due to the higher secondary methylation index (SMI) in the former (11.6) rather than the latter (10.0). Adjusting for matching factors (sex and unions), and the additional other covariates (age and water arsenic) significantly attenuated the differences in iAs%, SMI, and DMA%, respectively, though the difference in monomethylarsonic acid% was newly significant in the latter adjustment. Our study did not suggest any significant differences in urinary arsenic metabolites between diabetic and non-diabetic subjects.

The Association of Arsenic Exposure and Metabolism With Type 1 and Type 2 Diabetes in Youth: The SEARCH Case-Control Study

“…For cancer and cardiovascular disease, higher MMA% and lower DMA% in urine have generally been associated with a higher risk of disease (34,35). For diabetes, however, studies have shown that the relationship with arsenic metabolism is in the opposite direction, with a positive association between higher DMA% and diabetes in urine, including cross-sectional evidence from Bangladesh (36) and Mexico (11) and prospective evidence from the U.S. (9). Experimental findings support that increased DMA% could be related to diabetes development because the toxic trivalent form of DMA, DMA(III), has been shown to inhibit insulin-stimulated glucose uptake in cultured adipocytes (37) and as a potent inhibitor of glucose-stimulated insulin secretion by isolated pancreatic islets (7).…”

Knockout of arsenic (+3 oxidation state) methyltransferase is associated with adverse metabolic phenotype in mice: the role of sex and arsenic exposure

“…However, with only a limited number of laboratory studies carried out to date, mechanisms underlying the metabolic effects of iAs are poorly understood. Overwhelming evidence suggests that the capacity to methylate iAs plays a major role in susceptibility to these effects (Ahsan et al 2007; Chen et al 2003; Chen et al 2009; Del Razo et al 2011; Huang et al 2008; Kim et al, 2013; Li et al 2013; Maull et al 2012; Mendez et al, 2016; Nizam et al 2013; Yu et al 2000). The As3mt- KO mouse strain was created to facilitate laboratory research focusing on the role of iAs methylation in the adverse effects of iAs exposure.…”

“…Human exposures to iAs have also been linked to adverse metabolic phenotypes characterized by dysglycemia, dyslipidemia, inflammation and high blood pressure, the established risk factors for diabetes and cardiovascular disease (Abhyankar et al 2012; Chen et al 2012; Maull et al 2012; Moon et al 2012; States et al 2009; Wang et al 2007; Wu et al 2012). Notably, the capacity to methylate iAs (as characterized by profiles of iAs and the methylated metabolites in urine) have been consistently shown to affect the risk of cancers and cardiometabolic disease in populations chronically exposed to iAs (Ahsan et al 2007; Chen et al 2003; Chen et al 2009; Del Razo et al 2011; Huang et al 2008; Kim et al, 2013; Li et al 2013; Maull et al 2012; Mendez et al, 2016; Nizam et al 2013; Yu et al 2000). …”

Arsenic metabolism and one-carbon metabolism at low-moderate arsenic exposure: Evidence from the Strong Heart Study

“…(Chen et al 2003a; Chen et al 2003b; Chen et al 2005; Del Razo et al 1997; Hsueh et al 1997; Steinmaus et al 2006; Wu et al 2006; Yu et al 2000) Conversely, higher DMA% and lower MMA% have been associated with diabetes, metabolic syndrome and higher body mass index. (Chen et al 2012; Del Razo et al 2011; Kuo et al 2015; Mendez et al 2016; Nizam et al 2013; Wang et al 2007) Understanding non-modifiable (genetics, sex, life-stage) and modifiable (smoking, alcohol intake, kidney function, body mass index, nutrition) determinants of arsenic metabolism is important given the role of arsenic metabolism in arsenic toxicity. (Balakrishnan et al 2016; Council 2013; Gribble et al 2013; Jansen et al 2016)…”