Is mercury exposure causing diabetes, metabolic syndrome and insulin resistance? A systematic review of the literature
Introduction
Diabetes mellitus (DM) is characterized by either the pancreas not producing enough insulin or organs/tissues not responding adequately to insulin secretion. In both cases, the resulting effect is hyperglycemia that, if left untreated, can lead to DM and damage to susceptible organs. According to the World Health Organization, in 2014, 9% of adults had DM and in 2012, the disease had caused 1.5 million deaths worldwide (Organization WH, 2014a, Organization WH, 2014b). The metabolic syndrome (MS) comprises several cardiometabolic risk factors and symptoms; generally included are high waist circumference, high blood pressure, low high-density lipoprotein cholesterol, elevated plasma triglycerides and hyperglycemia. Individuals with MS exhibit an increased risk of developing DM (Wilson et al., 2005). Both conditions present serious potential health risks and several risk factors are currently being scrutinized in an attempt to limit cardiometabolic morbidity and mortality in populations worldwide.
Exposure to environmental toxicants may play a role in the development of DM and MS (Song et al., 2016, Taylor et al., 2013, Thiering et al., 2016). Mercury (Hg) is a ubiquitous pollutant that is targeted by the Minamata Convention on Mercury, which was adopted and opened for signature on October 10th, 2013 and will likely enter into force in 2017 (Minamata convention on mercury). This international convention aims at reducing Hg emissions worldwide (Kessler, 2013). Hg is released in the environment through burning of fossil fuel, volcano eruptions, industrial processes as well as artisanal and small-scale gold mining (Kessler, 2013).
There are three forms under which Hg can be found: metallic, inorganic and organic Hg. Metallic Hg is the elemental form of Hg and is found mainly in the environment as Hg vapor. With the exception of occupational exposure, humans are rarely significantly exposed to this form of Hg and therefore it will not be discussed further in this review. Inorganic Hg (iHg) is commonly found in contaminated soils as either Hg+ or Hg2+ salts (Park and Zheng, 2012). Populations can be exposed to iHg through various routes such as dental amalgams, skin products and dust present in contaminated areas (Park and Zheng, 2012). Once in water or soils, iHg is transformed by microorganisms to methylmercury (MeHg), the most toxic form of Hg that bioaccumulates and is biomagnified in aquatic food chains. Populations are then exposed to MeHg through the consumption of highly-contaminated predatory fish species (Pirrone et al., 2010).
The relationship between any form of Hg exposure and DM is unclear. However, it is known that Hg can impair the antioxidant defense system, thereby increasing lipid peroxidation and related oxidative stress (Kobal et al., 2004, Salonen et al., 2000, Sener et al., 2003, Wiggers et al., 2008). Elevated MeHg or iHg exposure induces damage in various cell types, including pancreatic islet β-cells. Oxidative stress may be involved in triggering β-cell apoptosis (Chen et al., 2006a). Furthermore, Chen et al. (2006b) reported β-cell damage in rats treated orally with doses of MeHg of 20 μg/kg during 2 weeks, resulting in hyperglycemia (Chen et al., 2006b).
A number of epidemiological studies have investigated the association between biomarkers of Hg exposure and DM or MS development, yielding inconsistent results (Eom et al., 2014, He et al., 2013, Jeppesen et al., 2015, Moon, 2013, Mozaffarian et al., 2013, Park et al., 2009, Virtanen et al., 2014). The lack of systematic literature review precludes any conclusion regarding a possible causal relationship. We used the weight of evidence (WoE) approach described by Adami et al. (2011) to assess whether there is a causal relationship between biomarkers of Hg exposure and cardiometabolic (DM or MS) outcomes (Adami et al., 2011).
Section snippets
Search strategy
We systematically searched the Web of Science (http://webofknowledge.com), MEDLINE (http://www.ncbi.nlm.nih.gov/pubmed), SciFinder (http://scifinder.cas.org) and Embase (http://www.embase.com/) using combinations of two keywords, each combination comprising one keyword selected from each of the following lists (list 1: diabetes, metabolic syndrome, insulin resistance; list 2: mercury, methylmercury). Therefore, six searches were performed in each database. There were no time period restrictions
Study selection
The search yielded 375 articles from the Web of Science, 363 from MEDLINE, 253 from SciFinder and 99 from Embase for a total of 1090 articles. Studies were screened for their title (777 excluded), duplicates (154 excluded) and abstract (116 excluded). By screening the reference lists of each eligible articles, we found one additional article. A total of 43 studies were assessed for their quality: 32 epidemiological studies, three in vivo experimental studies, six in vitro studies and two
Discussion
In this review, we used a WoE approach and determined that based on the lack of evidence of causality and the current knowledge in the literature, total Hg exposure, whether in the form of MeHg, iHg or both, is neither a cause of DM nor MS. This review was based on the knowledge of 25 original human-based articles as well as nine in vivo and in vitro studies. Total Hg concentrations in different biological matrices were associated with an increased risk of DM or MS in some cross-sectional
Conclusions
The main purpose of this paper was to review the results of epidemiological studies and supporting in vivo and in vitro studies and assess the likelihood of a causal interaction between total Hg exposure and the DM or MS development. Based on a WoE approach, there seems to be an association between total Hg concentration in various matrices and the development of either DM or MS, but we did not find sufficient evidence for a causal relationship. Confounding factors play an important role in the
Funding
No funding was provided for this research.
Conflict of interest
The authors do not have any conflict of interest.
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