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Several populations are exposed to mercury (Hg) via their environment, occupation or diet. It is hypothesized that Hg exposure can lead to the development of diabetes mellitus (DM). Metabolic syndrome (MS) is also a possible outcome as its symptoms are closely linked to those of DM.We conducted a systematic review of the literature by screening Web of Science, MEDLINE, SciFinder and Embase and we included original studies pertaining to the relationship of total Hg exposure (elemental, inorganic or organic) to DM, MS or insulin resistance. The studies were selected based on the PICOS (patients, intervention, comparator, outcomes and study design) criteria and their quality assessed using a nine-point scale. Study characteristics and results were extracted and presented in structured tables. We also extracted covariates entered as confounding factors to evaluate possible biases in selected studies. Finally, a weight of evidence approach was used to assess the causality of the relationship.A total of 34 studies were included in the present review. Epidemiological data assessment suggests a possible association between total Hg concentrations in different biological matrices and incidence of DM or MS, but the relationship is not consistent. In vivo and in vitro studies support the biological plausibility of the relation between Hg exposure and DM or MS. Five out of nine of Bradford Hill's criteria were fulfilled: strength, temporality, plausibility, coherence and analogy.Increased total Hg exposure may augment the risk of DM and MS, but the lack of consistency of the epidemiological evidence prevents inference of a causal relationship. Additional prospective cohort studies and careful consideration of confounding variables and interactions are required to conclude on the causal relationship of total Hg exposure on the development of DM or MS.Based on current knowledge, mercury exposure is not a cause of insulin resistance.There is a likely association between mercury exposure and insulin resistance.A weight of evidence approach was used to assess causality.Additional prospective studies on the subject would be useful to assess causality.Mercury specie and type of diabetes should be clearly defined in studies.