A Review of Diabetes Mellitus and Exposure to the Environmental Toxicant Cadmium with an Emphasis on Likely Mechanisms of Action

Abstract

There is increasing interest in how exposure to environmental substances can contribute to the onset of Type II diabetes mellitus (T2DM). Impaired insulin release is a hallmark of type I diabetes mellitus and is involved in the progression of T2DM. Both epidemiological and experimental studies show that exposure to the environmental pollutant cadmium (Cd), is associated with hyperglycemia, T2DM and reduced serum insulin. The goal of this review is to examine likely mechanisms of action of Cd-induced dysglycemia based on experimental studies in the literature and from the most recent findings in the Edwards lab. The primary focus of this review will examine how Cd may cause islet dysfunction and subsequent impaired insulin release. Recent findings in the Edwards lab indicate that Cd causes time-dependent and statistically significant changes in fasting leptin, Glucose-dependent Insulinotropic Polypeptide (GIP) and pancreas polypeptide hormone levels in a subchronic animal model of Cd-induced hyperglycemia. This review summarizes the most likely cellular mechanisms by which the ubiquitous environmental contaminant Cd disrupts glucose homeostasis. While individual cellular effects of Cd are reviewed it is likely that no one single mechanism is involved, rather multiple mechanisms exist and work synergistically resulting in islet dysfunction and ultimately dysglycemia.

Assessment of heavy metals by ICP‐OES and their impact on insulin stimulating hormone and carbohydrate metabolizing enzymes

“…Similarly, several studies conducted in various populations including United States, 15 Korea 16 and China, 17 suggest that a direct correlation exists between Cd exposure and risk of DM. Numerous studies have revealed that Cd‐induced hyperglycaemia resulted in enhanced lipid peroxidation, reduced insulin secretion, enhanced activity of gluconeogenic enzymes and impaired insulin receptor signalling 18,19 …”

Joint venture on the further development of chemical exposure assessment by use of probabilistic modelling

“…Diet and tobacco smoking are the primary sources of human exposure to cadmium (WHO, 2010b), which then accumulates in the body, as it has a half-time of over of 26 years (ATSDR, 2012). The deleterious effects include carcinogenicity (IARC, 2012), end-stage renal failure (Kobayashi et al, 2008), bone demineralisation, (Kjellstr € om, 1992), reproductive and developmental toxicity (Gupta, 2011) and disturbance of metabolism (Edward and Ackerman, 2016) and macro-and micronutrients homeostasis (Kim et al, 2007).…”

Diabetic nephropathy in type 2 diabetes – from pathological mechanisms to clinical occupational medicine practice

“…Concerning environmental and/or occupational exposure in the pathogeny of diabetes, several studies incriminated persistent organic pollutants (polychlorinated biphenyls, organochlorine pesticides, polyciclic aromatic hydrocarbons, phthalates etc) [6], metals (arsenic, cadmium) [7]. Therefore, with proper technical masures, all employees should avoid occupational contact with these substances.…”

“…Exposure to persistent organic pollutants (polychlorinated biphenyls, organochlorine pesticides, polycyclic aromatic hydrocarbons, phthalates etc) [6], heavy metals (arsenic, cadmium) [7] need to be avoided as they have a potential role in the pathogeny of diabetes. With correct technical measures, all employees should avoid occupational contact with these substances, not only by those already diagnosed with T2D.…”