Heavy metals include compounds such as mercury, lead, or cadmium.
Evidence suggests that exposure to heavy metals may play a role in the induction or exacerbation of several autoimmune diseases (Hemdan et al. 2007). These authors review the animal and human evidence linking heavy metals to autoimmunity. Metals such as cadmium and mercury are known to affect the immune system of animals. Heavy metals are likely to influence the development of autoimmunity depending on genetic background, duration of exposure, and current or past infections.
One interesting study compared the levels of toxic metals (arsenic, cadmium (see below), and lead) in mothers with insulin-dependent diabetes and their infants, to mothers without diabetes and their infants. The researchers found that levels of all these metals were significantly higher in the women with diabetes and their infants than in the women without diabetes and their infants. The researchers suggest that these metals may play a role in the development of diabetes (Kolachi et al. 2010). I have tried to confirm with the authors that this "insulin dependent" diabetes was indeed type 1, but have not heard.
Mercury is a pollutant ubiquitous in the environment (Selin et al. 2010). Each year, perhaps 300,000 U.S. children are born who were exposed in utero to blood levels of methylmercury that are above levels thought to be unsafe (Mahaffey et al. 2004).
Mercury is emitted from waste incinerators and coal-fired power plants. This inorganic mercury can be converted to methylmercury in the environment, which bioaccumulates in the food chain (Selin et al. 2010). Fish is the main source of human exposure to methylmercury. Exposure to inorganic mercury may be from dental fillings, cosmetics, or accidental spills (Mahaffey et al. 2004). Methylmercury can cause health effects such as immune suppression and neurodevelopmental delays (Selin et al. 2010).
A large, prospective study of US adults found that those with the highest levels of mercury exposure had a higher risk of diabetes, as well as lower beta cell function (He et al. 2013).
A number of studies have examined the effects of mercury on beta cells in laboratory experiments. One found that inorganic mercury has been found to cause beta cell death, and decrease insulin secretion from beta cells in laboratory experiments (Chen et al. 2010) (see the beta cell stress page). Another found that methylmercury, at concentrations similar to those found in fish (under the recommended limits), can damage beta cells and lead to beta cell dysfunction (Chen et al. 2006a). A third experiment involved exposing mice to low doses of methylmercury or inorganic mercury. It found that decreased insulin secretion and increased blood glucose levels. Interestingly, insulin and glucose levels gradually returned to normal after mercury exposure ended. The authors conclude, "these observations give further evidence to confirm the possibility that mercury is an environmental risk factor for diabetes" (Chen et al. 2006b).
In studies of humans, mercury has been linked to autoimmunity, in both people with high exposures, and people with lower exposure levels. (Nyland et al. 2011). Exposure to mercury can induce autoimmunity as well as worsen ongoing cases in some strains of mice genetically susceptible to autoimmunity (Hemdan et al. 2007). Mercury has also been shown to induce autoimmunity even in mice that are not genetically susceptible to autoimmunity (Abedi-Valugerdi 2009). The effects of mercury in part depend on the type of mercury. Inorganic mercury, for example, can induce autoimmunity in genetically susceptible mice, similar to the effect of the vaccine preservative thimerosal. Organic mercury leads first to immunosuppression and then to autoimmunity in these mice (Havarinasab and Hultman 2005).
Yet mercury has been found to activate the immune system and delay diabetes in NOD (non-obese diabetic) mice (Brenden et al. 2001), which are one of the lab animals used to model autoimmune diabetes. However, most interventions-- 195 of them so far-- delay or prevent disease in NOD mice, including some that have not shown the same effect in humans. This is one reason many researchers question the usefulness of NOD mice (Roep and Atkinson 2004) (discussed further on the of mice and men page). NOD mice, then, are probably not appropriate to use for examining the effects of environmental contaminants on type 1 diabetes in humans.
In humans, mercury has been associated with autoimmunity, yet it has not been studied in relation to diabetes. There is epidemiological evidence that shows associations between the autoimmune disease lupus and an oil field waste site contaminated with mercury and petroleum products (Dahlgren et al. 2007).
In Brazil, a study found elevated autoantibody levels in gold miners (exposed to high levels of inorganic mercury), as well as in people who ate fish containing methylmercury, as compared to less exposed people (Silva et al. 2004). A further study from Brazil has found that gold miners not only had higher levels of autoantibodies, but also higher levels of certain inflammatory cytokines that are associated with autoimmune disease than less exposed people (see the inflammation page for more on cytokines) (Gardner et al. 2010).
In a study of U.S. adults, urinary cadmium levels were associated with impaired fasting glucose levels and type 2 diabetes. This finding is supported by animal studies that show that cadmium can cause high blood glucose, damage beta cells, and cause diabetes in rodents (Schwartz et al. 2003). Edwards and Prozialeck (2009) review the literature concerning cadmium exposure, blood glucose levels, and diabetes. They conclude that cadmium can have direct toxic effects on the pancreas, and may be a factor in the development of diabetes. A study from cadmium-contaminated villages in Thailand did not find a significant association between cadmium exposure and diabetes in adults (Swaddiwudhipong et al. 2010), but comparing exposed villagers in 2005 with 2010, there was a significant increase in diabetes (Swaddiwudhipong et al. 2011).
Cadmium exposure has also been found to result in autoimmunity in animals (Bigazzi 1994).
For information on the relationship between type 1 and type 2 diabetes, see the other types of diabetes page.
Since deficiencies of essential metals are known to affect weight, it is possible that toxic metals could contribute to weight gain or loss as well. Some researchers have found associations between various metals and body mass index (BMI) / waist circumference (WC) in a study of U.S. residents. Higher levels of barium and thallium were associated with higher BMI/WC, while cadmium, lead, cobalt and cesium were associated with lower BMI/WC (Padilla et al. 2010).
A study from a contaminanted area in Taiwan found that people with the highest levels of exposure to both mercury and PCDD/Fs (persistent organic pollutants) had 11 times the risk of insulin resistance than those with the lowest exposures. Insulin resistance increased with both mercury and PCDD/F exposure, but simultaneous exposure to both compounds may increase the risk of insulin resistance more than exposure to one or the other alone. This study also found that each component of metabolic syndrome (common in people with type 1 or 2 diabetes) that they studied was associated with both mercury and PCDD/F exposure levels, including an increased waist circumference (Chang et al. 2010c).
See the insulin resistance and height and weight pages for information on these factors and and type 1 diabetes development.
Some metals, including lead and gold, have also been found to exacerbate autoimmunity in animals. Perhaps these contaminants contribute to a dysfunctional immune system, leading to an improper response to an infection, and resulting in autoimmune disease (Dietert et al. 2010). Some heavy metals, including lead, cadmium, and methylmercury, can affect the development of the immune system (see the autoimmunity page) (Holladay 1999). McCabe et al. (2003) describe a mechanism by which inorganic mercury affects the immune system and thereby could contribute to autoimmune disease, by interfering with apoptosis (programmed cell death) processes. Chen et al. (2010) and the other studies on mercury's effects on beta cells found that the mechanisms involved oxidative stress, a mechanism that may be involved in type 1 diabetes development.
Cadmium has been shown to have endocrine (hormone) disrupting effects (Byrne et al. 2009). And, many metals, including cadmium, chromium, mercury, and nickel, have been found to affect gene expression in animals (Baccarelli and Bollati 2009).
Some heavy metals may be able to influence other type 1 diabetes risk factors, including stress, viruses, and increased weight, and are sometimes present in vaccines. Some have been found to affect the intestine as well.
Based on the above findings, the possibility that heavy metals can contribute to the development of type 1 or type 2 should be studied further.