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Selenium

Selenium is an essential trace element, but it can also be toxic at high doses. Most Americans have high levels of selenium intake as compared to people in some other countries, due to the higher levels of selenium in U.S. soils as well as the use of dietary supplements containing selenium (Laclaustra et al. 2009). High levels of selenium have been found in streams subject to mountaintop mining and valley fills in central Appalachia. In some streams, selenium has bioaccumulated to four times the toxic level in the food chain, a level that can cause harm in fish and birds. Groundwater wells are also affected, and state advisories are in effect for consumption of fish due to high selenium levels (Palmer et al. 2010). There is a high prevalence of diabetes in many counties in central Appalachia (Centers for Disease Control and Prevention 2009).

Type 2 diabetes

Longitudinal studies in humans

The strongest evidence for the ability for environmental exposures to contribute to the development of diabetes comes from longitudinal studies. These are studies that take place over a period of time, where the exposure is measured before the disease develops.

One prospective study from France found that elderly men with higher selenium levels had a lower risk of later developing type 2 diabetes or impaired fasting glucose (there was no association in women) (Akbaraly et al. 2010). A long-term study found that higher toenail levels of selenium were associated with a lower risk of type 2 diabetes in U.S. adults, at dietary levels of intake (Park et al. 2012). However, a study of elderly Swedish men found no association between selenium levels and the development of type 2 diabetes, beta cell function, or insulin resistance 20 years later (Gao et al. 2014). Neither did an Italian study-- it found no association between toenail selenium levels in women and risk of type 2 diabetes 16 years later (Vinceti et al. 2014).

Cross-sectional studies in humans

Cross-sectional studies are studies that measure exposure and disease at one point in time. These provide weaker evidence than longitudinal studies, since the disease may potentially affect the exposure, and not vice versa.

Laclaustra et al. (2009) found that in U.S. adults exposed to background selenium levels, the prevalence of diabetes increased with increasing levels of selenium. Fasting glucose levels and hemoglobin A1C levels (a measure of long-term glucose control) increased with increasing selenium levels as well. Another study using the same dataset but from an earlier time period also found selenium levels to be associated with diabetes (Bleys et al. 2007). A study of elderly Taiwanese found that higher selenium levels were associated with higher fasting glucose (as well as higher triglycerides, cholesterol (Yang et al. 2010).

In countries with lower selenium levels, including Singapore and France, studies have generally not found associations between selenium and diabetes or glucose levels (Laclaustra et al. 2009).

Clinical trials of selenium supplementation

Since selenium is an essential element, it is sometimes found in dietary supplements. Interestingly, two trials of selenium supplementation suggest that selenium may increase the risk of type 2 diabetes. A randomized, double-blind, placebo-controlled study from the Eastern U.S. found that selenium supplementation may increase the risk of developing type 2 diabetes (Stranges et al. 2007). Another large, randomized, double-blind, placebo-controlled study, aimed to determine whether selenium (and/or vitamin E) supplements could prevent prostate and other cancers. It found instead that those who took selenium supplements alone had higher rates of type 2 diabetes (although the increased risk was not significant). The study was discontinued early. It was conducted in the U.S., Canada, and Puerto Rico (Lippman et al. 2009).

On the other hand, randomized, double-blind, placebo-controlled trials, from the western U.S., did not find any increase in diabetes risk or glucose levels with selenium supplementation in men at risk of or with prostate cancer (Algotar et al. 2013; Algotar et al. 2010).

A meta-analysis of four randomized controlled trials found that selenium supplementation did not find a preventative effect (or any statistically significant effect); if anything, there was a slight increased risk (not significant). The authors state, "Our findings do not support the routine application of selenium supplementation for type 2 diabetes prevention in Caucasians" (Mao et al. 2014).

The fact that some trials have shown an increased risk of type 2 diabetes with selenium supplementation has raised concern about the use of supplements in people who are not selenium deficient. Selenium is often added to multivitamins, but "Based on current evidence, the indiscriminate use of selenium supplements in individuals and populations with adequate-to-high selenium status cannot be justified and may increase [type 2 diabetes] risk" (Rayman and Stranges, 2013).

Metabolic syndrome, body weight, and insulin resistance

European women (without diabetes) who had higher levels of selenium in their blood were more likely to have metabolic syndrome than women with lower levels. There was no association in men (Arnaud et al. 2012).

Obese Korean adults with more insulin resistance had lower selenium levels in their hair than those with higher levels, perhaps indicating a mineral deficiency (Kim and Song, 2014). Obese children in Poland tended to have lower selenium levels in their blood, also perhaps indicating a mineral deficiency (Błażewicz et al. 2014).

Laboratory studies

With the confusing human data, laboratory studies may help illuminate what is going on. While selenium is an essential trace element, and necessary up to a certain level-- even helping to prevent diabetes and insulin resistance-- at too-high levels it can induce insulin resistance in rats (Wang et al. 2014). A review of the laboratory evidence finds that while earlier studies found selenium to act like insulin and help prevent diabetes, recent studies (both animal and human) have shown that prolonged, high intake of selenium can cause insulin resistance and/or diabetes in mice, rats, and pigs (Zhou et al. 2013). Even fish, exposed to selenium in water, have higher glucose levels than unexposed fish (Kim and Kang, 2014). In mice, long-term selenium supplements reduced glucose levels at first, but then increased insulin levels and led to fatty liver disease and other harmful effects (Wang et al. 2014).

Exposure during development

Female rats fed were fed a low-selenium or high-selenium diet while pregnant and lactating. A few months after birth, the offspring exposed to a high-selenium diet developed high insulin levels, insulin resistance, and glucose intolerance, as compared to the deficient rats (Zeng et al. 2012). The female lambs of pregnant sheep given selenium had higher birth weight, more fat storage and body weight later on, and selenium also affected their glucose tolerance (Vonnahme et al. 2010). These studies show the potential for selenium exposure to affect development of the offspring later in life.

Gestational diabetes

In the same study as above, the female rats who were fed a high-selenium diet developed high insulin levels, insulin resistance, and glucose intolerance while pregnant (similar to gestational diabetes in humans), as compared to the deficient rats (Zeng et al. 2012). This is a somewhat surprising result, considering that some human studies have found lower selenium levels in women with gestational diabetes, and a higher risk of gestational diabetes in women with inadequate selenium intake (Mariath et al. 2011; Askari et al. 2014). Again, however, it may be that certain levels of selenium are protective against diabetes, while excess selenium can be harmful.

The bottom line

High levels of selenium may increase the risk of type 2 diabetes, while lack of sufficient selenium may also promote diabetes. Selenium supplements should be avoided unless deficient, especially in the U.S., or in people with adequate selenium levels. Supplementation of people who already have adequate intake with additional selenium might increase their risk of type 2 diabetes (Rayman, 2012).

References

To download or see a list of all the references cited on this page, see the collection Selenium and diabetes/obesity in PubMed.