Home‎ > ‎Potential Mechanisms‎ > ‎

Endocrine Disruption

Endocrine disruptors
On this page:

The Endocrine System

The endocrine system of the body is made up of glands that secrete hormones. The pancreas, for example, is an endocrine organ that secretes the hormone insulin. The hormone/endocrine system is one system of communication within the body. Certain cells release hormones as a result of some signal (e.g., the beta cells in the pancreas release insulin when they sense that glucose levels in the blood are rising), and the hormone (in this case, insulin) travels through the blood to bind with hormone receptors (e.g., insulin receptors) on various cells. That triggers some effect, in this example, when insulin binds to a receptor, glucose can enter the cell. Almost all (or perhaps all) cells would have receptors for insulin, but only certain cells would have receptors for other hormones (e.g., estrogen or testosterone, etc.). The numbers and types of hormone receptors on cells change over time, and change depending on the concentration of the hormone in the blood, and on the stage of development of the organism.

Endocrine organs include, among others, the pancreasthymus, thyroid gland, and adrenal gland. Endocrinologists treat diseases of the endocrine system, such as diabetes and thyroid disease. There are many hormones in humans, estradiol, estrogen, testosterone, androgen, insulin, glucagon, glucocorticoid, thyroid hormones, and more. Vitamin D is also considered to be a secosteroid, a type of steroid hormone.

Endocrine Disrupting Chemicals

Substances that can interfere with the endocrine (hormone) system are called "endocrine disruptors." These substances may act like hormones, binding with their receptors, or block the receptors, preventing hormones from binding with them, affecting the ability of cells to produce or secrete hormones hormones, and more (Hotchkiss et al. 2008). For example, an estrogenic chemical is one that acts like estrogen, and binds to estrogen receptors on cells, triggering a response that normally estrogen would trigger. An anti-androgen is a chemicals that can block androgen hormones from binding with their receptors, preventing the cells from responding to an androgen hormone. Some chemicals can affect the ability of beta cells to either produce or secrete the hormone insulin, sometime increasing and sometimes decreasing these processes.

Which other chemicals are endocrine disruptors?

The Endocrine Disruption Exchange (TEDX) maintains a list of potential endocrine disruptors on its website. There are almost 1000 chemicals on the list. 
A number of environmental chemicals (as well as other substances, such as some pharmaceutical drugs) are endocrine disruptors (Hotchkiss et al. 2008). Gore et al. (2006) list some common characteristics of how endocrine disruptors can act:
  • the timing of the dose is critical to the outcome of the exposure (since it depends on when receptors are present, and how many);
  • exposure during fetal, perinatal, or early post-natal periods may produce life-long effects (whereas adult exposures may have more transient effects);
  • effects may be seen with low level exposures (like those found in the environment, since hormones act at very low levels);
  • effects may not increase predictably as the dose increases (they exhibit complex dose response curves; when there are low levels of a hormone in the blood, they body will respond easily, while when there are high levels of a hormone in the blood, the number of receptors may actually start to decline and the body will not respond as much); and
  • the effects may sometimes be transmitted to subsequent generations (probably involving epigenetic mechanisms).
A number of the chemicals considered here, including arsenic, some persistent organic pollutants (POPs) such as PCBs and dioxin, bisphenol A, phthalates, some pesticides, and possibly nitrate, are considered endocrine disruptors. Please visit those pages for studies on these chemicals.
 
Most research on endocrine disruptors thus far has focused on the reproductive system, but the effects of these chemicals on other body systems are now under investigation. The immune system, the digestive system, the cardiovascular system, the central nervous system, metabolism, and fat (adipose) tissue are also targets of endocrine disrupting compounds (Hotchkiss et al. 2008).

While everyone is exposed to endocrine disrupting chemicals, some are more highly exposed than others. For example, ethnic and racial minorities tend to be exposed to higher levels of BPA, phthalates, parabens, and flame retardants than whites (James-Todd et al. 2016). In fact, there is substantial evidence that these disparities in exposure levels play a role in the disparities found in type 2 diabetes (Ruiz et al. 2017).

Early Life Exposures

Endocrine Disruption Basics

Watch a webcast of a seminar on Hormone-Altering Chemicals from the Harvard T.H. Chan School of Public Health (Jan. 2017).
Endocrine disruption is important especially during a fetus/infant/child's development, because hormones play a critical role in controlling how the body develops. Endocrine disrupting chemicals are linked to changes in metabolic processes even in umbilical cord blood, which could contribute to metabolic disorders like diabetes or obesity later in life (Remy et al. 2016).

If you give animals hormones during development, it can affect their later risk of diabetes-related health effects. For example, researchers exposed pregnant ewes to androgen (testosterone), estrogen, and glucocorticoid hormones. The offspring of ewes exposed to androgens had altered development of their pancreas, leading to excess insulin secretion in adolescence (Ramaswamy et al. 2016). Gestational exposure to testosterone also causes insulin resistance in sheep (Puttabyatappa and Padmanabhan 2017).

Interestingly, since endocrine disruptors can affect the development (differentiation) of cells, they affect the activity of stem cells. Some authors argue that this has importance for the therapeutic uses of stem cells to treat diseases (Bateman et al. 2017).

Mixtures of Chemicals

While this webpage focuses on chemicals individually, we are all exposed to hundreds of endocrine disrupting compounds at the same time. What are the effects? We have no idea. One study studied exposure to low doses of 27 chemicals, similar to those found in humans. They found a variety of effects, including effects on weight and metabolism (Hadrup et al. 2016). We need more studies that address chemical mixtures or new methods to address this problem, and some are beginning to show up (e.g., see Lee and Jacobs 2015Watt et al. 2016). One finds, for example, that a mixture of endocrine disrupting chemicals has numerous metabolic effects on mice (Le Magueresse-Battistoni et al. 2017).

Interestingly, mixtures of other endocrine disrupting chemicals can actually affect the levels of other endocrine disrupting chemicals. Single doses of triclosan, parabens, phthalates, or other phenols (and a combination of all of them) raised BPA (and estrogen) levels in mice, perhaps because they interfere with enzymes that metabolize estrogen (Pollock et al. 2017). For an article about this study, see Compound Interest: Assessing the Effects of Chemical Mixtures, published in Environmental Health Perspectives (Konkel 2017).

Endocrine Disruptors and Diabetes: Is There a Link?

Some researchers are now trying to figure out how to screen endocrine disrupting chemicals for their potential effects on diabetes, obesity, and metabolism, e.g., by using stem cells. One study, for example, found that the endocrine disruptors TBT, PFOA, and the food additive BHT disrupt developing gut endocrine system cells (Rajamani et al. 2017). Aside from that method, there is much additional research on the possible links, discussed throughout this website. For example:

Type 2 Diabetes

It is becoming clear that numerous endocrine disruptors are linked to the development of type 2 diabetes. The strongest evidence exists for persistent organic pollutants (see Lee et al. 2014; Taylor et al. 2013) and arsenic (Wang et al. 2014; Maull et al. 2012). There is growing evidence for many other endocrine disrupting chemicals as well (see pages on individual chemicals for details) (Reviewed by Chevalier and Fénichel 2014; Fénichel and Chevalier 2017; Firmin et al. 2016). A systematic review and meta-analysis of 49 studies from diverse populations found that both persistent (PCBs, dioxin, chlorinated pesticides) and non-persistent (BPA, phthalates) endocrine disruptors were associated with type 2 diabetes, impaired fasting glucose, and insulin resistance (Song et al. 2015). Endocrine disruptors are also implicated in complications and diseases that relate to type 2 diabetes, including atherosclerosis and cardiovascular disease (Helsley and Zhou, 2017; Kirkley and Sargis, 2014).

In fact, there is so much research on this topic (explored all over this website), that researchers are now calling these chemicals "metabolism disrupting chemicals" (Nadal et al. 2017). These chemicals are implicated not only in type 2 diabetes, but also metabolic syndrome, obesity, non-alcoholic fatty liver disease (NAFLD) (Foulds et al. 2017), and more. They can affect metabolism using a variety of mechanisms (Mimoto et al. 2017).

It is clear that sex hormones play a role in type 2 diabetes, so it does make sense that chemicals that mimic these hormones do as well (Liu and Sun 2016). In fact sex hormones play a role in other types of diabetes as well, as well as obesity and metabolic syndrome, and in impaired fasting glucose and glucose intolerance (Mauvais-Jarvis 2017a; Mauvais-Jarvis 2017b).
Factsheet on Endocrine Disruptors by the National Institute of Environmental Health Sciences (NIEHS)

Type 1 Diabetes

We do not have much evidence regarding type 1 diabetes and endocrine disruptors; it is a largely unexplored field.

First, we might ask whether natural hormones can influence the development of type 1 diabetes. There is evidence that they can. For example,  Gender differences are present in type 1 diabetes, and it is possible that sex hormones may influence the risk of developing type 1 diabetes in some way (Gale and Gillespie 2001). The incidence of type 1 diabetes in children peaks at puberty, a time of hormonal changes. Pregnancy, another time of hormonal change, can lead to gestational diabetes, later followed by type 1 or 2 diabetes. Stress may be a risk factor for type 1 diabetes, and while the mechanism is unknown, perhaps hormones released during stress could play a role. In addition, the hormone vitamin D appears to be protective against type 1 diabetes development. The role of height and weight as risk factors for type 1 diabetes may also involve hormones.

In turn, all of these factors (puberty, pregnancy, stress, vitamin D, and height and weight), can be influenced by exposure to endocrine disrupting chemicals. For example, endocrine disruptors are a likely factor contributing to the earlier appearance of puberty, a possible accelerator of type 1 diabetes.

It is clear to me, as someone with type 1 diabetes, that hormone levels can also influence blood glucose levels and blood glucose control day-to-day. Again, times of natural hormonal changes like puberty and pregnancy make it hard to control type 1 diabetes. Even the hormonal fluctuations during the menstrual cycle can affect insulin sensitivity in women with type 1 diabetes (see Brown et al. 2015).
 
We do not know, however, if chemicals that interfere with the endocrine (hormone) system contribute to the development of type 1 diabetes, or affect blood sugar management. The following sections provide some evidence that this possibility exists, although this hypothesis has not yet really been tested.
Listen to Dr. Rodney Dietert of Cornell University discuss Endocrine Disruption and Immune Dysfunction on this call sponsored by the Collaborative on Health and the Environment.

The Immune System and Autoimmunity

The ability of many endocrine disruptors to interfere with the body's endocrine system may be important for the immune system, since the immune and endocrine systems interact. Evidence is growing that endocrine disruptors can affect the immune system, although exactly how is still under investigation (Clayton et al. 2011).
 
The effects of endocrine disruptors on the immune system may be particularly important for type 1 diabetes, since it is an autoimmune disease. Yet keep in mind that the effects of endocrine disruptors on the immune system may also be involved in the development of type 2 diabetes as well (Bansal et al. 2017).
 
Because females are more susceptible than males to many autoimmune diseases, some researchers hypothesize that environmental estrogens could promote autoimmune disease (e.g., see Walker et al. 1996; Ahmed et al. 1999; Ortona et al. 2016). Gender does influence the behavior of the immune system, since sex hormones interact directly with immune system cells, although how these hormones might affect the development of type 1 diabetes is not known. Type 1 diabetes, unlike other autoimmune diseases, is not more common in females (Gale and Gillespie 2001).
 
In animals, some estrogenic endocrine disruptors have been found to promote autoimmunity. For example, Yurino et al. (2004) found that bisphenol A enhances autoantibody production in mice. Bisphenol A is an estrogenic compound. These researchers also found that the estrogenic pharmaceutical diethylstilbestrol (DES) had the same effects. The weakly estrogenic organochlorine pesticide chlordecone accelerates the development of autoimmune disease in mice. Its effects were similar to estradiol, but not identical (Wang et al. 2007) (described further on the persistent organic pollutants page). In animals, estrogen can cause the thymus to shrink, affect thymocytes, and promote autoimmunity; estrogenic chemicals may act similarly (Ahmed et al. 1999). 
 
DES was given to pregnant women decades ago to prevent miscarriage (it didn't work, but instead led to various health problems in these women's offspring). There is some limited evidence linking autoimmunity and DES in humans: women exposed to DES in utero seem to have a higher incidence of autoimmune disease, but only when various autoimmune diseases are grouped together (Ahmed et al. 1999). Yet a more recent study that followed these women over 25 years found that there was not an overall increase in autoimmune diseases in DES exposed daughters, although type 1 diabetes was not included in this study (only four autoimmune diseases were included). However, there was an increased risk of the autoimmune disease rheumatoid arthritis in women under 45, and a lower risk in those over 45 (Strohsnitter et al. 2010).

Estrogens also have been found to protect beta cells-- this may be one reason type 1 diabetes is not more common in women as compared to men. And, while puberty leads to an increased incidence of type 1 in boys, this is not necessarily the case in girls (Mauvais-Jarvis, 2017c).
 
Yet other chemicals that act via different, non-estrogenic pathways also have been shown to promote autoimmunity in animals. Thus estrogenic compounds are not the only compounds of concern. Phthalates, for example, can induce autoantibodies in mice, although the resulting health effects depend on the strain of mouse (Lim and Ghosh 2005). And, dioxin exposure during immune system development has been shown to result in changes suggestive of autoimmune disease in mice (Mustafa et al. 2008). Several phthalates are anti-androgens, and dioxin acts on multiple components of the endocrine system, via the aryl hydrocarbon receptor (AhR) (Hotchkiss et al. 2008). And, some chemicals can affect a number of receptors. Bisphenol A, for example, affects the activation of not only estrogen receptors, but also androgen and AhR receptors (Kruger et al. 2008).
 
Karin Russ, CHE


Karin Russ, RN, National Coordinator of the Collaborative on Health and Environment's Working Group on Fertility and Reproductive Health, is concerned about the health impacts of endocrine disrupting chemical exposure, especially during gestation and early in life.
The hormone vitamin D is also involved in the immune system, and may be protective against some autoimmune diseases, including type 1 diabetes (Norris 2001). Some chemicals may be able to affect vitamin D levels in animals. Lilienthal et al. (2000) hypothesized that since PCBs can affect other hormones, it might make sense that they could interfere with vitamin D levels. Their study found that PCBs did reduce vitamin D levels in rats. See the vitamin D page for more studies on vitamin D, type 1 diabetes, and chemical effects on vitamin D levels.

Up to 25% of patients with type 1 diabetes have evidence of thyroid disease, the most common autoimmune disease associated with type 1 diabetes (Umpierrez et al. 2003). Endocrine disruptors can affect the thyroid hormone (for a review of the main thyroid-disrupting chemicals (PCBs, perchlorates, brominated flame retardants, and phthalates), see Jugan et al. (2010)). Since thyroid levels during pregnancy are critical to proper fetal development, these thyroid disrupting chemicals are also important during development. Thyroid hormones are also important for glucose levels and metabolism. Thus prenatal exposure to thyroid disruptors are also linked to changes in glucose and metabolism in the offspring (Molehin et al. 2016).
 
Glucocorticoids are other hormones involved in the immune system. Disturbed glucocorticoid action is associated with a number of conditions, including autoimmune disease, type 2 diabetes, and obesity. Chemicals that can disrupt glucocorticoid action include PCBs, organotins, arsenic, dithiocarbamate chemicals (found in some pesticides and cosmetics), and more (Odermatt et al. 2006).

Beta Cells

Some endocrine disruptors have been found to affect the insulin-producing beta cells or insulin secretion from beta cells, including bisphenol A, PCBs, dioxin, and arsenic, potentially leading to beta cell stress. See those pages for information on these studies.
 
Nadal et al. (2009) review how the beta cell is a target of estrogenic compounds. They discuss how an excess of estrogen or estrogenic compounds such as bisphenol A could produce an excess of insulin signaling and insulin secretion, overstimulating beta cells. This signaling in turn may provoke increased insulin resistance and beta cell exhaustion. The authors argue that these compounds may thus contribute to the development of type 2 diabetes, but we should also consider the possibility that they may contribute to the development of type 1 diabetes as well. Environmental factors that stress or overload beta cells may be a factor in the increased incidence of type 1 diabetes in children (Dahlquist 2006; Ludvigsson 2006), and increased insulin resistance may accelerate the appearance of type 1 diabetes (see the beta cell stress and insulin resistance pages). Estrogen, on the other hand, can also be protective of beta cells (Mauvais-Jarvis et al. 2017d), so the whole thing is complicated-- it may also depend on ratios of estrogen and testosterone, for example.
 
Dioxin has also been shown to stimulate insulin secretion from beta cells (Kim et al. 2009). Other researchers, however, found that dioxin impaired insulin secretion (Kurita et al. 2009). Like bisphenol A, dioxin has been associated with type 2 diabetes in humans, and autoimmunity in animals. Other chemicals that interfere with AhR include PCBs and polychlorinated dibenzofurans (PCDFs) (Hotchkiss et al. 2008).
 
Li et al. (2008) tested the hypothesis that androgen hormones (testosterone is an androgen hormone) and androgen receptors could be involved in the development of type 1 diabetes, perhaps helping to explain why type 1 diabetes is not more common in women than men. To test this idea, they looked for, and found, androgen receptors in beta cells. These receptors help to control the process of beta cell apoptosis (programmed cell death).
 
Could androgenic or anti-androgenic chemicals then affect beta cells? This question has not yet been researched. In rats, increased androgen levels impair insulin secretion by disrupting pancreatic beta cells (Wang et al. 2015). Some endocrine disrupting chemicals can influence androgen receptor actions and can be androgenic or antiandrogenic at levels found in the environment, although the health effects investigated so far are related to the reproductive system. Masculinized female fish have been found in living in rivers contaminated with effluent from pulp mills around the world, indicating androgenic activity. Yet the responsible androgenic chemicals in this effluent have not yet been identified. Androgenic action has also been found in effluent from cattle feedlot operations in the U.S. (Hotchkiss et al. 2008). Cadmium has also been shown to have androgenic effects (Byrne et al. 2009), and has been associated with type 2 diabetes (see the heavy metals page). Anti-androgens can interfere with androgen signaling and can affect androgen-sensitive organs in animals. Some anti-androgens include the persistent organic pollutant DDE, some fungicides (vinclozolin, procymidone, and prochloraz), the herbicide linuron, several phthalates, PBDE flame retardants (Hotchkiss et al. 2008), and bisphenol A and other components of plastics (Krüger et al. 2008).

Effects can be passed down the generations

The effects of endocrine disrupting chemicals are sometimes passed down from one generation to the next. Early life exposure to some chemicals cause obesity in animals, as well as in their offspring, and their offspring, and their offspring...

"Transgenerational effects of chemical exposure raise the stakes in the debate about whether and how endocrine disrupting chemicals should be regulated." 

Insulin Resistance and Body Weight

Some endocrine disruptors have been found to increase insulin resistance, including bisphenol A, some persistent organic pollutants (including dioxin, and PCBs), some pesticides, and phthalates.
 
Estradiol helps to maintain normal insulin sensitivity and beta cell function. Estrogen levels that are either too high or too low may promote insulin resistance and type 2 diabetes (Nadal et al. 2009). In fact, men with higher levels of natural estrogens are of at higher risk of type 2 diabetes, according to a large, long-term study (Jasuja et al. 2013). In obese women, levels of chemicals that act like estrogen are pervasive, and associated with inflammation, metabolic abnormalities, and cardiovascular risk (Teixeira et al. 2015). 

Other hormone receptors involved in obesity and insulin resistance are PPAR receptors. These receptors control metabolism, and some chemicals can interfere with them (Casals-Casas et al. 2008) (see the organotins and phthalates pages, for example). More and more chemicals are being screened for their ability to interact with PPAR receptors, and thereby be labeled as potential obesogens. For example, components of the crude oil dispersant used in the Deepwater Horizon oil spill was found to activate these receptors (Temkin et al. 2015). Sex hormones also play a role in the function of the PPAR receptors (Sato et al. 2014). Exposure to excess testosterone during development can also lead to adult metabolic disorders in animals (Abi Salloum et al. 2015; Lu et al. 2016). In sheep, those exposed to testosterone in the womb show insulin resistance and other metabolic effects later in life that could predispose them to metabolic diseases (Padmanabhan and Veiga-Lopez, 2014; Puttabyatappa et al. 2017).

Some endocrine disruptors have been shown to increase the formation of fat cells. For example, both nonylphenol and DES promote the formation of fat cells in laboratory studies, and increase body weight in mice (Hao et al. 2012a, Hao et al. 2012b). Certain parabens, chemicals found in cosmetics and other consumer products, increase fat cell development and are potential obesogens (Hu et al. 2017Hu et al. 2016Pereira-Fernandes et al. 2013). Wastewater discharged from water treatment plants also contains endocrine disrupting compounds, and mice who drank this water gained more fat (Biasiotto et al. 2016). For studies on other endocrine disrupting compounds linked to obesity, see the individual chemical pages.

The effects of endocrine disruptors are important during development. For example, a study found that higher levels of environmental estrogens in the placenta were associated with higher birth weight in boys (Vilahur et al. 2013). Other studies have found exposure to endocrine disrupting chemicals to be associated with low birth weight (Birks et al. 2016).
 
The May 25, 2009 issue of the journal Molecular and Cellular Endocrinology published a special issue on the role of environmental endocrine disrupting chemicals in the development of obesity and diabetes. For example, Heindel and vom Saal (2009) propose that the recent increase in obesity is due to both nutrition and environmental chemical exposures in early life. Grün and Blumberg (2009) review the evidence that a variety of endocrine disrupting chemicals can influence fat formation and obesity. Newbold et al. (2009) review the mechanisms involved in endocrine disruption and obesity.

More recent reviews also find that early-life exposure to endocrine disrupting compounds may play a role in the development of obesity (Botton et al. 2017Braun 2016; Giulivo et al. 2016; Heindel et al. 2016; Heindel et al. 2015Holmes 2016; Janesick and Blumberg 2016Lind et al. 2016Nappi et al. 2016; Petrakis et al. 2017Russ and Howard 2016; Shafei et al. 2017Wang et al. 2016).

The OBELIX Project is a pan-European effort to evaluate the role of endocrine disrupting chemicals in obesity, using both long-term human studies (focusing on exposure during development) and laboratory studies (Legler, 2013). OBELIX is an abbreviation for “OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life.”

A review of the evidence on endocrine disrupting chemicals and obesity notes that:
  • Endocrine disruptors are ubiquitous in the environment-- we are all exposed;
  • They have been shown to affect energy and metabolism;
  • They have been shown to affect body weight, fat content, fat cell development, glucose levels, obesity, insulin resistance, food intake, and more;
  • Their effects are most profound when exposure occurs during fetal development;
  • Their epigenetic effects may be significant for future generations;
  • Genes, poor diet, and sedentary behavior cannot fully explain obesity;
  • And finally, the evidence "provides a plausible basis for hypothesizing that endocrine disruptors are responsible for the rapid increase in obesity at the end of the last millennium." (Schneider et. al. 2014).

Gestational Diabetes

There is a dearth of research on endocrine disrupting compounds and gestational diabetes, although research has linked a few endocrine disrupting chemicals to gestational diabetes (search this website for gestational diabetes to see where links have been found, and for a review of the topic, see Ehrlich et al. 2016). Natural hormone levels are linked to an increased risk of gestational diabetes development (Hur et al. 2017). 

Identifying Endocrine Disruptors

There are a variety of methods to identify endocrine disrupting chemicals. The Endocrine Disruption Exchange hosts an online searchable list of potential endocrine disrupting chemicals. As of June 2015, there were almost 1000 chemicals on that list.

The U.S. Environmental Protection Agency (EPA) is supposed to be identifying endocrine disruptors using its Endocrine Disruption Screening Program, but they are way behind and have barely made a dent in screening chemicals. Money for this program may also be cut by the Trump administration.

The EPA wants to use more modern techniques than animal studies to screen chemicals. The advantage of these approaches is that they can screen hundreds of chemicals in a very short time. The disadvantage, so far, is that they may not be accurate. The debate continues.

While we wait for them to figure this out, we are experimenting on ourselves (but without an unexposed control group). For example, some scientists analyzed 65 compounds that migrate from polycarbonate plastic baby bottles (into milk), and found that 53 of them showed some endocrine activity (Simon et al. 2016). Exposing babies to these chemicals is just not ethical.

Economic Costs of Endocrine Disruptors

Some researchers have tried to estimate the economic costs of exposure to endocrine disrupting chemicals. For example, an expert panel of scientists has determined that exposure to 3 types of endocrine disrupting chemicals (BPA, DDE, and phthalates) in the European Union leads to economic costs of at least €18 billion per year -- for obesity and diabetes alone (not including other diseases) (Legler et al. 2015). Another study calculated that a reduction of chemical exposures (to phthalates, DDE, PCBs, and PFCs) could lead to a 13% reduction in diabetes. Extrapolating to Europe, they estimate that reducing chemical exposures could prevent 152,481 cases of diabetes in Europe and €4.51 billion/year in associated costs, compared with 469,172 cases prevented by reducing BMI (Trasande et al. 2016). Of course, these estimates are just estimates, and the true cost could be lower or higher. In fact, the estimates can vary quite a bit depending on what method is used to calculate them. Costs tend to be much higher when using human studies vs toxicological studies (Prichystalova et al. 2017).

Another study finds that environmental chemical exposures contribute costs that may exceed 10% of the global domestic product (Grandjean and Bellanger, 2017). 

The Bottom Line

The effects of endocrine disruptors on all endocrine glands, including the pancreas, and all relevant systems, including the immune system, are important areas to research. Suvorov and Takser (2008) point out that "the role of environmental contaminants in increasingly prevalent endocrine disorders such as childhood obesity and diabetes mellitus is an important research avenue."

The Endocrine Society's Second Scientific Statement on Endocrine-Disrupting Chemicals (EDCs) devotes a section to diabetes and obesity. Their summary points (Gore et al. 2015):
  • "Disruption of glucose and lipid homeostasis is a risk factor for metabolic disorders including obesity and diabetes mellitus.
  • BPA, phthalates, tributyltin, arsenic, PBDEs, perfluorooctanoic acid, dioxin, PCBs, and DDTs are known to have effects on cellular and animal models.
  • In animal models, prenatal and perinatal exposures to some EDCs disrupt the homeostatic control of adipogenesis and/or energy balance, and induce obesity. A growing number of EDCs alter insulin production, secretion, and/or function, increasing the susceptibility for type 2 diabetes mellitus (T2D). Some animal models suggest that EDCs have direct adverse effects on the cardiovascular system.
  • A number of cross-sectional epidemiological studies associate EDC levels with obesity, diabetes mellitus, and cardiovascular diseases in humans. There are important prospective studies associating exposure to persistent organic pollutants and T2D.
  • Obesogenic and diabetogenic effects are induced in a nonmonotonic dose-dependent manner. Exposures to different levels produce diverse phenotypes.
  • The molecular mechanisms involved are still largely unknown, but alteration of gene expression after binding to the aryl hydrocarbon receptor, PPAR, and ERs seems to play a role.
  • The interaction between EDC exposure and single nucleotide polymorphisms associated with obesity, T2D, and cardiovascular diseases is a key issue for future studies."
The Endocrine Society's Statement concludes, "...there is sufficient evidence to conclude that some EDCs act as obesogens and others act as diabetogens." Also, "...animal studies indicate that some EDCs directly target beta and alpha cells in the pancreas, adipocytes, and liver cells and provoke insulin resistance together with hyperinsulinemia."

They also call for more research on EDCs and type 1 diabetes: "Studies relating EDCs and other contaminants to T1D are beginning to emerge, although they are still very preliminary... this is an important area that deserves further research and more studies in humans" (Gore et al. 2015).

We do not know if endocrine disruptors contribute to the development of type 1 diabetes or the increased incidence of the disease in children, but judging from their effects on animals, the potential certainly exists, and should be investigated. It is critical to keep in mind that the health effects discussed on this page were almost all seen at very low doses, such as we encounter in the environment.

An expert panel estimated that exposure to endocrine disrupting chemicals has a median annual economic cost of €163 billion in the European Union. This estimate includes costs related to childhood obesity, adult obesity, and adult diabetes (Trasande et al. 2016).

References

To see these and many additional articles on endocrine disruption and diabetes/obesity, see my PubMed collection, Endocrine Disruption.