PCBs

PCBs and diabetes/obesity
Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs). The page focuses on PCBs; visit the POPs page for more information about these pollutants and for studies that consider multiple POPs together.

There are 209 different possible configurations, or congeners of PCBs. Different congeners sometimes act differently from one another, and some last longer than others in the environment. Some congeners act more like dioxin ("dioxin-like PCBs") and others act in other ways ("nondioxin-like PCBs"). Since people are never exposed to only one of these groups, people exposed to PCBs are at risk of all diseases caused by dioxin, as well as those caused by non-dioxin-like PCB congeners. Everyone living in developed countries has PCBs in their bodies; sources of exposure include food and air (Carpenter 2006).

Type 1 diabetes and autoimmunity

A 2001 study found that the levels of PCBs in pregnant women with diabetes was 30% higher than in the women without diabetes. The study used data from a U.S. study of women who were pregnant at some point during the period of 1959 to 1966, who did not have unusually high exposures to PCBs. While the dataset did not indicate the type of diabetes, the researchers suggest that most of the women had type 1. The results remained the same when the women who presumably had gestational diabetes were excluded. This study, however, was not able to show which came first, the diabetes or the PCBs (Longnecker et al. 2001). It may be that diabetes causes higher POP levels, although subsequent research has generally not supported this hypothesis (see Lee et al. (2006) and the POP page for a discussion of this point). PCBs may also indicate exposure to other POPs that may be more important for diabetes development, since these contaminants tend to travel together.

A Slovakian study found increased levels of antiglutamic acid decarboxylase (anti-GAD) antibodies in employees at a factory that produced PCBs. The study could not determine the prevalence of diabetes, but these antibodies are one of the markers of type 1 diabetes (Langer et al. 2002) (see the autoimmunity page). A German study of people occupationally exposed, however, found no association between PCB exposure levels and autoantibody levels (Esser et al. 2016).

An animal study of non-obese diabetic (NOD) mice found that PCB-153 decreased diabetes incidence in NOD mice (Kuiper et al. 2016). Perhaps this could be due to the known immuno-suppressive qualities of PCBs, or perhaps due to the characteristics of NOD mice (see the Of mice, dogs, and men page).

PCBs show a myriad of effects on cells, animals, and people, some of which may be significant for type 1 diabetes. For example, some PCB congeners can alter the cells of the immune system, and are therefore considered to be immunotoxicants (see the autoimmunity page). Exposure to PCBs can lead to a greater incidence of infections in people and animals, and may increase susceptibility to viruses. PCBs have other effects that may be also significant for type 1 diabetes. For example, PCBs can interfere with vitamin D synthesis (Lilienthal et al. 2000); vitamin D is likely protective against type 1 diabetes (see the vitamin D page). PCBs can also affect growth rates (see the height and weight page). PCBs may also be able to affect the intestinal barrier and gut permeability (see the diet and the gut page) Choi et al. 2010). 

PCBs and glucose and insulin levels in children

While the children in a Danish study did not have diabetes, those with higher PCB levels had lower insulin levels (and lower insulin resistance) than those with lower PCB levels. PCBs, then may be toxic to beta cells (Jensen et al. 2014).

Hudson River

The Hudson River is the largest Superfund site in the U.S. It is contaminated with PCBs, which can evaporate into the air or enter the food chain.

Type 2 diabetes

A long-term study from Michigan found that women (but not men) with higher PCB levels had twice the rate of diabetes as women with lower levels. It also found that levels of polybrominated biphenyls (PBBs), which are similar to PCBs, were not associated with diabetes risk (PBBs are discussed on the flame retardants page). Since this study followed people over a long period of time (25 years), and measurements of contaminants levels were taken before diabetes developed, it is likely that the PCBs contributed to the diabetes and not vice versa. These people were exposed to high levels of PBBs for about eight months during the 1970s, but not unusually high levels of PCBs (Vasiliu et al. 2006).

During the late 1970s, a number of people in Taiwan were poisoned by consuming PCB-laced rice-bran oil. Twenty-four years later, a follow-up study has found that exposed women have twice the incidence of type 2 diabetes than unexposed people. This level reaches 5.5 times among women who developed chloracne, a symptom of POP poisoning. The incidence of diabetes in men, however, was not significantly higher (Wang et al. 2008).

A study from Japan of obese and overweight people with no unusual exposure to PCBs, found that higher levels of PCB-180 were associated with an increased risk of type 2 diabetes, but that PCB-163/164 was associated with a decreased diabetes risk. Participants were tested for 13 different PCB congeners, and PCB-180 was one of the congeners that was most commonly found in the participants' bodies. PCBs were not associated with body mass index (BMI) in this study (Tanaka et al. 2011).

In a study of female former employees of a capacitor plant, levels of PCBs were associated with diabetes, presumably type 2. The study confirms other associations between PCBs and diabetes, and suggests possible hormonal influences that may play a role in diabetes development. In this study, insulin resistance was not associated with PCB levels, implying that some other factor is at play (although other studies, below, did find links between insulin resistance and PCBs) (Persky et al. 2011). A study by the same authors of men employed in this plant also found that PCB levels were associated with diabetes (and not insulin resistance) (Persky et al. 2012). A German study of people with similar PCB levels, also occupationally exposed, found an association between PCB levels and diabetes (diagnosed and undiagnosed), as well as an association with higher blood glucose levels (HbA1c). There was no association with the autoimmune antibodies linked to type 1 diabetes (Esser et al. 2016).

Tying together nutrition and POP levels, an analysis of U.S. adults found that higher fruit and vegetable intake (as measured by carotenoid levels in blood) was associated with a reduced the risk of type 2 diabetes in people with high dioxin-like PCB levels in their blood (the three PCBs measured were all associated with type 2 diabetes) (Hofe et al. 2014).

Insulin resistance and body weight

A large, long-term study of Spanish adults found that higher intake of PCBs was associated with a higher risk of obesity. The study estimated PCB levels using a questionnaire, instead of directly measuring blood PCB levels (Donat-Vargas et al. 2014).

A Taiwanese study of pregnant women without diabetes found that higher levels of some PCBs were associated with increased insulin resistance. The women lived in a city that had been polluted by dioxin, however, dioxin levels were not associated with insulin resistance in this study (Chen et al. 2008). 

A Lebanese study found that people with moderate PCB levels had a higher risk of overweight/obesity than those with low or high levels (overall, levels were lower than found in Western countries) (Harmouche-Karaki et al. 2016).

Exposure during development

Girls in Michigan who were exposed to PBBs in the womb during the 1970s via a food contamination incident did not show different height or weight than those unexposed. However, those whose mothers had higher PCB levels weighed less than those with average levels (Blanck et al. 2002). PCB exposure in the womb has been associated with higher or lower birth weight in humans (Lignell et al. 2013; Patandin et al. 1998).

Laboratory studies

Animal studies show that both dioxin-like and non-dioxin-like PCBs promote fat cell development, increase the size of fat cells, and cause insulin resistance (Kim et al. 2016).

In mice, PCB-77 has been found to promote inflammation and increase body weight (Arsenescu et al. 2008). Rats treated with PCBs had higher blood glucose levels than controls (Pereria and Rao, 2006). In mice, PCBs elevate blood glucose and increase body weight by causing higher insulin levels and insulin resistance, and also by decreasing pancreatic alpha cells (beta cell levels actually increased) (Zhang et al. 2015).

In vitro (test tube) and in vivo (animal) studies show that PCB-153 has a variety of effects. For example, it has been shown to induce and worsen (with a high-fat diet) blood glucose levels, insulin and glucose intolerance, fat mass, lipid levels, and inhibit glucose uptake (Wu et al. 2017). PCB-153 exposed mice gained more weight and showed other metabolic effects when fed a high-fat diet (but not a low-fat diet) (Wahlang et al. 2013). A mixture of PCBs have also been found to cause insulin resistance and high insulin levels in mice (Gray et al. 2013). A different lab has also shown that PCBs (PCB-77 and PCB-126) impair blood glucose tolerance in mice and showed effects in fatty tissue related to insulin resistance (Baker et al. 2013a), while Baker et al. 2013b). For an article about Baker et al.'s research, see PCBs and diabetes: Pinning down mechanisms, published in Environmental Health Perspectives (Weinhold 2013). 

A laboratory study showed that PCB-126 reduced glycogen stores in the liver, as did other dioxin-like PCBs, suggesting that these chemicals can disrupt glucose metabolism (Zhang et al. 2012). Another lab study on PCB-126 found that this chemical reduced glucose uptake from skeletal muscle, implying that it could play an important role in metabolic disorders (Mauger et al. 2016). A third study of PCB-126 found that it increased body weight gain and insulin resistance, and raised triglyceride, cholesterol, and insulin levels. It also increased oxidative stress on the islet cells, a sign of of early beta cell failure (Loiola et al. 2016).

Some PCBs stimulate the release of insulin from human beta cells. In animal studies, PCBs have been shown to change the structure of beta cells. Some PCBs produce reactive oxygen species, which are involved in oxidative stress. PCBs are endocrine disruptors, and while their effect varies by congener, their overall effect is to act like estrogens. These and other effects are reviewed in Carpenter (2006) and Carpenter (2008). PCBs can also induce inflammation, and alter insulin signalling (how the body responds to insulin) (Wang et al. 2010). Epigenetic mechanisms may also be involved in the effects of PCBs; these chemicals affect genes relating to metabolism in both the fat and the liver (Mesnier et al. 2015).

Exposure during development

Pregnant mice were exposed to PCB-126. Their offspring were not heavier, but they did show other changes in body composition. Female offspring showed higher fat levels and lower percentage of lean body mass (Rashid et al. 2013).

When pregnant and lactating mice were exposed to low levels of PCB-153 (similar to what humans encounter), their male offspring had higher glucose levels, and females had higher glucagon levels (van Esterik et al. 2015).

Exposure to PCB-126 during development affects the development of beta cells (Timme-Laragy et al. 2015.

Diabetes complications

PCBs are associated with complications from diabetes, such as cardiovascular disease, while things like exercise and nutrition may help decrease their toxicity (Perkins et al. 2015). In people without diabetes, PCB intake is associated with a higher risk of heart attacks (Bergkvist et al. 2015).

In laboratory studies, PCBs increase fat accumulation in the liver and may be involved in the development of NAFLD (non-alcoholic fatty liver disease) (Boucher et al. 2015); in fact, just a single dose of PCB-126 can disrupt the liver (Chapados and Boucher, 2016). And, animals with liver problems have worse effects from PCBs (Wahlang et al. 2017).

The bottom line

There is some evidence that high PCB levels may increase the risk of type 2 diabetes in women. It is not known whether PCB exposure at levels found in the general population can contribute to the development of type 1 or 2 diabetes. Yet based on the studies described above, the potential exists and should be studied. The effects of PCBs may vary by gender, and that should be taken into account. Individual people may also be more or less susceptible to the effects of PCBs due to their genetic background (Ng et al. 2015).

A review of the role of PCBs in obesity suggests that "further research into the specific mechanisms of PCBs-associated diseases is warranted." (Ghosh et al. 2014).

While exposure to PCBs, like other POPs, tends to come from food (especially animal fats), there is also evidence that we can be exposed to PCBs through the air, through inhalation, and that inhaled PCBs can increase the risk of diabetes, cardiovascular disease, and high blood pressure (Carpenter 2015).

References

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