Links Between PCBs and Diabetes/Obesity
Over 300 peer-reviewed studies published since 2006 in scientific journals have examined the relationship between PCBs and diabetes or obesity.
Some human epidemiological studies have found that people with higher exposures to PCBs have a higher risk of type 2 diabetes or obesity. This evidence includes long-term, longitudinal studies that follow people over time. The evidence linking PCBs to type 1 or gestational diabetes is only preliminary. 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). Another review looks at the mechanisms involved in PCBs and type 2 diabetes, obesity, and metabolic syndrome (Shan et al. 2020).
A meta-analysis of dioxin and dioxin-like PCBs and diabetes found that both sex and the type of exposure make a difference. When all 18 studies were considered in the meta-analysis, there was an increased diabetes incidence for both sexes, and the overall risk was higher in males than in females. However, when looking only at disaster-exposed populations, the risk was higher in females than males. In contrast, in non-disaster exposed populations, the risk for females was lower than males (Gang et al. 2022).
Exposure to PCBs in the womb or during early life-- key periods of susceptibility-- may affect the risk of developing diabetes or obesity later in life.
Laboratory studies on animals or cells show that PCBs exposures can cause biological effects related to diabetes/obesity, and have helped to identify the key periods of susceptibility and the mechanisms involved. These studies show that exposure to PCBs during early development can lead to diabetes/obesity-related effects not only in first generation offspring, but also in later generations.
Studies have also found links between PCBs exposure and the risk of diabetes complications.
The 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.
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 ("non-dioxin-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).
PCBs Increase Intestinal Permeability
Exposure to PCBs disrupts intestinal permeability in intestinal cells. (A) Intestinal permeability assessed 24 hours after PCB administration. B and C show staining of intestinal cells of PCB-exposed mice and unexposed controls ("vehicle"). Sections show individual villi; immunoreactivity is indicated by brown staining. In control animals, immunoreactivity is visible at the borders of adjacent epithelial cells (white arrows). PCB-126 disrupted the morphology of villi, as indicated by loss of the villus epithelium (B; black arrow).
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. In humans, PCB exposure is linked to epigenetic changes in genes that are associated with the immune system (Curtis et al. 2020).
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, which are linked to type 1 diabetes (see the Diet and the Gut page) (Chen et al. 2018; Choi et al. 2010; Petriello et al. 2018). In mice, developmental exposure to PCBs caused significant gut barrier defects including increased tight junction permeability, intestinal inflammation, and affected the gut microbiota of young offspring mice (Rude et al. 2019). Dioxin-like PCBs also affect gut microbiota, inflammation and oxidative stress in zebrafish intestines (Sun et al. 2019) and gut microbiota in adult mice (Zhang et al. 2022). In humans, prenatal exposure to PCBs are linked to gut microbiota changes in childhood (Laue et al. 2019).
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).
Type 2 Diabetes
A review finds that PCBs are linked to type 2 diabetes and obesity, perhaps via alterations in gene expression (Simhadri et al. 2020).
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).
Great Lakes Fish Consumers Have High PCB Levels in their Bodies
PCB levels are higher in Great Lakes (GL) sport-fish consumers compared to a representative sample of the U.S. population. Great Lakes sport-fish consumers were from a cohort of licensed Great Lakes charter boat captains and their spouses. The good news is that the PCB levels in fish and humans are declining.
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). A study of study of Iranian adults with occupational exposure to PCBs found that those with higher levels of PCBs had higher long-term blood glucose levels (HbA1c), although the difference was not statistically significant (Eftekhari et al. 2018).
In Italy, people exposed to PCBs from a chemical factory had higher blood pressure, but not diabetes (Raffetti et al. 2018). Another study of the same area also found no link to diabetes (Zani et al. 2019).
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).
Individual people may also be more or less susceptible to the effects of PCBs due to their genetic background (Ng et al. 2015).
Insulin Resistance, Metabolic Syndrome, 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).
In a polluted area of Italy, a prospective study found that PCB levels were associated with an increased risk of high blood pressure, particularly among overweight/obese people (Raffetti et al. 2020).
Taiwanese pregnant women without diabetes with higher levels of some PCBs had 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).
Eating Fruit and Vegetables Reduces the Risk of PCB-Associated Type 2 Diabetes
See Reducing the Risk of PCB-associated Type 2 Diabetes with Fruit and Vegetable Consumption, Research Brief 235 by the National Institute of Environmental Health Sciences, on the work by Hofe et al. 2014.
Lebanese 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. 2017). In Iran, people with higher PCBs concentrations (at normal population levels) had higher triglyceride levels, but not a higher BMI (Aminian et al. 2020).
In Canadian Inuit, PCB levels were associated with higher total cholesterol, triglycerides, and LDL ("bad") cholesterol, components of the metabolic syndrome (Singh and Chan, 2018).
Higher triglyceride and cholesterol levels were found in workers exposed to PCBs on the job, and after two years, a significant increase in triglycerides was found in exposed workers (Kimáková et al. 2018).
A long-term study from Scandinavia found that exposure to dioxin-like PCBs was associated with an increased risk of high blood pressure, a component of metabolic syndrome. The association was only in people born after 1950 (i.e., in those exposed to persistent organic pollutants in early life) (Donat-Vargas et al. 2018). Which leads us to:
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; Patel et al. 2018).
In the U.K., prenatal levels of PCBs were not associated with measures of body fatness in daughters at age 9 (Wang et al. 2019).
Laboratory Studies: Diabetes/Obesity
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).
If mice are exposed to PCBs in the womb, they develop deficiencies in their glucose metabolism (Rice et al. 2021).
PCBs and Fat Cells/Body Weight/Insulin Resistance
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. 2017).
In mice, PCB-77 has been found to promote inflammation and increase body weight (Arsenescu et al. 2008). PBC-138 helps fat cells resist cell death, a possible mechanism that would contribute to obesity (Kim et al. 2018).
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). PCB-153 also affects the development of fat cells (Mullerova et al. 2017). 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 resveratrol, the substance found in red wine, protects against PCB-induced impairment of glucose control in fat cells (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).
PCB 180 enhanced fat cell development in differentiating murine and human pre-fat cells (Yu et al. 2021).
As PCB levels decline in more polluted areas, fish living in these areas have improved metabolism that is becoming more like fish living in more pristine waters (Speranza et al. 2021).
PCBs Cause High Blood Glucose Levels in Mice
In mice, exposure to both PCB-77 and PCB-126 led to high glucose levels and impaired glucose tolerance compared to unexposed controls ("vehicle"), especially at the middle exposure levels (* or ** means the difference was statistically significant).
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 islets, a sign of of early beta cell failure (Loiola et al. 2016). And, it causes inflammation in fat cell precursors that would interfere with fat cell development (Gourronc et al. 2018), as well as affecting the "beiging" of fat cells (Gourronc et al. 2019), both of which may affect the risk of obesity and diabetes. Other studies also show effects of PCB-126 on fat cells (Caron et al. 2020).
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).
PCB-126 exposure during pregnancy caused low thyroid levels in mothers, leading to higher levels of leptin and lower levels of insulin and adiponectin in fetuses, as well as lower body weights in rat mothers and fetuses (Ahmed et al. 2018).
In zebrafish, developmental exposure to PCBs causes defects in the pancreas and other organs (Singleman et al. 2020).
PCBs and the Gut
The gut microbiome plays a role in the absorption, distribution, metabolism, and excretion of PCB metabolites, which in turn may affect health outcomes following PCB exposure (Li et al. 2020).
In mice, PCBs affected gut microbiota composition and diversity. Exposure to PCBs also resulted in higher body fat, bigger fat cells, and inflammation. These PCBs-induced changes were worsened by a high-fat diet, implying that obese individuals may be vulnerable to PCBs exposure (Chi et al. 2018). These authors also found that in mice, PCB-77 affected the gut microbiota and caused obesity, high cholesterol, and fatty liver, and weakened the bacterial functions relating to metabolism and the immune system (Chi et al. 2019).
Another lab also found that in mice, PCB 126 exposure disrupted the gut microbiota and metabolism and increased intestinal and systemic inflammation (Petriello et al. 2018). The prebiotic inulin reduced these effects (Hoffman et al. 2020). (These changes are linked to diabetes, especially type 1; see the Diet and the Gut page). Also in mice, PCB-126 affected gut microbial metabolism, including the bacterial fermentation processes and membrane disruption (Hoffman et al. 2019). Further research also supports a link between PCB exposure and gut microbiota (e.g., Cheng et al. 2018).
In adult mice, PCB-153 exposure led to gut microbiota health deterioration, obesity, cholesterol accumulation in the liver, and abdominal fat build up (Min et al. 2020).
PCBs Affect the Gut
See PCBs Increase Inflammation, Disrupt Gut Microbiome, and Alter Metabolism, Research Brief 287, by the National Institute of Environmental Health Sciences, on the work by Petriello et al. 2018.
PCBs and the Pancreas
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).
Different types of PCBs have differing effects on the structure and function of the pancreas (Shi et al. 2018). In mice, the PCB mixture Arochlor 1254 caused impaired glucose tolerance, then increased insulin levels to compensate, and increased beta cell mass. Eventually though the beta cells could not compensate, leading to high blood glucose levels, i.e., type 2 diabetes (Xi et al. 2019). Arochlor 1254 also affected pancreatic beta cell and alpha cell survival (Fang et al. 2019).
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, which can damage beta cells (Chen et al. 2018). 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). Scientists are trying to work out how estrogenic chemicals like PCBs contribute to metabolic changes (Doke et al. 2018). PCBs can also induce inflammation, and alter insulin signaling (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).
During weight loss, PCB-77 exposure led to glucose intolerance in male mice (but not females) (Jackson et al. 2019).
Additional studies have also looked at PCBs and their effects on metabolism as well (e.g., Li et al. 2019).
Developmental exposure to PCBs caused higher body weights in three generations of rats (Mennigen et al. 2018). This is seen with other chemicals as well, and raises an alarming possibility that early life exposure to chemicals can have effects over multiple generations.
PCBs Affect Glucose Levels Differently in Male and Female Mice During Weight Loss
See PCBs Alter Glucose Regulation Differently in Males and Females, Research Brief 296 by the National Institute of Environmental Health Sciences, on the work by Jackson et al. 2019.
U.S. women with higher levels of PCBs had a higher risk of gestational diabetes (Rahman et al. 2019). However, the Michigan women exposed to high levels of PBBs, did not have a higher risk of gestational diabetes (Neblett 2nd et al. 2020).
In pregnant overweight or obese Californian women, PCB levels were associated with higher fasting glucose and insulin levels, and higher insulin resistance (Mehta et al. 2020).
Diabetes Management and 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. 2016). In people without diabetes, PCB intake is associated with a higher risk of heart attacks (Bergkvist et al. 2016). People from Anniston, Alabama, those exposed to high levels of PCBs had higher blood pressure than those with lower levels (Pavuk et al. 2019) as well as liver injury (Cave et al. 2022). Reviews find that PCBs are linked to cardiovascular disease (Fu et al. 2020; Lind and Lind 2020).
In laboratory studies, PCBs increase fat accumulation in the liver and may be involved in the development of NAFLD (non-alcoholic fatty liver disease) (Armstrong and Guo, 2019; Boucher et al. 2015; Shan et al. 2020); in fact, just a single dose of PCB-126 can disrupt the liver (Chapados and Boucher, 2017). Exposure to PCBs during adolescence can cause NAFLD in mice (Ruan et al. 2019). PCB metabolites induce changes in the expression of genes related to circadian rhythm, and fatty acid metabolism, and trigger the onset of liver damage (Ochiai et al. 2018). And, animals with liver problems have worse effects from PCBs (Deng et al. 2019; Wahlang et al. 2017). PCB-126 can also increase inflammation and the development of plaque in arteries (Petriello et al. 2018).
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).