Persistent Organic Pollutants
Links Between Persistent Organic Pollutants and Diabetes/Obesity
Over 600 peer-reviewed studies published since 2006 in scientific journals have examined the relationship between persistent organic pollutants (POPs) and diabetes or obesity.
Overall, the vast majority of human epidemiological studies have found that people with higher exposures to POPs 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 POPs to type 1 or gestational diabetes is only preliminary.
Exposure to POPs in the womb or during early life-- key periods of susceptibility-- may increase the risk of developing diabetes or obesity later in life.
Laboratory studies on animals or cells show that POP 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 POPs 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 POP exposure and the risk of diabetes complications.
From Mother to Child, With Love: About Persistent Organic Pollutants (POPs)
Along with lots of love, one of the things every mother gives her baby is a dose of chemical contamination. Unfortunately, even in very high doses, love is not able to prevent the transfer of chemicals from mother to child.
A recent study measured levels of various contaminants in the placentas and breastmilk of Danish and Finnish women. The major chemicals found included p,p’-DDE, β-HCH, hexachlorobenzene (HCB), endosulfan-I, dieldrin, oxychlordane, cis-heptachlor epoxide and p,p’-DDT. What the heck are these things? Most are pesticides or industrial chemicals, and they can pass through the placenta to the fetus, or enter babies through breastmilk. Due to the higher fat content of milk, contaminant levels are higher in milk than the placenta, but, exposure to the developing fetus is likely to be more critical to physical development. Although the levels of many of these contaminants have declined since most developed countries restricted their use decades ago, they are persistent and remain in the environment, and our bodies, for long periods of time (Shen et al. 2007).
These persistent organic pollutants (POPs) include some of the most well known, and most toxic, environmental contaminants, such as PCBs and dioxin. They accumulate in the fatty tissue of animals and humans, and biomagnify in the food chain, so that the higher up an animal is on the food chain, the higher the contaminant levels are (Tanabe 2002). Here's a pop quiz: who is on the top of the food chain? Did you answer a top predator? Humans? Yes, and yes. But really, a nursing infant is even higher on the food chain than its mother.
There are several hundred POPs, and most humans are exposed to mixtures of them (Lee et al. 2007b). The U.S. Centers for Disease Control and Prevention periodically tests a representative sample of U.S. residents of POPs, and has found widespread contamination (Patterson et al. 2009). POPs are fat-soluble, and tend to move through the environment together. Therefore, it may be difficult to delineate the separate effects they may have on health (Codru et al. 2007).
The studies on this page considers the organochlorine pesticides such as DDT and HCB, as well as mixtures of these with PCBs and dioxin. For studies on the individual chemicals, see the PCBs and Dioxin pages. For other POPs, see the pages on Flame Retardants (PBDEs and more), Organotins (TBT and related compounds), and Perfluoroalkyl Substances (PFASs). Additional miscellaneous POPs are on this page below.
Since POPs contaminate virtually all people, even if they increase the risk of diabetes a small amount, these pollutants might have a large effect on the overall population (Porta 2006). In fact, an expert panel determined that in the European Union, exposure to DDE -- only one type of POP -- had a 40 - 69% probability of causing 1555 cases of overweight at age 10 in 2010 with associated costs of €24.6 million. DDE exposure also had a 20 - 39% probability of causing 28,200 cases of type 2 diabetes with associated costs of €835 million (Legler et al. 2015).
A "Striking" Relationship: POPs and Diabetes
A groundbreaking 2006 study found "striking" relationships between six POPs and diabetes in U.S. adults exposed to normal levels of POPs. The higher the levels of these POPs, the higher the prevalence of diabetes. In the highest exposure group, the risk of diabetes was 37.7 times higher than in the people with the lowest levels of exposure. That is a lot-- far higher than any other study I have ever seen. The POPs included the dioxins HpCDD and OCDD, DDE, PCB-153, oxychlordane, and trans-nonachlor, with the latter three showing the most significant relationships. (Oxychlordane and trans-nonachlor result from the use of the organochlorine pesticide chlordane) (Lee et al. 2006).
Surprisingly, this study found that obesity did not increase the risk of type 2 diabetes if those people had very low levels of POPs in their bodies. In an editorial in The Lancet, Porta (2006) writes, "This finding would imply that virtually all the risk of diabetes conferred by obesity is attributable to persistent organic pollutants, and that obesity is only a vehicle for such chemicals. This possibility is shocking."
The dataset used in this study, the National Health and Nutrition Examination Survey (NHANES) 1999–2002, includes both type 1 as well as type 2 diabetes, and does not distinguish between them. The authors believe that most of the subjects had type 2 diabetes, however, because most of the subjects were over 40. Yet they also point out that, "POPs may be involved in the pathogenesis [development] of type 1 diabetes as well as type 2 diabetes" (Lee et al. 2006).
In a further expansion of this study, the authors used the same dataset but analyzed 19 POPs, divided into five groups, to see which were most strongly associated with diabetes. They found that individually, most POPs were associated with diabetes, and PCBs and organochlorine pesticides were most strongly associated. Among the groups, only the dioxin-like PCBs and organochlorine pesticides were associated with diabetes (Lee et al. 2007c).
Since this 2006 study was published, there has been a flurry of research on POPs and type 2 diabetes, as well as related conditions, such as insulin resistance, metabolic syndrome, pre-diabetes, diabetes complications, obesity, and more. The rest of this page summarizes this research, with sections on type 1 diabetes, gestational diabetes, and diabetes complications at the end.
Dr. Duk-Hee Lee
In 2005, Dr. Duk-Hee Lee had never even heard of persistent organic pollutants. But she figured out that they could explain the increased risk of type 2 diabetes in the people she was studying. She has gone on to publish numerous studies on POPs and type 2 diabetes, and is interested in their potential role in type 1 as well.
Reviews of Persistent Organic Pollutants and Diabetes/Obesity
There have been a number of recent reviews of the evidence linking type 2 diabetes to POP exposures. Most of the individual studies reviewed are described in subsequent sections of this page. Here are conclusions from some of the reviews (in order of publication):
A literature review identified consistent research results on the topic of prenatal exposure to POPs and metabolic syndrome in children. The findings of human studies have been replicated in animal studies such that prenatal exposure to POPs have negative health outcomes such as obesity and increased waist circumference (González et al. 2021).
Among adults, the odds of having diabetes significantly increase with increasing levels of chlordanes. The data did not allow for a clear conclusion regarding the association with body weight (Mendes et al. 2021).
"Epidemiological and experimental studies have provided compelling evidence indicating that exposure to POPs increases the risk of developing insulin resistance and metabolic disorders." (Kim et al. 2019).
"Evidence is accumulating that endocrine disrupting chemicals might be involved in diabetes development. Best evidence exists for DDE. For other chemicals, both prospective studies and supporting animal data are still lacking." (Lind and Lind 2018).
"Increasing evidence suggest that POPs may act as obesogens and diabetogens to promote the development of obesity and diabetes and induce metabolic dysfunction." (Yang et al. 2017).
"The epidemiological evidence, supported by mechanistic studies, suggests an association between exposure to organochlorine pesticides and type 2 diabetes... Analysis by type of pesticide yielded an increased risk of diabetes for DDE, heptachlor, HCB, DDT, and trans-nonachlor or chlordane." (Evangelou et al. 2016).
"The evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal." (Jaacks and Staimez, 2015).
"Several epidemiological studies have reported an association between persistent organic pollutants and diabetes risk. These findings have been replicated in experimental studies both in human (in-vitro) and animals (in-vivo and in-vitro)." Ngwa et al. (2015).
"The majority of evidence reviewed from occupationally exposed, high-risk populations, and general-population studies is consistent with an independent relationship between POPs exposure and diabetes." (Magliano et al. 2014).
"The evidence as a whole suggests that, rather than a few individual POPs, it is background exposure to POP mixtures -including organochlorine pesticides and polychlorinated biphenyls- that can increase type 2 diabetes risk in humans... There is evidence in animal studies that low dose POP mixtures are obesogenic. However, relationships between POPs and obesity in humans have been inconsistent (Lee et al. 2014).
"...provides quantitative evidence supporting the conclusion that exposure to organochlorine pollutants is associated with an increased risk of incidence of type 2 diabetes," especially PCBs and DDE (Tang et al. 2014).
A number of human studies, supported by animal evidence, have found associations between various components of the metabolic syndrome and POPs. A systematic review and meta-analysis of human and laboratory evidence found that DDT and DDE are "presumed" to cause obesity in humans (Cano-Sancho et al. 2017). For an article about this review, see DDT and Obesity in Humans: Exploring the Evidence in a New Way, published in Environmental Health Perspectives (Barrett 2018).
POPs Are Associated With An Increased Risk of Diabetes
This graph shows how POPs were associated with an increased risk of diabetes, especially in people with a high BMI. People with the highest levels of POPs (G5) and the highest BMI (30+) had the highest risk of diabetes.
Surprisingly, in people with the lowest levels of POPs (G1), obesity/overweight was not associated with an increased risk of diabetes.
There are still a number of issues that haven't been addressed by the above review articles, or most of the studies below. For example, POPs may act more as mixtures than individually; their effects may interact with obesity; they may promote beta cell deficiency more than insulin resistance; and mitochondrial dysfunction may be an important mechanism in how they act (Lee et al. 2018). (Additional studies also investigate the role of mitochondrial dysfunction (e.g., Elmore and La Merrill, 2019, Ko et al. 2020).
In 2011, The U.S. National Toxicology Program (NTP) convened a workshop of experts to evaluate the role of environmental chemicals in diabetes and obesity. They have since published their findings. One of the types of chemicals they considered was POPs. Reviewing 72 human studies, they concluded that, "the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes... The strongest strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals." (Taylor et al. 2013).
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. These studies are important to show if chemicals lead to diabetes development, to rule out the possibility that diabetes itself somehow causes people to have higher chemical loads.
One longitudinal study used a dataset that measured POP exposures in U.S. residents before disease development, and again almost 20 years later when some participants had developed type 2 diabetes. They found that a number of POPs were associated with increased diabetes risk, with the highest risk at somewhat low doses. These POPs included trans-nonachlor, oxychlordane, mirex, highly chlorinated PCBs, and PBB 153 (Lee et al. 2010).
A more detailed U.S. study found that over a 23 year period, glucose homeostasis (as measured by fasting glucose levels, insulin resistance, and hemoglobin A1c) worsened after long-term exposure to numerous POPs, particularly after age 40 (Suarez-Lopez et al. 2015). Another U.S. study, measuring exposure in the 1990s and with 11 years of follow-up, found associations between various POPs and the development of type 2 diabetes (Zong et al. 2018).
Low Dose Exposures
These graphs show that for 31 (on the left) or 16 (right) POPs, the highest risk of diabetes is in people with moderate levels of these chemicals in their bodies (S2 or S3, which means the 2nd or 3rd sextile of exposure level). OR stands for odds ratio, which in this case is the risk of developing diabetes. Results are adjusted for age, sex, race, BMI, triglycerides, and total cholesterol.
Source: Lee et al. 2010, EHP
In Swedish women, higher PCB-153 and DDE levels were associated with a higher risk of type 2 diabetes (Rignell-Hydbom et al. 2007). Following these women over time, the researchers found that women with the highest levels of DDE showed an increased risk of developing type 2 diabetes, in the cases where diabetes was diagnosed more that six years after the original measurements were done. This finding shows that DDE exposure can be a risk factor for developing type 2 diabetes, supporting the idea that some POPs can affect the development of diabetes (Rignell-Hydbom et al. 2009). Also in Sweden, higher levels of various POPs were associated with an increased risk of developing type 2 diabetes (Tornevi et al. 2019). Another Swedish study also found that various POPs (PCBs and trans-nonachlor, but not dioxin) substantially increased the later risk of type 2 diabetes in the elderly (Lee et al. 2011). And also in Sweden, fatty fish would be protective against type 2 diabetes-- if it didn't contain POPs (which it does) (Shi et al. 2019).
DDE exposure (but not PCBs or PBDEs) was also found to be associated with type 2 diabetes in a long-term study from fish consumers in the Great Lakes region (fish is one of the main sources of POP exposure). These authors also found that higher exposures to PBDEs and DDE combined were associated with an increased risk of diabetes, suggesting interactive effects from different contaminant exposures (Turyk et al. 2009b). This group of fish consumers was followed for over 10 years, and POP levels were measured annually. The levels of POPs in people did not differ over time based on whether or not they had diabetes. This is an important finding, because it supports the idea that POPs might lead to diabetes, and not the other way around (that diabetes affects the levels of POPs in the body) (Turyk et al. 2009a). Dr. Turyk has measured levels of GAD autoantibodies (one of the markers of type 1 diabetes) in the people in this study, and found them to be low. Therefore the participants almost certainly have type 2, not type 1 diabetes (pers. comm. 2011). A more recent study by Dr. Turyk tried to tease out mechanisms by which POPs may be acting to promote diabetes. Various measurements of inflammation and oxidative stress, however, did not seem to be correlated to the effects of POPs on diabetes (Turyk et al. 2015). Note that a different study from Sweden found that fish consumption per se was not associated with type 2 diabetes development, but that the contaminant levels in fish may influence the results (Wallin et al. 2017).
A prospective study that measured various POP levels and later development of diabetes in U.S. nurses found that HCB Exposure was associated with type 2 diabetes. These authors also combined their data with those from other prospective studies in a meta-analysis, and found that both HCB and total PCB levels were associated with diabetes (Wu et al. 2013). However, a different study found that while PCB levels were associated with diabetes development over the long-term, HCB was associated with a decreased risk (Grice et al. 2017).
A Belgian study found that various POPs were associated with later development of diabetes: HCB, PCB 118, and DDE (in men). Other PCBs showed a negative association (Van Larebeke et al. 2015). In Germany, people who developed diabetes had higher levels of POPs at baseline, specifically PCB-138 and PCB-153, especially women and those not obese (Wolf et al. 2019). In France, a longitudinal, population-based study did not find any associations between POPs and type 2 diabetes development (Magliano et al. 2021).
A large, long-term study of pesticide applicators in the U.S. found that diabetes incidence increased with the use (both cumulative lifetime days of use and ever use) of the organochlorine pesticides aldrin, chlordane, and heptachlor (as well as some organophosphate pesticides; see the pesticides page). Those who had been diagnosed more than one year prior to the study were excluded, and the participants were followed over time, ensuring that exposures were reported prior to diagnosis. This study was based on data from the Agricultural Health Study, which includes over 33,000 participants from Iowa and North Carolina (Montgomery et al. 2008). A study of farmers' wives, also based on the Agricultural Health Study, found that the organochlorine pesticide dieldrin was associated with diabetes incidence, along with four other pesticides (discussed further on the pesticides page) (Starling et al. 2014).
In Norway, intake of lean fish, but not fatty fish or omega-3 supplements, was associated with lower risk of type 2 diabetes in women after pregnancy who were overweight or obese. Fatty fish, which contain dioxins and dioxin-like PCBs, did not increase the risk of type 2 diabetes, but intake did exceed the European tolerable weekly intake for dioxins and PCBs, which is a concern (Øyen et al. 2021).
The first study from India, where DDT is still widely used, found high levels of DDE in people, but there was no association between DDE and type 2 diabetes (Jaacks et al. 2019).
In Brazil, there was a greatly increased incidence of diabetes in people with two biological processes linked to POPs exposure levels (AhR ligand bioactivity and increased mitochondrial inhibition) (Duncan et al. 2020).
A 16 year longitudinal study from Spain that measured POP levels in fat tissue found positive dose-response relationships between POPs and type 2 diabetes risk, particularly for HCB. PCB-180 also increased type 2 diabetes risk, but in a non-linear manner. HCB and PCB-180 were also associated with increased insulin resistance at the beginning of the study. The associations were strongest in people who were not obese (Barrios-Rodríguez et al. 2021).
People with higher DDE levels had a higher risk of diabetes and higher post- meal high triglyceride levels after an oral fat tolerance test (Gupta et al 2020).
Studies in Children
South Korean children with higher levels of POPs (PCBs, trans-nonachlor, and β-HCH) had lower beta cell function and insulin secretion at age 7-9, two years later (Park et al. 2016).
In Dutch teenagers, prenatal and lactational exposure to POPs including dioxin was associated with lower insulin levels and higher blood glucose levels, presumably due to lower insulin secretion (Leijs et al. 2017).
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.
Another study that used the NHANES dataset found three additional chemicals to be associated with diagnosed diabetes: another type of dioxin (HxCDD), PCB-126, and DDT. PCB-126 and DDT were also associated with undiagnosed diabetes (Everett et al. 2007). An additional study by one of the same authors also used the NHANES dataset and included people over 20 who had diabetes or undiagnosed diabetes (hemoglobin A1c levels over 6.5% (HA1c is a measure of long-term blood glucose levels), and people with "pre-diabetes," defined as somewhat elevated HA1c levels (5.7-6.4%). This study analyzed levels of organochlorine pesticides, including DDT, DDE, beta-hexachlorocyclohexane, oxychlordane, trans-nonachlor, heptachlor epoxide, mirex, and dieldrin. It found that six of the eight pesticides were associated with diabetes (all except mirex and dieldrin), and that heptachlor epoxide and DDT were associated with pre-diabetes (Everett and Matheson 2010). Everett and Thompson (2012) also found that pre-diabetes with a high-ish HA1c was associated with PCB-126, and total diabetes was associated with 6 of 8 POPs tested (and having elevated levels of at least 4 POPs). Also in NHANES, perchlorate is associated with diabetes (Liu et al. 2017).
Tying together nutrition and POP levels, an analysis that also used the NHANES dataset 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 dixoin-like PCB levels in their blood (the three PCBs measured were all associated with type 2 diabetes) (Hofe et al. 2014).
An interesting study adapted the techniques used in genome-wide association studies, and instead conducted an "environment-wide association study" to consider 266 separate environmental factors and diabetes using the NHANES dataset. It found that the factors most associated with diabetes include heptachlor epoxide and PCBs (especially PCB 170). The effects of these factors are comparable to those found in genetic studies (Patel et al. 2010). Another similar study, also using NHANES data, found similar results but with a few extra PCBs and other POPs (Bell and Edwards 2015).
In a different set of data from the U.S., a study of military personnel found that DDE was associated with type 2 diabetes. Interestingly, a higher BMI was not associated with type 2 diabetes in African-Americans within this group (Eden et al. 2016).
In adult Native Americans of the Mohawk Nation, higher levels of HCB, some PCBs, and DDE (but not mirex) were associated with diabetes. The most elevated results were found for HCB (Codru et al. 2007). Additional studies of the Mohawk Nation found that POPs were associated with diabetes, and that associations were strongest with the more volatile, non-dioxin-like, low chlorinated PCB congeners and HCB (Aminov et al. 2016a; Aminov et al. 2016b). A Swedish study also found that the levels of HCB were significantly associated with diabetes, in women over 50. This study did not find associations between diabetes and various other POPs. They pointed out that diabetes may affect the levels of POPs in individuals, since they and others have found that recent weight change can influence POP levels (Glynn et al. 2003).
In Belgium, people with diabetes had significantly higher levels of multiple dioxins and PCBs in their bodies than people without diabetes (Fierens et al. 2003). Another Belgian study found that obese people with higher POP levels were more glucose intolerant (Dirinck et al. 2014).
In Mexican Americans, diabetes was associated with higher levels of various organochlorine pesticides (Cox et al. 2007). In Finland, higher exposure to oxychlordane, trans-nonachlor, PCB-153 and DDE were associated with an increased risk of diabetes (Airaksinen et al. 2011).
A study has looked at the associations between diabetes and POPs in Swedish fishermen and their wives, who eat a lot of fatty fish from the Baltic Sea, a major source of POP exposure in Sweden. The researchers measured levels of PCB-153 and DDE as markers of POPs, because they seem to correlate well with PCB and dioxin (TCDD) levels, and found that both PCB-153 and DDE were associated with diabetes prevalence. The subjects were older and presumably had type 2 diabetes, but two subjects with diabetes took insulin only, and may have had type 1 (Rylander et al. 2005). Incidentally, fish intake is associated with type 2 diabetes in a study from Croatia; presumably the levels of contaminants in these fish have something to do with this association (Sahay et al. 2015).
A small study from Korea found strong associations between a number of organochlorine pesticides and type 2 diabetes in people exposed to low, background levels of these substances. Since Asians tend to develop diabetes at a lower body mass index and younger age than people elsewhere, the findings may suggest that Asians are more susceptible to the effects of organochlorine pesticides. The authors suggest that this susceptibility might help to explain the current epidemic of type 2 diabetes in Asia (Son et al. 2010). Among South Asians living in the U.S., a doubling of levels of two DDTs were associated with insulin insensitivity, increased BMI and waist circumference, increased insulin levels, and an increased risk of obesity, prediabetes, diabetes, and fatty liver (La Merrill et al. 2019).
Another Korean study found that various POPs were associated with type 2 diabetes (and metabolic syndrome) (Kim et al. 2018). A study from Japan also found that POP levels were associated with diabetes (Uemura et al. 2008), as did a study from China, especially in males, and in people of all body weights (Han et al. 2019).
Danish adults with diabetes and prediabetes had higher POP levels than those without diabetes/prediabetes. Among those without diabetes, POP levels were associated with higher fasting blood glucose levels, but not insulin secretion or insulin sensitivity (Færch et al. 2012). A study of Spanish adults also found that those with diabetes and prediabetes had higher POP levels than those without (Gasull et al. 2012).
Spanish adults with higher levels of DDE in their fatty tissue had higher rates of diabetes, as well as a higher body mass index (BMI) (Arrebola et al. 2013). In the Canary Islands, diabetes is associated with DDE and PCB levels, and DDE with higher glucose levels (Henríquez-Hernández et al. 2017).
South Asian immigrants to London have a higher body burden of POPs than European whites. Diabetes is associated with higher DDE and β-HCH levels in this population, perhaps helping to explain why diabetes rates are higher in South Asians than in other populations and persist after migration (Daniels et al. 2018).
Saudi Arabian adults with higher levels of hexachlorocyclohexane, DDT, and DDE in their blood had higher rates of diabetes, as well as four of five components of the metabolic syndrome (high fasting glucose, high insulin resistance, high blood pressure, high triglycerides and lower "good" cholesterol (Al-Othman et al. 2015; Al-Othman et al. 2014). Also in Saudi Arabia, POP levels were higher in people with diabetes than those without it (Ali et al. 2016).
A study in New York state found an increase in the rate of hospitalization for diabetes among people residing in the ZIP codes containing toxic waste sites, especially those with waste sites containing POPs. The study also found that the rates of diabetes diagnosis were 36% higher among the Hudson River residents than those of clean sites, despite their healthier lifestyle; the Hudson River is contaminated with PCBs. This study included people 25-74 years old, and included all types of diabetes (90-95% of people with diabetes have type 2). While proximity to hazardous waste sites is a crude measure of exposure, residence near such sites may have constituted a risk to these populations in the past (Kouznetsova et al. 2007).
A study from the Mississippi River Delta found an association was found between increasing DDE levels and type 2 diabetes in men with lower serum DDE levels, but not in those with higher serum DDE levels, indicating a non-linear relationship (Meek et al. 2019). In other words, the risk increases and low exposure levels, and flattens out at higher exposure levels.
POPs, BMI, and Diabetes
In this population, PCB exposures were associated with an increased risk of diabetes, although obesity did still increase risk as well. Both combined-- a high BMI plus high levels of PCBs-- were associated with a very large increase in diabetes risk.
In China, higher levels of β-HCH were associated with type 2 diabetes. The risk was even higher in those with certain genes (Li et al. 2016). Also in China, higher levels of all six POPs studied (β-HCH, trans-chlordane, trans-nonachlor, DDE, DDT and mirex) were associated with type 2 diabetes in a linear dose-response manner. Levels of β-HCH and DDE were associated with higher levels of fasting plasma glucose in people without diabetes (Han et al. 2019).
In Africa, a study from Benin found that people with diabetes had high levels of POP exposures, especially those who were obese. However, the study did not have a control group (of people without diabetes), so we cannot say if levels were lower in people without diabetes. These authors plan to examine the relationships among diabetes, obesity, and POPs in future studies (Azandjeme et al. 2014).
In Algeria, POP levels were higher in people with diabetes than in those without, especially for DDE, HCB, and PCB-153 (Mansouri et al. 2020).
Higher-Level POP Exposures in Humans
What about people exposed to higher levels of POPs? Because POPs migrate to polar regions of the globe and accumulate in animal fats, and because the Inuit have a diet high in marine mammals, the Inuit have very high levels of POPs in their bodies. A study of type 2 diabetes, which is becoming more common among the Inuit, and POPs found that POP levels were not associated with diabetes or insulin resistance. This finding is actually consistent with others of humans exposed to high levels of POPs-- associations ave generally only been found among people exposed to lower levels of POPs (Jørgensen et al. 2008). The levels of PCBs and chlordanes found in the Inuit were 10-12 times higher than those found by Lee et al. (2006). The authors suggest that perhaps exposure above a certain level does not add to risk. If low levels of POPs can increase the risk of diabetes, and higher levels of exposure do not increase the risk further, then you might expect to find weak or no associations between exposure levels and diabetes in highly exposed populations (Son et al. 2010).
An interesting study comparing Inuit and Cree people-- both in northern Canada but with differing exposure levels-- found that in the range of exposures that they had in common, there were similar linear increases in the risk of diabetes with increasing contaminant exposure. While if you just look overall, the Inuit have higher exposure levels in general, but lower rates of diabetes. So the overall trend does not tell the whole picture. Among the Cree people, higher fasting glucose levels were associated with higher PBDE levels, and beta cell function was lower in people with higher levels of PCBs, DDT, PBDEs and all organochlorine pesticides. Among the Inuit people, contaminant levels were associated with lower insulin secretion, but the relation was nonlinear in that there was a greater reduction at intermediate levels of exposure (Cordier et al. 2020).
The blue line shows the risk of diabetes compared to levels of PCBs in residents of Anniston, AL. When the blue line is above the odds ratio (OR) of 1, that represents an increased risk of diabetes. These results are adjusted for age, sex, BMI, total lipids, race, family history of diabetes, and taking lipid-lowering medications. The dashed lines are the confidence intervals. The tick marks on the x-axis represent PCB measurements for each person.
Some studies of more highly exposed populations, however, have still found some associations between diabetes and POPs. One study of the Inuit people in the Canadian Arctic did find an increased risk of diabetes in people with higher PCB and DDE levels (Singh and Chan, 2017). A study of a First Nation community in Northern Ontario found that diabetes was associated with exposure to DDE and some PCBs. The levels of exposure in this community approached the range of some Inuit communities (Philibert et al. 2009). Another study from two First Nation communities in Northern Ontario also found that levels of many POPs were associated with diabetes, but not insulin resistance or insulin secretion in people without diabetes (Pal et al. 2013). Another study of Canadian First Nation communities found that POP exposure levels were associated with an increased risk of diabetes, and that a lot depends on the regional variations of POP levels in fish (Marushka et al. 2018; Marushka et al. 2021). A traditional diet, despite higher chemical exposure, may still be preferable to a Western "junk" food diet. A study of the Cree in Northern Quebec found that those who ate a traditional diet had higher levels of mercury and PCBs, but also higher omega-3 and vitamin D levels, while those who ate more junk food had higher insulin resistance (Johnson-Down et al. 2015). A study from Greenland found that higher POP levels were associated with higher levels of inflammation, and that a traditional diet was also associated with higher POP levels (Schæbel et al. 2017). Another Canadian study found that among First Nations people in the north, exposure to DDE and PCBs via fish were associated with an increased risk of type 2 diabetes as compared to people who ate no fish. However, the omega-3s in fish were associated with a lower risk of type 2 diabetes in older people (Marushka et al. 2017). In Cree First Nation communities, of PCBs, organochlorine pesticides, and metals, DDT was most important for increasing the risk of type 2 diabetes (Zuk et al. 2019).
A study from a polluted area of Eastern Slovakia found that people with higher levels of five POPs (including PCBs, DDE, DDT, HCB, and β-HCH) had higher rates of both prediabetes and diabetes. Those with the highest exposures to all of these POPs combined had 3 times higher rates of prediabetes and 6 times higher rates of diabetes, as compared to those with the lowest exposure levels (Ukropec et al. 2010). A subsequent study on this population found increased levels of diabetes markers (insulin and glucose levels) as well as obesity markers (body mass index, cholesterol, and triglycerides) (Langer et al. 2014). Those exposed via eating local fish had the highest POP levels, along with impaired fasting glucose (among other health problems) (Langer et al. 2007).
A study of elderly Faroe Islanders found that those with type 2 diabetes or impaired fasting glucose had higher PCB levels and higher past intake of traditional foods (which are high in POPs), especially in childhood and adolescence. For people without diabetes, higher PCB levels were associated with lower insulin levels but higher glucose levels. The authors suggest that impaired insulin secretion is an important part of diabetes development associated with these contaminant exposures (Grandjean et al. 2011).
Anniston, Alabama, was home to a Monsanto PCB manufacturing plant, and residents there have some of the highest PCB levels in the world. A study found an association between PCB levels and diabetes, especially in women and people under 55 years of age (Silverstone et al. 2012). PCB levels in this population are also associated with cholesterol levels (Aminov et al. 2013) and high blood pressure (Goncharov et al. 2011).
High levels of diabetes, hypertension, and autoimmune diseases were found among those exposed to high levels of POPs at an e-waste disposal center in China. Evidence suggests that dysfunctional telomeres and systemic chronic inflammation contributes to these diseases (Yuan et al. 2018).
The study of the Inuit people also found that POPs may affect insulin secretion from beta cells (see the beta cell dysfunction page), since those people with higher exposures had less insulin secretion (Jørgensen et al. 2008).
Studies in Children
In Inuit children, prenatal PCB levels were linked to a higher BMI in adolescent girls, and PCB levels during childhood were linked to lower BMI at adolescence in boys and girls (Tahir et al. 2020).
More on Beta Cell Function
An experimental study of humans finds that those with higher levels of organochlorine pesticides (and to a lesser extent, PCBs), had lower insulin secretion after a glucose-tolerance test-- the insulin levels of more highly exposed people were fully 30% lower than people with lower levels! Meanwhile, exposing laboratory beta cells to these POPs also decreased insulin secretion, even at very low levels (Lee et al. 2017).
Insulin Resistance, Body Weight, and Metabolic Syndrome
A number of studies have found associations between various POPs and increased insulin resistance and metabolic syndrome.
Longitudinal Studies in Humans
A study that followed U.S. residents over time (starting in young adulthood) found that POP levels were associated with development of increased insulin resistance, higher body mass index (BMI) (a measure of obesity) and other cardiovascular risk factors 20 years later. The main culprits included DDE and persistent PCBs (Lee et al. 2011). A further study of the same people found that after 23 years of follow-up, higher POP levels were also associated with higher total cholesterol, triglyceride, and LDL ("bad") cholesterol levels, especially in those with higher BMI (Suarez-Lopez et al. 2018).
Among Californian women farmworkers, BMI was associated with levels of DDT, β-HCH, and PBDE-47 , while PBDE-153 was associated with a lower BMI (Warner et al. 2018).
In a study of elderly Swedish adults, levels of various POPs (some PCBs, DDE, dioxin) at age 70 were associated with the development of abdominal obesity 5 years later. Other PCBs had an opposite association. (This study also included a cross-sectional analysis showed similar results) (Lee et al. 2012). In the same group of Swedish adults, high levels of certain POPs (organocholorine pesticides and less chlorinated PCBs) were associated with higher weight gain over the previous 50 years, while levels of the more chlorinated PCBs were associated with less weight gain over the same time period (Lind et al. 2013). Also in this group of Swedish adults, a mixture of POPs (mainly PCB126, PCB170, HCB and PCB118), after 10 years, increased the risk of metabolic syndrome (Lind et al. 2017).
How Are We Exposed to POPs?
Meat and dairy products are a major source of POPs, since they accumulate in the fatty tissue of animals.
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). Another long-term Spanish study, however, found that exposure to HCB and β-HCH was "consistently" associated with a higher risk of metabolic disorders, which included type 2 diabetes, high blood pressure, high triglycerides, or low HDL ("good") cholesterol (Mustieles et al. 2017).
In Korean adults, levels of most PCBs and some other POPs were associated with the development of metabolic syndrome 4 years later, especially with disturbances in glucose and lipid levels. The dose-response curve was not linear, as might be expected with endocrine disrupting chemicals (Lee YM et al. 2014).
Studies in Children
A study of Russian boys exposed to high levels of POPs found that POP levels at age 8-9 were associated with higher insulin resistance and lower leptin levels about 5 years later (leptin is a hormone that controls fat storage in the body) (Burns et al. 2014). Prior studies of these boys found associations between POP levels at 8-9 years of age and lower BMI around puberty; some POPs showed associations with lower height as well (Burns et al. 2012; Burns et al. 2011). Overall, the study found that persistent organochlorine chemicals (and lead) negatively affected growth during puberty (and that total toxic equivalents (TEQs), dioxin-like compounds, organochlorine pesticides and lead may delay puberty timing, while nondioxin-like-PCBs may advance puberty timing) (Sergeyev et al. 2017). They also found that higher levels of dioxins and PCBs around puberty were associated with a lower BMI over 11 years of follow-up, and that higher non-dioxin-like PCBs were associated with lower height (Burns et al. 2019).
In a Danish population with low POP exposure levels, POP levels at age 8-10 were generally not associated with weight gain at age 14-16 and 20-22 (Tang-Péronard et al. 2015).
A study of Korean children found that POP levels at age 7-9 were associated with various aspects of the metabolic syndrome one year later. In particular, PCB levels were associated with higher diastolic blood pressure and triglyceride levels, as well as an overall metabolic syndrome score (Lee et al. 2016).
Exposure During Development
Evidence is growing that exposure to pollution during critical developmental periods, such as in utero or during early childhood, may have effects later in life.
A study from France found that in girls, umbilical cord blood DDE levels were associated with lower insulin levels, also in cord blood, showing that POPs may have possible effects even at birth (Debost-Legrand et al. 2016).
A number of human studies have found associations between in utero exposure to various POPs and higher BMI in humans later in life. Verhulst et al. (2009) found that prenatal exposure to DDE and PCBs is associated with increased BMI during the first three years of life in Belgian children. Smink et al. (2008) found that in utero exposure to higher levels of HCB was associated with a higher BMI at age 6 in Spanish children. A study of 5-7 year old children from the Faroe Islands suggests that in utero exposure to PCBs and DDE may play a role in obesity development. Girls whose mothers had a higher BMI before pregnancy seem most affected (Tang-Péronard et al. 2014). Another study by the same authors of the same dataset found that girls with the highest prenatal POP exposure levels had the highest insulin levels at age 5 (Tang-Péronard et al. 2015). An additional study of Faroese children found that HCB levels (but not PCBs or DDE) in mothers after childbirth were associated with higher BMI at 18 months and 5 years of age (Karlsen et al. 2017). In Greece, prenatal DDE and HCB levels (but not PCBs) were associated higher BMI and abdominal obesity (and higher blood pressure) at age 4 (Vafeiadi et al. 2015). For an article about the last study, see Obesogen Holdover: Prenatal Exposure Predicts Cardiometabolic Risk Factors in Childhood, published in Environmental Health Perspectives (Konkel, 2015).
Mendez et al. (2011) found that in utero exposure to the POP DDE was associated with more rapid growth in the first 6 months of life, and higher BMI at 14 months of age, in children of normal weight mothers. A study of U.S. children born in the early 1960s, before most POPs were banned in this country, found that prenatal exposure to dieldrin (but not other POPs) was associated with obesity during childhood (Cupul-Uicab et al. 2013). Karmaus et al. (2009) found that in utero exposure to DDE, but not PCBs, is associated with increased weight and BMI in adult women from Michigan. And in the Netherlands, prenatal exposure to DDE was associated with changes in BMI and head circumference during the first year of life (de Cock et al. 2014). In Korea, in utero exposure to PCBs and dioxins were associated with changes in growth hormone levels in 8 year old children, but not weight or BMI (Su et al. 2015). A prior study from Korea also found growth hormone levels associated with dioxin levels at age 2 and 5 (Su et al. 2010).
Even in very young children, some POPs have been associated with excess weight gain. A study from Spain found that prenatal levels of DDE and HCB were associated with rapid grown between birth and 6 months of age, and overweight at 14 months of age (Valvi et al. 2014). These authors previously found that in utero levels of PCBs and DDT were associated with weight changes at age 6.5, in children with moderate exposure levels (Valvi et al. 2012). Follow up evidence notes that these changes persist into adolescence as well; both prenatal HCB and DDE were associated with higher BMI (Güil-Oumrait et al. 2021).
In the UK, a mixture of 31 chemicals, including PFAS, PCBs, and organochlorine pesticides, was inversely associated with postnatal body size (up to 19 months of age) (Marks et al. 2021).
A Danish study found that POP levels were associated with small birth size and then rapid growth in early life (Wohlfahrt-Veje et al. 2014).
A long-term Spanish study of 27 different endocrine disrupting chemicals found that in utero levels of various organochlorine chemicals (HCB, β-HCH, PCBs, and DDE) were associated with overweight/higher BMI at age 7, while other chemical levels (arsenic, BPA, phthalates, flame retardants, lead, and cadmium) were not associated (Agay-Shay et al. 2015).
In Japan, postnatal DDE levels were associated with increased BMI at 42 months of age, mostly in girls (Plouffe et al. 2020). In China, prenatal exposure to β-HCH was associated with increased BMI and higher risk of overweight status in infants, especially at 12 and 24 months of age, which seemed to be stronger in girls (Yang et al. 2021).
POPs may also affect growth trajectories and patterns, not just BMI levels. In boys, higher levels of DDT/DDE in mothers during pregnancy are associated with a BMI growth pattern that is normal until about age 5 and then shows increased growth through age 9 (Heggeseth et al. 2015). A study of Mexican-American children found that in utero DDT and DDE exposure was not significantly associated with obesity in 7 year old children, although as age increased, there was a trend toward a positive association. The researchers are continuing to follow these children as they grow, and will report on possible associations at older ages (Warner et al. 2013). A follow up study has indeed found that prenatal DDE and DDT levels were associated with obesity/overweight in these children at age 9, but only in boys (Warner et al. 2014), and the same findings hold at age 12 (Warner et al. 2017).
Not all studies show a higher BMI is associated with POP levels; some find lower BMI, especially in children more highly exposed to POPs. Girls in Michigan, for example, 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). A study from Norway found that levels of β-HCH in breastmilk was associated with slower infant growth (Criswell et al. 2017). A large European study found that levels of most POP (especially DDE, HCB, PCBs, and PBDE-153) during childhood were associated with a lower BMI in children, and that prenatal POP levels were not associated with BMI in childhood (Vrijheid et al. 2020).
Early exposure to POPs may even affect the risk of obesity much later in life. Maternal DDT exposure levels were associated with obesity risk in middle-aged Californian women (La Merrill et al. 2020).
A study from South Africa, where DDT is still used for malaria control, found that maternal DDT levels were associated with higher body weight in young girls, and that other insecticides were associated with lower body weight in young boys (Coker et al. 2018).
And some studies have found no association. A study of Mexican babies did not find associations between prenatal DDE levels and infant growth during the first year of life (Garced et al. 2012), nor did a study of Philadelphia children born in the 1960s (Gladen et al. 2004). A study of lactational exposure to DDE, PCBs, and DDT did not find an association between these chemicals and infant growth in the first year of life (Pan et al. 2010). And, a study of Ukrainian and Polish children found that prenatal and post natal DDE and CB-153 were not clearly associated with BMI at age 5-9 (Høyer et al. 2014).
However, the largest and most robust study, including data from 7 European cohorts, found that prenatal exposure to DDE was associated with increased growth over the first 2 years of life, while postnatal exposure to PCB-153 was associated with decreased growth (Iszatt et al. 2015).
In the U.S., women's o,p'-DDT levels were associated with obesity in their granddaughters among normal weight women, but not among overweight and obese women (and with early puberty in granddaughters among all women) (Cirillo et al. 2021).
Birth weight may also be affected by POP levels encountered by a fetus in the womb. A study of mothers from Ukraine, Greenland, and Poland found that maternal DDE levels (but not PCB-153) were associated with lower infant birth weight (Lenters et al. 2016). A (small) study from the Netherlands found that maternal DDE levels were associated with lower birth weight in boys but higher birth weight in girls (de Cock et al. 2016). In contrast, a large European study found that mothers' PCB levels (but not DDE) were associated with lower birth weight and impaired fetal growth (Govarts et al. 2012). A follow-up study confirmed the association between PCB levels and lower birth weight-- even at low levels of exposure-- and found that the association was strongest in daughters whose mothers smoked during pregnancy (Casas et al. 2015). U.S. women with higher PCB levels also have smaller babies (Murphy et al. 2010). In Spain, various POPs were associated with higher or lower birth weight, depending on sex and which chemical or mixtures it was (Cabrera-Rodríguez et al. 2019). Meanwhile, DDT levels in umbilical cord blood of Chinese babies were associated with higher birth weight (Xu et al. 2017). In Canada, mixtures of organochlorines were associated with lower birth weight, and trans-nonachlor had the greatest impact on birth weight (Hu et al. 2021).
Studies of more highly exposed pregnant Inuit women from Arctic Quebec found that the POPs PCB-153 and HCB were associated with reduced fetal growth, due to their association with shorter duration of pregnancy (Dallaire et al. 2013), whereas in Russia, DDT levels were linked to higher birth weight and length (Bravo et al. 2019).
Dr. Miquel Porta
In an editorial published in The Lancet on the subject of Dr. Lee's findings, Dr. Miquel Porta writes, "This finding would imply that virtually all the risk of diabetes conferred by obesity is attributable to persistent organic pollutants, and that obesity is only a vehicle for such chemicals. This possibility is shocking." (Porta, 2006).
Cross-Sectional Studies in Humans
A study by Lee et al. (2007a) found that some POPs (oxychlordane and trans-nonachlor, and two nondioxin-like PCBs) were associated with increased insulin resistance in adults without diabetes. They conclude that background exposure to organochlorine pesticides (oxychlordane and trans-nonachlor result from the use of the organochlorine pesticide chlordane) and nondioxin-like PCBs may increase type 2 diabetes risk by increasing insulin resistance, since increased insulin resistance often precedes type 2 diabetes. POPs may interact with obesity to increase the risk of type 2 diabetes. They also suggest that chlordane may be the most important POP involved in the development of type 2 diabetes by influencing insulin resistance.
In people of normal weight, those who were metabolically unhealthy had higher levels of POPs than those who were metabolically healthy (Ha et al. 2018).
Elobeid et al. (2010) found that people with higher levels of various POPs had higher BMI and waist circumference measurements. For example, individuals with higher DDT and octachlorodibenzo-p-dioxin (OCDD) levels had a higher BMI, and higher heptachlordibenzo-p-dioxin (HPCDD) levels had a larger waist circumference. Oxychlordane exposure was associated with a higher BMI in males but lower in females, perhaps due to hormonal differences. Dirinck et al. (2011) found that people with higher levels of beta-hexachlorocyclohexane (β-HCH) had a higher BMI and higher insulin resistance, although higher PCB levels were associated with lower BMI and lower insulin resistance.
In Spanish women with a past history of gestational diabetes, various POP levels were associated with higher insulin resistance and higher glucose levels 2 hours after a meal (Arrebola et al. 2015). Also in Spanish people, POPs were associated with metabolic syndrome and unhealthy metabolism, especially in people of normal weight (Gasull et al. 2018). In obese Portuguese women undergoing bariatric surgery, levels of POPs in fatty tissue were higher in those with higher blood pressure and with higher cardiovascular risk (Ferro et al. 2018).
A study from Sweden found that DDE levels were associated with higher fasting glucose, higher BMI, high blood pressure, and left ventricular mass in seniors (La Merrill et al. 2018). Another study from this cohort found DDE levels were linked to high triglycerides and other cholesterol-related measurements (Jugan et al. 2020). Another study from Scandinavia found that people with morbid obesity had a higher risk of metabolic syndrome if they had higher POP levels (Dusanov et al. 2018).
Organochlorine pesticides were most strongly associated with metabolic syndrome, similar to the findings of type 2 diabetes and increased insulin resistance. Interestingly, in this study PCBs showed unusual dose-response relationships, like has been seen with endocrine disruptors in laboratory experiments. The authors suggest the hypothesis that lower doses of some PCBs may be more harmful than higher doses, and that this possibility is worth more investigation (Lee et al. 2007b). A study from Spain also found non-linear dose-response relationships between various POPs (HCB and some PCBs) and obesity as well as lipid levels (Arrebola et al. 2014).
Park et al. (2010) found that the POP heptachlor epoxide was associated with metabolic syndrome in a small study of Koreans without diabetes. And in a study of Indian adults, the POPs aldrin and β-HCH were associated with having metabolic syndrome (Tomar et al. 2013).
A study from a contaminated area in Taiwan found that higher PCDD/F exposure was associated with an increased prevalence of metabolic syndrome (Chang et al. 2010a). These authors also found that increasing PCDD/F levels were associated with increasing insulin resistance in people without diabetes (Chang et al. 2010b). And, perhaps most significantly, they found that people with the highest levels of exposure to both PCDD/Fs and mercury 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 was associated with both mercury and PCDD/F exposure levels, including an increased waist circumference. Higher PCDD/F exposures were also associated with defective beta cell function in people without diabetes, which supports the idea that PCDD/Fs are involved in the development of diabetes (Chang et al. 2011).
A study from Korea found that dioxin-like POP levels were associated with glucose intolerance, fasting glucose levels, obesity, triglycerides, and blood pressure (Park et al. 2013). A study from Japan also implicated dioxin-like POPs in metabolic syndrome, especially glucose intolerance, triglycerides, and high blood pressure (Uemura et al. 2009).
In China, some organochlorine pesticides showed significantly positive associations with triglycerides, total cholesterol, and LDL cholesterol levels, and negative relationships with HDL cholesterol in people without diabetes (Han et al. 2019). Also in China, higher dietary intake of DDT and DDE were associated with lower HDL cholesterol levels (Wang et al. 2021).
A study from the PCB-contaminated area of Anniston, Alabama, found that while PCB levels were not associated with metabolic syndrome, levels of other organochlorine pesticides were (e.g., DDT and DDE) (Rosenbaum et al. 2017). In the Akwesasne Mohawks, various POPs were associated with various components of the metabolic syndrome (Aminov and Carpenter 2020). In the Cree in Northern Quebec, POPs were not associated with various measures of obesity (Akbar et al. 2020). In Indigenous peoples in Canada, higher POP levels were linked to higher blood pressure (Zuk et al. 2021).
Laboratory Studies: Diabetes/Obesity
When you give mice DDE, they develop high blood sugar. Specifically, adult mice given DDE for five days developed high fasting blood sugar (as compared to unexposed controls) that lasted for up to 21 days after the exposure ended. Curiously, this high blood sugar did not seem to be caused by increased insulin resistance (Howell et al. 2014). A different study by the same authors found that mice fed a high-fat diet and exposed to DDE developed high blood sugar after 4 and 8 weeks. Yet at 12-13 weeks, glucose levels normalized. (Howell et al. 2015).
In contrast, two animal studies have shown experimentally that exposure to POPs, taken from farmed Atlantic salmon, can cause increased insulin resistance and obesity in rats and mice. In one, organochlorine pesticides and DDT inhibited insulin action in fat cells. Some types of PCBs also reduced insulin action in the fat cells, but not as strongly. Polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) did not have an effect on insulin action in the fat cells (Ruzzin et al. 2010; Ibrahim et al. 2011). A further study by some of the same authors found that replacing some of the fish oil fed to Atlantic salmon with vegetable oil lowered the POP content of the fish. It also lowered the POP levels in mice who ate those fish. The replacement had no effect on the obesity levels of the mice, but replacing fish oil with rapeseed (canola) oil did improve the glucose tolerance of the mice. Replacement of fish oil with soybean oil worsened insulin resistance in the mice, despite lower POP levels, due to the higher linoleic acid levels in the fish (Midtbø et al. 2013). For an article on the Ruzzin et al. 2010 study, see Chew on this: persistent organic pollutants may promote insulin resistance syndrome, published by Environmental Health Perspectives (Tillett 2010).
A pair of studies of a mixture of POPs and other chemicals that are found in northern populations (the Inuit people) showed that these chemicals, when given to rats, impair pancreatic function (reducing beta and alpha cells), reduced insulin levels, increased cholesterol levels, and caused a fatty liver (Mailloux et al. 2014; Mailloux et al. 2015). Another study of mixtures shows that mice with lifelong exposure to low levels of PCBs, dioxin, BPA and phthalates caused changes to metabolism (e.g., high triglycerides), which were slightly different than the effects of a high-fat, high-sugar diet (Labaronne et al. 2017).
Mice exposed to PCBs developed glucose intolerance (as well as high cholesterol levels, systemic inflammation, and oxidative stress)-- but the interesting thing is that exercise significantly reduced these effects (Murphy et al. 2016).
Zebrafish, animals used to study the effects of toxic chemicals, exposed over their lifetime to natural mixtures of persistent organic pollutants from Norwegian lakes showed increased body weight, as well as changes in the regulation of a variety of genes associated with weight control and insulin signalling, showing that these chemicals appear to affect metabolism and may lead to weight gain or obesity Lyche et al. 2010; Lyche et al. 2011). Another study of POP mixtures finds that mixtures of POPs had effects on gene expression in liver cells (genes involved in metabolism and blood sugar levels), while individual POPs had only small effects (Ambolet-Camoit et al. 2015). Also in zebrafish, high fasting glucose and low insulin levels were observed only at lowest level of exposure to a mixture of organochlorine pesticides and only in females, indicating a non-linear and sexually dependent response (Lee et al. 2021).
In an animal study, researchers curious whether long term DDT exposure could cause cancer fed DDT to two species of monkeys for 130 months, beginning in 1969. The surviving monkeys were analyzed in 1994. While the researchers were not looking for diabetes, two of the 24 exposed (and none of the unexposed) monkeys developed diabetes (high blood glucose). Two also developed hypoglycemia (low blood glucose), implying that DDT affected glucose metabolism or insulin production. (Two of the exposed monkeys did develop malignant cancer, and three benign tumors, while none of the unexposed developed any tumors or cancer. There were a number of other health effects in the exposed group as well, from fatty changes in the liver to neurotoxic and estrogenic effects). Although all the treated monkeys received the same dose of DDT, the levels in the bodies varied substantially. This finding could be due to differences in the amount of body fat, metabolism, absorption, secretion, or fluctuating levels over time in the same individual (an effect also seen in humans) (Takayama et al. 1999).
DDE-exposed mice developed high blood sugar, insulin resistance, and body weight gain-- which were reversed with pectin, via changing the gut microbiota (Zhan et al. 2019). The POPs 2,3,7,8-tetrachlorodibenzofuran (TCDF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and polychlorinated biphenyls (PCB-123 and PCB-156) have direct effects on the gut microbiota as well (Tian et al. 2020).
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 resveratrol (the substance found in red wine) protected against these effects (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).
Chlordane, in combination with a high-fat diet, enhances the metabolic effects of the diet, suggesting it is a potential obesogen (Wang D et al. 2017). A review suggests that chlordane may be an obesogen as well (Silva et al. 2020). In fruit flies, exposure to low concentrations of chlordane caused disruption of glucose and lipid metabolism, increased insulin secretion and impaired insulin signaling, all diabetes-related effects (Wu et al. 2021).
A persistent chemical called 1,2-dichloroethane (1,2-DCE), used to manufacture PVC, leads to accumulation of glycogen, free fatty acids and triglycerides in the liver, higher blood triglyceride and free fatty acid levels, and lower blood glucose levels (Wang T et al. 2017).
Human blood cells exposed to PCBs show a gene expression that resembles the metabolic and endocrine diseases seen in human studies; scientists are looking at the possibility that these "gene fingerprints" could both help identify people at risk of disease, and be biomarkers of disease before the disease appears (Ghosh et al. 2015).
A metabolic study (of humans) found that DDE and HCB exposure were linked to certain metabolic changes related to fatty acid metabolism, and that each chemical was related to different metabolites (Salihovic et al. 2016).
Additional efforts are also underway to determine the mechanisms behind POP-induced diabetes (e.g., Ko 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).
Female mice exposed to DDT in the womb and for the first 5 days of life had a transient increase in body fat during early life. In adulthood, when fed a high-fat diet, they developed glucose intolerance, high insulin levels, disrupted cholesterol levels, implying increased susceptibility to metabolic syndrome. Interestingly, the exposed mice also had a lower body temperature throughout life than controls, which means a decreased energy expenditure. Perhaps the lower body temperature is one mechanism causing insulin resistance in these mice (La Merrill et al. 2014). (Interestingly, average body temperatures are apparently lower now than they used too be, before the industrial revolution (Protsiv et al. 2020). Some scientists hypothesize that endocrine disrupting chemicals that can affect thyroid levels (like some POPs do) are at least in part responsible for this change (Vancamp and Demeneix, 2020).)
At levels close to the accepted daily intake, treatment with endosulfan sulfate, a major metabolite of endosulfan, during fetal development, directly impacted glucose tolerance, liver triglyceride levels, and the gut microbiome in mice, with the specific effects dependent on the type of diet consumed (Yan et al. 2020).
In rats, preconception HCB exposure leads to an increase in body weight, among other metabolic effects (Dhaibar et al. 2020).
Oxygenated polycyclic aromatic hydrocarbon (OPAHs) exposure during development interferes with pancreatic beta cell development in zebrafish (Yun et al. 2019).
Dr. Damaskini Valvi
"Population studies now show that early-life exposure to chemicals may increase risk of obesity, an important risk factor for diabetes and cardiovascular disease."
- Dr. Damaskini Valvi, Harvard School of Public Health
The POP and organochlorine pesticide methoxychlor was given to pregnant mice for only 7 days. Their children, grandchildren, and great-grandchildren suffered from various disease, including obesity (Manikkam et al. 2014). Developmental exposure to PCBs also caused higher body weights in three generations of rats (Mennigen et al. 2018). DDT, when given to pregnant mice, led to obesity in their great-grand offspring (King et al. 2019; Skinner et al. 2013), and this effect can be transferred down either the maternal or paternal line (Ben Maamar et al. 2019). Fat cells from the great-grand offspring generation of rats ancestrally exposed to DDT (or the pesticide atrazine) had different epigenetic signs than fat cells from control rats (King et al. 2019).
Listen to Dr. Michael Skinner, University of Washington, discuss his research on the call, Transgenerational Effects of Prenatal Exposure to Environmental Obesogens in Rodents, sponsored by the Collaborative on Health and the Environment (2013).
DDE exposure during development affects the pancreas, causing impaired glucose tolerance, abnormal insulin secretion, and beta cell dysfunction. These effects can be transferred through two subsequent generations via the male line (Song and Yang, 2017). A variety of epigenetic mechanisms appear to be involved, and the mechanisms governing direct exposures are different than those involved in later generations (Skinner et al. 2018).
Developmental exposure to POPs affects cholesterol/triglyceride levels rats for two generations, and these effects are passed down through the fathers. If the original mothers took folic acid supplements while pregnant, their offspring had lower cholesterol levels, regardless of POPs exposure. But folic acid failed did not prevent other deleterious effects of prenatal POPs exposure (Navarro et al. 2019).
Lindane stimulated fat storage in four generations of roundworms, and caused different effects on insulin (inhibited or stimulated) among the various generations (Chen et al. 2018).
These studies raise the concern that exposure during development can lead to effects not only in the offspring, but also in subsequent generations.
What are the effects of mixtures of chemicals? Very few studies have been done on chemicals in combination with one another, although that is how humans are exposed. One study exposed mice -- starting from before conception -- throughout life to very low doses (at levels thought to be "safe") of a combination of chemicals commonly found in food, including phthalates, BPA, dioxin, and PCBs, and fed them a high-fat diet. As adults, compared to unexposed controls, pollutant-exposed females developed impaired glucose tolerance, and males showed liver and cholesterol effects, as well as epigenetic changes (Naville et al. 2013). The same authors subsequently fed mice a high-fat, high-sugar diet, both with and without this same low-dose mixture of chemicals. This time, the chemical-exposed females showed improvement in glucose tolerance, inflammation, and insulin resistance at 7 weeks of age, but then worsening of these factors at 12 weeks of age. Thus the chemicals cause at first an apparent improvement, then a worsening as aging takes place (as compared to the mice fed the same diet but without chemicals) (Naville et al. 2015).
Another study of mixtures by the same authors shows that mice with lifelong exposure to low levels of this BPA, phthalates, dioxin and PCB mixture caused changes to metabolism (e.g., high triglycerides), which were slightly different than the effects of a high-fat, high-sugar diet (Labaronne et al. 2017). This exposure not only resulted in significant changes in triglyceride levels, but also on the expression levels of a variety of genes, including those relating to metabolism, especially under a standard diet. Depending on nutritional conditions and on the metabolic tissue considered, the impact of pollutants mimicked or opposed the effects of the high-fat high-sugar diet (Naville et al. 2019).
Developmental exposure of zebrafish to a mixture of 29 POPs at levels found in humans caused increased length and weight, among other effects (Christou et al. 2021).
In Vitro Studies on Cells
Studies of cells have found that some POPs affect certain aspects of fat cell function/dysfunction that may be involved in obesity and type 2 diabetes. For example, researchers exposed mouse fat cells to POPs and found that DDE increased the release of some hormones from mature fat cells associated with obesity and type 2 diabetes (Howell and Mangum 2011). PCBs also mess with fat cells in the lab, interfering with lipid metabolism-- at levels that humans are exposed to (Ferrante et al. 2014). When pre-fat cells from humans were exposed to DDE and PCB-153, the cells proliferated more than unexposed controls (Chapados et al. 2012). DDT also enhanced the development of stem cells into fat cells (Strong et al. 2015). DDE also causes pre-fat cells to turn into fat cells, and to hold more fat (Kim et al. 2016; Mangum et al. 2015). DDE also causes fat cells to malfunction (Pestana et al. 2017), including when they are differentiating from stem cells to fat cells (Kladnicka et al. 2021).
Long-term exposure to DDE and DDT affect pancreatic beta cells, in a manner similar to other stressors (like high blood sugar and inflammation) (Pavlíková et al. 2015). DDE and DDT can affect the insulin content of beta cells, and affect the vitamin D-binding protein level (Pavlíková et al. 2019). High doses of DDT are toxic to beta cells (Pavlikova et al. 2020). DDE exposure can also increase insulin secretion from beta cells (Ward et al. 2021).
Exposure to low levels of organochlorine pesticides (chlordane, heptachlor, DDT, β-HCH, and HCB) suppressed insulin secretion from beta cells and and insulin-dependent glucose uptake in skeletal muscle cells (which is essentially causing insulin resistance) (Park et al. 2020).
Using human stem cells derived from fatty tissue, researchers examined the gene expression effects of dioxin, PCB-126 (a dioxin-like PCB), and PCB-153 (a non-dioxin-like PCB). They found that the pathways most affected by these chemicals were related to inflammation and immune response, as well as metabolism (and cancer). The dioxin-like compounds had stronger effects than the non-dioxin-like compound. A study in mice confirmed these results (Kim et al. 2012). For an article describing this study, see Another piece of the obesity–environment puzzle: Potential link between inflammation and POP-associated metabolic diseases, published in Environmental Health Perspectives (Barrett 2012).
In muscle cells, lindane causes insulin resistance (Singh et al. 2019a), as does DDT (Singh et al. 2019b). A mixture of organochlorine pesticides-- even at the lowest exposure levels-- reduced glucose uptake in skeletal muscle cells as well (Park et al. 2021).
In liver cells, exposure to individual POPs and the mixture, at levels found in humans, decreased glucose output, glucose oxidation, and glycogen content (Leblanc et al. 2019).
A Systems Biology Approach
Researchers used a computerized approach to examine the mechanisms by which POPs may contribute to metabolic disease. They looked at three different POPs (a PCB, a dioxin, and DDE) and found that while they each activate different receptors, these converge to promote inflammation in fat cells, liver, and the pancreas. These processes can affect fat cell development, beta cell dysfunction, insulin resistance, glucose intolerance, and liver disease. They also found that these chemicals may interact with each other at various points in the process, since they have overlapping and interconnected pathways (Ruiz et al. 2016).
Listen to Dr. Michele La Merrill, UC Davis, discuss her research on the call, Cold Feet: Perinatal DDT Exposure Increases Risk of Insulin Resistance, sponsored by the Collaborative on Health and the Environment (2014).
A Closer Look at POPs in Fatty Tissue
The body collects and stores POPs in fatty tissue. This can have both positive and negative ramifications. On the positive side, storing POPs in fat may help protect other organs from these chemicals. On the negative side, storing these chemicals in the body causes levels to build up over time. They are released into the blood continuously, especially during times of weight loss. In addition, fatty tissue is not just sitting there storing energy and POPs. Fatty tissue plays a role in a variety of body functions, aside from storing energy. For example, it produces hormones that control appetite and metabolism, responds to insulin released from the pancreas (or a syringe), and contains immune cells involved in inflammation. POPs, then, may affect these processes and have detrimental health effects when stored in fatty tissue (reviewed by La Merrill et al. 2013). For an article describing this paper, see POPs vs. Fat: Persistent Organic Pollutant Toxicity Targets and Is Modulated by Adipose Tissue, published by Environmental Health Perspectives (Barrett 2013). In sum, both obesity (with dysfunctional fat cells) and weight loss (where chemicals from fat are released into the blood stream) could potentially increase the chance of POPs reaching critical organs (Lee et al. 2017). There is a debate right now as to the benefits vs harms of storing POPs in fatty tissue (Jackson et al. 2017).
An interesting study found that in people with low levels of POPs in their bodies, more fat increased the risk of mortality. However, in people with high POP levels, more fat reduced the risk of mortality (this is known as "the obesity paradox"-- the idea that obesity may be protective against some causes of mortality). This study provides some evidence that fatty tissue may be a relatively safe place to store POPs (Hong et al. 2012). Further supporting this idea, people who are metabolically healthy but obese have lower levels of POPs in their bodies than those who are metabolically unhealthy and obese (Gauthier et al. 2014).
The Secret Life of Fat
POPs are stored in fat (adipose) tissue and the liver (left). This prevents the action of these pollutants in other tissues and may be protective to a certain extent. POPs released from fatty tissue during weight loss for example constitute a source of low-level internal exposure (right).
Listen to Dr. La Merrill discuss her review of POPs in fat, weight loss, and bariatric surgery in The Secret Life of Fat, with Michele La Merrill podcast, via Environmental Health Perspectives.
Subcutaneous vs. Visceral Fat
A few studies have examined whether POPs accumulate differently in different types of fatty tissue. For example, a study from Belgium measured POP levels in subcutaneous abdominal fat and visceral fat from obese individuals. They found that the levels of POP distribution in these two tissues were not significantly different from one another (Malavannan et al. 2013). Another study, however, found that concentrations of POPs did differ between subcutaneous fat and visceral fat. In particular, levels of PCBs were 5-10 times higher in visceral fat than subcutaneous fat. In addition, some of the POPs were associated with diabetes or insulin resistance (Kim et al. 2014). A Portuguese study also found that visceral fat contained higher levels of POPs than subcutaneous fat, and that the levels were associated with high blood sugar, high blood pressure, cardiovascular risk, and less weight loss (Pestana et al. 2014). A U.S. study found stronger associations between POPs in trunk fat vs. leg fat (Zong et al. 2015). And, another study found that POP levels varied in different types of fat depending on the individual, perhaps due to different lengths of exposure or different metabolic rates (Yu et al. 2011).
A German study found that in humans, levels of various POPs in fat tissue significantly correlated with inflammation, fat cell size, blood sugar levels, and insulin resistance. Levels in subcutaneous and visceral fat were the same (Rolle-Kampczyk et al. 2020).
Leptin and adiponectin are hormones secreted by adipose tissue. Leptin controls the amount of fat stored in the body, and adiponectin helps insulin do its job. Adiponectin levels tend to be reduced in people with type 2 diabetes, metabolic syndrome, or a high BMI. Adipnectin levels also have been associated with POPs; for example, Korean adults with higher POP levels, especially PCBs, have lower adiponectin levels (Lim and Jee 2015), and Czech women with higher PCBs had lower adiponectin as well (Mullerova et al. 2008). A detailed study found that markers of obesity (including leptin and adiponectin) were associated with POPs in fatty tissue, especially in visceral fat (Pereira-Fernandes et al. 2014).
If POPs Are Stored in Fat, What Happens When You Lose Weight?
Good question. A meta-analysis of data from numerous studies found that the majority of POP concentrations rose in the blood following weight loss, by 2-4% per kg of weight lost. Blood levels remained higher even 12 months following weight loss. (The authors point out that the benefits of losing weight still outweigh the potential health risks) (Jansen et al. 2017).
Here are some specific studies on the topic. In a study of postmenopausal overweight Seattle women, past weight loss of over 20 pounds were associated with higher blood levels of POPs (De Roos et al. 2012). Obese Belgian women had 50% higher PCB levels in their blood six months after weight loss-- but only those who lost weight by dieting, not by surgery-- and especially in those who lost more visceral fat (as compared to subcutaneous fat) (Dirinck et al. 2015). After 10 years, POP levels tend to be higher in people with long-term weight loss, and lower in those with long-term weight gain (Lim et al. 2011). Weight loss after bariatric surgery resulted in increases of POP levels in serum between 47%-83%. Five percent of the people in this study had PCB values that were over suggested limits (Jansen et al. 2018). (However, PFAS levels were found to be lower a year after bariatric surgery, so possibly it depends on the chemical (Jansen et al. 2019).) Another study also found that while most POP levels increased after weight loss, PFASs did not (Fénichel et al. 2021). Most studies show POP levels increasing after weight loss and bariatric surgery (e.g., Deshmukh et al. 2020).
Indeed, a number of human studies, discussed by La Merrill et al. (2013), have shown an increase in blood POP levels following weight loss (with or without surgery). Existing fatty tissue can take up these POPs, leading to higher concentrations in the remaining fat. However, total body burden may be lower after weight loss than before, after a period of time (Kim et al. 2011). A Belgian study also found that weight loss resulted in higher blood levels of POPs in general, but that the levels of each type of POP varied (that is, some were released from fat to blood more than others) (Dirtu et al. 2013). A Central European study found that after 3 months of weight loss, blood levels of POPs increased, but after 5 years, there were no differences (except HCB levels went up in those who gained weight again after 5 years) (Müllerová et al. 2015). A Belgian study found that metabolically unhealthy obese people had higher levels of PCBs in their bodies than metabolically healthy obese people. After weight loss (via surgery or lifestyle), both showed higher PCB levels at 6 months and 1 year, although the levels did not differ based on metabolism. In sum, they found that PCB levels did not seem to affect the metabolic benefits of weight loss (Dirinck et al. 2016). A small U.S. study did not find POPs changed after weight loss, but that was only after 4 weeks. Women who reported more weight cycling had lower DDT levels (Frugé et al. 2016). A study of Belgian adolescents found that weight loss caused POPs to be released into the bloodstream and redistributed in the body (Malarvannan et al. 2018). In Swedish elderly adults, however, those with larger decreases in body weight had the slowest decline in body burden of POPs over 5 years (Stubleski et al. 2018). In U.S. adults, blood POP levels increased with weight loss following bariatric surgery. Older adults had greater increases in PCBs, OCPs, and PBDEs associated with weight loss, while younger adults had greater increases in PFCs associated with weight loss (Brown et al. 2019).
Can POPs released via weight loss lead to changes in hormone levels? Perhaps. In Norwegians, a year after bariatric surgery, POP levels increased, and some POPs were associated with changes in hormone levels (Jansen et al. 2019).
Can POPs released via weight loss lead to toxic effects on other organs?
Perhaps. Weight loss can lead to unexpected health problems, perhaps due to the release of POPs. Drastic weight loss increases POP levels in the blood even more than slower weight loss (Cheikh Rouhou et al. 2016). While obese people who experienced drastic weight loss via surgery showed an improvement in various health measurements, those with high POP levels showed a delayed improvement. POPs, then, may counteract some of the positive effects of weight loss (Pestana et al. 2014). Some authors warn that avoiding the harmful health effects of POPs may contradict conventional recommendations about obesity and weight change (Lee et al. 2017).
One study finds that PCBs are released from weight loss pretty much equally between men and women. It also found that after a year, a "protein pacing" diet successfully prevented weight relapse, as compared to a regular "heart healthy" diet, without any adverse effects from the mobilized PCBs (He et al. 2017).
An animal study showed that PCBs counteract the beneficial effects of weight loss in obese mice. Specifically, while PCBs had no effect on glucose control in obese mice, PCB exposure did impair glucose control after those mice lost weight. In other words, the diabetes-promoting effects of PCBs were only apparent in obese mice when those mice lost weight (Baker et al. 2013a; Baker et al. 2015). In sheep, 3 weeks of undernutrition caused PCBs to be released from fatty tissue to blood (Lerch et al. 2016). In mice, fat tissue containing dioxin was grafted onto unexposed mice, and the dioxin was released from the fat and led to changes in the organs of recipient mice (Joffin et al. 2018).
It may be that weight loss may be beneficial in people with low POP levels, it may carry some risk in those with high levels Hong et al. 2012). Wouldn't that be great if people could easily find out their POP levels before starting a diet?
Another question is, does the release of POPs from fatty tissue during weight loss make it harder to lose weight? At this point, we don't know (Reginer and Sargis, 2014).
It turns out that midlife obesity is associated with increased risk of dementia, whereas late-life obesity is associated with a lower risk. Chronic exposure to POPs may help explain these differences. During midlife, weight gain may help sequester POPs in fatty tissue. As obesity is the most common reason that fat cells become dysfunctional, midlife obesity can increase dementia risk through the chronic release of POPs into circulation. However, late-life obesity potentially decreases dementia risk because weight loss after midlife will increase the release of POPs while weight gain may actually decrease the release (Lee et al. 2018). The Action for Health in Diabetes (Look AHEAD) study failed to show long-term benefits of intentional weight loss on cognition, despite substantial improvements in many known risk factors for dementia. The POPs released from fat can easily reach the brain. The intentional weight-loss group of the Look AHEAD study may have experienced a long-term disadvantage on their cognition due to POPs (Lee et al. 2020).
Breastfeeding is another way that POPs may be mobilized out of fatty tissue; for more on chemicals in breastmilk, see the breastfeeding page. Breastfeeding does reduce POP levels in the mother, it also reduces the risk of diabetes in the mother (Zong et al. 2016). Losing weight while breastfeeding does increase the POP levels in the milk, but the estimate average intake of POPs by the babies stayed the same since over time they drink less milk (Lignell et al. 2016).
Exercise can also cause POPs to leave the fat and enter the blood. In Danish children, the most fit and most lean had the highest PCB leves. The authors suggest that PCBs in fat tissue may play a dual role, promoting adverse health, and simultaneously providing a place to store PCBs. This trend might also mess up the finding of human studies on this topic... (Domazet et al. 2020).
Weight loss may also affect the results of studies on diabetes. If people have lost weight or show improved cholesterol levels, that can change their POP levels, which could weaken the results of cross-sectional studies on diabetes. (The prospective, longitudinal studies could account for these changes however) (Guo et al. 2019).
Obese mice exposed to POPs who had cranberry extract while they lost weight lost more fat, had better glucose levels, and changed gut microbiota, compared to those that did not (So-Yun Choi et al. 2020).
So How Should You Lose Weight?
Dr. Lee and other experts recommend "A moderate, rather than low-fat, and largely plant-based diet with intermittent fasting or caloric restriction... to facilitate biliary POP excretion, provide protective phytochemicals that induce or enhance cellular defense mechanisms, and reduce POP intake through avoidance of animal-derived fats." (re Lee et al. 2020 via Bennett 2020).
Type 1 Diabetes
Based on the above studies, some authors have hypothesized that POPs may contribute to the development of type 1 diabetes. Yet there are only a few human studies on this possibility.
Longitudinal Studies in Humans
A study from Finland found an association between lower plasma HCB concentrations in 12-month-old children and the appearance of diabetes-associated autoantibodies, but no association between early life exposure to 13 persistent organic pollutants and 14 PFASs and the development of type 1 diabetes (Salo et al. 2018).
Exposure During Development
A study from Sweden measured in utero exposures to PCB-153 and DDE, and compared the levels these contaminants in children who went on to develop type 1 diabetes and those who did not. (Sweden, like other Scandinavian countries, has very good medical research data, and this study included data from children born in 1970-1990, and followed until 2002). The authors found that POP exposure did not increase the risk of type 1 diabetes; in fact, mothers of children who developed type 1 had generally lower levels of exposure than mothers of children who did not develop type 1 (although the differences were not statistically significant). The authors suggest that their findings do not imply that POPs are protective against type 1. Instead, since in Sweden, higher POP levels are often due to higher fish consumption, it may be that the fatty acids found in the fish provide the possible protective effect (see the Nutrition page for more on these fatty acids and type 1 diabetes) (Rignell-Hydbom et al. 2010).
Cross-Sectional Studies in Humans
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 (Longnecker et al. 2001).
Egyptian children with newly diagnosed type 1 diabetes had statistically significantly higher levels of 8 of 9 pesticides, including all 6 organochlorine POPs, than healthy children. Also, the percentage of children with detectable levels of the organochlorines lindane, DDE, DDD, endrin and DDA in their blood was higher in those with type 1 diabetes than in healthy control children, and lower for DDT (El-Morsi et al. 2012).
While the children in a Danish study did not have diabetes, those with higher PCB, HCB and DDE 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).
A study from South Korea found that children with higher levels of POPs (PCBs, trans-nonachlor, and β-HCH) had lower beta cell function and insulin secretion at age 7-9 (Park et al. 2016).
There are very few animal studies on POPs and type 1 diabetes. One study found that chronic, high-dose exposure to DDE increased diabetes incidence and disease severity in treated female non-obese diabetic (NOD) mice. DDE was shown to affect the immune system of these animals, especially T-cell function, and has the potential to affect the development of type 1 diabetes (Cetkovic-Cvrlje et al. 2016). Another study, however, 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).
Many POPs are considered to be immunotoxicants, since they can affect the immune system (see the autoimmunity page) (Holladay 1999). Researchers at the University of Florida have been studying the effects of organochlorine pesticides on mice and their relation to autoimmunity. The researchers fed three organochlorine pesticides (o,p' DDT (a component of DDT), methoxychlor, and chlordecone) to genetically susceptible mice, and found that these compounds accelerated the appearance of the autoimmune disease lupus, with chlordecone having the most significant effect. O,p' DDT and methoxychlor produced effects even at very low doses, for methoxychlor, four times lower than the U.S. EPA's "No Observable Effect Level." In the case of chlordecone, levels of autoantibodies were dependent on the dose received (Sobel et al. 2005).
A follow-up study found that chlordecone increased the rate of progression of the disease in mice that were genetically susceptible to lupus, but not in mice that were not susceptible to this disease, showing the importance of genetic background for this effect (Sobel et al. 2006). Chlordecone interacts with viruses to promote autoimmunity in lab animals as well (Tabet et al. 2018).
In addition, autoimmune antibodies have been found to be higher in people who have higher levels of PCBs, DDE, and HCB in Slovakia (Cebecauer et al. 2009). These researchers found higher thyroid autoantibodies as well as impaired fasting glucose levels in people with higher exposures to these POPs (Langer et al. 2008). (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)). Researchers have found evidence that may show transgenerational endocrine disrupting effects in humans. Youth who lived in the polluted area but who had similar organochlorine levels to youth living in unpolluted areas, showed the same health effects as their parents, who were exposed to high levels. These health effects included impaired fasting glucose levels and the presence of thyroid antibodies (Langer et al. 2008). Low thyroid levels are also linked to POPs in Belgians (Dufour et al. 2019).
HCB exposure has effects on the immune systems of animals and humans, and autoimmunity might be one of these effects (Michielsen et al. 1999).
A cross-sectional study of the general U.S. population found that dioxin-like PCBs were associated with antinuclear antibodies, a type of autoantibody associated with numerous autoimmune diseases (Gallagher et al. 2013). I do not think these antibodies are associated with type 1 diabetes, however.
In 1973, Michigan residents were exposed to polybrominated biphenyl (PBB) when it was accidentally added to farm animal feed. A follow-up study found that PBB exposure is associated with epigenetic changes related to immune function and autoimmunity (Curtis et al. 2019).
In animals, early life exposure to some POPs can cause immune dysfunction that is associated with the development of autoimmunity (Leung-Gurung et al. 2018).
New York children with higher DDE levels in their blood had a 2-fold higher risk of celiac disease, an autoimmune disease common in people with type 1 diabetes. These findings raise further questions of how environmental chemicals may affect autoimmunity in genetically susceptible individuals (Gaylord et al. 2020). It also raises questions of how POPs can affect the gut...
POPs can affect the gut and gut microbiota, which is linked to the development of type 1 diabetes (see the Diet and the Gut page). For example, levels of various persistent organic pollutants (including PCBs, PBDEs, and PFASs) in breastmilk were associated with less microbiome diversity and with microbiome functionality in 1 month old infants (Iszatt et al. 2019). Hexachlorocyclohexane (HCH) exposure alters the microbiome of colostrum in breastfeeding mothers (Tang et al. 2019). The POP pentachloronitrobenzene (PCNB) directly impairs intestinal cells in the lab (Li et al. 2019), and TCDF causes gut inflammation in mice (Nichols et al. 2019). DDE also affects gut microbiota in lab animals, which may contribute to its effects on diabetes and obesity (Liang et al. 2020).
A study of Greek women found that PCB levels were associated with a much greater risk of gestational diabetes. Other POPs, including DDE and HCB, were not associated (Vafeiadi et al. 2017). A study from Iran found an association between total POP and total PCB levels and gestational diabetes (Eslami et al. 2016). A Taiwanese study of pregnant women without diabetes found that higher levels of some PCBs were associated with increased insulin resistance (Chen et al. 2008). A study from the Faroe Islands found that exposure to POPs was associated with gestational diabetes (Valvi et al. 2017). A Chinese study found that certain non-dioxin-like PCBs were associated with gestational diabetes (Zhang et al. 2018). A U.S. study found numerous POPs were associated with gestational diabetes, including PCBs, PBDEs, and PFASs (Rahman et al. 2019).
POP levels have also been associated with higher weight gain during pregnancy (Jaacks et al. 2016a). In Spanish women with a past history of gestational diabetes, various POP levels were associated with higher insulin resistance and higher glucose levels two hours after a meal (Arrebola et al. 2015), suggesting that perhaps POPs could increase the risk of permanent diabetes following gestational diabetes. However, another Spanish study found that POP levels (PBDEs and PCBs) were actually lower in the placentas of women with gestational diabetes than women without (Alvarez-Silvares et al. 2021).
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).
In China, higher body levels of a mixture of multiple POPs was associated with an increased gestational diabetes risk. Ranked in order of importance, dioxin-like compounds > PBDEs > PFAS > PCBs (Liu et al. 2021). In Korea, blood aryl hydrocarbon receptor trans-activating (AhRT) activity, a biomarker of persistent organic pollutants, is associated with an increased risk of gestational diabetes (Park et al. 2021).
However, other studies of POPs and gestational diabetes have not found an association. A Canadian study found that neither PCBs nor organochlorine pesticides were associated with gestational diabetes or impaired fasting glucose in pregnant women (Shapiro et al. 2016). A U.S. study also found that POPs were generally not associated with gestational diabetes (although PBDE flame retardants were) (Smarr et al. 2016). A study of U.S. women from Michigan and Texas found that exposure to PCBs and PBB were not consistently associated with gestational diabetes (Jaacks et al. 2016b). The POP chlordecone was used almost exclusively in the French West Indies. A study of pregnant women in Guadeloupe exposed to this pesticide found no association between chlordecone exposure and gestational diabetes (Saunders et al. 2014).
DDE/DDT levels were associated with high blood pressure in pregnant women who live in areas sprayed for malaria control (Murray et al. 2018).
POPs and Weight Gain During Pregnancy
Adequate weight gain during pregnancy may help protect the fetus from exposure to POPs. If a pregnant woman does not gain enough weight while pregnant, her body loses fat as the baby grows, releasing POPs into the blood which can enter the fetus. The newborn babies of women who have gained adequate weight while pregnant have lower levels of POPs than babies of women who do not gain enough weight (Vizcaino et al. 2014).
Does Diabetes Influence POP Levels?
It is possible that diabetes causes people to have higher levels of POPs, not vice versa. Yet Lee et al. (2006) point out a number of reasons why it is more likely that the POPs lead to diabetes instead of the other way around. For example, the idea that dioxin could cause diabetes is consistent with the known biology of these pollutants. As for the idea that diabetes changes the way the body processes POPs, one study has found that people with diabetes eliminate dioxin at the same rate as people without diabetes (see Michalek et al. 2003), implying that diabetes does not affect POP levels. In addition, since this papers were written, numerous longitudinal studies that followed people over time have confirmed that earlier exposure to POPs is associated with later development of diabetes.
One small pilot study from Scandinavia does suggest that factors related to type 2 diabetes do affect blood concentrations of POPs and may partly explain the positive associations between POPs and type 2, however (Berg et al. 2021). Another similar study from some of the same but some different findings (Tornevi et al. 2019).
Rising Rates of Disease; Falling Levels of POPs
While the levels of many environmental chemicals has risen over the past few decades, the levels of POPs in the environment fell after most developed countries restricted their use in the 1970s-1980s (Tanabe 2002). To explain how the rates of diabetes could be rising while levels of POPs fell, Lee et al. 2007b propose a number of explanations:
the toxicity of POPs may increase as obesity increases;
chemicals that have properties similar to other POPs and are still in use today may be important;
lower doses may be more harmful than higher doses for some POPs;
the current generation may be experiencing epigenetic changes due to exposure in utero or from their parents or grandparents; and
the possibility of a combination of effects of exposure to multiple POPs together.
Can We Reduce Our POP Levels?
This is difficult to do. Unfortunately breastfeeding and pregnancy are one way to reduce the mother's levels, but that is not ideal for the child!
A few approaches show promise in humans:
Higher carbohydrate intake was associated with lower levels of POPs. Higher fat intake was associated with lower POP levels, including both saturated and monosaturated fat (but not polysaturated). Similar to what is seen in animal studies, a moderate fat, lower carbohydrate diet might help reduce POP intake in food (Lee et al. 2019).
A vegetarian diet did NOT reduce POP levels as compared to a meat-containing diet, although this was a short term (12 week) trial that reduced calories as well, leading to weight loss and possibly the release of POPs from fat stores. However, this trial also found that changes in POP levels were associated with changes in HbA1c levels, glucose levels, and beta cell function that were unrelated to body weight change (Kahleova et al. 2016).
In general, a vegan diet is associated with lower POP levels compared to a meat-containing diet (Arguin et al. 2010).
A U.S. study found that vitamin C supplementation (1000 mg/day for 2 months) DID reduce PCB and DDT/DDE levels in women, but not PBDE levels (Guo et al. 2016). (Dietary vitamin C intake also happens to reduce the risk of type 2 diabetes (Zhou et al. 2016)).
Hennig et. al. (2007) discuss the role of nutrition in preventing chemical exposures.
Good nutrition, calorie restriction (especially restricting sugar), cognitive stimulation, and phytochemical intake may also help counteract the effects of POPs (Lee and Lee, 2019).
Regular exercise may also help reduce POP levels (Lee et al. 2020).
Many chemicals are excreted in perspiration (Genius et al. 2016).
While I am skeptical of detox programs, here is one study that shows lower body fat, blood glucose, triglycerides, and blood pressure as a result: Kim et al. (2016).
Mori and Todaka (2017) suggest a three-pronged approach, ranging from political action to individual action, such as eating high-fiber foods, reducing intake of high-POP meat, and by boiling or grilling meat.
Some authors recommend antioxidants to counteract the inflammation caused by POPs (Gupta et al. 2018).
In animals, mice fed a diet higher in protein and lower in sugar actually absorbed fewer POPs into their tissues, less obese than those fed a diet lower in protein and higher in sugar (Myrmel et al. 2016). Also in mice, dietary selenium supplementation helped reduce the metabolic harm caused by DDE (Morales-Prieto et al. 2018), although there are issues with selenium supplementation, as described on the selenium page.
Do POPs Affect Diabetes Management or Complications?
Researchers are just beginning to study whether contaminants can affect the blood glucose control or contribute to complications in those of us with diabetes. One study found that a variety of POPs were associated with higher hemoglobin A1c (HbA1c) levels, a measure of long-term glucose control, as well as a higher risk of peripheral neuropathy (nerve damage). Of the various POPs, organochlorine pesticides were the most strongly and most consistently associated with higher HA1c and neuropathy. If these findings are confirmed in other studies, the authors state, "new therapeutic approaches such as avoiding POPs or an increased excretion of POPs from the body can be developed for the management of type 2 diabetes" (Lee et al. 2008). Veterans exposed to dioxin via Agent Orange also have higher rates of neuropathy than those who were less exposed (Michalek et al. 2001). However, in Germany, POP levels were not associated with an increased risk of neuropathy in people with type 2 diabetes, prediabetes, or normal glucose tolerance; if anything, there was a decreased risk (Schwarz et al. 2021).
Among U.S. children with diabetes, mostly type 1, those with higher levels of some POPs in their bodies had higher HbA1c levels and lower beta cell function than those with lower levels, over a 5+ year period (Kaur et al. 2019).
A study from Japan also found that POP levels were associated with higher HbA1c levels in the general population (in addition to diabetes) (Uemura et al. 2008). A U.S. study found that DDE and PCB 118 were associated with higher HbA1c levels in people who eat fish from the Great Lakes-- although eating fish was associated with a lower HbA1c (Turyk et al. 2015).
Various POPs have also been associated with other conditions that are also diabetes complications, including higher levels of cholesterol and triglycerides, cardiovascular disease, high blood pressure, hardening of the arteries, heart attacks, strokes, and hypertension, in people without diabetes (Aminov et al. 2014, Arrebola et al. 2015, Bergkvist et al. 2015, Everett et al. 2011, Fu et al. 2020, Goncharov et al. 2008, Goncharov et al. 2010, Goncharov et al. 2011, Ha et al. 2007, Ha et al. 2009, Henríquez-Hernández et al. 2017, Lee et al. 2012, Lind and Lind 2020, Lind and Lind, 2012, Lind et al. 2012, Park et al. 2016, Penell et al. 2014, Sergeev and Carpenter 2011a, Sergeev and Carpenter 2011b, Sjöberg Lind et al. 2013, Van Larebeke et al. 2015), and in people with diabetes (Sergeev and Carpenter 2010a; Sergeev and Carpenter 2010b). Interestingly, in European children, DDE and HCB levels are actually associated with lower blood pressure, as are prenatal levels of PCB 118 (Warembourg et al. 2019).
DDE exposure increases blood pressure in rats (Sá et al. 2018). DDT exposure during development increases blood pressure in adult mice as well (LaMerrill et al. 2016), and HCB in adult rats (Castilla et al. 2018). Even in polar bears, POP levels are associated with higher cholesterol and lower HDL "good" cholesterol levels (Ciesielski et al. 2018), as well as other related changes in metabolism (Morris et al. 2018).
These complications may be associated with POPs in people with diabetes as well. A longitudinal study found PCB levels were associated with kidney disease (nephropathy) in people with diabetes, as well as the risk of death (Grice et al. 2017). A population-wide U.S. study found that DDT and heptachlor were associated with nephropathy as well (Everett and Thompson, 2015). These same authors found even more associations when focusing on Mexican Americans (DDT wasn't banned in Mexico until 2000). Both DDT and DDE were associated with diabetic nephropathy (Everett et al. 2017).
The ability of POPs to affect morality from cardiovascular disease may depend on fat mass. For example, in thin elders, higher POP levels increased the risk of dying from cardiovascular disease-- but not in heavier elders (Kim et al. 2015).
POPs may also contribute to non-alcoholic fatty liver disease (NAFLD) (Deierlein et al. 2017). In U.S. adults, some POPs were associated with an increased risk of NAFLD markers (Wahlang et al. 2019). In laboratory animals with diet-induced obesity, PCB exposure worsened inflammation in the liver and systemically, thus the combination of a poor diet and PCB exposure may contribute to NAFLD (Wahlang et al. 2014). In fact, a search of the toxicology literature found that PCBs and dioxin were among the most potent of the 123 chemicals associated with fatty liver in rodent studies (Al-Eryani et al. 2015). DDE affects fatty acid levels in the liver of lab animals as well, perhaps playing a role in NAFLD (Rodríguez-Alcalá et al. 2015). At levels found at contaminated sites, perchlorate causes NAFLD and may be an obesogen in stickleback fish (Minicozzi et al. 2019), but not in zebrafish, probably due to differences in the fish species (Minicozzi et al. 2021). In mice, exposure to the POP 2,3,7,8-tetrachlorodibenzofuran (TCDF) induced early-stage NAFLD, including excessive lipids in the liver and blood (Yuan et al. 2019).
While breast cancer is not generally seen as a complication of diabetes, some researchers propose that POPs, deposited in fatty tissue, in relation to obesity, can influence the risk of cancer as well (Reaves et al. 2015).
Risk of Type 2 Diabetes with Various POPs
It is interesting to look at some of the results of these studies graphically. In the figures below, from Taylor et al. 2013, you can see the risk of type 2 diabetes in relation to various POPs, according to various studies (each row is a study). The blue dots/lines show prospective/longitudinal studies, and the black dots/lines show cross-sectional studies. When the dots and lines are to the right of 1 (OR=Odds Ratio), that shows an increased risk of diabetes, and to the left shows a decreased risk. The dot is the amount of risk, and the lines show the 95% confidence interval. When the lines overlap 1, the level of risk is not statistically significant. So, for example, PFOA exposures generally show a decreased risk, mostly statistically insignificant (bottom figure), whereas transnonachlor studies generally show an increased risk, mostly statistically significant. You can also see that not all studies agree.
To download or see a list of all the references cited on this page, see the collection Persistent organic pollutants and diabetes/obesity in PubMed.
One additional reference not on PubMed is:
El-Morsi DA, Rahman RHA, Abou-Arab AAK. Pesticides Residues in Egyptian Diabetic Children: A Preliminary Study. J Clinic Toxicol. 2012;2:138. Full text