Persistent Organic Pollutants

Summary

Links Between Persistent Organic Pollutants and Diabetes/Obesity

Over 1,000 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.

The Details

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).

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). Also in elderly Swedes, levels of 42 contaminants were measured, and then diabetes incidence followed for 15 years. Nine contaminants (four metals, trans-nonachlor, the phthalate MiBP, PCB-126, PCB-169, and PFOS) improved the model predicting incident diabetes in the first 5 years of follow-up (Lind et al. 2022). 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 without obesity (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 with overweight/obesity. 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). Also in Norway, in a study that covered 1986-2016, most POPs were linked to an increased risk of type 2 diabetes, and most POP levels declined more slowly over time in people with diabetes than in those without (Charles 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 without obesity (Barrios-Rodríguez et al. 2021).

In Korea, blood concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/DFs) but not dioxin-like PCBs were associated with an increased risk of developing type 2 diabetes (and thyroid cancer) in women but not men (Lee et al. 2022). In China, higher levels of organochlorine pesticides were associated with an increased risk of type 2 diabetes, with β-BHC being the major contributor (Jia et al. 2023). 

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

U.S. adolescents with higher POP levels have higher blood glucose levels (Baumert et al. 2022).

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).

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 people with obesity who had 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).

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 China, PCB-126 and BDE-153 may increase the risk of type 2 diabetes (Chen et al. 2023). In China, higher exposure to short-chain paraffins (a type of POP) were associated with a higher risk of type 2 diabetes, and higher total and LDL cholesterol levels (Zhang et al. 2023).  In rural China, individual and mixtures of organochlorines were associated with an increased risk of type 2 diabetes, in part involving testosterone (Shi et al. 2023). In elderly Chinese people, the risk of type 2 diabetes was higher with higher exposure to a mixture of 39 pesticides, especially with β-hexachlorocyclohexane (β-HCH) and oxadiazon, and especially in women (Chen et al. 2024).  

In Africa, a study from Benin found that people with diabetes had high levels of POP exposures, especially those who had obesity. 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).

In India, people with higher POP levels in their bodies had a higher risk of having prediabetes or type 2 diabetes (Tyagi et al. 2020; Tyagi et al. 2021).

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). In Cree women specifically, higher DDT/DDE levels were associated with a higher prevalence of type 2 diabetes (Zuk et al. 2021).

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). A follow-up study of people living in Anniston found that exposure to PCBs, PCDDs, trans-nonachlor and DDE were associated with an increased risk of type 2 diabetes (Pavuk et al. 2023).

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). 

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).

In Pakistanis with type 2 diabetes, exposure to organochlorine pesticides was associated with an increased risk of obesity (Khwaja et al. 2022).

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). 

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).

In Sweden, prenatal exposure to a mixture of EDCs (phthalates, other plasticizers, phenols, PAHs, pesticides, PFAS, organochlorine pesticides, and PCBs) was associated with lower BMI and overweight among girls, and there were non-significant associations among boys at age 5 1/2 (Svensson et al. 2023).

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). This study also found interactions with nutrients. For example, the obesogenic effects of HCB were increased in children of women with higher B12 vitamin levels (Cano-Sancho et al. 2023). For an article describing this study, see Invited Perspective: Can Eating a Healthy Diet during Pregnancy Attenuate the Obesogenic Effects of Persistent Organic Pollutants?  (Jaacks et al. 2023).

In France and Spain, prenatal exposure to a POP mixture was associated with a higher BMI and percentage fat mass at age 12, mainly due to HCB; β-HCH and DDE were associated with higher systolic blood pressure (Rouxel et al. 2023).

In Dutch adolescents, higher prenatal levels of PCBs were associated with lower levels of HDL cholesterol and adiponectin in boys. There were significant differences by sex in the associations with hydroxylated PCBs (a subtype of PCBs) with lower HDL cholesterol, and higher fasting glucose, insulin resistance, height, and weight for boys (Berghuis et al. 2022). 

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).

In Greek children, prenatal exposure to various persistent organic pollutants (individually and in mixtures) was assocated with higher BMI (Colicino et al. 2022).  

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). In the French West Indies, prenatal chlordecone levels were associated with a slightly increased weight at age 7 (Costet et al. 2022). 

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). In Belgium, prenatal POP levels were not associated with long term growth in children, although somewhat with infant growth (Cai et al. 2023).

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).

Transgenerational Studies

In the U.S., women's o,p'-DDT levels were associated with obesity in their granddaughters among normal weight women, but not among with overweight/obesity (and with early puberty in granddaughters among all women) (Cirillo et al. 2021). 

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 Portuguese women with obesity 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). In surgery patients from Spain, levels of various POPs in visceral adipose tissue, especially HCB and γ-HCH, were associated with a higher risk of metabolic syndrome and its individual components of (e.g. higher fasting glucose) (Reina-Pérez et al. 2023). 

Luxembourg and Belgium, HCB and β-HCH were associated with an increased risk of obesity, and PCB-180 with high blood pressure (Peng et al. 2023). 

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). In Chinese adults, Higher exposure to β-HCH, DDE, and PCBs, as well as their mixtures, were correlated with an increased risk of metabolic syndrome (Zhang et al. 2023).  

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).

In Belgian adolescents, HCB and PCB-170 were associated with a lower BMI, and PCB-170 also with lower abdominal obesity (Cai et al. 2023).

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). Exposure to a mixture of POPs increased glucose levels and affected the gut microbiota in female zebrafish (Lee et al. 2023).

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).

Both DDT and DDE reduce the browning of white fat tissue and have obesogenic effects in adult male rats (Al-Obaidi et al. 2022).

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).

Exposure to trans-nonachlor affected metabolism in rats, including lower triglycerides, increased free fatty acids, and lower glucose levels, depending on diet (McDevitt et al. 2023).  

POPs can also affect glucagon-like peptide 1 (GLP-1) secretion, which perhaps is significant for diabetes (Shannon et al. 2019).

Ten chemicals suspected to induce metabolic disorders were screened and DDE was found to contribute to liver steatosis, which can lead to non-alcoholic fatty liver disease (NAFLD) (Le Mentec et al. 2023). 

Additional efforts are also underway to determine the mechanisms behind POP-induced diabetes (e.g., Ko et al. 2020).

The emerging contaminants polyhalogenated carbazoles affected glucose levels, gut microbiota, and the liver in mice, acting like dioxin (Ji et al. 2022). 

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; Wang et al. 2024). 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). 

Exposing father mice to DDT before conception led to glucose intolerance in male offspring (Chen et al. 2024), showing that effects can be passed down via sperm. 

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.

Chemical Mixtures

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).

The lowest dose of a mixture of organochlorine pesticides causes high glucose and low insulin levels in zebrafish (Gao et al. 2022). 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). Caloric restriction could actually protect zebrafish from the diabetes-related effects caused by a mixture of POPs (Lee et al. 2023).

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). Exposure to a mixture of organochlorine pesticides also alters fat cell function at levels humans are exposed to (Howell and Young, 2024). 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). The flavone luteolin reduced fat cell formation and fat accumulation caused by a mixture of POPs (Xie et al.  2023). 

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). Different types of HCH had different effects on beta cells: α-HCH and γ-HCH increased proinsulin and insulin levels in beta cells, while β-HCH reduced them (Pavlíková et al. 2023).  

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). Of ten different chemicals, one of the two with the largest effect on inducing fat in liver cells was DDE (Bernal et al. 2024).

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 individuals with obesity. 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).

POPs may also contribute to obesity by impairing the mass and function of brown adipose tissue (BAT, brown fat), which protects against obesity (Di Gregorio et al. 2019).

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 people with obesity had higher levels of PCBs in their bodies than metabolically healthy people with obesity. 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 PFAS 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 people with obesity 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 mice with obesity. Specifically, while PCBs had no effect on glucose control in mice with obesity, PCB exposure did impair glucose control after those mice lost weight. In other words, the diabetes-promoting effects of PCBs were only apparent in mice with obesity 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). In zebrafish, POPs released from fatty tissue affect organs (Yang et al. 2024).

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).

Laboratory Studies

Mice with obesity 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 If You Want To?

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).

A review suggests that physical activity can help counteract the adverse effects of POPs, although we need more research on how it impacts people undergoing bariatric surgery (Serrano et al. 2024).

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

In a U.S. study, exposure to DDE, trans-nonachlor, and PCB-153 were associated with type 1 diabetes in youth with normal insulin sensitivity, but not in those with insulin resistance. In experiments, treatment with DDE or PCB-153, at levels found in people, impaired the ability of pancreatic β-cells to produce and secrete insulin in response to glucose; longer treatment killed the β-cells (Bresson et al. 2022). 

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).

Animal Studies

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).

A mixture of POPs (that included PFASs) led to early signs of autoimmunity development in NOD mice (Berntsen et al. 2018). These authors also found that this mixture led to several metabolic changes in NOD mice-- changes that are linked to an increased risk of type 1 diabetes in humans (Sinioja et al. 2022). These authors note that, "The female NOD mice develop spontaneous disease also without any exposure and thus, comparison of diabetic versus non-diabetic animals was not feasible in this study set-up."

Autoimmunity

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). In Akwesasne Mohawk women, those with higher levels of DDE and some PCBs had a higher risk of autoimmune disease (Lee et al. 2022).

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). A closer look found possible links between PBB and some autoimmune diseases, but the links were not statistically significant (Hood et al. 2023).

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...

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).

Gestational Diabetes

A review of 16 studies concluded that some differences in exposure levels to POPs related to the risk of gestational diabetes (Kouiti et al. 2023).

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 Californian women with overweight or obesity, 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).

In Eastern China, those with higher levels of chlorinated paraffins had a much higher risk of gestational diabetes, with medium-chain having an inverted U-shaped association (implying possible endocrine disruption) (Yang et al. 2024).

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).

Laboratory Studies

Mice exposed to a low-dose mixture of EDCs (the pesticide atrazine, BPA, PFOA, and dioxin) while pregnant later had hyperglycemia with a persistent elevation in blood glucose two hours after glucose administration in a glucose tolerance test, while these effects were not observed in mixture-exposed non-pregnant females (six months after exposure). These findings provide biological plausibility for the associations seen between chemical exposures during pregnancy and subsequent maternal diabetes and shows that pregnancy itself can play a role in the effects of chemical exposures (Merrill et al.  2021).

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)).

  • In people who have been exposed to high levels of POPs, olestra has been successfully used to increase POP elimination (Geusau et al. 2002; Jandacek 2016; Redgrave et al. 2005).

  • 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 and reduce their effects (Lee et al. 2020; Liu and Hou 2023).

  • 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).

  • Others note that polyphenols, found in plant-based food, may be protective against the effects of POPs, in part due to their antioxidant ability (Żwierełło et al. 2019).

In animals, mice fed a diet higher in protein and lower in sugar actually absorbed fewer POPs into their tissues, with less obesity 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). In Belgian children with type 1 diabetes, levels of PCB-153  (and some phthalate metabolites) were associated with higher long-term blood glucose levels (HbA1c), and levels of PFHxS, BPF, PCB-138, and a phthalate were linked to thyroid hormone levels (Dufour et al. 2023). 

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, Donat-Vargas et al. 2023;  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).

Kidney disease is also associated with POP levels, in people without diabetes (Everett and Thompson, 2016), as well as mortality from albuminuria, a symptom of kidney disease (Kim et al. 2017).

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 Quebec, Canada, in utero exposures to POPs were associated with long lasting decreases in triglyceride in children, suggesting increased fat accumulation in the liver (Boutot et al. 2021). In China, PCBs, DDE, β-HCH and a POP mixture were associated with fatty liver disease, especially in those with an unhealthy lifestyle (Liu et al. 2023). 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). The polyhalogenated carbazole (industrial pollutants and potential persistent organic pollutants) 3,6-dichlorocarbazole (36-CCZ) caused fatty liver disease in zebrafish (Hou et al. 2024). 

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.

PFAS