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, beta-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 consider multiple POPs together; see the pages on PCBs and dioxin for information on studies on those contaminants in particular.
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 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.
A review of 41 human studies on diabetes and POPs concluded that, "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). Most (if not all) of the studies included are discussed below.
The U.S. National Toxicology Program (NTP) convened a workshop of experts in 2011 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).
A large review of the evidence, written by some of the same authors who conducted both the 2006 study described above, and numerous subsequent studies described below, finds that: "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).
A systematic review and meta-analysis of 23 studies "provides quantitative evidence supporting the conclusion that exposure to organochlorine pollutants is associated with an increased risk of incidence of type 2 diabetes," especially for PCBs and DDE (Tang et al. 2014).
A review of the evidence from 19 articles linking POPs to diabetes in Asia concluded that numerous POPs were associated with diabetes in Asian populations, but more research is needed to address the limitations of the literature (Jaacks and Staimez, 2014).
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). Another study from Sweden 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).
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).
A study of Swedish women found PCB-153 and DDE to be associated with 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).
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).
A prospective study that measured various POP levels and later development of diabetes in US 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).
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. 2014).
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).
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).
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).
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. 2014).
A study found that higher levels of HCB, some PCBs, and DDE (but not mirex) were associated with diabetes in adult Native Americans of the Mohawk Nation. The most elevated results were found for HCB. This study did not distinguish between type 1 and 2, but since the participants were over 30 and most did not use insulin, they presumably had type 2 (Codru et al. 2007). Another study also found that the levels of HCB were significantly associated with diabetes, in Swedish women over 50 (who presumably had type 2, although the study did not distinguish between them). 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).
A Belgian study found that 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).
A study of Mexican Americans found that diabetes was associated with higher levels of various organochlorine pesticides (Cox et al. 2007). Finnish study found that exposure to oxychlordane, trans-nonachlor, PCB-153 and DDE were associated with 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).
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). A study from Japan also found that POP levels were associated with diabetes (Uemura et al. 2008).
A study of Danish adults found that those 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). 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. 2014a; Al-Othman et al. 2014b).
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).
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).
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).
Some studies of more highly exposed populations, however, have still found some associations between diabetes and POPs. 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). Yet 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. 2014).
A study from a polluted area of Eastern Slovakia found that people with higher levels of five POPs (including PCBs, DDE, DDT, HCB, and beta-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). For an award-winning article on the situation in Anniston, see Dirty soil and diabetes: Anniston's toxic legacy, published by Environmental Health News.
A number of studies have found associations between various POPs and increased insulin resistance and metabolic syndrome.
A study that followed people over time 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). 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).
A large, long-term study of Spanish adults found that higher intake of PCBs was associated with a higher risk of obesity. The study estimated PCB levels using a questionnaire, instead of directly measuring blood PCB levels (Donat-Vargas et al. 2014).
In 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).
A study of Russian boys exposed to high levels of POPs found that POP level 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).
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 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). 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).
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).
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). 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, βHCH, 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).
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).
And some studies have found no association. 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 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).
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).
Birth weight may also be affected by POP levels encountered by a fetus in the womb. 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. 2014). A study 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). U.S. women with higher PCB levels also have smaller babies (Murphy et al. 2010).
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.
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 (betaHCH) 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. 2014).
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. 2010c).
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).
A New York study found that people who live in areas near environmental sources of POPs have a higher rate of hospitalization for metabolic syndrome (Sergeev and Carpenter 2011).
Laboratory studies are often used to determine the mechanisms through which environmental chemicals act.
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. 2014a). 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. 2014b).
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, and affected . 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).
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. 2015).
Zebrafish 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).
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).
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).
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).
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).
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). DDT, when given to pregnant mice, led to obesity in their great-grandchildren (Skinner et al. 2013). 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).
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. 2014).
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).
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).
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).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). 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).
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, 2014), 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).
Good question. In a study of postmenopausal overweight Seattle women, past weight loss of over 20 pounds were associated with higher levels of POPs (De Roos et al. 2012). 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).
Can POPs released via weight loss lead to toxic effects on other organs? Perhaps. 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 (Kim et al. 2011). A study of people undergoing bariatric surgery found that those with higher POP levels in their fatty tissue had less weight loss than those with lower levels (Pestana et al. 2014).
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).
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).
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). For an article about this study, see Weight gain during pregnancy may protect babies from chemicals, published by Environmental Health News.
Based on the above studies, some authors have hypothesized that POPs may contribute to the development of type 1 diabetes. Yet there are very few human studies on this possibility.
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).
A second study found that Egyptian children with newly diagnosed type 1 diabetes had higher levels of lindane, DDE, DDD, endrin and DDA (and lower levels of DDT) in their blood than healthy control children. They also tended to have more of these chemicals in their bodies than controls, many of whom had no detectable levels of organochlorine pesticides. (An organophosphorous pesticide, malathion, was also higher in type 1 patients, discussed on the pesticides page) (El-Morsi et al. 2012).
A third 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).
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).
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. 2015).
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).
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).
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.
There is very little research on POPs and gestational diabetes.
A Taiwanese study of pregnant women without diabetes found that higher levels of some PCBs were associated with increased insulin resistance. The women lived in a city that had been polluted by dioxin, however, dioxin levels were not associated with insulin resistance in this study (Chen et al. 2008).
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).
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. 2014). This suggests that perhaps POPs could increase the risk of permanent diabetes following gestational diabetes.
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.
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:
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).
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, Goncharov et al. 2008, Goncharov et al. 2010, Goncharov et al. 2011, Ha et al. 2007, Ha et al. 2009, Lee et al. 2012, Lind and Lind, 2012, Lind et al. 2012, Penell et al. 2014, Sjöberg Lind et al. 2013, Van Larebeke et al. 2014).
These complications may be association with POPs in people with diabetes as well. In a study of U.S. adults with diabetes, various POPs were associated with nephropathy (kidney disease), especially dioxin and dioxin-like compounds (Sergeev and Carpenter, 2010a, Sergeev and Carpenter 2010b).
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).
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 non-alcoholic fatty liver disease (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. 2014).
There is strong evidence that exposure to persistent organic pollutants, at levels commonly found in developed countries, can increase the risk of developing type 2 diabetes. The ability of some of these pollutants to also enhance autoimmunity implies that they could potentially contribute to the development of type 1 diabetes as well. This possibility should be studied.
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