Links Between Pesticides and Diabetes/Obesity
Over 300 peer-reviewed studies published since 2007 in scientific journals have examined the relationship between pesticides and diabetes or obesity.
The majority of human epidemiological studies have found that people with higher exposures to pesticides have a higher risk of type 2 diabetes, gestational diabetes, or obesity, especially at high exposure levels (e.g., in farmers). This evidence includes long-term, longitudinal studies that follow people over time.
One rodenticide, Vacor, was banned due to its ability to cause permanent type 1 diabetes in humans, but aside from Vacor, pesticides have generally not been studied in relation to type 1 diabetes.
People who are poisoned with pesticides sometimes develop high blood sugar as an immediate consequence, which tends to resolve over time, but can be misdiagnosed as diabetes.
Laboratory studies on animals or cells show that pesticides exposures can cause biological effects related to diabetes/obesity, and have helped to identify the mechanisms involved. These studies show that exposure to pesticides during early development can lead to obesity-related effects not only in first generation offspring, but also in later generations
The term "pesticides" include a number of chemicals, including herbicides, rodenticides, fungicides, and insecticides, most used in agriculture. Some of the pesticides discussed here include the widely-used organophosphate pesticides (including malathion, diazinon, parathion, and chlorpyrifos), atrazine (widely used in the U.S. but banned in Europe), and many others. (For information on banned organochlorine pesticides such as DDT, see the persistent organic pollutant page).
A number of reviews have been published and conclude that:
A review of the human and laboratory evidence finds that "exposure to insecticides is linked to increased risk of obesity and type 2 diabetes" (Xiao et al. 2017).
"There is now considerable evidence linking human exposure to agrochemicals with obesity" (Ren et al. 2020).
Organophosphorous pesticides are linked to the development of metabolic changes such as type 2 diabetes and obesity, and that exposure to these pesticides during early life may be important for these effects (Czajka et al. 2019).
Organophosphate pesticides are linked to an increased risk of diabetes (Lakshmi et al. 2019).
Chlorpyrifos can cause metabolic disruption (Li et al. 2019).
The pesticide 2,5-dichlorophenol was associated with obesity in children (Ribeiro et al. 2020).
In general, pesticides can potentially induce metabolic disorders such as diabetes and obesity by disturbing energy absorption in the intestine, energy storage in the liver, and by affecting fat tissue, skeletal muscle, the pancreas, and immune cells (He et al. 2020).
The organophosphate pesticide diazinon induces hyperglycemia and dyslipidemia in rodents and fish in a dose-dependent manner. Specifically, diazinon increased blood glucose levels, total and LDL cholesterol as well as triglyceride levels, and decreased HDL cholesterol (Aramjoo et al. 2020; Farkhondeh et al. 2020).
A review of the mechanisms that link pesticide exposure, gut microbiota, and metabolic diseases such as type 2 diabetes and obesity finds that certain gut microbiome changes are linked to both pesticides and metabolism, and that prebiotics may help prevent these effects (Djekkoun et al. 2021).
A review of findings from 61 publications on glycemic, lipid/cholesterol, insulin, and body weight changes in rodents and fish exposed to the pesticide chlorpyrifos found that most of the studies reported hyperglycemia, hyperlipidemia, and decreased insulin levels and body weight following exposure, depending on dose and timing (Farkhondeh et al. 2021).
A review of prenatal, perinatal, and postnatal exposure to organophosphate, organochlorine, pyrethroid, neonicotinoid, and carbamate, as well as a combined pesticide exposure and body weight finds that the effects of pesticide exposure on body weight are mostly inconclusive, with conflicting results in both humans and experimental animals (Pinos et al. 2021).
How Are We Exposed to Pesticides?
Type 2 Diabetes, Insulin Resistance, and Body Weight
Longitudinal Studies in Adults
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.
In U.S. pesticide applicators, diabetes incidence increased with the use (both cumulative lifetime days of use and ever use) of some organophosphate pesticides: dichlorvos, trichlorfon, alachlor, cyanazine, and the organochlorine pesticides aldrin, chlordane, and heptachlor. 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. While these people were exposed occupationally, many of these pesticides are available to the general public. 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).
Another longitudinal study, also using data from the Agricultural Health Study, looked at exposure data from farmers' wives. It found that diabetes incidence was associated with exposure to five pesticides: three organophosphate pesticides: fonofos, phorate, and parathion; as well as the organochlorine pesticide dieldrin, and the herbicide 2,4,5-T (Starling et al. 2014).
In a large prospective study from France, higher consumption of organic food consumption (which is linked to lower pesticide exposure levels) was associated with a lower risk of developing type 2 diabetes (Kesse-Guyot et al. 2020).
In Chinese farmers, various pesticides were associated with changes in glucose levels, as well as kidney, liver, and nerve damage (Huang et al. 2016). In Thailand, conventional farmers had higher levels of total cholesterol, LDL, HDL, glucose, systolic and diastolic blood pressure, BMI, and waist circumference, compared to organic farmers (Kongtip et al. 2020).
In Uganda, contrary to the authors' expectations, a study of small farmers found that a marker of insecticide exposures were associated with lower blood glucose levels (Hansen et al. 2020).
Longitudinal Studies in Children
A 40 day organic diet intervention trial reduced children's exposure to pesticides, and lowered markers of oxidative stress and inflammation. The organic diet was also linked to a lower BMI, although since caloric intake was also lower during the organic diet, this association may not be due to the organic diet but to calorie intake (Makris et al. 2019). Still, both oxidative stress and inflammation are linked to diabetes development.
Farmers are often exposed to high levels of pesticides, and thereby have a higher risk of type 2 diabetes.
Exposure During Development
Children exposed to modern-day pesticides in the womb (because their mothers worked in greenhouses) had a lower birth weight, and then an increased body fat accumulation from birth to school age than children who were not exposed to pesticides in the womb (the effects were increased if the mothers smoked as well) (Wohlfahrt-Veje et al. 2011). Later in life, in adolescence, these children (especially girls) had a higher percentage of total fat (Tinggaard et al. 2016), as well higher blood glucose levels (HbA1c) (Andersen et al. 2018). The same authors also found that the metabolic and cardiovascular effects associated with these pesticide exposures depended on genetic background (Andersen et al. 2012; Jørgensen et al. 2015) and appears to involve epigenetic mechanisms (Declerck et al. 2017).
Organophosphorous pesticide levels in the mother were associated with lower birth size in Black U.S. infants, but not in other ethnic groups (Harley et al. 2016). Also in the U.S., in New York City, there was little evidence of a relationship between prenatal organophosphorus pesticide exposures and child weight, although there was some suggestion of increased risk among offspring of mothers who were slow pesiticide metabolizers (Etzel et al. 2020).
In France, fetal exposure to organophosphate pesticides was associated with insulin levels as early as birth (Debost-Legrand et al. 2016).
A large European study found no association between prenatal or childhood organophosphate pesticide exposure levels and childhood BMI (Vrijheid et al. 2020).
In Korea, exposure to the pesticide 3-PBA during childhood was positively associated with BMI in 4-year-old girls, but exposure prenatally showed no association (Lee et al. 2019).
In China, prenatal exposure to 2,4,6-trichlorophenol (2,4,6-TCP) was associated with lower weight/BMI in boys and higher weight/BMI in girls at age 3. Postnatal exposure to 2,5-diclorophenol (2,5-DCP) was associated with higher weight in girls (Guo et al. 2019).
Cross-Sectional Studies in Humans
Cross-sectional studies are studies that measure exposure and disease at one point in time. These provide weaker evidence than longitudinal studies, since the disease may potentially affect the exposure, and not vice versa.
U.S. and Canada
A survey of farmers from Saskatchewan, Canada, found that men who worked with insecticides had an increased risk of diabetes as compared to farmers who did not work with insecticides. On the other hand, overall, living on a farm was associated with a decreased risk of diabetes (as compared to other rural residences), probably due to the outdoor lifestyle (Dyck et al. 2013). A follow-up study, however, found a higher risk of diabetes among farmers, especially insecticide users (Alam et al. 2020).
During the 1980s and 1990s in the northern U.S. Midwest, death rates from type 2 diabetes were higher in counties that had a higher level of spring wheat farming than in counties with lower levels of this crop. The herbicide 2,4-D is commonly used on this crop. A study compared people who have had a previous exposure to 2,4-D to those who had non-detectable levels of exposure, and found that exposure to 2,4-D was associated with adverse changes in glucose metabolism, a possible predisposing factor for diabetes. The effects were only seen in people with low levels of HDL, the "good" cholesterol (Schreinemachers 2010).
In a large U.S. study, levels of certain organophosphate metabolites are associated with various aspects of the metabolic syndrome, including higher blood pressure, lower HDL ("good") cholesterol, and higher triglycerides in adults. The outcomes worsened in those with a higher BMI, and the specific outcome differed for different metabolites (Ranjbar et al. 2015). Also in U.S. adults, higher levels of the most common pyrethoid pesticide metabolite was associated with a higher risk of diabetes (Park et al. 2018). Note that pyrethoids are being used now as substitutes for organophosphates, but this study implies that they may not be safer at all (which is a common problem with replacement chemicals). In California, chronic pyrethroid exposure is associated with epigenetic changes in genes linked to a wide variety of diseases, including diabetes (Furlong et al. 2020).
Urinary levels of a dichlorophenol pesticide, 2,5-DCP, has been associated diabetes in U.S. adults (Wei and Zhu 2016a), with obesity in U.S. children (Twum and Wei 2011), BMI and other measures of adiposity in US girls (Deierlein et al. 2017), obesity in U.S. adults (Wei et al. 2014), and with metabolic syndrome in U.S. adults without diabetes (Wei and Zhu 2016b). Both dichlorophenol pesticides, 2,4-DCP and 2,5-DCP, were associated with body weight measures (BMI, waist circumference, and obesity) in U.S. adolescents (Buser et al. 2014). In U.S. children and adolescents, of 9 chemicals studied using a few different statistical methods, 2,5-DCP was one that was most strongly associated with an increased risk of obesity (Wu et al. 2020).
The biocide acrolein was associated with insulin resistance in a large U.S. database (NHANES) (Feroe et al. 2016). Also in NHANES, parabens, antimicrobial preservatives, were associated with lower measures of weight in adults and children (Quirós-Alcalá et al. 2018).
In NHANES, re neonicotinoid pesticides, imidacloprid was associated with lower fasting insulin levels and lower insulin resistance. Acetamiprid was associated with higher glucose in males and lower glucose in women, as was imidacloprid with HbA1c (Vuong et al. 2021).
Eating Organic Food Lowers Pesticide Exposure
Metabolites of the pesticides malathion (MDA, top) and chlorpyrifos (TCPY, bottom) decreased when children began eating organic food, and increased when conventional food was resumed. (The top numbers on the x-axis are the number of children, and the bottom numbers are the day) (Lu et al. 2006, EHP).
Additional studies have also found that eating organic food reduces pesticide levels, including in pregnant women (Curl et al. 2019).
Central and South America
In Mexico, there were variations in blood sugar and cholesterol levels that varied by pesticide exposure level in obese/overweight urban workers who spray organophosphate pesticides (Molina-Pintor et al. 2020). Brazilian farmers had higher glucose levels than those unexposed to agricultural pesticides (Cestonaro et al. 2020). Comparing pesticide sprayers with unexposed controls in Bolivia, exposure to the pyrethroid pesticides was associated with pre-diabetes and higher blood glucose levels (HbA1c) in the sprayers (Hansen et al. 2014). Children who live near flower plantations in Ecuador have higher blood pressure than those who live farther away (Suarez-Lopez et al. 2018).
Staff of an Australian insecticide application program had higher mortality rates for diabetes, as compared with the general Australian population, especially those reporting occupational use of herbicides (Beard et al. 2003).
French adults who ate more organic food (and therefore likely to have lower pesticide exposures) were less likely to have metabolic syndrome (Baudry et al. 2018) and have a lower BMI (Baudry et al. 2019) (although this could be due to other related lifestyle factors as well).
Asia and Africa
Among Korean farmers, exposure to pesticides was associated with diabetes, and this association was stronger in overweight or obese individuals than in normal weight individuals (Park et al. 2018).
In Chinese women, levels of organophosphate metabolites were higher in those with a higher body mass index (BMI) (Chen et al. 2019). Long-term exposure to organophosphorous pesticides are linked to an increased risk of type 2 diabetes in China, especially in people with certain genes (Dong et al. 2019).
In Thai farmers, lifetime exposure to numerous pesticides was associated with diabetes prevalence. The pesticides included the organophosphate pesticide mevinphos, the carbamate carbaryl (Sevin), the fungicide benlate, rodenticides, and the organochlorine pesticide endosulfan (a persistent organic pollutant) (Juntarawijit and Juntarawijit 2018). Comparing organic farmers to conventional farmers (who use pesticides), another study of Thai farmers found that conventional farmers had significantly higher body mass index, waist circumference, body fat percentage, and levels of triglycerides, total cholesterol, and LDL cholesterol as compared to organic farmers (although some lifestyle factors were also different, e.g., smoking, exercise, etc.) (Kongtip et al. 2018). However, another Thai study found no association between insulin resistance and levels of organophosphate pesticide exposure (Seesen et al. 2020).
In Nepali subsistence farmers, who have low use of pesticides, there was a lower risk of diabetes among those who reported using any pesticides vs those who used some pesticides. Due to study limitations, there is likely no increased risk in any case (Hansen et al. 2019). In Indian rural farmers, organophosphate pesticide levels were associated with an increased risk of diabetes, with evidence of possible synergism between these pesticides and arsenic (Velmurugan et al. 2020).
Farmers in India exposed to pesticides have a higher risk of diabetes than those unexposed (Jamal et al. 2016). A study from rural India (mostly of farmers, who can be exposed to metals in fertilizers), found no association between diabetes and traditional risk factors such as body mass index, blood pressure and total cholesterol, but did find associations between diabetes and metals. Also in India, arsenic and other heavy metals were associated with diabetes, and arsenic and zinc were associated with pre-diabetes and atherosclerosis (Velmurugan et al. 2018).
Another study from rural India shows a high prevalence of diabetes in people directly exposed to organophosphates, as well as higher long-term blood glucose (HbA1c) levels. The authors also show that these pesticides affect the gut microbiota, and confirm these findings in animal studies. They conclude that the pesticides degrade the gut microbiota and thereby cause high blood glucose levels and diabetes (Velmurugan et al. 2017).
In Myanmar, higher organophosphate pesticide exposure was associated with higher insulin resistance (Pwint Phyu et al. 2020).
In Pakistan and Cameroon, organophosphate pesticide exposure was associated with an increased risk of diabetes, and dysregulation of insulin, blood sugar, adiponectin, and triglyceride levels (Leonel Javeres et al. 2020). Exposure was also linked to a higher BMI, higher insulin and blood glucose levels, dyslipidemia and hypertension (Leonel Javeres et al. 2021).
Egyptian farmers (without diabetes) with higher levels of malathion in their blood had higher insulin resistance, waist circumference, and body mass index (BMI). Not surprisingly, the farmers, who had been working with pesticides for 15-20 years, had higher levels of malathion in their blood than the comparison group who were not farmers (Raafat et al. 2012).
Pesticides may contribute to the growing rates of diabetes in sub-Saharan Africa. People in these countries may be more susceptible to the effects of pesticides due to a variety of factors, such as undernutrition, lack of access to health care, genetic predisposition, high exposure levels, and exposure during developmental periods, such as in the womb and during childhood (Azandjeme et al. 2013).
Three of four chlorophenol pesticides, 2,5-DCP, 2,4-DCP, and 2,4,5-TCP (but not 2,4,6-TCP) showed various associations with various measures of obesity in Iranian children and teens (Parastar et al. 2018).
A study of Iranian farmers showed that they had higher blood glucose levels (both fasting and after a glucose tolerance test), as well as neurological symptoms such as depression, as compared to a comparison group who were not exposed (Malekirad et al. 2013). Also in Iran, there was no association between pesticide exposure and type 2 diabetes in adults, based on a questionairre (Sharafi et al. 2021).
Pesticide Poisonings in Humans
There are case studies documented in the scientific literature of people who developed high blood sugar and what was thought to be diabetic ketoacidosis immediately after consuming pesticides (e.g., in a suicide attempt). For example:
A 15-year old girl, distressed from poor exam results, ingested an organophosphorous pesticide. Ten hours later, in the hospital, she had very high blood sugar levels and ketones in her urine, signs of diabetes. By the second day of treatment, however, her glucose levels were normal, and remained normal 4 weeks later. Pesticide poisoning can be misdiagnosed as diabetes due to some of the same symptoms (Swaminathan et al. 2013).
A 12-year old boy, who consumed 4 unwashed tomatoes in a field (in India), landed in a hospital and was thought to have ketoacidosis; it turned out he had pesticide poisoning, probably from the tomatoes (Kumar and Nayak, 2011; full text).
In a group of 23 Indian patients with pesticide poisoning, 69% had glucose in the urine, and 38% of those had high glucose levels as well (none had pre-existing diabetes) (Shobha and Prakash, 2000).
A 30-year old man ate and injected himself with a mixture of chlorpyrifos and cypermethrin in a suicide attempt. He developed high blood sugar and ketoacidosis (as well as stroke and other problems) (Badrane et al. 2014).
A girl in Ecuador who developed hyperglycemic ketoacidosis after coming in contact with an organophosphate pesticide (Vélez et al. 2016).
A 47-year old woman had total pancreatic failure after ingesting an organophosphate pesticide, and required insulin afterwards (Hou et al. 2018).
A larger study, of 184 people without diabetes who had been poisoned by organophosphate pesticides, found that 121 of them had high blood sugar levels when hospitalized. Those with the highest glucose levels had the highest risk of death. However, the fatality risk varied based on which type of pesticide it was (Moon et al. 2016). These cases present a challenge for endocrinologists (Shahid et al. 2014). A large study from India found that, of 100 people (without diabetes) who were poisoned with organophosphorous insecticides, 37% had low blood sugar, and 11% had high blood sugar, and that both groups had a high risk of mortality (Raghapriya et al. 2018).
However, acute, large-dose organophosphate pesticide poisonings, while increasing blood glucose and ketone levels in the short run, seem to resolve relatively quickly, and do not seem to trigger diabetes in the first month or so (although longer-term follow-up studies are needed). Nor does prior diabetes increase the risk of mortality from these poisonings, at least in one study from Taiwan (Liu et al. 2014). Follow-up from Sri Lanka and Bangladesh finds that the glucose dysregulation caused by pesticide poisonings tended to resolve in 3-12 months (Gifford et al. 2018).
Researchers are looking into substances that may be protective against the diabetes-related effects of acute pesticide exposures (da Luz Abreu et al. 2019).
Laboratory Studies: Diabetes/Obesity
A number of organophosphate pesticides have been found to disrupt beta cell function, including malathion (Hectors et al. 2011). Animals exposed to malathion develop high blood sugar levels, and their carbohydrate metabolism is affected in ways that could promote insulin resistance (Rezg et al. 2007; Rezg et al. 2010). In fact, more recent studies shows that malathion does indeed produce insulin resistance in adult rats, in addition to high blood sugar levels (Lasram et al. 2014), high insulin levels, and high HbA1c, whereas an anti-oxidant protects against these effects (Lasram et al. 2015). Acute exposure to malathion causes transitory high blood glucose in rats accompanied by glucagon depletion, implying that the malathion caused the liver to release its sugar stores, raising blood sugar levels. Triglycerides and LDL (the "bad" cholesterol) were also increased (Lasram et al. 2009). Both acute and chronic exposures to malathion increased blood glucose and insulin secretion in rats. The higher insulin levels were not enough to overcome the high blood sugar levels (Panahi et al. 2006). In another study, exposure to malathion increased blood glucose and insulin levels in rats, as well as decreased glycogen levels in the liver. Malathion also increased insulin resistance in these rats, which continued one month after exposure ended (Lasram et al. 2014b). A meta-analysis of 8 rat studies on malation found that blood glucose levels were over 3 times higher in exposed rats exposed than in controls, and the effect of malathion on blood glucose concentration showed a non-monotonic dose-response curve (Ramirez-Vargas et al. 2018).
A meta-analysis of data from 7 animal studies found that exposure to low doses of chlorpyrifos significantly increased blood glucose levels in exposed animals compared to unexposed animals, and high doses markedly decreased blood glucose levels in exposed rats versus the unexposed (Farkhondeh et al. 2019).
Exposure to low doses of chlorpyrifos for 2-4 weeks resulted in high blood glucose levels in rats (Lukaszewicz-Hussain, 2013). Short-term acute exposure-- a single dose-- raised blood glucose, LDL and triglyceride levels in rats as well (Acker and Noqueria 2012). Chronic exposure to chlorpyrifos also increased body weight in mice (Peris-Sampedro et al. 2015a); the same authors found that certain genes seem to increase susceptibility to the effects of chlorpyrifos (including increasing insulin resistance, blood sugar levels, food ingestion, and cholesterol levels) (Peris-Sampedro et al. 2015b). Researchers are working further to identify the mechanisms involved (Basaure et al. 2019; Peris-Sampedro et al. 2018; Wang et al. 2021). Chlorpyrifos reduces glucose uptake in muscle cells, which would lead to insulin resistance (Shrestha et al. 2018). In cells, chlorpyrifos and its metabolite increased the number of fat cells, and enhanced their capacity to store fat (Blanco et al. 2020). Advanced age may increase susceptibility to chlorpyrifos-induced disturbances, including high glucose levels and inflammation, as seen in lab animals (Samarghandian et al. 2020).
Even in fish, chlorpyrifos raised blood glucose levels and reduced levels of glycogen in the liver (Majumder et al. 2018). Chronic exposure also affects the gut microbiota, and reduces insulin levels in rats (Fang et al. 2018). Chlorpyrifos caused broken integrity of the gut barrier, leading to low-grade inflammation, weight gain, and insulin resistance in mice. Genetic background and diet had only limited influence on the results (Liang et al. 2019). Exposure to chlorpyrifos affected the gut microbiota in rats whether they were exposed after weaning or during adulthood, but the earlier exposures led to more severe effects (Li et al. 2019); early-life pre-weaning but post-natal exposure to chlorpyrifos affects the gut microbiome of rats as well (Perez-Fernandez et al. 2020). Genetic background plays a role in the specific effects of chlorpyrifos on the gut microbiota (Guardia-Escote et al. 2019). In zebrafish, chlorpyrifos affected gut microbiota and the liver, in pathways linked to glucose metabolism (Wang et al. 2019). Researchers have also found that giving the prebiotic inulin, which helps support gut microbiota, can actually correct the metabolic effects of early life exposure to chlorpyrifos in lab animals (Reygner et al. 2016). Similarly, giving alpha-lipoic acid protects against the metabolic effects of long-term exposure to a combination of chlorpyrifos and deltamethrin (Uchendu et al. 2017). Meanwhile retinoic acid (vitamin A, which promotes cell development) increases the development of stem cells into fat cells caused by chlorpyrifos (Sandhu et al. 2017). And obesity makes the effects of chlorpyrifos worse (Kondakala et al. 2017). Vitamin E, meanwhile, can only slightly reduce the diabetes-related effects of the pesticide phoxim in rats (the increase in glucose, insulin, and cholesterol levels, and increased insulin resistance) (Zhang et al. 2017). But vitamin E does help protect cells against the immunotoxic effects of deltamethrin (Kumar et al. 2019). (Deltamethrin also causes obesity-related effects in the lab (Yuan et al. 2019)).
Long-term exposure of rats to monocrotophos led to glucose intolerance, insulin resistance, high blood sugar, more fatty tissue, higher liver cholesterol and triglyceride levels, and other metabolic effects (Nagaraju et al. 2020a; Nagaraju et al. 2020b; Nagaraju et al. 2015). The same authors found that the exposed rats had increased beta cell function as a result (Nagaraju and Rajini 2016).
Animals exposed to diazinon, another organophosphate pesticide, were found to have impaired glucose tolerance and lower insulin levels (Pakzad et al. 2013). Diazinon has also been found to cause the liver to release glucose into the blood in rats, supporting the idea that diazinon exposure may predispose people to diabetes (Teimouri et al. 2006). Diazinon caused high blood glucose levels, worsened cholesterol levels, increased inflammation, and impaired liver and kidney function in both adult and aged rats (Yousefizadeh et al. 2019). Diazinon also increases fat storage in fat cells (Smith et al. 2018). In rats, diazinon caused increased fat cell size and more fat accumulation (Nili-Ahmadabadi et al. 2019). In mice, exposure to diazinon affects the gut microbiome, which is linked to diabetes and obesity (see the Diet and the Gut page) (Gao et al. 2017). In fish, glucose levels rise after exposure to diazinon (Ghasemzadeh et al. 2015). A review summarizes the many potential molecular mechanisms involved in how organophosphorous pesticides can contribute to insulin resistance and type 2 diabetes (Lasram et al. 2014b). Other researchers have found substances that protect rats from the beta cell damage caused by diazinon (Khaksar et al. 2017).
Dimethoate, another organophosphate pesticide, raises high glucose and lowers insulin levels in rats, and is known to be toxic to the pancreas. Some of these effects are reversed by fenugreek (Mesallam et al. 2018).
Dichlorvos, another organophosphorus pesticide, causes changes in energy metabolism genes in zebrafish (an animal used to test for toxic effects) (Bui-Nguyen et al. 2015). Diethyl phosphate (DEP), a metabolite of organophosphorus pesticides, affects the gut microbiota in rats (Yang et al. 2019). The organophosphorus pesticide trichlorfon damages the intestinal barrier, triggers inflammation, and alters the gut microbiota of fish (Chang et al. 2019). Prenatal exposure to the orgophosphate herbicide glufosinate disturbs the gut microbiome and metabolism in mice (Dong et al. 2020).
Various pesticides found on food as residues may alter gut barrier function (Guibourdenche et al. 2021).
A screening study found that the organophosphorus pesticides diazinon, phoxim, terbufos, and tolclofos-methyl might have obesogenic effects because they interact with the estrogen receptor (Kim et al. 2021).
Long term, low dose exposure to the herbicide atrazine resulted in increased body weight and increased insulin resistance in rats. Those rats that were exposed and also ate a high-fat diet showed exacerbated weight gain and insulin resistance (Lim et al. 2009). Fish exposed to atrazine developed high blood glucose levels-- the higher the dose, the higher the glucose. Seven days after the exposure was removed, blood glucose levels went back to normal. (Other studies have found this same pattern in fish exposed to other pesticides as well) (Blahova et al. 2014). Mice treated with the low dose (the 'no observed effect' level) of atrazine during puberty showed increased total and cumulative weight gain (Cook et al. 2019).
A fungicide, tolylfluanid, used in paint and on fruit crops, commonly detected in Europe, has been shown to promote the formation of fat cells as well as induce insulin resistance in fat cells. These findings raise a concern that this chemical, an endocrine disruptor, could disrupt metabolism and contribute to the development of diabetes (Sargis et al. 2012). Further investigation shows that tolylfluanid alters fat cell function by activating the glucocorticoid receptor, which plays an important role in controlling metabolism. This mechanism may be a new way that chemicals could promote metabolic diseases such as diabetes and obesity (Neel et al. 2013). Mice exposed to tolylfluanid had more weight gain, higher total fat mass, glucose intolerance, and increased insulin resistance (Reginer et al. 2015). Other authors found different effects, and were unable to repeat some of these earlier findings (Chen et al. 2018). However, it may be that this difference is because the effects were dependent on diet. The original authors subsequently found differing effects depending on what the mice were fed. In those fed a high-fat high-sucrose diet, tolyfluanid promoted glucose intolerance, while weight gain and insulin sensitivity were unchanged, and visceral fat was reduced. With a high-sucrose diet, tolyfluanid increased visceral fat, while glucose tolerance and insulin sensitivity were unchanged, and weight gain was reduced (Reginer et al. 2018). Tolyfluanid also affects skeletal muscle cells in ways that could promote insulin resistance (Davis et al. 2018).
Fungicide Causes Insulin Resistance
Dr. Robert Sargis, University of Illinois at Chicago, researches how a fungicide alters metabolism and may contribute to diabetes and obesity in rodents.
When researchers exposed fat cells to imidacloprid, a neonicotinoid insecticide (now restricted in Europe due to bee colony collapse disorder), they found that there was increased fat accumulation in these cells (Park et al. 2013). Screening a number of neonicotinoids for their effects, only imidacloprid showed effects related to fat accumulation (Mesnage et al. 2018). When researchers exposed fat, liver, and muscle cells to this insecticide, they found that there was increased insulin resistance. Essentially, the exposed cells did not take up as much glucose as unexposed cells did (Kim et al. 2013). It also promotes high-fat diet induced obesity and insulin resistance in both male and female mice (Sun et al. 2017). It rats, it caused high blood glucose levels, especially if exposure occurred during development, and affected the pancreas (Khalil et al. 2017). Exposure of pregnant mice to the neonicotinoid insecticide nitenpyram resulted in decreased levels of serum triglycerides, total cholesterol, and glucose in female offspring, as well as gut microbiota disturbances (Yan et al. 2020). Imidacloprid also affect the gut, affecting the gut microbiota and impairing the gut barrier (Yang et al. 2020). In pancreatic cells, the neonicotinoid insecticide acetamiprid decreased cell viability in a dose-dependent manner (Kara et al. 2020). Acetamiprid and chlorfenapyr affected the gut microbiota of mice, and treating those changes fixed the associated metabolic problems as well (Liu et al. 2021).
The commonly used fungicide pyraclostrobin increases triglyceride accumulation and disrupts metabolism, according to a study of fat cells (Luz et al. 2018). In rats, the fungicide mancozeb increased triglycerides and total cholesterol levels and decreased glucose levels, whereas withdrawal improved these measures (Yahia et al. 2019).
In amphibians, four of six widely-used pesticides induced high blood glucose levels, and the other two induced low blood glucose levels, while almost all decreased cholesterol levels (Paunescu et al. 2018).
Permethrin, an pyrethoid insecticide used as an insect repellent, impairs glucose homeostasis and alters fat cell development in laboratory studies (Kim et al. 2014), and reduces glucose uptake from muscle cells (Sun et al. 2017). It can cause insulin resistance, and raises glucose and insulin levels in mice, even without raising weight or fat mass (Xiao et al. 2017a), but can also cause weight gain as well (Xiao 2017b). Another study by the same authors sums it up: permethrin increased body weight, fat mass, and insulin resistance with a high fat diet, but not with a low fat diet-- without influencing the amount of food eaten. Permethrin also increased insulin, glucose, leptin, triglycerides, and cholesterol levels (Xiao et al. 2018). Also, early life exposure to permethrin leads to low vitamin D levels in adult offspring (Fedeli et al. 2013); vitamin D deficiency is linked to diabetes. In cells, the pyrethoid pesticide bifenthrin causes effects that are linked to obesity (Xiang et al. 2018). In mice, long-term exposure to low doses of bifenthrin induces fat deposition (Wei et al. 2019). In rats, bifenthrin increased inflammation, and total and LDL cholesterol levels. These effects were prevented by vitamin E and selenium (Feriani et al. 2018).
One pesticide, TFM, is used to kill sea lampreys (an invasive species) in the Great Lakes. One of the ways is works is by affecting glycogen levels in the lampreys, disturbing energy metabolism (curiously, adults are more susceptible to these effects) (Henry et al. 2015). Also in aquatic ecosystems, pesticide mixtures, in combination with temperature-induced stress, causes fish to have decreased production of glucose by the liver, and affected protein, lipid, and carbohydrate metabolism (Gandar et al. 2017).
The herbicide imazamox caused beta cell death and reduced islet size, increasing glucose levels in rats (Sevim et al. 2018).
Exposing fish to glyphosate (Roundup), at levels found in water bodies, affects glucose, glycogen, cholesterol, and triglyceride levels (de Moura et al. 2017). Glyphosate also altered pancreatic function in rats, leading to higher insulin and glucose levels (Tizhe et al. 2018). Glyphosate also altered gut microbiota and caused gut inflammation in rats (Dechartres et al. 2019; Tang et al. 2020), increased oxidative stress in the intestine of piglets (Qiu et al. 2019), and caused inflammation in fat tissue and liver in rats, suggesting the development of non-alcoholic fatty liver disease (NAFLD) (Pandey et al. 2019).
Of the pesticides glyphosate, 2,4-D, dicamba, mesotrione, isoxaflutole, and quizalofop-p-ethyl (QpE), only QpE caused triglyceride accumulation in fat cells. The QpE commercial formulation Targa Super was 100 times more toxic to cells than QpE alone (Biserni et al. 2019). In mice, perinatal glyphosate exposure combined with a high-fat diet in adulthood increases the risk of intestinal inflammation and dysfunction (Panza et al. 2021).
In rats, exposure to the fungicide flutriafol induced fat accumulation in the liver (Kwon et al. 2021).
Environmentally relevant levels of the fungicide boscalid inhibited the growth of adult zebrafish, induced damage in the kidneys and liver, increased glycogen and insulin in the liver, decreased triglyceride and cholesterol levels in the liver, and decreased blood glucose levels (Qian et al. 2019).
Exposure to the pesticide penconazole caused disorders in the gut microbiota in mice (Meng et al. 2019). The fungicide thiram disturbed the balance of the gut microbiota, and affected liver function and cholesterol levels in chickens (Kong et al. 2020).
Exposure During Development
Early life exposure to organophosphate pesticides causes metabolic dysfunction resembling pre-diabetes in animals, especially when adults eat a high-fat diet (Slotkin 2011). Male rats exposed to the organophosphate pesticide chlorpyrifos just after birth, showed high insulin levels when not fasting as adults that resembles the metabolic pattern seen in type 2 diabetes in humans (Slotkin et al. 2005). In zebrafish larvae, chlorpyrifos exposure affected lipid metabolism, including altering the transcription of genes linked to glucose levels (Wang et al. 2019). Early life exposure to the organophosphate insecticide acephate caused the offspring to be susceptible to type 2 diabetes in adulthood, and also affects the mother's glucose metabolism (Riberio et al. 2016).
Flies exposed to atrazine during development display insulin resistance, while those exposed to dichlorvos (an organophosphorus pesticide) show insulin deficiency (which the authors label "type 1 diabetes," but it's not really autoimmune type 1) (Gupta et al. 2019).
Early Life Pesticide Exposures Can Contribute to Diabetes and Obesity in Adults
See Childhood Exposures to Pesticides May Contribute to Obesity and Diabetes in Adults, Research Brief 185, by the National Institute of Environmental Health Sciences.
Male rats exposed to low doses of the organophosphate pesticide parathion just after birth showed high blood glucose levels and increased weight gain later in life (Lassiter et al. 2008). These authors point out that animals exposed to organophosphates as adults show increased weight gain and other diabetes-like changes. Exposures in early development may be even more significant. A further study by the same authors found that unlike chlorpyrifos and malathion, the effects of early life parathion exposure in rats lessened by adolescence, although other changes occur later that affect glucose utilization. The effects of parathion were not worsened by a high fat diet, but the effects of this diet and parathion were similar to each other (Adigun et al. 2010).
Gestational exposure to imidacloprid and chlorpyrifos induces high blood sugar and insulin resistance and negatively affects cholesterol levels in female rats as well as their offspring. The effects on offspring persist until adulthood (Ndonwi et al. 2020).
In mice, chronic prenatal exposure to glyphosate (Roundup) caused lipid metabolism disruption in offspring, including higher triglyceride and cholesterol levels (Ren et al. 2019).
When pregnant mice were exposed to very low levels (400-times below the EPA's "no observed adverse effect level") of triflumizole, a fungicide used on food and ornamental crops, their offspring had excess fatty tissue, as compared to unexposed controls. Triflumizole also caused stem cells and pre-fat cells to develop into fat cells (Li et al. 2012).
Early life exposure to another fungicide, vinclozolin, affects the development of fat cells (Boudalia et al. 2017), and causes higher body weight in offspring (Pietryk et al. 2018). Early life exposure to the fungicide difenoconazole causes adverse development in energy metabolism, amino acid metabolism, lipid metabolism, and the immune system (Teng et al. 2018). Difenoconazole also affects the gut microbiota, triglyceride levels, and gene expression of genes related to metabolism and diabetes (Jiang et al. 2020).
Gestational and lactational exposure to the fungicide tolylfluanid had contrasting metabolic effects in offspring later in life. Females had reduced glucose tolerance, lower insulin resistance, and lower weight, while males had impaired glucose tolerance (Ruiz et al. 2019).
Developmental exposure to a mixture of pesticides (boscalid, captan, chlopyrifos, thiachloprid, thiophanate, and ziram) did not affect body weight in mice, but did induce long-lasting changes in gut microbiota (Smith et al. 2020). Developmental exposure to the neonicotinoid insecticide nitenpyram also affects gut microbiota and increase intestinal inflammation in mice as well (Yan et al. 2020).
Exposure during development to the pyrethroid insecticide alpha-cypermethrin led to high glucose levels and higher triglycerides (Ghorzi et al. 2017). Another study found that low-dose exposure to alpha-cypermethrin during gestation causes an increase in body weight, glucose, and lipid levels not only in the offspring, but also in the mothers (Hocine et al. 2016).
Wild tadpoles collected in Sweden show unexplained higher body weight, similar to the effect other thyroid disrupting chemicals. While the researcher did not identify pesticides in the water the tadpoles were living it, perhaps they did not test for all pesticides, or there are other unknown reasons that could explain this (Carlsson 2019).
Atrazine exposure, beginning prenatally, affected metabolism in male mice (Harper et al. 2020).
Maternal exposure to the fungicide imazalil during pregnancy and lactation affected the intestinal barrier in multiple generations of mice. (Jin et al. 2020). Which leads us to...
Exposure to atrazine during development leads to changes that show up in the 2nd and 3rd generation down the line-- but which may not even show up in the 1st generation. These changes did not include diabetes or obesity-- but did affect body weight (making offspring more lean) (McBirney et al. 2017; Thorson et al. 2020). Fat cells from the great-grand offspring generation of rats ancestrally exposed to atrazine (or DDT) had different epigenetic signs than fat cells from control rats (King et al. 2019).
Exposure to the fungicide vinclozolin during development also didn't lead to changes in the first generation of offspring, but did lead to increased obesity in females in the 3rd generation of offspring (Nilsson et al. 2018). These effects can be transferred down the male or female line (Ben Maamar et al. 2019). A different study found that vinclozolin caused lifelong increased body weight in males (exposed paternally) of the 2nd generation (Krishnan et al. 2018).
Similarly, exposure to glyphosate (Roundup) during development also didn't lead to changes in the first generation of offspring, but did lead to obesity and other problems in the 2nd and 3rd generations (Kubsad et al. 2019).
Mixtures of Pesticides
One study analyzed potential long-term effects of early life exposure to a low dose mixture of six pesticides that individually cause low birth weight (cyromazine, MCPB, pirimicarb, quinoclamine, thiram, and ziram). Exposed male offspring displayed some degree of catch-up growth and there were altered leptin levels in both sexes, but there was no difference in insulin or glucagon levels, or in the liver or pancreas (Svingen et al. 2018).
A mixture of pesticides used in France impaired glucose and lipid metabolism in pregnant rats and their offspring (Bonvallot et al. 2018).
A year long exposure to doses around the acceptable daily intake of a mixture of thirteen common chemicals/pesticides caused an increase in appetite in rats (Docea et al. 2019).
Type 1 Diabetes
Only one study has looked at pesticide levels in people with type 1 diabetes. It found that Egyptian children with newly diagnosed type 1 diabetes had statistically significantly higher levels of the organophosphate pesticides malathion and profenofos in their blood than healthy controls (as well as numerous organochlorine pesticides, discussed on the persistent organic pollutants page). The percentage of children with detectable levels of organophosphates were also significantly different between those with type 1 and those without; the percentage was higher for malathion and lower for profenofos and chlorpyrifos-methyl (El-Morsi et al. 2012).
Pesticides are a food contaminant, as a result of their use in agriculture. Daily ingestion of low doses of diquat, an extensively used herbicide, induces intestinal inflammation in rats. The authors of this study suggest that repeated ingestion of small amounts of pesticides, as could be found in food, may have consequences for human health and may be involved in the development of gastrointestinal disorders (Anton et al. 2000). In mice, pre-treatment with a probiotic prevented intestinal permeability and gut microbiota changes that were caused by the pesticide diquat (Hao et al. 2021). A fungicide, carbendazim, reduces the richness and diversity of gut microbiota in mice (Jin et al. 2015). Chronic exposure to this fungicide not only changed the gut microbiota composition, but also increased fat levels, glucose levels, and triglyceride levels, and caused tissue inflammation in mice (Jin et al. 2018). It also caused changes to the liver that accompanied the gut microbiota changes in zebrafish (Bao et al. 2020).
Chlorpyrifos exposure during development affects the gut microbiota, impairs the intestinal lining, and stimulates the immune system of pup rats (Joly Condette et al. 2015). Another study also shows that chlorpyrifos affects gut microbiota, resulting in intestinal inflammation and abnormal intestinal permeability (Zhao et al. 2016). Intestinal disorders like these are common in people with type 1 diabetes (see the diet and the gut page for more studies on this topic). Interestingly, atrazine did not affect gut microbiota in frogs, however, the resistance to disease was affected by early life microbiota (Knutie et al. 2018). In adult zebrafish, however, atrazine did affect both intestinal microbiota and intestinal permeability (Chen et al. 2018). In mice, atrazine has detrimental effects on gut microbiota (Liu et al. 2021). Both chlorpyrifos and glyphosate altered the metabolism of gut bacteria, which could cause inflammation and an increased immune system response (Mendler et al. 2020). Yuan et al. (2019) review the effects of pesticides on gut microbiota; Román et al. (2019) review the effects of organophosphate pesticides on gut microbiota; Meng et al. (2020) review the interactions between gut microbiota, pesticides, and health effects; and Giambò et al. (2021) review the effects of pesticides on gut microbiota.
Organophosphate pesticides have been found to be toxic to the immune system in animals and sometimes humans (Galloway and Handy 2003). Humans chronically exposed to chlorpyrifos have also been found to have increased levels of autoantibodies (Thrasher et al. 2002). In animal studies, chlorpyrifos affects the immune system-- both stimulating and suppressing it (Noworyta-Głowacka et al. 2014). Another pesticide, carbaryl, causes inflammation and is toxic to the immune system, causing an unbalanced immune response that promotes autoimmunity in animals (Jorsaraei et al. 2014). Other pesticides are also known to affect the immune system, especially during development (e.g., Jiang et al. 2014). In farmers, lifetime exposure to some pesticides are linked to systemic autoimmunity (Parks et al. 2019).
A review on pesticides and immunotoxicity finds that there is some human and animal evidence indicates that some pesticides can affect the immune system. This evidence, however, is too sparse to be conclusive (Corsini et al. 2013). More research is ongoing (e.g., Lee et al. 2016).
In Uganda, children who were exposed to the carbamate pesticide bendiocarb in the womb had changes in their immune cells, such as decreased regulatory T cells-- cells that protect against autoimmunity (Prahl et al. 2021).
One chemical known to cause type 1 diabetes in humans is the now-banned rat poison Vacor. In the late 1970s, a few people tried to kill themselves by eating Vacor, and ended up with type 1 diabetes instead. Vacor destroys beta cells directly, but has also been found to be linked to type 1-related autoimmunity (Karam et al 1980).
U.S. women who mixed or applied pesticides to crops or repaired pesticide application equipment during the first trimester of pregnancy had a higher risk of developing gestational diabetes. In the women who reported agricultural exposure during pregnancy, the risk of gestational diabetes was associated with the use of four herbicides (2,4,5-T; 2,4,5-TP; atrazine; butylate) and three insecticides (diazinon; phorate; carbofuran) (Saldana et al. 2007).
In Canadian women, first-trimester levels of pesticides generally were not associated with gestational diabetes or impaired glucose tolerance during pregnancy. However women with higher levels of the organophosphate pesticides dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) had a lower risk of gestational diabetes. The authors propose that this could be because of increased fruit/vegetable consumption (which is also associated with higher pesticide levels) (Shapiro et al. 2016).
European women who ate organic food during pregnancy had a lower risk of gestational diabetes (as well as lower BMI) (Simões-Wüst et al. 2017).
Diabetes Management and Complications
Does pesticide exposure affect blood glucose control or the risk of complications in people with diabetes? Possibly.
Among U.S. children with diabetes, mostly type 1, those with higher levels of pesticides 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).
Diabetes is a risk factor for non-alcoholic fatty liver disease (NAFLD), which is associated with environmental chemical exposure, possibly specifically with pesticides (Armstrong and Guo, 2019; Yang and Park 2018). A search of the toxicological literature found that pesticides were among the most frequently identified chemicals associated with fatty liver in rodent studies. Of the 123 chemicals associated with fatty liver, 44% were pesticides-- especially fungicides and herbicides (Al-Eryani et al. 2015). Chlorpyrifos, for example, promotes fat accumulation in the liver (Howell III et al. 2016). Thiamethoxam, one of the major compounds of neonicotinoid insecticides, caused NAFLD in mice (Yang et al. 2021).
Some researchers have looked to see whether the pesticide diazinon affects rats with diabetes differently than rats without diabetes. An animal model of type 1 diabetes shows that diabetes increases the toxicity of diazinon (Ueyama et al. 2007). An animal model of type 2 diabetes shows that diazinon worsens glucose tolerance in these rats, leading to higher blood glucose levels (Ueyama et al. 2008).
The organophosphorous pesticide monocrotophos has been shown to exacerbate the complications in rats with chemically-induced type 1 diabetes, including raising glucose levels (Begum and Rajini, 2011), and causing intestinal dysfunction (Vismaya and Rajini, 2014).
Researchers are looking into whether pesticides play a role in the appearance of chronic kidney disease in agricultural workers around the world (Valcke et al. 2017). Occupational exposure to pesticides may also be linked to cardiovascular disease, but there is a large lack of research on this topic (Berg et al. 2019).
In addition, pesticides may affect both risk of diabetes and Alzheimer's Disease by common pathways (Paul et al. 2018).
To download or see a list of all the references cited on this page, as well as additional article on pesticides related to diabetes, see the collection Pesticides 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