Pesticide-Induced Diseases: Diabetes

According to the American Diabetes Association, diabetes is a group of diseases characterized by high blood glucose levels that result from defects in the body’s ability to produce and/or use insulin. Type 1 diabetes is usually diagnosed in children and young adults. In type 1 diabetes, the body does not produce insulin. Type 2 diabetes is the most common form of diabetes and is most common in communities of color and the aged population. In type 2 diabetes, either the body does not produce enough insulin or the cells ignore the insulin. Pesticides and other environmental factors are almost always linked to type 2 diabetes.

  • Exposure to DDT and diabetic nephropathy among Mexican Americans in the 1999-2004 National Health and Nutrition Examination Survey.
    Concentrations of the pesticide DDT (dichlorodiphenyltrichloroethane) and its metabolite DDE (dichlorodiphenyldichloroethylene), in the blood of Mexican Americans, were evaluated to determine their relationships with diabetes and diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted N = 1,411, population estimate = 13,760,609). The sample included teens, 12-19 years old, which accounted for 19.8% of the data. The time of the study overlapped the banning of DDT in Mexico in the year 2000, and those participants born in Mexico were exposed to DDT before they immigrated to the US. We sought to better understand the relationship of DDT with diabetes in a race/ethnicity group prone to develop diabetes and exposed to DDT. In this study, nephropathy was defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria, and total diabetes was defined as diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥ 6.5%). The proportion with the isomer p,p'-DDT >0.086 ng/g (above the maximum limit of detection) was 13.3% for Mexican Americans born in the US, and 36.9% for those born in Mexico. Levels of p,p'-DDT >0.086 ng/g were associated with total diabetes with nephropathy (odds ratio = 4.42, 95% CI 2.23-8.76), and with total diabetes without nephropathy (odds ratio = 2.02, 95% CI 1.19-3.44). The third quartile of p,p'-DDE (2.99-7.67 ng/g) and the fourth quartile of p,p'-DDE (≥7.68 ng/g) were associated with diabetic nephropathy and had odds ratios of 5.32 (95% CI 1.05-26.87) and 14.95 (95% CI 2.96-75.48) compared to less than the median, respectively, whereas p,p'-DDE was not associated with total diabetes without nephropathy. The findings of this study differ from those of a prior investigation of the general adult US population in that there were more associations found with the Mexican Americans sample.
    [Everett CJ, Thompson OM, Dismuke CE. Environ Pollut. 222:132-137.]
  • Persistent organic pollutants and risk of diabetes and obesity on healthy adults: Results from a cross-sectional study in Spain.
    Environmental exposure to persistent organic pollutants (POPs) has been reported to be relevant in the population of the Canary Islands (Spain), especially that of organochlorine pesticides. On the other hand, the population of this archipelago presents a high prevalence of type 2 diabetes (T2D), and it has been recently reported that environmental chemical contamination could play a role in the development of this disease. Researchers performed a cross-sectional study in a representative sample from this archipelago to evaluate whether serum levels of selected POPs could be considered as risk factors for diabetes in this population. Serum levels of 30 POPs were determined in 429 adults (9.3% with T2D). Serum levels of p,p'-DDE (DDE), PCB-153 and PCB-118 were significantly higher among subjects having diabetes than in non-diabetic subjects (p=0.001, p=0.046, and p<0.0001, respectively). A positive correlation between serum p,p'-DDE and glucose levels was observed. Serum p,p'-DDE was identified as a risk factor for diabetes in univariate analysis in the whole series, and it remained as an independent risk factor for diabetes in subjects with serum glucose <126mg/dL (multivariate analysis, Exp(B)=1.283, CI 95% (1.023-1.611), p=0.031). Those normoglycemic subjects that are most exposed to p,p'-DDE (95th percentile: serum p,p'-DDE>5μg/L) seem to be those people at higher risk. Results showed that p,p'-DDE levels were significantly higher among subjects having diabetes. These findings should be considered by public health Authorities to implement measures devoted to minimize human exposure to pollutants that could be harmful to the population.
    [Henríquez-Hernández LA, Luzardo OP, Valerón PF, et al. 2017. Sci Total Environ. 607-608:1096-1102.]
  • Persistent organic pollutants in early pregnancy and risk of gestational diabetes mellitus.
    Persistent organic pollutants (POPs) are a group of diverse substances, including polychlorinated biphenyls (PCBs) and organochlorine pesticides that are resistant to biodegradation and ubiquitously present in our environment. Exposure to endocrine disrupting chemicals such as POPs has been linked to type 2 diabetes and metabolic disturbances in epidemiological and animal studies, but little is known about POPs exposure during pregnancy and the development of gestational diabetes mellitus (GDM). The purpose of this study was to determine the extent to which exposure to current low levels of different POPs in the first trimester of pregnancy is associated with GDM risk in 939 women from the "Rhea" pregnancy cohort in Crete, Greece. Concentrations of several PCBs, dichlorodiphenyldichloroethene (DDE), and hexachlorobenzene (HCB) were determined in first trimester maternal serum by triple quadrupole mass spectrometry. Pregnant women were screened for gestational diabetes mellitus (GDM) between 24 and 28weeks of gestation, and GDM was defined by the criteria proposed by Carpenter and Coustan. Of the 939 women, 68 (7%) developed GDM. Serum concentrations of POPs were higher in women with GDM. Women in the medium and high tertiles of PCBs had 3.90 (95% CI: 1.37, 11.06) and 3.60 (95% CI: 1.14, 11.39) fold respectively higher odds of developing GDM compared to women in the lowest tertile of PCB exposure after adjusting for pre-pregnancy BMI and several other confounders. Odds of GDM for women in the medium and high tertiles of dioxin-like PCBs was 5.63 (95% CI: 1.81, 17.51) and 4.71 (95% CI: 1.38, 16.01) and for nondioxin-like PCBs 2.36 (95% CI: 0.89, 6.23) and 2.26 (95% CI: 0.77, 6.68) respectively. Prenatal DDE and HCB exposure were not significantly associated GDM risk.These findings suggest that women with high PCBs levels in early pregnancy had higher risk for GDM. Further studies are needed to replicate these results and to evaluate potential biological mechanisms underlying the observed associations.
    [Vafeiadi M, Roumeliotaki T, Chalkiadaki G, Rantakokko P, et al. Environ Int;98:89-95]
  • Adulthood dietary exposure to a common pesticide leads to an obese-like phenotype and a diabetic profile in apoE3 mice.
    Increasing evidence links the widespread exposure to organophosphate (OP) pesticides to the global epidemics of type 2 diabetes and obesity. Recent data highlighted gene×environment interactions: mice expressing the human apolipoprotein E3 (apoE3) isoform were more prone to develop obesity than those expressing apoE2 or apoE4 upon dietary challenge with chlorpyrifos (CPF), the most used OP worldwide. Study aimed to further explore the contribution of the APOE3 genotype on the emergence of obesity and related metabolic dysfunctions upon subchronic exposure to CPF. Seven-month-old targeted replacement apoE3 and C57BL/6N male mice were orally exposed to CPF at 0 or 2mg/kg body weight/day for 8 consecutive weeks. CPF exposure generally increased food ingestion, glucose and total cholesterol concentrations, and tended to elevate acyl ghrelin levels. Nonetheless, excess weight gain and increased leptin levels were inherent to apoE3 mice. Moreover, the propensity towards a diabetic profile was markedly higher in these animals than in C57BL/6N, as they showed a higher homeostatic model assessment for insulin resistance index and higher insulin levels. Although both genotypes were metabolically affected by CPF, the results of the present investigation revealed that apoE3 mice were the most vulnerable to developing obesity and related disturbances following CPF administration through the diet. Since the APOE3 genotype is the most prevalent worldwide, current findings have particular implications for human health.
    [Peris-Sampedro F, Cabré M, Basaure P, Reverte I, et al. 2015. Environ Res. 142:169-76]
  • Association of persistent organic pollutants and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia: A systematic review.
    Over half of the people with diabetes in the world live in Asia. Emerging scientific evidence suggests that diabetes is associated with environmental pollutants, exposures that are also abundant in Asia.
    The aim of this study was to systematically review the literature concerning the association of persistent organic pollutants (POPs) and non-persistent pesticides with diabetes and diabetes-related health outcomes in Asia.A total of 19 articles met the inclusion criteria and were evaluated in this review.To date, the evidence relating POPs and non-persistent pesticides with diabetes in Asian populations is equivocal. Positive associations were reported between serum concentrations of polychlorinated dibenzodioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs), and several organochlorine pesticides (DDT, DDE, oxychlordane, trans-nonachlor, hexachlorobenzene, hexachlorocyclohexane) with diabetes. PCDD/Fs were also associated with blood glucose and insulin resistance, but not beta-cell function. There were substantial limitations of the literature including: most studies were cross-sectional, few studies addressed selection bias and confounding, and most effect estimates had exceptionally wide confidence intervals. Few studies evaluated the effects of organophosphates.Well-conducted research is urgently needed on these pervasive exposures to inform policies to mitigate the diabetes epidemic in Asia.
    [Jaacks LM and Staimez LR. 2015. Environ Int. 76:57-70]
  • Persistent organic pollutants in young adults and changes in glucose related metabolism over a 23-year follow-up.
    Substantial evidence associates persistent organic pollutants (POP) with metabolic disturbances related to diabetes, but longitudinal studies with repeated measures are scarce. Study aimed to characterize the association between background exposures to POPs with repeated measures of glucose homeostasis over 23-years.Study measured POPs in serum obtained in 1987-88 (follow-up year 2) in 90 non-diabetic controls and 90 cases diabetes-free at year 2 who became diabetic by year 20. 32 POPs were detectable in ≥75% of participants and created summary scores for 32 POPs, 23 polychlorinated biphenyls (PCB), and 8 organochlorine pesticides (OCP). Dependent variables were measures of glucose homeostasis at years 0-25 (up to 8 examinations).The associations between the three summary scores and measures of glucose homeostasis were present for observations at ages 40-55 years, and particularly between 48-55 years. No associations were observed at younger ages.Glucose homeostasis may worsen after decades of exposure to PCBs and OCPs at background environmental levels, independent of BMI and after participants reached the 5th decade of life.
    [Suarez-Lopez JR, Lee DH, Porta M, et al. 2015. Environ Res. 137:485-94.]
  • Exposure to Organochlorine Pollutants and Type 2 Diabetes: A Systematic Review and Meta-Analysis
    Though exposure to organochlorine pollutants (OCPs) is considered a risk factor for type 2 diabetes (T2DM), epidemiological evidence for the association remains controversial. A systematic review and meta-analysis was applied to quantitatively evaluate the association between exposure to OCPs and incidence of T2DM and pool the inconsistent evidence. Quantitative estimates and information regarding study characteristics were extracted from 23 original studies. We retrieved 23 eligible articles to conduct this meta-analysis. OR (odds ratio) or RR (risk ratio) estimates in each subgroup were discussed, and the strong associations were observed in PCB-153 , PCBs , and p,p′-DDE based on a random-effects model. This meta-analysis provides quantitative evidence supporting the conclusion that exposure to organochlorine pollutants is associated with an increased risk of incidence of T2DM.
    [Tang M, Chen,K et al. 2014. PLoS One. 9(10): e85556.]
  • Is cumulated pyrethroid exposure associated with prediabetes? A cross-sectional study.
    Pyrethroids are a class of insecticides used widely for vector control programs. Acute pyrethroid poisoning is rare, but well documented, whereas effects of cumulative exposure are insufficiently described, including possible negative effect on glucose regulation. The objective of this study was to investigate an association between exposure to pyrethroids and abnormal glucose regulation (prediabetes or diabetes). A cross-sectional study was performed among 116 pesticide sprayers from public vector control programs in Bolivia and 92 nonexposed controls. Blood samples were analyzed for glycosylated hemoglobin (HbA1c), a measure of glucose regulation. No association was found between pyrethroid exposure and diabetes symptoms. The prevalence of abnormal glucose regulation (defined as HbA1c ≥ 5.6%) was 61.1% among sprayers and 7.9% among nonexposed controls, corresponding to an adjusted odds ratio for all sprayers of 11.8 [4.2-33.2] and 18.5 [5.5-62.5] for pyrethroid-exposed only. Among sprayers who had only used pyrethroids, a significant positive trend was observed between cumulative pesticide exposure (total number of hours sprayed) and adjusted OR of abnormal glucose regulation, with OR 14.7 [0.9-235] in the third exposure quintile. The study found a severely increased prevalence of prediabetes among Bolivian pesticide sprayers compared with a control group, but the relevance of the control group is critical. Within the spraying group, an association between cumulative exposure to pyrethroids and abnormal glucose regulation was seen. Further studies are needed to confirm this association.
    [Hansen MR, Jørs E, Lander F, et al. 2014. J Agromedicine. 19(4):417-26]
  • Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study
    Study ained to estimate associations between use of specific agricultural pesticides and incident diabetes in women. Researchers used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators and their spouses in Iowa and North Carolina. Data was limited analysis to 13 637 farmers' wives who reported ever personally mixing or applying pesticides at enrolment (1993-1997), who provided complete data on required covariates and diabetes diagnosis and who reported no previous diagnosis of diabetes at enrolment. Participants reported ever-use of 50 specific pesticides at enrolment and incident diabetes at one of two follow-up interviews within an average of 12 years of enrolment. Five pesticides were positively associated with incident diabetes: three organophosphates, fonofos, phorate and parathion; the organochlorine dieldrin; and the herbicide 2,4,5-T/2,4,5-TP. With phorate and fonofos together in one model to account for their correlation, risks for both remained elevated, though attenuated compared with separate models. Results are consistent with previous studies reporting an association between specific organochlorines and diabetes and add to growing evidence that certain organophosphates also may increase risk.
    [Starling AP, Umbach DM, Kamel F, et al. 2014. Occup Environ Med. 71(9):629-35]
  • Growing burden of diabetes in sub- saharan Africa: contribution of pesticides ?
    The diabetes burden is growing in Sub-Saharan Africa (SSA). The low overall access to health care has been documented to contribute to the high diabetes-related mortality. Due to economic, demographic, epidemiological and nutrition transitions in SSA, the growing prevalence of diabetes appears to be related to obesogenic lifestyles and the intergenerational impact of malnutrition in women of childbearing age. Both overnutrition and undernutrition have been associated with the development of diabetes and other chronic diseases. Africans are also suspected of being genetically predisposed to diabetes. According to existing data in developed countries, exposure to pesticides, particularly organochlorines and metabolites, is associated with a higher risk of developing type 2 diabetes and its comorbidities. In African countries, pesticide exposure levels often appear much higher than in developed countries. Furthermore, undernutrition, which is still highly prevalent in SSA, could increase susceptibility to the adverse effects of organic pollutants. Therefore, the growing and inadequate use of pesticides may well represent an additional risk factor for diabetes in SSA. Additionally, high exposure to pesticides in African infants in utero and during the perinatal period may increase the intergenerational risk of developing diabetes in SSA.
    [Azandjeme CS, Bouchard M, Fayomi B, et al. 2013. Curr Diabetes Rev. 9(6):437-49]
  • Pesticides and human diabetes: a link worth exploring?
    Traditionally, the risk factors for diabetes have largely focused on genetics and lifestyle. Great emphasis is placed on lifestyle measures and finding novel pharmacological treatment options to combat diabetes, but there is increasing evidence linking environmental pollutants, especially pesticides, to the development of insulin resistance and Type 2 diabetes. Pesticide use has increased dramatically worldwide and the effects of pesticides on glucose metabolism are too significant for a possible diabetogenic link to be dismissed. The aim of this review article was to assess the links between pesticides and human diabetes with the goal of stimulating further research in this area.
    [Swaminathan K. 2013. Diabet Med. 30(11):1268-71]
  • Sublethal exposures of diazinon alters glucose homostasis in Wistar rats: Biochemical and molecular evidences of oxidative stress in adipose tissues.
    Disorder of glucose homeostasis is one of the most important complications following exposure to organophosphorous (OPs) pesticides. The present study focused on tumor necrosis factor alpha (TNFα), glucose transporter type 4 (GLUT4), and nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB) in a sublethal model of toxicity by diazinon as a common OPs. Animals were treated for 4 weeks and serum insulin was measured in fasting condition. In adipose tissue, oxidative stress markers including reactive oxygen species (ROS), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and TNFα were evaluated. The mRNA expression of GLUT4, Nf-κB and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were also determined by real time reverse transcription polymerase chain reaction (RT-PCR). Diazinon at dose of 70mg/kg/day impaired GTT and diminished insulin level while augmented ROS, NADPH oxidase, and TNFα. On the basis of biochemical and molecular findings, it is concluded that diazinon impairs glucose homeostasis through oxidative stress and related proinflammatory markers in a way to result in a reduced function of insulin inside adipose tissue. Although, diazinon interfered with pancreatic influence on the adipose tissue most probably via stimulation of muscarinic receptors, current data are not sufficient to introduce adipose tissue as a target organ to OPs toxicity. Considering the potential of OPs to accumulate in adipose tissue, it seems a good candidate organ for future studies. Although, hyperglycemia was not induced by diazinon but increased AUC0-180min leads us to the point that diazinon induces kind of instability in glucose homostasis and diabetes.
    [Pakzad M, Fouladdel S, et al. 2013. Pestic Biochem Physiol. 105(1):57-61]
  • Does early-life exposure to organophosphate insecticides lead to prediabetes and obesity
    Researchers gave neonatal rats chlorpyrifos, diazinon or parathion in doses devoid of any acute signs of toxicity, straddling the threshold for barely-detectable cholinesterase inhibition. Organophosphate exposure during a critical developmental window altered the trajectory of hepatic adenylyl cyclase/cyclic AMP signaling, culminating in hyperresponsiveness to gluconeogenic stimuli. Consequently, the animals developed metabolic dysfunction resembling prediabetes. When the organophosphate-exposed animals consumed a high fat diet in adulthood, metabolic defects were exacerbated and animals gained excess weight compared to unexposed rats on the same diet. At the same time, the high fat diet ameliorated many of the central synaptic defects caused by organophosphate exposure, pointing to nonpharmacologic therapeutic interventions to offset neurodevelopmental abnormalities, as well as toward fostering dietary choices favoring high fat intake. These studies show how common insecticides may contribute to the increased worldwide incidence of obesity and diabetes.
    [Slotkin, T.A. 2011. Reproductive Toxicology. 31: 297–301.]
  • An Environment-Wide Association Study (EWAS) on Type 2 Diabetes Mellitus
    An analysis of 266 potential environmental contributors to type 2 diabetes links the disease to individuals who have higher levels of polychlorinated biphenyls (PCBs) and the pesticide heptachlor, as well a form of vitamin E found at high levels in soybean and corn oil. The researchers used NHANES data from 1999 to 2006. Type 2 diabetes prevalence among those with high levels of heptachlor epoxide, a break down product of heptachlor, was at about two times higher than those with low levels of the compound.
    [Patel CJ, et al. 2010. PLoS ONE 5(5): e10746.]
  • Low Dose of Some Persistent Organic Pollutants Predicts Type 2 Diabetes: A Nested Case–Control Study
    Study links low dose exposure to some persistent organic pollutants (POPs) to type 2 diabetes. The authors report that some POPs, including highly chlorinated PCBs, PBB153 and the organochlorine insecticides trans-nonachlor, oxychlordane and mirex, were associated with type 2 diabetes over an 18-year period, especially in obsese people. However, POPs did not show a traditional dose–response relationship with diabetes. Instead, POPs showed strong associations at relatively low exposures. The authors conclude that exposure to relatively low concentrations of certain POPs may play a role in the increased incidence of diabetes in the United States.
    [Lee D-H, et al. 2010. Environ Health Perspect 118(9): doi:10.1289/ehp.0901480]
  • Arsenic Exposure and Prevalence of Type 2 Diabetes in US Adults
    Using National Health and Nutrition Examination Survey (NHANES) data, this study investigates the association of arsenic exposure, as measured in urine, with the prevalence of type 2 diabetes in a representative sample of US adults. Common sources of inorganic arsenic exposure include dietary exposure, drinking water pollution, and contamination associated with arsenic wood preservatives such as sawdust, smoke, direct contact, and hazardous waste sites. After adjustment for diabetes risk factors and markers of seafood intake, participants with type 2 diabetes had a 26% higher level of total arsenic (95% confidence interval [CI], 2.0%-56.0%) than participants without type 2 diabetes.
    [Navas-Acien, Ana, et al. 2008. JAMA. 300(7):814-822]
  • Environmental pollution and diabetes: a neglected association
    Using cross-sectional data from the 1999–2002 National Health and Nutrition Examination Survey (NHANES), University of Cambridge scientists reported a strong correlation between insulin resistance (which can lead to adult onset diabetes) and serum concentrations of persistent organic pollutants (POPs), especially for organochlorine pesticide compounds. The scientists are advocating additional research into the little understood links between environmental pollution and adult onset diabetes.
    [Oliver, AH et al. 2008. The Lancet, Vol. 371, Issue 9609, Pages 287-288]
  • Incident Diabetes and Pesticide Exposure among Licensed Pesticide Applicators: Agricultural Health Study, 1993–2003
    A study by the National Institutes of Health (NIH), including the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), finds pesticide applicators with regular exposure to pesticides to be at a greater risk of type-2 diabetes. Seven different pesticides produced an increase in risk. Applicators who had used the insecticides aldrin, chlordane, and heptachlor more than 100 lifetime days had 51%, 63%, and 94% increased odds of diabetes, respectively. Researchers looked
    [Montgomery et al. American Journal of Epidemiology 2008 167(10):1235-1246]
  • Pesticide Exposure and Self-Reported Gestational Diabetes Mellitus in the Agricultural Health Study
    Study finds exposure of pregnant women to agricultural pesticides during the first trimester may double the risk of gestational diabetes. The study group was comprised of 11,273 women married to licensed pesticide applicators. Agricultural pesticide exposure during pregnancy, such as mixing or applying pesticides or repairing pesticide application equipment, resulted in an odds ratio of 2.2 (95% CI 1.5-3.3).
    [Saldana, T., et al. Diabetes Care. March 2007 30:529-534]
  • A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002
    Cross-sectional associations of the serum concentrations of persistent organic pollutants (POPs) with diabetes prevalence were investigated in 2,016 adult participants in the National Health and Nutrition Examination Survey 1999-2002. Six POPs (2,2',4,4',5,5'-hexachlorobiphenyl, 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin, 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin, oxychlordane, p,p'-dichlorodiphenyltrichloroethane, and trans-nonachlor) were selected, because they were detectable in >or=80% of participants. Compared with subjects with serum concentrations below the limit of detection, after adjustment for age, sex, race and ethnicity, poverty income ratio, BMI, and waist circumference, diabetes prevalence was strongly positively associated with lipid-adjusted serum concentrations of all six POPs. The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. There were striking dose-response relations between serum concentrations of six selected POPs and the prevalence of diabetes. The strong graded association could offer a compelling challenge to future epidemiologic and toxicological research.
    [Lee DH, Lee IK, Song K, Steffes M, Toscano W, et al. 2006. Diabetes Care. 29(7):1638-44.]
  • Increased Rate of Hospitalization for Diabetes and Residential Proximity of Hazardous Waste Sites
    Study finds increased rate of hospitalization for diabetes in those who live close to hazardous waste sites containing persistent organic pollutants (POPs), including pesticides. The rate ratios for diabetes discharges for people residing in POP sites, after adjustment for potential confounders were 1.23 [95% confidence interval (CI), 1.15–1.32]. In a subset of POP sites along the Hudson River, where there is higher income, less smoking, better diet, and more exercise, the rate ratio was 1.36 (95% CI, 1.26–1.47) compared to clean sites.
    [Kouznetsova M, et al. 2006 Environ Health Perspect 115(1)]