Advances in Autism Research
compiled by Teresa Binstock for
Autism Research Institute
April 2008
Pesticides and Other Pollutants
in
Metabolic Syndrome, Insulin Resistance, and Diabetes
Introduction. Using a large CDC database, DH Lee & colleagues have found that intra-body organochlorine levels are more strongly associated than is obesity: with metabolic syndrome, insulin resistance, and diabetes (1-4). These findings are relevant to autism because Windham et al 2007 - via a tightly bound experimental protocol - described an association between organochlorine pesticides and autism (5), a finding with implications similar to findings reported by D'Amelio et al 2005 for a weak alleles of the PON1 gene, whose gene product aids in the detoxification of organophosphates (6).
1: Extended analyses of the association between serum concentrations of persistent organic pollutants and diabetes
Lee DH et al.
Diabetes Care. 2007 Jun;30(6):1596-8.
http://care.diabetesjournals.org/cgi/reprint/30/6/1596
Introduction: We recently reported on serum concentrations of six persistent organic pollutants (POPs) and prevalence of diabetes in a random U.S. sample (1). Most previous epidemiological studies were restricted from studying several POPs given cost and serum amounts needed. Focus on selected POPs may be appropriate in occupational or accidental high exposure, but, in the general population with only background POP exposure, there is a need to study the concentrations of many interrelated POPs. Our initial approach to risk characterization was to calculate a summary to accumulate risk of exposure across six POPs (1). Even though the summary of six POPs was strongly associated with diabetes, individual POPs had substantial differences in strength of association (1). Thus, it is also of interest to estimate risk within subclasses of POPs that have similar physical and chemical properties. All POPs measured in the National Health and Nutrition Examination Survey (NHANES) can be divided into five subclasses: polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), dioxin-like polychlorinated biphenyls (PCBs), nondioxin-like PCBs, and organochlorine (OC) pesticides. Such specificity about diabetogenicity of POP subclasses would be especially important from the viewpoints of both toxicology and regulation. Therefore, in this article we report on the diabetes associations of 19 POPs within five POP subclasses, each detected among at least 60% of study subjects, i.e., in a manner identical to our most recent analysis of POPs and insulin resistance in the NHANES dataset (2).
PMID: 17363745
2: A strong dose-response relation between serum concentrations of persistent organic pollutants and diabetes: results from the National Health and Examination Survey 1999-2002
Lee DH et al.
Diabetes Care. 2006 Jul;29(7):1638-44.
http://care.diabetesjournals.org/cgi/reprint/29/7/1638
OBJECTIVE: Low-level exposure to some persistent organic pollutants (POPs) has recently become a focus because of their possible link with the risk of diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations of the serum concentrations of 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. RESULTS: 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. When the participants were classified according to the sum of category numbers of the six POPs, adjusted odds ratios were 1.0, 14.0, 14.7, 38.3, and 37.7 (P for trend < 0.001). The association was consistent in stratified analyses and stronger in younger participants, Mexican Americans, and obese individuals. CONCLUSIONS: 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.
PMID: 16801591
3: Association between serum concentrations of persistent organic pollutants and insulin resistance among nondiabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002
Lee DH et al.
Diabetes Care. 2007 Mar;30(3):622-8.
http://care.diabetesjournals.org/cgi/reprint/30/3/622
OBJECTIVE: We reported strong relations between serum concentrations of persistent organic pollutants (POPs), especially organochlorine (OC) pesticides or nondioxin-like polychlorinated biphenyls (PCBs), and prevalence of diabetes in a U.S population with background exposure to POPs. Here, we investigated POPs and insulin resistance, a frequent pathogenic precursor of type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum POPs and homeostasis model assessment of insulin resistance (HOMA-IR) were investigated cross-sectionally in 749 nondiabetic participants aged > or = 20 years. Nineteen POPs in five subclasses were selected, detectable in > or = 60% of participants. RESULTS: Among subclasses, OC pesticides were most strongly associated with HOMA-IR. Adjusted geometric means of HOMA were 3.27, 3.36, 3.48, and 3.85 (P for trend <0.01) across quartiles of OC pesticides. The relationship strengthened with increasing HOMA-IR percentile: adjusted odds ratios comparing the highest versus lowest POPs quartile were 1.8 for being > or = 50th percentile of HOMA-IR, 4.4 for being > or = 75th percentile, and 7.5 for being > or = 90th percentile. Associations with elevated HOMA-IR appeared to be specific to oxychlordane and trans-nonachlor but also were found for two nondioxin-like PCBs. No HOMA-IR associations were seen in the other three POP subclasses. The association between OC pesticides and HOMA-IR tended to strengthen as waist circumference increased, with no apparent association in the lowest quartile of OC pesticide concentrations. CONCLUSIONS: These findings, coupled with those concerning diabetes prevalence, suggest that OC pesticides and nondioxin-like PCBs may be associated with type 2 diabetes risk by increasing insulin resistance, and POPs may interact with obesity to increase the risk of type 2 diabetes.
PMID: 17327331
4: Relationship between serum concentrations of persistent organic pollutants and the prevalence of metabolic syndrome among non-diabetic adults: results from the National Health and Nutrition Examination Survey 1999-2002
Lee DH, Lee IK, Porta M, Steffes M, Jacobs DR Jr.
Diabetologia. 2007 Sep;50(9):1841-51. Epub 2007 Jul 12.
AIMS/HYPOTHESIS: We recently reported associations of some persistent organic pollutants (POPs) with both prevalence of type 2 diabetes and insulin resistance in a US population with background exposure to POPs. Restricted to non-diabetic participants, we now investigate the relationship between POPs and the metabolic syndrome, a prediabetic state. MATERIALS AND METHODS: Cross-sectional associations were investigated in 721 non-diabetic participants aged > or =20 years. Nineteen POPs in five subclasses were selected because they were detectable in > or =60% of participants. RESULTS: Among five POPs subclasses, organochlorine (OC) pesticides were most strongly and consistently associated with metabolic syndrome: adjusted odds ratios (ORs) of 1.0, 1.5, 2.3 and 5.3 across OC pesticide quartiles (p for trend <0.01). Dioxin-like polychlorinated biphenyls (PCBs) were also positively associated with adjusted ORs of 1.0, 1.1, 2.2 and 2.1 (p for trend = 0.01). However, non-dioxin-like PCBs showed an inverted U-shaped association with adjusted ORs of 1.0, 1.3, 1.8 and 1.0 (p for quadratic term <0.01). Associations of specific POPs varied across five components of the metabolic syndrome. OC pesticides were positively and significantly associated with four of the five components, especially elevated triacylglycerol and high fasting glucose, but not high blood pressure. PCBs were significantly associated with waist circumference, triacylglycerol and impaired fasting glucose. Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans showed small but significant associations only with high blood pressure. CONCLUSIONS/INTERPRETATION: This study suggests that the prevalence of a cluster of cardiovascular risk factors relates to background exposure to a mixture of POPs, several of which are also related to the prevalence of diabetes. POPs associated differentially with different components of the metabolic syndrome.
PMID: 17624515
5: Maternal residence near agricultural pesticide applications and autism spectrum disorders among children in the California Central Valley
Roberts EM et al.
Environ Health Perspect. 2007 Oct;115(10):1482-9.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2022638&blobtype=pdf
PMID: 17938740
6. Paraoxonase gene variants are associated with autism in North America, but not in Italy: possible regional specificity in gene-environment interactions
D'Amelio et al.
Mol Psychiatry. 2005 Nov;10(11):1006-16.
PMID: 16027737
7: Association between serum concentrations of persistent organic pollutants and self-reported cardiovascular disease prevalence: results from the National Health and Nutrition Examination Survey, 1999-2002
Ha MH, Lee DH, Jacobs DR.
Environ Health Perspect. 2007 Aug;115(8):1204-9.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1940073&blobtype=pdf
BACKGROUND: There is now increasing evidence that exposure to persistent organic pollutants (POPs) can contribute to the development of inflammatory diseases such as atherosclerosis. OBJECTIVE: The objective of this study was to examine associations of serum concentrations of POPs with self-reported history of cardiovascular disease (CVD). DESIGN: Cross-sectional associations of serum POPs concentrations with the prevalence of self-reported CVD were investigated in 889 adults >or= 40 years of age in the National Health and Nutrition Examination Survey, 1999-2002. We selected 21 POPs [3 polychlorinated dibenzo-p-dioxins (PCDDs), 3 polychlorinated dibenzofurans (PCDFs), 5 dioxin-like polychlorinated biphenyls (PCBs), 6 nondioxin-like PCBs, and 4 organochlorine (OC) pesticides] because they were detectable in >or= 60% of participants. RESULTS: Dioxin-like PCBs, nondioxin-like PCBs, and OC pesticides were positively associated with the prevalence of CVD only among females. Compared with those in the lowest quartile of serum concentration, the odds ratios for CVD across increasing quartiles were 0.9, 2.0, and 5.0 for dioxin-like PCBs (p for trend < 0.01), 1.2, 1.2, and 3.8 for nondioxin-like PCBs (p for trend < 0.01), and 1.9, 1.7, and 4.0 for OC pesticides (p for trend = 0.03). PCDDs showed positive trends with the prevalence of CVD in both males and females; adjusted odds ratios were 1.4, 1.7, and 1.9 (p for trend = 0.07, males and females combined). CONCLUSIONS: Our findings need to be carefully interpreted because of the cross-sectional design and use of self-reported CVD. Prospective studies are needed to clarify these associations.
PMID: 17687448
8: Positive associations of serum concentration of polychlorinated biphenyls or organochlorine pesticides with self-reported arthritis, especially rheumatoid type, in women
Lee DH et al.
Environ Health Perspect. 2007 Jun;115(6):883-8.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1892126&blobtype=pdf
BACKGROUND: Persistent organic pollutants (POPs) can influence the immune system, possibly increasing the risk of rheumatoid arthritis (RA). In addition, as metabolic change due to obesity has been proposed as one mechanism of osteoarthritis (OA), POPs stored in adipose tissue may be also associated with OA. OBJECTIVE: Our goal in this study was to examine associations of background exposure to POPs with arthritis among the general population. DESIGN: We investigated cross-sectional associations of serum POPs concentrations with the prevalence of self-reported arthritis in 1,721 adults >/= 20 years of age in the National Health and Nutrition Examination Survey 1999-2002. RESULTS: Among several POPs, dioxin-like polychlorinated biphenyls (PCBs) or nondioxin-like PCBs were positively associated with arthritis in women. After adjusting for possible confounders, odds ratios (ORs) were 1.0, 2.1, 3.5, and 2.9 across quartiles of dioxin-like PCBs (p for trend = 0.02). Corresponding figures for nondioxin-like PCBs were 1.0, 1.6, 2.6, and 2.5 (p for trend = 0.02). Organochlorine (OC) pesticides were also weakly associated with arthritis in women. For subtypes of arthritis, respectively, RA was more strongly associated with PCBs than was OA. The adjusted ORs for RA were 1.0, 7.6, 6.1, and 8.5 for dioxin-like PCBs (p for trend = 0.05), 1.0, 2.2, 4.4, and 5.4 for nondioxin-like PCBs (p for trend < 0.01), and 1.0, 2.8, 2.7, and 3.5 for OC pesticides (p for trend = 0.15). POPs in men did not show any clear relation with arthritis. CONCLUSIONS: The possibility that background exposure to PCBs may be involved in pathogenesis of arthritis, especially RA, in women should be investigated in prospective studies.
PMID: 17589595
9: Diabetes in relation to serum levels of polychlorinated biphenyls and chlorinated pesticides in adult Native Americans
Codru N et al.
Environ Health Perspect. 2007 Oct;115(10):1442-7.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2022671&blobtype=pdf
BACKGROUND: Recent research suggests that diabetes, a condition whose incidence is increasing, is associated with exposure to polychlorinated biphenyls (PCBs) and chlorinated pesticides. OBJECTIVES: We investigated the potential association between diabetes and serum levels of PCBs, dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB), and mirex in a cross-sectional study of an adult Native-American (Mohawk) population. METHODS: Through a standardized questionnaire we collected demographic, medical, and lifestyle information from 352 adults, > or =30 years of age. We collected fasting serum samples that were analyzed for 101 PCB congeners, DDE, HCB, and mirex along with fasting glucose, triglycerides, and cholesterol. Participants who had fasting-glucose values > 125 mg/dL and/or who were taking antidiabetic medication were defined as persons with diabetes. We conducted logistic regression to assess the potential association between organochlorine serum levels and diabetes, while controlling for the potential confounding variables of age, body mass index (BMI), smoking, sex, and serum lipid levels. Organochlorine serum levels were categorized in tertiles, and the lowest tertile was used as the reference category. RESULTS: The prevalence of diabetes was 20.2%. The odds ratio (OR) of having diabetes for participants in the highest tertile of total PCB concentration compared with the lowest tertile was 3.9 (95% confidence interval, 1.5-10.6). The corresponding ORs for DDE and HCB were even higher. Elevated serum mirex was not associated with diabetes. After adjustment for other analytes, the OR for HCB remained significant, whereas ORs for PCBs and DDE remained elevated but not statistically significant. In contrast, after adjustment for other analytes, the OR for mirex became statistically significant and indicated an inverse association. CONCLUSIONS: In this study of adult Native Americans, elevated serum PCBs, DDE, and HCB were positively associated with diabetes after controlling for potential confounders, whereas a negative association was observed for mirex.
PMID: 17938733
10: Exposure to persistent organochlorine pollutants and type 2 diabetes mellitus
Rignell-Hydbom A et al.
Hum Exp Toxicol. 2007 May;26(5):447-52.
Persistent organochlorine pollutants (POPs), such as polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), dichloro diphenyl trichloroethane (DDT) and its major metabolite 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p' -DDE) have been associated with type 2 diabetes mellitus (T2DM) in recent epidemiological studies. We have analysed 2,2',4,4',5,5' -hexachlorobiphenyl (CB-153) and p,p'-DDE in 544 serum-samples from Swedish women with a median age of 50 years. The participants were asked if they had diabetes and if so, what type of diabetes, years since diagnosis and what kind of treatment they had. Associations between exposure and T2DM were analysed by logistic regression. Moreover, trends of T2DM prevalence were tested with Jonckheere-Terpstrá test. Sixteen of the 544 women (3%) had diabetes, of which 15 were classified as T2DM. There was a significant association with T2DM for both CB-153 (an increase of 100 ng/g lipid corresponded to an odds ratio [OR] of 1. 6, 95% confidence interval [CI] 1. 0, 2. 7) and p,p9-DDE (OR 1. 3, 95%CI 1. 1, 1. 6). In addition, significant positive trends between quartiles of CB-153 and T2DM (P 5 0. 004) and p,p9-DDE and T2DM (P 5 0. 002) were observed. The study shows an association between POP serum concentrations and an increased prevalence of T2DM.
PMID: 17623770