Persistent organic pollutants and gestational diabetes: A multi-center prospective cohort study of healthy US women

Rahman, Mohammad L.; Zhang, Cuilin; Smarr, Melissa M.; Lee, Sun-Mi; Honda, Masato; Kannan, Kurunthachalam; Tekola‐Ayele, Fasil; Louis, Germaine M. Buck

doi:10.1016/j.envint.2019.01.027

Cited by 81 publications

(51 citation statements)

References 66 publications

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“…In particular, diabetes and/or MetS are positively associated with high body burdens of individual PBDE congeners including: BDE-28, -153, and -47, one of the most abundant PBDE congeners detected in the environment and in human tissues 29,34,35,36 . Additionally, exposure to BDE-28, -47, -99, -153, -154 and -183 increases the risk of gestational diabetes mellitus (GDM) in healthy US women 37,38,39 , a physiologically demanding condition that may increase the risk of MetS in adult offspring 40 . All of the PBDE congeners that have been associated with T2D are found in DE-71, a commercial mixture of PBDEs with high environmental and human relevance 41 .…”

Section: Introductionmentioning

confidence: 99%

Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

Kozlova

Chinthirla

Perez

et al. 2020

Preprint

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Polybrominated diphenyl ethers (PBDEs) are brominated flame retardant chemicals and environmental contaminants with endocrine-disrupting properties that are associated with diabetes and metabolic syndrome in humans. However, their diabetogenic actions are not completely characterized or understood. In this study, we investigated the effects of DE-71, a commercial penta-mixture of PBDEs, on glucose regulatory parameters in a perinatal exposure model using female C57Bl/6 mice. Results from in vivo glucose and insulin tolerance tests and ex vivo analyses showed that DE-71 produced fasting hyperglycemia, glucose intolerance, reduced sensitivity and delayed glucose clearance after insulin challenge, and exaggerated hepatic endocannabinoid tone in F1 offspring exposed to 0.1 mg/kg DE-71 relative to control. DE-71 effects on F0 dams were more limited indicating that indirect exposure to developing offspring is more detrimental. Other ex vivo glycemic correlates occur more generally in exposed F0 and F1, i.e., reduced plasma insulin and altered glucoregulatory endocrines, exaggerated sympathoadrenal activity, decreased thermogenic brown adipose tissue mass and reduced hepatic glutamate dehydrogenase enzymatic activity. Hepatic PBDE congener analysis indicated maternal transfer of BDE-28 and −153 to F1 at a collective level of 200 ng/g lipid, in range with maximum values detected in serum of human females. Given the persistent diabetogenic phenotype, especially pronounced in female offspring after developmental exposure to environmentally relevant levels of DE-71, additional animal studies should be conducted that further characterize PBDE-induced diabetic pathophysiology and identify critical developmental time windows of susceptibility. Longitudinal human studies should also be conducted to determine the risk of long-lasting metabolic consequences after maternal transfer of PBDEs during early-life development.

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Section: Introductionmentioning

confidence: 99%

Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

Kozlova

Chinthirla

Perez

et al. 2020

Preprint

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“…Thus far, epidemiological studies investigating the association between POP exposure during pregnancy and diabetes incidence have been inconsistent. Some studies have shown a positive association between GDM and serum POP levels, including polychlorinated biphenyls (PCB) [29][30][31], polyfluoroalkyl (PFAS) [30], and polybrominated diphenyl ethers (PBDEs) [30,32]. A positive association between GDM and self-reported pesticide exposure during pregnancy has also been reported [37].…”

Section: Discussionmentioning

confidence: 99%

“…Failure to compensate for these changes can lead to hyperglycemia, gestational diabetes mellitus (GDM), and long-term metabolic complications in the mothers and their offspring [28]. The limited number of epidemiological studies that assessed the association between chronic POP exposure and GDM have reported inconsistent results, with some studies showing a positive association between POP serum levels and GDM [29][30][31][32] and others showing no association [32][33][34]. In addition, these are all cross-sectional studies and therefore do not provide information about the timing of events and cannot rule out the possibility of reverse causality (i.e.…”

Section: Introductionmentioning

confidence: 99%

Female mice exposed to low-doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes

Hoyeck

Merhi

Blair

et al. 2020

Preprint

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AbstractAim/hypothesisPersistent organic pollutants have consistently been associated with increased diabetes risk in humans. However, very few studies have assessed the risk of chronic low-dose exposure to pollutants during pregnancy. We investigated the short- and long-term impact of chronic low-dose dioxin exposure during pregnancy and lactation on glucose homeostasis and beta cell function in female mice, including their response to a metabolic stressor later in life.MethodsFemale mice were injected with either corn oil (CO; vehicle control) or 20 ng/kg/d TCDD 2x/week throughout mating, pregnancy, and lactation, and then tracked for 6-10 weeks after chemical exposure stopped. A subset of CO- and TCDD-exposed dams were then transferred to a 45% high fat diet (HFD) or remained on standard chow diet for an additional 11 weeks to assess long-term effects of TCDD on adaptability to a metabolic stressor.ResultsDioxin-exposed dams were hypoglycemic at birth but otherwise had normal glucose homeostasis during and post-dioxin exposure. However, dioxin-exposed dams were modestly heavier than controls starting 5 weeks after the last dioxin injection, and their weight gain accelerated after transitioning to a HFD. Dioxin-exposed dams fed HFD also had accelerated onset of hyperglycemia, dysregulated insulin secretion, reduced islet size, increased MAFA- beta cells, and impaired proinsulin processing compared to control dams on HFD.Conclusions/interpretationsOur study suggests that chronic low-dose dioxin exposure during pregnancy may contribute to the rapid rise in obesity and diabetes incidence seen worldwide.

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“…However, an optimal index for exposure to POPs has not been established. Most studies have used plasma concentrations of 76 POPs as an index, which is determined by standard procedures using gas-and liquid chromatography (LC) with mass spectrophotometry 10 . Limited numbers of POPs have been identified due to the limited number of facilities available to measure them, the large volume of blood needed, and the high cost.…”

mentioning

confidence: 99%

“…A recent study has demonstrated that serum concentrations of POPs, including mainly chlorinated PCBs and some PFAS and PBDE, have positive associations with GDM risk in US non-obese women in the multi-center prospective cohort study 10 and pregnant Greek women 11 . Here, we examined the hypothesis that AhRT bioactivity in the serum is positively associated with GDM risk in Korean pregnant women at 24-28 weeks of pregnancy.…”

mentioning

confidence: 99%

Association of aryl hydrocarbon receptor transactivating activity, a potential biomarker for persistent organic pollutants, with the risk of gestational diabetes mellitus

Park

Chon

Park

et al. 2021

Sci Rep

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Persistent organic pollutants(POPs) are suggested to be potential risk factors for gestational diabetes mellitus(GDM). We examined the hypothesis that the aryl hydrocarbon receptor trans-activating(AhRT) activity, a potential biomarker for the presence of POPs, could be a GDM risk factor in pregnant women. A total of 390 GDM and 100 normal pregnant(non-GDM) subjects in the Korea National Diabetes Program cohort voluntarily participated. We measured AhRT activity and concentrations of ATP and reactive oxygen in the serum collected at the screening of the participants for GDM using recombinant Hepa1c1c7 cells. Odds ratios(ORs) and 95% confidence intervals(CIs) were estimated using multivariable logistic regression models. The sensitivity and specificity of AhRT activity for GDM diagnostics were measured by receiver operating characteristic(ROC) analysis. Body mass index at pre-pregnancy and delivery and systolic blood pressure were significantly higher in the GDM group. AhRT activity was higher, and ATP concentrations were lower in the GDM group than the non-GDM group(P < 0.0001). AhRT activity was significantly higher in the GDM group(OR 29.3, 95% CI 10.9–79.1) compared with non-GDM(P < 0.0001). Serum glucose concentration at 1 h after a 50 g glucose challenge(glucose-50) was moderately correlated with AhRT activity(r2 = 0.387) and negatively correlated with ATP production(r2 = −0.650). In the ROC curve, AhRT activity had 70.9% sensitivity and 90.0% specificity for glucose-50, a GDM screening method. In conclusion, this study suggests that serum AhRT activity is positively associated with the risk of GDM.

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Persistent organic pollutants and gestational diabetes: A multi-center prospective cohort study of healthy US women

Cited by 81 publications

References 66 publications

Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

Maternal Transfer of Environmentally Relevant Polybrominated Diphenyl Ethers (PBDEs) Produces a Diabetic Phenotype and Disrupts Glucoregulatory Hormones and Hepatic Endocannabinoids in Adult Mouse Female Offspring

Female mice exposed to low-doses of dioxin during pregnancy and lactation have increased susceptibility to diet-induced obesity and diabetes

Association of aryl hydrocarbon receptor transactivating activity, a potential biomarker for persistent organic pollutants, with the risk of gestational diabetes mellitus

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