Environmental exposure to BDE47 is associated with increased diabetes prevalence: Evidence from community-based case-control studies and an animal experiment

Abstract

Brominated flame retardants exposure has been associated with increasing trends of diabetes and metabolic disease. Thus, the purpose of this study was to provide evidence of polybrominated diphenyl ethers (PBDEs) exposure in relation to diabetes prevalence and to reveal the potential underlying mechanism in epidemiological and animal studies. All the participants received a questionnaire, health examination, and the detection of 7 PBDE congeners in serum in two independent community-based studies from 2011 to 2012 in China. Male rats were exposed to 2,2’4,4’-tetrabromodiphenyl ether (BDE47) for 8 weeks to explore its effects on glucose homeostasis and potential mechanisms using high-throughput genomic analysis. Among the 7 congeners, BDE47 showed significant high detection rate and concentration in cases in Study I and Study II. Every tertile of BDE47 exposure significantly increased the risk of diabetes prevalence in Study I (Ptrend = 0.001) and Study II (Ptrend < 0.001). Additionally, BDE47 treatments induced hyperglycemia in rats. Furthermore, gene microarray analysis showed that diabetes pathway and three gene ontology terms involved in glucose transport were enriched. The results indicated that environmental exposure to BDE47 was associated with increased diabetes prevalence. However, further prospective and mechanistic studies are needed to the causation of diabetes in relation to BDE47.

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

“…The inhibitory effects of DE-71 on both glucagon and insulin may indicate an altered capacity of -and -cell function in the pancreas, respectively. Interestingly, adult exposure to BDE-47 produced reduced gene expression for the rat GLP-1 receptor 29 .…”

“…Studies have shown that levels of insulin, glucagon and glucagon-like peptide 1 (GLP-1) are altered in T2D leading to pathological glucose dyshomeostasis 57 36 . Animal studies have failed to show changes in insulin levels with adult exposure to BDE-47 29 or postnatal exposure to BDE-47 31 or perinatal exposure to a mixture of BFRs, including PBDEs and HBCDD 52 . In 0.4 mg/kg F1 insulin reduction was less pronounced, and glucagon was decreased, which could explain the less marked glucose intolerance.…”

“…Epidemiological studies suggest that the escalating production and environmental presence of a number of metabolic disrupting chemicals (MDC) over the past four decades may contribute to the pathogenesis of metabolic diseases 25 . Mounting evidence has implicated brominated POPs in the pathogenesis of T2D and metabolic syndrome (MetS) 26,27,28,29,30,31,32,33,34 . 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 .…”

“…Mounting evidence has implicated brominated POPs in the pathogenesis of T2D and metabolic syndrome (MetS) 26,27,28,29,30,31,32,33,34 . 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 .…”

Gestational and Lactational Exposure to an Environmentally‐Relevant Mixture of Brominated Flame Retardants: Effects on Neurodevelopment and Metabolism

“…Adult male mice exposed to DE‐71 exhibited increased glucose‐to‐insulin ratios, suggesting that exposure to the technical mixture can alter glucose homeostasis (Dunnick et al, ; Nash et al, ). Similarly, human studies have revealed that serum PBDE levels are higher in people with diabetes (Lim et al, ; Zhang et al, ). However, in these studies, exposure occurred during adulthood with concurrent testing, whereas, in the current study, exposure occurred during early life with later testing.…”