Association of brominated flame retardants with diabetes and metabolic syndrome in the U.S. population, 2003-2004

OBJECTIVE—Chlorinated persistent organic pollutants (POPs), endocrine disruptors accumulated in adipose tissue, were associated with diabetes and metabolic syndrome. Brominated flame retardants (BFRs), such as polybrominated diphenyl ethers (PBDEs) or polybrominated biphenyls (PBBs), are another class of POPs for which body burden is increasing. Cross-sectional associations of serum concentrations of BFRs with diabetes and metabolic syndrome were studied.RESEARCH DESIGN AND METHODS—In the National Health and Nutrition Examination Survey 2003–2004, 1,367 adults were examined with respect to diabetes status. Five PBDEs and one PBB were selected, detectable in ≥60% of participants. For the outcome metabolic syndrome, we restricted the analysis to 637 participants with a morning fasting sample.RESULTS—Compared with subjects with serum concentrations below the limit of detection, prevalent diabetes had differing dose-response associations with serum concentrations of PBB-153 and PBDE-153. Adjusted odds ratios across quartiles of serum concentrations for PBB-153 or PBDE-153 were 1.0, 0.7, 1.4, 1.6, and 1.9 (P for trend <0.01) and 1.0, 1.6, 2.6, 2.7, and 1.8 (P for quadratic term <0.01), respectively. PBB-153 was also positively associated with the prevalence of metabolic syndrome with adjusted odds ratios of 1.0, 1.5, 3.1, 3.1, and 3.1 (P for trend<0.01). As in its association with diabetes, PBDE-153 showed an inverted U-shaped association with metabolic syndrome.CONCLUSIONS—Pending confirmation in prospective studies, lipophilic xenobiotics, including brominated POPs stored in adipose tissue, may be involved in the pathogenesis of diabetes and metabolic syndrome.We have recently reported strong cross-sectional associations of serum concentrations of chlorinated persistent organic pollutants (POPs) with diabetes (1,2). In addition to diabetes, POPs were associated with most components of metabolic syndrome, although specific associations differed depending on chemicals (3). Based on both these epidemiological and previous experimental findings, we have proposed that POPs stored in adipose tissue may play a key role in the pathogenesis of metabolic syndrome and type 2 diabetes (4). As well-known endocrine disruptors, their persistence in adipose tissue may disturb normal function of lipid and glucose metabolism in adipose tissue (4).These lipophilic pollutants are a mixture of several hundred chemicals with similar properties, such as resistance to biodegradation and bioaccumulation in adipose tissue. Aside from the chlorinated POPs we studied before (dioxins, furans, polychlorinated biphenyls [PCBs], or organochlorine pesticides), there are other important subclasses of POPs. Among them, chemicals belonging to brominated flame retardants (BFRs) are of special interest because of the recent marked increase in levels of polybrominated diphenyl ethers (PBDEs), the most well-known class of BFR, in humans as well as in the environment (5,6). PBDEs are extensively used in a variety of consumer products, such as home/office furnishings and electronics, as flame retardants, and their body burdens in North America are much higher than those of Europeans (5).Similar to chlorinated POPs, BFRs bioaccumulate in adipose tissue in living organisms and are suspected to be endocrine disruptors (7). Such lipophilic xenobiotics in adipose tissue have been suspected to disrupt hormonal signaling in adipose tissue as endocrine disruptors (8,9). They are chemically and toxicologically similar to PCBs, which were strongly associated with hyperglycemia and dyslipidemia in our previous studies (5). Thus, BFRs may also be associated with disturbance of lipid and glucose metabolism.Serum concentrations of biologically important BFRs were measured in subsamples of the National Health and Examination Survey (NHANES) 2003–2004 (10). Our analyses were performed to investigate associations of prevalence of diabetes and metabolic syndrome with the serum concentrations of BFRs.