Plasma concentrations of lipophilic persistent organic pollutants and glucose homeostasis in youth populations

Background: Exposure to lipophilic persistent organic pollutants (POPs) is ubiquitous. POPs are metabolic disrupting chemicals and are potentially diabetogenic. Methods: Using a multi-cohort study including overweight adolescents from the Study of Latino Adolescents at Risk (SOLAR, N = 301, 2001–2012) and young adults from the Southern California Children's Health Study (CHS, N = 135, 2014–2018), we examined associations of POPs and risk factors for type 2 diabetes. SOLAR participants underwent annual visits for a median of 2.2 years and CHS participants performed a single visit, during which a 2-h oral glucose tolerance test was performed. Linear mixed models were used to examine associations between plasma concentrations of POPs [4,4′-dichlorodiphenyldichloroethylene (4,4′-DDE), hexachlorobenzene (HCB), PCBs-153, 138, 118, 180 and PBDEs-154, 153, 100, 85, 47] and changes in glucose homeostasis across age and pubertal stage. Results: In SOLAR, exposure to HCB, PCB-118, and PBDE-153 was associated with dysregulated glucose metabolism. For example, each two-fold increase in HCB was associated with approximately 2 mg/dL higher glucose concentrations at 30 min (p = 0.001), 45 min (p = 0.0006), and 60 min (p = 0.03) post glucose challenge. Compared to individuals with low levels of PCB-118, individuals with high levels exhibited a 4.7 mg/dL (p = 0.02) higher glucose concentration at 15 min and a 3.6 mg/dL (p = 0.01) higher glucose concentration at 30 min. The effects observed with exposure to organochlorine compounds were independent of pubertal stages. PBDE-153 was associated with the development of dysregulated glucose metabolism beginning in late puberty. At Tanner stage 4, exposure to PBDE-153 was associated with a 12.7 mg/dL higher 60-min glucose concentration (p = 0.009) and a 16.1 mg*dl⁻¹*hr⁻¹ higher glucose AUC (p = 0.01). These associations persisted at Tanner 5. In CHS, PBDE-153 and total PBDE were associated with similar increases in glucose concentrations. Conclusion: Our results suggest that childhood exposure to lipophilic POPs is associated with dysregulated glucose metabolism.