{"doi":"10.1016/j.envint.2022.107175","title":"Associations between persistent organic pollutants and type 1 diabetes in youth","abstract":"Diabetes affects millions of people worldwide with a continued increase in incidence occurring within the pediatric population. The potential contribution of persistent organic pollutants (POPs) to diabetes in youth remains poorly known, especially regarding type 1 diabetes (T1D), generally the most prevalent form of diabetes in youth. We investigated the associations between POPs and T1D in youth and studied the impacts of POPs on pancreatic β-cell function and viability in vitro. We used data and plasma samples from the SEARCH for Diabetes in Youth Case Control Study (SEARCH-CC). Participants were categorized as Controls, T1D with normal insulin sensitivity (T1D/IS), and T1D with insulin resistance (T1D/IR). We assessed plasma concentrations of polychlorinated biphenyls (PCBs) and organochlorine pesticides and estimated the odds of T1D through multivariable logistic regression. In addition, we performed in vitro experiments with the INS-1E pancreatic β-cells. Cells were treated with PCB-153 or p,p’-DDE at environmentally relevant doses. We measured insulin production and secretion and assessed the mRNA expression of key regulators involved in insulin synthesis (Ins1, Ins2, Pdx1, Mafa, Pcsk1/3, and Pcsk2), glucose sensing (Slc2a2 and Gck), and insulin secretion (Abcc8, Kcnj11, Cacna1d, Cacna1b, Stx1a, Snap25, and Sytl4). Finally, we assessed the effects of PCB-153 and p,p’-DDE on β-cell viability. Among 442 youths, 112 were controls, 182 were classified with T1D/IS and 148 with T1D/IR. The odds ratios (OR) of T1D/IS versus controls were statistically significant for p,p’-DDE (OR 2.0, 95% confidence interval (CI) 1.0, 3.8 and 2.4, 95% CI 1.2, 5.0 for 2nd and 3rd tertiles, respectively), trans-nonachlor (OR 2.5, 95% CI 1.3, 5.0 and OR 2.3, 95% CI 1.1, 5.1 for 2nd and 3rd tertiles, respectively), and PCB-153 (OR 2.3, 95% CI 1.1, 4.6 for 3rd tertile). However, these associations were not observed in participants with T1D/IR. At an experimental level, treatment with p,p’-DDE or PCB-153, at concentrations ranging from 1 × 10-15 M to 5 × 10-6 M, impaired the ability of pancreatic β-cells to produce and secrete insulin in response to glucose. These failures were paralleled by impaired Ins1 and Ins2 mRNA expression. In addition, among different targeted genes, PCB-153 significantly reduced Slc2a2 and Gck mRNA expression whereas p,p’-DDE mainly affected Abcc8 and Kcnj11. While treatment with PCB-153 or p,p’-DDE for 2 days did not affect β-cell viability, longer treatment progressively killed the β-cells. These results support a potential role of POPs in T1D etiology and demonstrate a high sensitivity of pancreatic β-cells to POPs.","journal":"Environment International","year":2022,"id":254182,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":406589,"name":"Scott Isom","orcid":"0000-0002-6658-3865","position":1,"is_corresponding":false},{"id":325080,"name":"Elizabeth T. Jensen","orcid":"0000-0003-2704-6634","position":2,"is_corresponding":false},{"id":704746,"name":"Sandra Huber","orcid":"0000-0003-4745-8767","position":3,"is_corresponding":false},{"id":897152,"name":"Youssef Oulhote","orcid":"0000-0002-2323-1982","position":4,"is_corresponding":false},{"id":811,"name":"Joseph Rigdon","orcid":"0000-0001-6265-0752","position":5,"is_corresponding":false},{"id":408557,"name":"James Lovato","orcid":"0000-0001-5429-4890","position":6,"is_corresponding":false},{"id":342444,"name":"Angela D. Liese","orcid":"0000-0002-7022-0178","position":7,"is_corresponding":false},{"id":342442,"name":"Catherine Pihoker","orcid":"0000-0001-9074-7770","position":8,"is_corresponding":false},{"id":249641,"name":"Dana Dabelea","orcid":"0000-0001-9514-8929","position":9,"is_corresponding":false},{"id":546627,"name":"Shelley Ehrlich","orcid":"0000-0003-3861-1950","position":10,"is_corresponding":false},{"id":900723,"name":"Jérôme Ruzzin","orcid":"0000-0003-3676-8145","position":11,"is_corresponding":false},{"id":510531,"name":"Sophie Emilie Bresson","orcid":"0000-0002-8623-2237","position":0,"is_corresponding":true}],"reference_count":56,"raw_metadata":null,"created_at":"2026-07-19T00:25:03.918844Z","pmid":"35303528","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}