{"doi":"10.3390/ijms262311613","title":"Environmental Mechanisms Influencing the Pathogenesis and Progression of Type 1 Diabetes","abstract":"<jats:p>Type 1 diabetes (T1D) is a complex autoimmune disorder characterized by the selective destruction of insulin-producing pancreatic β-cells. While genetic predisposition establishes susceptibility, environmental factors play a pivotal role in triggering and modulating the autoimmune process. This narrative review synthesizes current evidence from epidemiological, clinical, and experimental studies to elucidate the mechanisms by which environmental exposures influence the pathogenesis and progression of T1D. We discuss how persistent organic pollutants, heavy metals, air pollutants, viral infections, and gut microbiome alterations contribute to β-cell dysfunction, loss of immune tolerance, and enhanced autoimmunity. Our analysis reveals that these environmental triggers act through multiple interconnected pathways, including oxidative stress, mitochondrial dysfunction, epigenetic modifications, innate immune activation, and gut barrier disruption. Understanding these mechanisms provides critical insights for developing preventive strategies and targeted interventions to mitigate environmental risks. These findings underscore the importance of addressing environmental exposures as modifiable risk factors, offering a potential framework for early interventions aimed at preventing or slowing T1D progression in at-risk populations.</jats:p>","journal":"International Journal of Molecular Sciences","year":2025,"id":600383,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1539191,"name":"Weizhou Wang","orcid":null,"position":1,"is_corresponding":false},{"id":1539192,"name":"Zhengsha Huang","orcid":null,"position":2,"is_corresponding":false},{"id":1251072,"name":"Chenxi Zhang","orcid":"0000-0002-1336-9451","position":3,"is_corresponding":false},{"id":1192745,"name":"Jia Zhang","orcid":"0009-0007-6235-1278","position":4,"is_corresponding":false},{"id":1539193,"name":"Yafang Pang","orcid":null,"position":5,"is_corresponding":false},{"id":1539194,"name":"Shangze Li","orcid":"0000-0003-3134-532X","position":6,"is_corresponding":false},{"id":1539189,"name":"Yuntao Tang","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Environmental Mechanisms Influencing the Pathogenesis and Progression of Type 1 Diabetes","abstract":"<jats:p>Type 1 diabetes (T1D) is a complex autoimmune disorder characterized by the selective destruction of insulin-producing pancreatic β-cells. While genetic predisposition establishes susceptibility, environmental factors play a pivotal role in triggering and modulating the autoimmune process. This narrative review synthesizes current evidence from epidemiological, clinical, and experimental studies to elucidate the mechanisms by which environmental exposures influence the pathogenesis and progression of T1D. We discuss how persistent organic pollutants, heavy metals, air pollutants, viral infections, and gut microbiome alterations contribute to β-cell dysfunction, loss of immune tolerance, and enhanced autoimmunity. Our analysis reveals that these environmental triggers act through multiple interconnected pathways, including oxidative stress, mitochondrial dysfunction, epigenetic modifications, innate immune activation, and gut barrier disruption. Understanding these mechanisms provides critical insights for developing preventive strategies and targeted interventions to mitigate environmental risks. These findings underscore the importance of addressing environmental exposures as modifiable risk factors, offering a potential framework for early interventions aimed at preventing or slowing T1D progression in at-risk populations.</jats:p>","is_dataset_classified":null,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"41373764","pmcid":"PMC12692568","openalex_id":"https://openalex.org/W4416843944","authors":[],"funders":[{"funder_name":"National Natural Science Foundation of China","grant_id":"32270760","title":null},{"funder_name":"the Fundamental Research Funds for the National Key R&D Projec","grant_id":"2022YFF0710700","title":null}],"total_grants":2,"fwci":1.9509,"citation_percentile":0.8823869,"influential_citations":0,"citation_trend":[{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://www.mdpi.com/1422-0067/26/23/11613/pdf?version=1764485795","host_type":"journal"},{"url":"https://www.mdpi.com/1422-0067/26/23/11613/pdf?version=1764485795","host_type":"publisher"},{"url":"https://www.mdpi.com/1422-0067/26/23/11613/pdf","host_type":"publisher"},{"url":"https://doi.org/10.3390/ijms262311613","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/41373764","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12692568/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12692568","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12692568?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":["Diabetes and associated disorders","Pancreatic function and diabetes","Diabetes Management and Research","Humans","Diabetes Mellitus, Type 1","Environmental Exposure","Disease Progression","Animals","Gastrointestinal Microbiome","Oxidative Stress","Insulin-Secreting Cells","Autoimmunity"],"mesh_terms":["Gastrointestinal Microbiome","Animals","Diabetes Mellitus, Type 1","Environmental Exposure","Humans","Autoimmunity","Oxidative Stress","Disease Progression","Insulin-Secreting Cells"],"keywords":["Type 1 diabetes","Microbiome","Genetic predisposition","Immune system","Epigenetics","Pathogenesis","Gut flora","Mechanism (biology)","Environmental factors","Oxidative stress","Viral infection","epigenetic modification","Gut Microbiota","Gene-environment Interaction","Immune Dysregulation","Pancreatic Β-cell"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T13:00:40.970844Z","pmid":null,"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":[]}