{"doi":"10.1016/j.ebiom.2021.103279","title":"Plasma epoxyeicosatrienoic acids and dihydroxyeicosatrieonic acids, insulin, glucose and risk of diabetes: The strong heart study","abstract":"BACKGROUND: Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid with multiple biological functions. Rodent experiments suggest EETs play a role in insulin sensitivity and diabetes, but evidence in humans is limited. To address this knowledge gap, we conducted a case-cohort study in the Strong Heart Family Study, a prospective cohort among American Indians. METHODS: We measured 4 EET species and 4 species of corresponding downstream metabolites, dihydroxyeicosatrieonic acids (DHETs), in plasma samples from 1161 participants, including 310 with type 2 diabetes. We estimated the associations of total (esterified and free) EETs and DHETs with incident diabetes risk, adjusting for known risk factors. We also examined cross-sectional associations with plasma fasting insulin and glucose in the case-cohort and in 271 participants without diabetes from the older Strong Heart Study cohort, and meta-analyzed the results from the 2 cohorts. FINDINGS: We observed no significant association of total EET or DHET levels with incident diabetes. In addition, plasma EETs were not associated with plasma insulin or plasma glucose. However, higher plasma 14,15-DHET was associated with lower plasma insulin and lower plasma glucose. INTERPRETATION: In this first prospective study of EETs and diabetes, we found no evidence for a role of total plasma EETs in diabetes. The novel associations of 14,15-DHET with insulin and glucose warrant replication and exploration of possible mechanisms. FUNDING: US National Institutes of Health.","journal":"EBioMedicine","year":2021,"id":194645,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8428,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":23102,"name":"Paul N. Jensen","orcid":"0000-0001-5836-821X","position":1,"is_corresponding":false},{"id":764602,"name":"Maxwell Zeigler","orcid":"0000-0002-7983-6120","position":2,"is_corresponding":false},{"id":765187,"name":"Julie Denham","orcid":null,"position":3,"is_corresponding":false},{"id":305414,"name":"Amanda M. Fretts","orcid":"0000-0002-5358-2345","position":4,"is_corresponding":false},{"id":390060,"name":"Jason G. Umans","orcid":"0000-0002-2746-3350","position":5,"is_corresponding":false},{"id":549897,"name":"Barbara V. Howard","orcid":"0009-0008-0197-4161","position":6,"is_corresponding":false},{"id":291147,"name":"Colleen M. Sitlani","orcid":"0000-0001-7656-7482","position":7,"is_corresponding":false},{"id":305430,"name":"Barbara McKnight","orcid":"0000-0002-3180-666X","position":8,"is_corresponding":false},{"id":91938,"name":"Sina A. Gharib","orcid":"0000-0002-2480-4367","position":9,"is_corresponding":false},{"id":548384,"name":"Irena B. King","orcid":"0000-0002-8658-0020","position":10,"is_corresponding":false},{"id":267326,"name":"David S. Siscovick","orcid":"0000-0003-0461-175X","position":11,"is_corresponding":false},{"id":17625,"name":"Bruce M. Psaty","orcid":"0000-0002-7278-2190","position":12,"is_corresponding":false},{"id":24890,"name":"Nona Sotoodehnia","orcid":"0000-0002-2705-6237","position":13,"is_corresponding":false},{"id":369065,"name":"Rheem A. Totah","orcid":"0000-0003-1664-4874","position":14,"is_corresponding":false},{"id":305438,"name":"Rozenn N. Lemaître","orcid":"0000-0002-7038-1844","position":0,"is_corresponding":true}],"reference_count":47,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:49:59.476757Z","pmid":"33752126","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":[]}