{"doi":"10.1210/clinem/dgab234","title":"HDL Containing Apolipoprotein C-III is Associated with Insulin Sensitivity: A Multicenter Cohort Study","abstract":"CONTEXT: High density lipoprotein (HDL) in humans is composed of a heterogeneous group of particles varying in protein composition as well as biological effects. OBJECTIVE: We investigated the prospective associations between HDL subspecies containing and lacking apolipoprotein (apo) C-III at baseline and insulin sensitivity at year 3. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study of 864 healthy volunteers drawn from the relationship between insulin sensitivity and cardiovascular disease (RISC) study, a multicenter European clinical investigation, whose recruitment initiated in 2002, with a follow-up of 3 years. MAIN MEASURES: Insulin sensitivity was estimated from an oral glucose tolerance test at baseline and year 3, and by euglycemic-hyperinsulinemic clamp at baseline only. The apolipoprotein concentrations were measured at baseline by a sandwich enzyme-linked immunosorbent assay (ELISA)-based method. RESULTS: The 2 HDL subspecies demonstrated significantly opposite associations with insulin sensitivity at year 3 (P-heterogeneity = 0.004). The highest quintile of HDL containing apoC-III was associated with a 1.2% reduction in insulin sensitivity (P-trend = 0.02), while the highest quintile of HDL lacking apoC-III was associated with a 1.3% increase (P-trend = 0.01), compared to the lowest quintile. No significant association was observed for total HDL, and very low density lipoprotein (VLDL) and low density lipoprotein (LDL) containing apoC-III. ApoC-III contained in HDL was associated with a decrease in insulin sensitivity even more strongly than plasma total apoC-III. CONCLUSION: Both HDL containing apoC-III and apoC-III in HDL adversely affect the beneficial properties of HDL on insulin response to glucose. Our results support the potential of HDL-associated apoC-III as a promising target for diabetes prevention and treatment.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":187302,"datarank":0.7039824615163899,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.2623166146414238,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.2623166146414238,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":12,"citers_with_citation_signal":11,"citers_with_endowment":11,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.821,"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":347293,"name":"Majken K. Jensen","orcid":"0000-0003-4729-7545","position":1,"is_corresponding":false},{"id":730126,"name":"Sarah A. Aroner","orcid":"0000-0002-8533-6181","position":2,"is_corresponding":false},{"id":311094,"name":"Jeremy D. Furtado","orcid":"0000-0002-5258-1869","position":3,"is_corresponding":false},{"id":246330,"name":"Bernard Rosner","orcid":"0000-0001-6907-0056","position":4,"is_corresponding":false},{"id":55333,"name":"Frank B. Hu","orcid":"0000-0002-8233-6274","position":5,"is_corresponding":false},{"id":600736,"name":"Beverley Balkau","orcid":"0000-0003-2021-413X","position":6,"is_corresponding":false},{"id":746401,"name":"Andrea Natali","orcid":"0000-0002-8465-7717","position":7,"is_corresponding":false},{"id":21872,"name":"Ele Ferrannini","orcid":"0000-0002-1384-1584","position":8,"is_corresponding":false},{"id":746402,"name":"Simona Baldi","orcid":"0000-0002-8296-4238","position":9,"is_corresponding":false},{"id":39750,"name":"Frank M. Sacks","orcid":"0000-0003-1341-1995","position":10,"is_corresponding":false},{"id":746400,"name":"Rain Yamamoto","orcid":"0000-0002-8928-8797","position":0,"is_corresponding":true}],"reference_count":34,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:48:51.315888Z","pmid":"33839794","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":[]}