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dc.contributor.authorBagheri, M.
dc.contributor.authorO'connell, J.
dc.contributor.authorMontasser, M.
dc.date.accessioned2020-07-07T19:59:38Z
dc.date.available2020-07-07T19:59:38Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85087141963&doi=10.1186%2fs12944-020-01321-8&partnerID=40&md5=10dda360108c84f64eb7f8d407a174cd
dc.identifier.urihttp://hdl.handle.net/10713/13225
dc.description.abstractBackground The lipoprotein insulin resistance (LPIR) score was shown to predict insulin resistance (IR) and type 2 diabetes (T2D) in healthy adults. However, the molecular basis underlying the LPIR utility for classification remains unclear. Objective To identify small molecule lipids associated with variation in the LPIR score, a weighted index of lipoproteins measured by nuclear magnetic resonance, in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 980). Methods Linear mixed effects models were used to test the association between the LPIR score and 413 lipid species and their principal component analysis-derived groups. Significant associations were tested for replication with homeostatic model assessment-IR (HOMA-IR), a phenotype correlated with the LPIR score (r = 0.48, p <  0.001), in the Heredity and Phenotype Intervention (HAPI) Heart Study (n = 590). Results In GOLDN, 319 lipids were associated with the LPIR score (false discovery rate-adjusted p-values ranging from 4.59 × 10− 161 to 49.50 × 10− 3). Factors 1 (triglycerides and diglycerides/storage lipids) and 3 (mixed lipids) were positively (β = 0.025, p = 4.52 × 10− 71 and β = 0.021, p = 5.84 × 10− 41, respectively) and factor 2 (phospholipids/non-storage lipids) was inversely (β = − 0.013, p = 2.28 × 10− 18) associated with the LPIR score. These findings were replicated for HOMA-IR in the HAPI Heart Study (β = 0.10, p = 1.21 × 10− 02 for storage, β = − 0.13, p = 3.14 × 10− 04 for non-storage, and β = 0.19, p = 8.40 × 10− 07 for mixed lipids). Conclusions Non-storage lipidomics species show a significant inverse association with the LPIR metabolic dysfunction score and present a promising focus for future therapeutic and prevention studies.en_US
dc.description.sponsorshipNational Heart, Lung, and Blood Institute, NHLBI: R01HL091357; National Heart, Lung, and Blood Institute, NHLBI: U01HL072524-04en_US
dc.description.urihttps://doi.org/10.1186/s12944-020-01321-8en_US
dc.language.isoen_USen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofLipids in health and disease
dc.subjectDiglycerideen_US
dc.subjectGOLDNen_US
dc.subjectInsulin resistanceen_US
dc.subjectLipidomicsen_US
dc.subjectLipidsen_US
dc.subjectLipoproteinen_US
dc.subjectPhospholipiden_US
dc.subjectTriglycerideen_US
dc.titleA lipidome-wide association study of the lipoprotein insulin resistance indexen_US
dc.typeArticleen_US
dc.identifier.doi10.1186/s12944-020-01321-8
dc.identifier.pmid32586392


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