A lipidome-wide association study of the lipoprotein insulin resistance index
JournalLipids in health and disease
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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.
SponsorsNational Heart, Lung, and Blood Institute, NHLBI: R01HL091357; National Heart, Lung, and Blood Institute, NHLBI: U01HL072524-04
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85087141963&doi=10.1186%2fs12944-020-01321-8&partnerID=40&md5=10dda360108c84f64eb7f8d407a174cd; http://hdl.handle.net/10713/13225