A lipidome-wide association study of the lipoprotein insulin resistance index
JournalLipids in health and disease
MetadataShow full item record
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
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