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. 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). 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). 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). 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.

中文翻译：

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脂蛋白胰岛素抵抗指数的全脂质组关联研究。

脂蛋白胰岛素抵抗（LPIR）得分显示可预测健康成年人的胰岛素抵抗（IR）和2型糖尿病（T2D）。但是，用于分类的LPIR实用程序的分子基础仍然不清楚。为确定与LPIR得分变化相关的小分子脂质，LPIR得分是通过核磁共振测量的脂蛋白加权指数，在降脂药物和饮食网络遗传学（GOLDN）研究中（n = 980）。线性混合效应模型用于检验LPIR得分与413种脂质及其主要成分分析来源的组之间的关联。使用稳态模型评估IR（HOMA-IR）（与LPIR评分相关的表型）对显着的关联进行了复制测试（r = 0.48，p <0.001），遗传和表型干预（HAPI）心脏研究的研究（n = 590）。在GOLDN中，有319种脂质与LPIR得分相关（错误发现率调整后的p值范围为4.59×10−161至49.50×10-3）。因子1（甘油三酸酯和甘油二酸酯/存储脂质）和3（混合脂质）呈阳性（分别为β= 0.025，p = 4.52×10- 71和β= 0.021，p = 5.84×10- 41）和因子2（磷脂/非存储脂质）与LPIR得分呈反比（β= − 0.013，p = 2.28×10−18）。这些发现在HAPI心脏研究的HOMA-IR中得到了重复（β= 0.10，p = 1.21×10−02用于存储，β= − 0.13，p = 3.14×10−04用于非存储，β= 0.19，对于混合脂质，p = 8.40×10−07）。