Plasma metabolites associated with homeostatic model assessment of insulin resistance: metabolite-model design and external validation
Research output: Contribution to journal › Journal article › Research › peer-review
- Hernandez-Alonso et al_Scientific Reports_2019_Vol 9_e13895
Final published version, 1.31 MB, PDF document
Different plasma metabolites have been related to insulin resistance (IR). However, there is a lack of metabolite models predicting IR with external validation. The aim of this study is to identify a multi-metabolite model associated to the homeostatic model assessment (HOMA)-IR values. We performed a cross-sectional metabolomics analysis of samples collected from overweight and obese subjects from two independent studies. The training step was performed in 236 subjects from the SATIN study and validated in 102 subjects from the GLYNDIET study. Plasma metabolomics profile was analyzed using three different approaches: GC/quadrupole-TOF, LC/quadrupole-TOF, and nuclear magnetic resonance (NMR). Associations between metabolites and HOMA-IR were assessed using elastic net regression analysis with a leave-one-out cross validation (CV) and 100 CV runs. HOMA-IR was analyzed both as linear and categorical (median or lower versus higher than the median). Receiver operating characteristic curves were constructed based on metabolites' weighted models. A set of 30 metabolites discriminating extremes of HOMA-IR were consistently selected. These metabolites comprised some amino acids, lipid species and different organic acids. The area under the curve (AUC) for the discrimination between HOMA-IR extreme categories was 0.82 (95% CI: 0.74-0.90), based on the multi-metabolite model weighted with the regression coefficients of metabolites in the validation dataset. We identified a set of metabolites discriminating between extremes of HOMA-IR and able to predict HOMA-IR with high accuracy.
|Number of pages||9|
|Publication status||Published - 2019|
Number of downloads are based on statistics from Google Scholar and www.ku.dk