Metabolomics profiling
For the metabolomics analysis, fasting blood samples were collected at baseline and after 1 year in EDTA-containing tubes and stored in freezers at − 80 °C. Participant samples were then randomly ordered and analyzed in pairs (at baseline and 1-year follow-up visits) for quantitative metabolic profiling. Metabolomics assays of the plasma samples were performed at the Broad Institute using high-throughput two-liquid chromatography-tandem mass spectrometry (LC-MS) [Mass spectrometry analyses were carried out using electrospray ionization in the positive-ion mode, and full-scan spectra were acquired over 70–800 Standardized values were generated using the ratio of the value in each sample over the nearest pooled plasma reference and multiplied by the median value measured across the pooled references. After quality filtering and standardization, 399 named metabolites qualified for primary analyses. Three metabolites (1,2-didodecanoyl-sn-glycero-3-phosphocholine, valine-d8, and phenylalanine-d8) were removed because they were internal standards, and 11 more because they had a high number of missing values (i.e., > 20%). In total, 385 metabolites were used in the final analysis.