Thus, in order to determine plasma metabolites, which are able to predict insulin resistance in an earlier stage and explore their interaction with glucose and lipid fluxes in the fasting state, liquid chromatography mass spectrometry (LC‐MS)–based untargeted plasma metabolomics (Metabolon) was applied in 60 participants with obesity with an extensive range of Rd as determined by a two‐step HIEC with stable isotopes [6,6‐2H2]glucose and [1,1,2,3,3‐2H5]glycerol, which also allowed for the measurement of insulin regulated lipolysis (Ra). Here, INS is linked to Obesity.