By combining targeted plasma metabolomics with gold standard stable isotope‐based glucose and lipid fluxes in participants with obesity with an extensive range of Rd, some well‐known and some less known indicators are provided for insulin resistance and a panel of these metabolites is shown that may possibly be used to predict Rd to a similar extend as fasting insulin and HOMA. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.