Metabolomic prediction of diabetes and cardiovascular risk.

diabetes (impaired fasting glucose, impaired glucose tolerance) and even those with high-normal glucose levels [3] . Numerous studies have demonstrated greater insulin resistance (i.e., lower insulin sensitivity) in certain demographic groups: older subjects vs. younger subjects; African Americans vs. Caucasians; sedentary persons vs. active persons, among other examples. However, these differences in insulin sensitivity have not been fully explained at the biological or molecular level. Recently, studies utilizing metabolite profiling have found different metabolomic signatures in insulin-sensitive vs. insulin-resistant subjects, under both fasting and nonfasting conditions [2, 4, 5] . Under fasting conditions, plasma levels of BCAAs, AAAs, proline and methionine are correlated with measures of insulin sensitivity [2, 4, 5] . When the internal milieu is challenged with exogenous glucose (as occurs during oral glucose tolerance test), discernible excursions occur in the plasma levels of amino acids and other metabolites in healthy subjects. Interestingly, the expected excursions in BCAAs, methionine, and bile acids are markedly attenuated in prediabetic individuals with insulin resistance [6] . Based on regression analysis, excursions in leucine, isoleucine and glycerol levels predicted fasting insulin (a surrogate of insulin resistance) more robustly than any individual metabolite excursion. Thus, fasting and glucose-stimulated levels of BCAAs and other metabolites predict insulin resistance, and by extension the risk of T2DM [2, 4, 5] . Metabolomics