Metabolomic Predictors of Insulin Resistance and Diabetes

Our lab has identified and validated novel metabolite profiles of those destined to develop overt T2D. These metabolites were elevated up to 12 years before the onset of T2D in individuals who were initially glucose-tolerant; improved prediction of T2D beyond clinical risk factors and established biochemical markers; and have been validated by other groups. We have now extended our studies to participants in the [Jackson Heart Study](https://www.jacksonheartstudy.org/) (JHS), an African American (AA) population with a high prevalence of T2D and its complications. We have also tested the predictive value of metabolites in a key clinical trial, the [Diabetes Prevention Program](https://www.cdc.gov/diabetes/prevention/index.html) (DPP).

Our study has leveraged critical advances. Beyond the named metabolites that we have associated with incident T2D, our recent "whole metabolome" analyses of T2D and related traits in JHS have nominated hundreds of unknown compounds that are uncorrelated with existing biochemical markers for unambiguous identification. We have used novel, in-house mass spectrometry (MS) and bioinformatics tools to unambiguously identify these compounds. To complement the MS work, genome wide association studies (GWAS) and genetic correlation analyses of metabolites and proteins were used to assign metabolite peaks to pathways (e.g., based on association with known metabolites or with enzymes or solute carriers) that informed their identity. Available data will include metabolomics datasets and gwas summary statistics.