Biomarkers for type 2 diabetes and impaired fasting glucose using a non-targeted metabolomics approach

Cristina Menni, Eric Fauman, Idil Erte, John R. B. Perry, Gabi Kastenmüller, So-Youn Shin, Ann-Kristin Petersen, Craig Hyde, Maria Psatha, Kirsten J. Ward, Wei Yuan, Mike Milburn, Colin N. A. Palmer, Timothy M. Frayling, Jeff Trimmer, Jordana T. Bell, Christian Gieger, Rob Mohney, Mary Julia Brosnan, Karsten SuhreNicole Soranzo, Tim D. Spector

    Research output: Contribution to journalArticlepeer-review

    222 Citations (Scopus)

    Abstract

    Using a non-targeted metabolomics approach of 447 fasting plasma metabolites, we searched for novel molecular markers that arise before and after hyperglycaemia in a large population-based cohort of 2,204 females (115 Type 2 Diabetes-T2D cases, 192 individuals with impaired fasting glucose- IFG and 1,897 controls) from TwinsUK.Forty-two metabolites from three major fuel sources, carbohydrates, lipids and proteins, were found to significantly correlate with T2D after adjusting for multiple testing; of these, 22 were previously reported as associated with T2D or insulin resistance. Fourteen metabolites were found to be associated with IFG. Among the metabolites identified, the branched-chain-keto-acid metabolite 3-methyl-2-oxovalerate, was the strongest predictive biomarker for IFG after glucose (OR=1.65, 95%CI=1.39,1.95, P=8.46x10(-9)) and was moderately heritable (h(2)=0.20). The association was replicated in an independent population (n=720, OR=1.68, 95%CI=1.34, 2.11, P=6.52x10(-6)) and validated in 189 Twins with urine metabolomics taken at the same time as plasma (OR=1.87, 95%CI=1.27,2.75, P=1x10(-3)). Results confirm an important role for catabolism of branched-chain-amino-acids in T2D and IFG.In conclusion, this T2D-IFG biomarker study has surveyed the broadest panel of non-targeted metabolites to date, revealing both novel and known associated metabolites and providing potential novel targets for clinical prediction and a deeper understanding of causal mechanisms.
    Original languageEnglish
    JournalDiabetes
    Early online date24 Jul 2013
    DOIs
    Publication statusPublished - 2013

    Fingerprint

    Dive into the research topics of 'Biomarkers for type 2 diabetes and impaired fasting glucose using a non-targeted metabolomics approach'. Together they form a unique fingerprint.

    Cite this