Role of human plasma metabolites in prediabetes and type 2 diabetes from the IMI‑DIRECT study – published online 30/09/2024

Sapna Sharma, Qiuling Dong, Mark Haid, Jonathan Adam, Roberto Bizzotto, Juan J. Fernandez‑Tajes, Angus G. Jones, Andrea Tura, Anna Artati, Cornelia Prehn, Gabi Kastenmüller, Robert W. Koivula, Paul W. Franks, Mark Walker, Ian M. Forgie, Giuseppe Giordano, Imre Pavo, Hartmut Ruetten, Manolis Dermitzakis, Mark I. McCarthy, Oluf Pedersen, Jochen M. Schwenk, Konstantinos D. Tsirigos, Federico De Masi, Soren Brunak, Ana Viñuela, Andrea Mari, Timothy J. McDonald, Tarja Kokkola, Jerzy Adamski, Ewan R. Pearson, Harald Grallert

Genomic and transcriptomic studies often fail to explain the complexity of a biological system, thus leaving us with a huge gap in the map from genotype to phenotype. The approach that is closest to fill this gap is metabolomics. Metabolomics is a high-throughput study of the metabolome, which includes all the small molecules (50–1500 Da) with diverse physiochemical characteristics and dynamic range of abundance, commonly known as metabolites. In this issue, Sharma, Dong and Haid et al (https://doi.org/10.1007/s00125-024-06282-6) identify key biomarkers, including branched-chain amino acids, lipids and newly discovered N-lactoyl-amino acid metabolites, that are linked to prediabetes and diabetes. The authors provide evidence that these markers affect disease progression over time, with genetic analysis pointing to disruptions in lipid metabolism and n-3 fatty acids as major factors in the onset of type 2 diabetes. The authors conclude that their study’s findings could help classify individuals based on their risk levels, paving the way for more targeted and personalised diabetes interventions.