Longitudinal metabolite and protein trajectories prior to diabetes mellitus diagnosis in Danish blood donors: a nested case–control study – published online 30/07/2024

Agnete T. Lundgaard, David Westergaard, Timo Röder, Kristoffer S. Burgdorf, Margit H. Larsen, Michael Schwinn, Lise W. Thørner, Erik Sørensen, DBDS Genomic Consortium, Kaspar R. Nielsen, Henrik Hjalgrim, Christian Erikstrup, Bertram D. Kjerulff, Lotte Hindhede, Thomas F. Hansen, Mette Nyegaard, Ewan Birney, Hreinn Stefansson, Kári Stefánsson, Ole B. V. Pedersen, Sisse R. Ostrowski, Peter Rossing, Henrik Ullum, Laust H. Mortensen, Dorte Vistisen, Karina Banasik, Søren Brunak

Previous studies have shown that glucose and lipid metabolism demonstrate time-dependent changes years before type 2 diabetes is clinically diagnosed. However, little is known about other molecular changes taking place during disease development, such as inflammation, a key feature of both type 1 and type 2 diabetes. In this issue, Lundgaard et al (https://doi.org/10.1007/s00125-024-06231-3) use biobank plasma samples from Danish blood donors to investigate health-to-disease changes in 225 markers involved in inflammation, endothelial function, and glucose and lipid metabolism up to 10 years before a type 1 or type 2 diabetes diagnosis. The authors identify several new biomarkers with distinct, time-dependent trajectories, along with many biomarkers showing persistently altered levels, in the years leading up to a diabetes diagnosis, and highlight that these changes, to some extent, are specific to either type 1 or type 2 diabetes. Biomarker panels that improve the prediction of diabetes up to 10 years before a diagnosis are also described. The authors conclude that including temporal biomarkers in future risk assessment tools may improve the precision of patient-specific risk assessment.