Early metabolic features of genetic liability to type 2 diabetes: cohort study with repeated metabolomics across early life

Using data from up to 4,761 offspring from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, researchers examined genetic liability to adult type 2 diabetes in relation to detailed traits from targeted metabolomics among the same individuals at four key stages of early life.

Early consistent perturbations in the metabolic traits are expected to reflect early signs of disease that are detectable in circulation. Results support perturbed HDL lipid metabolism, particularly in large and very large particle subtypes, as one of the earliest features of type 2 diabetes liability which precedes higher branched chain amino acid and inflammatory glycoprotein acetyl levels. This feature is apparent in childhood as early as age 8 years, decades before the clinical onset of disease.