ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 10.7 | DOI: 10.1530/ey.18.10.7

Diabetologia. 2019;62(12):2287–2297. doi: 10.1007/s00125-019-04980-0

This study identified different circulatory metabolite profiles in children who subsequently progress to T1D compared to children who progress to islet autoimmunity but not T1D, and antibody-negative control children.

In addition to altered T cell immunity and autoantibody appearance, metabolic dysregulation may precede the onset of T1D. However, these metabolic disturbances and their specific role in disease initiation remain poorly understood. In this study, polar metabolites were measured using two-dimensional gas chromatography (GC) high-speed time of flight mass spectrometry (MS) in 415 longitudinal plasma samples in a cohort of children. Three study groups were compared: children who progressed to T1D; children who seroconverted to one islet autoantibody but not to T1D; and an antibody-negative control group.

In early infancy, progression to T1D was associated with lower amino acids, sugar derivatives and fatty acid metabolites, including catabolites of microbial origin, compared to control children. Methionine remained persistently upregulated in those who progressed to T1D. The appearance of islet autoantibodies was associated with decreased glutamic and aspartic acids.

These findings suggest that children who later progress to T1D already have a unique metabolic profile, which is, altered again and even more so with the appearance of islet autoantibodies. These findings may add to the tools that are available for early prediction of the T1D, such as the presence of autoantibodies and HLA typing.