Intra- and inter-individual metabolic profiling highlights carnitine and lysophosphatidylcholine pathways as key molecular defects in type-2 diabetes

In this study we explored a unique cohort of 43 samples to build a map of metabolites varying in T2D across five different tissues (subcutaneous adipose tissue, liver, pancreatic islets, skeletal muscle and blood serum). The samples originate from the Excellence in Diabetes biobank (EXODIAB) in Sweden. To our knowledge, this is the first attempt to create a map of metabolites across various metabolic-relevant tissues for the same cohort of individuals. In total we identified 286 unique metabolites, 32% of which were significantly altered between non-diabetes and T2D. We found evidence that amino acids (AAs) and bile acids are elevated for specific tissues in T2D and significantly associated to the percentage of glycosylated hemoglobin A1c (HbA1c). We showed that carnitines and lysophosphatidylcholines (LPCs) are the most significantly altered metabolites in muscle, liver and serum in T2D. Finally, we attempted to explore the progression to overt T2D and suggest potential biomarkers in the early development of T2D, i.e. from non-diabetes to pre-diabetes to T2D.