Short-term variability of the human serum metabolome depending on nutritional and metabolic health status

The intra-individual variability of the human serum metabolome over a period of 4 weeks and its dependence on metabolic health and nutritional status was investigated in a single-center study under tightly controlled conditions in healthy controls, pre-diabetic individuals and patients with type-2 diabetes mellitus (T2DM, n=10 each). Untargeted metabolomics in serum samples taken at three different days after overnight fasts and following intake of a standardized mixed meal showed that the human serum metabolome is remarkably stable: The median intra-class correlation coefficient (ICC) across all metabolites and all study participants was determined as 0.65. ICCs were similar for the three different health groups, before and after meal intake, and for different metabolic pathways. Only 147 out of 1438 metabolites (10%) had an ICC below 0.4 indicating poor stability over time. In addition, we confirmed previously identified metabolic signatures differentiating healthy, pre-diabetic and diabetic individuals. To our knowledge, this is the most comprehensive study investigating the temporal variability of the human serum metabolome under such tightly controlled conditions.