Reliability of Serum Metabolites over a Two-Year Period: A Targeted Metabolomic Approach in Fasting and Non-Fasting Samples from EPIC

Marion Carayol, Idlir Licaj, David Achaintre, Carlotta Sacerdote, Paolo Vineis, Timothy J Key, N Charlotte Onland Moret, Augustin Scalbert, Sabina Rinaldi, Pietro Ferrari, Marion Carayol, Idlir Licaj, David Achaintre, Carlotta Sacerdote, Paolo Vineis, Timothy J Key, N Charlotte Onland Moret, Augustin Scalbert, Sabina Rinaldi, Pietro Ferrari

Abstract

Objective: Although metabolic profiles have been associated with chronic disease risk, lack of temporal stability of metabolite levels could limit their use in epidemiological investigations. The present study aims to evaluate the reliability over a two-year period of 158 metabolites and compare reliability over time in fasting and non-fasting serum samples.

Methods: Metabolites were measured with the AbsolueIDQp180 kit (Biocrates, Innsbruck, Austria) by mass spectrometry and included acylcarnitines, amino acids, biogenic amines, hexoses, phosphatidylcholines and sphingomyelins. Measurements were performed on repeat serum samples collected two years apart in 27 fasting men from Turin, Italy, and 39 non-fasting women from Utrecht, The Netherlands, all participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Reproducibility was assessed by estimating intraclass correlation coefficients (ICCs) in multivariable mixed models.

Results: In fasting samples, a median ICC of 0.70 was observed. ICC values were <0.50 for 48% of amino acids, 27% of acylcarnitines, 18% of lysophosphatidylcholines and 4% of phosphatidylcholines. In non-fasting samples, the median ICC was 0.54. ICC values were <0.50 for 71% of acylcarnitines, 48% of amino acids, 44% of biogenic amines, 36% of sphingomyelins, 34% of phosphatidylcholines and 33% of lysophosphatidylcholines. Overall, reproducibility was lower in non-fasting as compared to fasting samples, with a statistically significant difference for 19-36% of acylcarnitines, phosphatidylcholines and sphingomyelins.

Conclusion: A single measurement per individual may be sufficient for the study of 73% and 52% of the metabolites showing ICCs >0.50 in fasting and non-fasting samples, respectively. ICCs were higher in fasting samples that are preferable to non-fasting.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Intra-class correlation coefficients (ICCs) of…
Fig 1. Intra-class correlation coefficients (ICCs) of serum sugars, amino acids, biogenic amines (A), acylcarnitines and sphingolipids (B) targeted metabolites in 27 fasting men and 39 non-fasting women.
*P-values

Fig 2. Intra-class correlation coefficients (ICCs) of…

Fig 2. Intra-class correlation coefficients (ICCs) of serum targeted phosphatidylcholines in 27 fasting men and…

Fig 2. Intra-class correlation coefficients (ICCs) of serum targeted phosphatidylcholines in 27 fasting men and 39 non-fasting women according to their ICC values: ICCs
*P-values
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References
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This work was supported by the European Union (EUROCAN FP7-KBBE-2010.2.4.1-2 grant #260791). AS received the funding. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The work reported in this paper was undertaken during the tenure of MC's postdoctoral fellowship awarded by the International Agency for Research on Cancer.
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Fig 2. Intra-class correlation coefficients (ICCs) of…
Fig 2. Intra-class correlation coefficients (ICCs) of serum targeted phosphatidylcholines in 27 fasting men and 39 non-fasting women according to their ICC values: ICCs
*P-values

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