Serum and plasma amino acids as markers of prediabetes, insulin resistance, and incident diabetes

Abstract

Presently, routine screening misses many cases of prediabetes and early type 2 diabetes (T2D). Therefore, better biomarkers are needed for a simple and early detection of abnormalities of glucose metabolism and prediction of future T2D. Possible candidates for this include plasma or serum amino acids because glucose and amino acid metabolism are closely connected. This review presents the available evidence of this connectivity and discusses its clinical implications. First, we examine the underlying physiological, pre-analytical, and analytical issues. Then, we summarize results of human studies that evaluate amino acid levels as markers for insulin resistance, prediabetes, and future incident T2D. Finally, we illustrate the interconnection of amino acid levels and metabolic syndrome with our own data from a deeply phenotyped human cohort. We also discuss how amino acids may contribute to the pathophysiology of T2D. We conclude that elevated branched-chain amino acids and reduced glycine are currently the most robust and consistent amino acid markers for prediabetes, insulin resistance, and future T2D. Yet, we are cautious regarding the clinical potential even of these parameters because their discriminatory power is insufficient and their levels depend not only on glycemia, but also on other components of the metabolic syndrome. The identification of more precise intermediates of amino acid metabolism or combinations with other biomarkers will, therefore, be necessary to obtain in order to develop laboratory tests that can improve T2D screening.

Keywords:

• Metabolomics
• prediction
• biomarker panel
• metabolism

Acknowledgments

We are grateful to all participants in the PPSDiab study and to the diabetes care team of the Medical Center of the University of Munich (Klinikum der Universität München). We thank Werner Römisch-Margl, Katharina Faschinger, and Silke Becker for the metabolomics measurements performed at the Metabolomics Core Facility, Genome Analysis Center, Helmholtz Zentrum München and Mary Carlyle White Scholz for the language editing. We also thank the Helmholtz Zentrum München, the Medical Center of the University of Munich (Klinikum der Universität München), the German Center for Diabetes Research (DZD e.V.), and the project DeTecT2D (an EIT Health Project) for supporting the PPSDiab study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Data availability

The datasets generated during and/or analyzed during this study are not publicly available due to restricted consent obtained from study participants but are available from the corresponding author on reasonable request.

Disclosure statement

The authors report no declarations of interest.