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Crit Rev Clin Lab Sci. 2018 Jan;55(1):21-32. doi: 10.1080/10408363.2017.1414143. Epub 2017 Dec 14.

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

Gar C1,2,3, Rottenkolber M1,2,3, Prehn C4, Adamski J3,4,5, Seissler J1,2,3, Lechner A1,2,3.

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a Diabetes Research Group , Medizinische Klinik und Poliklinik IV, Klinikum der Universität München , Munich , Germany.
b Clinical Cooperation Group Type 2 Diabetes , Helmholtz Zentrum München , Neuherberg , Germany.
c Deutsches Zentrum für Diabetesforschung (DZD) , Neuherberg , Germany.
d Institute of Experimental Genetics, Genome Analysis Center , Helmholtz Zentrum München, German Research Center for Environmental Health , Neuherberg , Germany.
e Lehrstuhl fu¨r Experimentelle Genetik , Technische Universität München , Freising , Germany.


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.


Metabolomics; biomarker panel; metabolism; prediction

[Indexed for MEDLINE]

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