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.

Establishment of the circadian metabolic phenotype strategy in spontaneously hypertensive rats: a dynamic metabolomics study

“…Because amino acids can be used for gluconeogenesis under energy deprivation [43], rhythm disorders in the catabolism of amino acids, especially BCAAs, including leucine, isoleucine, and valine, can lead to serious cardiovascular diseases [44]. Serum amino acids are markers of prediabetes, insulin resistance and incident diabetes [45]. Abnormal amino acid metabolism was also observed in hypertension.…”

Diabetes and branched‐chain amino acids: What is the link?

“…The metabolism of BCAA involves two processes: (i) a reversible process catalysed by a branched‐chain aminotransferase (BCAT), either cytosolic or mitochondrial, requiring pyridoxal to function as an amino group carrier, by which the BCAA with 2‐ketoglutarate produce a branched‐chain keto acid plus glutamate; and (ii) the irreversible mitochondrial process catalysed by branched‐chain keto acid dehydrogenase (BCKDH) leading to formation of acetyl‐coenzyme A (CoA), propionyl‐CoA, and 2‐methylbutyryl‐CoA from leucine, valine, and isoleucine, respectively, which enter the tricarboxylic acid (Krebs) cycle as acetyl‐CoA, propionyl‐CoA, and 2‐methylbutyryl‐CoA, respectively, leading to ATP formation . The BCAA stimulate secretion of both insulin and glucagon and, when given orally, of both glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP), with oral administration leading to greater and more prolonged insulin and glucagon secretion .…”

Stability of amino acids and related amines in human serum under different preprocessing and pre-storage conditions based on iTRAQ®-LC-MS/MS

“…The amino acid synthesis defects are presented by many clinical symptoms including central nervous system and mental disability for children, skin disorders such as cutis laxa in defects of proline synthesis, collodion-like skin and ichthyosis in serine deficiency, and necrolytic erythema in glutamine deficiency [2]. Increasing literatures have implicated the role of free amino acids in a number of diseases such as cardiovascular diseases [3][4][5], insulin resistance and type 2 diabetes [6,7], renal diseases [8], hepatic disorders [9] and cancer [10,11].…”