Serum amino acid profiles and risk of type 2 diabetes among Japanese adults in the Hitachi Health Study

Abstract

Amino acids have emerged as novel biomarkers for predicting type 2 diabetes (T2D), but the epidemiologic data linking circulating amino acid profiles with T2D are sparse in Asian populations. We conducted a nested case-control study within a cohort of 4,754 nondiabetic Japanese employees who attended a comprehensive health checkup in 2008–2009 and agreed to provide blood samples. During a 5-year follow-up, incident T2D cases were ascertained based on plasma glucose, glycated hemoglobin, and self-report. Two controls matched to each case on sex, age, and the date of serum sampling were randomly selected by using density sampling, resulting in 284 cases and 560 controls with amino acid measures. High concentrations of valine, leucine, isoleucine, phenylalanine, tyrosine, alanine, glutamate, ornithine, and lysine were associated with an increased risk of incident T2D, in a linear manner. High glutamine concentrations were associated with a decreased risk of incident T2D. Further adjustment for the homeostasis model assessment of insulin resistance attenuated these associations. Overall, these amino acids may be novel useful biomarkers in the identification of people at risk of T2D before overt symptoms. Insulin resistance may account for or mediate the relationship between these amino acids and risk of incident T2D.

Detection of Early Disease Risk Factors Associated with Metabolic Syndrome: A New Era with the NMR Metabolomics Assessment

“…Besides BCAAs and AAAs, other common amino acids are potential biomarkers, such as glutamine and glutamate, of the dysregulation of carbohydrates metabolism. In recent studies, the profile of amino acids, including BCAAs, AAAs and glutamine and glutamate, has been linked with risk factors related to T2D [28,147]. In this section, plasma glutamine, glutamate and their ratio will be discussed as potential biomarkers for T2D as it is showed in several studies [148].…”

Altered Metabolome of Lipids and Amino Acids Species: A Source of Early Signature Biomarkers of T2DM

“…AA: Elevated (serum/plasma) AA level is an important early biomarker of glucose intolerance, insulin insensitivity and, subsequently, diabetes. Many epidemiological cohort studies have witnessed an increased level of AA in newly diagnosed diabetic patients in the follow up investigations hinting towards an impaired glucose/hexoses metabolism [14]. An increased serum AA level reduced the insulin sensitivity and uptake of hexoses by offering competition at the substrate level to glucose oxidation and also by interfering with insulin signaling [11,13].…”

Glutaminostatin: Another facet of glucagon as a regulator of plasma amino acid concentrations

“…Indeed, the association between plasma amino acid levels and the risk of type 2 diabetes has been analyzed in a number of studies. In particular, Chen et al 8 reported that a high glutamine concentration and glutamine-to-glutamate ratio were associated with a decreased risk of the incidence of type 2 diabetes in a nested case-control study in non-diabetic Japanese individuals. As glucagon levels were not analyzed in the study, the association between glutamine concentration and glucagon levels in plasma remains a matter of conjecture.…”