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

Sanmei Chen,Shamima Akter,Tohru Nakagawa,Mitsuhiko Noda,Shuichiro Yamamoto,Tetsuya Mizoue,Keisuke Kuwahara,Takeshi Hayashi,Maki Konishi,Yumi Matsushita,Toru Honda

doi:10.1038/s41598-019-43431-z

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.

Highlights

Type 2 diabetes (T2D) is a highly prevalent metabolic disorder, characterized by complex disturbances in glucose and lipid metabolism resulting from a combination of resistance to insulin action and an inadequate insulin secretion response[1]
The highest correlation coefficients with homeostasis model assessment of insulin resistance (HOMA-IR) were found for branched-chain amino acids (BCAAs) and aromatic amino acids, followed by alanine, asparagine, methionine, proline, and glycine
Sensitivity analyses using conditional logistic analyses showed a virtually similar pattern of associations between amino acid profiles and the risk of type 2 diabetes (T2D). In this prospective nested case-control study among Japanese working adults, we demonstrated that fasting serum concentrations of several amino acids, including BCAAs, aromatic amino acids, gluconeogenic amino acids, and other amino acids, were associated with the risk of T2D

Summary

Introduction

Type 2 diabetes (T2D) is a highly prevalent metabolic disorder, characterized by complex disturbances in glucose and lipid metabolism resulting from a combination of resistance to insulin action and an inadequate insulin secretion response[1]. Circulating branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) and aromatic amino acids (phenylalanine and tyrosine) have consistently shown positive associations with the risk of developing T2D4–12. A prospective study in China examined three BCAAs and two aromatic amino acids in association with T2D9. A prospective study in Japanese adults reported associations of a composite amino acid score of 19 amino acids with diabetes[14]. Ethnic differences in patterns of associations between amino acids and T2D have been identified between Europeans and South Asian Europeans[8]. Provided Westerners’ and Eastern Asians’ interethnic differences in interaction between genetic, pathophysiological, cultural, and lifestyle factors related to the development of T2D15, amino acid profiles may show a distinct pattern of associations with www.nature.com/scientificreports/. We carried out a case-control study nested within a Japanese cohort, to examine associations between circulating amino acids and the risk of T2D

Methods

Results

Conclusion