Characteristic changes in plasma glutamate levels and free amino acid profiles in Japanese patients with type 1 diabetes mellitus

ABSTRACT Aims/Introduction In addition to absolute insulin deficiency, dysregulated glucagon in type 1 diabetes is considered pathophysiologically important. Previously, we confirmed the presence of dysregulated glucagon in Japanese patients with type 1 diabetes, and found a significant correlation between plasma glucagon and blood urea nitrogen levels, suggesting an association between glucagon and amino acid metabolism. In this study, we evaluated plasma amino acid levels in Japanese patients with type 1 diabetes in the context of their functional relationship with glucagon. Materials and Methods We assessed plasma free amino acid levels using liquid chromatography–mass spectrometry in 77 Japanese patients with type 1 diabetes, and statistically analyzed their characteristics and relationships with clinical parameters, including glucagon. Results Participants with type 1 diabetes showed a large decrease in glutamate levels together with a characteristic change in plasma free amino acid profiles. The network structural prediction analyses showed correlations between each amino acid and glucagon in type 1 diabetes. Conclusions Participants with type 1 diabetes showed characteristic changes in plasma glutamate levels and free amino acid profiles compared with controls and type 2 diabetes patients. Glucagon showed a closer correlation with amino acids than with parameters of glucose metabolism, suggesting that type 1 diabetes includes dysregulation in amino acids through dysregulated glucagon from remaining pancreatic α‐cells, together with that in glucose by insulin deficiency. In T1D, glucagon displayed a closer correlation with amino acids than with parameters of glucose metabolism. Subjects with T1D displayed characteristic changes in plasma glutamate levels and free amino acid profiles compared to control and T2D.