Metabolic signatures of β‐cell destruction in type 1 diabetes

• Published in: Journal of diabetes investigation Vol. 14; no. 1; pp. 48 - 57
• Main Authors: Noso, Shinsuke, Babaya, Naru, Hiromine, Yoshihisa, Taketomo, Yasunori, Niwano, Fumimaru, Yoshida, Sawa, Ikegami, Hiroshi
• Format: Journal Article
• Language: English
• Published: Japan John Wiley & Sons, Inc 01.01.2023; John Wiley and Sons Inc; Wiley
• Subjects: 5-Methylcytosine; Amino acids; Antibodies; Autoimmune diseases; Beta cells; Biomarkers; Body mass index; Capillary electrophoresis; Cross-Sectional Studies; Diabetes; Diabetes mellitus (insulin dependent); Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Insulin; Mass spectrometry; Metabolism; Metabolites; Metabolome; Metabolomics; Original; Oxidants; Peptides; Regression analysis; Scientific imaging; Software; Statistical analysis; Taurine; Type 1 diabetes; β‐cell; United States > US; Japan; Metabolome; Type 1 diabetes; β-cell
• ISSN: 2040-1116; 2040-1124
• DOI: 10.1111/jdi.13926

ABSTRACT Aims/Introduction In the development of type 1 diabetes, metabolites are significantly altered and might be involved in β‐cell destruction and protection. We aimed to identify new metabolic markers of β‐cell destruction in type 1 diabetes patients. Materials and Methods A total of 33 participants were recruited for this cross‐sectional observational study: 23 with type 1 diabetes, seven with type 2 diabetes and three healthy controls. Those with type 1 diabetes were further subdivided into three groups: new‐onset, microsecretors and complete lack of endogenous insulin in type 1 diabetes. Results Metabolomic analysis identified a total of 737 peaks, and partial least square analysis was successful in discriminating between the three groups of type 1 diabetes. Among the factor loadings discriminating type 1 diabetes, 3‐phenylpropionic acid (r = 0.80, P = 4.7E−6) and hypotaurine (r = −0.484, P = 1.9E−2) strongly contributed to identifying new‐onset type 1 diabetes, and 5‐methylcytosine to identifying complete‐lack type 1 diabetes (r = 0.586, P = 6.5E−3). Reporter operating characteristics analysis, including all type 1 diabetes, type 2 diabetes and healthy controls, showed that high 3‐phenylpropionic acid (Pc <0.0001) and low hypotaurine (Pc <0.0001) were useful for identifying new‐onset type 1 diabetes, and high 5‐methylcytosine (Pc = 0.002) for the complete‐lack type 1 diabetes. Conclusions In the present study, metabolic signatures were shown to be useful in identifying type 1 diabetes at different clinical stages, and 3‐phenylpropionic acid and hypotaurine are novel biomarkers for identifying new‐onset type 1 diabetes, suggesting the involvement of the gut bacterial environment, anti‐oxidant mechanisms through the hypotaurine‐taurine pathway and methylated deoxyribonucleic acid fragmentation in the process of β‐cell destruction. Metabolomic analysis successfully discriminated type 1 diabetes at different clinical stages, and 3‐phenylpropionic acid and hypotaurine were found to be novel biomarkers for identifying new‐onset type 1 diabetes.