Metabolic signatures of β‐cell destruction in type 1 diabetes

Abstract

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.

Keywords

• Metabolome
• Type 1 diabetes
• β‐cell