Metabolic signatures of β-cell destruction in type 1 diabetes

Aims/Introduction: In the development of type 1 diabetes, metabolites are significantly altered and might be involved in beta-cell destruction and protection. We aimed to identify new metabolic markers of beta-cell destruction in type 1 diabetes patients. Materials and Methods: A total of 33 participants were recruited for this crosssectional 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 beta-cell destruction.

Automated summary

Metabolic markers have been found to be useful in identifying different clinical stages of type 1 diabetes, and 3-phenylpropionic acid and hypotaurine are identified as novel biomarkers for new-onset type 1 diabetes.