Untargeted metabolomics of impaired fasting glucose and type 2 diabetes mellitus

Background Diabetes is a chronic metabolic disease whose prevalence and progression are closely related to many factors, including genetics, environment, and lifestyle. Impaired fasting glucose (IFG) is an early manifestation of type 2 diabetes mellitus (T2DM), but the underlying mechanisms are not yet fully understood. In this study, we explored the differentially expressed metabolites in patients with IFG and T2DM by using an untargeted metabolomics approach. Objective In this study, we explored the differentially expressed metabolites in patients with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM) by using an untargeted metabolomics approach. Methods Patients were assigned to three groups as follows: an IFG group, T2DM group, and normal control group. After matching baseline data that comprised sex, age, aminopherase, creatinine, and uric acid, we selected 16 cases in each group. Fasting serum metabolomes were profiled using ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS). Results The study population consisted of a cohort of 48 patients: 16 patients in the normal control group, 16 in the IFG group, and 16 in the T2DM group. Untargeted metabolomic analysis demonstrated 25 differentially expressed metabolites in the IFG group and 51 differentially expressed metabolites in the T2DM group. In the IFG group, differentially expressed metabolites were mainly enriched in glycerophospholipid metabolism, ether lipid metabolism, amino acid metabolism and biosynthesis, and pyruvate metabolism. In the T2DM group, the enriched pathways included glycerophospholipid metabolism, pyruvate metabolism, multiple amino acid-related pathways (glycine, serine, threonine, alanine, aspartate, glutamate, phenylalanine), phenylalanine-tyrosine-tryptophan biosynthesis, the citrate cycle, and butanoate metabolism. Conclusions This pilot metabolomic investigation suggests that changes in metabolic characteristics may already occurred early in the development of T2DM. There may still exist some metabolic differences between patients with IFG and those with T2DM, and differentially expressed metabolites were concentrated in the amino acid and lipid metabolism pathways. But this study is still in the exploratory stage; future work with larger, longitudinal cohorts is warranted to validate these findings and assess their clinical relevance.