NMR-Based Serum Metabolomics and Correlation Analysis Unraveled Metabolic Alterations Underlying Pathophysiology of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is a growing global health concern, with a high prevalence among individuals aged 45-50 years and above. Chronic inflammation, oxidative stress, and mitochondrial dysfunction play pivotal roles in its progression. This clinical metabolomics study aimed to identify distinct metabolic alterations associated with insulin resistance and other clinical features of T2DM. Fasting serum samples from 43 T2DM patients (mean age 51 ± 9 years) and 34 age- and sex-matched controls (mean age 49 ± 11 years) were analyzed using 800 MHz NMR spectroscopy. Serum metabolite concentrations were quantified using CHENOMX software and compared using multivariate and univariate statistical methods, with the diagnostic potential evaluated through receiver operating characteristic (ROC) curve analysis. T2DM patients exhibited elevated levels of glucose, mannose, urea, glutamate, and phenylalanine-to-tyrosine ratio (PTR), alongside reduced levels of alanine, valine, threonine, histidine, glutamine, and key metabolic ratios such as glutamine-to-glucose (QGR), alanine-to-glucose (AGR), glutamine-to-glutamate (QER), and glutamine-to-mannose (QMR). Metabolic alterations suggest heightened inflammation, oxidative stress, mitochondrial dysfunction, which is disrupting glucose-alanine cycling, the tricarboxylic acid cycle (TCA), and glutamine and amino acid metabolism. This study highlights the role of metabolomics in understanding T2DM pathophysiology and offers potential biomarkers for improved diagnosis and disease management.